Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024240
The proliferative capacity of cardiomyocytes is limited in adult mammals, and replacing lost tissue following acute ischemic injury is challenging. Previous studies have demonstrated that miR-199a-3p can promote cardiomyocyte proliferation, but the exact mechanism by which this occurs remains unclear, although multiple targets of miR-199a-3p have been identified. We recently showed that very-low-density-lipoprotein receptor (Vldlr) inhibits cardiomyocyte proliferation, and in this study we aim to test whether Vldlr is a functional target gene of miR-199a-3p. 3′UTR reporter assays demonstrate that miR-199a-3p directly binds to the 3′UTR of Vldlr and inhibits its translation. Overexpressing Vldlr blunts the pro-proliferative effect of miR-199a-3p on cardiomyocytes, suggesting that Vldlr is indeed a functional target of miR-199a-3p. Mechanistically, Vldlr reduces S807/811 phosphorylation of RB1, and inhibiting CDK4/6 to prevent RB1 phosphorylation can block the pro-proliferative effect of both Vldlr knockdown and miR-199a-3p, suggesting that RB1 phosphorylation is required for the cardiomyocyte proliferation induced by miR-199a-3p and Vldlr knockdown. The findings of this study reveal Vldlr as a novel functional target of miR-199a-3p in cardiomyocytes and identify RB1 as a downstream effector of cardiomyocyte proliferation. The identification of the role of the miR-199a-3p-Vldlr-RB1 axis in cardiomyocyte proliferation may provide potential therapeutic targets for cardiac regenerative medicine.
Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpb/art_1126
Since its establishment in 2013, BioLiP has become one of the widely used resources for protein–ligand interactions. Nevertheless, several known issues occurred with it over the past decade. For example, the protein–ligand interactions are represented in the form of single chain-based tertiary structures, which may be inappropriate as many interactions involve multiple protein chains (known as quaternary structures). We sought to address these issues, resulting in Q-BioLiP, a comprehensive resource for quaternary structure-based protein–ligand interactions. The major features of Q-BioLiP include: (1) representing protein structures in the form of quaternary structures rather than single chain-based tertiary structures; (2) pairing DNA/RNA chains properly rather than separation; (3) providing both experimental and predicted binding affinities; (4) retaining both biologically relevant and irrelevant interactions to alleviate the wrong justification of ligands’ biological relevance; and (5) developing a new quaternary structure-based algorithm for the modelling of protein–ligand complex structure. With these new features, Q-BioLiP is expected to be a valuable resource for studying biomolecule interactions, including protein–small molecule interaction, protein–metal ion interaction, protein–peptide interaction, protein–protein interaction, protein–DNA/RNA interaction, and RNA–small molecule interaction. Q-BioLiP is freely available at https://yanglab.qd.sdu.edu.cn/Q-BioLiP/.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04989-4
Background Chemotherapy-induced premature ovarian failure (POF) is a major cause of infertility, with limited treatment options. Mesenchymal stem cell-derived exosomes (MSC-Exos) have therapeutic potential. This study investigated whether preconditioning MSCs with the antioxidant flavonoid isorhamnetin (ISO) enhances the efficacy of their exosomes (ISO-MSC-Exos) against POF. Methods A cyclophosphamide-induced POF rat model was established, and the role of the ferroptosis inhibitor ferrostatin-1 was evaluated. MSC-Exos and ISO-MSC-Exos were isolated by ultracentrifugation and administered via tail vein injection. Ovarian recovery was assessed by monitoring the oestrous cycle, serum hormone levels, and histological findings. Lipid peroxidation and iron metabolism were evaluated by quantifying malondialdehyde, glutathione, iron deposition, and mitochondrial ultrastructure. Immunohistochemistry was used to assess the expression levels of GPX4, ACSL4, and FTH1. Proteomic analyses were performed to explore the underlying mechanisms. Results Ferroptosis plays a pivotal role in the cyclophosphamide-induced POF rat model. Both exosome therapies improved ovarian function and suppressed ferroptosis, with ISO-MSC-Exos showing superior efficacy. ISO-MSC-Exos significantly restored hormone levels, ameliorated oestrous cycle disorders, reduced follicular atresia, and enhanced fertility. Furthermore, ISO-MSC-Exos more effectively elevated glutathione levels, reduced malondialdehyde and Fe2⁺ levels, and reversed the abnormal expression of ferroptosis-related proteins GPX4, ACSL4, and FTH1. Proteomic analysis suggested that ISO-MSC-Exos effectively inhibit ferroptosis by downregulating Alox15 and Tf, thereby reducing lipid peroxidation substrates and cellular iron uptake. This finding represents a potential molecular mechanism underlying their superior efficacy compared with that of MSC-Exos. Conclusions ISO-MSC-Exos showed superior efficacy compared with MSC-Exos in restoring ovarian function and inhibiting ferroptosis, suggesting that ISO pretreatment enhances the therapeutic effect of MSC-Exos in the POF
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05051-z
Background Intervertebral disc degeneration (IVDD) is a major cause of low back pain, characterized by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtuin 1 (SIRT1), a key regulator of mitochondrial quality control, is downregulated in degenerated discs. Salidroside (Sal), a natural compound from Rhodiola rosea, has shown potential in enhancing mitophagy, but its mechanism in IVDD remains unclear. Methods Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD. Results Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal’s protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04896-8
Background The development of vascular calcification (VC) in diabetes is closely related to the endothelial-to-mesenchymal transition (EndMT). We found that microRNA-32-5p (miR-32) was elevated in the plasma of calcification patients. However, it is unclear whether miR-32 mediates the function of bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) in type 2 diabetes (T2D) VC. Methods BMSC-EVs were characterized by TEM, NTA, Western blotting, and confocal microscopy. Alizarin Red and ALP staining assessed the severity of VC. qRT-PCR and Western blotting evaluated the expression of BMP2, RUNX2, GPX4, SLC7A11, VE-cadherin, and N-cadherin, while immunofluorescence was used for detecting VE-cadherin and N-cadherin. In vivo validation was performed using miR-32–/– and ApoE–/– mice. RNA sequencing (RNA-seq) and bioinformatics analysis was conducted to explore underlying mechanisms. Results We demonstrated that BMSC-EVs attenuate VC in endothelial cells (ECs) and inhibit EndMT. In vivo, histological analysis showed that treatment with BMSC-EVs significantly reduced the severity of VC associated with T2D. Notably, knockout of miR-32 further enhanced the inhibitory effect of BMSC-EVs on VC. Mechanistically, transcriptomic and functional analyses suggest that the protective effect of BMSC-EVs on VC is associated with regulation of the MAPK/FoxO signaling pathway, potentially mediated by modulation of ferroptosis. Conclusion These findings demonstrate that BMSC-EVs attenuate T2D-associated VC, partially through miR-32-mediated suppression of EC ferroptosis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Background Osteoporosis (OP) is a systemic bone disease characterized by damage to bone strength, leading to increased bone fragility and fracture risk. Cadherin 19 (CDH19) is located on chromosomes 18q22-q23, and 18q deletion is associated with terminal deletion diseases, including foot/hand deformities. However, the role of CDH19 in bone remains undefined. Methods A conditional knockout mouse model of the CDH19 gene was constructed using the Cre-loxP system, and the bone mass and bone morphology in mice were investigated using microCT and histological staining. Osteoblasts were isolated and cultured from wild-type and CDH19 knockout mice. Cell proliferation and differentiation were explored through EdU labeling, qPCR, alkaline phosphatase (ALP)/ alizarin red S (ARS) staining, and Western blot assays. The expression of genes altered in CDH19 gene knockout osteoblast was checked by RNA sequencing (RNA-seq), and subsequently confirmed by immunofluorescence and Western blot. Results We found that CDH19 could maintain the normal proliferation and differentiation in osteoblasts. After knocking out the CDH19 gene, the abilities of proliferation and osteogenesis were significantly inhibited in osteoblasts. Moreover, the bone mass of CDH19 knockout mice was significantly reduced, characterized by decreases in bone density, trabecular number, and bone volume fraction. The RNAseq analysis and western blot showed the PI3K/AKT signaling pathway was significantly inhibited in osteoblasts with CDH19 deletion. Furthermore, we demonstrated that administration of PI3K/AKT signaling pathway agonist 740Y-P partially alleviated the inhibition of osteogenic differentiation caused by CDH19 deletion in vitro and in vivo. Conclusion This study demonstrated that CDH19 regulated osteogenic differentiation by modulating the PI3K/AKT signaling pathway in osteoblasts. CDH19 may become a novel target for the treatment of bone diseases.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04900-1
Background The human endometrium is a regenerative tissue essential for fertility, but pathological conditions like Asherman syndrome, endometrial atrophy, and thin endometrium can impair its function. Current therapies lack efficacy, driving demand for innovative regenerative therapies. In this context, endometrial-derived hydrogels and organoids have shown promise individually for tissue regeneration, but their combined therapeutic potential has not been previously evaluated in vivo. This study explores a dual regenerative strategy combining a hybrid hydrogel — composed of synthetic PuraMatrix® and endometrial extracellular matrix hydrogel — with human endometrial organoids in an immunocompetent murine model with uterine damage. Methods Endometrial damage model was established in female C57BL/6 mice (n = 46) via uterine injury using 70° ethanol. After 4 days of endometrial damage, human endometrial organoids were co-injected with the hybrid hydrogel into the uterine horns. Two weeks post-injection, a subset of mice (n = 25) was sacrificed for biocompatibility, histological, and transcriptomic analyses. Functional recovery of the endometrium was assessed in the remaining animals (n = 21) through fertility outcome evaluation. For endometrial regeneration analyses, normally distributed data were analyzed by one-way ANOVA and Tukey’s multiple comparisons, while non-normally distributed data were analyzed by the Kruskal–Wallis test with Dunn’s multiple comparisons. For fertility outcomes, t-test or Mann–Whitney U tests for 2-by-2 comparisons were performed.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05008-2
Background The therapeutic efficacy of mesenchymal stem cells (MSCs) can be improved by enhancing their adaptation to the inflammatory microenvironment. Autophagy maintains MSCs functionality, and autophagy-related gene 5 (ATG5) mediates autophagy and regulates the biological functions and therapeutic efficacy of these cells. The aim of this study was to investigate the role of ATG5 in the antioxidant capacity and evaluate the therapeutic effect of ATG5-engineered MSCs for colitis treatment. Methods Cell viability was assessed using a Cell Counting Kit-8. The mRNA expression of autophagy-, antioxidant-, and polarization-related genes was determined through real-time quantitative polymerase chain reaction, and protein expression was analyzed via western blotting. Macrophage polarization markers were analyzed using flow cytometry. Multiomics approaches, including RNA transcriptome sequencing, untargeted metabolomics, and 16S ribosomal RNA microbiota analysis, were also used. Mice with dextran sulfate sodium-induced colitis were used to evaluate the therapeutic efficacy of MSCs. Results Preconditioning MSCs with hypoxia (1% O₂) and serum deprivation significantly enhanced autophagy and upregulated ATG5 expression. Adenovirus-mediated ATG5 overexpression in MSCs (MSCs-ATG5) enhanced their autophagic activity and antioxidant capacity, upregulated HMOX-1, SOD2, and CAT expression, and increased glutathione peroxidase and catalase enzymatic activity, while enhancing cell proliferation, without altering surface marker expression. Further, MSCs-ATG5 significantly promoted M2 macrophage polarization and regulated oxidative stress-related signaling pathways. Additionally, MSCs-ATG5-based therapy markedly ameliorated colitis disease signs in mice. Transcriptome analysis revealed that MSCs-ATG5 suppressed the IL-17/NF-κB inflammatory signaling pathway. This treatment also regulated levels of the anti-inflammatory metabolite prostaglandin D2 (PGD2) in colon tissues.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04780-x
Background Liver fibrosis is a crucial pathological stage in the progression of chronic liver diseases. Yiguanjian (YGJ), a Chinese herbal formula, exhibits anti-inflammatory, anti-fibrotic, and hepatoprotective effects. Extracellular vesicles from bone-marrow mesenchymal stem cells (BMSC-EVs) have shown potential in treating various disorders, including liver fibrosis. This study investigated the regulatory effects of EVs from YGJ-preconditioned BMSCs (YGJ-EVs) on TGF-β1-stimulated hepatic stellate cells (HSCs) and their therapeutic potential in a mouse model of liver fibrosis, with a focus on identifying the causative microRNA cargo. Methods YGJ-EVs and control EVs were isolated from BMSC culture supernatants and characterized via western blotting, transmission electron microscopy, and nanoparticle tracking analysis. Their cellular uptake in vitro and in vivo was evaluated using DIR labeling. To identify candidate miRNAs mediating YGJ-EV bioactivity, miRNA microarray analysis was conducted. To assess the effect of YGJ-EVs on liver fibrosis, TGF-β1-activated HSC cells were treated with YGJ-EVs or control-EVs for 24 h, and then the expression of proteins related to fibrotic activation (COL1-A1 and α-SMA), lysosomal biogenesis (LAMP1, TPP1, CTSD, and CTSB) mitophagy (p62, LC3, PINK1, and Parkin), and the Akt/AMPK/TFEB pathway was assessed. To determine whether miR-7045-5p is the causative factor, HSC cells transfected with miR-7045-5p were similarly analyzed. Results miRNA microarray analysis revealed miR-7045-5p upregulation in YGJ-EVs versus control EVs. In CCl4-treated mice, YGJ-EV-derived miR-7045-5p ameliorated the liver fibrosis, improved the hepatic function, and suppressed the HSC activation by inhibiting the Akt/AMPK/TFEB pathway. In vitro, miR-7045-5p overexpression attenuated TGF-β1-induced HSC activation. Conclusion YGJ increases miR-7045-5p abundance in BMSC-EVs. YGJ-EVs alleviate liver fibrosis by delivering the anti-fibrotic miRNA miR-7045-5p, which inhibits the Akt/AMPK/TFEB pathway, thereby promoting lysosomal biogenesis and mitophagy in HSCs.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04148-1
Background The long-term effects and outcomes of human mesenchymal stem cell (MSC) therapy in patients with severe coronavirus disease 2019 (COVID-19) remain poorly understood. This study aimed to evaluate the extended safety and efficacy of MSC treatment in severe patients with COVID-19 who participated in our earlier randomized, double-blind, placebo-controlled clinical trial, with follow-up conducted over 3 years. Methods One hundred patients with severe COVID-19 were randomized to receive either an MSC infusion (n=65, 4×10^7 cells/dose, on days 0, 3, and 6) or a placebo, with both groups receiving the standard of care. At 36 months post-MSC therapy, patients were followed up to long-term safety and efficacy, particularly the effects of MSC therapy on persistent COVID-19 symptoms. Evaluated outcomes included lung imaging results, 6-min walking distance (6-MWD), pulmonary function test results, quality of life scores based on the Short Form-36 (SF-36) health survey, Long COVID symptoms, new-onset comorbidities, tumor marker levels, and rates of COVID-19 reinfection. Results Three years post-treatment, 46.94% (23/49) of patients in the MSC group and 34.48% (10/29) in the placebo group showed normal findings on computed tomography (CT) images (odds ratio [OR]=1.68, 95% confidence interval [CI]: 0.65–4.34). The general health (GH) score from the SF-36 was higher in the MSC group (67.0) compared to the placebo group (50.0), with a difference of 12.86 (95% CI: 1.44–24.28). Both groups showed similar results for total lung severity scores (TSS), 6-MWD, pulmonary function tests, and Long COVID symptoms. No significant differences between groups were observed in new-onset complications (including tumorigenesis) or tumor marker levels. After adjusting for China’s dynamic zero-COVID-19 strategy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection rates were 53.06% (26/49) in the MSC group and 67.86% (19/28) in the placebo group (OR=0.54, 95% CI: 0.20–1.41). Conclusions These findings support the long-term safety of MSC therapy in patients with severe COVID-19 over 3 years. MSC treatment may offer potential benefits for lung recovery and improved quality of life in patients experiencing Long COVID symptoms. Trial registration: ClinicalTrials.gov, NCT04288102. Registered 28 February 2020, https://clinicaltrials.gov/study/NCT04288102.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04613-x
Background Osteoarthritis (OA) is a joint disorder that severely affects patients’ mobility, overall health, and ability to perform daily activities. Despite advancements in therapeutic strategies, stem cell-based therapies for OA still face challenges, particularly in enhancing the antioxidative capacity of stem cells to improve therapeutic outcomes. Therefore, this study aimed to explore the potential of β-sitosterol in this context. Methods This study evaluated the protective effects of β-sitosterol on bone marrow-derived mesenchymal stem cells (BMSCs) and chondrocytes under oxidative stress conditions and assessed its potential in promoting cartilage repair in a rabbit OA model. Cell viability, gene expression, oxidative stress markers, and mitochondrial function were examined. In vivo therapeutic effects were evaluated through histological and immunohistochemical analyses. Results The results revealed that β-sitosterol significantly enhanced BMSC viability, upregulated the expression of Col2a1 and aggrecan, while inhibiting MMP13 expression. Furthermore, β-sitosterol effectively alleviated oxidative stress and preserved mitochondrial function in BMSCs. Notably, BMSCs pretreated with β-Sitosterol exhibited a higher potential for facilitating cartilage regeneration in the OA model, as evidence by histopathological analysis. Conclusions These findings suggest that β-sitosterol possesses significant antioxidative and chondroprotective properties, which enhance the therapeutic efficacy of BMSCs in addressing OA-related cartilage damage.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04258-w
Background Tumors and injuries often lead to large mandibular defects. Accelerating the osteogenesis of large bone defect areas is a major concern in current research. In this study, dental pulp mesenchymal stem cells (DPSCs) were used as seed cells, and the local pulsatile parathyroid hormone (PTH) delivery system was used as an osteogenic-inducing active ingredient to act on DPSCs and osteoblasts, which were applied to the jaw defect area to evaluate its therapeutic effect on bone regeneration. Methods Pulsatile delivery systems, both with and without PTH, were developed following the protocols outlined in our previous study. In vitro, the biocompatibility of the pulsatile delivery system with DPSCs was assessed using the Cell Counting Kit-8 (CCK8) assay and live/dead cell staining. Osteogenic differentiation was evaluated through alkaline phosphatase staining and alizarin red staining. In vivo, critical bone defects with a diameter of 10 mm were created in the mandibles of white rabbits. The osteogenic effect was further assessed through gross observation, X-ray imaging, and histological examination. Results In vitro experiments using CCK8 assays and live/dead cell staining demonstrated that DPSCs successfully adhered to the surface of the PTH pulsatile delivery system, showing no significant difference compared to the control group. Furthermore, alkaline phosphatase staining and Alizarin Red staining confirmed that the localized pulsatile parathyroid hormone delivery system effectively induced the differentiation of DPSCs into osteoblasts, leading to the secretion of abundant calcium nodules. Animal studies further revealed that the PTH pulsatile delivery system promoted the osteogenic differentiation of DPSCs, facilitating the repair of critical mandibular bone defects.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04463-7
Background: Recent advances in clinical trials have involved the transplantation of induced retinal pigment epithelium (iRPE) cells from stem cells in creating a functional monolayer that mimics the characteristics of natural adult RPE cells. One method of achieving this goal is through the use of tissue engineering. In this research, decellularised femtosecond laser intrastromal lenticules (dfLEN) were employed as a scaffold for cultivating a bioengineered iRPE monolayer sheet. Methods: iRPE cells were obtained by differentiating induced pluripotent stem cells (iPSC). These cells were then seeded on decellularized FLI-lenticules (dfLEN). The functionality, characterization, and oxidative stress of iRPE cultured on dfLEN were compared with those cultured on plates (TCP) using various assays such as immunofluorescence (IF), Edu, CCK8, ELISA, DFCH-DA, and JC-1. Additionally, RNA-seq assays and electron microscope (SEM and TEM) were used to test the iRPE characteristic on engineered dfLEN. Finally, we evaluated the biocompatibility of iRPE-dfLEN sheets by transplanting them into the subretinal space of New Zealand white rabbits. Results: The iRPE cells cultured on dfLEN exhibited morphology and physiology similar to that of native RPE tissue. The dfLEN not only increased the resistance capacity of iRPE cells but also improved their functional properties compared to TCP. In addition, our results indicate that dfLEN enhances the expression of genes associated with cilium assembly, resulting in notable improvements in ciliogenesis in iRPE cells. Finally, the dfLEN-iRPE sheets demonstrated favorable biocompatibility and some viability when transplanted into the subretinal space of rabbits for a period of 14 days.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04480-6
Background Diabetic foot ulcers (DFU) typically exhibit impaired healing due to dysregulated re-epithelialization and excessive inflammation. Succinate, a key metabolic intermediate, is now understood to regulate inflammation through G Protein-Coupled Receptor 91 (GPR91) and succinate dehydrogenase (SDH), although its role in DFU remains unclear. Methods Co-cultures of M2 macrophages and epithelial cells, along with clinical samples, were used to analyze the expression of GPR91 and SDH. Functional assays were performed using high glucose (HG)-treated M2 macrophages (HG-M2) and an in vivo model. Cytokine and growth factor levels in cell supernatant were measured, and molecular mechanisms were explored via qRT-PCR, flow cytometry, and western blot analysis. Results Elevated glucose concentrations increased succinate levels and disrupted M2 macrophage–epidermal stem cells (EpSCs) interactions. GPR91 knockdown worsened HG-M2 dysfunction, while GPR91 overexpression (OE-GPR91) enhanced anti-inflammatory responses and reduced succinate. OE-GPR91-conditioned medium preserved EpSCs stemness and promoted migration mediated by hepatocyte growth factor (HGF). SDH inhibition (via Dimethyl malonate, DMM) boosted M2 macrophage activity by reducing reactive oxygen species (ROS) and upregulating Gpr91 expression. Mechanistically, GPR91 activated the pAkt/pGSK3β/β-catenin pathway, while DMM enhanced M2 macrophage function via the PI3K-Akt/pERK1/2 pathway. Conclusions GPR91 upregulation and SDH inhibition improve HG-M2 macrophage function, reduce inflammation, and enhance HGF-mediated EpSCs repair. Targeting both pathways may represent a promising approach to promote DFU healing.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04366-7
Background Osteoarthritis (OA) is a common degenerative disease caused by multiple pathological mechanisms wherein subchondral bone malfunction plays a substantial role. Recently, subchondral (SC) injection of orthobiologics has been attracting growing interest albeit the mainstream delivery method of mesenchymal stem cells (MSCs) is through intra-articular (IA). This study investigates the effect of SC injection of human umbilical cord mesenchymal stem cells (UCMSCs) on OA and its possible therapeutic mechanism compared to IA injection. Methods Male Sprague-Dawley rats with anterior cruciate ligament transection (ACLT) received saline or UCMSC injections via SC or IA. Consecutive injections once a week for three weeks and withdrawal for another four weeks, followed by Radiographical scanning, histopathological, immunohistochemical, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) staining. Cell counting Kit-8 (CCK-8) assay, alkaline phosphatase (ALP), alizarin red staining (ARS), TUNEL, flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed in TNFα-induced MC3T3-E1 cells to illustrate the exact pathogenesis mechanism. Results IA and SC UCMSC injections preserved cartilage, synovium, and subchondral bone parameters like trabecular bone volume fraction (BV/TV). SC injection uniquely improved Trabecular separation (Tb.Sp) and Trabecular number (Tb.N). SC and IA injections of UCMSCs demonstrated equivalent efficacy in promoting osteoblastic bone formation and attenuating aberrant angiogenesis of subchondral bone. In addition, we demonstrated that osteoblast apoptosis and Smad2-dependent TGF-beta (TGF-β) are crucial and interactive subchondral bone pathological features in OA. In vivo and vitro studies further revealed that UCMSCs inhibited excessive TGF-β/pSmad2 signaling to regulate osteoblast apoptosis and bone remodeling, thereby ameliorating OA progression. These findings suggest that SC injection of UCMSCs is a promising therapeutic strategy for OA, potentially offering advantages over IA injection in improving subchondral bone microarchitecture.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04751-2
Background Sepsis survivors frequently develop compromised humoral immunity, manifesting as prolonged immunosuppression that increases susceptibility to secondary infections with high associated mortality. While mesenchymal stromal cells (MSCs) have demonstrated efficacy in mitigating initial inflammatory responses and improving early survival rates in murine cecal ligation and puncture (CLP) models, they show limited effectiveness against subsequent secondary infections. Given that lymphopenia represents a primary driver of this infection vulnerability, we sought to investigate whether spleen-targeted MSC therapy could prevent lymphocyte depletion and enhance protection against secondary infections. Methods In this study, we developed CXCR5-overexpressing MSCs (MSCCXCR5) to enhance their targeted migration toward splenic CXCL13. Using a CLP mouse model followed by secondary Staphylococcus aureus (S. aureus) infection, we systematically evaluated the therapeutic potential of MSCCXCR5 in combating post-sepsis immunosuppression. Results MSCCXCR5 demonstrated enhanced splenic migration, specifically homing to CXCL13-rich B-cell zones, and conferred significant protection against both S. aureus secondary infection and sepsis-induced lymphopenia. Mechanistic investigations revealed that MSCCXCR5 treatment preserved follicular and germinal center B-cell populations, maintaining splenic architecture and potentiating antigen-specific B-cell responses to CLP challenge. These effects collectively contributed to markedly improved survival outcomes in CLP mice following secondary infection. Conclusion Our findings demonstrate that MSCCXCR5 confers dual-phase protection in sepsis, improving survival during both the initial hyperinflammatory phase and subsequent immunosuppressive period. This comprehensive
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04214-8
The authors wish to note the following correction: The images in Fig. 2D of our paper, which were intended to show Annexin V staining for apoptosis of human dental pulp stem cells (hDPSCs) and HGF-transfected hDPSCs (HGF-hDPSCs) under hypoxic conditions or serum-free media, were incorrect. The original results demonstrated that more apoptotic cells were observed in the hDPSCs group compared to the HGF-hDPSCs group. However, we inadvertently used images of Annexin V staining for apoptosis in human bone marrow mesenchymal stem cells (hBMSCs) and HGF-transfected hBMSCs (HGF-hBMSCs). Upon reviewing the original experimental records, we discovered that the incorrect images were included during the manuscript preparation process due to insufficient verification. We have now provided the correct images for hDPSCs and HGF-hDPSCs in Fig. 2D (see attachment). We sincerely apologize for this oversight. This error occurred because our research group has been extensively engaged in studying the biological characteristics of HGF gene-transfected mesenchymal stem cells. Unfortunately, due to carelessness, we mistakenly selected the wrong images. Nevertheless, our research consistently demonstrates that the anti-apoptotic ability of mesenchymal stem cells (including rBMSCs, hBMSCs, and hDPSCs) is enhanced under hypoxic conditions or serum-free media following HGF gene transfection. The methodology and results remain consistent with our previous studies. After thoroughly reviewing all data and experimental records, we confirm that this correction does not affect the validity of the original study’s results or conclusions.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04727-2
Introduction Type 1 diabetes (T1D) results from the destruction of pancreatic β-cells, leading to insulin deficiency. As insulin therapy does not affect disease progression, advancements in immune regulation therapies have emerged, including the reconstitution of the insulin secretory system. Cysteine-rich acidic secretory protein (SPARC) is an extracellular matrix glycoprotein that regulates cell adhesion, facilitating cell migration, and mediating interactions between cells and their extracellular matrix. SPARC is overexpressed during tissue repair and is involved in β-cells survival. However, the potential of SPARC-modified mesenchymal stem cells (MSCs) to improve insulin secretion has not been thoroughly investigated. This study investigated the therapeutic effects of SPARC-MSCs in vivo and in vitro and assessed whether SPARC enhances survival and insulin secretion after β-cells injury. Methods In vivo, we established T1D models in mice and canine using SPARC-MSCs for cell transplantation. In vitro, MIN6 cells were damaged with STZ, and SPARC-MSC supernatant was co-cultured with MIN6 for various assays. Results Our study demonstrated that SPARC enhanced the regenerative capacity and migratory efficiency of MSCs after H2O2 injury and improved their morphology. In STZ-induced canine and mice diabetes models, SPARC-MSCs therapy significantly reduced hyperglycemia, improved oral glucose tolerance test (OGTT), and reversed weight loss in canine. Biochemical analyses showed improved liver function, and histological examination revealed restored islet area was significantly restored. Transcriptome and proteome sequencing indicated significant enrichment in calcium binding and cell migration pathways. Co-culturing SPARC-MSC supernatant with MIN6 cells after STZ injury restored their regenerative ability, enhancing insulin secretion and ATP content under high glucose stimulation. SPARC treatment also significantly increased intracellular Ca2+ levels in MIN6 cells. Conclusion SPARC significantly promotes cell regeneration and stimulates insulin secretion by increasing intracellular ATP and Ca2+ influx. In diabetic canine and mice models, it alleviated hyperglycemia, improved glucose tolerance, and enhanced pancreatic islet area and insulin secretion.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04527-8
Background Although both pre-clinical and clinical studies show promising outcomes, resulting in rapid growth of clinical trials of MSC-based therapies in recent years, the heterogeneity and therapeutic inconsistency of MSCs have severely hampered their clinical applications. Purifying homogenous MSC populations with enhanced specific functions represents one promising approach. We have demonstrated recently that the CD317+ MSCs have enhanced anti-inflammatory functions and improved therapeutic efficacy and consistency.
Methods In the current study, we performed both in vitro and in vivo investigations to delineate whether and how CD317 regulates the immune modulation function of MSCs.
Results Our data here indicate that the CD317 directly contributes to the immune suppression function of MSCs stimulated by TNF-α through up-regulating TSG6 via CD317/lipid-raft/TNFR1 complex. The CD317 stabilizes the TNFR1 complex, resulting in hyper-activation of the NF-κB pathway and up-regulation of TSG6, which confers the therapeutic effects of MSCs on the mouse model of ALI (acute lung injury) and IBD (inflammatory bowel disease).
Conclusions Thus, the CD317 stabilizes TNFR1 and confers the anti-inflammatory functions of MSCs via NF-κB/TSG6 Pathway.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-025-04862-w
Using adipose-derived stem cells (ADSCs) has recently become a crucial approach for treating bone defects owing to their ease of accessibility and substantial differentiation potential. N6-methyladenosine (m6A) modification greatly influences biological processes and determines the differentiation fate of stem cells. However, the specific mechanisms by which m6A modification influences the osteogenic differentiation of ADSCs remain unclear. We identified FOXO1 as the key m6A-modified gene during the osteogenesis of ADSCs. Furthermore, demethylase FTO enhanced RUNX2 expression while inhibiting PPARG expression by modifying FOXO1, thereby facilitating ADSC osteogenesis. FTO knockdown inhibited ADSC migration and proliferation and impaired osteogenesis by suppressing FOXO1. At the mechanistic level, we first revealed that FTO was exported to the cytoplasm and then directly bound with FOXO1 mRNA at its 1760th bp site. Consistent use of non-steroidal anti-inflammatory drugs (NSAIDs) containing FTO inhibitors impeded ADSC-mediated bone formation both in vivo and in vitro. In summary, our study reveals the role of m6A modification based on the FTO–FOXO1–RUNX2/PPARG axis in regulating the osteogenic differentiation of ADSCs, thereby improving the clinical use of ADSCs and providing strategies for related drug applications in bone regeneration.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04565-2
This correction article addresses an error in the scale of the control group image in Fig. 4E of the original article. The corrected image is provided. The original article can be found online at https://doi.org/10.1186/s13287-025-04468-2.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04203-x
Background Mesenchymal stem cell (MSC) -derived exosomes, especially adipose-derived mesenchymal stem cell exosomes (ADSC-Exos), have emerged as a promising alternative for skin damage repair with anti-inflammatory, angiogenic and cell proliferation effects while overcoming some of the limitations of MSC. However, the mechanism by which ADSC-Exos regulates inflammatory cells during wound healing remains unclear. This study investigated how ADSC-Exos regulate macrophages to promote wound healing. Methods ADSC-Exos were isolated using ultracentrifugation, with subsequent quantification of exosomes particle number. To investigate their role in wound healing, the effects of ADSC-Exos on inflammation, angiogenesis, collagen deposition and macrophage polarization were evaluated through immunohistochemical staining, immunofluorescence and western blotting. Changes in gene expression associated with ADSC-Exos-induced macrophage polarization were analyzed using qPCR. RNA sequencing was performed to identify differentially expressed genes affected by ADSC-Exos. The critical role of IL-33 in the wound healing process was further confirmed using Il33−/− mice. Additionally, co-culture experiments were conducted to explore the effects of IL-33 on keratinocyte proliferation, collagen deposition and epithelialization. Results ADSC-Exos inhibited the expression of TNF-α and IL-6, induced M2 macrophage polarization, promoted collagen deposition and angiogenesis, and accelerated wound healing. RNA sequencing identified IL-33 as a key mediator in this process. In Il33−/− mice, impaired wound healing and decreased M2 macrophage polarization were observed. The co-culture experiments showed that IL-33 enhanced keratinocyte function through activation of the Wnt/β-catenin signaling pathway. These findings highlight the therapeutic potential of ADSC-Exos in wound healing by modulating IL-33. Conclusions ADSC-Exos promote wound healing by regulating macrophage polarization and enhancing IL-33 release which drives keratinocyte proliferation, collagen deposition and epithelialization via the Wnt/β-catenin
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04523-y
Current therapeutic interventions for intestinal pathologies, including anti-inflammatory agents, immunosuppressants, and surgical procedures, frequently incur substantial adverse effects, elevated recurrence rates, and suboptimal tissue regeneration. Cellular therapy has emerged as a paradigm-shifting strategy, capitalizing on regenerative potential and immunomodulatory properties. Mesenchymal stem cells (MSCs), distinguished by their potent immunoregulatory capacity and multipotent differentiation plasticity, have recently demonstrated remarkable therapeutic promise in inflammatory bowel disease (IBD), ischemia–reperfusion injury, oncological interventions, and radio-chemotherapy-induced complications. This systematic review critically evaluates MSC biological characteristics, clinical translation progress, and cutting-edge advancements in tissue engineering applications. Mechanistic insights into MSC-mediated intestinal repair are elucidated, with particular emphasis on emerging evidence suggesting MSC-derived exosomes may modulate ZBP1-associated H3K27 acetylation to attenuate intestinal epithelial apoptosis—a novel epigenetic regulatory axis for gastrointestinal restitution. Future translational trajectories and clinical implementation challenges are comprehensively discussed.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03898-8
Background Hepatic progenitor cells serve not only as the origin of combined hepatocellular cholangiocarcinoma (cHCC-CCA) but are also responsible for malignancy recurrence after surgical resection. Nucleophosmin 1 (NPM1) has been implicated in cancer metastasis and poor prognosis. This study aimed to determine the expression of NPM1 by hepatic progenitor cells in cHCC-CCA and the effects of targeting NPM1 on hepatic progenitor cells and BEL-7402 cells with characteristics of both progenitor cells and cHCC-CCA. Methods First, NPM1 was detected by RT‒PCR, western blotting, and double-immunofluorescence staining in cHCC-CCA tissues. NPM1 expression was subsequently analysed in rat hepatic progenitor cells cultured in vitro and in interleukin 6 (IL6)-treated cells. The effects and mechanism of NPM1 on hepatic progenitor cells were determined by knocking down NPM1 and performing RNA sequencing analysis. Finally, NSC348884, a small-molecule inhibitor that disrupts NPM1 dimer formation, was used to confirm the function of NPM1 in BEL-7402 cells. Results Both human hepatic progenitor cells in cHCC-CCA tissues and rat in vitro cultured hepatic progenitor cells highly expressed NPM1. IL6, a cytokine involved in the malignant transformation of hepatic progenitor cells, dose-dependently increased NPM1 and PCNA expression. Knocking down NPM1 reduced IL6R transcription (P < 0.0001) and inhibited the proliferation (P = 0.0065) of hepatic progenitor cells by suppressing the mTOR signalling pathway and activating the apoptosis pathway. Furthermore, knocking down NPM1 in hepatic progenitor cells resulted in more apoptotic cells (7.33 ± 0.09% vs. 3.76 ± 0.13%, P < 0.0001) but fewer apoptotic cells in the presence of NSC348884 (47.57 ± 0.49% vs. 63.40 ± 0.05%, P = 0.0008) than in the control cells, suggesting that low-NPM1-expressing cells are more resistant to NSC348884. In addition, NSC348884 induced the apoptosis of BEL-7402 cells with an IC50 of 2.77 μmol/L via the downregulation of the IL-6R and mTOR signalling pathways and inhibited the growth of BEL-7402 cells in a subcutaneous xenograft tumour model (P = 0.0457). Conclusions Targeting NPM1 inhibits proliferation and induces apoptosis in hepatic progenitor cells and BEL-7402 cells, thus serving as a potential therapy for cHCC-CCA.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03872-4
Collection of hematopoietic progenitor cell products [HPC(A)] is deferred if the donor is symptomatic and tests positive for Covid-19. However, donor questionnaires are subjective and may miss minimally symptomatic donors. Alternatively, myalgia associated with Covid-19 infection can be falsely dismissed as an adverse effect of granulocyte stimulating factor (Filgrastim) administered prior to product collection. The likelihood of donors with an underlying acute but minimally symptomatic infection undergoing successful product collection is significant. In these circumstances, it is less known whether Covid-19 infection results in product viremia or alters the clinical outcome of transplant. We aimed to evaluate the above question by studying a donor whose product was collected during acute Covid-19 infection. Aliquots of the product tested negative for SARS-CoV-2 RNA by reverse-transcriptase polymerase chain reaction assay (RT-PCR). Importantly, the donor received an autologous stem cell transplant using the product collected at the time of infection, and their case will be described in this report. We describe one of the very few reports of successful transplant of HPC(A) product collected during acute Covid-19 infection.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03718-z
Background Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem. Methods In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay. Results Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary. Conclusions The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn’t proliferate in the reconstituted ovary, this
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04092-6
Background Multi-lineage differentiation of mesenchymal adult stem cells (m-ASCs) is crucial for tissue regeneration and accompanied with metabolism reprogramming, among which dental-pulp-derived m-ASCs has obvious advantage of easy accessibility. Stem cell fate determination and differentiation are closely related to metabolism status in cell microenvironment, which could actively interact with epigenetic modification. In recent years, glutamine-α-ketoglutarate (αKG) axis was proved to be related to aging, tumorigenesis, osteogenesis etc., while its role in m-ASCs still lack adequate research evidence. Methods We employed metabolomic analysis to explore the change pattern of metabolites during dental-pulp-derived m-ASCs differentiation. A murine incisor clipping model was established to investigate the influence of αKG on dental tissue repairment. shRNA technique was used to knockdown the expression of related key enzyme-dehydrogenase 1(GLUD1). RNA-seq, m6A evaluation and MeRIP-qPCR were used to dig into the underlying epigenetic mechanism. Results Here we found that the glutamine-αKG axis displayed an increased tendency along with the osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, same as expression pattern of GLUD1. Further, the key metabolite αKG was found able to accelerate the repairment of clipped mice incisor and promote dentin formation. Exogenous DM-αKG was proved able to promote osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, while the inhibition of glutamine-derived αKG level via GLUD1 knockdown had the opposite effect. Under the circumstance of GLUD1 knockdown, extracellular matrix (ECM) function and PI3k-Akt signaling pathway was screened out to be widely involved in the process with insulin-like growth factor 2 (IGF2) participation via RNA-seq. Inhibition of glutamine-αKG axis may affect IGF2 translation efficiency via m6A methylation and can be significantly rescued by αKG supplementation.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03943-6
Although liver transplantation (LT) is an effective strategy for end-stage liver diseases, the shortage of donor organs and the immune rejection hinder its widespread implementation in clinical practice. Mesenchymal stem cells (MSCs) transplantation offers a promising approach for patients undergoing liver transplantation due to their immune regulatory capabilities, hepatic protection properties, and multidirectional differentiation potential. In this review, we summarize the potential applications of MSCs transplantation in various LT scenarios. MSCs transplantation has demonstrated effectiveness in alleviating hepatic ischemia-reperfusion injury, enhancing the viability of liver grafts, preventing acute graft-versus-host disease, and promoting liver regeneration in split LT therapy. We also discuss the clinical progress, and explore the immunomodulatory functions of MSCs in response to both adaptive and innate immune responses. Furthermore, we emphasize the interactions between MSCs and different immune cells, including T cells, B cells, plasma cells, natural killer cells, dendritic cells, Kupffer cells, and neutrophils, to provide new insights into the immunomodulatory properties of MSCs in adoptive cell therapy.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03882-2
Background Periodontal tissue loss is the main reason for tooth mobility and loss caused by periodontal disease. Dental follicle stem cells (DFSCs) have significant therapeutic potential in periodontal regeneration, which maybe mainly depends on their potent immunomodulatory capacity. Consequently, this study aims to elucidate the impact of implanted xenogenous DFSCs on innate immune responses during early and late stages in the periodontal defect repair period. Methods To trace and investigate the immunomodulation mechanisms of DFSCs in vivo, DFSCs were engineered (E-DFSCs) using lentiviral vectors expressing CD63-enhanced green fluorescent protein (CD63-EGFP) and β-Actin-mCherry protein (ACTB-mCherry) to exhibit green and red fluorescence. The biological characteristics and functions of E-DFSCs were verified by proliferation, differentiation, and co-culture experiments in vitro. In vivo, the periodontal regeneration capacity of E-DFSCs was detected by implantation of murine periodontal defect model, and the response of innate immune cells was detected at the 1st, 3rd, and 5th days (early stage) and 4th week (late stage) after implantation. Results In vitro assessments showed that E-DFSCs retain similar properties to their non-engineered counterparts but exhibit enhanced macrophage immunomodulation capability. In mice models, four-week micro-CT and histological evaluations indicated that E-DFSCs have equivalent efficiency to DFSCs in periodontal defect regeneration. At the early stage of repair in mice periodontal defect, fluorescence tracking showed that implanted E-DFSCs might primarily activate endogenous cells through direct contact and indirect actions, and most of these cells are myeloperoxidase-positive neutrophils. Additionally, compared with the control group, the neutrophilic infiltration and conversion of N2-type were significantly increased in the E-DFSC group. At the late stage of defect regeneration, more M2-type
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03938-3
Background: Despite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems. Objectives: This study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques. Methods: Human adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining. Results: Mitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group. Conclusions: This study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-023-03619-7
Background Beyond the observed alterations in cellular structure and mitochondria, the mechanisms linking rare genetic mutations to the development of heart failure in patients affected by desmin mutations remain unclear due in part, to the lack of relevant human cardiomyocyte models. Methods To shed light on the role of mitochondria in these mechanisms, we investigated cardiomyocytes derived from human induced pluripotent stem cells carrying the heterozygous DESE439K mutation that were either isolated from a patient or generated by gene editing. To increase physiological relevance, cardiomyocytes were either cultured on an anisotropic micropatterned surface to obtain elongated and aligned cardiomyocytes, or as a cardiac spheroid to create a micro-tissue. Moreover, when applicable, results from cardiomyocytes were confirmed with heart biopsies of suddenly died patient of the same family harboring DESE439K mutation, and post-mortem heart samples from five control healthy donors. Results The heterozygous DESE439K mutation leads to dramatic changes in the overall cytoarchitecture of cardiomyocytes, including cell size and morphology. Most importantly, mutant cardiomyocytes display altered mitochondrial architecture, mitochondrial respiratory capacity and metabolic activity reminiscent of defects observed in patient’s heart tissue. Finally, to challenge the pathological mechanism, we transferred normal mitochondria inside the mutant cardiomyocytes and demonstrated that this treatment was able to restore mitochondrial and contractile functions of cardiomyocytes. Conclusions This work highlights the deleterious effects of DESE439K mutation, demonstrates the crucial role of mitochondrial abnormalities in the pathophysiology of desmin-related cardiomyopathy, and opens up new potential therapeutic perspectives for this disease.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04021-7
Background This phase II randomized controlled trial tested whether the intracarotid arterial administration (ICAA) of autologous CD34+ cells to patients within 14±7 days after acute ischemic stroke (IS) could be safe and further improve short- and long-term outcomes. Methods Between January 2018 and March 2022, 28 consecutive patients were equally randomly allocated to the cell-treated group (CD34+ cells/3.0×107/patient) or the control group (receiving optimal medical therapy). CD34+ cells were transfused into the ipsilateral brain infarct zone of cell-treated patients via the ICAA in the catheterization room. Results The results demonstrated 100% safety and success rates for the procedure, and no long-term tumorigenesis was observed in cell-treated patients. In cell-treated patients, the angiogenesis capacity of circulating endothelial progenitor cells (EPCs)/Matrigel was significantly greater after treatment than before treatment with granulocyte colony-stimulating factor (all p<0.001). Blood samples from the right internal jugular vein of the cell-treated patients presented significantly greater levels of the stromal cell-derived factor 1α/EPC at 5, 10 and 30 min compared with 0 min (all p<0.005). The National Institute of Health Stroke Scale scores were similar upon presentation, but a greater response was observed by Days 30 and 90 in the cell-treated group than in the control group. Tc-99 m brain perfusion was significantly greater at 180 days in the cell-treated group than in the control group (p=0.046). The combined long-term end points (defined as death/recurrent stroke/or severe disability) were notably lower in the control group compared with the cell-treated group (14.3% vs. 50.0%, p=0.103). Conclusion Intracarotid transfusion of autologous CD34+ cells is safe and might improve long-term outcomes in patients with acute IS. Trial registration ISRCTN, ISRCTN15677760. Registered 23 April 2018- Retrospectively registered, https://doi.org/10.1186/ISRCTN15677760
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03741-0
Background Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and many other non-cardiomyocyte cells. Retinoic acid (RA) plays an important role in regulation of the spatiotemporal development of the embryonic heart. Methods CMs were derived from hiPSC (hi-PCS-CM) using different concentrations of RA (Control without RA, LRA with 0.05μM and HRA with 0.1 μM) between day 3-6 of the differentiation process. Engineered heart tissues (EHTs) were generated by assembling hiPSC-CM at high cell density in a low collagen hydrogel. Results In the HRA group, hiPSC-CMs exhibited highest expression of contractile proteins MYH6, MYH7 and cTnT. The expression of TBX5, NKX2.5 and CORIN, which are marker genes for left ventricular CMs, was also the highest in the HRA group. In terms of EHT, the HRA group displayed the highest contraction force, the lowest beating frequency, and the highest sensitivity to hypoxia and isoprenaline, which means it was functionally more similar to the left ventricle. RNAsequencing revealed that the heightened contractility of EHT within the HRA group can be attributed to the promotion of augmented extracellular matrix strength by RA. Conclusion By interfering with the differentiation process of hiPSC with a specific concentration of RA at a specific time, we were able to successfully induce CMs and EHTs with a phenotype similar to that of the left ventricle or right ventricle.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03654-y
Background Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) plays a pivotal role in inducing metabolic inflammation in diabetes. Additionally, the NOD1 ligand disrupts the equilibrium of bone marrow-derived hematopoietic stem/progenitor cells, a process that has immense significance in the development of diabetic retinopathy (DR). We hypothesized that NOD1 depletion impedes the advancement of DR by resolving bone marrow dysfunction. Methods We generated NOD1−/−-Akita double-mutant mice and chimeric mice with hematopoietic-specific NOD1 depletion to study the role of NOD1 in the bone marrow–retina axis. Results Elevated circulating NOD1 activators were observed in Akita mice after 6 months of diabetes. NOD1 depletion partially restored diabetes-induced structural changes and retinal electrical responses in NOD1−/−-Akita mice. Loss of NOD1 significantly ameliorated the progression of diabetic retinal vascular degeneration, as determined by acellular capillary quantification. The preventive effect of NOD1 depletion on DR is linked to bone marrow phenotype alterations, including a restored HSC pool and a shift in hematopoiesis toward myelopoiesis. We also generated chimeric mice with hematopoietic-specific NOD1 ablation, and the results further indicated that NOD1 had a protective effect against DR. Mechanistically, loss of hematopoietic NOD1 resulted in reduced bone marrow-derived macrophage infiltration and decreased CXCL1 and CXCL2 secretion within the retina, subsequently leading to diminished neutrophil chemoattraction and NETosis. Conclusions The results of our study unveil, for the first time, the critical role of NOD1 as a trigger for a hematopoietic imbalance toward myelopoiesis and local retinal inflammation, culminating in DR progression. Targeting NOD1 in bone marrow may be a potential strategy for the prevention and treatment of DR.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026076
In Arabidopsis, the PPR proteins EMB1006, EMB1270, and EMB976 are all essential for the splicing of plastid clpP1 intron 2 (clpP1.2), although each also targets other distinct RNAs. The precise mechanism underlying their co-ordinated action in clpP1.2 splicing remains unclear. In this study, RNA electrophoretic mobility shift assays, guided by PPR code prediction, confirm that EMB1006 specifically binds to a sequence near the 3′ end of clpP1 exon 2. Additionally, immunoprecipitation coupled with mass spectrometry reveals that EMB1006 forms a complex with EMB1270, EMB976, and CFM2. Direct interactions between EMB1006 and EMB1270 or CFM2 are further supported by yeast two-hybrid (Y2H) and semi-in vivo pull-down assays. However, no direct interactions between EMB976 and EMB1006, CFM2 or EMB1270 are detected by Y2H. Based on these findings and previous evidence that EMB1270 binds to clpP1 intron 2 and interacts with CFM2, we propose a model in which EMB1006 and EMB1270 bind to distinct sites on clpP1 pre-mRNA. Together with CFM2 and possible indirect association with EMB976, they assemble into a protein-RNA complex that facilitates the splicing of clpP1.2 in chloroplasts.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026054
The anti-inflammatory properties of the traditional herb Salvia miltiorrhiza Bunge are well-established, yet its precise mechanism of action in ulcerative colitis (UC) remains unclear. Herein, we evaluate the therapeutic potential of four major tanshinones–tanshinone IIA (Tan IIA), miltirone, neocryptotanshinone, and dihydrotanshinone I–in a murine dextran sulfate sodium (DSS)-induced colitis model. Our results show that tanshinones effectively alleviate disease severity, suppress systemic and local inflammation, and restore intestinal barrier integrity. Integrated multi-omics analysis reveals that the therapeutic efficacy originates from a comprehensive reprogramming of the gut microbiota-metabolite axis. Specifically, tanshinones reverse colitis-associated dysbiosis and rectify metabolic disturbances in linoleic acid metabolism, bile acid biosynthesis, and amino acid utilization. Correlation network analysis identifies key functional modules linking beneficial microbes (e.g., Akkermansia) to anti-inflammatory lipid mediators and associating pathobionts (e.g., Desulfovibrio) with disrupted bile acid metabolism. Notably, supplementation with Akkermansia muciniphila synergizes with Tan IIA to amplify barrier restoration and metabolic normalization. Our findings establish that tanshinones ameliorate UC through microbiota-driven metabolic reprogramming, wherein the restructured microbial community actively shapes a therapeutic metabolic output. This work elucidates a metabolite-mediated mechanism of action and positions tanshinones as promising microbiome-targeting therapeutics for inflammatory bowel disease.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025206
Anti-aging foods not only benefit elderly individuals but also drive the development of safe and effective natural drugs. Here, we report that the addition of total flavonoids of litchi seed (TFL) delays replicative senescence and stress-induced senescence. TFL alleviates the senescence-associated secretory phenotype (SASP) and reduces the degree of DNA damage caused by bleomycin (BLM). TFL also counteracts stress-induced pulmonary senescence and fibrosis. TFL reduces the protein level of p21 in mouse lung and alleviates pulmonary fibrosis. Transcriptome profiling further reveals that TFL plays a key role in its anti-aging mechanism by inhibiting the SASP. Mechanistically, TFL suppresses p65 protein expression, thereby inhibiting IL-1α and IL-1β and delaying cellular senescence. Gut microbiome analysis reveals that the abundance and functions of the mouse gut microbiome change after BLM exposure and that TFL treatment reverses these changes. Overall, we provide a theoretical basis for the future application of TFL as a potential anti-aging product.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025055
Platelets circulate in an inactive form in the body until they contact with defective areas of endothelial cells or encounter a clotting cascade [1]. Activated platelets release and express bioactive substances and acquire the ability to bind plasma fibrinogen. Abnormal activation of platelets is involved in atherosclerosis and thrombosis [2,3]. When platelets are stimulated and activated, phospholipase A2 is activated at the same time, which then cleaves membrane phospholipids and frees arachidonic acid (AA) [4]. The latter catalyzes thromboxane A2 (TXA2) via thromboxane synthetase [5], which is induced by the cyclooxygenase COX-1 to produce prostaglandins G2 and H2 [6]. TXA2 is highly unstable, with a half-life of only 30 s, and it is rapidly hydrolyzed to relatively stable thromboxane B2 (TXB2), which is then converted in the liver to 11-dehydrothromboxane B2 (11dH-TXB2), which has a longer half-life and is excreted in the urine [7]. Dehydrothromboxane B2 is the final stable metabolite of thromboxane A2, which is derived only from arachidonic acid metabolism and can represent thromboxane A2 level in the body [8]. Specifically, by inhibiting the action of COX-1, the most important enzyme in the process of arachidonic acid metabolism, aspirin inhibits the production of thromboxane A2, that is, the concentration of TXA2 affects the effect of aspirin on platelet aggregation. However, the half-life of TXA2 (including the metabolic intermediate TXB2) is too short to be accurately measured, so the detection of its metabolic end product 11dH-TXB2 can very accurately reflect the sensitivity of the body to aspirin [7]. The concentration of 11dH-TXB2 in the serum correlates well with the concentration of 11dH-TXB2 in the urine, so the determination of 11dH-TXB2 in the urine can more effectively reflect the production of TXA2 in vivo [8]. The 11dH-TXB2 concentration needs to be corrected with the urinary creatinine concentration to rule out the effects of the urine concentration and renal function, so random urine samples can be used for testing [6]. Aspirin can acetylate serine at the key site of cyclooxygenase and thus irreversibly inhibits the activity of COX-1, reduces the synthesis of TXA2, and blocks the production of TXA2 and its induced platelet aggregation. Low-dose aspirin (30–75 mg/day) can effectively inhibit 95% of COX-1 activity [7]. Since the production of TXA2 in serum is largely dependent on platelet COX-1 (a therapeutic target of aspirin), 11dH-TXB2 can be used as a monitor for aspirin-induced platelet inhibition [3]. Creatinine is a metabolic byproduct of muscle metabolism that is primarily excreted via glomerular filtration, and its level is indicative of renal function [9]. The 24-h creatinine clearance can also be used to determine the integrity of the sample or to correct the urine sample concentration with the creatinine ratio [10]. Currently, creatinine detection methods include the Jaffe method, enzymolysis spectrophotometry, HPLC, capillary electrophoresis, capillary zone electrophoresis, gas chromatography tandem mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) [11]. At present, there is no method for the simultaneous detection of 11dH-TXB2 and creatinine. When both analytes are needed, separate tests must be performed, increasing the workload and sample volume requirements. Thus, developing a method that enables the concurrent quantification of 11dH-TXB2 and creatinine in a single assay remains a critical challenge. The aim of this study was to provide a method for the simultaneous detection of 11dH-TXB2 and creatinine and to alleviate the problem that 11dH-TXB2 and creatinine cannot be simultaneously detected. By developing a standardized quantitative approach for measuring 11dHTXB2 and creatinine in human urine, this study aims to provide reliable concentration data, thereby facilitating further clinical research and methodology optimization.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025079
This is a corrigendum to the original article published in Acta Biochim Biophys Sin (Shanghai) 2021, 53(12): 1670–1680. In the original version, errors were found in Figure 2 and Figure 6. The correct figures are shown in this corrigendum. The authors apologize for the error.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024183
Traumatic brain injury (TBI) is a recognized global public health problem. However, there are still limitations in the available therapeutic approaches and a lack of clinically effective drugs. Therefore, an in-depth exploration of the secondary pathological mechanism of TBI and the identification of new effective drugs are urgently needed. Cannabidiol (CBD), a component derived from the cannabis plant, has potential therapeutic effects on neurological diseases and has received increasing attention. However, few reports on CBD intervention in TBI patients exist. Here, we use the Feeney free-fall method to establish a rat TBI model. CBD significantly improves neurological deficit scores, neuronal damage and blood-brain barrier permeability in rats and significantly inhibits the expressions of the brain injury markers S-100β and NSE. Mechanistically, CBD attenuates TBI-induced astrocyte activation, reduces inflammation, and attenuates the expressions of inflammatory prostaglandin system indicators. The use of TG6-10-1 (EP2 inhibitor) and H-89 (PKA inhibitor) indicates that CBD attenuates TBI-induced neurological damage via the PGE2-EP2-cAMP-PKA signaling pathway. Overall, this research provides a novel drug candidate for the treatment of clinical brain trauma.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025046
The cGAS-STING signaling pathway serves as a pivotal surveillance mechanism for cytosolic double-stranded DNA (dsDNA) detection in mammalian systems. While STING-mediated type I interferon production is crucial for host defense, sustained activation of this pathway contributes to autoimmune pathologies, including systemic lupus erythematosus (SLE). Maintaining immune homeostasis requires precise regulation of STING activity to prevent hyperactivation. Our study identifies TRIM21 as a novel positive regulator of cGAS-STING signaling in SLE pathogenesis. Our results demonstrate that TRIM21 overexpression stabilizes STING by suppressing autophagic degradation, whereas TRIM21 depletion accelerates this clearance process. Mechanistically, TRIM21 catalyzes the K63-linked polyubiquitylation of the selective autophagy receptor p62/SQSTM1, disrupting its interaction with STING. This post-translational modification prevents the sequestration of STING into autophagosomes, thereby stabilizing the adaptor protein and amplifying downstream type I interferon responses. Our findings reveal a previously unrecognized regulatory circuit in which TRIM21 orchestrates cross-talk between ubiquitin signaling and autophagy to control STING turnover. The TRIM21-p62 axis represents a potential therapeutic target for attenuating pathological interferon production in STING-dependent autoimmune disorders. This work advances our understanding of immune regulation by demonstrating how E3 ligase-mediated ubiquitin modifications modulate cargo recognition in selective autophagy pathways. The identified mechanism provides new insights into the molecular interplay between protein ubiquitylation and autophagic degradation in maintaining the innate immune balance, offering novel perspectives for developing targeted therapies against interferonopathies associated with cGAS-STING hyperactivity.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025008
The tumor suppressor p53, an indispensable nuclear transcription factor, plays a central role in orchestrating cellular responses when DNA damage occurs. In this study, we demonstrate that in the initial phases of DNA double-strand break (DSB) repair, p53 is rapidly recruited to sites of damage and the surrounding chromatin, where it enhances DSB repair efficiency. This enhancement occurs through the modulation of chromatin dynamics and the promotion of a more relaxed chromatin configuration, a process influenced by p53 in response to DSB-inducing factors such as etoposide, ultraviolet radiation, and nucleases. These results underscore the pivotal function of p53 as a rapid responder to DSBs, delineating a significant departure from its traditionally recognized role as a downstream transcriptional regulator in DNA damage repair processes. This study emphasizes that the direct engagement of p53 in DNA repair through chromatin structure regulation extends beyond its established involvement in UV irradiation-induced nucleotide excision repair (NER), demonstrating analogous mechanistic attributes in the context of DSB repair. This newly illuminated perspective enhances our understanding of the multifaceted roles of p53 in genome stability and integrity.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025212
Spatial biology aims to elucidate cellular organization, function, and interactions within native tissue contexts, offering key insights into both normal physiology and disease. Spatial proteomics complements this by enabling high-resolution mapping of protein localization and abundance, directly reflecting functional cellular states. Unlike transcriptomics, which infers potential activity, proteomics captures actual molecular functions, including post-translational modifications and dynamic interactions. However, in situ protein profiling poses significant challenges, as proteins cannot be directly sequenced or easily targeted via nucleic acid hybridization. Antibody-oligonucleotide conjugates (AOCs) address this limitation by converting protein recognition into a DNA-based readout, thereby enabling sensitive and scalable detection. In this review, we outline the core principles of AOC-based spatial proteomic technologies, including multiplexed protein analysis, in situ protein-protein interactions, and integration with other biomolecular data. We highlight their applications in decoding tissue complexity and disease pathology and examine key technical challenges that remain. Overall, AOCs offer distinct advantages, including DNA-mediated signal amplification, spatially resolved proteomic profiling, and compatibility with multi-omics approaches, positioning them as powerful platforms in the advancement of spatial biology.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025230
The diverse antibodies of adaptive immunity comprise an antibody repertoire that combats various pathogens. This repertoire is shaped by both intrinsic antibody gene diversification and extrinsic cellular selection. Conversely, an antibody repertoire contains multiple layers of immunological information, including the history of pathogen exposure. High-throughput sequencing-based antibody repertoire cloning approaches have revealed unexpected features of adaptive immunity. However, our understanding of antibody repertoire data is still in its infancy. In this review, we introduce the emerging concepts and discuss the application of deep learning approaches to understanding antibody repertoires. First, we introduce the definition and functional features of antibody clonotype. Next, we review the evolution of antibody clonotypes and discuss potential antibody repertoire-directed vaccination approaches. Lastly, we summarize the application of deep learning in predicting antibody binding, generating specific antibodies, and making immunologic diagnoses. Recently, artificial intelligence (AI) has made revolutionary progress in biology. Leveraging high-dimensional antibody repertoire information, deep learning models have the potential to transform our understanding of antibody repertoire.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025010
Hypersensitivity pneumonitis (HP), including pigeon breeder’s lung (PBL), often progresses from acute inflammation to fibrosis, impairing lung function and limiting targeted therapeutic strategies. Mechanistic studies on PBL progression are limited by the lack of preclinical animal models and a predominant focus on patient data. This study explores the immunopathological characteristics of all stages of PBL in mice and evaluates the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) during the non-fibrotic stage. PBL models are created in A/J mice through tracheal instillation of pigeon dropping extract (PDE) protein powder. Different doses (0.4 × 106, 0.8 × 106, and 1.6 × 106 cells per animal) and frequencies (1–2 times) are administered to the model. The immunopathological characteristics of PBL and the therapeutic effects of UC-MSCs are assessed using micro-CT, pulmonary function, histopathology, cell counts in BALF, HYP levels, inflammatory factor levels, immunohistochemistry, and fibrosis marker expression in lung tissues. The results show that PDE exposure consistently impairs pulmonary function and increases the levels of inflammation and fibrosis markers as the disease progresses. Model mice experience non-fibrotic stages (acute inflammation) from days 0–36, mild fibrosis from days 37–77, and severe fibrosis from day 78 onwards. UC-MSCs, particularly at the highest dose (1.6 × 106 cells), effectively treat non-fibrotic PBL by improving pulmonary function (lung ventilation area recovers) and reducing inflammation and fibrosis. This study successfully establishes PBL mouse models reflecting both the acute (inflammatory) and chronic (fibrotic) stages, and UC-MSCs have the potential to delay fibrosis, providing new therapeutic options for PBL and other inflammation-induced lung fibrotic diseases.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025130
Tumor radioresistance and severe toxicity make reirradiation for recurrent nasopharyngeal carcinoma (NPC) a significant clinical challenge. This study aims to investigate the ability of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib to sensitize recurrent NPC cells irradiated with photon or carbon ion (C-ion), and to explore the underlying mechanism of the synergistic promotion of cell death by olaparib and ionizing radiation. The results show that olaparib has significant X-ray and C-ion radiosensitization effects on recurrent NPC cells and the associated HK-RR photon-resistant model. Radiation, particularly C-ion exposure, induces a homologous recombination (HR)-deficient gene signature in HR-proficient NPC cells, potentially increasing their sensitivity to PARP inhibition. C-ion and X-ray irradiation induces similar modes of cell death, and multiple cell death pathways [including apoptosis, necrosis, ferroptosis, senescence, and autophagic cell death (ACD)] contribute to the cytotoxic effects of radiation combined with olaparib, with ACD being the dominant pathway. Both the pharmacological and genetic inhibition of autophagy significantly attenuate the radiosensitization effect of olaparib. In conclusion, olaparib effectively sensitizes recurrent NPC cells to both X-ray irradiation and C-ion irradiation, with autophagy playing a central role in mediating this effect.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024078
Neural tube defects (NTDs) are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous system anomalies during early development. Recent microRNA (miRNA) expression profiling studies have revealed that the dysregulation of several miRNAs plays an important role in retinoic acid (RA)-induced NTDs. However, the molecular functions of these miRNAs in NTDs remain largely unidentified. Here, we show that miR-10a-5p is significantly upregulated in RA-induced NTDs and results in reduced cell growth due to cell cycle arrest and dysregulation of cell differentiation. Moreover, the cell adhesion molecule L1-like (Chl1) is identified as a direct target of miR-10a-5p in neural stem cells (NSCs) in vitro, and its expression is reduced in RA-induced NTDs. siRNA-mediated knockdown of intracellular Chl1 affects cell proliferation and differentiation similar to those of miR-10a-5p overexpression, which further leads to the inhibition of the expressions of downstream ERK1/2 MAPK signaling pathway proteins. These cellular responses are abrogated by either increased expression of the direct target of miR-10a-5p (Chl1) or an ERK agonist such as honokiol. Overall, our study demonstrates that miR-10a-5p plays a major role in the process of NSC growth and differentiation by directly targeting Chl1, which in turn induces the downregulation of the ERK1/2 cascade, suggesting that miR-10a-5p and Chl1 are critical for NTD formation in the development of embryos.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024050
The interaction between bacteria and the host plays a vital role in the initiation and progression of systemic diseases, including gastrointestinal and oral diseases, due to the secretion of various virulence factors from these pathogens. GroEL, a potent virulence factor secreted by multiple oral pathogenic bacteria, is implicated in the damage of gingival epithelium, periodontal ligament, alveolar bone and other peripheral tissues. However, the underlying biomechanism is still largely unknown. In the present study, we verify that GroEL can trigger the activation of NLRP3 inflammasome and its downstream effector molecules, IL-1β and IL-18, in human periodontal ligament stem cells (hPDLSCs) and resultantly induce high activation of gelatinases (MMP-2 and MMP-9) to promote the degradation of extracellular matrix (ECM). GroEL-mediated activation of the NLRP3 inflammasome requires the participation of Toll-like receptors (TLR2 and TLR4). High upregulation of TLR2 and TLR4 induces the enhancement of NF-κB (p-p65) signaling and promotes its nuclear accumulation, thus activating the NLRP3 inflammasome. These results are verified in a rat model with direct injection of GroEL. Collectively, this study provides insight into the role of virulence factors in bacteria-induced host immune response and may also provide a new clue for the prevention of periodontitis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025213
Myocardial infarction (MI) causes irreversible cardiomyocyte loss, creating a need for cardiac repair therapies. The role of cell division cycle 5-like (CDC5L), a cell cycle regulator, in cardiac repair is unknown. This study aims to define the role of CDC5L in mitigating ischemia-reperfusion (I/R) injury by assessing its impact on cardiomyocyte proliferation and apoptosis and to determine the mechanism involving the FGF10-YAP axis. We model cardiac injury using in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) in neonatal mouse cardiomyocytes and in vivo I/R in adult mice. To investigate CDC5L function, we modulate its expression via adenoviral or AAV9-mediated overexpression or knockdown. Proliferation markers (EdU+, Ki67+, pH3+), apoptosis (TUNEL staining, Bax/Bcl-2 ratio), and cardiac function (echocardiography) are assessed. Through transcriptomic screening, we identify CDC5L downstream targets and validate their functional roles using FGF10 knockdown rescue assays. We find that CDC5L is upregulated in the post-I/R murine myocardium. Its overexpression enhances cardiomyocyte proliferation, preserves cardiac function, reduces apoptosis, and diminishes infarct size. Transcriptomic analysis identifies FGF10 as a key downstream effector, and we confirm that CDC5L upregulates FGF10 expression. Notably, FGF10 knockdown reverses the proliferative and anti-apoptotic effects of CDC5L. Moreover, the CDC5L-mediated reduction in YAP phosphorylation is also dependent on FGF10, as this effect is abolished upon FGF10 knockdown. In conclusion, CDC5L attenuates cardiac I/R injury by promoting cardiomyocyte proliferation and inhibiting apoptosis through the FGF10-YAP pathway. This CDC5L-FGF10-YAP axis represents a promising therapeutic target to improve myocardial regeneration and recovery after myocardial infarction.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025090
Ovarian aging is a natural process characterized by a decline in both the quantity and quality of oocytes, which subsequently leads to diminished fertility, particularly in women over the age of 35. Given the societal trend toward postponing childbirth, it is imperative to understand the molecular mechanisms that underpin ovarian aging to address infertility issues. Melatonin (MT) is recognized for its therapeutic potential in mitigating ovarian aging; however, the specific epigenetic mechanisms involved, particularly concerning m6A methylation, remain inadequately defined. Our investigation demonstrates that MT mitigates ovarian aging in murine models, significantly decreasing m6A methylation levels. In vitro analyses of ovarian granulosa (KGN) cells reveals a marked increase in YTHDF2 expression, with differentially methylated genes being notably enriched in the polyubiquitination pathway. Further examination shows that YTHDF2 enhances the expression of the E3 ligase UBE3C by modulating the m6A methylation of UBE3C mRNA, thereby reducing the expression of the P53 senescence factor and alleviating the effects of ovarian aging.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024060
Medial arterial calcification (MAC) accompanying chronic kidney disease (CKD) leads to increased vessel wall stiffness, myocardial ischemia, heart failure, and increased cardiovascular morbidity and mortality. Unfortunately, there are currently no drugs available to treat MAC. The natural polyphenol epigallocatechin-3-gallate (EGCG) has been demonstrated to protect against cardiovascular disease; however, whether EGCG supplementation inhibits MAC in CKD remains unclear. In this study, we utilize a CKD-associated MAC model to investigate the effects of EGCG on vascular calcification and elucidate the underlying mechanisms involved. Our findings demonstrate that EGCG treatment significantly reduces calcium phosphate deposition and osteogenic differentiation of VSMCs in vivo and in vitro in a dose-dependent manner. In addition, through RNA sequencing (RNA-seq) analysis, we show a significant activation of the transcription factor JunB both in CKD mouse arteries and in osteoblast-like VSMCs. Notably, EGCG effectively suppresses CKD-associated MAC by inhibiting the activity of JunB. In addition, overexpression of JunB can abolish while knockdown of JunB can enhance the inhibitory effect of EGCG on the osteogenic differentiation of VSMCs. Furthermore, EGCG supplementation inhibits MAC in CKD via modulation of the JunB-dependent Ras/Raf/MEK/ERK signaling pathway. In conclusion, our study highlights the potential therapeutic value of EGCG for managing CKD-associated MAC, as it mitigates this pathological process through targeted inactivation of JunB.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024192
Clitoria ternatea L. flowers are used as traditional herbal medicines and are known for their advanced pharmacological activities. Flavonoids and anthocyanins reportedly contribute to the therapeutic properties of C. ternatea flowers; however, their potential anti-bladder cancer effects and molecular mechanisms remain unknown. In this study, flavonoid- and anthocyanin-rich samples from C. ternatea flowers (DDH) are prepared via macroporous resin-based extraction coupled with an efficient and reliable two-dimensional UPLC-DAD-MS/MS method. In vitro and in vivo studies reveal that DDH can inhibit bladder cancer cell growth and enhance the anti-bladder cancer activity of cisplatin. RNA-seq combined with KEGG analysis reveals that fatty acid synthesis is closely related to the anti-bladder cancer effect of DDH. Furthermore, DDH dose-dependently reduces cellular fatty acid levels in bladder cancer cells, and the addition of fatty acids significantly mitigates DDH-induced cell growth inhibition. Subsequent findings reveal that DDH downregulates sterol regulatory element-binding protein 1 (SREBP1), a key transcriptional regulator of de novo fatty acid synthesis in cancer cells, and its downstream targets (FASN, SCD1, and ACC). Additionally, this study demonstrates that gallic acid not only enhances the stability of DDH but also synergistically potentiates its anti-bladder cancer activity. Our study suggests that targeting the SREBP1 pathway is an effective strategy in bladder cancer therapy, and the ability of DDH to induce cell death by inhibiting the SREBP1 pathway and its good tolerance in mice make it a promising strategy for preventing and treating bladder cancer.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025012
Pyroptosis is a regulated inflammatory cell death process that plays an essential role in various diseases. This study investigates the role of proline/serine-rich coiled-coil protein 1 (PSRC1) in pyroptosis and inflammation in macrophages. This study reports that PSRC1 expression is decreased in pyroptotic macrophages and that knockout of PSRC1 exacerbates pyroptosis and inflammation. PSRC1 overexpression alleviates pyroptosis and inflammation in macrophages. RNA-seq analysis reveals that PSRC1 regulates the expression of genes involved in the extracellular matrix (ECM). Specifically, PSRC1 downregulates the expression of periostin (POSTN), an ECM component. Knockdown of POSTN suppresses macrophage pyroptosis mediated by low expression of PSRC1. These findings suggest that PSRC1 can alleviate pyroptosis and inflammation in bone marrow-derived macrophages (BMDMs) by regulating the ECM and negatively regulating POSTN. This study provides insights into the role of PSRC1 in macrophage pyroptosis and identifies a potential target for the treatment of inflammatory diseases. Further research is needed to confirm these findings in vivo and in various disease models.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025156
CD19-directed chimeric antigen receptor T (CAR-T) cell therapy is promising for treating relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), yet its long-term efficacy remains limited by CAR-T-cell exhaustion. Given the broad immunomodulatory activities of vitamin D, we investigate whether its active form, 1α,25(OH)2D3, enhances CAR-T-cell functionality and improves therapeutic outcomes. We demonstrate that 1α,25(OH)2D3 treatment significantly mitigates exhaustion and enhances the antitumor activity of CD19 CAR-T cells derived from both healthy donors and DLBCL patients, which is further validated in xenograft mouse models. Mechanistically, we show that 1α,25(OH)2D3 upregulates the expression of the vitamin D receptor (VDR), promoting transcriptional reprogramming associated with memory-like differentiation and downregulation of exhaustion-related genes, thereby reshaping the functional heterogeneity of CAR-T cells under tumor stimulation. Our study highlights 1α,25(OH)2D3 supplementation as a safe and accessible approach to mitigate terminal differentiation and exhaustion of CAR-T cells, offering a promising strategy to enhance the clinical efficacy of CAR-T therapy in patients with R/R DLBCL.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025015
Graphene and its derivatives exhibit excellent electrical and mechanical properties, including a high specific surface area, excellent electron mobility, and good biocompatibility, which make them ideal materials for fabricating biosensor devices. Nevertheless, sensors based on pure graphene sensors still have certain limitations. For example, the number of dangling chemical bonds on the graphene surface is insufficient, which restricts the chemisorption of target molecules on the graphene surface. Additionally, graphene tends to stack and self-polymerize due to the presence of strong π-π interactions, van der Waals forces, and high surface energy, which leads to limitations in its semiconductor applications. The incorporation of other nanomaterials (e.g., metals, metal oxides, and conductive polymers) into graphene sheets has been demonstrated to prevent graphene agglomeration and improve the nanostructure. Conductive polymers have been the subject of considerable interest within the context of electronic device manufacturing and the development of electrochemical sensors. This is due to a number of factors, including their low cost, simple preparation, high electrical conductivity, and high compatibility with modern electronic devices. Polypyrrole (PPY), a widely used conductive polymer, has attracted attention, particularly in electrode modification. PPY exhibits excellent electrical conductivity, redox reversibility, biocompatibility, and environmental stability while also offering low production costs, making it an attractive option for use as a conductive polymer. Concurrently, the distinctive structural characteristics of graphene and its oxides render them prospective conductive fillers for conductive polymers. Consequently, the incorporation of graphene into polymers can compensate for their inherent limitations and enhance the long-term stability of sensing materials. The combination of graphene and conducting polymers represents a powerful means of preparing modified electrodes with good electrochemical properties, which have been successfully applied to the electrochemical detection of various biomolecules. For example, Oliveira et al. developed an electrochemical gene sensor based on PPY and graphene quantum dots for the detection of the PML/RARα fusion gene in childhood acute promyelocytic leukemia. As a graphene derivative, reduced graphene oxide (rGO) is similar to graphene in numerous aspects, including favourable electrical conductivity, flexibility, low cytotoxicity, hydrophilicity, a substantial surface-area-to-volume ratio, and elevated chemical resistance. These attributes render rGO an exemplary matrix for nanocomposites. Owing to the presence of hydrophilic and reactive functional groups, rGO is ideal for use in biosensors. The hydrophilic nature of rGO is instrumental in the assembly of biosensors, enabling the fabrication of sensing platforms through techniques such as drop-casting, spin-coating, ink-jet printing, and processing of electrode materials. In the present study, a “sandwich” DNA hybridisation strategy was employed to construct an electrochemical DNA sensor based on PPY-rGO composite nanomaterials. PPY-rGO nanocomplexes were initially prepared by electrochemical deposition and subsequently modified on the surface of a screen-printed carbon electrode (SPCE) to increase the conductivity of the electrode, with SARS-CoV-2 serving as the target. The PPY-rGO nanocomplexes possess a substantial specific surface area and excellent conductivity, in addition to providing many attachment sites for the subsequent electrodeposition of AuNPs by cyclic voltammetry (CV). This enables the immobilization of a greater number of single-stranded DNA (ssDNA) probes, thereby enhancing the sensitivity and specificity of the sensor for the detection of target molecules. To further improve the specificity of detection, two DNA probes were designed on the basis of a sandwich hybridization strategy. One is a specific capture DNA (CDNA) with a sulfhydryl tag, and the other is a signal DNA (SDNA) with a biotin moiety, which can bind to horseradish peroxidase-streptavidin biofunctionalized gold nanoparticles (SA-HRP-AuNPs). Hybridization of the CDNA, target DNA (tDNA), and SDNA on the electrode surface formed a sandwich structure, whereby the SA-HRP-AuNPs bound to the biotin moiety. The detection of tDNA sequences was achieved via differential pulse voltammetry (DPV), which measures the current change of the sensor in hydrogen peroxide (H2O2) and hydroquinone (HQ) as the solvent electrochemical test solution. Electrochemical characterization and sensor performance testing were performed via a convenient electrochemical workstation and PSTrace software from PalmSens (Houten, Netherlands). SPCE electrodes were
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024216
The persistent global burden of hepatitis B virus (HBV) infection has prompted ongoing investigations into host determinants of viral control. In this study, we investigate the regulatory influence of the host gene cleavage stimulation factor subunit 2 (CSTF2) on HBV replication dynamics. We demonstrate differential CSTF2 expression across the spectrum of HBV infection phases, with upregulated expression noted during the immune-reactive and inactive carrier states compared with the immune-tolerant phase. Notably, dose-responsive attenuation of HBV DNA, as well as surface and core protein levels, is observed subsequent to CSTF2 overexpression, whereas HBV RNA levels remain unaffected. Upon HBV transfection, a notable alteration in CSTF2 subcellular localization is discerned, suggesting active relocalization to the cytoplasm, potentially mediated through interaction with the HBV posttranscriptional regulatory element (PRE). This interaction appears to impede the nuclear export of HBV RNA. Additionally, distinct antiviral efficacies are attributed to the functional domains of the CSTF2 protein, indicating a multifaceted host defense mechanism. These insights increase the understanding of host-virus interplay and identify CSTF2 as a candidate for antiviral therapeutic strategies.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024181
MicroRNAs (miRNAs) have emerged as essential regulators that play important roles in the development of multiple systems. Recent studies have identified significant roles for miRNAs in the progression of cardiac hypertrophy. This study aims to investigate the effects of miR-133b-3p on angiotensin II (Ang II)-induced cardiac hypertrophy and apoptosis, as well as explore its underlying mechanisms. Our experimental results reveal that miR-133b-3p expression is significantly decreased in both animal and cell models of cardiac hypertrophy induced by Ang II. Overexpression of miR-133b-3p reverses the hypertrophic manifestations and apoptosis induced by Ang II. Through bioinformatics analysis and dual-luciferase reporter assays, CDIP1 (cell death inducing p53 target 1) is identified as a direct target of miR-133b-3p, and the overexpression of miR-133b-3p reduces CDIP1 expression. Additionally, CDIP1 silencing suppresses cardiomyocyte hypertrophy and apoptosis induced by Ang II. In summary, these results suggest that miR-133b-3p may serve as a potential diagnostic marker for cardiac hypertrophy and that the upregulation of miR-133b-3p inhibits cardiac hypertrophy by targeting CDIP1.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025083
The urea cycle occurs mainly in the liver and undergoes changes during hepatocarcinogenesis. Argininosuccinate synthase 1 (ASS1) is a key enzyme in the urea cycle and is expressed at low levels in certain cancers. LM2I, a specific activator of ASS1, exhibits significant antitumor activity. However, the antitumor mechanism of LM2I in liver cancer remains unclear. In this study, we find that LM2I is more effective for liver cancer cells with low ASS1 expression. The results of the IP-LC/MS experiments reveal that ASS1 interacts with CAD. The expressions of ASS1 and CAD in liver cancer tissues and cells are negatively correlated. LM2I promotes the ubiquitination of CAD protein through ASS1. LM2I inhibits the proliferation of liver cancer cells in vivo and in vitro. However, its efficacy is weak in liver cancer cells stably overexpressing CAD. The H&E staining results reveal that LM2I has no toxicity in mice. In terms of metabolism, LM2I increases the urea content and decreases the pyrimidine content in liver cancer cells. Overexpression of CAD can reduce the inhibitory effect of LM2I on pyrimidine. Pyrimidine supplementation facilitates the proliferation of liver cancer cells, particularly when they are treated with LM2I. In summary, ASS1 interacts with CAD, and LM2I enhances CAD degradation through the activation of ASS1, consequently inhibiting pyrimidine synthesis and the progression of liver cancer.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025101
Abnormal proliferation and migration of endothelial cells are key contributors to tumor angiogenesis. Recent studies have shown that the crucial role of E3 ubiquitin ligase neuronal precursor cell expression developmentally downregulated 4-like (NEDD4L) in tumorigenesis. However, the precise mechanisms by which NEDD4L functions in endothelial cells remain unclear. In this study, we investigate the mechanisms by which NEDD4L influences the function of human umbilical vein endothelial cells (HUVECs) and its effect on tumor angiogenesis. Our results show that NEDD4L overexpression in HUVECs suppresses both cell proliferation and migration. Additionally, we find that the autophagic activity in NEDD4L-overexpressing cells is increased. Proteomic profiling and ubiquitination assays reveal that NEDD4L interacts with eEF1A1, promoting K48-linked ubiquitination-mediated degradation of eEF1A1. This post-translational modification is a key step in the NEDD4L-mediated regulation of autophagy and cellular function. Moreover, we find that loss of endothelial NEDD4L significantly enhances tumor growth and promotes angiogenesis in vivo. Overall, NEDD4L plays a crucial role in inhibiting tumor angiogenesis by regulating eEF1A1 ubiquitination and degradation, providing new insights into the NEDD4L-eEF1A1 axis and its potential as a therapeutic target.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024122
The main protease (Mpro) of coronaviruses plays a key role in viral replication, thus serving as a hot target for drug design. PF-00835231 is a promising inhibitor of SARS-CoV-2 Mpro. Here, we report the inhibitory potency of PF-00835231 against SARS-CoV-2 Mpro and seven Mpro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) from SARS-CoV-2 variants. The results confirm that PF-00835231 has broad-spectrum inhibition against various coronaviral Mpros. In addition, the crystal structures of SARS-CoV-2 Mpro, SARS-CoV Mpro, MERS-CoV Mpro, and seven SARS-CoV-2 Mpro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) in complex with PF-00835231 are solved. A detailed analysis of these structures reveals key determinants essential for inhibition and elucidates the binding modes of different coronaviral Mpros. Given the importance of the main protease for the treatment of coronaviral infection, structural insights into Mpro inhibition by PF-00835231 can accelerate the design of novel antivirals with broad-spectrum efficacy against different human coronaviruses.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023259
The most frequent primary brain tumor in adults is glioma, yet no effective curative treatments are currently available. Our previous study demonstrated the enhancing effects of JARID2 on glioma sensitivity to TMZ treatment. In this study, miR-155 is predicted to target JARID2. miR-155 is overexpressed in clinical glioma specimens and cell lines. miR-155 overexpression in glioma cells enhances cell viability and represses cell apoptosis. Through targeting, miR-155 inhibits JARID2 expression. miR-155 inhibition inhibits glioma cell viability and enhances cell apoptosis, whereas JARID2 knockdown enhances cell viability and inhibits cell apoptosis; JARID2 knockdown partially reverses miR-155 inhibition effects on glioma phenotypes. miR-155 inhibition reduces but knockdown of JARID2 promotes the tumor formation ability of glioma cells in vivo. Valproic acid (VPA) upregulates JARID2 expression, inhibits glioma cell viability and enhances cell apoptosis. VPA downregulates the expression level of miR-155 by increasing the methylation level of the miR-155 promoter, suggesting that the miR-155/JARID2 axis is implicated in VPA inhibition of glioma cell viability and enhancement of glioma cell apoptosis. This study demonstrates a new mechanism of VPA treatment of gliomas by affecting the miR-155/JARID2 axis, which could be regarded as a new strategy for the prevention and treatment of glioma.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024074
Alcoholic liver disease (ALD) poses a significant health challenge, so comprehensive research efforts to improve our understanding and treatment strategies are needed. However, the development of effective treatments is hindered by the limitation of existing liver disease models. Liver organoids, characterized by their cellular complexity and three-dimensional (3D) tissue structure closely resembling the human liver, hold promise as ideal models for liver disease research. In this study, we use a meticulously designed protocol involving the differentiation of human induced pluripotent stem cells (hiPSCs) into liver organoids. This process incorporates a precise combination of cytokines and small molecule compounds within a 3D culture system to guide the differentiation process. Subsequently, these differentiated liver organoids are subject to ethanol treatment to induce ALD, thus establishing a disease model. A rigorous assessment through a series of experiments reveals that this model partially recapitulates key pathological features observed in clinical ALD, including cellular mitochondrial damage, elevated cellular reactive oxygen species (ROS) levels, fatty liver, and hepatocyte necrosis. In addition, this model offers potential use in screening drugs for ALD treatment. Overall, the liver organoid model of ALD, which is derived from hiPSC differentiation, has emerged as an invaluable platform for advancing our understanding and management of ALD in clinical settings.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024150
Atherosclerosis (AS), a chronic inflammatory disease involving the large and middle arteries, is characterized by inflammation, abnormal deposition of lipids, and other pathological events. Endothelial cell injury, the migration and proliferation of vascular smooth muscle cells, and the inflammatory polarization of macrophages play crucial roles in the formation and progression of atherosclerotic plaques. The renin–angiotensin system (RAS), an essential regulator of the inflammatory response, is closely correlated with atherosclerotic plaque formation. Targeting the components of the RAS could be a promising therapeutic strategy for AS. (Pro)renin receptor (PRR), a single transmembrane protein, works as a key regulator of the local RAS with nearly equal affinity to bind to renin and (pro)renin and plays essential roles in cardiovascular homeostasis by targeting multiple RAS-dependent and RAS-independent intracellular signals in cardiovascular cells. sPRR, a soluble form of PRR, is generated by proteases (Furin, a disintegrin and metalloproteinase 19, site-1-protease, or an unknown convertase)-mediated cleavage of the full-length PRR and is released into extracellular spaces, including the plasma and urine, where it participates in various physio-pathological processes. An increasing number of studies have demonstrated an increase in circulating sPRR levels in patients and animals with various cardiovascular diseases, including hypertension and heart failure, which may be promising indicators of these cardiovascular diseases. Amari et al. reported that serum sPRR levels were significantly greater in hemodialysis patients with an ankle–brachial index (ABI) < 0.9 (an indicator of severe AS or obstruction of lower limb arteries) than in patients with an ABI ≥0.9. They reported a negative correlation between serum sPRR levels and ABI independent of other atherogenic risk factors, including age and hemoglobin A1c, suggesting an association between serum sPRR levels and severe AS of the lower limbs. Thus, increased serum sPRR levels may be a marker for AS progression. However, the clinical significance of the sPRR in patients with AS remains unclear. To further determine the association between plasma sPRR levels and the severity of AS, we prospectively enrolled 236 participants in the present study, including 63 subjects with non-AS (n = 63, 58.8 ± 11.7 years) and 173 with AS (n = 173, 67.1 ± 11.0 years, P < 0.001 vs the non-AS group). The diagnosis of subclinical atherosclerosis was established after the carotid intima–media thickness and plaque area were evaluated via bilateral carotid ultrasonography. Patients with heart diseases (rheumatic heart disease, valvular heart disease, and cardiomyopathy), hepatic failure, chronic kidney disease, hyperthyroidism, chronic inflammatory disorders, malignancy, or pulmonary embolism were excluded. The baseline clinical characteristics are shown in Supplementary Table S1. Although plasma brain natriuretic peptide, urea nitrogen, and triglyceride levels were slightly higher in the AS group than in the non-AS group, there were no significant differences in sex, body mass index, comorbidities, blood pressure, parameters reflecting cardiac function, and plasma creatine, uric acid, low-density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), and total cholesterol between the two groups. The ApoE–/– mice were fed with a high-fat diet (HFD) for 16 weeks to establish an atherosclerotic mouse model successfully, which was determined by Oil-red-O staining of the full-length aorta and the aortic root as well as H&E staining of the aortic root (Supplementary Figure S1). The studies involving human participants were reviewed and approved by the Affiliated Hospital of Jiangxi University of Chinese Medicine (JZFYLL20230208002). The patients/participants provided written informed consent to participate in this study. The studies involving animals were reviewed and approved by the Animal Care and Use Committee, which approved the animal protocols at Jiangxi University of Chinese Medicine (No. JZLLSC20230254). The levels of plasma sPRR in AS patients were significantly higher than those in the non-AS groups (15.9 ± 6.9 vs 11.5 ± 4.0 ng/mL, P < 0.001, Figure 1A). After HFD feeding for 16 weeks, the levels of plasma sPRR in ApoE–/– mice were also significantly greater than those in ApoE–/– mice fed with a normal diet (24.1 ± 8.6 vs 10.3 ± 3.1 ng/mL, P < 0.001; Figure 2A). Thus, plasma sPRR levels are significantly elevated under atherosclerotic
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024137
Immunoglobulin G (IgG) is an important serum glycoprotein and a major component of antibodies. Glycans on IgG affect the binding of IgG to the Fc receptor or complement C1q, which in turn affects the biological activity and biological function of IgG. Altered glycosylation patterns on IgG emerge as important biomarkers in the aging process and age-related diseases. Key aging-related alterations observed in IgG glycosylation include reductions in galactosylation and sialylation, alongside increases in agalactosylation, and bisecting GlcNAc. Understanding the role of IgG glycosylation in aging-related diseases offers insights into disease mechanisms and provides opportunities for the development of diagnostic and therapeutic strategies. This review summarizes five aspects of IgG: an overview of IgG, IgG glycosylation, IgG glycosylation with inflammation mediation, IgG glycan changes with normal aging, as well as the relevance of IgG glycan changes to aging-related diseases. This review provides a reference for further investigation of the regulatory mechanisms of IgG glycosylation in aging-related diseases, as well as for evaluating the potential of IgG glycosylation changes as markers of aging and aging-related diseases.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024145
In eukaryotic cells, gene expression begins with transcription in the nucleus, followed by the maturation of messenger RNAs (mRNAs). These mRNA molecules are then exported to the cytoplasm through the nuclear pore complex (NPC), a process that serves as a critical regulatory phase of gene expression. The export of mRNA is intricately linked to precursor mRNA (pre-mRNA) processing, ensuring that only properly processed mRNA reaches the cytoplasm. This coordination is essential, as recent studies have revealed that mRNA export factors not only assist in transport but also influence upstream processing steps, adding a layer of complexity to gene regulation. Furthermore, the export process competes with RNA processing and degradation pathways, maintaining a delicate balance vital for accurate gene expression. While these mechanisms are generally conserved across eukaryotes, significant differences exist between yeast and higher eukaryotic cells, particularly due to the more genome complexity of the latter. This review delves into the current research on mRNA export in higher eukaryotic cells, focusing on its role in the broader context of gene expression regulation and highlighting how it interacts with other gene expression processes to ensure precise and efficient gene functionality in complex organisms.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024207
Liver fibrosis is a critical stage in the progression of various chronic liver diseases to cirrhosis and liver cancer. Early inhibition of liver fibrosis is crucial for the treatment of liver disease. Hepatectomy, a common treatment for liver-related diseases, promotes liver regeneration. However, in the context of liver fibrosis, liver regeneration is hindered. Many studies have shown that mesenchymal stem cells (MSCs) can promote liver regeneration after partial hepatectomy (PH). However, there are few reports on the impact of MSC therapy on liver regeneration post-PH in the context of hepatic fibrosis. The objective of this study is to examine the impact of MSCs on liver regeneration following PH in the fibrotic liver and uncover the related molecular mechanisms. This study reveals that MSC therapy significantly enhances liver function and mitigates liver inflammation after PH in the context of hepatic fibrosis. MSCs also significantly promote liver regeneration and alleviate liver fibrosis. In addition, this study identifies the role of MSCs in promoting liver regeneration and alleviating liver fibrosis via the activation of Wnt/β-catenin signaling. The combination of MSCs with hepatectomy may offer a novel approach for the treatment of liver fibrotic diseases.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024144
Three-dimensional (3D) reconstruction serves as a crucial instrument for the analysis of biological structures. In particular, a comprehensive and accurate 3D ultrastructural examination of rat sperm is vital for understanding and diagnosing male fertility issues and the underlying causes of infertility. In this study, we utilize the automated tape-collecting ultramicrotome scanning electron microscopy (ATUM-SEM) imaging technique, which is a highly effective method for 3D cellular ultrastructural analysis. Our findings reveal that during spermiogenesis, the volume of the nucleus significantly decreases, shrinking to just 10% of its original size. The acrosomal vesicles derived from the Golgi apparatus converge and elongate along the spermatid nucleus. These vesicles then attach to the nucleus via a cap-like structure, thereby defining the head side of the spermatozoa. In the initial stages of spermiogenesis, the mitochondria in spermatids are distributed beneath the cell membrane. As the process progresses, these mitochondria gradually migrate to the sperm tail, where they form the mitochondrial sheath. This sheath plays a crucial role in providing the energy required for the movement of the sperm. In addition, we reconstruct the mRNA-stroring structure-chromatoid body in sperm cells, which are cloud-like or net-like structures in the cytoplasm. The precise and comprehensive nature of 3D ultrastructural examination allows for a deeper understanding of the morphological process of spermiogenesis, thereby contributing to our knowledge of male fertility and the causes of infertility. Our research has significantly advanced the understanding of the 3D ultrastructure of sperm more comprehensively than ever before.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024028
Bronchial thermoplasty (BT), an effective treatment for severe asthma, requires heat to reach the airway to reduce the mass of airway smooth muscle cells (ASMCs). Autophagy is involved in the pathological process of airway remodeling in patients with asthma. However, it remains unclear whether autophagy participates in controlling airway remodeling induced by BT. In this study, we aim to elucidate the autophagy-mediated molecular mechanisms in BT. Our study reveal that the number of autophagosomes and the level of alpha-smooth muscle actin (α-SMA) fluorescence are significantly decreased in airway biopsy tissues after BT. As the temperature increased, BT causes a decrease in cell proliferation and a concomitant increase in the apoptosis of human airway smooth muscle cells (HASMCs). Furthermore, increase in temperature significantly downregulates cellular autophagy, autophagosome accumulation, the LC3II/LC3I ratio, and Beclin-1 expression, upregulates p62 expression, and inhibits the AMPK/mTOR pathway. Furthermore, cotreatment with AICAR (an AMPK agonist) or RAPA (an mTOR antagonist) abolishes the inhibition of autophagy and attenuates the increase in the apoptosis rate of HASMCs induced by the thermal effect. Therefore, we conclude that BT decreases airway remodeling by blocking autophagy induced by the AMPK/mTOR signaling pathway in HASMCs.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024015
Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database. Breast cancer-related genes are obtained from the GeneCards database. Major targets and pathways related to SYF treatment in breast cancer are identified by analyzing the above data. By conducting molecular docking analysis, we find that the active ingredients quercetin and luteolin bind well to the key targets KDR1, PPARG, SOD1, and VCAM1. In vitro experiments verify that SYF can reduce the proliferation, migration, and invasion ability of TNBC cells. Using a TNBC xenograft mouse model, we show that SYF could delay tumor growth and effectively inhibit the occurrence of breast cancer lung metastasis in vivo. PPARG, SOD1, KDR1, and VCAM1 are all regulated by SYF and may play important roles in SYF-mediated inhibition of TNBC recurrence and metastasis.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024016
Atherosclerosis (AS), the main contributor to acute cardiovascular events, such as myocardial infarction and ischemic stroke, is characterized by necrotic core formation and plaque instability induced by cell death. The mechanisms of cell death in AS have recently been identified and elucidated. Ferroptosis, a novel iron-dependent form of cell death, has been proven to participate in atherosclerotic progression by increasing endothelial reactive oxygen species (ROS) levels and lipid peroxidation. Furthermore, accumulated intracellular iron activates various signaling pathways or risk factors for AS, such as abnormal lipid metabolism, oxidative stress, and inflammation, which can eventually lead to the disordered function of macrophages, vascular smooth muscle cells, and vascular endothelial cells. However, the molecular pathways through which ferroptosis affects AS development and progression are not entirely understood. This review systematically summarizes the interactions between AS and ferroptosis and provides a feasible approach for inhibiting AS progression from the perspective of ferroptosis.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024109
Lung adenocarcinoma (LUAD) remains a predominant cause of cancer-related mortality globally, underscoring the urgency for targeted therapeutic strategies. The specific role and impact of the SEC61 translocon gamma subunit (SEC61G) in LUAD progression and metastasis remain largely unexplored. In this study, we use a multifaceted approach, combining bioinformatics analysis with experimental validation, to elucidate the pivotal role of SEC61G and its associated molecular mechanisms in LUAD. Our integrated analyses reveal a significant positive correlation between SEC61G expression and the glycolytic activity of LUAD, as evidenced by increased fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT scans. Further investigations show the potential influence of SEC61G on metabolic reprogramming, which contributes to the immunosuppressive tumor microenvironment (TME). Remarkably, we identify a negative association between SEC61G expression levels and the infiltration of critical immune cell populations within the TME, along with correlations with immune checkpoint gene expression and tumor heterogeneity scores in LUAD. Functional studies demonstrate that SEC61G knockdown markedly inhibits the migration of A549 and H2030 LUAD cells. This inhibitory effect is accompanied by a significant down-regulation of key regulators of tumor progression, including hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A, and genes involved in the epithelial-mesenchymal transition pathway. In conclusion, our comprehensive analyses position SEC61G as a potential prognostic biomarker intricately linked to glycolytic metabolism, the EMT pathway, and the establishment of an immune-suppressive phenotype in LUAD. These findings underscore the potential of SEC61G as a therapeutic target and predictive marker for immunotherapeutic responses in LUAD patients.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024048
Bone cancer pain (BCP), due to cancer bone metastasis and bone destruction, is a common symptom of tumors, including breast, prostate, and lung tumors. Patients often experience severe pain without effective treatment. Here, using a mouse model of bone cancer, we report that MOTS-c, a novel mitochondrial-derived peptide, confers remarkable protection against cancer pain and bone destruction. Briefly, we find that the plasma level of endogenous MOTS-c is significantly lower in the BCP group than in the sham group. Accordingly, intraperitoneal administration of MOTS-c robustly attenuates bone cancer-induced pain. These effects are blocked by compound C, an AMPK inhibitor. Furthermore, MOTS-c treatment significantly enhances AMPKα1/2 phosphorylation. Interestingly, mechanical studies indicate that at the spinal cord level, MOTS-c relieves pain by restoring mitochondrial biogenesis, suppressing microglial activation, and decreasing the production of inflammatory factors, which directly contribute to neuronal modulation. However, in the periphery, MOTS-c protects against local bone destruction by modulating osteoclast and immune cell function in the tumor microenvironment, providing long-term relief from cancer pain. Additionally, we find that chronic administration of MOTS-c has little effect on liver, renal, lipid or cardiac function in mice. In conclusion, MOTS-c improves BCP through peripheral and central synergistic effects on nociceptors, immune cells, and osteoclasts, providing a pharmacological and biological rationale for the development of mitochondrial peptide-based therapeutic agents for cancer-induced pain.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023279
RNA terminal phosphorylase B (RTCB) has been shown to play a significant role in multiple physiological processes. However, the specific role of RTCB in the mouse colon remains unclear. In this study, we employ a conditional knockout mouse model to investigate the effects of RTCB depletion on the colon and the potential molecular mechanisms. We assess the efficiency and phenotype of Rtcb knockout using PCR, western blot analysis, histological staining, and immunohistochemistry. Compared with the control mice, the Rtcb-knockout mice exhibit compromised colonic barrier integrity and prominent inflammatory cell infiltration. In the colonic tissues of Rtcb-knockout mice, the protein levels of TNF-α, IL-8, and p-p65 are increased, whereas the levels of IKKβ and IκBα are decreased. Moreover, the level of GSK3β is increased, whereas the levels of Wnt3a, β-catenin, and LGR5 are decreased. Collectively, our findings unveil a close association between RTCB and colonic tissue homeostasis and demonstrate that RTCB deficiency can lead to dysregulation of both the NF-κB and Wnt/β-catenin signaling pathways in colonic cells.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023275
Acute liver failure (ALF) is a significant global issue with elevated morbidity and mortality rates. There is an urgent and pressing need for secure and effective treatments. Ferroptosis, a novel iron-dependent regulation of cell death, plays a significant role in multiple pathological processes associated with liver diseases, including ALF. Several studies have demonstrated that mesenchymal stem cells (MSCs) have promising therapeutic potential in the treatment of ALF. This study aims to investigate the positive effects of MSCs against ferroptosis in an ALF model and explore the underlying molecular mechanisms of their therapeutic function. Our results show that intravenously injected MSCs protect against ferroptosis in ALF mouse models. MSCs decrease iron deposition in the liver of ALF mice by downregulating hepcidin level and upregulating FPN1 level. MSCs labelled with Dil are mainly observed in the hepatic sinusoid and exhibit colocalization with the macrophage marker CD11b fluorescence. ELISA demonstrates a high level of IGF1 in the CCL4+MSC group. Suppressing the IGF1 effect by the PPP blocks the therapeutic effect of MSCs against ferroptosis in ALF mice. Furthermore, disruption of IGF1 function results in iron deposition in the liver tissue due to impaired inhibitory effects of MSCs on hepcidin level. Our findings suggest that MSCs alleviate ferroptosis induced by disorders of iron metabolism in ALF mice by elevating IGF1 level. Moreover, MSCs are identified as a promising cell source for ferroptosis treatment in ALF mice.
Chinese Journal of Pathophysiology•2025•DOI: 10.3969/j.issn.1000-4718.2025.06.001
AIM: Regulatory T cells (Tregs) are a specialized subset of CD4+ T cells primarily involved in immunosuppressive functions. AMP-activated protein kinase (AMPK) serves as a metabolic sensor that governs the differentiation, maturation, and immune functions of Tregs through metabolic reprogramming. However, the impact of AMPKα1 (the catalytic subunit of AMPK) knockout specifically in Tregs on the host's immune microenvironment remains largely unexplored. METHODS: Histological changes in immune organs were assessed using HE staining. The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox (AMPKα1fl/fl) mice and Treg-specific AMPKα1 knockout mice (AMPKα1fl/flFoxp3cre mice). RESULTS: Compared to AMPKα1fl/fl mice, the percentage of eosinophils in the bone marrow of AMPKα1fl/flFoxp3cre mice was significantly reduced. Additionally, while the thymus of AMPKα1fl/flFoxp3cre mice exhibited normal structure, both its size and the ratio of thymus weight to body weight were significantly decreased. The knockout of AMPKα1 in Tregs led to a notable reduction in the total percentage of immature double-negative (DN) cells. Consequently, the percentage of CD4+ T cells derived from these DN cells also decreased, even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1fl/flFoxp3cre mice compared to AMPKα1fl/fl mice. Importantly, the proportion of Siglec-F+ CD11b+ eosinophils in the thymus was significantly lower in AMPKα1fl/flFoxp3cre mice. Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4+ T cells in peripheral blood, alongside a decrease in the proportion of mature CD8+ T cells. Similarly, the proportion of CD4+ T cells in the spleen of AMPKα1fl/flFoxp3cre mice was elevated compared to AMPKα1fl/fl mice. In contrast, the proportion of neutrophils significantly decreased, while mononuclear cell proportions increased in the spleen of AMPKα1fl/flFoxp3cre mice. In lymph nodes, the medullary boundaries in AMPKα1fl/flFoxp3cre mice were blurred, and the lymphoid follicles were missing, a feature not observed in AMPKα1fl/fl mice. Furthermore, the knockout of AMPKα1 in Tregs reduced the CD3+ T cell population, particularly the CD8+ T cell population, in lymph nodes. Although the mature Treg cell population was significantly lower in AMPKα1fl/flFoxp3cre mice, the percentage of CD4+ T cells was markedly increased. In contrast, there was no statistically significant difference in granulocyte populations between AMPKα1fl/flFoxp3cre and AMPKα1fl/fl mice. CONCLUSION: The populations of mature Tregs, CD8+ T cells and eosinophils in various immune organs were significantly altered in mice with Treg-specific AMPKα1 knockout, suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.
Chinese Journal of Pathophysiology•2025•DOI: 10.3969/j.issn.1000-4718.2025.12.001
AIM: To evaluate the function and mechanisms of forskolin in treating ataxia-like behavior in Celsr3 conditional knockout (cKO) mice. METHODS: The efficiency of intraperitoneally administered forskolin was evaluated by behavioral tests, and the molecular mechanisms were investigated by patch-clamp experiments. RESULTS: The loss of Celsr3 led to ataxia-like behavior, accompanied by impaired miniature excitatory postsynaptic currents (mEPSCs) and postsynaptic long-term potentiation (LTP) in PCs. The cAMP activator forskolin ameliorated ataxia-like behavior and abrogated the mEPSCs impairment and LTP in model mice. Interestingly, the effects of forskolin could be blocked by SQ22536 (a cAMP antagonist) and ESI-08 (exchange protein activated by cAMP antagonist; Epac) but the H89 (a PKA antagonist) could not block the effects. CONCLUSION: Celsr3 plays an important role in motor coordination by modulating synaptic function, and forskolin may be a valuable therapeutic drug for certain types of inherited cerebellar ataxia.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03780-7
Diabetes mellitus, a significant global public health challenge, severely impacts human health worldwide. The organoid, an innovative in vitro three-dimensional (3D) culture model, closely mimics tissues or organs in vivo. Insulin-secreting islet organoid, derived from stem cells induced in vitro with 3D structures, has emerged as a potential alternative for islet transplantation and as a possible disease model that mirrors the human body’s in vivo environment, eliminating species difference. This technology has gained considerable attention for its potential in diabetes treatment. Despite advances, the process of stem cell differentiation into islet organoid and its cultivation demonstrates deficiencies, prompting ongoing efforts to develop more efficient differentiation protocols and 3D biomimetic materials. At present, the constructed islet organoid exhibit limitations in their composition, structure, and functionality when compared to natural islets. Consequently, further research is imperative to achieve a multi-tissue system composition and improved insulin secretion functionality in islet organoid, while addressing transplantation-related safety concerns, such as tumorigenicity, immune rejection, infection, and thrombosis. This review delves into the methodologies and strategies for constructing the islet organoid, its application in diabetes treatment, and the pivotal scientific challenges within organoid research, offering fresh perspectives for a deeper understanding of diabetes pathogenesis and the development of therapeutic interventions.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261512
Casticin, a polymethoxyflavone derived from Vitex trifolia, was evaluated for its therapeutic efficacy and mechanism in colitis-associated colorectal cancer (CAC) using an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model. Casticin intervention significantly attenuated body weight loss, reduced disease activity index, and decreased colonic tumor volume and tumor burden (P < 0.05), while improving survival rates of tumor-bearing mice. Safety assessments revealed no significant abnormalities in serum liver function indicators or major organ histomorphology. 16S rRNA sequencing demonstrated that casticin reversed CAC-induced gut dysbiosis, notably downregulating the pro-carcinogenic phyla Fusobacteriota and Patescibacteria, and enriching anti-inflammatory short-chain fatty acid-producing genera Lachnospiraceae_NK4A136_group and Prevotellaceae_UCG-001. Proteomic profiling identified the complement and coagulation cascades as the core responsive pathway, with dose-dependent restoration of serine protease inhibitor 1 (Serpine1) and integrin alpha M (Itgam) expression. Western blotting confirmed significant downregulation of Itgam and Serpine1 in colonic tissue (P < 0.01 and P < 0.001, respectively), consistent with proteomic trends. Correlation analysis further revealed that beneficial genera such as Lachnospiraceae_NK4A136_group were negatively correlated with Serpine1 expression, whereas pro-carcinogenic Fusobacteriota was positively correlated with Itgam expression. These findings indicate that casticin ameliorates CAC by remodeling gut microbiota composition and modulating key molecules in the complement and coagulation cascades, thereby synergistically blocking the inflammation-to-cancer transition.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261511
This study integrates network pharmacology, molecular docking, and in vitro experiments to elucidate the anti-gastric cancer mechanism of morin, an active flavonoid from Mori Ramulus. Network analysis identified 178 potential targets of Mori Ramulus and 13,100 gastric cancer-related targets, with 159 intersecting targets. Enrichment analysis highlighted the PI3K/Akt pathway as a key mediator. Molecular docking and dynamics simulations confirmed stable binding between morin and PIK3R1, which is significantly overexpressed in gastric cancer tissues. In vitro, morin (100–400 μmol/L) dose-dependently inhibited AGS cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis (P<0.05, 0.01). Western blotting revealed downregulation of PI3K/Akt pathway proteins (p85α, p110β, p-Akt) and cell cycle-related proteins (Bcl-2, CCND1, CDK4, CDK6), alongside upregulation of Bax and p21 (P<0.05, 0.01). Co-treatment with the PI3K agonist 740Y-P significantly reversed these effects (P<0.05, 0.01), confirming pathway dependence. These findings demonstrate that morin targets PIK3R1 to suppress PI3K/Akt signaling, thereby inhibiting proliferation and inducing apoptosis and cell cycle arrest in gastric cancer cells. The study underscores morin's potential as a natural, multi-target lead compound with low toxicity, though further validation in additional cell lines and gene-level manipulations is warranted.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261626
The botanical origin of the traditional Chinese medicine Tong-guan-teng was investigated using ultra-high-performance liquid chromatography coupled with charged aerosol detection (UHPLC-CAD) to establish a semi-quantitative fingerprinting method for quality control. Reference material, 12 batches of commercial Tong-guan-teng, and vine samples of two putative origin species, Marsdenia tenacissima and M. cavaleriei, were analyzed on an ACQUITY BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with 0.1% formic acid aqueous solution–acetonitrile gradient elution at 0.5 mL/min and 2 μL injection volume. Similarity evaluation was performed using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (2012 edition). The method demonstrated satisfactory precision, stability, and repeatability. Similarity between the reference and commercial batches ranged from 0.927 to 0.988. The reference fingerprint differed significantly from M. tenacissima stems but showed high consistency with M. cavaleriei stems (similarity > 0.85), with comparable major component contents. The relative contents of eight major components followed the order: tenacissoside A > marsdenoside H > marsdenoside K > tenacissoside B > tenacissoside H > tenacissoside D > tenacissoside I > tenacissoside E. Besides the pharmacopoeial marker tenacissoside H, tenacissoside A, marsdenoside H, marsdenoside K, and tenacissoside B were abundant and are proposed as potential quality markers. These chemical findings support revising the botanical origin of Tong-guan-teng in the Chinese Pharmacopoeia (2025 edition) from M. tenacissima to M. cavaleriei, providing a scientific basis for origin identification and quality standard improvement.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261623
Endophytic bacterial communities associated with the medicinal plant Duchesnea indica were profiled across root, stem, leaf, and fruit tissues using Illumina paired-end high-throughput sequencing. A total of 1,914,360 raw sequences were generated and processed via DADA2 and Vsearch pipelines. At the phylum level, Proteobacteria dominated all tissues. Tissue-specific variation was pronounced: the stem harbored the highest richness, whereas the root exhibited the highest diversity. Sphingomonas was identified as a key biomarker discriminating intergroup differences and displayed a significant positive correlation with Pseudomonas. Both genera were principal contributors to the N10-formyltetrahydrofolate biosynthesis pathway. Leaf, fruit, and stem communities clustered with high similarity, while root communities were distinctly separated. Functional prediction indicated that Pseudomonas and Sphingomonas may act synergistically in secondary metabolite synthesis or host stress resistance. These findings establish a microbiological basis for the pharmacological activity of D. indica and suggest that endophytic community modulation could enhance the accumulation of bioactive flavonoids, triterpenoids, and polyphenols, offering a novel avenue for the sustainable development of traditional Chinese medicine resources.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261616
This study interrogates the therapeutic efficacy and molecular mechanism of aconitine combined with paeoniflorin in a rat model of knee osteoarthritis (KOA), focusing on the Indian hedgehog (Ihh)-glioma-associated oncogene homolog (Gli) signaling axis. Anterior cruciate ligament transection (ACLT) was performed on male rats, which were then allocated to sham, model, celecoxib (24 mg/kg), and three aconitine-paeoniflorin dose groups (5+50, 10+100, 20+200 μg/kg; n=10 per group). Behavioral tests, hematoxylin-eosin staining, micro-computed tomography, ELISA for matrix metalloproteinase 13 (MMP13) and type II collagen (Col II), immunofluorescence, and qRT-PCR for Ihh, Gli, patched 1 (Ptch1), and MMP13 were conducted. Molecular docking assessed binding affinities. Safety was evaluated via serum aspartate aminotransferase, creatinine, blood urea nitrogen, urinary protein, and histopathology of heart, liver, and kidney. Results demonstrated that the combination significantly elevated mechanical and thermal pain thresholds (P<0.05, 0.01, 0.001), restored cartilage matrix integrity, improved bone microarchitecture, decreased serum MMP13, and increased Col II (P<0.05, 0.01, 0.001). Ihh, Gli, Ptch1, and MMP13 protein and gene expressions were markedly downregulated (P<0.05, 0.01, 0.001). Docking confirmed binding energies ≤−5 kcal/mol for aconitine and paeoniflorin with Ihh, Gli, ADAMTS5, and MMP13. No significant hepatic, renal, or cardiac toxicity was observed. The combination inhibits aberrant Ihh-Gli pathway activation, suppresses cartilage matrix degradation, and offers a safer, multi-target alternative to celecoxib for KOA management.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04989-4
Chemotherapy-induced premature ovarian failure (POF) remains a major cause of infertility with limited therapeutic options. This study evaluated whether preconditioning mesenchymal stem cells (MSCs) with the antioxidant flavonoid isorhamnetin (ISO) enhances the efficacy of their exosomes (ISO-MSC-Exos) against cyclophosphamide (CTX)-induced POF. A CTX-induced POF rat model was established, and the ferroptosis inhibitor ferrostatin-1 was used to confirm the role of ferroptosis. MSC-Exos and ISO-MSC-Exos were isolated by ultracentrifugation and administered via tail vein injection. Ovarian recovery was assessed by oestrous cycle monitoring, serum hormone levels, and histology. Lipid peroxidation and iron metabolism were evaluated by quantifying malondialdehyde (MDA), glutathione (GSH), iron deposition, and mitochondrial ultrastructure. Immunohistochemistry assessed GPX4, ACSL4, and FTH1 expression. Proteomic analysis explored underlying mechanisms. Ferroptosis was pivotal in CTX-induced POF. Both exosome therapies improved ovarian function and suppressed ferroptosis, with ISO-MSC-Exos showing superior efficacy. ISO-MSC-Exos significantly restored hormone levels, ameliorated oestrous cycle disorders, reduced follicular atresia, and enhanced fertility. They more effectively elevated GSH, reduced MDA and Fe2+ levels, and reversed abnormal expression of GPX4, ACSL4, and FTH1. Proteomics suggested ISO-MSC-Exos inhibit ferroptosis by downregulating Alox15 and Tf, reducing lipid peroxidation substrates and cellular iron uptake. ISO-MSC-Exos demonstrate superior efficacy over MSC-Exos in restoring ovarian function and inhibiting ferroptosis, suggesting ISO preconditioning enhances therapeutic effect in POF.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05051-z
Intervertebral disc degeneration (IVDD) is a leading cause of low back pain, driven by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtuin 1 (SIRT1), a key regulator of mitochondrial quality control, is downregulated in degenerated discs. Salidroside (Sal), a natural compound from Rhodiola rosea, has shown potential in enhancing mitophagy, but its mechanism in IVDD remains unclear. Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD. Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal’s protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration. These effects are closely associated with the activation of SIRT1/FOXO3 signaling and the restoration of functional mitophagic flux. Our work highlights the SIRT1/FOXO3-mitophagy axis as a promising target for further investigation in the development of therapeutic strategies for IVDD.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04896-8
Vascular calcification (VC) in type 2 diabetes (T2D) is driven by endothelial-to-mesenchymal transition (EndMT), yet effective therapies remain elusive. Elevated plasma microRNA-32-5p (miR-32) correlates with calcification, but its role in bone marrow mesenchymal stem cell-derived extracellular vesicle (BMSC-EV) therapy is undefined. We characterized BMSC-EVs by TEM, NTA, Western blotting, and confocal microscopy. Alizarin Red and ALP staining quantified VC severity. qRT-PCR and Western blotting assessed BMP2, RUNX2, GPX4, SLC7A11, VE-cadherin, and N-cadherin; immunofluorescence localized VE-cadherin and N-cadherin. In vivo validation used miR-32–/– and ApoE–/– mice. RNA sequencing and bioinformatics explored mechanisms. BMSC-EVs attenuated VC in endothelial cells (ECs) and inhibited EndMT. In vivo, BMSC-EV treatment significantly reduced T2D-associated VC severity. Notably, miR-32 knockout further enhanced the inhibitory effect of BMSC-EVs on VC. Transcriptomic and functional analyses linked the protective effect to MAPK/FoxO signaling modulation, potentially via ferroptosis regulation. These findings demonstrate that BMSC-EVs attenuate T2D-associated VC, partially through miR-32-mediated suppression of EC ferroptosis, providing a mechanistic foundation for EV-based therapeutics.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Osteoporosis is characterized by impaired bone formation relative to resorption, yet the molecular drivers of osteoblast dysfunction remain incompletely defined. Cadherin 19 (CDH19), located at chromosome 18q22-q23, has been linked to 18q deletion syndromes presenting with skeletal deformities, but its role in bone homeostasis was previously unknown. Using a Cre-loxP conditional knockout model, we demonstrate that CDH19 deletion in mice significantly reduces bone mass, with decreases in bone density, trabecular number, and bone volume fraction. Osteoblasts isolated from CDH19 knockout mice exhibit suppressed proliferation and osteogenic differentiation, as evidenced by EdU labeling, qPCR, alkaline phosphatase and alizarin red S staining, and Western blot. RNA sequencing and subsequent immunofluorescence and Western blot analyses reveal that the PI3K/AKT signaling pathway is markedly inhibited in CDH19-deficient osteoblasts. Administration of the PI3K/AKT agonist 740Y-P partially rescues the osteogenic differentiation deficit both in vitro and in vivo. These findings establish CDH19 as a critical regulator of osteoblast function through PI3K/AKT signaling and identify it as a potential therapeutic target for bone diseases such as osteoporosis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04900-1
Background: The human endometrium is a regenerative tissue essential for fertility, but pathological conditions such as Asherman syndrome, endometrial atrophy, and thin endometrium impair its function. Current therapies lack efficacy, driving demand for innovative regenerative therapies. Endometrial-derived hydrogels and organoids have shown promise individually for tissue regeneration, but their combined therapeutic potential has not been previously evaluated in vivo. This study explores a dual regenerative strategy combining a hybrid hydrogel—composed of synthetic PuraMatrix® and endometrial extracellular matrix hydrogel—with human endometrial organoids in an immunocompetent murine model with uterine damage. Methods: Endometrial damage was established in female C57BL/6 mice (n=46) via uterine injury using 70° ethanol. After 4 days, human endometrial organoids were co-injected with the hybrid hydrogel into the uterine horns. Two weeks post-injection, a subset of mice (n=25) was sacrificed for biocompatibility, histological, and transcriptomic analyses. Functional recovery was assessed in the remaining animals (n=21) through fertility outcome evaluation. Normally distributed data were analyzed by one-way ANOVA and Tukey’s multiple comparisons; non-normally distributed data by Kruskal–Wallis test with Dunn’s multiple comparisons. Fertility outcomes used t-test or Mann–Whitney U tests. Results: The combination of hybrid hydrogel (PM+EndoECM) with human endometrial organoids promoted endometrial regeneration, restored endometrial parameters, increased angiogenesis, and reduced fibrosis and ferroptosis, while promoting a regenerative immune microenvironment. Conclusions: This dual treatment demonstrates synergistic efficacy in an immunocompetent murine model of AS/EA/TE. Further investigation is needed to optimize hydrogel duration to fully unlock reproductive potential.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05008-2
Background: The therapeutic efficacy of mesenchymal stem cells (MSCs) can be improved by enhancing their adaptation to the inflammatory microenvironment. Autophagy maintains MSCs functionality, and autophagy-related gene 5 (ATG5) mediates autophagy and regulates the biological functions and therapeutic efficacy of these cells. The aim of this study was to investigate the role of ATG5 in the antioxidant capacity and evaluate the therapeutic effect of ATG5-engineered MSCs for colitis treatment. Methods: Cell viability was assessed using a Cell Counting Kit-8. The mRNA expression of autophagy-, antioxidant-, and polarization-related genes was determined through real-time quantitative polymerase chain reaction, and protein expression was analyzed via western blotting. Macrophage polarization markers were analyzed using flow cytometry. Multiomics approaches, including RNA transcriptome sequencing, untargeted metabolomics, and 16S ribosomal RNA microbiota analysis, were also used. Mice with dextran sulfate sodium-induced colitis were used to evaluate the therapeutic efficacy of MSCs. Results: Preconditioning MSCs with hypoxia (1% O₂) and serum deprivation significantly enhanced autophagy and upregulated ATG5 expression. Adenovirus-mediated ATG5 overexpression in MSCs (MSCs-ATG5) enhanced their autophagic activity and antioxidant capacity, upregulated HMOX-1, SOD2, and CAT expression, and increased glutathione peroxidase and catalase enzymatic activity, while enhancing cell proliferation, without altering surface marker expression. Further, MSCs-ATG5 significantly promoted M2 macrophage polarization and regulated oxidative stress-related signaling pathways. Additionally, MSCs-ATG5-based therapy markedly ameliorated colitis disease signs in mice. Transcriptome analysis revealed that MSCs-ATG5 suppressed the IL-17/NF-κB inflammatory signaling pathway. This treatment also regulated levels of the anti-inflammatory metabolite prostaglandin D2 (PGD2) in colon tissues. Conclusions: ATG5 overexpression enhances the therapeutic efficacy of MSCs in a mouse colitis model by augmenting anti-inflammatory and antioxidative mechanisms, providing a potential clinical efficacy of MSCs-ATG5-based therapies on IBD.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026054
The anti-inflammatory properties of the traditional herb Salvia miltiorrhiza Bunge are well-established, yet its precise mechanism of action in ulcerative colitis (UC) remains unclear. Herein, we evaluate the therapeutic potential of four major tanshinones–tanshinone IIA (Tan IIA), miltirone, neocryptotanshinone, and dihydrotanshinone I–in a murine dextran sulfate sodium (DSS)-induced colitis model. Our results show that tanshinones effectively alleviate disease severity, suppress systemic and local inflammation, and restore intestinal barrier integrity. Integrated multi-omics analysis reveals that the therapeutic efficacy originates from a comprehensive reprogramming of the gut microbiota-metabolite axis. Specifically, tanshinones reverse colitis-associated dysbiosis and rectify metabolic disturbances in linoleic acid metabolism, bile acid biosynthesis, and amino acid utilization. Correlation network analysis identifies key functional modules linking beneficial microbes (e.g., Akkermansia) to anti-inflammatory lipid mediators and associating pathobionts (e.g., Desulfovibrio) with disrupted bile acid metabolism. Notably, supplementation with Akkermansia muciniphila synergizes with Tan IIA to amplify barrier restoration and metabolic normalization. Our findings establish that tanshinones ameliorate UC through microbiota-driven metabolic reprogramming, wherein the restructured microbial community actively shapes a therapeutic metabolic output. This work elucidates a metabolite-mediated mechanism of action and positions tanshinones as promising microbiome-targeting therapeutics for inflammatory bowel disease.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025206
Anti-aging foods not only benefit elderly individuals but also drive the development of safe and effective natural drugs. Here, we report that the addition of total flavonoids of litchi seed (TFL) delays replicative senescence and stress-induced senescence. TFL alleviates the senescence-associated secretory phenotype (SASP) and reduces the degree of DNA damage caused by bleomycin (BLM). TFL also counteracts stress-induced pulmonary senescence and fibrosis. TFL reduces the protein level of p21 in mouse lung and alleviates pulmonary fibrosis. Transcriptome profiling further reveals that TFL plays a key role in its anti-aging mechanism by inhibiting the SASP. Mechanistically, TFL suppresses p65 protein expression, thereby inhibiting IL-1α and IL-1β and delaying cellular senescence. Gut microbiome analysis reveals that the abundance and functions of the mouse gut microbiome change after BLM exposure and that TFL treatment reverses these changes. Overall, we provide a theoretical basis for the future application of TFL as a potential anti-aging product.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026076
In Arabidopsis, the PPR proteins EMB1006, EMB1270, and EMB976 are all essential for the splicing of plastid clpP1 intron 2 (clpP1.2), although each also targets other distinct RNAs. The precise mechanism underlying their coordinated action in clpP1.2 splicing remains unclear. In this study, RNA electrophoretic mobility shift assays, guided by PPR code prediction, confirm that EMB1006 specifically binds to a sequence near the 3′ end of clpP1 exon 2. Additionally, immunoprecipitation coupled with mass spectrometry reveals that EMB1006 forms a complex with EMB1270, EMB976, and CFM2. Direct interactions between EMB1006 and EMB1270 or CFM2 are further supported by yeast two-hybrid (Y2H) and semi-in vivo pull-down assays. However, no direct interactions between EMB976 and EMB1006, CFM2 or EMB1270 are detected by Y2H. Based on these findings and previous evidence that EMB1270 binds to clpP1 intron 2 and interacts with CFM2, we propose a model in which EMB1006 and EMB1270 bind to distinct sites on clpP1 pre-mRNA. Together with CFM2 and possible indirect association with EMB976, they assemble into a protein-RNA complex that facilitates the splicing of clpP1.2 in chloroplasts.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21222
BACKGROUND: Cobalt chloride solution is commonly used to induce osteoarthritis cell models in vitro. However, its ability to construct animal models of osteoarthritis by intra-articular injection remains unknown. OBJECTIVE: To investigate the effect of intra-articular injection of different concentrations of cobalt chloride solution on cartilage degeneration in the knee joint. METHODS: Thirty-six healthy adult male New Zealand rabbits were randomly divided into four groups: low, medium and high dose cobalt chloride groups and control group. The right hind knee was intra-articularly injected with 100, 200, and 300 μmol/(L·kg) of cobalt chloride, while the left hind knee served as the control knee and was injected with an equal amount of normal saline. At 4, 8 and 12 weeks after operation, four rabbits were killed respectively. The cartilage on the surface of the femur was exposed for gross morphological observation, and then the cartilage tissues were taken for hematoxylin-eosin staining, safranine O-fast green staining, the Osteoarthritis Research Society International scoring, and immunohistochemical staining of interleukin 1 and tumor necrosis factor α, to determine cartilage degeneration in various aspects. RESULTS AND CONCLUSION: (1) Gross observation: At the same postoperative time point, with the increase of cobalt chloride concentration, cartilage degeneration showed a progressive aggravation trend, and the high-dose cobalt chloride group even involved the deep layer of cartilage and subchondral bone; under the same concentration of cobalt chloride, with the prolongation of modeling time, cartilage degeneration progressed progressively. (2) Hematoxylin-eosin staining, safranine O-fast green staining, and Osteoarthritis Research Society International scoring showed that at the same postoperative time point, with the increase of cobalt chloride concentration, the cartilage surface gradually became rough, the superficial layer became thinner, and the destruction aggravated, and the Osteoarthritis Research Society International score gradually increased (P < 0.05); under the same concentration of cobalt chloride, with the prolongation of modeling time, the arrangement of chondrocytes tended to be disordered, polarity was lost, and the destruction of superficial cartilage and subchondral bone progressively aggravated, and the Osteoarthritis Research Society International score gradually increased (P < 0.05). (3) Immunohistochemistry showed that at the same postoperative time point, with the increase of cobalt chloride concentration, cartilage degeneration aggravated, intracellular brown particles increased, and the positive expression of interleukin 1 and tumor necrosis factor α increased (P < 0.01); under the same concentration of cobalt chloride, with the prolongation of modeling time, cartilage destruction and fissures aggravated, and the positive expression of interleukin 1 and tumor necrosis factor α increased (P < 0.01). This experiment successfully established an osteoarthritis model of New Zealand rabbits induced by intra-articular injection of cobalt chloride solution, preliminarily verified the stability and reliability of the animal model, and also proved that with the increase of modeling concentration and the prolongation of modeling time, cartilage degeneration progressed progressively.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21279
Objective: To systematically compare the acute effects of blood flow restriction combined with preconditioning (to induce post-activation performance enhancement) versus preconditioning alone or sitting, low-intensity preconditioning combined with blood flow restriction versus high-intensity preconditioning, and sitting combined with blood flow restriction versus sitting on sports performance using a multilevel meta-analysis. Methods: Following the PRISMA guidelines, Web of Science, PubMed, SPORTDiscus, and CNKI databases were systematically searched (from inception to May 24, 2025). Inclusion criteria: (1) healthy individuals who were at least physically active; (2) studies with at least one of the following four comparisons: preconditioning + blood flow restriction vs. preconditioning alone; preconditioning + blood flow restriction vs. sitting; low-intensity preconditioning + blood flow restriction vs. high-intensity preconditioning; sitting + blood flow restriction vs. sitting; (3) sports performance (e.g., jump, sprint, bench press throw) as the primary outcome; (4) randomized or non-randomized crossover/parallel designs; (5) published in peer-reviewed Chinese or English journals. Risk of bias was assessed using ROB-2, and evidence quality was evaluated with GRADE. Data were fitted using cluster robust variance estimation and a three-level mixed-effects model, with small-sample corrections. Subgroup analyses and meta-regression explored moderators and sources of heterogeneity. Results: Twelve studies (196 participants, 12 women, 184 men) were included. Main findings: (1) Preconditioning + blood flow restriction was more effective than preconditioning alone in enhancing sports performance (ES=0.21, 95%CI=0.01-0.40, GRADE=low), with the best effect at recovery times of 4-12 min and 50% arterial occlusion pressure (ES=1.49); (2) Preconditioning + blood flow restriction did not significantly differ from sitting (ES=0.52, 95%CI=-0.12-1.15, GRADE=very low), but preconditioning + 140 mmHg blood flow restriction was superior to preconditioning alone (ES=1.21, 95%CI=0.14-2.28); (3) Low-intensity preconditioning + blood flow restriction did not differ from high-intensity preconditioning (ES=-0.10, 95%CI=-0.84-0.64, GRADE=low); (4) Sitting + blood flow restriction did not significantly differ from sitting (ES=0.24, 95%CI=-0.03-0.52, GRADE=very low). Notably, the effects of the latter two comparisons significantly decreased with recovery time (β=-0.04, P < 0.01 and β=-0.04, P=0.02). Conclusion: Preconditioning combined with blood flow restriction is more effective than preconditioning alone in inducing post-activation performance enhancement, preliminarily suggesting the use of 50% arterial occlusion pressure and 4-12 min recovery time. However, preconditioning combined with blood flow restriction does not appear to be more effective than sitting, possibly due to insufficient number of included studies. Additionally, low-intensity preconditioning + blood flow restriction can achieve similar post-activation performance enhancement as high-intensity preconditioning, while the potential benefit of sitting + blood flow restriction on sports performance may diminish over time. Overall, it is preliminarily recommended to use low-intensity preconditioning (e.g., 30% one-repetition maximum squat or bodyweight training) combined with 50% arterial occlusion pressure or 140 mmHg blood flow restriction, with 4-12 min recovery before subsequent performance testing.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21266
BACKGROUND: Shear-wave elastography is valuable for rehabilitation diagnosis and treatment, but it has not been sufficiently promoted in clinical practice. OBJECTIVE: To explore the trends and hotspots of ultrasound shear wave elastography in skeletal muscle research by visualizing and analyzing the international literature from the past 10 years, thereby providing a reference for clinical diagnosis and follow-up research. METHODS: Based on the Web of Science Core Collection database (2015-2024), the number of publications, countries/regions, institutions, authors, journals, cited literature, and key words from the 978 included articles were visualized and analyzed using CiteSpace software. RESULTS AND CONCLUSION: (1) With a 16.2% average annual growth in global publications, China has the highest number of publications worldwide (197), but its international collaborative network is relatively weak. The University of Nantes in France has the highest number of publications (50), and the University of Queensland has the most influential collaborative network. (2) Ultrasound in Medicine and Biology is the journal with the most publications (33). Noriaki Ichihashi is the most prolific author. (3) The gastrocnemius muscle is one of the most frequently examined sites. Shear wave elastography shows significant clinical potential in central nervous system diseases and sports injuries. (4) The research focus has shifted from basic biomechanics to dynamic clinical assessment and therapeutic interventions. (5) Future diagnostic techniques should be more standardized and refined, establishing normative data ranges for muscle tissue, while considering individual biological variability in elasticity values.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21293
BACKGROUND: As the primary organ for arsenic metabolism in the body, the liver has become a focal point for research on the mechanisms of arsenic toxicity. OBJECTIVE: To investigate the role of pregnane X receptor in sodium arsenite-induced oxidative stress and inflammatory injury in human normal hepatocytes. METHODS: Human normal hepatocyte MIHA cells were exposed to 0 (control), 10, 20, 30 μmol/L sodium arsenite for 48 hours. Changes in cell morphology were observed. Cell viability was measured via the cell counting kit-8 assay. Intracellular reactive oxygen species levels were detected using fluorescence probe staining combined with a microplate reader. Malondialdehyde levels were measured by thiobarbituric acid method. Glutathione reductase activity was detected by NADPH method. Total superoxide dismutase activity was measured by WST-8 method. Levels of interleukin-6, interleukin-1β, and tumor necrosis factor-α in cell supernatant were detected by ELISA. mRNA expression of pregnane X receptor and cytochrome P450 3A4 enzyme was detected by qRT-PCR. Protein expression of pregnane X receptor, cytochrome P450 3A4, nuclear factor-κB p65, nuclear factor-κB p-p65, proliferating cell nuclear antigen, interleukin-6, interleukin-1β, tumor necrosis factor-α, nuclear factor-κB inhibitor protein α, cyclooxygenase-2, p-nuclear factor-κB inhibitor protein α, nuclear factor erythroid 2-related factor 2, Keap1, and p-nuclear factor erythroid 2-related factor 2 was detected by western blot. RESULTS AND CONCLUSION: Compared with the control group, cells in all sodium arsenite groups showed unclear cell membrane boundaries, reduced cytoplasm, decreased cell fusion rate, and widened intercellular spaces. Compared with the control group, intracellular reactive oxygen species and malondialdehyde levels were increased (P < 0.05), levels of interleukin-6, interleukin-1β, and tumor necrosis factor-α in cell supernatant were increased (P < 0.05), protein expression of p-nuclear factor-κB inhibitor protein α, nuclear factor-κB p-p65, nuclear factor-κB p65, tumor necrosis factor-α, and interleukin-1β were increased (P < 0.05), cell viability was decreased (P < 0.05), protein expression of proliferating cell nuclear antigen, nuclear factor erythroid 2-related factor 2, p-nuclear factor erythroid 2-related factor 2 and total superoxide dismutase activity were decreased (P < 0.05), and mRNA and protein expression of pregnane X receptor and cytochrome P450 3A4 enzyme were decreased (P < 0.05). Compared with the control group, glutathione reductase activity was decreased in 20 and 30 μmol/L sodium arsenite groups (P < 0.05), and protein expression of Keap1, interleukin-6, and cyclooxygenase-2 was increased (P < 0.05). These results indicate that sodium arsenite may induce oxidative stress and inflammatory injury in hepatocytes by downregulating pregnane X receptor expression, inhibiting the nuclear factor erythroid 2-related factor 2 antioxidant pathway, and activating the nuclear factor-κB inflammatory pathway, while also inhibiting the expression of the drug-metabolizing enzyme cytochrome P450 3A4.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21424
BACKGROUND: A combination of subjective and objective evaluation criteria is often required to more accurately and comprehensively assess knee function in patients undergoing anterior cruciate ligament reconstruction. OBJECTIVE: To review the evolving trends in effectiveness and safety evaluation criteria after anterior cruciate ligament reconstruction and analyze the dynamic shift in the use of subjective and objective assessment tools. METHODS: A systematic search of PubMed and Embase was conducted up to August 22, 2023 to identify studies assessing knee function after anterior cruciate ligament reconstruction. A total of 136 eligible studies meeting the inclusion criteria were included. The frequency of each evaluation standard was extracted and analyzed over time using Origin 2025 software. RESULTS AND CONCLUSION: (1) Between 1990 and 2005, objective measures were widely applied. Since 2005, subjective scoring systems, particularly patient-reported outcome measures, have increased sharply, surpassing objective standards in frequency from 2009 onward. (2) Early use was dominated by the Lysholm scale and Tegner activity score, while the International Knee Documentation Committee-Subjective Knee Form, Knee Injury and Osteoarthritis Outcome Score, and anterior cruciate ligament–return to sport after injury gradually emerged as the main tools in later years. (3) In contrast, objective assessments such as the KT1000/2000 arthrometer, Lachman test, and hop test remained relatively stable but showed an overall declining trend. (4) These findings indicate a paradigm shift from objective knee stability to patient-centered subjective experience in evaluating ACL reconstruction outcomes. (5) This study is the first to quantitatively reveal the dynamic evolution of mainstream evaluation tools, highlighting the current emphasis on combining subjective and objective criteria. The recommended combination is the International Knee Documentation Committee-Subjective Knee Form or Knee Injury and Osteoarthritis Outcome Score plus anterior cruciate ligament–return to sport after injury plus KT1000/2000 or hop test, to comprehensively reflect knee function recovery and patient perception, providing an evidence base for future comprehensive assessment approaches.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21392
BACKGROUND: Effective analgesia after total knee arthroplasty is crucial for rehabilitation, and adductor canal block is a common method. Traditional single injection of local anesthetic has limited analgesic duration, while continuous catheter infusion is complex and costly. OBJECTIVE: To compare the efficacy and safety of single-dose liposomal bupivacaine versus continuous catheter infusion of ropivacaine for adductor canal block analgesia after total knee arthroplasty. METHODS: Eighty patients undergoing primary unilateral knee arthroplasty at Gaoyou People's Hospital from March 2024 to February 2025 were randomly divided into liposomal bupivacaine group and continuous catheter infusion group. The liposomal bupivacaine group received a single adductor canal block with 133 mg (10 mL) liposomal bupivacaine mixed with 5 mL of 0.75% ropivacaine. The continuous catheter infusion group received an adductor canal catheter with 0.25% ropivacaine via a pump (load 10 mL, infusion rate 6 mL/h). Pain scores at different time points, pain-free time, morphine rescue dose, and walking distance were compared to assess analgesic efficacy; complications were observed for safety. Operation time, cost, patient satisfaction, and hospital stay were also compared. RESULTS AND CONCLUSION: (1) At 6, 12, 24, 48, and 72 h postoperatively, there were no significant differences in resting and movement pain scores between groups (P > 0.05). Pain-free time was 19 h in the liposomal bupivacaine group and 22 h in the continuous infusion group (P > 0.05). (2) At 72 h, morphine rescue dose was 78.6 mg morphine equivalents in the liposomal bupivacaine group and 80.5 mg in the continuous infusion group (P > 0.05). (3) Operation time was significantly shorter in the liposomal bupivacaine group (6.1±1.4 min vs. 20.3±1.2 min, P < 0.05). (4) Patient satisfaction, hospital stay, and walking ability showed no significant differences (P > 0.05). (5) One case of transient femoral nerve palsy occurred in the continuous infusion group at 6 h postoperatively, resolving spontaneously. Each patient in the liposomal bupivacaine group saved 132 RMB in analgesic costs. (6) Within 72 h after total knee arthroplasty, single-dose liposomal bupivacaine and continuous ropivacaine infusion showed no differences in analgesic scores, pain-free time, morphine rescue dose, hospital stay, satisfaction, or walking ability, but single-dose liposomal bupivacaine was more convenient, saving time and cost.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21384
BACKGROUND: Endplate defects are one of the important causative factors of lumbar degeneration, and their morphological characteristics may significantly affect the local mechanical environment of the spine. However, the effects of their different morphologic defects on the biomechanical properties of the lumbar spine have not been fully elucidated. OBJECTIVE: To investigate the effects of focal marginal defects, focal central defects, and angular defects on the stress distribution of lumbar endplates, intervertebral discs, and small joints, and to reveal their underlying biomechanical mechanisms. METHODS: Lumbar CT images were obtained from a healthy 36-year-old male volunteer, and a complete endplate model of the L4-L5 segment was reconstructed. Three typical endplate defect models (focal marginal defect, focal central defect, and angular defect) were constructed based on the classification of vertebral endplate defects in clinical imaging studies. By applying dynamic loads and corresponding moments to simulate physiological spinal muscle loads and typical motion loads, such as stance, forward flexion, backward extension, lateral bending, and rotation, the biomechanical stress distribution characteristics and peak changes in the vertebral cartilage endplates, intervertebral disc annulus fibrosus, nucleus pulposus, and facet joints during physiological spinal movements were evaluated. The effects of different defect types on the biomechanical stability of the lumbar spine were explored. RESULTS AND CONCLUSION: (1) Different defect types significantly altered the stress transmission pathways of the endplate and adjacent structures; marginal defects mainly affected the lateral annulus fibrosus stress distribution, while central defects significantly changed load bearing during extension. (2) There was obvious stress gradient concentration at the defect edges, suggesting potential microdamage risk. (3) Angular endplate defects produced significant stress concentration under dynamic loads, possibly being one of the high-risk factors leading to segmental instability and accelerated degeneration. (4) The experimental results provide biomechanical evidence for the involvement of endplate defects in intervertebral disc degeneration and facet joint damage, and have important guiding value for early clinical identification of high-risk defect types and formulation of targeted prevention strategies.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21364
BACKGROUND: Diabetes wound is one of the serious complications of diabetes patients, and its complex pathological mechanism and clinical treatment dilemma is still a major challenge. In recent years, exosomes have become a new focus in the field of diabetes wound research because they play a key role in intercellular communication, immune regulation, and tissue repair.
OBJECTIVE: To investigate the research hotspots and evolutionary trends of exosomes in diabetic wound healing.
METHODS: A systematic search was conducted in the Web of Science core collection to identify English literature focusing on exosomes in diabetic wound healing and published between the inception of the database and December 31, 2024. The annual publication volume was analyzed to track changes over time. Visual analyses using VOSviewer and CiteSpace software were performed on the retrieved literature to examine key aspects such as authors, countries, institutions, journals, and keywords, providing insights into the current research landscape and evolving hot topics in exosomes for diabetic wound healing.
RESULTS AND CONCLUSION: From 2014 to 2024, a total of 424 publications on exosome-promoted diabetic wound healing were produced, contributed by 2,883 authors from 46 countries and featured in 199 journals. In the realm of exosome-promoted diabetic wound healing, China had the highest number of publications, followed by the United States. The journals 'Journal of Nanobiotechnology' and 'Advanced Healthcare Materials' published the most papers and had high influence. Author Chen Zhenbing and Huazhong University of Science and Technology were the most productive author and institution, respectively, but the researcher clusters have not yet reached a certain scale, and future collaboration needs to be strengthened. Global research focus mainly concentrated on 10 thematic clusters including adipose stem cells, diabetic wounds, diabetic wound healing, wound healing, endoplasmic reticulum stress, microvesicles, collagen, proteomics, and diabetic foot infection. The research hotspots in this field are undergoing a transition from molecular mechanisms to systematic interventions. Future research hotspots will focus on angiogenesis, macrophages, antibacterial, and hydrogels. On this basis, integrating multidisciplinary technologies to achieve more effective precision treatment and optimize management strategies for diabetic wounds.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21363
OBJECTIVE: To conduct a meta-analysis concerning the effects of human umbilical cord blood mesenchymal stem cells on pain and function in patients with knee osteoarthritis. METHODS: Using the Chinese search terms “human umbilical cord blood, mesenchymal stem cells, knee joint-related diseases” and the English search terms “human cord blood, mesenchymal stem cell, MSC, knee osteoarthritis, knee joint disease, knee joint disorders, knee OA,” we conducted searches in the CNKI, WanFang, VIP, PubMed, Elsevier, and Web of Science databases. The search timeframe spanned from the establishment of each database until June 13, 2024. The quality of the included literature was assessed using the Cochrane Risk of Bias tool and the ROBINS-I tool. For meta-analysis, the Revman software was utilized, calculating mean differences for continuous variables and relative risks for dichotomous variables, along with 95% confidence intervals. RESULTS: Three randomized controlled trials and three case-control studies were included, totaling 248 subjects, with moderate quality. Meta-analysis showed: (1) The visual analog scale score in the experimental group was lower than that in the control group, with a significant difference (χ²=44.98, P < 0.001, I²=91%); (2) The Western Ontario and McMaster Universities Osteoarthritis Index in the experimental group was lower than that in the control group, with a significant difference (χ²=16.84, P < 0.001, I²=88%); (3) The Lysholm knee function score in the experimental group was higher than that in the control group, with a significant difference (χ²=0.12, P=0.73, I²=0%); (4) The incidence of adverse reactions in the experimental group was higher than that in the control group, with a significant difference (χ²=4.99, P < 0.001, I²=20%), with a combined risk difference of 0.21, translating to a number needed to treat of 5. CONCLUSION: Human umbilical cord blood mesenchymal stem cells can reduce pain and improve knee function in patients with knee osteoarthritis, achieving a good balance between safety and efficacy.