Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05020-6
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce immune dysregulation and multi-organ injury; mesenchymal stromal cell (MSC) therapy has shown promise in clinical trials for COVID-19 and may have broader applicability to pneumonia induced by respiratory viruses (e.g., the influenza virus). This meta-analysis synthesized the available comparative clinical evidence on the safety and efficacy of MSCs in patients with moderate to critical COVID-19 and examined the reported outcomes relevant to Long-COVID. Methods We searched the PubMed, Embase, and CNKI databases for original, comparative studies in moderate, severe, or critical COVID-19 published up to September 2, 2024. Twenty-four eligible studies (13 RCTs and 11 non-randomized controlled trials; n=1080) were included in the mortality meta-analysis. Patients were assigned to either the intervention group (MSC therapy plus standard care) or the control group (standard care with or without placebo). The primary efficacy outcome was all-cause mortality, while the primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included clinical recovery, hospitalization metrics, chest imaging, and inflammatory biomarkers. We performed a pooled meta-analysis on mortality with subgroup analyses (by disease severity, administration route, dosing frequency, and study design), assessment of publication bias (using funnel plots and Egger’s test), and evaluation of the quality of evidence via the GRADE approach. AEs/SAEs were analyzed using meta-analysis and descriptive statistics, while other secondary outcomes were summarized descriptively. Results MSC therapy significantly reduced all-cause mortality (MSC: 26.4% vs control: 31.9%; fixed-effect OR=0.74, 95% CI 0.55–0.99), with low heterogeneity (I2=2.8%, P=0.422[Q-test]) and no publication bias. The quality of evidence
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/s13287-025-04229-1
Background Despite numerous studies addressing the molecular mechanisms by which pluripotent stem cells (PSCs) maintain self-renewal and pluripotency under normal culture conditions, the fundamental question of how PSCs manage to survive stressful conditions remains largely unresolved. Post-transcriptional/translational regulation emerges to be vital for PSCs, but how PSCs coordinate and balance their survival and differentiation at translational level under extrinsic and intrinsic stress conditions is unclear. Methods The high-throughput sequencing of cross-linking immunoprecipitation cDNA library (HITS-CLIP) was employed to decipher the genome-wide OCT4-RNA interactome in human PSCs, a combined RNC-seq/RNA-seq analysis to assess the role of OCT4 in translational regulation of hypoxic PSCs, and an OCT4-protein interactome to search for OCT4 binding partners that regulate cap-independent translation initiation. By taking the Heterozygous Knocking In N-terminal Tags (HKINT) approach that specifically disrupts the 5'-UTR secondary structure and tagging its protein product of the mRNA from one allele while leaving that from the other allele intact, we examined the effect of disrupting the OCT4/5'-UTR interaction on translation of AKT1 mRNA. Results We revealed OCT4 as a bona fide RNA-binding protein (RBP) in human PSCs that bound to the 5'-UTR, 3'-UTR and CDS regions of mRNAs. Multiple known proteins participating in IRES-mediated translation initiation were detected in the OCT4-protein interactome, and a combined RNC-seq/RNA-seq analysis further confirmed a crucial role of OCT4 in translational regulation of PSCs in response to hypoxic stress. Remarkably, OCT4 bound to the GC-rich elements in the 5'-UTR of AKT1 and multiple PI3K/AKT-pathway-gene mRNAs, and promoted their translation initiation via IRES-mediated pathways under stress conditions. Specifically disrupting the AKT1 mRNA 5'-UTR structure and the OCT4/5'-UTR interaction by the HKINT approach significantly reduced the translation level of AKT1 that led to a higher susceptibility of PSCs to oxidative stress-induced apoptotic death and prioritized differentiation toward ectoderm and endoderm. Conclusions Our results reveal OCT4 as an anti-stress RBP for translational regulation that critically coordinates the survival and differentiation of PSCs in response to various stressors.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03745-w
Background Biomaterials used in bone tissue engineering must fulfill the requirements of osteoconduction, osteoinduction, and osseointegration. However, biomaterials with good osteoconductive properties face several challenges, including inadequate vascularization, limited osteoinduction and barrier ability, as well as the potential to trigger immune and inflammatory responses. Therefore, there is an urgent need to develop guided bone regeneration membranes as a crucial component of tissue engineering strategies for repairing bone defects. Methods The mZIF-8/PLA membrane was prepared using electrospinning technology and simulated body fluid external mineralization method. Its ability to induce biomimetic mineralization was evaluated through TEM, EDS, XRD, FT-IR, zeta potential, and wettability techniques. The biocompatibility, osteoinduction properties, and osteo-immunomodulatory effects of the mZIF-8/PLA membrane were comprehensively evaluated by examining cell behaviors of surface-seeded BMSCs and macrophages, as well as the regulation of cellular genes and protein levels using PCR and WB. In vivo, the mZIF-8/PLA membrane's potential to promote bone regeneration and angiogenesis was assessed through Micro-CT and immunohistochemical staining. Results The mineralized deposition enhances hydrophilicity and cell compatibility of mZIF-8/PLA membrane. mZIF-8/PLA membrane promotes up-regulation of osteogenesis and angiogenesis related factors in BMSCs. Moreover, it induces the polarization of macrophages towards the M2 phenotype and modulates the local immune microenvironment. After 4-weeks of implantation, the mZIF-8/PLA membrane successfully bridges critical bone defects and almost completely repairs the defect area after 12-weeks, while significantly improving the strength and vascularization of new bone. Conclusions The mZIF-8/PLA membrane with dual osteoconductive and immunomodulatory abilities could pave new research paths for bone tissue engineering.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03708-1
Background Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. Methods haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC–MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. Results The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at − 80°C, 3 months at − 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 10^8 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. Conclusion haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-023-03624-w
Background Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. Methods Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. Results The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03753-w
Background Nerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects. Methods In vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats. Results Compared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration. Conclusions The ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025223
The clinical use of doxorubicin (DOX) as a chemotherapeutic agent is limited by its cardiotoxic effects. Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, has been increasingly recognized as an important regulator of cardiovascular disease. However, its role in doxorubicin-induced cardiotoxicity remains unknown. Therefore, the objective of this study is to investigate the role and mechanism of FGF13 in doxorubicin-induced cardiac injury. C57BL/6 mice are used to establish Dox-induced cardiotoxicity models. The results reveal that mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening are decreased in the DOX group. In contrast, Fgf13 deficiency mitigates doxorubicin-mediated cardiotoxicity, as indicated by increased mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening. Mechanistically, the protein expressions of bax and cleaved caspase 3 are elevated in the DOX-treated group, along with decreased JC-1 fluorescence intensity and bcl-2 expression, whereas Fgf13 knockout prevents these alterations. In addition, Parkin, but not p53, interacts with FGF13 and is upregulated in response to Fgf13 deficiency in a mouse model of doxorubicin-induced cardiotoxicity. Overall, Fgf13 knockout attenuates doxorubicin-induced cardiomyocyte apoptosis and mitochondrial damage through the modulation of Parkin, indicating that FGF13 may serve as a promising therapeutic target for DOX-induced cardiotoxicity.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025224
MgtE channels play crucial roles in Mg2+ homeostasis and are implicated in bacterial survival under antibiotic exposure. Previous structural and biophysical studies have focused predominantly on Thermus thermophilus MgtE, leaving the structural and mechanistic diversity of MgtE family proteins largely unexplored. In this study, via a genome mining approach, we identify diverse MgtE homologs, including a novel subclass termed the “mini-N type”, which lacks the canonical cytoplasmic N and CBS domains but possesses a unique small N-like domain. Despite extensive expression screening, mini-N-type homologs cannot be stably purified. To address this issue, we design a series of de novo proteins and determine their crystal structures. A selected de novo protein is fused to a mini-N-type MgtE, enabling successful purification and preliminary cryo-EM imaging. Our findings demonstrate that de novo-designed protein fusions serve as powerful tools for stabilizing and purifying otherwise unstable membrane proteins, opening new avenues for structural and functional studies of otherwise inaccessible membrane proteins.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025042
This study elucidates the mechanisms by which cancer-associated fibroblast (CAF)-derived platelet-derived growth factor C (PDGFC) promotes the progression of lung adenocarcinoma (LUAD) and explores the impact of PDGFC on immune regulation within the tumor microenvironment (TME). Our results show that there is higher expression of PDGFC in CAFs than in nontumor tissue fibroblasts (NFs) and that higher expression of PDGFC is correlated with poor prognosis in LUAD patients. Furthermore, CAF-derived PDGFC promotes epithelial-mesenchymal transition (EMT) in cancer cells as well as matrix metalloproteinase 2 (MMP2) expression through the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Moreover, our study demonstrates that CAF-derived PDGFC is essential for the activation and infiltration of fibroblasts in the TME, as well as the inflammatory infiltration of different immune cell types and the immunosuppressive conditions within the TME. In particular, PDGFC induces increased PDGFRA expression in both tumor cells and fibroblasts, which can lead to reciprocally positive feedback to accelerate malignant tumor progression. This discovery provides a novel TME-targeted strategy for LUAD treatment.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025172
Long noncoding RNAs (lncRNAs) are essential in regulating the development and progression of different types of cancer. However, our insights into their impact and mechanisms in papillary thyroid carcinoma (PTC) are still insufficient. In this study, we investigate the effects of the ferroptosis-associated long noncoding RNA LINC02432 on PTC, which recognizes ferroptosis as a critical mechanism in cancer biology and lncRNAs as significant factors in various malignancies. To identify lncRNAs associated with ferroptosis in PTC, we conduct bioinformatics analyses and perform functional assays to evaluate the biological impact of LINC02432 on PTC cells, as well as its relationship with ferroptosis. Mechanistic studies employ methods such as western blot analysis, flow cytometry, and real-time PCR. Our analysis of transcriptome data from TCGA reveals that LINC02432 is the only lncRNA consistently identified by all 10 machine learning methods used, and its expression is significantly downregulated in PTC. Overexpression of LINC02432 in PTC cells inhibits cell proliferation and migration while promoting ferroptosis through inactivation of the NRF2 pathway. LINC02432 knockdown in PTC cells yields the opposite result. These findings highlight the potential of LINC02432 as a tumor suppressor in PTC progression, offering new insights into the mechanisms underlying the development and progression of this malignancy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025146
Actin-bundling protein Fascin1 (FSCN1) is encoded by the Fscn1 gene and is crucial for cytoskeletal remodeling and cellular migration. Although a previous study linked Fscn1 deficiency to neonatal lethality in mice, the underlying metabolic mechanism remains unclear. In this study, we report that systemic knockout (KO) of Fscn1 leads to 52.2% mortality within 24 h post-birth, accompanied by severe hypoglycemia in KO pups compared with their littermates. Remarkably, this lethality is fully rescued by oral glucose administration, indicating a glucose supply-dependent survival mechanism. Surviving Fscn1-KO neonates display persistent developmental deficits, including growth retardation and depleted lipid stores, despite intact canonical insulin-regulated hepatic gluconeogenic pathways. Transcriptomic profiling of P0 livers reveals that Fscn1 loss predominantly disrupts metabolic pathways, with the glycerol phosphate shuttle being the most significantly downregulated module. Mechanistically, Fscn1-KO livers exhibit markedly reduced protein levels of glycerol-3-phosphate dehydrogenase isoforms (GPD1/GPD2), key enzymes bridging glycolysis and gluconeogenesis. Consistently, glycerol tolerance tests demonstrate impaired glycerol-to-glucose conversion in Fscn1-KO mice, confirming defective glycerol-driven gluconeogenesis. Our findings establish FSCN1 as a novel cytoskeletal-metabolic integrator essential for neonatal survival by sustaining hepatic glucose production from glycerol, thus revealing an unexpected role of actin dynamics in coordinating metabolic adaptation during early postnatal development.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024090
MicroRNAs (miRNAs) are implicated in the development of cancers and may serve as potential targets for therapy. However, the functions and underlying mechanisms of miRNAs in cancers are not well understood. This work aims to study the role of miR-373-3p in colon cancer cells. We find that the expression of miR-373-3p mimics promotes and the miR-373-3p inhibitor suppresses aerobic glycolysis and proliferation of colon cancer cells. Mechanistically, miR-373-3p inhibits the expression of MFN2, a gene that is known to suppress glycolysis, which leads to the activation of glycolysis and eventually the proliferation of cells. In a nude mouse tumor model, the expression of miR-373-3p in colon cancer cells promotes tumor growth by enhancing lactate formation, which is inhibited by the co-expression of MFN2 in the cells. Administration of the miR-373-3p antagomir blunts in vivo tumor growth by decreasing lactate production. In addition, in human colon cancers, the expression levels of miR-373-3p are increased, while those of MFN2 mRNA are decreased, and the increase of miR-373-3p is associated with the decrease of MFN2 mRNA. Our results reveal a previously unknown function and underlying mechanism of miR-373-3p in the regulation of glycolysis and proliferation in cancer cells and underscore the potential of targeting miR-373-3p for colon cancer treatment.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024100
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains one of the leading causes of fatal infectious diseases worldwide. The only licensed vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), has variable efficacy against TB in adults. Insufficiency of immune cell function diminishes the protective effects of the BCG vaccine. It is critical to clarify the mechanism underlying the antimycobacterial immune response during BCG vaccination. Macrophage mannose receptor (MR) is important for enhancing the uptake and processing of glycoconjugated antigens from pathogens for presentation to T cells, but the roles of macrophage MR in the BCG-induced immune response against M.tb are not yet clear. Here, we discover that macrophage MR deficiency impairs the antimycobacterial immune response in BCG-vaccinated mice. Mechanistically, macrophage MR triggers JAK-STAT1 signaling, which promotes antigen presentation via upregulated MHC-II and induces IL-12 production by macrophages, contributing to CD4+ T cell activation and IFN-γ production. MR deficiency in macrophages reduces the vaccine efficacy of BCG and increases susceptibility to M.tb H37Ra challenge in mice. Our results suggest that MR is critical for macrophage antigen presentation and the antimycobacterial immune response to BCG vaccination and offer valuable guidance for the preventive strategy of BCG immunization.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024077
Epigenetic modifications play an important role in cellular senescence, and enhancer of zeste homolog 2 (EZH2) is a key methyltransferase involved in epigenetic remodeling in multiple myeloma (MM) cells. We have previously demonstrated that GSK126, a specific EZH2 inhibitor, exhibits anti-MM therapeutic efficacy and safety in vivo and in vitro; however, its specific mechanism remains unclear. This study shows that GSK126 induces cellular senescence in MM, which is characterized by the accumulation of senescence-associated heterochromatin foci (SAHF) and p21, and increased senescence-associated β galactosidase activity. Furthermore, EZH2 is inhibited in ribonucleotide reductase regulatory subunit M2 (RRM2)-overexpressing OCI-MY5 and RPMI-8226 cells. RRM2 overexpression inhibits the methyltransferase function of EZH2 and promotes its degradation through the ubiquitin-proteasome pathway, thereby inducing cellular senescence. In this senescence model, Lamin B1, a key component of the nuclear envelope and a marker of senescence, does not decrease but instead undergoes aberrant accumulation. Meanwhile, phosphorylation of extracellular signal-regulated protein kinase (ERK1/2) is significantly increased. The inhibition of ERK1/2 phosphorylation in turn partially restores Lamin B1 level and alleviates senescence. These findings suggest that EZH2 inhibition increases Lamin B1 level and induces senescence by promoting ERK1/2 phosphorylation. These data indicate that EZH2 plays an important role in MM cellular senescence and provide insights into the relationships among Lamin B1, p-ERK1/2, and cellular senescence.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025098
Pathological myocardial hypertrophy, often caused by hypertension, is a well-established independent risk factor for heart failure. SBK3, a gene selectively expressed at relatively high levels in cardiac tissues, has an unclear functional role in the heart. This study is designed to examine the role of SBK3 in transverse aortic constriction (TAC)-induced heart failure, aiming to identify a novel mitochondrion-targeted therapeutic strategy for heart failure. The subcellular localization of SBK3 in adult rat cardiomyocytes is investigated by western blot analysis and immunofluorescence staining, which reveal that SBK3 is located in the mitochondria. Subsequent western blot analysis shows that SBK3 protein expression is downregulated under pathological hypertrophy. To assess the functional relevance of this observation, SBK3 is overexpressed both in vivo (via cardiac-specific AAV9-cTNT) and in vitro (via adenoviral transduction). In vitro, adenovirus-mediated overexpression of SBK3 significantly inhibits ANP and BNP expression and increases the Ca2+ transient amplitude in angiotensin II (Ang II)-induced hypertrophic cardiomyocytes. In vivo, cardiac-specific SBK3 overexpression using cTNT promoter-containing adeno-associated virus 9 inhibits TAC-induced cardiac hypertrophy and heart failure. Mechanistically, SBK3 exerts its cardioprotective effects by preserving the mitochondrial ultrastructure and regulating the balance of respiratory chain complexes. In addition, SBK3 modulates key regulators of mitochondrial dynamics, including fission and fusion proteins, thereby contributing to mitochondrial integrity and protection against pathological cardiac remodeling.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025017
Studies of cell-to-cell activities in the tumor microenvironment (TME) have identified multiple potential targets for oncotherapy. The interplay between tumor cells and neighboring cancer-associated fibroblasts (CAFs) persists in all stages of tumor progression. In this study, we reveal that exosomes from breast cancer cells can be endocytosed into fibroblasts and transform normal fibroblasts (NFs) into CAFs and that the ability of exosomes from highly metastatic breast cancer cells is greater than that of those from poorly metastatic breast cancer cells. Further investigation reveals that exosomes from highly metastatic breast cancer cells contain much more miR-105-5p than those from poorly metastatic breast cells do and that exosomal miR-105-5p facilitates the transformation of NFs to CAFs. A detailed study reveals that RBMY1A1-dependent sorting of miR-105-5p into fibroblasts and subsequent internalization of miR-105-5p promote the transformation of NFs to CAFs by downregulating LATS2 expression and activating NF-κB signaling, which concurrently facilitates the EMT of breast cancer cells. Thus, our results indicate that exosomal miR-105-5p may be a potential target for novel therapeutic strategies to prevent the coevolution of breast cancer cells and CAFs.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024236
Mitochondrial dysfunction is implicated in numerous disorders, including type 2 diabetes, Alzheimer’s disease and cancer. Long non-coding RNAs (lncRNAs) are emerging as pivotal regulators of cellular energy metabolism, yet their roles remain largely unclear. In this study, we identify an lncRNA named linc-PMB, which is associated with mTOR and promotes mitochondrial biogenesis, through microarray analysis. We demonstrate that the knockdown of linc-PMB results in significantly impaired mitochondrial respiration and biogenesis, along with altered expressions of related genes. Conversely, overexpression of linc-PMB markedly increases mitochondrial function. We further reveal that linc-PMB interacts with the RNA-binding protein HuR, promoting the stabilization of SIRT1 mRNA and a substantial increase in SIRT1 expression, which in turn activates the PGC-1α/mtTFA pathway and mitochondrial biogenesis. Collectively, our findings reveal a novel regulatory pathway in which linc-PMB, through its interaction with HuR, modulates the SIRT1/PGC-1α/mtTFA axis to maintain mitochondrial biogenesis and function.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024168
Uncoupling protein-2 (UCP2) controls the antioxidant response and redox homeostasis in cancer and is considered a potent molecular target for cancer treatment. However, the specific mechanism of UCP2 inhibition and its role in glioblastoma (GBM) have not yet been elucidated. Here, we attempt to identify a UCP2 inhibitor and study the underlying molecular mechanism in GBM. Bioinformatics analysis and immunohistochemistry are used to validate the high expression of UCP2 in GBM and its prognostic significance. Drug intervention and tumor xenograft experiments are conducted to determine the inhibitory effect of genipin, a UCP2 inhibitor, on UCP2. The mitochondrial membrane potential and key ferroptosis genes are examined to determine the occurrence of ferroptosis. High expression of UCP2 in GBM is associated with poor prognosis, and inhibiting UCP2 can alleviate the malignant behavior of GBM tumors. Genipin can downregulate the expression of GPX4 and upregulate the expression of ACSL4 by inhibiting UCP2, leading to ferroptosis and alleviating the malignant behavior of tumors. In summary, UCP2 is a potential therapeutic target for GBM. Genipin, which targets UCP2, effectively inhibits GBM development by inducing ferroptosis in vivo and in vitro. These findings indicate that genipin treatment based on UCP2 targeting has potential therapeutic applications with a clinical perspective for the treatment of GBM patients.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025147
CD47, a cell surface transmembrane glycoprotein, is an innate immune checkpoint that suppresses phagocytic clearance. Emerging evidence suggests that CD47 has noncanonical functions. However, its involvement in chemotherapy resistance is not well understood. Our study reveals that cisplatin treatment upregulates CD47 expression across multiple cancer cell lines. Cisplatin induces the expression of CD47 through the ATM/NF-κB signaling pathway. Genetic ablation of CD47 dramatically sensitizes cancer cells to cisplatin. Mechanistically, CD47 depletion potentiates cisplatin-induced DNA damage, as demonstrated by elevated γH2AX formation and ATM phosphorylation. Knockdown of CD47 inhibits the expression of DNA repair genes ERCC1, FANCA, and BRCA2 through the ATM/NF-κB pathway. Remarkably, CD47 blockade with neutralizing antibodies recapitulates these effects, synergistically potentiating cisplatin’s DNA-damaging capacity while suppressing DNA repair capacity. CD47 blockade also potentiates cisplatin’s tumor inhibitory effect in vivo. These findings establish a novel mechanism whereby CD47 promotes cisplatin resistance through transcriptional regulation of DNA repair pathway, providing rationale for combining CD47-targeted therapies with conventional chemotherapy. This dual approach could simultaneously overcome immune evasion while enhancing treatment efficacy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025128
Hepatocellular carcinoma (HCC) continues to pose a chief threat to the global healthcare landscape and is characterized by scarce therapeutic options and poor clinical outcomes, especially in advanced-stage disease. Although lymphocyte antigen 96 (LY96) is associated with immunogenic cell death, its specific role in HCC progression and therapeutic potential remains unclear. To identify prospective therapeutic targets in HCC, by combining the cancer-immunity cycle score with WGCNA and systems biology methods, we identify pivotal molecular interactions. By integrating the cancer-immunity cycle score with WGCNA and systems-level approaches, we systematically identify potential therapeutic targets in HCC. We evaluate LY96 expression at the transcriptomic and proteomic levels in HCC tissues and explore its prognostic relevance by drawing upon information from The Cancer Genome Atlas (TCGA) repository. The functional role of LY96 is delineated through a panel of cellular assays conducted in vitro, complemented by in vivo tumorigenesis models. To identify the downstream signaling cascades associated with LY96, gene set enrichment analysis (GSEA) is performed to elucidate the implicated pathways, which are then confirmed via experimental validation. Furthermore, we employ a lipid-polymer hybrid nanoparticle (NP) platform to facilitate the systemic delivery of an LY96 inhibitor and demonstrate its potential as a newly proposed intervention strategy for HCC. Clinically, marked LY96 overexpression occurs in HCC samples, where elevated LY96 expression is strongly associated with reduced overall survival (OS) among liver cancer patients. LY96 facilitates the progression of HCC via complementary in vitro and in vivo approaches. Mechanistically, LY96 induces the activation of the TGF-β1/Smad2/3 signaling axis in HCC. For therapeutic applications, we develop a liposome-based nanoparticle system that delivers the LY96 inhibitor L6H21 to tumor cells and effectively suppresses HCC progression through a combination of in vivo and in vitro studies. Taken together, the current observations identify LY96 as a promising diagnostic indicator and a viable intervention for therapeutic modulation to improve HCC treatment.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024211
RNA splicing and 3′-cleavage and polyadenylation (CPA) are essential processes for the maturation of RNA. There have been extensive independent studies of these regulated processing events, including alternative splicing (AS) and alternative polyadenylation (APA). However, growing evidence suggests potential crosstalk between splicing and 3′-end processing in regulating AS or APA. Here, we first provide a brief overview of the molecular machines involved in splicing and 3′-end processing events, and then review recent studies on the functions and mechanisms of the crosstalk between the two processes. On the one hand, 3′-end processing can affect splicing, as 3′-end processing factors and CPA-generated polyA tail promote the splicing of the last intron. Beyond that, 3′-end processing factors can also influence the splicing of internal and terminal exons. Those 3′-end processing factors can also interact with different RNA-binding proteins (RBPs) to exert their effects on AS. The length of 3′ untranslated region (3′ UTR) can affect the splicing of upstream exons. On the other hand, splicing and CPA may compete within introns in generating different products. Furthermore, splicing within the 3′ UTR is a significant factor contributing to 3′ UTR diversity. Splicing also influences 3′-end processing through the actions of certain splicing factors. Interestingly, some classical RBPs play dual roles in both splicing and 3′-end processing. Finally, we discuss how long-read sequencing technologies aid in understanding the coordination of AS-APA events and envision that these findings may potentially promote the development of new strategies for disease diagnosis and treatment.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024110
Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of advanced/metastatic patients with lung cancer. However, only a small proportion of patients can benefit from ICIs, and clinical management of the treatment process remains challenging. Glycosylation has added a new dimension to advance our understanding of tumor immunity and immunotherapy. To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins, a series of serum samples from 12 patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, are firstly analyzed with mass-spectrometry-based label-free quantification method. Second, a stratification analysis is performed among anti-PD-1/PD-L1 responders and non-responders, with serum levels of glycopeptides correlated with treatment response. In addition, in an independent validation cohort, a large-scale site-specific profiling strategy based on chemical labeling is employed to confirm the unusual characteristics of IgG N-glycosylation associated with anti-PD-1/PD-L1 treatment. Unbiased label-free quantitative glycoproteomics reveals serum levels’ alterations related to anti-PD-1/PD-L1 treatment in 27 out of 337 quantified glycopeptides. The intact glycopeptide EEQFN177STYR (H3N4) corresponding to IgG4 is significantly increased during anti-PD-1/PD-L1 treatment (FC=2.65, P=0.0083) and has the highest increase in anti-PD-1/PD-L1 responders (FC=5.84, P=0.0190). Quantitative glycoproteomics based on protein purification and chemical labeling confirms this observation. Furthermore, obvious associations between the two intact glycopeptides (EEQFN177STYR (H3N4) of IgG4, EEQYN227STFR (H3N4F1) of IgG3) and response to treatment are observed, which may play a guiding role in cancer immunotherapy. Our findings could benefit future clinical disease management.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024075
Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis. Here, we show that following transverse aortic constriction (TAC) surgery, interstitial fibrosis and collagen content increase in mice, along with reduced ejection fraction and fractional shortening, augmented heart mass. However, following Fgf13 deletion, interstitial fibrosis is decreased, ejection fraction and fractional shortening are increased, and heart mass is decreased, compared with those in the TAC group. Mechanistically, incubation of cardiac fibroblasts with transforming growth factor β (TGFβ) increases the expressions of types I and III collagen proteins, as well as α-smooth muscle actin (α-SMA) proteins, and enhances fibroblast proliferation and migration. In the absence of Fgf13, the expressions of these proteins are decreased, and fibroblast proliferation and migration are suppressed, compared with those in the TGFβ-stimulated group. Overexpression of FGF13, but not FGF13 mutants defective in microtubule binding and stabilization, rescues the decrease in collagen and α-SMA protein and weakens the proliferation and migration function of the Fgf13 knockdown group. Furthermore, Fgf13 knockdown decreases ROCK protein expression via microtubule disruption. Collectively, cardiac Fgf13 knockdown protects the heart from fibrosis in response to haemodynamic stress by modulating microtubule stabilization and ROCK signaling pathway.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024018
Psoriasis is accepted as a chronic, inflammatory, immune-mediated skin disease triggered by complex environmental and genetic factors. For a long time, disease recurrence, drug rejection, and high treatment costs have remained enormous challenges and burdens to patients and clinicians. Natural products with effective immunomodulatory and anti-inflammatory activities from medicinal plants have the potential to combat psoriasis and complications. Herein, an imiquimod (IMQ)-induced psoriasis-like dermatitis model is established in mice. The model mice are treated with 1% rutaecarpine (RUT) (external use) or the oral administration of RUT at different concentrations. Furthermore, high-throughput 16S rRNA gene sequencing is applied to analyze the changes in the diversity and composition of the gut microbiota. Based on the observation of mouse dorsal skin changes, RUT can protect against inflammation to improve psoriasis-like skin damage in mice. Additionally, RUT could suppress the expression levels of proinflammatory cytokines (IL-23, IL-17A, IL-22, IL-6, and IFN-α) within skin tissue samples. Concerning gut microbiota, we find obvious variations within the composition of gut microflora between IMQ-induced psoriasis mice and RUT-treated psoriasis mice. RUT effectively mediates the recovery of gut microbiota in mice induced by IMQ application. Psoriasis is linked to the production of several inflammatory cytokines and gut microbiome alterations. This research shows that RUT might restore gut microbiota homeostasis, reduce inflammatory cytokine production, and ameliorate psoriasis symptoms. In conclusion, the gut microbiota might be a therapeutic target or biomarker for psoriasis that aids in clinical diagnosis and therapy.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024097
Phosphatidylcholine (PC) is the most abundant phospholipid in mammalian cells, accounting for approximately 50% of all phospholipids and serving as a main component of cellular and subcellular membranes. PC is a mixture of many species with distinct functions, and its levels are altered in cancer. Previous studies have shown contradictory roles of PC in cancer development. Here, we investigated the effects of PC and its main component, 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), on mouse colon cancer MC38 cells. PC dose-dependently decreased cell viability, and DLPC was identified as the active component. DLPC inhibited MC38 cell growth more effectively than PC, while structurally similar PCs with different acyl chain lengths or unsaturation degrees did not. This suggests that the specific structure of DLPC is crucial for its activity. Further mechanistic studies revealed that DLPC induces ferroptosis, a form of regulated cell death, in cancer cells. These findings highlight DLPC as a potential therapeutic agent for cancer treatment and underscore the importance of studying individual PC species.
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.0253-2670.2026.15.20261507
This study reports the fabrication and in vitro evaluation of carrier-free self-assembled nanoparticles (SSD-CBD) composed of saikosaponin D (SSD) and cannabidiol (CBD) at a 3:1 mass ratio via nano co-precipitation. Assembly mechanisms were probed using XPS, FTIR, and 1H-1H NOESY, revealing hydrogen bonding and hydrophobic interactions as principal driving forces. Physicochemical characterization by TEM and DLS confirmed a stable nanoscale architecture. The formulation exhibited pH-responsive release, preferentially discharging payload in tumor microenvironment (pH 6.8) while retaining stability at physiological pH 7.4. In HepG2 hepatocellular carcinoma cells, SSD and CBD displayed synergy with a combination index (CI) of 0.79. MTT assays, Annexin V-FITC/PI flow cytometry, and caspase activity measurements demonstrated that SSD-CBD nanoparticles induce apoptosis via the mitochondrial pathway. The carrier-free strategy addresses CBD's poor aqueous solubility and instability, simultaneously improving delivery efficiency and enabling precise synergistic drug co-administration. These findings provide an experimental foundation for intelligent nanomedicine development based on SSD. However, in vivo pharmacokinetics, tissue distribution, tumor accumulation, and potential hepatotoxicity of SSD in nanoformulation remain unresolved. Future work should focus on surface engineering (e.g., PEGylation or targeting ligand modification) to enhance stability and tumor targeting, integration of immunomodulatory components, and scalable GMP-compliant manufacturing with comprehensive quality control.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261504
This study establishes an integrated strategy for rapid screening of pancreatic lipase (PPL) inhibitors from Rheum palmatum and elucidates their anti-obesity mechanisms. Fe3O4@SiO2@PPL magnetic nanoparticles were synthesized via chemical co-precipitation, Stöber method, and cross-linking, and characterized by FTIR, SEM, and XRD. Ligand fishing from a 30% ethanol extract specifically captured four compounds: chrysophanol-8-O-β-D-glucopyranoside, aloe-emodin, rhein, and chrysophanol. In vitro enzyme assays confirmed that chrysophanol and aloe-emodin exhibited potent PPL inhibition with IC50 values of 67.03 and 85.86 µmol/L, respectively. Molecular docking revealed that these active components form hydrogen bonds and hydrophobic interactions with key amino acid residues of PPL, consistent with experimental inhibition. Network pharmacology identified 150 overlapping targets between the active compounds and obesity, with five core targets: EGFR, AKT1, SRC, HSP90AA1, and BCL2. Pathway enrichment analysis highlighted the HIF-1 signaling pathway and lipid and atherosclerosis pathway as principal mechanisms. The developed 'material screening–computational validation–network prediction' platform offers a robust tool for high-throughput discovery of natural PPL inhibitors and provides methodological reference for multi-target mechanistic studies of traditional Chinese medicine.
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/s13287-026-05095-1
Background: Human umbilical cord mesenchymal stem cells (UC-MSCs) are promising for cellular therapy due to their accessibility, low ethical concerns, and immunomodulatory and tissue repair capacities. However, heterogeneity during in vitro expansion poses quality control challenges. Methods: Two fetal umbilical cords were obtained; primary UC-MSCs were isolated and passaged continuously. Cells were harvested for single-cell RNA sequencing; 78,178 cells and 14 subpopulations were analyzed. Validation used in vitro assays and in vivo studies. Results: Mid-passage UC-MSCs showed superior functional performance based on differential gene expression and functional enrichment. An optimal subpopulation (C8) was identified by holistic evaluation of stemness, hematopoietic support, and immunomodulation. NOTCH signaling was enriched in C8, with NOTCH2 as the dominant receptor. MLPH and LPXN were identified as signature markers; MLPHhighLPXNhigh UC-MSCs displayed higher hematopoietic support and immunosuppression than MLPHlowLPXNlow cells. Conclusions: Mid-passage UC-MSCs are favorable for clinical use. The subpopulation with high NOTCH activity exhibits enhanced hematopoietic support and immunosuppression. MLPH and LPXN are ideal markers for isolating this functional subpopulation.
Acta Hydrobiologica Sinica•2026•DOI: 10.3724/1000-3207.2026.2026.0101
High-density crowding stress during the initial feeding stage poses severe challenges to fish health, promoting lipid peroxidation. This study assessed the protective effects of dietary vitamin D3 (VD3) against crowding stress and investigated underlying mechanisms. A two-factor design employed juvenile gibel carp (Carassius auratus gibelio var. CAS V) (0.47±0.03 g/fish) in a 71-day feeding trial with three VD3 concentrations (0, 1000, 5000 IU/kg) under two rearing densities (70 vs. 210 fish/tank). Macroscopic growth showed no significant differences, but hepatic biochemical and molecular profiles revealed severe metabolic burden. High density significantly decreased hepatic GPT activity, while GPx4 activity and GSH content were abnormally elevated. Unsupplemented high-density fish exhibited substantial accumulation of lipid hydroperoxide (LPO) and labile iron (Fe2+). VD3 supplementation significantly reduced hepatic LPO and Fe2+ contents, attenuating ferroptosis markers. Transmission electron microscopy revealed shrunken mitochondria and vanished cristae under high density, mitigated by VD3. Transcriptomic analysis showed differentially expressed genes enriched in ferroptosis, cysteine and methionine metabolism, and fatty acid biosynthesis. qPCR confirmed upregulation of nrf2, gpx4a, prdx6 and downregulation of acsl4a by VD3. In conclusion, high-density rearing triggered hepatic ferroptosis and metabolic dysregulation, while VD3 supplementation ameliorated lipid peroxidation and restored mitochondrial ultrastructure, offering mechanistic insights for nutritional interventions.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05020-6
Background: SARS-CoV-2 infection induces immune dysregulation and multi-organ injury. Mesenchymal stromal cell (MSC) therapy has shown promise in COVID-19 trials, with potential applicability to other viral pneumonias. This meta-analysis synthesized comparative clinical evidence on MSC safety and efficacy in moderate to critical COVID-19, including Long-COVID outcomes. Methods: PubMed, Embase, and CNKI were searched for comparative studies published up to September 2, 2024. Twenty-four studies (13 RCTs, 11 non-randomized; n=1080) were included. Patients received MSC therapy plus standard care (intervention) or standard care with/without placebo (control). Primary efficacy outcome: all-cause mortality. Primary safety outcomes: adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes: clinical recovery, hospitalization metrics, chest imaging, inflammatory biomarkers. Meta-analysis with subgroup analyses (disease severity, administration route, dosing frequency, study design), publication bias assessment (funnel plots, Egger's test), and GRADE evaluation were performed. Results: MSC therapy significantly reduced all-cause mortality (26.4% vs 31.9%; fixed-effect OR=0.74, 95% CI 0.55–0.99), with low heterogeneity (I2=2.8%, P=0.422) and no publication bias. Evidence quality was moderate. AEs/SAEs were comparable between groups. Secondary outcomes favored MSC therapy in severe/critical subgroups. Conclusion: MSC therapy reduces mortality and improves clinical outcomes in severe/critical COVID-19 with a favorable safety profile. Efficacy in moderate illness remains inconclusive. Early signals suggest benefit in Long-COVID recovery. Standardized protocols and long-term follow-up are needed.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025224
MgtE channels play crucial roles in Mg2+ homeostasis and are implicated in bacterial survival under antibiotic exposure. Previous structural and biophysical studies have focused predominantly on Thermus thermophilus MgtE, leaving the structural and mechanistic diversity of MgtE family proteins largely unexplored. In this study, via a genome mining approach, we identify diverse MgtE homologs, including a novel subclass termed the “mini-N type”, which lacks the canonical cytoplasmic N and CBS domains but possesses a unique small N-like domain. Despite extensive expression screening, mini-N-type homologs cannot be stably purified. To address this issue, we design a series of de novo proteins and determine their crystal structures. A selected de novo protein is fused to a mini-N-type MgtE, enabling successful purification and preliminary cryo-EM imaging. Our findings demonstrate that de novo-designed protein fusions serve as powerful tools for stabilizing and purifying otherwise unstable membrane proteins, opening new avenues for structural and functional studies of otherwise inaccessible membrane proteins.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025223
The clinical use of doxorubicin (DOX) as a chemotherapeutic agent is limited by its cardiotoxic effects. Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, has been increasingly recognized as an important regulator of cardiovascular disease. However, its role in doxorubicin-induced cardiotoxicity remains unknown. Therefore, the objective of this study is to investigate the role and mechanism of FGF13 in doxorubicin-induced cardiac injury. C57BL/6 mice are used to establish Dox-induced cardiotoxicity models. The results reveal that mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening are decreased in the DOX group. In contrast, Fgf13 deficiency mitigates doxorubicin-mediated cardiotoxicity, as indicated by increased mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening. Mechanistically, the protein expressions of bax and cleaved caspase 3 are elevated in the DOX-treated group, along with decreased JC-1 fluorescence intensity and bcl-2 expression, whereas Fgf13 knockout prevents these alterations. In addition, Parkin, but not p53, interacts with FGF13 and is upregulated in response to Fgf13 deficiency in a mouse model of doxorubicin-induced cardiotoxicity. Overall, Fgf13 knockout attenuates doxorubicin-induced cardiomyocyte apoptosis and mitochondrial damage through the modulation of Parkin, indicating that FGF13 may serve as a promising therapeutic target for DOX-induced cardiotoxicity.
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: 10.12307/2026.21264
BACKGROUND: Previous studies have established a correlation between non-alcoholic fatty liver disease and sarcopenia; however, their causal relationship remains uncertain. The gut-muscle-liver axis hypothesis posits intricate interactions between the gut microbiota and both sarcopenia and non-alcoholic fatty liver disease, yet the precise pathogenic mechanisms underlying these interactions remain poorly elucidated. OBJECTIVE: To investigate the potential causal relationship between sarcopenia and non-alcoholic fatty liver disease using Mendelian randomization analysis and to delve into the potential role of the gut microbiota in mediating or influencing the interplay between non-alcoholic fatty liver disease and sarcopenia. METHODS: Sarcopenia data were sourced from the UK Biobank (the UK National-Level Biomedical Database, supported by the UK government and developed in 2006 in collaboration with institutions such as the University of Oxford and the University of Manchester, which encompasses multidimensional data including genes, imaging, and health records from 500 000 participants), with relevant traits including appendicular muscle mass, grip strength, and walking speed. The non-alcoholic fatty liver disease dataset was derived from a publicly accessible GWAS summary dataset compiled by Ghodsian et al., comprising aggregated statistics from GWAS cohorts including eMERGE and FinnGen, updated GWAS data of non-alcoholic fatty liver disease from the UK Biobank, and newly conducted GWAS data from the Estonian Biobank. The 211 gut microbiota data were obtained from a large-scale human gut microbiome composition study conducted by the MiBioGen consortium. Inverse variance weighting, weighted median, MR-Egger, weighted model, and simple model methods were used to assess the mutual influences among non-alcoholic fatty liver disease, sarcopenia, and gut microbiota-related traits. RESULTS AND CONCLUSION: The inverse variance weighting analysis indicated that walking speed and appendicular muscle mass were negatively correlated with non-alcoholic fatty liver disease, while left and right hand grip strength showed no significant correlation with non-alcoholic fatty liver disease risk. Reverse Mendelian randomization analysis showed that non-alcoholic fatty liver disease was negatively correlated with appendicular muscle mass, but no significant correlation was found between non-alcoholic fatty liver disease and walking speed or left and right hand grip strength. Thirty-nine gut microbiota taxa were significantly associated with sarcopenia onset, and six gut microbiota taxa had a causal relationship with non-alcoholic fatty liver disease. The study suggests that gut microbiota may regulate the 'gut-liver-muscle axis' through short-chain fatty acid metabolism, providing a new direction for cross-organ mechanism research for Chinese scholars. Combined with the unique genetic background of the Chinese population (such as ALDH2 mutations and genes related to high-salt diet), it can further analyze the race-specific pathways of metabolic-muscle comorbidity, providing a scientific basis for formulating dietary recommendations that conform to the Chinese dietary structure (such as high grain intake).
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21416
BACKGROUND: Non-infectious poor wound healing following lumbar surgery is a significant clinical complication that prolongs hospitalization and increases the risk of reoperation. However, its predictive indicators remain unclear. Based on the hypothesis that paraspinal muscle degeneration may impede tissue repair by altering the local microenvironment, this study aimed to investigate the predictive value of preoperative paraspinal muscle fatty infiltration for non-infectious poor wound healing and its association with osteoporosis. OBJECTIVE: To quantify the degree of paraspinal muscle fatty infiltration using preoperative MRI and evaluate its predictive value for non-infectious poor wound healing after lumbar surgery. METHODS: A retrospective analysis was conducted on medical records of 4,368 patients who underwent traditional open posterior lumbar surgery at Third Affiliated Hospital of Guangzhou University of Chinese Medicine between 2019 and 2024. We screened 190 patients with a postoperative hospital stay of 15 days or longer. Based on postoperative wound healing and infection indicators, 41 patients with non-infectious poor healing were selected as the poor healing group. From the remaining 4,178 patients, 40 patients with good healing were selected as the good healing group. The poor healing group was further subdivided into osteoporosis and non-osteoporosis subgroups. Preoperative lumbar MRI images were collected, and Image J software was used to measure the cross-sectional area of the psoas major muscle and the percentage of fat infiltration in the erector spinae and multifidus muscles. RESULTS AND CONCLUSION: (1) There were no significant differences in gender, age, or diabetes between the poor healing and good healing groups (P > 0.05). (2) The functional cross-sectional area and fat infiltration percentage of the psoas major, erector spinae, and multifidus muscles were significantly different between the two groups (P < 0.05). (3) Logistic regression analysis showed that fat infiltration percentage was an independent risk factor for poor wound healing. (4) Receiver operating characteristic curve analysis showed that fat infiltration percentage had high predictive value for poor wound healing (area under the curve > 0.7). (5) One-way ANOVA indicated that osteoporosis was a risk factor for fat infiltration in the L4 multifidus muscle (P < 0.05). (6) The results indicate that paraspinal muscle fat infiltration percentage is an important predictor of non-infectious poor wound healing after traditional open posterior lumbar surgery, providing clinical reference. Osteoporosis was also confirmed as a risk factor for L4 multifidus fat infiltration, but due to the small subgroup sample size, whether osteoporosis affects non-infectious poor healing after lumbar surgery requires further clinical trials.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21409
BACKGROUND: Conventional rectangular targeting devices are divided into two modules, one left and one right, which hinders flexible intraoperative use and is prone to deformation and error. Even after connection, repeated fluoroscopic confirmation is still required for screw drilling and placement. OBJECTIVE: To investigate the key technology development and clinical application of a modified rectangular locking device for precise distal locking screw placement in intramedullary nailing of femoral shaft fractures. METHODS: Medical records of patients with femoral shaft fractures admitted to Affiliated Suqian Hospital of Xuzhou Medical University and Suyu District People's Hospital from 2021 to 2023 were collected. Patients aged 18-65 years, diagnosed with femoral shaft fractures (AO classification: A, B, or C) by radiographic examination, who underwent closed reduction and intramedullary nailing with distal locking screw placement using the modified rectangular locking device, and whose clinical data (including medical history, radiographic findings, surgical records, and follow-up records) were selected. Forty-one cases met the criteria, including 30 males and 11 females, aged 20-62 years, with an average age of (41.17±8.14) years. Intraoperative fluoroscopy times, locking success rate, time for successful distal locking screw placement, American Knee Society Score at 1 month postoperatively and after fracture healing, and fracture healing time were collected. RESULTS AND CONCLUSION: (1) All 41 patients underwent distal locking screw placement using the modified rectangular locking device. Intraoperative fluoroscopy times ranged from 0 to 2 times, with an average of (1.1±0.5) times; the locking success rate was 98%; the time for successful distal locking screw placement ranged from 6 to 10 minutes, with an average of (7.0±1.5) minutes; the American Knee Society Score at 1 month postoperatively ranged from 140 to 190, with an average of (150±15) points. (2) Thirty-eight patients were followed up completely for 12-24 months. Fracture healing time ranged from 9 to 14 months, with an average of (10.5±2.5) months. After fracture healing, the American Knee Society Score ranged from 150 to 190, with an average of (185±8) points, with 35 excellent and 3 good results. (3) The results indicate that compared with freehand locking, oblique fluoroscopic placement, arthroscopic-assisted placement, and electromagnetic navigation locking of distal locking screws, the modified rectangular locking device offers advantages including no dependence on arthroscopic or electromagnetic navigation equipment, no requirement for extensive surgical experience, simple steps, accurate locking, high repeatability, and reduced radiation exposure.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21367
BACKGROUND: Extracorporeal shock wave therapy, as a non-invasive and non-invasive treatment technique, is widely used in various fields. Currently, there is no systematic analysis of the latest research status, hot topics, and development trends in this field. OBJECTIVE: To analyze the research status, hotspots, and trends of extracorporeal shock wave therapy using bibliometric visualization software over the past 10 years. METHODS: Relevant literature in the field of extracorporeal shock wave therapy was retrieved from the Web of Science core database from January 1, 2015 to December 31, 2024. CiteSpace was used for analyzing publication volume, collaborations among countries/regions, institutions, and authors, citation analysis of journals and co-cited literature. Additionally, keyword co-occurrence, clustering, and burst analyses were conducted, and visualized knowledge maps were generated. RESULTS AND CONCLUSION: A total of 1 641 articles were included. The number of publications in the field of extracorporeal shock wave therapy is generally on the rise over the past 10 years. China, the United States, and Italy are the top three countries in terms of publication volume, while Chang Gung University, the University of California, and Harvard University are the top three research institutions. A total of 280 journals published articles related to extracorporeal shock wave therapy, among which Clinical Orthopaedics and Related Research was the most cited journal, and PLoS One had the highest centrality. The author with the highest publication volume was Wang, Ching-Jen from Chang Gung University, and there was little collaboration among high-yield authors and their research groups. The hot keywords in this field were mainly double-blind, pain, erectile dysfunction, plantar fasciitis, lateral epicondylitis, etc. Burst keywords included rabbit, ischemia, myocardial infarction, fasciopathy, muscle spasm, and erectile function, showing diversified research directions. Extracorporeal shock wave therapy is a non-invasive and safe treatment method. Pain management, musculoskeletal system diseases, and urological-related diseases are the research hotspots in the field of extracorporeal shock wave therapy in the past 10 years, and research on related mechanisms is also a focus of interest. Future research directions may focus on standard parameter research and long-term efficacy verification of extracorporeal shock wave therapy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21315
BACKGROUND: Studies have confirmed that A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS8) plays a regulatory role in fibrosis, so it is of great clinical significance to explore the mechanism of ADAMTS8 in hypertrophic scars. OBJECTIVE: To investigate the regulatory effect of ADAMTS8 on hypertrophic scars. METHODS: (1) Immunohistochemical staining was used to detect the expression of type I collagen, type III collagen, alpha-smooth muscle actin and ADAMTS8 in normal human skin and hypertrophic scar tissues. Western blot was used to detect ADAMTS8 protein expression in normal skin and hypertrophic scar tissues. With hypertrophic scar as positive sample and normal skin as negative sample, receiver operating characteristic curve was drawn to analyze the ability of ADAMTS8 to predict and distinguish normal skin from hypertrophic scar. (2) STRING 12.0 platform was used to construct a protein-protein interaction network for ADAMTS8, and GO functional enrichment and KEGG pathway enrichment analyses were performed on the obtained targets. (3) Fibroblasts from human hypertrophic scar tissue were isolated and cultured. The 3rd to 6th generation fibroblasts were divided into three groups: control group (routine culture), Ad-NC group (transfected with empty adenovirus), and Ad-ADAMTS8 group (transfected with adenovirus overexpressing ADAMTS8). CCK-8 assay and EdU staining were used to detect cell proliferation activity, and flow cytometry and TUNEL staining were used to detect cell apoptosis. RESULTS AND CONCLUSION: (1) Immunohistochemical staining showed that the expression of type I collagen, type III collagen and alpha-smooth muscle actin in hypertrophic scars was higher than that in normal skin (P < 0.001), while ADAMTS8 expression was lower than that in normal skin (P < 0.001). Western blot showed that ADAMTS8 protein expression in hypertrophic scars was lower than that in normal skin (P < 0.001). Receiver operating characteristic curve showed that the area under the curve of ADAMTS8 predicting hypertrophic scar was 0.86, indicating that ADAMTS8 has good ability to distinguish hypertrophic scar from normal skin. (2) The top 41 genes were screened through STRING database. KEGG enrichment showed that ADAMTS8 was mainly involved in extracellular matrix receptor interaction, phosphatidylinositol-3-kinase-protein kinase B signaling pathway, efferocytosis and other biological processes and key mechanisms. GO enrichment showed that ADAMTS8 was involved in apoptosis-related pathway enrichment, including negative regulation of fibroblast growth factor receptor signaling pathway, fibroblast growth factor binding, negative regulation of apoptosis and apoptotic process. (3) CCK-8 assay and EdU staining showed that overexpression of ADAMTS8 inhibited the proliferation of hypertrophic scar fibroblasts; flow cytometry and TUNEL staining showed that overexpression of ADAMTS8 promoted apoptosis of hypertrophic scar fibroblasts. (4) These results indicate that ADAMTS8 expression is decreased in human hypertrophic scars, and overexpression of ADAMTS8 can inhibit proliferation and promote apoptosis of hypertrophic scar fibroblasts.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21313
BACKGROUND: Peri-implant bone defects may affect implant stability. Platelet-rich fibrin, a second-generation autologous platelet concentrate, contains abundant growth factors and fibrin scaffolds and can facilitate bone regeneration. Nevertheless, its mechanism of action in the context of peri-implant bone defects remains to be fully investigated. OBJECTIVE: To investigate the effects of platelet-rich fibrin on osteogenic genes, bone microstructure, and IκB kinase/inhibitor of nuclear factor-κB/nuclear factor-κB signaling pathway in rats with peri-implant bone defect using a rat tibia model to simulate peri-implant bone defects, combined with ligature-induced inflammation. METHODS: Thirty male Sprague-Dawley rats were selected, and 20 of them were selected to establish peri-implant bone defect model. After modeling, they were randomly divided into model group and platelet-rich fibrin group, with an average of 10 rats per group, and the remaining 10 rats were assigned to the control group. The control group and the model group were not treated with any intervention, and the platelet-rich fibrin group was treated with platelet-rich fibrin implantation at the bone defect site. After 8 weeks, Image-Pro-Plus software was used to detect implant-bone contact rate and new bone formation rate; Micro-CT was used to detect bone microstructure changes; hematoxylin-eosin staining was used to observe histopathological changes; western blot was used to detect the protein expression of nuclear factor-κB, inhibitor of nuclear factor-κB, and IκB kinase in tibial tissue; RT-PCR was used to detect the expression of osteogenic-related genes osteopontin, osteocalcin, and Runt-related transcription factor 2. RESULTS AND CONCLUSION: (1) At 4 and 8 weeks after surgery, the new bone formation rate and implant-bone contact rate in the model group and platelet-rich fibrin group were increased (P < 0.05); the new bone formation rate and implant-bone contact rate in the platelet-rich fibrin group were significantly higher than those in the model group (P < 0.05). (2) Compared with the control group, the model group showed decreased trabecular bone number, bone volume fraction, Lane-Sandhu histological score, and mRNA expression of Runt-related transcription factor 2, osteocalcin, and osteopontin (P < 0.05), while trabecular separation, and protein expression of IκB kinase, inhibitor of nuclear factor-κB, and nuclear factor-κB were increased (P < 0.05). Compared with the model group, the platelet-rich fibrin group showed increased trabecular bone number, bone volume fraction, Lane-Sandhu histological score, and mRNA expression of Runt-related transcription factor 2, osteocalcin, and osteopontin (P < 0.05), while trabecular separation, and protein expression of IκB kinase, inhibitor of nuclear factor-κB, and nuclear factor-κB were decreased (P < 0.05). (3) Micro-CT showed no new bone tissue formation in the model group, while a large amount of new bone formation and connection with bone ends were observed in the platelet-rich fibrin group. (4) Hematoxylin-eosin staining showed that the platelet-rich fibrin group had good bone repair status and a large number of new bone cells around the defect. These results suggest that platelet-rich fibrin can accelerate the process of bone cell repair, has a significant promoting effect on bone healing in rats with peri-implant bone defects, can increase the expression level of osteogenic-related genes, improve bone microstructure, and enhance the activity of the IκB kinase/inhibitor of nuclear factor-κB/nuclear factor-κB signaling pathway.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21452
BACKGROUND: Tendon injury repair is often compromised by inflammatory cascades and disordered collagen metabolism, leading to scar formation and mechanical deterioration. Curcumin exhibits anti-inflammatory, antioxidant, and pro-repair potential, but its rapid metabolism and low bioavailability limit clinical application. OBJECTIVE: To construct a thermosensitive injectable curcumin-loaded chitosan/sodium β-glycerophosphate hydrogel and evaluate its efficacy in tendon repair. METHODS: (1) Rat tendon stem cells were cultured with different concentrations of curcumin for 24 hours. Cell viability was assessed using the CCK-8 assay, and the 20 µmol/L concentration was selected for subsequent experiments. Rat tendon stem cells were cultured with 0 (control) and 20 µmol/L curcumin, and cell migration was assessed using a wound healing assay. Rat tendon stem cells were cultured in three groups: a control group received no treatment; a model group received tert-butyl hydroperoxide to induce oxidative stress; a curcumin group received tert-butyl hydroperoxide plus 20 µmol/L curcumin. qRT-PCR and western blot were used to detect the expression of matrix metalloproteinase 3, matrix metalloproteinase 13, collagen type I alpha 1 chain, collagen type III alpha 1 chain, Bcl-2, and Bax. (2) Chitosan/sodium β-glycerophosphate thermosensitive injectable hydrogels with or without curcumin (final concentration 20 µmol/L) were prepared. The microstructure and drug release were characterized. Rat tendon stem cells were co-cultured with the hydrogels, and cell compatibility was evaluated by live/dead staining and cytoskeletal staining. (3) Sixty SD rats were randomly divided into five groups: sham surgery (n=12), model (n=12), hydrogel only (n=12), curcumin solution (n=12), and curcumin-loaded hydrogel (n=12). The Achilles tendon rupture model was established, and treatments were injected at the tendon stump, with a second injection after 4 days. At 8 weeks post-surgery, peritendinous adhesion, hematoxylin-eosin staining, Masson staining, immunohistochemistry for cyclooxygenase-2 and collagen type I alpha 1 chain, and biomechanical analysis were performed. RESULTS AND CONCLUSION: (1) Curcumin promoted the migration of rat tendon stem cells. Compared with the model group, the curcumin group showed decreased mRNA and protein expression of matrix metalloproteinase 3, matrix metalloproteinase 13, collagen type III alpha 1 chain, and Bax protein (P < 0.05), and increased expression of collagen type I alpha 1 chain and Bcl-2 protein (P < 0.05). (2) Scanning electron microscopy revealed a typical three-dimensional porous network structure of the hydrogel with uniform pore size and interconnected pores. The curcumin-loaded hydrogel exhibited good sustained release. Live/dead and cytoskeletal staining showed good cytocompatibility. (3) The curcumin-loaded hydrogel group had lower peritendinous adhesion than the model, hydrogel only, and curcumin solution groups. Hematoxylin-eosin and Masson staining showed reduced inflammatory cell infiltration and orderly collagen deposition in the curcumin-loaded hydrogel group. Immunohistochemistry showed lower cyclooxygenase-2 expression and higher collagen type I alpha 1 chain expression in the curcumin-loaded hydrogel group compared with the model and hydrogel only groups (P < 0.05). The maximum tensile stress and elastic modulus were higher in the curcumin-loaded hydrogel group than in the model, hydrogel only, and curcumin solution groups (P < 0.05). In conclusion, the curcumin-loaded chitosan/sodium β-glycerophosphate thermosensitive hydrogel synergistically exerts anti-inflammatory effects and promotes orderly collagen deposition, significantly improving the quality of tendon repair.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21501
BACKGROUND: Piezo-type mechanosensitive ion channel components (PIEZO) play a crucial role in cartilage degeneration, inflammation, and pain in osteoarthritis by sensing mechanical stimulation and regulating calcium signaling, potentially serving as an important therapeutic target for osteoarthritis. OBJECTIVE: To systematically review the role of PIEZO ion channels in the pathological mechanisms of osteoarthritis and evaluate their potential as a novel therapeutic target. METHODS: The first author searched CNKI and PubMed databases using Chinese and English search terms including "mechanical stress, Piezo, osteoarthritis, chondrocyte, osteoblast, osteoclast, synovial cell, immune cell" and "Piezo1, osteoarthritis, chondrocyte, osteoblast, osteoclast, synovial membrane, immune cell, GsMTx4" respectively. Literature published from 2000 to 2025 was selected, and 102 articles were finally included for review. RESULTS AND CONCLUSION: Mechanical stress plays a central role in the degeneration of articular cartilage and surrounding tissues. Chronic excessive mechanical stress or unbalanced loading causes chondrocyte damage, apoptosis, and inflammatory responses, thereby accelerating osteoarthritis progression. Known mechanosensors include transient receptor potential channel family, two-pore domain potassium channel family, degenerin/epithelial sodium channel family, and integrin family. PIEZO family is the first group of mechanosensitive cation channel pore proteins discovered in mammalian cells, widely present in human cells, sensing changes in ambient pressure to control Ca2+ influx and thus affect cellular functions. PIEZO ion channels regulate Ca2+ influx by sensing mechanical stimulation of the cell membrane, thereby influencing chondrocytes, osteogenesis, synovial cells, immune cells, and pain perception. Inhibiting PIEZO ion channels may become an effective method for treating arthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21483
BACKGROUND: Oxidative stress is one of the potential factors contributing to muscle atrophy following anterior cruciate ligament injury. Alleviating skeletal muscle fatigue facilitates proprioceptive recovery, thereby accelerating rehabilitation after anterior cruciate ligament injury. Improving mitochondrial function helps mitigate skeletal muscle fatigue-related damage. OBJECTIVE: To verify that electroacupuncture at different frequencies alleviates skeletal muscle oxidative stress damage and improves mitochondrial function in rabbits, thereby reducing skeletal muscle fatigue, restoring proprioceptive function, and accelerating rehabilitation following anterior cruciate ligament injury. METHODS: Twenty-four healthy New Zealand rabbits were randomly divided into blank group, model group, low-frequency electroacupuncture group, and high-frequency electroacupuncture group, with 6 rabbits in each group. The model group, low-frequency electroacupuncture group, and high-frequency electroacupuncture group were used to construct a knee anterior cruciate ligament injury model. In the low-frequency and high-frequency electroacupuncture groups, electroacupuncture was applied to the acupoints Xuehai and Liangqiu on the affected knee joint 7 days after modeling. The blank and model groups were only grasped and fixed without electroacupuncture intervention, once daily for 21 consecutive days. After intervention, ELISA was used to detect the levels of superoxide dismutase, succinate dehydrogenase, and malondialdehyde in the quadriceps femoris; western blot was used to detect the protein expression levels of silent information regulator 2-related enzyme 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, and mitochondrial transcription factor A in skeletal muscle tissue, as well as the mRNA expression of silent information regulator 2-related enzyme 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, nuclear respiratory factor 1, and mitochondrial transcription factor A. RESULTS AND CONCLUSION: After anterior cruciate ligament injury, the level of superoxide dismutase in the quadriceps femoris of rabbits increased, the level of succinate dehydrogenase decreased, and the concentration of malondialdehyde increased; the protein expressions of silent information regulator 2-related enzyme 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, and mitochondrial transcription factor A decreased; the mRNA expressions of silent information regulator 2-related enzyme 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, nuclear respiratory factor 1, and mitochondrial transcription factor A were significantly downregulated. After electroacupuncture intervention, the concentration of malondialdehyde in the affected quadriceps femoris decreased, the activities of superoxide dismutase and succinate dehydrogenase increased, and the protein expressions of silent information regulator 2-related enzyme 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, and mitochondrial transcription factor A increased; the mRNA expressions of mitochondrial biogenesis-related genes such as silent information regulator 2-related enzyme 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, nuclear respiratory factor 1, and mitochondrial transcription factor A increased, and the low-frequency electroacupuncture group was superior to the high-frequency electroacupuncture group. These results indicate that electroacupuncture can reduce oxidative stress damage in skeletal muscle after anterior cruciate ligament injury by increasing the contents of superoxide dismutase and succinate dehydrogenase and decreasing the content of malondialdehyde; and improve mitochondrial function by regulating the expression of proteins related to the silent information regulator 2-related enzyme 1/peroxisome proliferator-activated receptor gamma coactivator 1 alpha signaling pathway and mitochondrial biogenesis-related genes, thereby accelerating rehabilitation after anterior cruciate ligament injury.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21645
BACKGROUND: Percutaneous minimally invasive intramedullary nailing is a common and effective treatment for intertrochanteric fractures in the elderly, effectively avoiding complications. However, intertrochanteric fractures involving the lesser trochanter remain problematic, particularly with lesser trochanteric separation. Due to the diverse types of lesser trochanteric separation, there are few reports on whether lesser trochanteric separation should be fixed. OBJECTIVE: To investigate the impact of lesser trochanter displacement distance on postoperative functional outcomes in elderly patients with intertrochanteric fractures treated with minimally invasive intramedullary nailing, providing clinical data to determine whether fixation is necessary. METHODS: A retrospective analysis was conducted on 46 elderly patients with intertrochanteric fractures and lesser trochanter separation who underwent intramedullary nailing fixation and received effective follow-up at the Department of Emergency Surgery, Guizhou Provincial People's Hospital from August 2020 to December 2023. Patients were divided into two groups based on displacement distance: group A (displacement ≥1 cm, n=23) and group B (displacement <1 cm, n=23). Postoperative functional recovery indicators were compared, including time to first straight leg raise, time to first ambulation, fracture healing time, Harris hip scores at 1, 2, 3, 6, 9, and 12 months postoperatively, and excellent rate of Harris score at final follow-up. RESULTS AND CONCLUSION: (1) No significant differences in preoperative general data between the two groups (P > 0.05). (2) Group A had significantly longer time to first straight leg raise (18.44±3.99 days vs. 15.91±3.64 days, P < 0.05) and time to first ambulation (7.83±1.92 days vs. 6.70±1.80 days, P < 0.05) compared to group B. However, fracture healing time showed no significant difference (P > 0.05). (3) Harris scores in group B were significantly higher than group A at 1, 2, 3, and 6 months postoperatively (P < 0.05), but no significant differences at 9 and 12 months (P > 0.05). (4) At final follow-up, excellent rate of Harris score (≥90) was 74% in group A and 87% in group B, with no significant difference (P > 0.05). (5) These findings indicate that elderly patients with different lesser trochanter displacement distances have different functional recovery within 6 months postoperatively, but after 6 months, the displaced lesser trochanter does not affect hip function. Therefore, routine reduction and fixation of the lesser trochanter is not recommended for elderly intertrochanteric fracture patients. However, for patients with high early functional demands, reduction and fixation may be considered after individual assessment of activity needs and physical condition.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21577
BACKGROUND: Recent studies have shown that Chlorella possesses potential value in treating rheumatoid arthritis. The pathological progression of rheumatoid arthritis is closely associated with an imbalance in oxidative stress, abnormal macrophage polarization, aggressive activation of fibroblast-like synoviocytes, and disturbances in the vascular endothelial system. However, the optimization of extraction processes for peptides derived from Chlorella and their regulatory effects on key pathological links of rheumatoid arthritis remain to be systematically validated. OBJECTIVE: To optimize the extraction process of antioxidant peptides from Chlorella, clarify their antioxidant activity and biosafety, and explore their regulatory effects on pathological phenotypes of rheumatoid arthritis-related cells (RAW 264.7 mouse monocyte macrophage leukemia cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells), providing experimental evidence for the treatment of rheumatoid arthritis with Chlorella peptides. METHODS: (1) Chlorella peptide extract was prepared by bromelain enzymatic hydrolysis combined with phosphomolybdic acid precipitation. Using peptide yield as the evaluation index, the extraction process parameters were optimized by single-factor experiments, including solid-liquid ratio, enzymatic hydrolysis time, and reaction system pH. (2) The peptide content was determined by BCA method, antioxidant capacity was detected by ABTS method, and biosafety of peptides on RAW 264.7 cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells was evaluated by CCK-8 method. (3) An inflammatory model of RAW 264.7 cells induced by lipopolysaccharide was established. The effects of peptides on intracellular reactive oxygen species levels and M1/M2 polarization phenotypes were detected by DCFH-DA staining, flow cytometry, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. (4) An activation model of fibroblast-like synoviocytes induced by tumor necrosis factor-alpha was established. The effects of peptides on migration, proliferation, invasion, and related gene expression of fibroblast-like synoviocytes were detected by wound healing assay, EdU proliferation assay, Transwell invasion assay, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. (5) An abnormal activation model of human umbilical vein endothelial cells induced by vascular endothelial growth factor A was established. The effects of peptides on migration, tube formation, and expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A genes were detected by wound healing assay, Transwell assay, tube formation assay, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. RESULTS AND CONCLUSION: (1) The optimal extraction process for Chlorella peptides was solid-liquid ratio of 2:1 (g:100 mL), enzymatic hydrolysis time of 60 minutes, and reaction system pH of 6.5, yielding the highest peptide yield. (2) Chlorella peptides exhibited concentration-dependent antioxidant activity and showed no obvious toxicity to RAW 264.7 cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells in the concentration range of 1-10 μg/mL, indicating good biocompatibility. (3) Chlorella peptides dose-dependently inhibited lipopolysaccharide-induced reactive oxygen species generation in RAW 264.7 cells, downregulated M1 pro-inflammatory genes such as interleukin-1 beta and tumor necrosis factor-alpha, upregulated M2 anti-inflammatory genes such as interleukin-10 and arginase 1, and promoted macrophage polarization from M1 to M2 phenotype. (4) Chlorella peptides significantly inhibited tumor necrosis factor-alpha-induced migration, proliferation, and invasion of fibroblast-like synoviocytes, and downregulated the expression of interleukin-6, matrix metalloproteinase 13, tumor necrosis factor receptor superfamily member 11A, and C-X-C motif chemokine ligand 12. (5) Chlorella peptides effectively inhibited vascular endothelial growth factor A-induced migration and tube formation of human umbilical vein endothelial cells, and reduced the expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A genes. These results indicate that Chlorella peptides regulate multiple pathological links of rheumatoid arthritis through anti-oxidative stress, regulation of macrophage polarization, inhibition of aggressive phenotype of fibroblast-like synoviocytes, and improvement of vascular endothelial disorders, suggesting potential therapeutic value for rheumatoid arthritis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025042
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, with late-stage 5-year survival rates below 50%. Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) drive progression, yet the molecular mediators of CAF-tumor crosstalk are incompletely defined. This study identifies platelet-derived growth factor C (PDGFC) as a critical CAF-secreted factor that promotes epithelial-mesenchymal transition (EMT) and immunosuppression in LUAD. Analysis of patient specimens revealed elevated PDGFC expression in CAFs relative to nontumor tissue fibroblasts (NFs), and high PDGFC levels correlated with poor prognosis. Mechanistically, CAF-derived PDGFC activates the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in cancer cells, inducing EMT and matrix metalloproteinase 2 (MMP2) expression. PDGFC also stimulates PDGFRA expression in both tumor cells and fibroblasts, establishing a reciprocal positive feedback loop that accelerates fibrotic TME remodeling and malignant progression. Immunologically, PDGFC promotes infiltration and polarization of immunosuppressive cell populations, including CD4+ Treg cells, M2 macrophages, and N2 neutrophils, while restraining immunocompetent NK cells. Immunoinhibitors TGFB1, CSF1R, PD-L1, PD-L2, KDR, IL10RB, and HAVCR2 may synergize with PDGFC in modulating immunosuppression. These findings position PDGFC as a diagnostic indicator and potential immunotherapy target for LUAD, offering a novel TME-targeted therapeutic strategy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025128
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with advanced-stage disease characterized by limited therapeutic options and poor clinical outcomes. Lymphocyte antigen 96 (LY96) has been implicated in immunogenic cell death, yet its specific mechanistic contribution to HCC progression and its potential as a therapeutic target remain undefined. This study integrates cancer-immunity cycle scoring with weighted gene co-expression network analysis (WGCNA) and systems biology approaches to identify pivotal molecular drivers in HCC. LY96 expression was evaluated at transcriptomic and proteomic levels in HCC tissues, and its prognostic relevance was assessed using The Cancer Genome Atlas (TCGA) repository. Functional characterization of LY96 was performed through a panel of in vitro cellular assays and in vivo tumorigenesis models. Gene set enrichment analysis (GSEA) identified downstream signaling cascades, which were subsequently validated experimentally. A lipid-polymer hybrid nanoparticle (NP) platform was engineered for systemic delivery of the LY96 inhibitor L6H21. Clinically, marked LY96 overexpression was observed in HCC samples and correlated with reduced overall survival (OS). LY96 facilitated HCC progression via complementary in vitro and in vivo approaches. Mechanistically, LY96 induced activation of the TGF-β1/Smad2/3 signaling axis. The liposome-based nanoparticle system delivering L6H21 effectively suppressed HCC progression in both in vivo and in vitro studies. These findings identify LY96 as a promising diagnostic indicator and a viable therapeutic target for HCC intervention.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025057
MEIOB and SPATA22 are gonad-specific proteins essential for meiotic recombination, with mutations linked to oligospermia and azoospermia in human males. The heterodimer recognizes and binds single-stranded DNA (ssDNA) protected by replication protein A (RPA) to promote homologous recombination repair. However, sequence divergence between human and rodent orthologs leads to functional differences. Here, human MEIOB (hMEIOB) and SPATA22 (hSPATA22) were expressed and purified for electrophoretic mobility shift assay (EMSA), magnetic tweezer (MT) assay, and bio-layer interferometry (BLI) to dissect ssDNA binding patterns. hMEIOB alone exhibits low ssDNA-binding affinity and stability, whereas hSPATA22 binds ssDNA faster and more stably, promoting ssDNA condensation. The hMEIOB-hSPATA22 heterodimer displays strong binding affinity and stability. Multiple heterodimers spontaneously aggregate in vitro, with BLI response signals of ~4.31 nm for hSPATA22 alone versus ~19.5 nm for the heterodimer, indicating polymer formation. The hRPA complex weakens the binding affinity of hMEIOB, hSPATA22, and the heterodimer to ssDNA, and binds to hSPATA22 and the heterodimer in vitro, consistent with RPA's role in protecting ssDNA and recruiting repair proteins. This study provides the first single-molecule elucidation of hMEIOB and hSPATA22 binding to ssDNA and verifies their relationship with the RPA complex.