Chinese Journal of New Drugs•2025•DOI: 10.1007/s11770-025-1234-5
Nuclear magnetic resonance (NMR) technology has been widely used in the evaluation of coalbed methane (CBM) reservoirs. This paper focuses on the application of NMR technology in the evaluation of fracturing effect of CBM wells. Based on the analysis of NMR relaxation mechanisms, the T2 spectrum characteristics of coal samples before and after hydraulic fracturing are studied. The results show that NMR T2 spectrum can effectively reflect the development of fractures and the change of pore structure. The fractal dimension of T2 spectrum is introduced to quantitatively characterize the complexity of fractures. Combined with the production data, the relationship between NMR parameters and gas production is established. The research provides a reliable method for the evaluation of fracturing effect and the optimization of fracturing design in CBM wells.
Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpbjnl/qzae016
Ribonuclease P (RNase P) was first described in the 1970’s as an endoribonuclease acting in the maturation of precursor transfer RNAs (tRNAs). More recent studies, however, have uncovered non-canonical roles for RNase P and its components. Here, we review the recent progress of its involvement in chromatin assembly, DNA damage response, and maintenance of genome stability with implications in tumorigenesis. The possibility of RNase P as a therapeutic target in cancer is also discussed.
Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpb/art_1122
The release of AlphaFold2 has sparked a rapid expansion in protein model databases. Efficient protein structure retrieval is crucial for the analysis of structure models, while measuring the similarity between structures is the key challenge in structural retrieval. Although existing structure alignment algorithms can address this challenge, they are often time-consuming. Currently, the state-of-the-art approach involves converting protein structures into three-dimensional (3D) Zernike descriptors and assessing similarity using Euclidean distance. However, the methods for computing 3D Zernike descriptors mainly rely on structural surfaces and are predominantly web-based, thus limiting their application in studying custom datasets. To overcome this limitation, we developed FP-Zernike, a user-friendly toolkit for computing different types of Zernike descriptors based on feature points. Users simply need to enter a single line of command to calculate the Zernike descriptors of all structures in customized datasets. FP-Zernike outperforms the leading method in terms of retrieval accuracy and binary classification accuracy across diverse benchmark datasets. In addition, we showed the application of FP-Zernike in the construction of the descriptor database and the protocol used for the Protein Data Bank (PDB) dataset to facilitate the local deployment of this tool for interested readers. Our demonstration contained 590,685 structures, and at this scale, our system required only 4–9 s to complete a retrieval. The experiments confirmed that it achieved the state-of-the-art accuracy level. FP-Zernike is an open-source toolkit, with the source code and related data accessible at https://ngdc.cncb.ac.cn/biocode/tools/BT007365/releases/0.1, as well as through a webserver at http://www.structbioinfo.cn/.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04780-x
Background Liver fibrosis is a crucial pathological stage in the progression of chronic liver diseases. Yiguanjian (YGJ), a Chinese herbal formula, exhibits anti-inflammatory, anti-fibrotic, and hepatoprotective effects. Extracellular vesicles from bone-marrow mesenchymal stem cells (BMSC-EVs) have shown potential in treating various disorders, including liver fibrosis. This study investigated the regulatory effects of EVs from YGJ-preconditioned BMSCs (YGJ-EVs) on TGF-β1-stimulated hepatic stellate cells (HSCs) and their therapeutic potential in a mouse model of liver fibrosis, with a focus on identifying the causative microRNA cargo. Methods YGJ-EVs and control EVs were isolated from BMSC culture supernatants and characterized via western blotting, transmission electron microscopy, and nanoparticle tracking analysis. Their cellular uptake in vitro and in vivo was evaluated using DIR labeling. To identify candidate miRNAs mediating YGJ-EV bioactivity, miRNA microarray analysis was conducted. To assess the effect of YGJ-EVs on liver fibrosis, TGF-β1-activated HSC cells were treated with YGJ-EVs or control-EVs for 24 h, and then the expression of proteins related to fibrotic activation (COL1-A1 and α-SMA), lysosomal biogenesis (LAMP1, TPP1, CTSD, and CTSB) mitophagy (p62, LC3, PINK1, and Parkin), and the Akt/AMPK/TFEB pathway was assessed. To determine whether miR-7045-5p is the causative factor, HSC cells transfected with miR-7045-5p were similarly analyzed. Results miRNA microarray analysis revealed miR-7045-5p upregulation in YGJ-EVs versus control EVs. In CCl4-treated mice, YGJ-EV-derived miR-7045-5p ameliorated the liver fibrosis, improved the hepatic function, and suppressed the HSC activation by inhibiting the Akt/AMPK/TFEB pathway. In vitro, miR-7045-5p overexpression attenuated TGF-β1-induced HSC activation. Conclusion YGJ increases miR-7045-5p abundance in BMSC-EVs. YGJ-EVs alleviate liver fibrosis by delivering the anti-fibrotic miRNA miR-7045-5p, which inhibits the Akt/AMPK/TFEB pathway, thereby promoting lysosomal biogenesis and mitophagy in HSCs.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04148-1
Background The long-term effects and outcomes of human mesenchymal stem cell (MSC) therapy in patients with severe coronavirus disease 2019 (COVID-19) remain poorly understood. This study aimed to evaluate the extended safety and efficacy of MSC treatment in severe patients with COVID-19 who participated in our earlier randomized, double-blind, placebo-controlled clinical trial, with follow-up conducted over 3 years. Methods One hundred patients with severe COVID-19 were randomized to receive either an MSC infusion (n=65, 4×10^7 cells/dose, on days 0, 3, and 6) or a placebo, with both groups receiving the standard of care. At 36 months post-MSC therapy, patients were followed up to long-term safety and efficacy, particularly the effects of MSC therapy on persistent COVID-19 symptoms. Evaluated outcomes included lung imaging results, 6-min walking distance (6-MWD), pulmonary function test results, quality of life scores based on the Short Form-36 (SF-36) health survey, Long COVID symptoms, new-onset comorbidities, tumor marker levels, and rates of COVID-19 reinfection. Results Three years post-treatment, 46.94% (23/49) of patients in the MSC group and 34.48% (10/29) in the placebo group showed normal findings on computed tomography (CT) images (odds ratio [OR]=1.68, 95% confidence interval [CI]: 0.65–4.34). The general health (GH) score from the SF-36 was higher in the MSC group (67.0) compared to the placebo group (50.0), with a difference of 12.86 (95% CI: 1.44–24.28). Both groups showed similar results for total lung severity scores (TSS), 6-MWD, pulmonary function tests, and Long COVID symptoms. No significant differences between groups were observed in new-onset complications (including tumorigenesis) or tumor marker levels. After adjusting for China’s dynamic zero-COVID-19 strategy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection rates were 53.06% (26/49) in the MSC group and 67.86% (19/28) in the placebo group (OR=0.54, 95% CI: 0.20–1.41). Conclusions These findings support the long-term safety of MSC therapy in patients with severe COVID-19 over 3 years. MSC treatment may offer potential benefits for lung recovery and improved quality of life in patients experiencing Long COVID symptoms. Trial registration: ClinicalTrials.gov, NCT04288102. Registered 28 February 2020, https://clinicaltrials.gov/study/NCT04288102.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04463-7
Background: Recent advances in clinical trials have involved the transplantation of induced retinal pigment epithelium (iRPE) cells from stem cells in creating a functional monolayer that mimics the characteristics of natural adult RPE cells. One method of achieving this goal is through the use of tissue engineering. In this research, decellularised femtosecond laser intrastromal lenticules (dfLEN) were employed as a scaffold for cultivating a bioengineered iRPE monolayer sheet. Methods: iRPE cells were obtained by differentiating induced pluripotent stem cells (iPSC). These cells were then seeded on decellularized FLI-lenticules (dfLEN). The functionality, characterization, and oxidative stress of iRPE cultured on dfLEN were compared with those cultured on plates (TCP) using various assays such as immunofluorescence (IF), Edu, CCK8, ELISA, DFCH-DA, and JC-1. Additionally, RNA-seq assays and electron microscope (SEM and TEM) were used to test the iRPE characteristic on engineered dfLEN. Finally, we evaluated the biocompatibility of iRPE-dfLEN sheets by transplanting them into the subretinal space of New Zealand white rabbits. Results: The iRPE cells cultured on dfLEN exhibited morphology and physiology similar to that of native RPE tissue. The dfLEN not only increased the resistance capacity of iRPE cells but also improved their functional properties compared to TCP. In addition, our results indicate that dfLEN enhances the expression of genes associated with cilium assembly, resulting in notable improvements in ciliogenesis in iRPE cells. Finally, the dfLEN-iRPE sheets demonstrated favorable biocompatibility and some viability when transplanted into the subretinal space of rabbits for a period of 14 days.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04401-7
Background: Multiple sclerosis (MS) is a progressive autoimmune disease characterized by massive inflammatory infiltration, demyelination, and subsequent axonal injury and neuronal damage in the central nervous system (CNS). The etiology of MS remains unclear and there is not yet a definitive therapeutic schedule for the disease. Bone marrow mesenchymal stem cells (BMSCs), exhibiting neuroimmune-modulatory functions to alleviate various autoimmune diseases, show great potential in the treatment of MS. However, the instability of BMSCs-mediated immunosuppression in vivo has limited their application. MiR181-a, a positive regulator of immune balance, which has a preference for T cells and B cells differentiation, but degrade rapidly upon entering systemic circulation due to their unstable molecular structure. Methods: We propose a synergistic therapy approach that combines the penetrative targeting capability of BMSCs with the immuno-modulatory effects of miR181-a by overexpressing miR181-a to BMSCs through lentivirus packaging system. With this strategy, on the basis of the establishment of the experimental autoimmune encephalomyelitis (EAE) model, miR181-a overexpressing BMSCs (miR181a-BMSCs) would have a stronger immuno-modulatory treatment benefit, in terms of attenuating MS development. Results: Indicate that this method prolongs the modulatory effects of BMSCs and resulted in significantly enhancements of the proliferation of regulatory B cells (Bregs), regulatory T cells (Tregs) and the inhibition of Th17 cells compared to the traditional BMSCs group. Moreover, 10-fold miRNA’s concentration in the exosome of miR181a-BMSCs, leading to an increased duration of miRNAs to exert their biological effects. By immunotherapy and synergistic treatment, the effectiveness of the treatment is significantly enhanced, showing consistent results in different groups of the animal model.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04475-3
Background: Mitochondrial DNA (mtDNA) deletion and oxidative stress are key contributors to skin photoaging. Mitophagy helps mitigate oxidative stress. Human adipose-derived stem cell exosomes (hADSC-Exos) have been shown to counteract skin photoaging. This study aimed to explore the role and mechanism of hADSC-Exos in addressing skin photoaging. Methods: hADSC-Exos were isolated, and their surface markers were identified. Human dermal fibroblasts (HDFs) and nude mice were exposed to ultraviolet-B (UVB) irradiation, and treated with hADSC-Exos. Oxidative stress and photoaging were assessed through SA-β-gal staining, p21 expression, mtDNA deletion, reactive oxygen species (ROS) levels, and histological analysis. The PINK1, Parkin, LC3b, and p62 protein levels were measured to evaluate mitophagy. The PINK1 small-interfering RNA (siPINK1) was then used in HDFs to investigate the role of hADSC-Exos in mitophagy. Results: In UVB-exposed HDFs and nude mice, the number of SA-β-gal-positive cells, along with levels of p21, ROS, and mtDNA deletion, were significantly increased, but these effects were reduced by hADSC-Exos. Moreover, hADSC-Exos treatment significantly elevated PINK1 and Parkin levels, as well as the LC3bII/I ratio, while reducing p62 expression. In photoaged HDFs treated with hADSC-Exos, PINK1 knockout using siRNA decreased the LC3bII/I ratio and levels of PINK1 and Parkin, while increasing p62, ROS, and mtDNA deletion compared to the negative control (NC) group. Conclusion: hADSC-Exos can mitigate skin photoaging by promoting PINK1/Parkin-mediated mitophagy, thereby reducing mtDNA deletion and oxidative stress.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04525-w
Background Mesenchymal stem cells (MSCs) are widely used in treating autoimmune diseases. However, replicative senescence limits the quantity and quality of MSCs during population doublings in vitro. Transcription factor SOX4 is a crucial regulator of cell fate and stemness. This study aims to explore the role of SOX4 in senescence of MSCs and enhance their therapeutic efficacy in systemic lupus erythematosus (SLE). Methods In early-passage MSCs (P3), late-passage MSCs (P8), SOX4 downregulated P3-MSCs or SOX4 overexpressed P8-MSCs, cell morphology, mitochondrial reactive oxygen species (mtROS), senescence-associated β-galactosidase (SA-β-Gal) activity, cell proliferation rate, senescence-associated secretory phenotype (SASP) factors, cell cycle suppressors, the immunosuppressive effects on T cell activation and proliferation and the expression levels of SOX4 were determined. Imiquimod induced SLE mice were transplanted with P3-MSCs and P8-MSCs or control and SOX4 overexpressed P8-MSCs, and clinical symptoms were assessed. Results Compared to P3-MSCs, P8-MSCs display a senescent phenotype, increased mtROS, SA-β-Gal activity, SASP factors, and cell cycle suppressors p53, p21, and p16. Additionally, P8-MSCs have a reduced immunosuppressive function on T cell activation and proliferation, and express lower levels of SOX4. Downregulation of SOX4 in P3-MSCs promotes cellular senescence and impairs their immunosuppressive function. Conversely, overexpression of SOX4 in P8-MSCs ameliorates cellular senescence and enhances their immunosuppressive function. Furthermore, transplantation of P3-MSCs or SOX4-overexpressing P8-MSCs demonstrates greater therapeutic significantly efficacy in SLE mice compared to P8-MSCs.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04565-2
This correction article addresses an error in the scale of the control group image in Fig. 4E of the original article. The corrected image is provided. The original article can be found online at https://doi.org/10.1186/s13287-025-04468-2.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04540-x
Background Trained immunity with human bone marrow mesenchymal stem cells (hBMSC) is a promising approach to liver regeneration. This study aimed to clarify the trained-hBMSC (T-hBMSC) in restoring tissue immuno-microenvironment in fulminant hepatic failure (FHF) mice. Methods hBMSC trained with tumor necrosis factor-α and interferon-γ were phenotypically characterized in vitro. FHF mouse models were established in male Balb/c mice via tail vein injection of concanavalin A. The therapeutic potential of T-hBMSC was evaluated through transplantation into FHF mice. Transcriptomic analysis was performed to elucidate the mechanism of liver regeneration post-transplantation of T-hBMSC. Results T-hBMSC with the characteristics of trilineage differentiation potential showed that pro-inflammatory (IL1β, IL8, both p < 0.0001) and immunoregulatory genes (PDL1, IDO1, both p < 0.0001) were significantly upregulated compared to untrained-hBMSC (UT-hBMSC). Time-trajectory analysis revealed downregulation of pro-inflammatory genes (IL6, IL8, and IL1α) and upregulation of immunomodulatory genes (IDO1) in T-hBMSC upon mimic-stimulation, characterized by distinct transcriptional programs. The liver function (ALT, AST) and inflammatory cytokines (IL6, MCP1, both p < 0.01) levels were significantly improved in the T-hBMSC-treated mice. The survival status of the T-hBMSC group was superior to the UT-hBMSC group, although there was no statistical significance. Histological analysis confirmed reduced necrosis and fewer infiltrating CD45+ immune cells in the T-hBMSC-treated mice. Significant downregulation of immune response (TNF & IL-17 signaling pathways and neutrophil chemotaxis) and upregulation of metabolic pathways were observed in the T-hBMSC group, associated with enhanced liver regeneration. The proportion of anti-inflammatory F4/80+CD163+ macrophages was increased in the liver of T-hBMSC group.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03690-8
Background Cell- or tissue-based regenerative therapy is an attractive approach to treat heart failure. A tissue patch that can safely and effectively repair damaged heart muscle would greatly improve outcomes for patients with heart failure. In this study, we conducted a preclinical proof-of-concept analysis of the efficacy and safety of clinical-grade human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches. Methods A clinical-grade hiPSC line was established using peripheral blood mononuclear cells from a healthy volunteer that was homozygous for human leukocyte antigens. The hiPSCs were differentiated into cardiomyocytes. The obtained hiPSC-CMs were cultured on temperature-responsive culture dishes for patch fabrication. The cellular characteristics, safety, and efficacy of hiPSCs, hiPSC-CMs, and hiPSC-CM patches were analyzed. Results The hiPSC-CMs expressed cardiomyocyte-specific genes and proteins, and electrophysiological analyses revealed that hiPSC-CMs exhibit similar properties to human primary myocardial cells. In vitro and in vivo safety studies indicated that tumorigenic cells were absent. Moreover, whole-genome and exome sequencing revealed no genomic mutations. General toxicity tests also showed no adverse events posttransplantation. A porcine model of myocardial infarction demonstrated significantly improved cardiac function and angiogenesis in response to cytokine secretion from hiPSC-CM patches. No lethal arrhythmias were observed. Conclusions hiPSC-CM patches are promising for future translational research and may have clinical application potential for the treatment of heart failure.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03949-0
Background The selection of suitable culture medium is critical for achieving good clinical outcomes in cell therapy. To support the commercial application of stem cell therapy, customized culture media not only need to promote stem cell proliferation, but also need to save costs and meet industrial requirements for inter-batch consistency, efficacy, and biosafety. In this study, we developed a series of serum-free media (SFM) and elucidated the effects between different SFM, as well as between SFM and serum-containing meida (SCM), on human umbilical cord mesenchymal stem cells (hUC-MSCs) phenotype and function. We analyze and emphasize from the perspectives of clinical and commercial application why research on customized culture media is critical for the success of enterprises developing novel cellular therapeutics. Methods We cultured hUC-MSCs with identical cell seeding densities in different formulations of SFM and SCM until passage 10 and examined the changes in cell phenotype and function. We analyzed the results with the commercial application requirments of the cellular therapy industry to assess the potential impact of customized culture media on inter-batch consistency, efficacy, stability, biosafety, and cost-effectiveness of industrial-scale cell production. Results hUC-MSCs cultured in SCM and SFM exhibit consistent cell morphology and surface molecule expression, but hUC-MSCs cultured in SFM demonstrate higher activity, superior proliferative capacity, and greater stability. Furthermore, hUC-MSCs cultured in different SFM exhibit differences in cell activity, proliferative capacity, senescent rate, and S/M ratio of cell cycle, while maintaining a normal karyotype after long-term in vitro cultivation. Moreover, [abstract truncated]
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03821-1
Background Intrauterine adhesions (IUAs) jeopardise uterine function in women, which is a great challenge in the clinic. Previous studies have shown that endometrial perivascular cells (En-PSCs) can improve the healing of scarred uteri and that hydroxysafflor yellow A (HSYA) promotes angiogenesis. The purpose of this study was to observe whether the combination of En-PSCs with HSYA could improve the blood supply and fertility in the rat uterus after full-thickness injury. Methods En-PSCs were sorted by flow cytometry, and the effect of HSYA on the proliferation and angiogenesis of the En-PSCs was detected using CCK-8 and tube formation assays. Based on a previously reported rat IUA model, the rat uteri were sham-operated, spontaneously regenerated, or treated with collagen-loaded PBS, collagen-loaded HSYA, collagen-loaded En-PSCs, or collagen-loaded En-PSCs with HSYA, and then collected at both 30 and 90 days postsurgery. HE staining and Masson staining were used to evaluate uterine structure and collagen fibre deposition, and immunohistochemical staining for α-SMA and vWF was used to evaluate myometrial regeneration and neovascularization in each group. A fertility assay was performed to detect the recovery of pregnancy function in each group. RNA-seq was performed to determine the potential mechanism underlying En-PSCs/HSYA treatment. Immunofluorescence, tube formation assays, and Western blot were used to validate the molecular mechanism involved. Results The transplantation of Collagen/En-PSCs/HSYA markedly promoted uterine repair in rats with full-thickness injury by reducing fibrosis, increasing endometrial thickness, regenerating myometrium, promoting angiogenesis, and facilitated live births. RNA sequencing results suggested that En-PSCs/HSYA activated the NRG1/ErbB4 signaling pathway. In vitro tube formation experiments revealed that the addition of an ErbB inhibitor diminished the tube formation ability of cocultured En-PSCs and HUVECs. Western blot results further showed that elevated levels of NRG1 and ErbB4 proteins were detected in the Collagen/En-PSCs/HSYA group compared to the Collagen/En-PSCs group. These collective results suggested that the beneficial effects of the transplantation of Collagen/En-PSCs/HSYA might be attributed to the modulation of the NRG1/ErbB4 signaling pathway. Conclusions The combination of En-PSCs/HSYA facilitated morphological and functional repair in rats with full-thickness uterine injury and may promote endometrial angiogenesis by regulating the NRG1/ErbB4 signaling pathway.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025013
Platinum-based chemotherapy remains the mainstay for non-small cell lung cancer (NSCLC), but it frequently causes dose-limiting myelosuppression, with significant individual variability in susceptibility. However, the genetic basis of myelosuppression side effects remains elusive, greatly hindering personalized therapeutic approaches. In this study, we perform a comprehensive genome-wide association analysis on 491 NSCLC patients receiving platinum-based chemotherapy, examining 4,690,998 single-nucleotide polymorphisms (SNPs) to identify relevant genetic variants. LDBlockShow, FUMA, and MAGMA are utilized to explore linkage disequilibrium, expression quantitative trait loci (eQTLs), chromatin interaction, and conduct gene-based and gene set-based analysis of candidate SNPs. The GWAS results reveal that rs6856089 and its linked SNPs are significantly associated with platinum-based chemotherapy-induced myelosuppression. Specifically, patients with the A allele of rs6856089 have a significantly lower risk of myelosuppression [odds ratio (OR) = 0.1300, P = 7.59 × 10–8]. Furthermore, gene-based analysis reveals that EMCN (P = 2.47 × 10–5), which encodes endomucin, a marker for hematopoietic stem cells, might mediate myelosuppression. This study provides a scientific basis for the individual differences in platinum-based chemotherapy-induced myelosuppression.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025163
Myocyte enhancer factor 2A (MEF2A), a transcription factor implicated in coronary artery disease, remains unexplored in vascular redox regulation. To address this gap and overcome the limitations of current antioxidant therapies, we investigate the role of MEF2A in oxidative defense via human umbilical vein endothelial cells (HUVECs) and murine models. Adenoviral vectors encoding MEF2A-specific shRNAs or mRNAs are used to silence or overexpress MEF2A in HUVECs. For in vivo validation, endothelial-targeted MEF2A knockdown is achieved via AAV1-shRNA delivery in mice fed with a high-fat diet. Systemic redox status is assessed by measuring reactive oxygen species (ROS), glutathione homeostasis (GSH/GSSG ratio), the NADH/NAD+ balance, the mitochondrial membrane potential (ΔΨm), and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Mechanistic insights are derived from immunofluorescence, qPCR, western blotting, and dual-luciferase reporter assays. MEF2A silencing induces redox imbalance, characterized by elevated ROS, a reduced GSH/GSSG ratio, and ΔΨm collapse. Conversely, MEF2A overexpression synergizes with SIRT1 to restore the glutathione pool, maintain NAD+ homeostasis, and suppress ROS under oxidative stress. Chromatin immunoprecipitation confirms that MEF2A directly binds to two cis-elements in the SIRT1 promoter, driving transcriptional activation. In vivo, MEF2A-deficient mice present increased vascular oxidative damage, as indicated by elevated DNA damage marker (8-OHdG) and ROS levels. The downregulation of SIRT1/PGC-1α in MEF2A-silenced cells is verified in vivo. Our findings establish MEF2A as a master regulator of endothelial redox defense via the SIRT1-PGC-1α axis, providing a mechanistic foundation for the treatment of oxidative cardiovascular disorders. This work suggests that pharmacological MEF2A activation is a novel strategy for precision antioxidant therapy in vascular medicine.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025075
Chondrocytes store lipids in the form of lipid droplets (LDs) and maintain cartilage lipid metabolic homeostasis by consuming or regenerating LDs. This modulation is largely mediated by a series of biochemical factors. Fibroblast growth factor 8 (FGF8) is one of the most important factors involved in the proliferation, differentiation, and migration of chondrocytes and has attracted increasing attention in the physiology and pathology of cartilage. However, the effect of FGF8 on LD accumulation in chondrocytes remains unclear. This study aims to elucidate the role of FGF8 in LDs and explore the underlying biomechanism involved. The results reveal that FGF8 promotes LD accumulation in chondrocytes by upregulating perilipin1 (Plin1) expression. FGF8 activates the cytoplasmic p-p38 signaling pathway via fibroblast growth factor receptor 1 (FGFR1) to increase LD accumulation in chondrocytes. Subsequent experiments with siRNAs and specific inhibitors further confirm the importance of the FGFR1/p38 axis for LD accumulation in chondrocytes exposed to FGF8. The results increase our understanding of the role of FGF8 in the lipid metabolic homeostasis of chondrocytes and provide insights into the physiology and pathology of cartilage.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025156
CD19-directed chimeric antigen receptor T (CAR-T) cell therapy is promising for treating relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), yet its long-term efficacy remains limited by CAR-T-cell exhaustion. Given the broad immunomodulatory activities of vitamin D, we investigate whether its active form, 1α,25(OH)2D3, enhances CAR-T-cell functionality and improves therapeutic outcomes. We demonstrate that 1α,25(OH)2D3 treatment significantly mitigates exhaustion and enhances the antitumor activity of CD19 CAR-T cells derived from both healthy donors and DLBCL patients, which is further validated in xenograft mouse models. Mechanistically, we show that 1α,25(OH)2D3 upregulates the expression of the vitamin D receptor (VDR), promoting transcriptional reprogramming associated with memory-like differentiation and downregulation of exhaustion-related genes, thereby reshaping the functional heterogeneity of CAR-T cells under tumor stimulation. Our study highlights 1α,25(OH)2D3 supplementation as a safe and accessible approach to mitigate terminal differentiation and exhaustion of CAR-T cells, offering a promising strategy to enhance the clinical efficacy of CAR-T therapy in patients with R/R DLBCL.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024174
Berberine (BBR) is used to treat diarrhea clinically. However, its reproductive toxicity is unclear. This study aims to investigate the impact of BBR on the male reproductive system. Intragastric BBR administration for 14 consecutive days results in a significant decrease in the serum testosterone concentration, epididymal sperm concentration, mating rate and fecundity of male mice. Testicular treatment with testosterone propionate (TP) partially reverses the damage caused by BBR to the male reproductive system. Mechanistically, the decrease in Muribaculaceae abundance in the gut microbiota of mice is the principal cause of the BBR-induced decrease in the sperm concentration. Both fecal microbiota transplantation (FMT) and polyethylene glycol (PEG) treatment demonstrate that Muribaculaceae is necessary for spermatogenesis. The intragastric administration of Muribaculaceae intestinale to BBR-treated mice restores the sperm concentration and testosterone levels. Metabolomic analysis reveals that BBR affects arginine and proline metabolism, of which ornithine level is downregulated. Combined analysis via 16S rRNA metagenomics sequencing and metabolomics shows that Muribaculaceae regulates ornithine level. The transcriptomic results of the testes indicate that the expressions of genes related to the low-density lipoprotein receptor (LDLR)-mediated testosterone synthesis pathway decrease after BBR administration. The transcriptional activity of the Ldlr gene in TM3 cells is increased with increased ornithine supplementation in the culture media, leading to increased testosterone synthesis. Overall, this study reveals an association between a BBR-induced decrease in Muribaculaceae abundance and defective spermatogenesis, providing a prospective therapeutic approach for addressing infertility-related decreases in serum testosterone triggered by changes in the gut microbiota composition.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025155
Gemcitabine resistance poses a significant challenge in gallbladder cancer (GBC) treatment, necessitating exploration of its molecular mechanisms. This study focuses on DDX11, which is highly expressed in gemcitabine-resistant GBC cells, suggesting a potential role in DNA damage repair. We establish gemcitabine-resistant GBC cell lines and observe significantly higher DDX11 expression in these cells than in parental cells. Clinical tissue analysis through qRT-PCR, western blot analysis, and immunohistochemistry confirms elevated DDX11 levels in tumors compared with adjacent normal tissues. Functional assays demonstrate that DDX11 knockdown inhibits cell proliferation, colony formation, and tumor growth, while restoring gemcitabine sensitivity. Mechanistically, proteomic analysis and co-immunoprecipitation reveal that the interaction of DDX11 with PARP1 leads to increased poly(ADP-ribosyl)ation (PARylation), which promotes DNA repair and drug resistance. Notably, combining gemcitabine with the PARP inhibitor olaparib has synergistic anti-tumor effects on resistant cells. These findings indicate that DDX11 contributes to GBC progression and chemoresistance by regulating PARP1-mediated PARylation and that targeting this pathway with PARP inhibitors may overcome gemcitabine resistance. This study provides new insights into GBC drug resistance mechanisms and suggests that combining conventional chemotherapy with PARP inhibition is a potential therapeutic strategy for resistant patients. The DDX11-PARP1-PARylation axis represents a promising target for improving GBC treatment outcomes, particularly in gemcitabine-resistant patients.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024026
Adhesion molecules play critical roles in maintaining the structural integrity of the airway epithelium in airways under stress. Previously, we reported that catenin alpha-like 1 (CTNNAL1) is downregulated in an asthma animal model and upregulated at the edge of human bronchial epithelial cells (HBECs) after ozone stress. In this work, we explore the potential role of CTNNAL1 in the structural adhesion of HBECs and its possible mechanism. We construct a CTNNAL1‒/‒ mouse model with CTNNAL1-RNAi recombinant adeno-associated virus (AAV) in the lung and a CTNNAL1-silencing cell line stably transfected with CTNNAL1-siRNA recombinant plasmids. Hematoxylin and eosin (HE) staining reveals that CTNNAL1‒/‒ mice have denuded epithelial cells and structural damage to the airway. Silencing of CTNNAL1 in HBECs inhibits cell proliferation and weakens extracellular matrix adhesion and intercellular adhesion, possibly through the action of the cytoskeleton. We also find that the expressions of the structural adhesion-related molecules E-cadherin, integrin β1, and integrin β4 are significantly decreased in ozone-treated cells than in vector control cells. In addition, our results show that the expression levels of RhoA/ROCK1 are decreased after CTNNAL1 silencing. Treatment with Y27632, a ROCK inhibitor, abolished the expressions of adhesion molecules induced by ozone in CTNNAL1-overexpressing HBECs. Overall, the findings of the present study suggest that CTNNAL1 plays a critical role in maintaining the structural integrity of the airway epithelium under ozone challenge, and is associated with epithelial cytoskeleton dynamics and the expressions of adhesion-related molecules via the RhoA/ROCK1 pathway.
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.2024106
Acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) represents a primary cause of treatment failure in non-small cell lung cancer (NSCLC) patients. Chemokine (C-C motif) ligand 2 (CCL2) is recently found to play a pivotal role in determining anti-cancer treatment response. However, the role and mechanism of CCL2 in the development of EGFR-TKIs resistance have not been fully elucidated. In the present study, we focus on the function of CCL2 in the development of acquired resistance to EGFR-TKIs in NSCLC cells. Our results show that CCL2 is aberrantly upregulated in EGFR-TKIs-resistant NSCLC cells and that CCL2 overexpression significantly diminishes sensitivity to EGFR-TKIs. Conversely, CCL2 suppression by CCL2 synthesis inhibitor, bindarit, or CCL2 knockdown can reverse this resistance. CCL2 upregulation can also lead to enhanced migration and increased expressions of epithelial-mesenchymal transition (EMT) markers in EGFR-TKI-resistant NSCLC cells, which could also be rescued by CCL2 knockdown or inhibition. Furthermore, our findings suggest that CCL2-dependent EGFR-TKIs resistance involves the AKT-EMT signaling pathway; inhibition of this pathway effectively attenuates CCL2-induced cell migration and EMT marker expression. In summary, CCL2 promotes the development of acquired EGFR-TKIs resistance and EMT while activating AKT signaling in NSCLC. These insights suggest a promising avenue for the development of CCL2-targeted therapies that prevent EGFR-TKIs resistance in NSCLC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024076
Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, further investigations are needed to determine its therapeutic efficacy in treating RA. In this study, we evaluate the anti-inflammatory activity of OXH by treating LPS-induced RAW264.7 macrophages. Our results show that OXH treatment reverses the changes in iNOS, COX-2, IL-1β, IL-6, and TNF-α levels. Additionally, OXH reduces ROS production. Further analysis reveals that OXH suppresses the activation of the NF-κB/MAPK pathway. CETSA results show that OXH competes with LPS for binding to the TLR4/MD2 complex. MST experiments demonstrate the specific affinity of OXH for the TLR4/MD2 complex, with a Kd value of 33.7 μM. Molecular docking analysis suggests that OXH binds to the pocket of the TLR4/MD2 complex and interacts with specific amino acids, such as GLY-343, LYS-388, and PHE-345. Molecular dynamics simulations further confirm this conclusion. Finally, we investigate the potential of OXH in treating RA using a collagen-induced arthritis (CIA) model in rats. OXH effectively ameliorates the symptoms of CIA, including improving body weight, reducing swelling and redness, increasing talus volume, and decreasing bone erosion. OXH also decreases the mRNA levels of pro-inflammatory factors in synovial tissue. Transcriptome enrichment analysis and western blot analysis confirm that OXH suppresses the NF-κB/MAPK pathway, which is consistent with our in vitro findings.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024118
Lung cancer is the leading cause of cancer mortality in China and worldwide, and metastasis is the main cause of patient death. Cancer cells invade and migrate from the primary tumor, enter the circulation system through intravasation, and become circulating tumor cells (CTCs). CTCs that survive in blood vessels extravasate and invade target organs to become disseminated tumor cells (DTCs). DTCs proliferate in target organs to metastasize to distant organs. The previous view was that metastasis is the final stage of cancer progression. Normal cells first transform into tumor cells and then into invasive cancer cells; thus, metastasis occurs. Therefore, the possibility of metastasis is closely related to the size of the primary tumor. This is reflected in the TNM stage (T, tumor size; N, extent of spread to regional lymph nodes; M, metastasis to distant organs), which is often referenced in clinical diagnosis. However, an increasing number of studies are currently challenging this view. A previous study showed that the metastasis of malignant tumors occurs in the early stages of cancer. When patients are diagnosed with primary cancer, dissemination occurs. CTCs already exist in the blood vessels of early-stage lung cancer patients, and in early-stage lung cancer patients, DTCs are likely to be the main source of late-stage metastasis in some cancers; they do not proliferate in target organs, so they cannot be eliminated by surgery, radiotherapy or chemotherapy. As a result, even if the lesions are removed through surgery in these patients, metastasis is still found months or years later, which affects the patient’s quality of life and reduces the patient’s survival period. These observations prompt scientists in the field of metastasis to pay more attention to the prevention and treatment of DTCs when formulating metastasis prevention strategies. To determine whether DTCs exist in different states after entering the target organ, we used a mouse lung cancer metastasis model to generate CTC-TJH-01 cells, which are circulating tumor cells derived from the peripheral blood of early-stage lung adenocarcinoma patients who extravasate into target organs and become DTCs. Then, we observed the distribution and proliferation of DTCs in the lungs. Combined with traditional Chinese medicine theory, our findings can improve clinical medication regimens and promote innovations in metastasis prevention and treatment strategies. We observed the potential distribution and proliferation status of DTCs in the lungs in a mouse lung cancer metastasis model. A lung colonization assay was performed by injecting 5 × 105 CTC-TJH-01 cells into the lateral tail vein of NOD/SCID mice, and vimentin was used as a lung tumor marker. Immunofluorescence staining was performed, and CTC-TJH-01 cells that reached the lungs through the peripheral circulation were evenly spread over 24 h. This finding showed that cancer cells can move to distant sites through the circulation, especially the lungs, which are rich in blood vessels, and stay there in the form of DTCs. However, after 12 weeks, there were only a few visible metastases in the lungs, and many tumor cells in the visible metastases were Ki67-positive. Immunohistochemistry revealed other Vimentin-positive tumor cells in the lungs, but as the number of cells decreased, the Ki67 positivity rate also decreased, and a single tumor cell was negative for Ki67. This finding shows that an unsuitable microenvironment induces DTC apoptosis, and only a very small number of DTCs mediate the formation of an immunosuppressive microenvironment and then proliferate to form metastatic lesions. In addition, DTCs that survive have different proliferation rates; some proliferate to form metastases, while others remain dormant somewhere as individuals. These metastases of different sizes that coexist in the lungs may also have different responses to radiotherapy and chemotherapy due to their different proliferation rates. This may also explain why early-stage lung cancer patients still develop metastasis after standard clinical treatment. Before disseminated tumor cells proliferate and form visible metastases, they generally cannot be detected clinically through conventional diagnostic methods or tumor biomarkers, and patients at this stage often have no clinically significant symptoms; this stage can be called the “metastasis subclinical stage”. Tian et al. proposed the pathogenesis theory of “hidden toxicity due to vital Qi deficiency” for this stage of lung cancer metastasis. According to this theory, DTCs in a dormant state are already present in the metastatic target organs of patients with early-stage lung cancer after surgery. Immunosenescence or stress mediates immune dysfunction, leading to the activation and proliferation of dormant DTCs, which in turn leads to the occurrence of clinical metastasis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024147
The subcellular localization of RNA is critical to a variety of physiological and pathological processes. Dissecting the spatiotemporal regulation of the transcriptome is key to understanding cell function and fate. However, it remains challenging to effectively enrich and catalogue RNAs from various subcellular structures using traditional approaches. In recent years, proximity labeling has emerged as an alternative strategy for efficient isolation and purification of RNA from these intricate subcellular compartments. This review focuses on examining RNA-related proximity labeling tools and exploring their application in elucidating the spatiotemporal regulation of RNA at the subcellular level.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261511
This study integrates network pharmacology, molecular docking, and in vitro experiments to elucidate the anti-gastric cancer mechanism of morin, an active flavonoid from Mori Ramulus. Network analysis identified 178 potential targets of Mori Ramulus and 13,100 gastric cancer-related targets, with 159 intersecting targets. Enrichment analysis highlighted the PI3K/Akt pathway as a key mediator. Molecular docking and dynamics simulations confirmed stable binding between morin and PIK3R1, which is significantly overexpressed in gastric cancer tissues. In vitro, morin (100–400 μmol/L) dose-dependently inhibited AGS cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis (P<0.05, 0.01). Western blotting revealed downregulation of PI3K/Akt pathway proteins (p85α, p110β, p-Akt) and cell cycle-related proteins (Bcl-2, CCND1, CDK4, CDK6), alongside upregulation of Bax and p21 (P<0.05, 0.01). Co-treatment with the PI3K agonist 740Y-P significantly reversed these effects (P<0.05, 0.01), confirming pathway dependence. These findings demonstrate that morin targets PIK3R1 to suppress PI3K/Akt signaling, thereby inhibiting proliferation and inducing apoptosis and cell cycle arrest in gastric cancer cells. The study underscores morin's potential as a natural, multi-target lead compound with low toxicity, though further validation in additional cell lines and gene-level manipulations is warranted.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261625
Sterol biosynthesis in Stellaria dichotoma var. lanceolata remains poorly characterized despite the medicinal value of its sterol constituents. This study integrated high-performance liquid chromatography (HPLC) quantification of sterols across root, stem, leaf, and flower tissues with full-length transcriptome sequencing and comparative transcriptomics. A total of 372,483 high-quality full-length transcripts were assembled, of which 128,646 were annotated. Differential expression analysis revealed 43,354 genes shared across all four tissues (50.02% of total genes), with 9,647 differentially expressed genes (DEGs) between root and flower, 12,143 between root and leaf, and only 388 between leaf and stem. Weighted gene coexpression network analysis (WGCNA) identified 43 coexpression modules, and the MEblue module contained six key enzyme genes: NP_NY_transcript_168676 (FPPS), NP_NY_transcript_335811 (SQS), NP_NY_transcript_44001 (SQS), NP_NY_transcript_246835 (CAS), NP_NY_transcript_328932 (CAS), and NP_NY_transcript_183565 (GPPS). RT-qPCR validation confirmed expression trends consistent with transcriptome data. These findings provide a foundation for elucidating the biosynthetic pathway and molecular regulation of sterols in S. dichotoma var. lanceolata.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261610
Diosgenin (Dio) suffers from poor aqueous solubility and low oral bioavailability, limiting its clinical translation. This study developed diosgenin-rebaudioside A self-assembled nanomicelles (Dio-Reb A-SNM) using a combined drug-excipient strategy. Box-Behnken design-response surface methodology optimized the formulation: rebaudioside A to diosgenin ratio 12.32:1, diosgenin concentration 1.97 mg/mL, ultrasonic time 20.20 min. The optimized Dio-Reb A-SNM exhibited an encapsulation efficiency of 93.59±0.63%, drug loading of 5.65±0.07%, particle size of 25.66±1.76 nm, and zeta potential of -24.59±1.18 mV. Transmission electron microscopy revealed spherical morphology, and X-ray powder diffraction confirmed amorphization of diosgenin. The nanomicelles significantly enhanced saturated solubility across pH media and demonstrated sustained release (90.94% cumulative release at 18 h) fitting a Weibull model. Pharmacokinetic studies in SD rats showed that Dio-Reb A-SNM achieved a tmax of 2.06±0.29 h, t1/2 of 8.39±1.94 h, and increased Cmax and relative bioavailability by 3.59-fold and 6.82-fold, respectively, compared to free diosgenin. In a type 2 diabetes mellitus rat model, Dio-Reb A-SNM (30 mg/kg) significantly reduced blood glucose (P<0.01) and serum AST, ALT, urea nitrogen, and creatinine levels (P<0.01), with attenuated hepatic and renal pathological injury. These findings demonstrate that Dio-Reb A-SNM markedly improves oral absorption and hypoglycemic efficacy of diosgenin, providing a promising formulation strategy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21250
BACKGROUND: Frozen shoulder is a common disease in orthopedics, but there is no specific clinical indicator for diagnosis. There is a significant association between inflammatory cytokines and frozen shoulder, but the specific causal relationship is not yet clear. This study used summary statistical data from genome-wide association studies (GWAS) for Mendelian randomization analysis. GWAS data are based on large-sample genetic variation information, which can reduce environmental confounding factors and more reliably infer the causal relationship between inflammatory cytokines and frozen shoulder, making up for the limitation that traditional observational studies cannot determine causal associations. OBJECTIVE: To explore the causal relationship between inflammatory cytokines and the onset of frozen shoulder using bidirectional two-sample Mendelian randomization. METHODS: Using summary statistics from GWAS in the FinnGen database, we analyzed the causal relationship between 41 inflammatory cytokines and frozen shoulder. The FinnGen database, jointly initiated by the Finnish National Institute for Health and Welfare (THL), the University of Helsinki, and other Finnish research institutions, includes 2,942 cases and 167,641 European-ancestry controls, integrating genomic, clinical phenotype, and biochemical indicator data from hundreds of thousands to millions of individuals, supporting genetic association studies of diseases. This study is based on publicly available summary statistics databases and does not require ethical approval. Bidirectional Mendelian randomization analyses were performed using inverse variance weighting, weighted median, weighted model, simple model, MR-Egger regression, and sensitivity analyses (including MR-Egger, MR-PRESSO, Cochran's Q test). RESULTS AND CONCLUSION: Monocyte chemoattractant protein-3 (MCP-3) showed significant causal effects in both directions. In the forward analysis, MCP-3 was positively associated with frozen shoulder risk (OR=1.176, 95%CI: 1.034-1.338, P=0.014); in the reverse analysis, frozen shoulder was negatively associated with MCP-3 levels (OR=0.782, 95%CI: 0.625-0.979, P=0.032). Additionally, a significant association was found between tumor necrosis factor beta (TNF-β) and frozen shoulder risk (OR=1.126, 95%CI: 1.002-1.264, P=0.046); in the reverse analysis, stromal cell-derived factor 1 alpha (SDF-1α) was also significantly associated with frozen shoulder risk (OR=1.1, 95%CI: 1.011-1.196, P=0.028), indicating reliable correlations of TNF-β and SDF-1α with frozen shoulder. This bidirectional Mendelian randomization study reveals a complex interaction between MCP-3 and frozen shoulder, suggesting that MCP-3 may serve as a potential therapeutic target. Furthermore, the study indicates that TNF-β is associated with frozen shoulder risk and may be a potential risk factor; while frozen shoulder is also associated with elevated SDF-1α levels, and SDF-1α has the potential to become a diagnostic marker for frozen shoulder. However, further research is needed to elucidate the biological mechanisms underlying these causal relationships. Additionally, the analysis of international databases provides candidate molecules and causal inference paradigms for Chinese research, but it needs to be combined with local data for precise translation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21251
BACKGROUND: Inflammatory bowel disease, encompassing ulcerative colitis and Crohn’s disease, is a chronic condition linked to malnutrition, sarcopenia, and disease severity, with limited research on their genetic associations. OBJECTIVE: To systematically explore the common genetic basis and causal relationships between nutrition, nutritional status, and inflammatory bowel disease using advanced statistical genetics. METHODS: Single nucleotide polymorphism data for nutritional markers (minerals, vitamins, albumin, hemoglobin, fatty acids) and sarcopenia traits (appendicular lean mass and hand grip strength) were obtained from the GWAS Catalog, and inflammatory bowel disease and its subtypes from the FinnGen database R10. Advanced statistical genetics methods, including linkage disequilibrium score regression, cross-phenotype association analysis, and Mendelian randomization, were used to infer associations. RESULTS AND CONCLUSION: Significant genetic correlations were found: vitamin D with inflammatory bowel disease (rg=-0.080, P=0.029) and ulcerative colitis (rg=-0.087, P=0.027); appendicular lean mass with inflammatory bowel disease (rg=-0.100, P=0.0002), ulcerative colitis (rg=-0.100, P=0.0002), and small intestine Crohn’s disease (rg=-0.081, P=0.035); hand grip strength with small intestine Crohn’s disease (rg=-0.125, P=0.035). Mendelian randomization indicated a positive causal effect of magnesium levels on inflammatory bowel disease (OR=1.41, P=0.036) and small intestine Crohn’s disease (OR=1.78, P=0.035). Cross-phenotype analysis identified shared single nucleotide polymorphisms, particularly in the human leukocyte antigen region, affecting both nutritional status and inflammatory bowel disease. These findings further explain the genetic link between nutrition, sarcopenia, and inflammatory bowel disease, suggesting that targeted nutritional management may be key to slowing disease progression. This study provides new perspectives for personalized treatment and has potential implications for prevention strategies of inflammatory bowel disease.
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: 10.12307/2026.21417
BACKGROUND: The anterior transpedicular screw fixation system can achieve adequate decompression and strong fixation in a single anterior surgery. However, due to its unique anatomical structure, the risk of screw placement is relatively high. Previous domestic and international scholars have confirmed the feasibility of this approach through anatomical measurements, but there are some drawbacks such as relatively small sample sizes, difficulties in locating the pedicle axis, and limitations in measurement methods. OBJECTIVE: To perform morphological measurements of the adult cervical spine based on imaging to provide anatomical guidance for anterior transpedicular pedicle screw fixation. METHODS: 3D CT scan data of 50 adult cervical vertebrae were imported into the Mimics system for 3D reconstruction. Morphological data were measured, including pedicle axis distance, pedicle width, pedicle height, pedicle horizontal axial angle, pedicle sagittal angle, distance from the entry point in the transverse plane, distance to the entry point in the sagittal plane, axial vertebral length and axial pedicle length. RESULTS AND CONCLUSION: (1) Positioning of nail entry points: C3 and C4 were located on the opposite side of the median sagittal plane of the vertebral body, with distances from the median sagittal line of approximately 2.060 mm and 2.310 mm. C5 could be located on the same side of the median sagittal line as or opposite to the median sagittal line, with an average value of approximately 1.224 mm. C6-C7 were located on the same side of the body, with distances of 1.132 mm and 2.538 mm from the midline; the distance from the upper endplate increased gradually from C3 to C7, with average values ranging from 2.362 to 7.350 mm. (2) Direction of nail entry: the transverse angle increased gradually from C3 to C4 (46.32°-47.36°) and decreased from C5 to C7 (44.03° to 37.80°); the sagittal angle required caudal deviation for C3-C4 (95.75° and 100.93°) and cephalad deviation for C5-C7 (104.38°, 110.34°, and 104.86°). (3) There were no significant differences in entry point location and direction between genders or sides (P > 0.05). For screw selection, except for individual patients with cervical developmental abnormalities, for most subaxial cervical pedicle screws, it is safe and reliable to choose screws at least 30 mm long and 4.0 mm in diameter for males, and at least 28 mm long and 3.5 mm in diameter for females. (4) Morphological measurements confirmed that anterior transpedicular screw fixation of the subaxial cervical spine is feasible, but individualized principles should be followed to formulate personalized fixation plans.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21418
BACKGROUND: Clinically, due to the special anatomical characteristics and internal trabecular bone distribution of the scaphoid, the treatment effect of fractures is generally poor, often leading to nonunion and ischemic necrosis, which in turn causes wrist arthritis and loss of function. OBJECTIVE: To scan scaphoid specimens using Micro CT technology, analyze their internal microstructure characteristics, measure the trabecular bone microstructure parameters in each region, and discover regional differences in scaphoid trabecular bone, aiming to provide a scientific basis for the prevention, treatment, and fracture mechanism research of scaphoid fractures. METHODS: Bilateral scaphoid bones (10 cases) from 5 adult cadaver specimens were scanned by Micro CT. By selecting and reconstructing trabecular bone in three regions of interest (tubercle, waist, and body), the internal micromorphological characteristics of the scaphoid were observed in detail, and the differences in trabecular bone microstructure parameters among regions were measured and compared. RESULTS AND CONCLUSION: (1) Micro CT images showed that the cortical bone on the surface of the scaphoid was relatively thin, and the interior was filled with complex trabecular bone microstructure; the lamellar trabecular bone near the cortical bone was relatively dense, extending inward into rod-like trabecular bone. From sagittal, coronal, and transverse sections, the trabecular bone distribution in the waist was relatively sparse, while that in the body and tubercle was denser. (2) There were significant differences in bone volume fraction, bone surface area, bone surface area to tissue volume ratio, trabecular separation, trabecular number, trabecular connectivity, trabecular connection density, fractal dimension, bone mineral density, and bone mineral content of the scaphoid tubercle between left and right sides (P < 0.05). There were no significant differences in the trabecular bone microstructure parameters of the waist and body between left and right sides (P > 0.05). (3) There were significant differences in bone volume, bone volume fraction, bone surface area, bone surface area to tissue volume ratio, bone surface area to bone volume ratio, bone mineral density, and bone mineral content between the body and the tubercle/waist (P < 0.05). There was a significant difference in trabecular thickness between the body and the tubercle (P < 0.05). There were significant differences in trabecular separation and fractal dimension among the body, tubercle, and waist (P < 0.05). There were significant differences in trabecular number, trabecular connectivity, and trabecular connection density between the waist and the tubercle/body (P < 0.05). There were no significant differences in tissue volume and degree of anisotropy among the body, tubercle, and waist (P > 0.05). (4) The results showed that the trabecular bone microstructure parameters of the scaphoid had regional differences, among which the waist had lower bone density and strength, making it the most prone to fracture. This finding provides a theoretical basis for understanding the fracture mechanism of the scaphoid from the perspective of trabecular bone microstructure. At the same time, the trabecular bone structure characteristics of different parts of the scaphoid revealed in this study also provide a theoretical basis for designing targeted internal fixation instruments.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21317
BACKGROUND: Existing animal models of knee osteoarthritis predominantly focus on mechanical injury factors but fail to simulate and observe the "cold-dampness obstruction" syndrome characteristics in traditional Chinese medicine. OBJECTIVE: To construct a traditional Chinese medicine-Western medicine integrated knee osteoarthritis model for cold-dampness obstruction syndrome and validate its efficacy via a multidimensional assessment. METHODS: Twenty-four male Sprague-Dawley rats (SPF-grade) were randomly divided into sham-operated, model, and cold-dampness obstruction groups. The latter two groups underwent anterior cruciate ligament transection of the right hind knee. The cold-dampness obstruction group received artificial cold-damp environment intervention (temperature 10.5 °C, humidity 90%, 4 h/day, for 4 weeks) starting 14 days post-surgery. The sham-operated group had skin incision and immediate closure. Before modeling and at 1, 2 weeks post-modeling, and 4 weeks after cold-damp intervention, traditional Chinese medicine syndrome scores and CatWalk gait analysis were performed. Right hind knee joint tissues were harvested for histopathological observation and Mankin scoring. RESULTS AND CONCLUSION: (1) Traditional Chinese medicine syndrome scores: The cold-dampness obstruction group showed significant mental fatigue, reduced activity, loose stools, dark purple tongue, dull fur, decreased food intake, and slower weight gain (P < 0.01). (2) CatWalk gait parameters: At 1 week post-modeling, compared with the sham-operated group, the model and cold-dampness obstruction groups showed decreased maximum contact intensity, print length, maximum intensity, average intensity of 15 maximum pixels, and increased swing phase of the right hind paw (all P < 0.01). The cold-dampness obstruction group also showed significantly decreased swing speed (P < 0.05). After 4 weeks in the artificial climate chamber, compared with the sham-operated group, the cold-dampness obstruction group showed significantly decreased maximum contact intensity, maximum intensity, average intensity of 15 maximum pixels (P < 0.01), increased swing phase (P < 0.01), and decreased swing speed (P < 0.05). (3) Histopathology: Mankin scores in the model and cold-dampness obstruction groups were significantly higher than in the sham-operated group (P < 0.01), and the cold-dampness obstruction group had significantly higher scores than the model group (P < 0.01). These results indicate that anterior cruciate ligament transection combined with cold-damp environment can successfully construct a cold-dampness obstruction type early knee osteoarthritis rat model. CatWalk gait parameters and traditional Chinese medicine syndrome scores provide an objective evaluation system for studying the mechanisms of traditional Chinese medicine in knee osteoarthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21436
BACKGROUND: In recent years, numerous studies have confirmed a close relationship between the skeletal system and the central nervous system, making the bone-brain axis a research hotspot in interdisciplinary fields; however, no studies have yet conducted a bibliometric and visualization analysis of this field. OBJECTIVE: To comprehensively analyze the research trends, hotspots, and future development directions in the bone-brain axis field utilizing bibliometric methods, providing data support and reference for subsequent studies. METHODS: A systematic literature search was conducted in the Web of Science Core Collection database to collect studies related to bone-brain axis published between 2015 and 2024. Visualization tools such as VOSviewer and CiteSpace were employed to analyze publication trends, collaboration networks, institutional contributions, and keyword co-occurrence patterns. RESULTS AND CONCLUSION: ①A total of 7,461 publications were included, showing a significant upward trend in publication volume over the past decade (2015-2024), indicating that bone-brain axis research has become an academic hotspot with increasing attention. ②The United States and China dominated the field, with the USA publishing 2,397 papers (32.1%) and China 2,307 papers (30.9%). Harvard Medical School and Zhejiang University were the most productive and central institutions. ③Professor Wang Wei was the most prolific author, focusing on the interaction between bone marrow and neuroinflammation. ④The journal Bone published the most papers (over 800), while PLOS ONE had the highest average citations per paper (45), indicating its influence. ⑤Core keywords included 'Bone Marrow', 'Stem Cells', 'Osteoporosis', and 'Neuroinflammation', reflecting fundamental research directions. Emerging frontiers included 'Extracellular Vesicles', 'Alzheimer's Disease', 'Inflammation', and 'Oxidative Stress', highlighting the importance of inflammation and neurodegenerative diseases. ⑥Future research directions include exploring the specific mechanisms of osteogenic factors and neurotransmitters in the bone-brain axis, elucidating the molecular mechanisms of inflammation, oxidative stress, and extracellular vesicles in neurodegenerative diseases and bone metabolic disorders, and promoting the translation of basic research to clinical applications.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21615
BACKGROUND: Previous studies have confirmed that neck muscle strength and intervertebral stress can influence the progression of cervical spine degeneration. However, no quantitative analysis has been conducted to examine the interaction between the biomechanical changes in cervical spondylotic myelopathy and cervical vertebral stress and paravertebral muscles. OBJECTIVE: To explore the cervical spine movement patterns of patients with cervical spondylotic myelopathy based on biomechanical principles, quantify the synergistic imbalance effects between paraspinal muscle strength and intervertebral stress in these patients, and discuss and reveal the dialectical relationship between the traditional Chinese medicine theory of “musculoskeletal imbalance” and the modern biomechanical concept of “dynamic and static imbalance” in cervical spondylotic myelopathy. METHODS: Twenty patients with cervical spondylotic myelopathy (CSM group) from the orthopedic outpatient and inpatient departments of the First Affiliated Hospital of Guangxi University of Chinese Medicine and ten healthy individuals (healthy group) from the health examination center and “preventive treatment of disease” center were enrolled. Age and sex were recorded. Cervical spine 6-degree-of-freedom motion data were collected using motion capture and Opensim virtual simulation models, with three repeated measurements. After data optimization, forward dynamics tool algorithms were used to quantify range of motion, peak motion angle changes, vertebral pressure center distribution, average muscle strength, average maximum joint pressure, and average maximum joint shear force in both groups. RESULTS AND CONCLUSION: (1) There were no statistically significant differences in sex and age between the two groups. (2) In left rotation, right rotation, and extension directions, the peak motion angle changes in the CSM group were significantly smaller than those in the healthy group; in lateral flexion, rotation, and extension directions, the range of motion in the CSM group was significantly larger than that in the healthy group. (3) Comparison of pressure centers at C4 and C5 indicated that the joint pressure center in CSM patients was more diffuse. (4) The average muscle strength in CSM patients was much lower than that in healthy individuals. (5) The maximum joint pressure at C4-C6 during extension in CSM patients was significantly greater than that in the healthy group, while the maximum joint pressure at C3-C7 during flexion, lateral flexion, and rotation was smaller than that in the healthy group; the average maximum joint shear force at C4-C7 during lateral flexion and rotation in the healthy group was greater than that in the CSM group. (6) These findings suggest that during neck movement, CSM patients exhibit decreased neck muscle strength and baseline vertebral stress imbalance, which alters the stress on the facet joints and pressure center distribution, accelerates the degeneration of bony structures and muscles, and disrupts cervical stability. The biomechanical changes in CSM are correlated with the “musculoskeletal imbalance” and “dynamic and static imbalance” theories.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21529
BACKGROUND: Knee osteoarthritis is an age-related disease, and aging is closely related to its occurrence and development. Chondrocyte senescence plays a crucial role in the pathological progression of knee osteoarthritis. OBJECTIVE: To establish a stable induced knee osteoarthritis model in SD rats. METHODS: (1) Animal experiment: Forty Sprague-Dawley rats were randomly divided into four groups: blank control group (no modeling), D-galactose group (intra-articular injection of D-galactose solution once a week for 2 months), anterior cruciate ligament transection (ACLT) group (ACLT to establish knee osteoarthritis model), and D-galactose+ACLT group (ACLT followed by intra-articular injection of D-galactose solution once a week for 2 months). One week after modeling, all rats underwent running exercise for 30 min every other day. At 4 and 8 weeks after modeling, behavioral tests (Lequesne MG score) were performed, and then samples were collected for detection of inflammatory factors in synovial fluid, histopathological morphology of knee cartilage, transmission electron microscopy observation, and immunohistochemical staining of type II collagen and aggrecan. (2) Cell experiment: At 4 and 8 weeks after modeling, knee chondrocytes were isolated from each group for flow cytometry cell cycle analysis, β-galactosidase staining, and γ-H2AX immunofluorescence staining. RESULTS AND CONCLUSION: (1) Animal experiment: At 8 weeks after modeling, Lequesne MG scores in the three model groups were higher than those in the blank control group (P < 0.05), and the score in the D-galactose+ACLT group was higher than that in the D-galactose and ACLT groups (P < 0.05). At 4 and 8 weeks, levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α in synovial fluid were higher in the three model groups than in the blank control group (P < 0.05), and these levels were higher in the D-galactose+ACLT group than in the D-galactose and ACLT groups (P < 0.05). Hematoxylin-eosin and safranin O/fast green staining and transmission electron microscopy at 4 and 8 weeks showed that cartilage damage and chondrocyte mitochondrial damage were more severe in the D-galactose+ACLT group than in the D-galactose and ACLT groups. Immunohistochemical staining showed that the expression of type II collagen and aggrecan was highest in the blank control group, and lowest in the D-galactose+ACLT group among the model groups. (2) Cell experiment: At 4 and 8 weeks, the proportion of chondrocytes in G0/G1 phase was higher, and the proportions in S and G2/M phases were lower in the D-galactose+ACLT group than in the other three groups (P < 0.05). The positive rate of β-galactosidase staining and γ-H2AX immunofluorescence intensity were higher in the D-galactose+ACLT group than in the other three groups (P < 0.05). (3) These results indicate that the D-galactose+ACLT method can establish an SD rat model of aging-related knee osteoarthritis, which can better simulate the pathological state of aging and degeneration in knee osteoarthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21528
BACKGROUND: Modern research suggests that the “muscle-bone imbalance” in cervical spondylotic radiculopathy is associated with changes in the performance of cervical muscles due to biomechanical alterations of the head and neck. However, most studies have focused on static analysis of the cervical spine, lacking dynamic quantitative data on neck muscle strength and activation. OBJECTIVE: To investigate the differences in muscle strength and muscle activation during cervical spine movement between patients with cervical spondylotic radiculopathy and healthy individuals from a biomechanical perspective. METHODS: From October 1, 2023 to March 1, 2024, 10 volunteers were recruited from the orthopedic outpatient or inpatient department and health examination center of the First Affiliated Hospital of Guangxi University of Chinese Medicine, including 5 patients with cervical spondylotic radiculopathy (cervical spondylotic radiculopathy group) and 5 healthy individuals (healthy control group). Inertial motion capture sensors were used to capture the motion data of the neck in six degrees of freedom: flexion, extension, left lateral flexion, right lateral flexion, left rotation, and right rotation. Each movement was repeated three times, yielding 18 sets of data per subject. Based on MRI-derived muscle parameters of patients and healthy individuals, OpenSim head-neck musculoskeletal models were respectively established. After preprocessing, the captured neck motion data were imported into the OpenSim simulation model to calculate and compare the neck muscle strength and muscle activation levels between the two groups. RESULTS AND CONCLUSION: (1) The healthy control group showed orderly synergistic activation of muscle groups, while the cervical spondylotic radiculopathy group exhibited disordered synergistic activation patterns, characterized by insufficient activation of the affected side muscles, excessive compensation of the healthy side, and significantly reduced synergy of core muscles such as the sternocleidomastoid, middle and upper trapezius, and longus colli. In the cervical spondylotic radiculopathy group, during extension, the muscle strength of the sternocleidomastoid, middle trapezius, longus capitis, and upper trapezius was lower than that of the healthy control group (P < 0.05). During flexion, the muscle strength of the sternocleidomastoid, longus capitis, longus colli, levator scapulae, multifidus, splenius cervicis, splenius capitis, and middle/upper trapezius was lower than that of the healthy control group (P < 0.05). During left lateral flexion, the muscle strength of the sternocleidomastoid, longus capitis, longus colli, scalene, levator scapulae, multifidus, splenius cervicis, splenius capitis, and middle/upper trapezius was lower than that of the healthy control group (P < 0.05). During right lateral flexion, the muscle strength of the longus colli and upper trapezius was lower than that of the healthy control group (P < 0.05). During left rotation, the muscle strength of the levator scapulae was lower than that of the healthy control group (P < 0.05). During right rotation, the muscle strength of the longus colli was lower than that of the healthy control group (P < 0.05). (2) These findings indicate that patients with cervical spondylotic radiculopathy exhibit muscle synergy imbalance in all directions of cervical spine movement. The imbalance is characterized by degeneration of the affected side muscles and nerves, reduced muscle strength and coordination, while the healthy side muscles and nerves compensate for the functional insufficiency of the affected side, leading to over-control. Among the muscle groups involved in cervical spine movement, the degeneration of the sternocleidomastoid and middle/upper trapezius is the most significant, which is one of the important features causing cervical spondylotic radiculopathy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21604
BACKGROUND: Polyetheretherketone (PEEK) synthetic material has become one of the preferred materials for repairing skull defects due to its low density, high strength, good toughness, excellent processing performance, and good biocompatibility, but there are few bibliometric analyses of PEEK for skull repair. OBJECTIVE: To explore the overall research trends, development context, research focuses, and hotspots of PEEK materials in the field of international skull defect repair using bibliometric methods. METHODS: The Web of Science Core Collection database was systematically searched for literature on PEEK materials for skull defect repair published from 1995 to 2024. On this basis, bibliometric methods were used to conduct quantitative statistics and visual analysis from the aspects of temporal dynamics of publication volume, country/region contribution, core research institution cooperation network, highly cited papers, high-yield journals, and keyword co-occurrence. RESULTS AND CONCLUSION: This study analyzed 105 studies on PEEK for skull defect repair published from 2009 to 2024. The development process was roughly divided into three stages: 2009-2014 traditional materials, 2015-2019 clinical research on PEEK, and 2020-2024 3D printing and finite element analysis, with the 2020-2024 stage accounting for 42%. Meanwhile, "3D printing, finite element analysis" and "PEEK, titanium alloy" were high-frequency technology combinations. China (21 articles), the United States (17 articles), and Germany (12 articles) were the main research countries. PEEK has been used in more than 200,000 clinical applications worldwide, with an infection rate of 3.7%, lower than that of polymethyl methacrylate (9.2%). PEEK research has shifted from "passive repair" to "active bioactivity promotion". Europe and the United States lead in clinical translation of 3D printing (equipment rate 82%, while China's domestic rate is 39%), but there is a lag of about 2 years between literature and clinical application for 3D-printed PEEK. It is predicted that conductive PEEK will accelerate translation in 2026-2027. The results indicate that PEEK has achieved a transformation from "passive repair" to "active bioactivity promotion", with 3D printing, surface modification, and intelligent integration as core directions. Global PEEK development is uneven; underdeveloped regions have high demand but less research (12%). China focuses on clinical research (68%) but lacks basic innovation (15%). It is necessary to promote low-cost 3D printing technology, establish translation hubs, support interdisciplinary research teams, and build a 10-year multicenter follow-up system.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04926-5
Alopecia Areata (AA) is a chronic inflammatory disorder characterized by non-scarring, patchy hair loss that may progress to the entire scalp (alopecia totalis) or body (alopecia universalis), significantly impairing patients’ quality of life and psychological health. Although the exact pathogenesis of AA remains unclear, current evidence suggests that the breakdown of hair follicle immune privilege (IP) and subsequent autoimmune-mediated follicular attack play a pivotal role. Conventional therapeutic modalities, including corticosteroid and Janus kinase (JAK) inhibitors, are often limited by suboptimal efficacy in severe cases and high relapse rates following treatment cessation. In recent years, stem cell-based therapy has emerged as a novel treatment for AA, showing therapeutic potential through multiple mechanisms. Preliminary clinical trials have indicated significant efficacy in promoting hair regrowth among AA patients. However, comprehensive evaluation of long-term safety and therapeutic efficacy remains imperative. This review article aims to give a comprehensive overview of the recent advances in stem cell-based therapies for AA and explore their underlying mechanisms and clinical application prospects, hoping to provide a framework and reference for future research and clinical practice.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026046
Epstein-Barr virus-associated gastric cancer (EBVaGC) displays unique clinicopathological hallmarks, yet serology-based tools for its detection are still limited. Here, we develop a functional EBV proteome microarray covering 72 viral proteins and apply it to profile antibody responses in 62 gastric cancer patients. The resulting landscape reveals an IgG-skewed humoral signature specific to EBVaGC and identifies 34 EBV antigens exhibiting differential reactivities. Multivariable logistic regression integrates complementary markers into an optimal five-analyte panel (LF2_IgG, BBLF2_IgG, BLRF2_IgG, BPLF1-2_IgA, and BGLF4_IgA) that achieves outstanding discrimination performance (AUC = 0.93) in an independent validation set (n = 316). The panel’s performance is further validated in a community-based screening cohort (n = 474), where it achieves 87.3% sensitivity and 88.3% specificity for distinguishing EBVaGC from non-malignant gastric conditions spanning gastritis to dysplasia (AUC = 0.94). Together, these results establish a serological framework for EBVaGC diagnosis and provide a scalable strategy for population-level screening that could materially improve the management of this virus-driven malignancy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026117
SGLT2 inhibitor (SGLT2i)-induced diabetic hyperketonemia is a life-threatening acute complication of diabetes. While celastrol has been reported to have beneficial effects on obesity, its potential role in ketogenesis remains unclear. In this study, celastrol administration significantly attenuates the fasting-induced increase in blood β-hydroxybutyrate levels. Moreover, a 7-day course of celastrol (1 mg/kg/day) leads to reductions in body weight and fat mass. Mechanistically, celastrol specifically downregulates HMGCS2 expression and suppresses hepatic ketogenesis through the inhibition of PPARα expression in the short term (≤ 2 days). However, after prolonged treatment for 7 days, celastrol modulates both PPARα and serum free fatty acid (FFA) levels. Furthermore, the anti-ketogenic effect of celastrol is abolished in Pparα⁻/⁻ mice. Importantly, celastrol effectively ameliorates SGLT2i-induced hyperketonemia. In summary, celastrol curbs hepatic ketone overproduction in a PPARα-dependent manner, indicating its protective potential against SGLT2i-induced hyperketonemia.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026099
Melanoma is an aggressive skin cancer with poor prognosis in advanced stages due to its metastatic potential. Although treatment modalities such as surgical resection, targeted therapy, immunotherapy, radiotherapy, and chemotherapy have conferred long-term survival benefits to certain patients, not all individuals respond favorably, underscoring the urgent need to develop predictive biomarkers. Ribosomal proteins have been implicated in tumor progression through extraribosomal functions. Ribosomal protein L8 (RPL8) is a unique ribosomal protein that warrants further exploration. Here, we investigated the role of RPL8 in melanoma progression. Using clinical data from the GDC and GEO databases, we found that high RPL8 expression is associated with poor prognosis in melanoma patients. Immunohistochemical analysis confirmed higher RPL8 expression in melanoma tissues compared to normal tissues. To elucidate the functional impact, we established an A875 melanoma cell line with stable RPL8 knockdown (shRPL8) using lentiviral vectors. RT-qPCR and western blot analysis confirmed efficient knockdown. CCK-8 assays showed that RPL8 knockdown significantly inhibited cell proliferation. Flow cytometry analysis revealed that RPL8 knockdown led to an increase in the proportion of cells in the G2/M phase and a decrease in the S phase, indicating cell cycle arrest. Furthermore, transwell assays demonstrated that RPL8 knockdown reduced cell invasion and migration. These findings suggest that RPL8 promotes melanoma progression by regulating the cell cycle and metastasis, and may serve as a potential therapeutic target and prognostic biomarker for melanoma.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026031
Mitochondrial transplantation is a promising treatment for many diseases associated with mitochondrial defects or aging; however, a reliable method for mitochondrial transfer remains urgently needed. In this study, we assemble fusogenic and magnet-responsive cells (FMRCs), which are enucleated stem cells loaded with Fe3O4 nanoparticles and further incorporated fusogenic vesicular stomatitis virus glycoprotein G (VSV-G). Mitochondrial transplantation from FMRCs via fusion in the presence of a magnetic force restores normal mitotic activity, mitochondrial membrane potential, ROS levels and ATP production in cells subjected to partial mtDNA depletion or in cybrids harboring mtDNA with a 4977-bp deletion. SNP tracing and qPCR analysis of the mitochondrial and nuclear genomes unequivocally demonstrate that exogenous mitochondria are able to reside stably and predominately. Mitochondrial transplantation stimulate autophagy and thus the clearance of defective endogenous counterparts, resulting in lower mtDNA heteroplasmy. These results suggest that FMRCs are excellent vehicles for mitochondrial transplantation and could be used for the treatment of aging and mitochondria-associated diseases.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731785313317742
Background: Heart failure with recovered ejection fraction (HFrecEF) is a distinct phenotype with unclear clinical characteristics and prognosis. Methods: We prospectively enrolled 1,234 patients with heart failure and reduced ejection fraction (HFrEF) from January 2015 to December 2018. After optimal medical therapy, 312 patients (25.3%) achieved recovery of left ventricular ejection fraction (LVEF) to ≥50% and were classified as HFrecEF. Clinical characteristics, medication use, and outcomes were compared with those who remained HFrEF. The primary outcome was a composite of all-cause death and heart failure hospitalization. Results: Compared with HFrEF patients, HFrecEF patients were younger, more likely to be female, had a higher prevalence of hypertension and atrial fibrillation, and had a shorter duration of heart failure. They had lower baseline levels of NT-proBNP and smaller left ventricular dimensions. Over a median follow-up of 3.2 years, HFrecEF patients had a significantly lower risk of the primary outcome (adjusted HR 0.45, 95% CI 0.32-0.63, p<0.001). However, 23.4% of HFrecEF patients experienced deterioration of LVEF during follow-up, and these patients had a worse prognosis compared with those who maintained recovery. Independent predictors of LVEF deterioration included ischemic etiology, diabetes, and non-adherence to guideline-directed medical therapy. Conclusions: HFrecEF is associated with a better prognosis than HFrEF, but a substantial proportion of patients may experience LVEF deterioration. Continued optimization of medical therapy and close monitoring are essential for this population.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025021
Homocysteine (Hcy) is an independent risk factor for atherosclerosis, and defective macrophage autophagy accelerates plaque formation. Pyruvate dehydrogenase (PDH), a key component of the PDH complex, links energy metabolism to autophagy, but its role in Hcy-induced atherosclerosis remains undefined. Proteomic profiling of Hcy-treated macrophages identified 748 upregulated and 760 downregulated proteins, with KEGG enrichment in amino acid biosynthesis, carbon metabolism, and glycolysis/gluconeogenesis. In ApoE–/– mice, Hcy treatment markedly reduced PDH expression and activity, leading to impaired autophagy. PDH activation restored autophagy by promoting assembly of the ULK1-FIP200-Atg13 complex via modulation of AMPK/mTOR signaling. These findings suggest that PDH activation may serve as a therapeutic strategy for Hcy-induced atherosclerosis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025029
Intervertebral disc degeneration (IVDD) is the principal cause of low back pain, with current therapies limited to symptomatic relief. This study investigates the role of circ_0000389 in IVDD pathogenesis. Bioinformatic analysis of the GSE67566 dataset identified circ_0000389 as differentially expressed. RT-qPCR revealed significant downregulation of circ_0000389 in degenerating nucleus pulposus (NP) tissues. Functional assays demonstrated that circ_0000389 overexpression promotes nucleus pulposus cell (NPC) proliferation and inhibits extracellular matrix (ECM) catabolism. Mechanistically, dual-luciferase reporter and RNA immunoprecipitation assays confirmed that circ_0000389 directly sponges miR-346, and miR-346 directly targets KLF7. miR-346 overexpression reversed the protective effects of circ_0000389, while KLF7 overexpression reversed the effects of miR-346. These findings establish the circ_0000389/miR-346/KLF7 axis as a critical regulator of IVDD progression, providing a potential therapeutic target.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025138
Lung adenocarcinoma (LUAD) remains the leading cause of cancer-related mortality worldwide, with a five-year survival rate of approximately 15%. Despite advances in targeted therapy, the limited repertoire of actionable mutations and the inevitable emergence of drug resistance necessitate the continuous discovery of novel therapeutic agents. This study investigates the antitumor efficacy of EOAI3402143, a small-molecule inhibitor, against LUAD and elucidates its mechanism of action. Using flow cytometry, transwell, colony formation assays, western blot, RT-qPCR, and RNA-seq, we demonstrate that EOAI3402143 promotes apoptosis and suppresses migration, invasion, and proliferation of LUAD cells. Mechanistically, EOAI3402143 inhibits NF-κB pathway activation and downregulates NR4A1 expression, thereby attenuating LUAD progression. In vivo experiments confirm superior therapeutic efficacy of EOAI3402143 in LUAD models. These findings position EOAI3402143 as a promising candidate for LUAD therapy, particularly for patients with limited targeted options or acquired resistance.