Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpb/art_1123
Gametogenesis plays an important role in the reproduction and evolution of species. The transcriptomic and epigenetic alterations in this process can influence the reproductive capacity, fertilization, and embryonic development. The rapidly increasing single-cell studies have provided valuable multi-omics resources. However, data from different layers and sequencing platforms have not been uniformed and integrated, which greatly limits their use for exploring the molecular mechanisms that underlie oogenesis and spermatogenesis. Here, we develop GametesOmics, a comprehensive database that integrates the data of gene expression, DNA methylation, and chromatin accessibility during oogenesis and spermatogenesis in humans and mice. GametesOmics provides a user-friendly website and various tools, including Search and Advanced Search for querying the expression and epigenetic modification(s) of each gene; Tools with Differentially expressed gene (DEG) analysis for identifying DEGs, Correlation analysis for demonstrating the genetic and epigenetic changes, Visualization for displaying single-cell clusters and screening marker genes as well as master transcription factors (TFs), and MethylView for studying the genomic distribution of epigenetic modifications. GametesOmics also provides Genome Browser and Ortholog for tracking and comparing gene expression, DNA methylation, and chromatin accessibility between humans and mice. GametesOmics offers a comprehensive resource for biologists and clinicians to decipher the cell fate transition in germ cell development, and can be accessed at http://gametesomics.cn/.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Background Osteoporosis (OP) is a systemic bone disease characterized by damage to bone strength, leading to increased bone fragility and fracture risk. Cadherin 19 (CDH19) is located on chromosomes 18q22-q23, and 18q deletion is associated with terminal deletion diseases, including foot/hand deformities. However, the role of CDH19 in bone remains undefined. Methods A conditional knockout mouse model of the CDH19 gene was constructed using the Cre-loxP system, and the bone mass and bone morphology in mice were investigated using microCT and histological staining. Osteoblasts were isolated and cultured from wild-type and CDH19 knockout mice. Cell proliferation and differentiation were explored through EdU labeling, qPCR, alkaline phosphatase (ALP)/ alizarin red S (ARS) staining, and Western blot assays. The expression of genes altered in CDH19 gene knockout osteoblast was checked by RNA sequencing (RNA-seq), and subsequently confirmed by immunofluorescence and Western blot. Results We found that CDH19 could maintain the normal proliferation and differentiation in osteoblasts. After knocking out the CDH19 gene, the abilities of proliferation and osteogenesis were significantly inhibited in osteoblasts. Moreover, the bone mass of CDH19 knockout mice was significantly reduced, characterized by decreases in bone density, trabecular number, and bone volume fraction. The RNAseq analysis and western blot showed the PI3K/AKT signaling pathway was significantly inhibited in osteoblasts with CDH19 deletion. Furthermore, we demonstrated that administration of PI3K/AKT signaling pathway agonist 740Y-P partially alleviated the inhibition of osteogenic differentiation caused by CDH19 deletion in vitro and in vivo. Conclusion This study demonstrated that CDH19 regulated osteogenic differentiation by modulating the PI3K/AKT signaling pathway in osteoblasts. CDH19 may become a novel target for the treatment of bone diseases.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04613-x
Background Osteoarthritis (OA) is a joint disorder that severely affects patients’ mobility, overall health, and ability to perform daily activities. Despite advancements in therapeutic strategies, stem cell-based therapies for OA still face challenges, particularly in enhancing the antioxidative capacity of stem cells to improve therapeutic outcomes. Therefore, this study aimed to explore the potential of β-sitosterol in this context. Methods This study evaluated the protective effects of β-sitosterol on bone marrow-derived mesenchymal stem cells (BMSCs) and chondrocytes under oxidative stress conditions and assessed its potential in promoting cartilage repair in a rabbit OA model. Cell viability, gene expression, oxidative stress markers, and mitochondrial function were examined. In vivo therapeutic effects were evaluated through histological and immunohistochemical analyses. Results The results revealed that β-sitosterol significantly enhanced BMSC viability, upregulated the expression of Col2a1 and aggrecan, while inhibiting MMP13 expression. Furthermore, β-sitosterol effectively alleviated oxidative stress and preserved mitochondrial function in BMSCs. Notably, BMSCs pretreated with β-Sitosterol exhibited a higher potential for facilitating cartilage regeneration in the OA model, as evidence by histopathological analysis. Conclusions These findings suggest that β-sitosterol possesses significant antioxidative and chondroprotective properties, which enhance the therapeutic efficacy of BMSCs in addressing OA-related cartilage damage.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04480-6
Background Diabetic foot ulcers (DFU) typically exhibit impaired healing due to dysregulated re-epithelialization and excessive inflammation. Succinate, a key metabolic intermediate, is now understood to regulate inflammation through G Protein-Coupled Receptor 91 (GPR91) and succinate dehydrogenase (SDH), although its role in DFU remains unclear. Methods Co-cultures of M2 macrophages and epithelial cells, along with clinical samples, were used to analyze the expression of GPR91 and SDH. Functional assays were performed using high glucose (HG)-treated M2 macrophages (HG-M2) and an in vivo model. Cytokine and growth factor levels in cell supernatant were measured, and molecular mechanisms were explored via qRT-PCR, flow cytometry, and western blot analysis. Results Elevated glucose concentrations increased succinate levels and disrupted M2 macrophage–epidermal stem cells (EpSCs) interactions. GPR91 knockdown worsened HG-M2 dysfunction, while GPR91 overexpression (OE-GPR91) enhanced anti-inflammatory responses and reduced succinate. OE-GPR91-conditioned medium preserved EpSCs stemness and promoted migration mediated by hepatocyte growth factor (HGF). SDH inhibition (via Dimethyl malonate, DMM) boosted M2 macrophage activity by reducing reactive oxygen species (ROS) and upregulating Gpr91 expression. Mechanistically, GPR91 activated the pAkt/pGSK3β/β-catenin pathway, while DMM enhanced M2 macrophage function via the PI3K-Akt/pERK1/2 pathway. Conclusions GPR91 upregulation and SDH inhibition improve HG-M2 macrophage function, reduce inflammation, and enhance HGF-mediated EpSCs repair. Targeting both pathways may represent a promising approach to promote DFU healing.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04245-1
Background Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral arterial disease (PAD). Mesenchymal stem cell (MSC) transplantation holds promise as a treatment for CLTI; however, the harsh local environment poses challenges to its effectiveness. Apoptotic vesicles (ApoVs) are extracellular vesicles produced by cells undergoing apoptosis, and they can carry various biomolecules from their parent cells, including proteins, RNA, DNA, lipids, ions, and gas neurotransmitters. ApoVs play significant roles in anti-inflammatory responses, anti-tumor activities, and tissue regeneration through intercellular communication, and they have demonstrated potential as drug carriers. In this study, we investigated the potential of bone marrow stem cell (BMSC)-derived ApoVs for treating CLTI. Methods In vivo, we explored the therapeutic effect of ApoVs on a hindlimb ischemia model through Laser Doppler, matrigel plug assay, and histological analysis. In vitro, we analyzed the effects of ApoVs on the proliferation, migration, and angiogenesis of HUVECs and explored the uptake process of ApoVs. In addition, Proteomic analysis, western blotting, quantitative real-time PCR, shRNA, and siRNA were used to analyze ApoVs-induced HUVECs activation and downstream signaling pathways. Results BMSCs transplantation showed improvement in a hind limb ischemia model, and this effect still exists after apoptosis of BMSCs. Subsequently, ApoVs of BMSCs were isolated and found to improve mouse hind limb ischemia in vivo. In vitro, ApoVs can be ingested by HUVECs through dynamin-, clathrin-, and caveolin-mediated endocytosis and promote its proliferation, migration, and angiogenesis. Mechanistically, ApoVs transferred NAMPT to HUVECs, therefore activating the NAMPT/SIRT1/FOXO1 axis, influencing the transcriptional activity of FOXO1, and promoting angiogenesis. Conclusions Our results demonstrate that the transplanted BMSCs can ameliorate hindlimb ischemia by releasing ApoVs during apoptosis. The main mechanism of this effect is promoting the proliferation, migration, and angiogenesis of endothelial cells via the NAMPT/SIRT1/FOXO1 axis.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04642-6
Introduction: Osteosarcopenic fractures, an emerging geriatric syndrome characterized by sarcopenia-osteoporotic fractures coexistence, delayed fracture healing, and elevated risk of re-fracture. Limited research has investigated the mechanisms by which skeletal muscle satellite cells (SMSCs) promote muscle regeneration and osteoporotic fracture healing. The aim of this study was to investigate the impact of a traditional herbal decoction (HD), the Invigorate the Spleen and Tonify the Kidney Formula, on SMSC regulation, muscle regeneration, and fracture healing. Method: Using conditional knockout mice, the role of SMSCs in promoting fracture healing and mitigating sarcopenia was evaluated by visualizing the fracture area and surrounding muscle tissue. The signaling pathways involved were comprehensively analyzed using a combination of Western blotting, real-time PCR analysis, immunohistochemical staining, and immunofluorescent staining. And the key elements and compounds facilitating osteogenesis and myogenesis were identified using HPLC and network pharmacology analysis. Results: This study demonstrated that the herbal decoction mediates the β-catenin signaling pathway, mobilizes SMSCs to migrate to the fracture area, facilitates their osteogenic and myogenic differentiation, and enhances osteoporotic fracture healing. Knockdown of β-catenin in SMSCs in Pax7-CreERT2/+;β-cateninfx/fx conditional knockout mice led to sarcopenia and osteoporosis. Additionally, the herbal decoction significantly increased bone mass, repaired bone microstructure, and promoted muscle fiber remodeling around fractures in mice. Conclusions: These findings provide the first evidence that the HD, as a β-catenin agonist, not only promotes fracture healing by modulating the osteogenic and myogenic effects of SMSCs but also ameliorates sarcopenia.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04417-z
Background Urothelial regeneration is a crucial part of bladder tissue engineering. However, there is a lack of ideal “seed cells” in current practices. Here, we demonstrated that a sub-population of p63 positive basal cells could be activated and differentiate into intermediate and superficial umbrella cells after full-thickness mucosal resection in rabbit.
Methods A focal mucosal resection model was used to characterize the role of different urothelial cells during regeneration. Urothelial basal cells were isolated from rabbit bladder mucosa and cultured in vitro. The basal cells were then transplanted in vivo in a manner of cell sheet for reconstruction.
Results Via single-cell RNA sequencing (scRNA-seq), it has been confirmed that the cluster of KRT5high TP63-expressing cells possesses a ‘stemness’ signature which can give rise to lineage cell types sequentially. With a strong support from the underneath pre-set capsule vascular bed, the transplanted cell sheet could develop into a physio-morphology resembled to the native mucosa in vivo. Importantly, we validated that the bioengineered urothelium implemented perfect barrier function after implanted to bladder.
Conclusions In summary, bioengineering urothelium with KRT5high TP63-expressing basal cells on a capsule vascular bed offers a promising strategy for bladder tissue engineering and provides a model for drug screening and bladder disease research.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04788-3
End-stage liver disease (ESLD) is one of the predominant diseases contributing to high morbidity and mortality worldwide, with etiologies including alcoholic liver disease, viral hepatitis, non-alcoholic fatty liver disease, and metabolic-associated liver disease. Currently, liver transplantation remains the only effective treatment, however, its clinical application is significantly limited by donor shortages, immune rejection, and high medical costs. Among the five types of stem cells that have been experimentally applied to liver diseases, mesenchymal stem cells (MSCs) have emerged as the most extensively studied, with the largest number of experimental and clinical research platforms worldwide. This review compiles findings from 25 preclinical and clinical studies on MSCs in the treatment of ESLD, aiming to elucidate the core mechanisms of action and then outline both the challenges in MSC clinical translation and the novel opportunities arising from cutting-edge research.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04241-5
Background Chronic diabetic wounds pose a significant clinical challenge due to the limited efficacy of current treatments. This study aimed to investigate the role and potential mechanisms of adipose-derived mesenchymal stem cells (ADSCs) overexpressing acidic fibroblast growth factor (aFGF) in diabetic wound healing in a rat model. Methods ADSCs were genetically modified to achieve stable overexpression of aFGF. Varying doses of aFGF-ADSCs (1×10⁶, 2×10⁶, 3×10⁶, 4×10⁶) were injected into the muscular tissue surrounding diabetic rat wounds. We assessed aFGF expression and its impact on various stages of wound healing, including angiogenesis, inflammatory response, epithelialization, and collagen deposition. Transcriptomic sequencing was performed to explore the underlying mechanisms driving enhanced wound healing. Results Lentiviral transduction successfully induced stable aFGF overexpression in ADSCs. In vivo experiments revealed that varying doses of aFGF-ADSCs markedly enhanced wound healing in diabetic rats in a dose-dependent manner. The dose of 3×10⁶ aFGF-ADSCs demonstrated the most significant effect. In the 3×10⁶ aFGF-ADSCs group, expression levels of aFGF, CD31, and CD163 were significantly higher than in other groups (p < 0.05), while CD86 expression was significantly lower (p < 0.05). Conclusion Single doses of aFGF-ADSCs comprehensively improved various aspects of wound repair in diabetic rats, offering a potential new approach for treating chronic diabetic wounds. The mechanism of action involves promoting angiogenesis, modulating inflammatory responses, accelerating epithelialization, and optimizing collagen deposition.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04203-x
Background Mesenchymal stem cell (MSC) -derived exosomes, especially adipose-derived mesenchymal stem cell exosomes (ADSC-Exos), have emerged as a promising alternative for skin damage repair with anti-inflammatory, angiogenic and cell proliferation effects while overcoming some of the limitations of MSC. However, the mechanism by which ADSC-Exos regulates inflammatory cells during wound healing remains unclear. This study investigated how ADSC-Exos regulate macrophages to promote wound healing. Methods ADSC-Exos were isolated using ultracentrifugation, with subsequent quantification of exosomes particle number. To investigate their role in wound healing, the effects of ADSC-Exos on inflammation, angiogenesis, collagen deposition and macrophage polarization were evaluated through immunohistochemical staining, immunofluorescence and western blotting. Changes in gene expression associated with ADSC-Exos-induced macrophage polarization were analyzed using qPCR. RNA sequencing was performed to identify differentially expressed genes affected by ADSC-Exos. The critical role of IL-33 in the wound healing process was further confirmed using Il33−/− mice. Additionally, co-culture experiments were conducted to explore the effects of IL-33 on keratinocyte proliferation, collagen deposition and epithelialization. Results ADSC-Exos inhibited the expression of TNF-α and IL-6, induced M2 macrophage polarization, promoted collagen deposition and angiogenesis, and accelerated wound healing. RNA sequencing identified IL-33 as a key mediator in this process. In Il33−/− mice, impaired wound healing and decreased M2 macrophage polarization were observed. The co-culture experiments showed that IL-33 enhanced keratinocyte function through activation of the Wnt/β-catenin signaling pathway. These findings highlight the therapeutic potential of ADSC-Exos in wound healing by modulating IL-33. Conclusions ADSC-Exos promote wound healing by regulating macrophage polarization and enhancing IL-33 release which drives keratinocyte proliferation, collagen deposition and epithelialization via the Wnt/β-catenin
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04267-9
Background: In premature newborn infants, preterm white matter injury (PWMI) causes motor and cognitive disabilities. Accumulating evidence suggests that PWMI may result from defected differentiation of oligodendrocyte precursor cells (OPCs) and impaired maturation of oligodendrocytes. However, the underlying mechanisms remain unclear. Methods: Using RNAscope, we analyzed the expression level of RNA-binding protein LIN28A in individual OPCs. Knockout of one or both alleles of Lin28a in OPCs was achieved by administrating tamoxifen to NG2CreER::Ai14::Lin28aflox/+ or NG2CreER::Ai14::Lin28aflox/flox mice. Lentivirus expressing FLEX-Lin28a was used in NG2CreER mice to overexpress LIN28A in OPCs. A series of behavioral tests were performed to assess the cognitive functions of mice. Two-tailed unpaired t-tests was carried out for statistical analysis between groups. Results: We found that the expression of Lin28a was decreased in OPCs in a PWMI mouse model. Knockout of one or both alleles of Lin28a in OPCs postnatally resulted in reduced OPC differentiation, decreased myelinogenesis and impaired cognitive functions. Supplementing LIN28A in OPCs postnatally was able to promote OPC differentiation and enhance myelinogenesis, thus rescuing the cognitive functions in PWMI mice. Conclusion: Our study reveals that LIN28A is critical in regulating postnatal myelinogenesis. Overexpression of LIN28A in OPCs rescues cognitive deficits in PWMI mice by promoting myelinogenesis, thus providing a potential strategy for the treatment of PWMI.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03745-w
Background Biomaterials used in bone tissue engineering must fulfill the requirements of osteoconduction, osteoinduction, and osseointegration. However, biomaterials with good osteoconductive properties face several challenges, including inadequate vascularization, limited osteoinduction and barrier ability, as well as the potential to trigger immune and inflammatory responses. Therefore, there is an urgent need to develop guided bone regeneration membranes as a crucial component of tissue engineering strategies for repairing bone defects. Methods The mZIF-8/PLA membrane was prepared using electrospinning technology and simulated body fluid external mineralization method. Its ability to induce biomimetic mineralization was evaluated through TEM, EDS, XRD, FT-IR, zeta potential, and wettability techniques. The biocompatibility, osteoinduction properties, and osteo-immunomodulatory effects of the mZIF-8/PLA membrane were comprehensively evaluated by examining cell behaviors of surface-seeded BMSCs and macrophages, as well as the regulation of cellular genes and protein levels using PCR and WB. In vivo, the mZIF-8/PLA membrane's potential to promote bone regeneration and angiogenesis was assessed through Micro-CT and immunohistochemical staining. Results The mineralized deposition enhances hydrophilicity and cell compatibility of mZIF-8/PLA membrane. mZIF-8/PLA membrane promotes up-regulation of osteogenesis and angiogenesis related factors in BMSCs. Moreover, it induces the polarization of macrophages towards the M2 phenotype and modulates the local immune microenvironment. After 4-weeks of implantation, the mZIF-8/PLA membrane successfully bridges critical bone defects and almost completely repairs the defect area after 12-weeks, while significantly improving the strength and vascularization of new bone. Conclusions The mZIF-8/PLA membrane with dual osteoconductive and immunomodulatory abilities could pave new research paths for bone tissue engineering.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-023-03624-w
Background Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. Methods Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. Results The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04021-7
Background This phase II randomized controlled trial tested whether the intracarotid arterial administration (ICAA) of autologous CD34+ cells to patients within 14±7 days after acute ischemic stroke (IS) could be safe and further improve short- and long-term outcomes. Methods Between January 2018 and March 2022, 28 consecutive patients were equally randomly allocated to the cell-treated group (CD34+ cells/3.0×107/patient) or the control group (receiving optimal medical therapy). CD34+ cells were transfused into the ipsilateral brain infarct zone of cell-treated patients via the ICAA in the catheterization room. Results The results demonstrated 100% safety and success rates for the procedure, and no long-term tumorigenesis was observed in cell-treated patients. In cell-treated patients, the angiogenesis capacity of circulating endothelial progenitor cells (EPCs)/Matrigel was significantly greater after treatment than before treatment with granulocyte colony-stimulating factor (all p<0.001). Blood samples from the right internal jugular vein of the cell-treated patients presented significantly greater levels of the stromal cell-derived factor 1α/EPC at 5, 10 and 30 min compared with 0 min (all p<0.005). The National Institute of Health Stroke Scale scores were similar upon presentation, but a greater response was observed by Days 30 and 90 in the cell-treated group than in the control group. Tc-99 m brain perfusion was significantly greater at 180 days in the cell-treated group than in the control group (p=0.046). The combined long-term end points (defined as death/recurrent stroke/or severe disability) were notably lower in the control group compared with the cell-treated group (14.3% vs. 50.0%, p=0.103). Conclusion Intracarotid transfusion of autologous CD34+ cells is safe and might improve long-term outcomes in patients with acute IS. Trial registration ISRCTN, ISRCTN15677760. Registered 23 April 2018- Retrospectively registered, https://doi.org/10.1186/ISRCTN15677760
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03781-6
Due to the advanced studies on stem cells in developmental biology, the roles of stem cells in the body and their phenotypes in related diseases have not been covered clearly. Meanwhile, with the intensive research on the mechanisms of stem cells in regulating various diseases, stem cell therapy is increasingly being attention because of its effectiveness and safety. As one of the most widely used stem cell in stem cell therapies, hematopoietic stem cell transplantation shows huge advantage in treatment of leukemia and other blood-malignant diseases. Besides, due to the effect of anti-inflammatory and immunomodulatory, mesenchymal stem cells could be a potential therapeutic strategy for variety infectious diseases. In this review, we summarized the effects of Staphylococcus aureus (S. aureus) and its components on different types of adult stem cells and their downstream signaling pathways. Also, we reviewed the roles of different kinds of stem cells in various disease models caused by S. aureus, providing new insights for applying stem cell therapy to treat infectious diseases.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03967-y
Background The metabolic patterns of human placental-derived mesenchymal stem cell (hP-MSC) treatment for primary sclerosing cholangitis (PSC) remain unclear, and therapeutic effects significantly vary due to individual differences. Therefore, it is crucial to investigate the serological response to hP-MSC transplantation through small molecular metabolites and identify easily detectable markers for efficacy evaluation. Methods Using Mdr2−/− mice as a PSC model and Mdr2+/+ mice as controls, the efficacy of hP-MSC treatment was assessed based on liver pathology, liver enzymes, and inflammatory factors. Serum samples were collected for 12C-/13C-dansylation and DmPA labeling LC–MS analysis to investigate changes in metabolic pathways after hP-MSC treatment. Key metabolites and regulatory enzymes were validated by qRT-PCR and Western blotting. Potential biomarkers of hP-MSC efficacy were identified through correlation analysis and machine learning. Results Collectively, the results of the liver histology, serum liver enzyme levels, and inflammatory factors supported the therapeutic efficacy of hP-MSC treatment. Based on significant differences, 41 differentially expressed metabolites were initially identified; these were enriched in bile acid, lipid, and hydroxyproline metabolism. After treatment, bile acid transport was accelerated, whereas bile acid production was reduced; unsaturated fatty acid synthesis was upregulated overall, with increased FADS2 and elongase expression and enhanced fatty acid β-oxidation; hepatic proline 4-hydroxylase expression was decreased, leading to reduced hydroxyproline production. Correlation analysis of liver enzymes and metabolites, combined with time trends, identified eight potential biomarkers: 2-aminomuconate semialdehyde, l-1-pyrroline-3-hydroxy-5-carboxylic acid, l-isoglutamine, and maleamic acid were more abundant in model mice but decreased after hP-MSC treatment. Conversely, 15-methylpalmitic, eicosenoic, nonadecanoic, and octadecanoic acids were less abundant in model mice but increased after hP-MSC treatment. Conclusions This study revealed metabolic regulatory changes in PSC model mice after hP-MSC treatment and identified eight promising biomarkers, providing preclinical evidence to support therapeutic applications of hP-MSC.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025100
Sulfasalazine (SAS), a clinically utilized anti-inflammatory drug, has been shown to induce ferroptosis by inhibiting system Xc− activity, thereby causing cellular glutathione depletion. Recently, protein disulfide isomerase (PDI) was shown to be an upstream mediator of the oxidative cell death (oxytosis/ferroptosis) induced by glutamate, erastin, RSL3 and SAS. The present study aims to further characterize the detailed biochemical and cellular mechanisms of SAS-induced ferroptosis in two cell lines, i.e., H9C2 rat cardiomyocytes and BRL-3A rat hepatocytes, with a focus on elucidating the critical role of PDI in mediating SAS-induced toxicity. We find that SAS can induce ferroptosis in H9C2 and BRL-3A cells, which is accompanied by a sequential increase in the buildup of cellular nitric oxide (NO), reactive oxygen species (ROS) and lipid-ROS. SAS activates PDI-mediated dimerization of inducible NO synthase (iNOS) and cellular accumulation of NO, and these effects are followed by ROS and lipid-ROS accumulation. Furthermore, SAS markedly upregulates the iNOS protein levels in these cells. Knockdown of PDI or pharmacological inhibition of PDI catalytic activity effectively suppresses SAS-induced iNOS dimerization, abrogates SAS-induced accumulation of NO, ROS and lipid-ROS, and prevents ferroptosis. On the other hand, PDI activation through the use of TrxR1 inhibitors sensitizes these cells to SAS-induced ferroptosis. These findings provide further experimental support for a pivotal role of PDI in SAS-induced cytotoxicity through the activation of the PDI-NOS-NO axis, which then leads to the accumulation of cellular ROS and lipid-ROS and ultimately the induction of oxidative cell death.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025209
Given the critical role of the cGAS-STING pathway in antitumor immunity, this study investigates the functional role of STING in head and neck squamous cell carcinoma (HNSCC) to evaluate the therapeutic potential of STING agonists. Analysis of the TCGA-HNSC dataset reveals that elevated expression of the STING-encoding gene TMEM173 is significantly correlated with increased M1 macrophage infiltration and enrichment of macrophage polarization-related signaling pathways. In vitro experiments in which RAW 264.7 cells are co-cultured with tumor cell-conditioned medium demonstrate that the STING agonist MSA-2 effectively reprograms tumor-induced M2-polarized macrophages toward the M1 phenotype. This MSA-2-induced M1 polarization is accompanied by increased expressions of IFN-α, IFN-β, IFN-γ, TNF-α, and IL-6, while the STING inhibitor H-151 reverses these effects. Flow cytometry further reveals that MSA-2 treatment reduces PD-1 and increases MHC II expression on macrophages. Immunohistochemical analysis of clinical samples confirms that high STING expression is correlated with increased numbers of CD68⁺ and CD80⁺ (M1-like) macrophages. In support of translational relevance, analysis of single-cell RNA-seq data from HNSCC patients receiving neoadjuvant immunotherapy indicates that TMEM173 is expressed primarily in T cells and macrophages and that the cGAS-STING pathway score is significantly higher in patients who respond to treatment. Collectively, these findings provide systematic clinical and experimental evidence supporting the potential of STING agonists, such as MSA-2, to enhance antitumor immunity in HNSCC, particularly when combined with immunotherapy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024217
Ageing is an independent factor for cognitive dysfunction. Ageing-associated alterations in the gut microbiota also affect cognition. The present study is designed to investigate changes in the gut microbiota and their participation in ageing-associated cognitive impairment. Both 10-week-old and 18-month-old mice are used. Mouse cognition is examined by novel object recognition and T-maze tests. Mouse feces are collected for sequencing and transplantation. Protein expression in the mouse intestine and hippocampus is studied using immunohistochemistry and immunofluorescence staining. Senescent neurons are induced by hydrogen peroxide in vitro. The cell lysates are used for western blot analysis and adenosine triphosphate (ATP) measurement. Our results show that 18-month-old mice exhibit cognitive dysfunction compared with young mice. In aged mice, transplanting the microbiota of young mice increases the protein presence of synaptophysin in the hippocampus and partially restores cognition. The protein expressions of mucin-2 and E-cadherin in the intestine are reduced in aged mice but are increased by transplantation. Gut microbiota analyses reveal that the reduced abundance of the microbe Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus in aged mice is restored by transplantation. Fecal microbiota transplantation in young mice increases the serum level of acetic acid in aged mice. Hydrogen peroxide stimulation induces senescence and reduces the protein expression levels of synaptophysin and acetyl-coenzyme A synthetase member 2 (ACSS2) in primary neurons. Incubation with acetic acid upregulates the protein expressions of ACSS2 and synaptophysin and further increases ATP production in senescent neurons. In summary, gut microbiota transplantation increases the abundance of Lactobacillales, elevates serum acetic acid level, and improves cognitive function in aged mice. Gut microbiota transplantation has therapeutic importance for ageing-associated cognitive decline.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024208
Escherichia coli is widely used in industrial chemical synthesis but faces significant challenges due to bacteriophage contamination, which reduces product quality and yield. Therefore, developing an efficient antiphage system is essential. In this study, we develop a CRISPR-Cas9-based antiphage system (CAPS) targeting essential genes of the T7 phage (gene 5 and gene 19) with single gRNAs transformed into MG1655 strains expressing Cas9. While CAPS provides limited resistance, with plating efficiencies ranging from 10–5 to 10–1, further optimization is needed. To enhance efficacy, we design a double-site-targeting CRISPR-Cas9-based antiphage system (D-CAPS). D-CAPS demonstrates complete resistance, with no plaques observed even at a high multiplicity of infection (MOI of 2), and growth curve analysis reveals that antiphage E. coli strains grow normally, similar to the wild-type strain, even at a high multiplicity of infection. Furthermore, D-CAPS is effective against BL21(DE3) strains, showing strong resistance and demonstrating its versatility across different E. coli strains. Protein expression analysis via green fluorescent protein confirms that E. coli carrying D-CAPS could maintain normal protein expression levels even in the presence of phages, comparable to wild-type strains. Overall, D-CAPS offers a robust and versatile approach to enhancing E. coli resistance to phages, providing a practical solution for protecting industrial E. coli strains and improving fermentation processes.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025172
Long noncoding RNAs (lncRNAs) are essential in regulating the development and progression of different types of cancer. However, our insights into their impact and mechanisms in papillary thyroid carcinoma (PTC) are still insufficient. In this study, we investigate the effects of the ferroptosis-associated long noncoding RNA LINC02432 on PTC, which recognizes ferroptosis as a critical mechanism in cancer biology and lncRNAs as significant factors in various malignancies. To identify lncRNAs associated with ferroptosis in PTC, we conduct bioinformatics analyses and perform functional assays to evaluate the biological impact of LINC02432 on PTC cells, as well as its relationship with ferroptosis. Mechanistic studies employ methods such as western blot analysis, flow cytometry, and real-time PCR. Our analysis of transcriptome data from TCGA reveals that LINC02432 is the only lncRNA consistently identified by all 10 machine learning methods used, and its expression is significantly downregulated in PTC. Overexpression of LINC02432 in PTC cells inhibits cell proliferation and migration while promoting ferroptosis through inactivation of the NRF2 pathway. LINC02432 knockdown in PTC cells yields the opposite result. These findings highlight the potential of LINC02432 as a tumor suppressor in PTC progression, offering new insights into the mechanisms underlying the development and progression of this malignancy.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024088
Cloning short DNA fragments, such as shRNA and sgRNA, is a routine but time-consuming task in molecular biology. Traditional methods require annealing of complementary oligos or PCR amplification, which are labor-intensive and time-consuming. Here, we report a novel PCR-independent, annealing-free cloning method that enables the insertion of short DNA fragments using a single oligo. The method relies on T4 DNA ligase for ligation and host cell DNA polymerase for complementary strand synthesis. We demonstrate that adding T4 DNA polymerase and dNTPs to the ligation mixture significantly improves cloning efficiency. This approach simplifies the cloning process, reduces time to less than 1 hour, and is compatible with standard laboratory reagents. Our method provides a rapid and efficient alternative for cloning short DNA fragments, with broad applications in gene knockdown and genome editing.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024134
SUN5, a testis-specific gene, is associated with acephalic spermatozoa syndrome (ASS). Here, we demonstrate that SUN5 is involved in mRNA export. In Sun5-knockout mice (Sun5–/–), poly(A)+ RNA accumulates in the nuclei of germ cells, leading to reduced sperm counts, decreased sperm motility and disrupted sperm head-to-tail junctions. Additionally, in the GC-2 germ cell line with RNA interference of Sun5, heterogeneous nuclear ribonucleoproteins (hnRNPs) and poly (A)+ RNA (mainly mRNA) are retained in the nucleus. Further mechanistic studies reveal that SUN5 interacts with Nxf1 (nuclear RNA export factor 1) and nucleoporin 93 (Nup93). Interference with Nup93 inhibits mRNA export. Treatment with leptomycin B to block the CRM1 pathway indicates that Sun5 regulates mRNA export through an Nxf1-dependent pathway. In Sun5–/– mice, the binding of Nxf1 and Nup93 decreases due to loss of Sun5 function, and the process of submitting Nxf1-binding mRNPs to Nup93 is inhibited, resulting in abnormal spermatogenesis. Together, these data may elucidate a novel pathway for mRNA export in male germ cells.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024024
Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to different types of cell death. The degree of irreversible myocardial damage is closely related to age, and ferroptosis is involved in cardiomyocyte damage. However, the mechanisms underlying ferroptosis regulation in aging myocardial I/R injury are still unclear. The present study aims to explore the underlying mechanism of piRNA regulation in ferroptosis. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line (H9C2) to construct an aging cardiomyocyte model, we investigate whether ferroptosis occurs after reperfusion injury in vitro and in vivo. This study focuses on the upregulation of piR-000699 after hypoxia/reoxygenation treatment in aging cardiomyocytes by observing hypoxia/reoxygenation (H/R) injury indicators and ferroptosis-related indicators and clarifying the role of piR-000699 in H/R injury caused by ferroptosis in aging cardiomyocytes. Bioinformatics analysis reveals that SLC39A14 is a gene that binds to piR-000699. Our data show that ferroptosis plays an important role in I/R injury both in vivo and in vitro. Furthermore, the results show the potential role of piR-000699 in regulating SLC39A14 in ferroptosis in aging cardiomyocytes under hypoxia/reoxygenation conditions. Together, our results reveal that the mechanism by which piR-000699 binds to SLC39A14 regulates ferroptosis in aging myocardial I/R injury.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025059
The transcriptional heterogeneity and cellular ecosystem diversity of HCC await further exploration. Single-cell and bulk RNA sequencing data from HCC cells are analyzed to generate a LASSO model for HCC prognostication. CCK-8, scratch assay, flow cytometry, and ROS assays are used to validate how TREM1 may affect HCC cell biological behaviors in vitro. qPCR, western blot analysis, immunohistochemistry, and flow cytometry are applied in a xenograft model to test the effects of TREM1 knockdown on carcinogenesis and the tumor microenvironment. A single-cell atlas of the multicellular ecosystem comprising 13 cell types in HCC is constructed. On the basis of ligand-receptor marker genes specifically extracted from the cell populations, a prognostic model is defined and subsequently validated in additional clinical cohorts. For the first time, a heterogeneous immune microenvironment is observed between low- and high-risk patients, primarily involving macrophages, CD4+ T cells, M1 macrophages, and regulatory T (Treg) cells. Sufficient evidence validates the positive effects of TREM1 on HCC cell proliferation, migration, and apoptosis. Additionally, TREM1 positively modulates the levels of the proinflammatory cytokines IL-1β, TNF-α, and MCP-1. TREM1 downregulation alters the proportions of M1 macrophages and Tregs in the tumor tissue from our HCC xenograft model. Eventually, the Nrf2/Keap1 signaling pathway, which is related to oxidative stress, is shown to be a key pathway downstream of TREM1 downregulation. In summary, we construct a novel prognostic model for HCC on the basis of ligand-receptor marker genes and investigate the role of TREM1 in HCC progression and its impact on the TME.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025092
Accumulating evidence suggests that NLRP3-mediated alveolar macrophage (AM) pyroptosis and subsequent high mobility group box protein 1 (HMGB1) secretion play significant roles in the pathogenesis of acute respiratory distress syndrome (ARDS). Nrf2 has been shown to be individually involved in regulating pyroptosis. In this study, we investigate the ability of CDDO-imidazolide, a potent Nrf2 activator, to regulate AM pyroptosis and HMGB1 secretion in sepsis-associated ARDS, along with its underlying mechanism. The in vitro alveolar macrophage (AM) pyroptosis model, established by stimulating J774A.1 cells with LPS and ATP, was treated with CDDO-imidazolide or utilized Nrf2-knockout cells. The mice are intraperitoneally administered with CDDO-imidazolide before the in vivo sepsis-associated ARDS model is constructed via caecal ligation perforation and the Nrf2 inhibitor, ML385. In vitro studies reveal that the use of 3-MA to prohibit PINK1/Parkin-dependent mitophagy aggravates NLRP3-mediated pyroptosis and HMGB1 release in J774A.1 cells via LPS and ATP exposure. CDDO-imidazolide also significantly prevents NLRP3-mediated pyroptosis and HMGB1 release to increase PINK1/Parkin-dependent mitophagy, but these effects are not detected in Nrf2-knockout macrophages. Most importantly, CDDO-imidazolide significantly alleviates NLRP3 inflammasome protein expression in the lung tissues of septic mice and HMGB1 protein levels in the serum and bronchoalveolar lavage fluid (BALF), which can be reversed by ML385. Taken together, our results demonstrate that CDDO-imidazolide prominently protects the lungs by promoting Nrf2 activation and enhancing PINK1/Parkin mitophagy to inhibit AM pyroptosis and HMGB1 release. These findings provide novel insights for therapeutic strategies for sepsis-associated ARDS.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025105
This review delves into the crosstalk network between oligodendrocytes and other glial cells in the context of demyelinating diseases. Oligodendrocytes, the myelin-forming cells in the central nervous system (CNS), are crucial for maintaining the function and integrity of axons and myelin sheaths. In demyelination pathologies, various factors hinder the normal differentiation of oligodendrocyte precursor cells, obstructing the myelin regeneration process, which is a primary barrier to therapeutic myelin repair. Emerging evidence highlights the critical role of glial cell interactions in CNS homeostasis and myelin regeneration, increasing interest in the treatment of demyelinating diseases. This article reviews the role of interactions between oligodendrocytes and other CNS glial cells in demyelinating and neurological diseases. Previous findings suggest that other CNS glial cells influence the survival and metabolic activity of oligodendrocytes through cell interactions, significantly affecting myelin formation and impacting demyelinating diseases characterized by myelin regeneration disorders. Targeted modulation of oligodendrocytes and their interactions with other cells at specific temporal stages may indicate a novel therapeutic direction for demyelinating diseases and offer fresh perspectives on the study of mechanisms and therapeutic approaches for related neurological conditions.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024226
Glutaminolysis and glycolysis promote the malignant progression of colorectal cancer. The role of activating transcription factor 4 (ATF4) in solute carrier family 1 member 5 (SLC1A5)-mediated glutaminolysis and glycolysis remains to be elucidated. SLC1A5 and ATF4 expression levels are detected in colorectal cancer tissues. ATF4 is knocked down or overexpressed to assess its role in cell viability, migration and invasion. SLC1A5 is knocked down to evaluate its role in cell viability, migration, invasion, and metastasis and the metabolism of glutamine and glucose. The regulatory effect of the transcription factor ATF4 on SLC1A5 transcription and expression is determined using a luciferase reporter assay and chromatin immunoprecipitation (ChIP) techniques. Upregulated ATF4 and SLC1A5 expressions are observed in tumor tissue, which is positively correlated with the tumor, node, and metastasis (TNM) stages. ATF4-overexpressing SW480 cells show the increased cell viability, migration and invasion. Conversely, ATF4 knockdown decreases the viability, migration and invasion of HCT-116 cells. SLC1A5 knockdown inhibits viability, migration, invasion, and metastasis and the metabolism of glutamine and glucose in HT-29 cells, as well as the expressions of two key glycolytic enzymes, hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2). The luciferase activity of the SLC1A5 promoter is increased by ATF4 overexpression. SLC1A5 promoter enrichment is increased by anti-ATF4 antibody immunoprecipitation in ATF4-overexpressing colorectal cells, indicating that ATF4 targets SLC1A5 to promote glutamine and glucose metabolism in these cells. In summary, the ATF4/SLC1A5 axis plays a significant role in the progression of colorectal cancer by regulating glutamine metabolism and glycolysis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025067
Adrenocortical carcinoma (ACC) is a rare epithelial tumor originating from adrenal cortical cells, notable for its high degree of malignancy and poor prognosis. Owing to heterogeneity, patient outcomes vary significantly. Current biomarkers for ACC risk stratification have notable limitations. However, with the advancement of multi-omics sequencing technology, we can utilize multi-omics data to explore the heterogeneity of ACC, thereby identifying novel biomarkers. In this study, we establish multicenter transcriptomics and ATAC-seq data from the TCGA and GEO databases to perform weighted gene coexpression network analysis (WGCNA) clustering and conduct comprehensive analyses of various ACC samples. These findings are integrated with univariate Cox regression, receiver operating characteristic (ROC) curve analysis, and survival analysis to identify potential biomarkers. We establish FSCN1 as an independent risk factor associated with poor ACC prognosis. ATAC-seq data demonstrate higher chromatin accessibility of FSCN1 in ACC patients with progressive disease. Immunohistochemical analysis confirms the expression of FSCN1 at the protein level, while functional cell assays reveal its role in promoting tumor invasion and proliferation. Functional enrichment analyses highlight the biological characteristics of FSCN1, and estimation of TME-infiltrating cells suggests that FSCN1 expression contributes to poor prognosis by inhibiting CD8+ T-cell infiltration within the ACC microenvironment. Finally, multi-omics analyses elucidate the role of FSCN1 at the mutation level. Taken together, our findings highlight FSCN1 as a promising novel biomarker and potential therapeutic target, underscoring its value in guiding the strategic management of ACC.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025002
Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Reactive oxygen species (ROS) stress induces NLRP3 inflammasome activation, and this, along with extracellular matrix metabolism (ECM) degradation in nucleus pulposus cells (NPCs), plays a crucial role in the progression of IDD. Daphnetin (DAP) is a biologically active phytochemical extracted from plants of the Genus Daphne, which possesses various bioactivities, including antioxidant properties. In the present study, we demonstrate that DAP significantly attenuates tert-butyl hydroperoxide (TBHP)-induced ECM degradation, oxidative stress and NLRP3 inflammasome activation in NPCs. Furthermore, DAP could facilitate mitophagy to increase the removal of damaged mitochondria, consequently reducing mitochondrial ROS accumulation and alleviating NLRP3 inflammasome activation. Mechanistically, we unveil that DAP activates mitophagy by stimulating the Nrf2/PINK1 signaling pathway in TBHP-induced NPCs. In vivo experiments further corroborate the protective effect of DAP against IDD progression in a rat model induced by disc puncture. Accordingly, our findings reveal that DAP could be a promising therapeutic candidate for the treatment of IDD.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025186
Bone remodeling represents a dynamic equilibrium orchestrated by mechanobiological and endocrine signals, with YAP/TAZ and ERα emerging as pivotal regulators of skeletal adaptation. YAP/TAZ functions as the central mechanotransduction hub of the Hippo pathway, converting biomechanical cues, including microenvironment matrix stiffness and shear stress, into osteogenic transcriptional programs. Concurrently, ERα integrates both mechanical stimuli and estradiol (E2) signaling to coordinate osteoblast-osteoclast coupling through the transcriptional regulation of RUNX2 activity and RANKL suppression. Although increasing evidence suggests that these two systems might engage in functional crosstalk, there is still no consensus on this issue. This review synthesizes the current understanding of YAP/TAZ-ERα interactions across three dimensions: (1) mechanohormonal integration in skeletal remodeling, (2) context-dependent reciprocity in breast carcinogenesis, and (3) tissue-specific regulatory paradigms in extra-skeletal systems. Key findings reveal that YAP/TAZ and ERα exhibit both synergistic cooperation (enhanced osteogenic differentiation via promoter co-occupancy) and pathway antagonism (competitive TEAD binding), with their interaction dynamics being critically shaped by the cellular microenvironmental context. Notably, mechanical potentiation of ERα transcriptional activity requires YAP/TAZ co-activation in bone mesenchymal stem cells, whereas estrogen signaling modulates YAP mechanosensitivity through cytoskeletal remodeling. These mechanistic insights indicate that the YAP/TAZ-ERα axis is a promising therapeutic target for osteoporotic bone loss, particularly in alveolar bone preservation. By bridging endocrine and mechanobiological perspectives, this work provides a conceptual framework for developing combinatorial therapies that simultaneously address hormonal imbalance and mechanical insufficiency in skeletal pathologies.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025084
The in vitro culture of ovarian tissue is emerging as a popular technology to study female reproductive medicine. However, standard in vitro culture conditions usually increase the level of reactive oxygen species (ROS), hindering ovarian development. Here, we establish an in vitro visualized mouse ovarian explant 3D culture model with the GFP-BVSC reporter system and obtain the early follicle pool from fetal female gonads. This model recapitulates in vivo ovarian characteristics and allows non-invasive monitoring of ovarian development. Importantly, supplementation with quercetin, a plant-derived natural antioxidant, increases the tissue area and total follicle count in cultured ovaries by protecting mitochondria and reducing ROS, thus more closely mimicking in vivo growth conditions. Finally, this visualized and optimized ovarian explant culture platform has been proven to be effective in modelling female ovarian diseases, such as the fetal reproductive aberrations of female offspring affected by gestational diabetes mellitus (GDM). Overall, our work extends the understanding of ovarian biology and creates an efficient and simplified platform for the morphological monitoring of ovarian development, as well as for drug screening and the clinical treatment of ovarian hypofunction.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024095
Eimeria spp. can invade different intestines of chickens. Among them, Eimeria acervulina (E. acervulina, Ea) is the most virulent, and it is characterized by disruption of the intestinal nutrient uptake mechanism, leading to weight loss and even death. As a result, coccidia have caused a heavy burden on the poultry industry [1]. Currently, understanding the invasion mechanism of E. acervulina in host cells is the basis for developing the most effective preventive method for coccidiosis. However, the specific mechanism of E. acervulina invasion is unclear, so the interactions between parasite and host cells need to be studied in depth. Serine thiol proteinase inhibitors widely exist in bacteria, viruses and parasites. It can protect against the dissolution of host proteins and the development of pathogens in the process of pathogen invasion [2]. The serine protease inhibitor (SERPIN) of Toxoplasma gondii, which has the ability to inhibit trypsin activity, was the first SERPIN to be studied in parasites. SERPIN in T. gondii may play an important role in protecting against the degradation of host intestinal proteases and reducing the ability of host proteins to hydrolyse T. gondii [3]. SERPIN in T. gondii can also promote the growth of tachyzoites in the host. Subsequently, a 79-amino acid protease inhibitor, SERPIN, which can completely inhibit the activity of bacterial subtilisin, was found in Neospora caninum [4]. SERPIN plays an important role not only in parasite physiology but also in the interactions with the host. Real-time quantitative PCR analysis at all developmental stages of E. tenella showed that SERPIN1 is highly expressed in sporozoites [5]. Previous studies have shown that the secreted SERPIN protein in sporozoites may also regulate the host immune pathway. In Schistosoma mansoni, SERPIN can inhibit neutrophil proteases and regulate the degradation of tissues to promote the migration of parasites in the host [6]. SERPIN secreted by parasites can also be used to protect themselves from degradation by host proteases, thus manipulating the host response to parasites. Studies have shown that they are mainly involved in physiological processes such as blood sucking, digestion, reproduction and immune response and affect the interaction between parasites and hosts [7]. SERPIN from Trichinella spiralis (TsSPI) is not directly involved in the growth and reproduction of parasites but regulates the interaction between T. spiralis and its host to a certain extent. TsSPIs can regulate the polarization of macrophages and subsequently affect the balance among host inflammatory factors to regulate the host immune response and create a favorable environment for the colonization of Trichinella spiralis in the host [8]. Taeniasis solium SERPIN can play a biological role by participating in the inflammatory and apoptotic pathways of the host [9]. Previous studies have shown that SERPIN plays important roles during host-cell invasion, and 66 related proteins that interact with E. tenella SERPIN on the host have been preliminarily screened [10]. However, few studies have focused on the binding partner of Ea-SERPIN. To identify the ligand-binding partner molecules that may play an important role in the invasion process of E. acervulina, a yeast two-hybrid system was used to screen the associated proteins from the yeast complementary DNA (cDNA) library of chicken duodenal epithelium cells using Ea-SERPIN as bait. In this study, a close genetic relationship was identified between E. acervulina and E. maxima and between E. acervulina and T. gondii. The protein homology of SERPIN between E. acervulina and E. maxima was 87%, and that between E. acervulina and Toxoplasma gondii was 43% (Supplementary Figure S1). The yeast cDNA library of chicken duodenal epithelium cells in the pGADT7 vector was constructed using a Matchmaker Library Construction and Screening kit (Clontech, Palo Alto, USA) as the prey. Preys containing a Gal4 activation domain (AD prey) were transformed into the yeast strain Y187. The efficiency of transformation and the size of the insert fragment satisfied the quality requirements of the yeast library. For yeast two-hybrid screening, SERPIN was amplified by polymerase chain reaction (PCR) using the forward primer 5′-CCC CATATGATGGCATTATTAAGTAAATTAACTCG-3′ and the reverse primer 5′-CCCCTGCAGTTACTGCTGTGCAGCTGTCGGGTCAG-3′ from E. acervulina cDNA and then ligated into the NdeI-PstI sites of pGBKT7 as a bait. The recombinant plasmid was transformed into Y2H GOLD yeast cells, and the transformants were separately grown on plates containing minimal yeast medium without tryptoph
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023259
The most frequent primary brain tumor in adults is glioma, yet no effective curative treatments are currently available. Our previous study demonstrated the enhancing effects of JARID2 on glioma sensitivity to TMZ treatment. In this study, miR-155 is predicted to target JARID2. miR-155 is overexpressed in clinical glioma specimens and cell lines. miR-155 overexpression in glioma cells enhances cell viability and represses cell apoptosis. Through targeting, miR-155 inhibits JARID2 expression. miR-155 inhibition inhibits glioma cell viability and enhances cell apoptosis, whereas JARID2 knockdown enhances cell viability and inhibits cell apoptosis; JARID2 knockdown partially reverses miR-155 inhibition effects on glioma phenotypes. miR-155 inhibition reduces but knockdown of JARID2 promotes the tumor formation ability of glioma cells in vivo. Valproic acid (VPA) upregulates JARID2 expression, inhibits glioma cell viability and enhances cell apoptosis. VPA downregulates the expression level of miR-155 by increasing the methylation level of the miR-155 promoter, suggesting that the miR-155/JARID2 axis is implicated in VPA inhibition of glioma cell viability and enhancement of glioma cell apoptosis. This study demonstrates a new mechanism of VPA treatment of gliomas by affecting the miR-155/JARID2 axis, which could be regarded as a new strategy for the prevention and treatment of glioma.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.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.2024154
The pathological proliferation and migration of vascular smooth muscle cells (VSMCs) are key processes during vascular neointimal hyperplasia (NIH) and restenosis. Phosphoenolpyruvate carboxy kinase 1 (PCK1) is closely related to a variety of malignant proliferative diseases. However, the role of PCK1 in VSMCs has rarely been investigated. This study aims to examine the role of PCK1 in the proliferation and migration of VSMCs and vascular NIH after injury. In vivo, extensive NIH and increased expression of PCK1 within the neointima are observed in injured arteries. Interestingly, the administration of adeno-associated virus-9 (AAV-9) carrying Pck1 short hairpin RNA (shPck1) significantly attenuates NIH and stenosis of the vascular lumen. In vitro, Pck1 small interfering RNA (siPck1)-induced PCK1 silencing inhibits VSMC proliferation and migration. Additionally, silencing of PCK1 leads to reduced expression of dynamin-related protein 1 (DRP1) and attenuated mitochondrial fission. Lentivirus-mediated DRP1 overexpression markedly reverses the inhibitory effects of PCK1 silencing on VSMC proliferation, migration, and mitochondrial fission. Finally, PCK1 inhibition attenuates the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Activation of STAT3 abolishes the suppressive effects of PCK1 silencing on DRP1 expression, mitochondrial fission, proliferation, and migration in VSMCs. In conclusion, PCK1 inhibition attenuates the mitochondrial fission, proliferation, and migration of VSMCs by inhibiting the STAT3/DRP1 axis, thereby suppressing vascular NIH and restenosis.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024089
Growth hormone deficiency (GHD) is the most common pituitary hormone deficiency and is clinically characterized by short stature, delayed bone age and central distribution of body fat, and it has also been proven to be mildly heritable. Treatment with recombinant human growth hormone (r-hGH) is primary and safe for GHD children, and a dose of 0.15‒0.20 mg/kg each week results in a considerable increase in height velocity, with noteworthy growth during the first year of therapy [1]. Previous studies have shown that serum IGF-1 is strongly correlated with the growth response [2]. Therefore, IGF-1 can serve as a clinical indicator for monitoring compliance, efficacy and safety. However, the response to GH therapy shows significant individual variation, which is strongly associated with genetic factors. The prevalence rate of severe childhood GHD-related short stature varies from 1:4000 to 1:10,000 [3], while approximately 3%‒4% of the population in China suffers from short stature with an increasing trend. Therefore, an open-label, prospective, multicentric, noncomparative, nonrandomized phase IV interventional study (NCT01187550, Merck Serono Study 27709) was conducted to investigate the relationship between the prospective biomarkers of GHD patients and the individual variation in the primary therapeutic response following 4 weeks of r-hGH therapy. Given the significance of predicting GHD treatment response and the gaps in previous research, we sought to adopt a comprehensive strategy to accurately predict the therapeutic response utilizing the transcriptome, single nucleotide polymorphisms (SNPs) and clinical factors. We employed continuous variables and standard deviation scores of differences in serum IGF-1 levels after 4 weeks of r-hGH therapy (ΔIGF-1) as targets to filter possible influencing variables. Furthermore, we compared several potential machine learning techniques, validated by PCA and PLS-DA, and ultimately applied the elastic net algorithm to determine the optimized predictive factors with consistent effect sizes. Additionally, expression quantitative trait locus (eQTL) analysis and differentially expressed gene (DEG) analysis were conducted to identify significant biomarkers for GHD treatment.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024016
Atherosclerosis (AS), the main contributor to acute cardiovascular events, such as myocardial infarction and ischemic stroke, is characterized by necrotic core formation and plaque instability induced by cell death. The mechanisms of cell death in AS have recently been identified and elucidated. Ferroptosis, a novel iron-dependent form of cell death, has been proven to participate in atherosclerotic progression by increasing endothelial reactive oxygen species (ROS) levels and lipid peroxidation. Furthermore, accumulated intracellular iron activates various signaling pathways or risk factors for AS, such as abnormal lipid metabolism, oxidative stress, and inflammation, which can eventually lead to the disordered function of macrophages, vascular smooth muscle cells, and vascular endothelial cells. However, the molecular pathways through which ferroptosis affects AS development and progression are not entirely understood. This review systematically summarizes the interactions between AS and ferroptosis and provides a feasible approach for inhibiting AS progression from the perspective of ferroptosis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024223
Adult skeletal muscle possesses an exceptional regenerative capacity, fundamentally reliant on adult muscle stem cells, known as satellite cells, which reside beneath the basal lamina of myofibers [1]. In their resting state, satellite cells remain quiescent; however, they activate, proliferate, differentiate, and fuse in response to pathological stress or injury, ultimately contributing to the repair and restoration of damaged myofibers [2]. Aging and the onset of skeletal muscle degenerative diseases significantly impair this regenerative ability, leading to a marked reduction in muscle mass and strength, which culminates in progressive muscle weakness and dysfunction [3,4]. Two notable examples of such degenerative conditions are age-related sarcopenia and muscular dystrophy, both of which present considerable public health challenges due to their increasing global prevalence. Currently, these diseases lack definitive therapeutic interventions, underscoring the urgent need for innovative treatments. Restoring the regenerative capacity of skeletal muscle may offer a promising therapeutic approach to halt or even reverse the progression of these muscular degenerative disorders. Buzhong Yiqi Decoction (BYD), a traditional Chinese medicine formula known for its qi-supplementing properties, comprises several key herbs, including Huangqi (Astragalus membranaceus), Baizhu (Atractylodes atractylodes), Chenpi (Pericarpium citri reticulatae), Shengma (Rhizoma cimicifugae), Chaihu (Radix bupleuri), Rensheng (Ginseng), Gancao (Liquo rice), and Danggui (Radix Angelicae Sinensis). Clinically, BYD is utilized to treat conditions such as allergic rhinitis, gut microbiota disorders, and chronic obstructive pulmonary disease. Notably, BYD is frequently prescribed for myasthenia gravis, a condition characterized by partial or systemic skeletal muscle weakness and fatigue. Modified BYD treatments have been shown to alleviate fatigue and muscle weakness while improving the quality of life for patients with myasthenia gravis [5,6]. Numerous clinical observations indicate that combining BYD with Western medicine is more effective than Western medicine alone in managing myasthenia gravis [7,8]. A randomized controlled trial conducted by Hu et al. [9] demonstrated the efficacy of BYD in addressing cancer-related fatigue and weakness in patients with cervical carcinoma. The effectiveness of BYD in alleviating myasthenia gravis and mitigating cancer-related fatigue suggests its potential role in regulating skeletal muscle homeostasis and function. The maintenance of skeletal muscle homeostasis is primarily achieved through effective muscle regeneration in response to injury or pathological stress. However, no experimental evidence indicates whether BYD can enhance skeletal muscle regeneration. To explore the potential role of BYD in regulating skeletal muscle regeneration, we established a cardiotoxin (CTX)-induced muscle injury and regeneration model in mice. All animal procedures were approved by the Animal Ethics Committee of Peking Union Medical College (ACUC-A01-2019-012). The tibialis anterior (TA) muscle of 8-week-old male C57BL/6j mice was injured via intramuscular injection of CTX (20 μL of 10 μM), followed by daily intragastric administration of BYD (15 μL/g body weight) (Figure 1A). Mice receiving daily intragastric administration of double-distilled water (ddH2O) served as vehicle controls (Figure 1A). Muscle regeneration was assessed at 3, 5, 7 and 14 days post-injury (dpi) through hematoxylin and eosin (H&E) staining (Figure 1B) and by quantifying the size of regenerating myofibers (Figure 1C,D). The H&E-stained cross-section of the TA muscle revealed a significant infiltration of immune cells in the injured muscle at the early time point of 3 dpi (Figure 1B). Notably, we observed a reduction in immune cell presence at 5 dpi in the BYD-treated group compared to the vehicle control (Figure 1B), indicating that BYD promotes the subsidence of inflammation during acute muscle injury and regeneration. Both H&E staining and quantification data demonstrated that regenerating myofibers, characterized by centralized myonuclei, were significantly larger at 7 dpi (Figure 1B,C) and 14 dpi (Figure 1B,D) in the BYD-treated group compared to controls, suggesting that BYD accelerates skeletal muscle regeneration.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261612
Critical-sized bone defects (CSBD) remain a clinical bottleneck due to insufficient osteogenic drive and uncontrolled degradation of current grafts. This study evaluates a photocrosslinked hydrogel composed of cuttlebone (CB) and bovine serum albumin (BSA) for repairing 5 mm rat calvarial CSBD. SD rats were randomized into control, positive control (Bio-Oss® Collagen), BSA, 0.5% CB/BSA, 1.5% CB/BSA, and 3.0% CB/BSA groups (n=6). After 8 weeks, micro-CT revealed no new bone in controls, whereas all CB/BSA groups exhibited significant increases in bone volume fraction, bone mineral density, and trabecular thickness (P<0.05), with reduced bone surface-to-volume ratio (P<0.05). Histology confirmed new bone formation in hydrogel groups versus loose fibrous tissue in controls. Immunohistochemistry and immunofluorescence showed elevated COL1A1, PECAM-1, and OCN expression (P<0.05). qRT-PCR and Western blotting demonstrated upregulation of WNT3A, β-catenin, VEGFA, COL1A1, PECAM-1, and OCN (P<0.05). The 3.0% CB/BSA group exhibited the most pronounced osteogenic effect. Blood routine and serum liver/kidney function tests showed no abnormalities, and major organs displayed no inflammation, necrosis, or fibrosis. These findings indicate that CB/BSA photocrosslinked hydrogel promotes bone repair with favorable in vivo safety, likely through activation of the Wnt/β-catenin signaling pathway.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Osteoporosis is characterized by impaired bone formation relative to resorption, yet the molecular drivers of osteoblast dysfunction remain incompletely defined. Cadherin 19 (CDH19), located at chromosome 18q22-q23, has been linked to 18q deletion syndromes presenting with skeletal deformities, but its role in bone homeostasis was previously unknown. Using a Cre-loxP conditional knockout model, we demonstrate that CDH19 deletion in mice significantly reduces bone mass, with decreases in bone density, trabecular number, and bone volume fraction. Osteoblasts isolated from CDH19 knockout mice exhibit suppressed proliferation and osteogenic differentiation, as evidenced by EdU labeling, qPCR, alkaline phosphatase and alizarin red S staining, and Western blot. RNA sequencing and subsequent immunofluorescence and Western blot analyses reveal that the PI3K/AKT signaling pathway is markedly inhibited in CDH19-deficient osteoblasts. Administration of the PI3K/AKT agonist 740Y-P partially rescues the osteogenic differentiation deficit both in vitro and in vivo. These findings establish CDH19 as a critical regulator of osteoblast function through PI3K/AKT signaling and identify it as a potential therapeutic target for bone diseases such as osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21368
BACKGROUND: In the process of applying artificial intelligence to orthopedic imaging, the technical system exhibits a clear hierarchical structure: machine learning is the primary pathway to achieving artificial intelligence, while convolutional neural networks, a branch of deep learning, have become the core model for image analysis. Clarifying this technical lineage helps to systematically review the research evolution and trends in this field through bibliometric methods. OBJECTIVE: To comprehensively analyze the research status and development trends of artificial intelligence in the field of orthopedic imaging based on bibliometric methods, providing ideas and methods for future research. METHODS: By searching the Web of Science Core Collection database, with keywords including artificial intelligence, deep learning, convolutional neural network, and orthopedic imaging, a total of 460 relevant English articles published between 2015 and 2025 were included. CiteSpace 6.4.R1, VOSviewer 1.6.20, and Bibliometrix software were used to conduct visual analysis from dimensions such as annual publication volume, country and institution distribution, author collaboration network, keyword co-occurrence, clustering, and burst word evolution. RESULTS AND CONCLUSION: (1) The number of publications in this field has steadily increased over the past 10 years. (2) China and the United States are the main publishing countries, with the United States showing outstanding performance in citation frequency and international collaboration influence; Sichuan University, the University of California, and Harvard University constitute a core collaborative institutional network. (3) Research hotspots mainly focus on bone age assessment, automated image segmentation, and the application of deep learning in fracture detection and osteoarthritis diagnosis. Related keywords such as bone age assessment, automated segmentation, and deep learning have continued to burst, indicating the evolutionary trajectory of research focus. (4) The research enthusiasm for artificial intelligence in orthopedic imaging continues to rise, with intelligent segmentation, disease grading, and multimodal data fusion being important future research directions. (5) This paper systematically reviews the field from a macro perspective, providing a reference for promoting the deep integration of artificial intelligence technology in orthopedic clinical practice; through bibliometric analysis, it constructs a knowledge map of the application of artificial intelligence in orthopedic imaging, systematically summarizes the research status and hotspots in this field, and aims to provide reference and guidance for future related research.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21350
BACKGROUND: Clarifying the interactions between multiple signaling pathways and axonal pathological alterations, and elucidating the role and mechanisms of axonal degeneration in the onset and progression of Parkinson's disease will pave the way for research on the pathogenesis and pathological mechanisms of Parkinson's disease centered around axonal degenerative changes. OBJECTIVE: Through in-depth analysis of the roles and interactions of the signaling pathways mentioned in this review during the occurrence and development of Parkinson's disease, to uncover potential clinical early warning mechanisms and explore novel strategies for prevention and treatment, including targeted gene sites, drug therapy, and rehabilitation interventions. METHODS: A search of the PubMed database was conducted using the following keywords: "Parkinson, PD, axonal regeneration, aging, α-syn, pathological mechanism, autopsy, mitochondria, ER stress, inflammatory response, Nrf2/ Keap1, BDNF, NGF, NT3/TrkC, GDNF, RhoA, Rac/Cdc42, Wnt/β-catenin, SHH, Notch, Slit-Robo, Ephrin, Netrin, Semaphorin, integrin, ubiquitin-proteasome, autophagy-lysosome, apoptosis, exercise." Another search of CNKI database was conducted using the search terms of "Parkinson's, axonal degeneration, exercise, oxidative stress, brain-derived neurotrophic factor." Literature was screened based on inclusion and exclusion criteria, and 101 articles were finally included for review and analysis. RESULTS AND CONCLUSION: Studies have shown that Parkinson's disease lesions initially occur in the limbic system region of the brain or the olfactory bulb, and that early axonal degeneration usually precedes cytosolic degeneration. Abnormal protein folding and aggregation, mitochondrial dysfunction, endoplasmic reticulum stress, and inflammatory responses may directly lead to axonal damage; meanwhile, cellular stress responses, neurotrophic factors, cytoskeletal regulation, development and regeneration, axonal growth and guidance, and clearance of abnormal proteins contribute to the repair of damaged axons. Therefore, prevention and treatment strategies for Parkinson's disease should focus on promoting the activation and expression of repair pathways, such as the use of quinacrine and niclosamide or exercise-induced activation of brain-derived neurotrophic factor and other axonal repair pathways, which can effectively promote axonal repair; at the same time, inhibiting abnormal activation of damage pathways is also a key strategy, including knocking out α-synuclein, Parkin genes or using drugs such as empagliflozin to reduce oxidative stress and inflammatory responses, potentially delaying the progression of Parkinson's disease.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21348
BACKGROUND: Platelets are important blood resources, yet in routine blood bank processes they are often filtered out along with white blood cells as medical waste. Optimizing whole blood separation processes to prepare platelet lysate products and exploring their applications in tissue engineering and regenerative medicine is of great value. OBJECTIVE: To optimize whole blood separation to prepare therapeutic-grade platelet lysate and to investigate the protective effect of platelet lysate on hypoxic injury of cardiomyocytes. METHODS: Platelets were isolated from 21 qualified whole blood units under closed blood bag and tubing conditions, and 21 platelet lysates were prepared by freeze-thawing. The mass concentration ranges of platelet-derived growth factor AA, platelet-derived growth factor BB, platelet-derived growth factor AB, vascular endothelial growth factor, epidermal growth factor, insulin-like growth factor 1, fibroblast growth factor, and transforming growth factor beta 1 in platelet lysates were measured using enzyme-linked immunosorbent assay kits. Bacterial contamination was assessed by colony culture method and mycoplasma contamination by PCR detection kit. A cardiomyocyte hypoxia model was established to evaluate the protective effect of platelet lysate on hypoxic injury. RESULTS AND CONCLUSION: (1) The mass concentration ranges of major growth factors and cytokines in platelet lysates were: platelet-derived growth factor AA 12.86-24.17 μg/L, platelet-derived growth factor BB 0.25-0.32 μg/L, platelet-derived growth factor AB 85.09-114.91 μg/L, vascular endothelial growth factor 10.57-58.37 μg/L, epidermal growth factor 0.43-0.69 μg/L, insulin-like growth factor 1 106-204.9 μg/L, fibroblast growth factor 0.03-0.06 μg/L, and transforming growth factor beta 1 124.17-192.38 μg/L. (2) Colony culture and mycoplasma detection results were negative. (3) Low volume fraction (1%) platelet lysate yielded the highest proliferation efficiency of cardiomyocytes; low volume fraction (1%) platelet lysate stimulated cardiomyocytes to produce high levels of superoxide dismutase and glutathione peroxidase to protect cardiomyocytes. This study established a method for preparing therapeutic-grade platelet lysate by optimizing the whole blood separation process, which can improve the utilization rate of blood resources. Platelet lysate has high levels of major growth factors and can significantly promote the repair of hypoxic injured cardiomyocytes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21339
BACKGROUND: Mixed lineage kinase domain-like protein is one of the key executor proteins in the necroptosis pathway and plays an important role in various diseases. However, the mechanism by which its lactylation affects the formation and differentiation of breast tumor stem cells remains unclear. OBJECTIVE: To investigate the effect of mixed lineage kinase domain-like protein K230 site lactylation on the stemness expression of breast tumor stem cells. METHODS: The differences in protein lactylation between breast tumor MCF-7 adherent cells and spheroidal stem cells were analyzed by mass spectrometry. The mixed lineage kinase domain-like protein and its lactylation sites related to tumor stem cells were screened. A mixed lineage kinase domain-like protein K230R mutant plasmid vector was constructed and transfected into MCF-7 breast tumor cells. The proliferation and migration abilities of the cells were detected by CCK-8 and scratch assays. The effect of mixed lineage kinase domain-like protein K230R mutation on the formation of breast tumor stem cells was verified by suspension spheroid formation assay. Western blot was used to detect the expression of stemness and epithelial-mesenchymal transition-related proteins. RESULTS AND CONCLUSION: The lactylation level of mixed lineage kinase domain-like protein at K230 was higher in breast tumor stem cells. Compared with the wild-type group, the K230R mutant group showed significantly reduced scratch healing rate and spheroid formation rate, significantly increased expression of epithelial-related proteins, and significantly decreased expression of mesenchymal-related and stemness-related proteins. The study indicates that lactylation of mixed lineage kinase domain-like protein at K230 promotes epithelial-mesenchymal transition and enhances stemness expression of breast tumor stem cells, thereby promoting the occurrence and development of breast tumors.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21437
BACKGROUND: Osteonecrosis is a disabling and refractory disease with a high prevalence rate in China, necessitating the exploration of potential biomarkers for early prevention, diagnosis, and treatment. Metabolomic studies have demonstrated correlations between human metabolites and osteonecrosis; however, the causal relationship between plasma metabolites and osteonecrosis remains unclear. OBJECTIVE: To investigate the causal association between 1,400 plasma metabolites and osteonecrosis using Mendelian randomization and provide supporting evidence. METHODS: Public data on 1,400 plasma metabolites (exposure factors) and osteonecrosis (outcome factor) were collected. The plasma metabolite data were derived from a genome-wide association study (GWAS) on blood metabolites published in Nature Genetics in January 2023, which included 1,091 blood metabolites and 309 metabolite ratios from 8,299 individuals in the Canadian Longitudinal Study on Aging (CLSA) cohort. The single-nucleotide polymorphism data for osteonecrosis were obtained from the FinnGen public database R12 dataset, comprising 475,307 samples, including 2,043 osteonecrosis cases and 473,264 controls, all of European ancestry. Mendelian randomization analyses (inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode) were performed using Rstudio software, followed by heterogeneity tests, pleiotropy tests, and Steiger directionality tests to ensure robustness and reliability. RESULTS AND CONCLUSION: Three plasma metabolites showed significant causal associations with osteonecrosis (P < 0.05): adenosine monophosphate to valine ratio (OR=1.303, 95%CI=1.110-1.531, P=0.001, PFDR=0.07), oxidized cysteinylglycine level (OR=0.888, 95%CI=0.791-0.998, P=0.046, PFDR=0.05), and 3β,17β-androstenediol disulfate level (OR=1.121, 95%CI=1.020-1.231, P=0.018, PFDR=0.06). The adenosine monophosphate to valine ratio and 3β,17β-androstenediol disulfate level were risk factors for osteonecrosis, while oxidized cysteinylglycine level was a protective factor. These findings suggest causal relationships between three plasma metabolites and osteonecrosis, potentially serving as biomarkers for early diagnosis and targets for intervention. Although based on European population data, this study provides valuable reference for osteonecrosis research in China, and future domestic researchers may achieve early diagnosis and precise treatment by detecting and regulating metabolite levels.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21407
BACKGROUND: The pathological process of intervertebral disc degeneration is accompanied by angiogenesis-lymphatic imbalance and changes in the immune microenvironment, both of which play important roles in intervertebral disc degeneration. OBJECTIVE: To systematically summarize the roles of angiogenesis-lymphatic imbalance-related cytokines in intervertebral disc degeneration. METHODS: The first author searched relevant literature published between January 2000 and April 2025 in the PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. The Chinese search terms included "intervertebral disc degeneration, vascular-lymphatic imbalance, angiogenesis, vascular endothelial growth factor (VEGF), lymphatic vessel, Prox-1, immune microenvironment." A total of 65 articles were ultimately included for review. RESULTS AND CONCLUSION: During intervertebral disc degeneration, the vascular-lymphatic system and immune microenvironment play crucial roles in maintaining disc homeostasis. When disc degeneration occurs, angiogenesis and lymphatic disruption increase inflammatory factors within the disc, leading to enhanced degradation of the extracellular matrix. Concurrently, changes in the immune microenvironment, characterized by increased immune cell infiltration, elevated levels of pro-inflammatory cytokines and chemokines, and activation of local immune responses, modulate vascular and lymphatic vessels, ultimately reducing disc repair capacity and inducing chronic pain, thereby exacerbating the degree of disc degeneration.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21486
BACKGROUND: Studies have shown that tissue clearing technology enables the three-dimensional (3D) visualization of neurons in the spinal cord injury area, clearly presenting morphological changes of neurons, including soma atrophy, dendrite fragmentation, and axonal degeneration. OBJECTIVE: To systematically evaluate the application potential of tissue clearing technology in a rat model of chronic spinal cord injury. METHODS: Thirty-six female Sprague-Dawley rats were randomly and equally divided into a normal group (n=12), a sham surgery group (n=12), and a surgery group (n=12). The normal group received no treatment. The sham group underwent implantation and immediate removal of a poly(vinyl alcohol)/polyacrylamide interpenetrating network hydrogel into the C5-C7 spinal canal. The surgery group received implantation of the hydrogel to compress the spinal cord at C5-C7 to establish a chronic spinal cord injury model. At postoperative days 1, 3, 7, and 14, motor function was assessed using the Basso, Beattie, and Bresnahan (BBB) score and the modified Rivlin inclined plane test. At day 14, spinal cord tissue was harvested for hematoxylin-eosin staining to observe morphology, and tissue clearing combined with neuron-specific nuclear protein immunofluorescence labeling was used for three-dimensional reconstruction and cross-sectional view analysis. RESULTS AND CONCLUSION: (1) The BBB scores and inclined plane test angles in the surgery group were significantly lower than those in the normal and sham groups at all time points (P < 0.001). (2) Hematoxylin-eosin staining showed significant spinal cord injury in the surgery group, with swelling and destruction of nerve cells in the gray matter, loss of uniformity in white matter structure, disappearance of some nuclei, reduced cell number, massive glial cell proliferation and aggregation in the compression area, disordered white matter structure, and formation of numerous cavities. (3) Three-dimensional reconstruction and cross-sectional analysis of the spinal cord showed that in the normal and sham groups, the spinal cord appeared continuous and full, with uniform distribution of neuron-specific nuclear protein red fluorescence, dense layered arrangement of neurons in the anterior horn of the gray matter, and intact white matter fiber tracts. In the surgery group, the spinal cord appeared depressed or even interrupted, with significantly reduced fluorescence intensity of neuron-specific nuclear protein in the compressed segment, disrupted gray matter neuronal layer structure, and regional fluorescence interruption. These results indicate that tissue clearing technology can effectively display structural changes after spinal cord injury, providing strong support for studying the pathological mechanisms of spinal cord injury.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21476
BACKGROUND: Recent studies have found that immune cells play an important role in bone metabolism. Myeloid-derived suppressor cells, as a type of immunosuppressive cell, play a significant role in tumor development, but their role in primary osteoporosis remains unclear. OBJECTIVE: To investigate the osteoclastogenic potential of myeloid-derived suppressor cells in naturally aged and ovariectomy-induced osteoporosis mouse models. METHODS: (1) Myeloid-derived suppressor cells and bone marrow-derived macrophages were isolated from 6-8-week-old female C57BL/6 mice. Both cell types were induced for osteoclast differentiation. After 5 days of induction, osteoclast formation was detected by tartrate-resistant acid phosphatase staining. After 3 days of induction, mRNA expression of nuclear factor of activated T-cells 1 and osteoclast-associated immunoglobulin-like receptor was detected by qRT-PCR. (2) 6-8-week-old female C57BL/6 mice (young group, n=6) and 18-month-old female C57BL/6 mice (naturally aged group, n=6) were taken. Bone microstructure of the distal femur was analyzed by Micro-CT. Bone marrow cells were collected from both groups, and the proportion of myeloid-derived suppressor cells was detected by flow cytometry. Myeloid-derived suppressor cells were isolated and induced for osteoclast differentiation. After 5 days of induction, osteoclast formation was detected by tartrate-resistant acid phosphatase staining; after 3 days of induction, mRNA expression of nuclear factor of activated T-cells 1 and osteoclast-associated immunoglobulin-like receptor was detected by qRT-PCR. (3) 6-8-week-old female C57BL/6 mice were randomly divided into sham-operated group (n=6) and ovariectomy group (n=6). Eight weeks after ovariectomy, bone microstructure of the distal femur was analyzed by Micro-CT. Bone marrow cells were collected from both groups, and the proportion of myeloid-derived suppressor cells was detected by flow cytometry. Serum levels of tumor necrosis factor-alpha and interleukin-6 were measured by ELISA. Myeloid-derived suppressor cells were isolated and induced for osteoclast differentiation. After 5 days of induction, osteoclast formation was detected by tartrate-resistant acid phosphatase staining; after 3 days of induction, mRNA expression of nuclear factor of activated T-cells 1 and osteoclast-associated immunoglobulin-like receptor was detected by qRT-PCR. RESULTS AND CONCLUSION: (1) Tartrate-resistant acid phosphatase staining and qRT-PCR showed that the osteoclast differentiation ability of myeloid-derived suppressor cells was stronger than that of bone marrow-derived macrophages. (2) Micro-CT analysis showed that compared with the young group, the naturally aged group had lower bone mineral density, bone volume fraction, and trabecular number (P < 0.05), and increased trabecular separation (P < 0.05). The proportion of myeloid-derived suppressor cells in the naturally aged group was higher than that in the young group (P < 0.05). Tartrate-resistant acid phosphatase staining and qRT-PCR showed that the osteoclast differentiation ability of myeloid-derived suppressor cells in the naturally aged group was stronger than that in the young group. (3) Micro-CT analysis showed that compared with the sham-operated group, the ovariectomy group had lower bone mineral density, bone volume fraction, and trabecular number (P < 0.05), and increased trabecular separation (P < 0.05). The proportion of myeloid-derived suppressor cells and serum levels of tumor necrosis factor-alpha and interleukin-6 in the ovariectomy group were higher than those in the sham-operated group (P < 0.05). Tartrate-resistant acid phosphatase staining and qRT-PCR showed that the osteoclast differentiation ability of myeloid-derived suppressor cells in the ovariectomy group was stronger than that in the sham-operated group. (4) These results indicate that the proportion and osteoclastogenic ability of myeloid-derived suppressor cells increase under conditions of natural aging and estrogen deficiency, which may participate in the occurrence and development of osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21600
BACKGROUND: Combining exosomes with biomaterials such as hydrogels and biological scaffolds enables targeted delivery, providing effective support for damaged tissue and significantly enhancing the therapeutic efficiency of exosomes, thus positively impacting spinal cord injury repair. OBJECTIVE: To review the action mechanisms and research progress of exosomes combined with biomaterials in spinal cord injury. METHODS: Databases including CNKI, PubMed, and Web of Science were searched using the Chinese and English search terms “spinal cord injury, exosomes, hydrogel, biological scaffold, neuroinflammation, oxidative stress, axonal regeneration, angiogenesis.” Based on the inclusion criteria, 106 articles were finally included in this review. RESULTS AND CONCLUSION: Current research focuses on the repair of secondary injury after spinal cord injury, and how to better alleviate the damage caused by secondary injury is a key research question. Exosomes combined with biomaterials treat spinal cord injury mainly through regulating neuroinflammation, promoting axonal regeneration, and alleviating oxidative stress. This approach avoids immune rejection, solves the problem of low bioavailability of exosomes, and provides effective tissue support, thereby alleviating secondary symptoms after spinal cord injury. Most studies on exosome-loaded biomaterials for spinal cord injury are limited to cell and animal experiments, lacking clinical trial data. Future research should focus on further mechanistic studies, safety evaluations, and related clinical trials.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21598
BACKGROUND: In recent years, the involvement of non-apoptotic regulated cell death in the development of ischemic stroke has become a research hotspot. OBJECTIVE: To summarize the roles and action mechanisms of non-apoptotic regulated cell death subroutines such as autophagy, ferroptosis, cuproptosis, disulfidptosis, necroptosis, and pyroptosis in the neuronal damage caused by ischemic stroke. METHODS: Relevant literature on non-apoptotic regulated cell death and ischemic stroke was retrieved from the China National Knowledge Infrastructure and PubMed databases. The search terms included "ischemic stroke, regulated cell death, autophagy, ferroptosis, cuproptosis, disulfidptosis, necroptosis, pyroptosis, alkaliptosis, oxeiptosis, parthanatos, mitochondrial permeability transition-driven necrosis, neutrophil extracellular trap-related death, lysosome-dependent cell death, immunogenic cell death, anoikis" in English and corresponding Chinese terms. Based on inclusion criteria, 176 articles were finally included for analysis and summary. RESULTS AND CONCLUSION: The regulatory mechanisms of non-apoptotic regulated cell death mainly include autophagy, ferroptosis, anoikis, cuproptosis, disulfidptosis, necroptosis, pyroptosis, oxeiptosis, alkaliptosis, parthanatos, mitochondrial permeability transition-driven necrosis, neutrophil extracellular trap-related death, lysosome-dependent cell death, and immunogenic cell death. Autophagy plays a dual regulatory role in neuronal injury after ischemic stroke: under ischemic conditions, autophagy exerts a neuroprotective effect, whereas excessive autophagy during reperfusion can lead to neuronal death. Ferroptosis can aggravate neuronal injury in ischemic stroke through iron overload and lipid peroxidation. Cuproptosis can regulate glutathione-induced ferroptosis by modulating the protein ferredoxin 1. There is partial crosstalk between disulfidptosis and ferroptosis; under glucose deprivation, upregulation of solute carrier family 7 member 11 consumes NADPH, leading to abnormal accumulation of disulfide compounds and promoting disulfidptosis in neurons. Mixed lineage kinase domain-like pseudokinase, a key participant in necroptosis, is also associated with activation of the pyroptosis-related protein NLRP3 inflammasome, further promoting neuronal pyroptosis during necroptosis in ischemic stroke. Neutrophil extracellular trap-related death in ischemic stroke is mainly caused by citrullination, stress-triggered neutrophil extracellular trap formation, and inflammatory responses mediated by release of various cytotoxic proteases. Other emerging subtypes such as immunogenic cell death cause neuronal damage in ischemic stroke through various specific mechanisms.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21565
BACKGROUND: The vicious cycle of osteoarthritis initiation and progression is driven by the combined effects of mechanical microenvironment disruption and collapse of osmotic pressure homeostasis. Sustained abnormal osmotic pressure disrupts chondrocyte homeostasis and markedly impairs the ability of bone marrow mesenchymal stem cells to differentiate into chondrocytes. Consequently, this compromises the regenerative capacity of cartilage and accelerates the degeneration of articular cartilage. OBJECTIVE: To develop a pathological osmotic pressure model for use in osmotic intervention experiments, in order to investigate the effects of osmotic pressure on chondrogenic differentiation of bone marrow mesenchymal stem cells and chondrocyte matrix metabolism, and to explore the role of imbalanced osmotic pressure within the joint cavity in the pathogenesis of osteoarthritis. METHODS: Bone marrow mesenchymal stem cells were isolated from 6- to 8-week-old rats and cultured to the third passage. Third-passage rat chondrocytes were revived and performed expansion culture. Physiological or pathological osmotic pressure regulating solutions were prepared by adding NaCl to the culture medium, and their biocompatibility was assessed via cell counting kit-8 assays. Bone marrow mesenchymal stem cells were treated with different osmotic pressure regulating solutions in chondrogenic induction medium for 7 or 14 days. Safranin O staining was used to identify the secretion of glycosaminoglycan (a cartilage marker). Quantitative real-time PCR was used to detect the expression of cartilage synthesis-related genes. The effects of physiological or pathological osmotic pressure regulating solutions on chondrocyte anabolic and catabolic metabolism after interleukin-1β inflammation induction were detected. Furthermore, RNA-seq was used to identify differentially expressed genes between the physiological and pathological osmotic pressure groups and perform enrichment analysis. RESULTS AND CONCLUSION: (1) Third-passage bone marrow mesenchymal stem cells were successfully isolated and cultured, and third-passage chondrocytes were successfully revived and expanded. (2) CCK-8 assay results showed that both pathological and physiological osmotic pressure regulating solutions had good biocompatibility. (3) Safranin O staining indicated that at days 7 and 14, the chondrogenic capacity of the physiological osmotic pressure group was significantly enhanced compared with the pathological osmotic pressure group. (4) qRT-PCR results further showed that compared with the interleukin-1β group and the pathological osmotic pressure group, the physiological osmotic pressure group significantly upregulated the expression of cartilage synthesis-related genes aggrecan and collagen type II alpha 1, while downregulating the expression of catabolism-related genes matrix metalloproteinase 13 and matrix metalloproteinase 3. (5) RNA-seq results showed that under physiological osmotic pressure conditions, multiple molecules and signaling pathways related to osteoarthritis pathogenesis were significantly downregulated.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21562
BACKGROUND: Previous studies have confirmed that the Bushen Jianpi Huoxue Formula can increase bone mineral density in osteoporotic rats. OBJECTIVE: To investigate the effect of Bushen Jianpi Huoxue Formula on bone loss and trabecular biomechanical parameters in ovariectomized rats. METHODS: Fifty female Sprague-Dawley rats were randomly divided into five groups: normal group (n=10) without any intervention, sham-operated group (n=10) with removal of adipose tissue near the ovaries, ovariectomized group (n=10), Bushen Jianpi Huoxue Formula group (n=10), and alendronate group (n=10). The latter three groups underwent bilateral ovariectomy to establish osteoporosis models. After 12 weeks of modeling, the Bushen Jianpi Huoxue Formula group and alendronate group were administered the respective drugs by gavage once daily for 12 weeks, while the other three groups received normal saline. After treatment, lumbar spine bone mineral density was measured, micro-CT analysis of the distal femur and proximal tibia was performed, hematoxylin-eosin staining was used to observe the histological morphology of the proximal tibia, and finite element analysis was used to analyze the strain and stress of the distal femur. RESULTS AND CONCLUSION: (1) The lumbar spine bone mineral density in the ovariectomized group was lower than that in the normal and sham-operated groups (P < 0.05), while the Bushen Jianpi Huoxue Formula and alendronate groups had higher lumbar spine bone mineral density than the ovariectomized group (P < 0.05). (2) Micro-CT analysis showed that compared with the normal and sham-operated groups, the ovariectomized group had lower bone volume fraction, bone surface density, and trabecular number in the proximal tibia (or distal femur) (P < 0.05), and higher trabecular separation and structure model index (P < 0.05). Compared with the ovariectomized group, the Bushen Jianpi Huoxue Formula and alendronate groups had higher bone volume fraction, bone surface density, and trabecular number in the distal femur (P < 0.05), and lower trabecular separation and structure model index in the distal femur (P < 0.05); in the proximal tibia, bone volume fraction, bone surface density, and trabecular number were also higher (P < 0.05). (3) Hematoxylin-eosin staining showed that the degree of bone marrow fat infiltration in the ovariectomized group was higher than that in the normal and sham-operated groups, while the Bushen Jianpi Huoxue Formula and alendronate groups showed significant improvement. (4) Finite element analysis showed that under the same load, the trabecular stress and strain in the ovariectomized group were higher than those in the normal and sham-operated groups (P < 0.05), while the Bushen Jianpi Huoxue Formula and alendronate groups had lower trabecular stress and strain than the ovariectomized group (P < 0.05). These results indicate that Bushen Jianpi Huoxue Formula can prevent bone loss and improve trabecular biomechanical properties in ovariectomized rats, suggesting potential efficacy in preventing osteoporotic fractures.
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.2026093
Transfer RNA (tRNA) acts not only as an indispensable adaptor in protein synthesis but also as a key contributor to tumorigenesis when its regulation is disrupted. This review systematically summarizes aberrant tRNA-related mechanisms in cancer, including altered tRNA expression profiles, abnormal post-transcriptional modifications, dysregulated aminoacylation, production of tRNA-derived small RNAs (tdRs), and defects in tRNA trafficking and translational fidelity. Notably, the metabolically abnormal tumor microenvironment actively shapes tRNA reprogramming to facilitate adaptive survival, while dysregulated tRNA elements, such as specific modifications and tdRs, further drive cancer stem cell properties and therapeutic resistance. Collectively, these alterations reprogram the oncoproteome and signaling networks, thereby promoting tumor cell proliferation, metastasis, immune evasion, and drug resistance. Targeting these mechanisms represents a promising strategy for developing novel cancer therapies. Potential approaches include the use of suppressor tRNAs to restore tumor suppressor gene function, the employment of tdRs to modulate oncogenic signaling pathways, or direct inhibition of enzymes involved in tRNA biogenesis. These strategies aim to remodel the dysfunctional tRNA network in cancer and offer new avenues for innovative treatments.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026080
DNAJC9, an HSP40 family member with histone chaperone function, exhibits unclear roles in cervical cancer. DNAJC9 is specifically overexpressed in malignant cervical cancer cells, and downregulation of DNAJC9 inhibits proliferation, induces G1/S arrest, and suppresses tumorigenicity. GLI1 has been identified as a key downstream effector of DNAJC9, and GLI1 rescue reverses proliferation defects. Mechanistically, DNAJC9 promotes the p300-H3 interaction to sustain H3K27ac at the GLI1 enhancer and facilitate GLI1 transcription, driving proliferation. Furthermore, DNAJC9 expression correlates positively with GLI1 in clinical specimens, suggesting that the DNAJC9-GLI1 axis is a potential prognostic marker and therapeutic target.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026066
Fibroblast growth factor 10 (FGF10) plays a critical role in ocular surface homeostasis, yet its function in early meibomian gland (MG) development remains largely unknown. Here, we generated an Fgf10 mutant mouse model with deletion of exon 2, leading to loss of function. Adult Fgf10+/− mice exhibited lacrimal gland agenesis, smaller Harderian glands, increased corneal fluorescein staining, and reduced tear volume. Histological analysis revealed multilayered hyperplastic epithelium in Harderian glands and MG atrophy. Time-series Oil Red O staining showed shorter, thinner, and disordered MGs in Fgf10+/− mice at P14 and P21, with unrecoverable defects at P135. RNA sequencing of MGs at P14 and P21 revealed significant dysregulation of macrophage-related genes and immune-related pathways, including antigen processing and presentation and macrophage chemotaxis. Using Cx3cr1GFP/+ reporter mice, we observed a significant reduction in CX3CR1-positive cells in the inter-acinar stroma of Fgf10+/− MGs. Pharmacological ablation of CSF1R-expressing cells with PLX3397 in wild-type mice recapitulated the MG developmental defects, confirming that FGF10 acts through immune cells to regulate MG development. Collectively, our findings establish that FGF10 haploinsufficiency leads to severe glandular malformations, impaired tear production, and compromised corneal integrity, highlighting the essential role of FGF10 in postnatal MG development and immune cell regulation.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025059
Hepatocellular carcinoma (HCC) remains a highly aggressive malignancy with a five-year survival rate of 12–15%, and unresectable cases exhibit unsatisfactory responses to approved multikinase inhibitors and immune checkpoint blockade. This study integrated single-cell and bulk RNA sequencing to construct a 13-cell-type atlas of the HCC ecosystem and derived a ligand-receptor-based LASSO prognostic model. The model stratified patients into low- and high-risk groups with divergent immune microenvironments, primarily involving macrophages, CD4+ T cells, M1 macrophages, and regulatory T cells. Experimental validation demonstrated that TREM1 promotes HCC cell proliferation, migration, and suppresses apoptosis, while positively modulating IL-1β, TNF-α, and MCP-1. TREM1 knockdown altered M1 macrophage and Treg proportions in a xenograft model and downregulated the Nrf2/Keap1 oxidative stress pathway. Despite a relatively low AUC compared to specialized models, this general network approach offers a novel signature and identifies TREM1 as a potential therapeutic target, though real-world validation and deeper mechanistic studies are warranted.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025092
Sepsis-associated acute respiratory distress syndrome (ARDS) is driven by alveolar macrophage (AM) pyroptosis and high mobility group box 1 (HMGB1) release, yet therapeutic options remain limited. This study evaluates CDDO-imidazolide (CDDO-Im), a potent Nrf2 activator, in modulating AM pyroptosis and HMGB1 secretion. In vitro, J774A.1 macrophages stimulated with LPS and ATP exhibited NLRP3-mediated pyroptosis and HMGB1 release, which was aggravated by 3-MA inhibition of PINK1/Parkin-dependent mitophagy. CDDO-Im significantly attenuated pyroptosis and HMGB1 release while enhancing PINK1/Parkin mitophagy; these effects were abolished in Nrf2-knockout macrophages. In vivo, caecal ligation perforation (CLP) induced septic ARDS in mice. Intraperitoneal CDDO-Im reduced NLRP3 inflammasome protein expression in lung tissues and HMGB1 levels in serum and bronchoalveolar lavage fluid (BALF). Co-administration of the Nrf2 inhibitor ML385 reversed these protective effects. The data demonstrate that CDDO-Im activates Nrf2, which promotes PINK1/Parkin-mediated mitophagy, thereby suppressing AM pyroptosis and HMGB1 release. This mechanism alleviates sepsis-induced ARDS, offering a potential therapeutic strategy. The study was supported by the National Natural Science Foundation of China (81900081, 82170089), and the authors declare no conflicts of interest.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025100
Sulfasalazine (SAS), a clinically utilized anti-inflammatory drug, induces ferroptosis by inhibiting system Xc− and depleting glutathione. This study characterizes the biochemical and cellular mechanisms of SAS-induced ferroptosis in H9C2 rat cardiomyocytes and BRL-3A rat hepatocytes, focusing on protein disulfide isomerase (PDI). SAS induced ferroptosis with sequential increases in cellular nitric oxide (NO), reactive oxygen species (ROS), and lipid-ROS. SAS activated PDI-mediated dimerization of inducible NO synthase (iNOS) and NO accumulation, followed by ROS and lipid-ROS buildup. SAS also upregulated iNOS protein levels. PDI knockdown or pharmacological inhibition suppressed iNOS dimerization, abrogated NO, ROS, and lipid-ROS accumulation, and prevented ferroptosis. Conversely, PDI activation via TrxR1 inhibitors sensitized cells to SAS-induced ferroptosis. These findings support a pivotal role of the PDI-NOS-NO axis in SAS-induced cytotoxicity, leading to oxidative cell death. The study provides mechanistic insights and suggests strategies for sensitizing cancer cells to SAS-induced ferroptosis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025105
Demyelinating diseases of the central nervous system (CNS) are characterized by failed remyelination, largely due to arrested oligodendrocyte precursor cell (OPC) differentiation. This review synthesizes evidence on the crosstalk between oligodendrocytes (OLGs) and other glial cells—astrocytes, microglia, and neurons—in the context of demyelination. OLGs, the myelin-forming cells of the CNS, are essential for axonal integrity and saltatory conduction. Under pathological conditions, factors including astrocyte-derived PDGF and leukemia inhibitory factor (LIF), microglial polarization states, and neuronal activity modulate OLG survival, metabolic support, and process outgrowth. Astrocytes promote process outgrowth via basic fibroblast growth factor (bFGF) and extracellular matrix interactions, while also regulating iron metabolism and exosomal secretion from OPCs through integrin β4-mediated adhesion. Microglial heterogeneity, with M1/M2 polarization, influences neuroinflammation and remyelination outcomes. The review highlights that astrocyte activation via STAT3 signaling determines the balance between oligodendrocyte and Schwann cell remyelination. These intercellular interactions significantly impact myelin regeneration and offer potential therapeutic targets. Modulating these interactions at specific temporal stages may provide novel strategies for treating demyelinating diseases and related neurological conditions. The integration of single-cell resolution data on microglial heterogeneity and spatial-temporal dynamics is critical for developing targeted interventions.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025089
Cuproptosis, a copper-dependent cell death modality driven by acylated protein aggregation and mitochondrial proteotoxic stress, intersects with inflammatory signaling. Hexokinase domain-containing protein 1 (HKDC1), the fifth hexokinase, regulates mitochondrial function, yet its role in cuproptosis and LPS-induced macrophage inflammation remains undefined. Using THP-1-derived macrophages, we assessed plasticity via CCK8 viability and phagocytosis assays, quantified inflammatory factors and cuproptosis-related proteins by western blot and RT-qPCR, and mapped HKDC1 expression/localization through ChIP-qPCR and immunofluorescence. LPS elevated inflammatory cytokines, suppressed cuproptosis, activated glycolysis, and induced HKDC1 via TLR4. HKDC1 knockdown reversed these effects, inhibiting glycolysis and triggering cuproptosis. Mechanistically, LPS promoted Yin Yang 1 (YY1) binding to the HKDC1 promoter, driving transcription. HKDC1 interacted with HSCB and FDX1, increasing intracellular copper and cuproptosis. In vivo, HKDC1 knockdown alleviated acute sepsis by activating copper-dependent cell death. These findings establish HKDC1 as a central node linking LPS, glycolysis, and cuproptosis, proposing a cuproptosis-dependent anti-inflammatory strategy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025036
Oocyte maturation is a critical determinant of mammalian reproductive efficiency, yet the epigenetic mechanisms by which luteinizing hormone (LH) coordinates follicular somatic cell function in sheep remain poorly defined. Histone deacetylase 11 (HDAC11), the sole class IV HDAC, has been implicated in oocyte maturation in mice and pigs, but its role in ovine granulosa cells under LH induction is unknown. This study evaluated the effects of granulosa cell-derived HDAC11 on oocyte maturation in Tan sheep. Expression dynamics of HDAC11 and associated proteins were assessed via immunofluorescence, immunohistochemistry, western blotting, and ELISA. Results demonstrate that HDAC11 levels in follicular granulosa cells and oocytes increase with follicular growth and maturation. Specific inhibition of HDAC11 by SIS17 significantly reduced the oocyte maturation rate under in vitro LH supplementation. Concurrently, H3K9 acetylation in granulosa cells increased, while the EGF-like growth factor AREG decreased markedly. HDAC11 inhibition also lowered YAP1, a negative regulator of AREG. These findings establish that HDAC11 in Tan sheep granulosa cells supports LH-induced AREG production during oocyte in vitro maturation by decreasing H3K9 acetylation and increasing YAP1 levels. This study provides a mechanistic framework for epigenetic regulation of follicular growth and oocyte maturation in sheep, with potential implications for improving in vitro maturation efficiency in domestic animals.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025102
Influenza A viruses (IAVs) remain a global health burden, with seasonal epidemics causing 290,000–650,000 deaths annually. Licensed antivirals—M2 ion-channel inhibitors, neuraminidase (NA) inhibitors, RNA polymerase inhibitors, and cap-dependent endonuclease inhibitors—are compromised by adaptive mutations, particularly in M2 and NA. We screened approximately 5,500 compounds and identified nanchangmycin as a potent IAV inhibitor with robust in vitro and in vivo antiviral activity. Nanchangmycin exhibits broad-spectrum efficacy against pseudorabies virus, herpes virus, porcine epidemic diarrhea virus, and porcine reproductive and respiratory syndrome virus. Notably, it inhibits oseltamivir-resistant IAV strains in sub-μM ranges and promotes survival of MDCK cells infected with an oseltamivir-resistant strain. Mechanistic studies reveal that nanchangmycin blocks nuclear migration of viral nucleoproteins (NPs), causing NP accumulation in the cytoplasm, particularly within perinuclear endosomes. It acts by blocking endosomal acidification, a step essential for viral uncoating. These findings position nanchangmycin as a promising lead for anti-influenza therapeutics, particularly against oseltamivir-resistant strains.