Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpbjnl/qzae016
Ribonuclease P (RNase P) was first described in the 1970’s as an endoribonuclease acting in the maturation of precursor transfer RNAs (tRNAs). More recent studies, however, have uncovered non-canonical roles for RNase P and its components. Here, we review the recent progress of its involvement in chromatin assembly, DNA damage response, and maintenance of genome stability with implications in tumorigenesis. The possibility of RNase P as a therapeutic target in cancer is also discussed.
Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpbjnl/qzae008
Tandem duplication (TD) is a major type of structural variations (SVs) that plays an important role in novel gene formation and human diseases. However, TDs are often missed or incorrectly classified as insertions by most modern SV detection methods due to the lack of specialized operation on TD-related mutational signals. Herein, we developed a TD detection module for the Pindel tool, referred to as Pindel-TD, based on a TD-specific pattern growth approach. Pindel-TD is capable of detecting TDs with a wide size range at single nucleotide resolution. Using simulated and real read data from HG002, we demonstrated that Pindel-TD outperforms other leading methods in terms of precision, recall, F1-score, and robustness. Furthermore, by applying Pindel-TD to data generated from the K562 cancer cell line, we identified a TD located at the seventh exon of SAGE1, providing an explanation for its high expression. Pindel-TD is available for non-commercial use at https://github.com/xjtu-omics/pindel.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04936-3
Background The abnormal immune response mediated by CD4+T cells is a key factor in Immune thrombocytopenia(ITP) progression. While Ningxue Shengban Decoction (NXSBD) is an effective therapeutic, its underlying mechanism and targets remain obscure. Aim This study aims to clarify the role of exosomal miR-199a-5p derived from bone marrow mesenchymal stem cells (BMSCs) in immune homeostasis, and to explore the therapeutic effects of exosomes from BMSCs(BMSCs-Exo) pretreated with NXSBD containing serum on ITP. Method We co-cultured CD4+T cells with BMSCs or pre-treated BMSCs-Exo. The proliferation and differentiation of CD4+T cells were then assessed using CFSE staining and flow cytometry (FCM). Additionally, an active ITP murine model was employed to assess the therapeutic efficacy of pre-treated BMSCs-Exo. Platelet counts were measured and organ indices were calculated. Serum autoantibody levels were measured by FCM and ELISA, changes in CD4⁺T cells subsets in the spleen were analyzed by FCM, megakaryocyte number and morphology in bone marrow tissues were examined by H&E staining, and key cytokine levels in mouse serum were quantified by ELISA. Results Our results indicate that the immunomodulatory effect of BMSCs-Exo on CD4+T cells is mediated by miR-199a-5p, and that NXSBD containing serum enhances this effect by increasing miR-199a-5p levels. In an active ITP murine model, BMSCs-Exo treatment significantly ameliorated the pathological features of ITP, as evidenced by increased peripheral platelet counts, reduced spleen and thymus indices, and decreased levels of autoantibodies. Immunophenotypic analysis revealed that an increased percentage of splenic Treg and Th2 cells, and a decreased percentage of Th17 and Th1 cells, were observed after BMSCs-Exo treatment. Additionally, BMSCs-Exo enhanced the production of mature megakaryocytes. Following BMSCs-Exo treatment, the levels of pro-inflammatory cytokines were sharply lowered, whereas anti-inflammatory cytokine levels were markedly elevated. BMSCs-Exo pretreated with NXSBD containing serum exert superior therapeutic efficacy compared with those derived from untreated BMSCs.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05044-y
Tooth loss remains a major unmet clinical challenge, and current prosthetic approaches cannot restore the biological complexity, sensory function, or regenerative capacity of natural teeth. Recent progress in stem cell biology, developmental engineering, and regenerative biomaterials has opened new possibilities for biological tooth regeneration. This review integrates advances across three major research domains that together define the current landscape of translational regenerative dentistry. First, we discuss stem cell-based, scaffold-guided strategies for tooth regeneration. These approaches combine dental and nondental stem cells, including DPSCs, SCAPs, PDLSCs, SHED, and iPSC-derived lineages, with bioactive materials such as HA/TCP ceramics, dentin-derived extracellular matrix scaffolds, and natural or synthetic polymers to promote odontogenic differentiation, vascularization, and periodontal attachment. Second, we summarize emerging tooth organoid and bioengineered tooth germ technologies that recapitulate epithelial–mesenchymal interactions and enable controlled reconstruction of dentin–pulp and periodontal compartments for modeling human odontogenesis. Third, we highlight molecular regulation-driven therapeutic strategies, focusing on the modulation of Wnt, BMP, FGF, TGF-β, and USAG-1 pathways to stimulate endogenous tooth regeneration and correct developmental defects. Despite marked progress, challenges remain, including stable neurovascular integration, optimization of stem cell–material crosstalk, precise control of spatiotemporal signaling, and long-term functional stability in vivo. Finally, we outline future directions involving smart biomaterials, gene- and protein-based molecular targeting, organoid-guided regeneration, and iPSC-enabled personalized therapies, which may further accelerate the clinical translation of stem cell-based tooth regeneration.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04401-7
Background: Multiple sclerosis (MS) is a progressive autoimmune disease characterized by massive inflammatory infiltration, demyelination, and subsequent axonal injury and neuronal damage in the central nervous system (CNS). The etiology of MS remains unclear and there is not yet a definitive therapeutic schedule for the disease. Bone marrow mesenchymal stem cells (BMSCs), exhibiting neuroimmune-modulatory functions to alleviate various autoimmune diseases, show great potential in the treatment of MS. However, the instability of BMSCs-mediated immunosuppression in vivo has limited their application. MiR181-a, a positive regulator of immune balance, which has a preference for T cells and B cells differentiation, but degrade rapidly upon entering systemic circulation due to their unstable molecular structure. Methods: We propose a synergistic therapy approach that combines the penetrative targeting capability of BMSCs with the immuno-modulatory effects of miR181-a by overexpressing miR181-a to BMSCs through lentivirus packaging system. With this strategy, on the basis of the establishment of the experimental autoimmune encephalomyelitis (EAE) model, miR181-a overexpressing BMSCs (miR181a-BMSCs) would have a stronger immuno-modulatory treatment benefit, in terms of attenuating MS development. Results: Indicate that this method prolongs the modulatory effects of BMSCs and resulted in significantly enhancements of the proliferation of regulatory B cells (Bregs), regulatory T cells (Tregs) and the inhibition of Th17 cells compared to the traditional BMSCs group. Moreover, 10-fold miRNA’s concentration in the exosome of miR181a-BMSCs, leading to an increased duration of miRNAs to exert their biological effects. By immunotherapy and synergistic treatment, the effectiveness of the treatment is significantly enhanced, showing consistent results in different groups of the animal model.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04806-4
Background The human umbilical cord (hUC)–mesenchymal stem cell (MSC) secretome (SCT) is a cell-free therapy that may emerge as a novel therapeutic strategy for hair loss prevention. Here, we aimed to elucidate the underlying mechanisms through which SCT regulates hair growth and cycle transition. Methods Using C57BL/6 mice, ex vivo follicles, and cell experiments, we studied the effects and mechanisms of SCT on hair growth and cycling using untargeted metabolomics and phosphoproteomics. A three-month double-blind clinical study was conducted to validate the effects of SCT on human hair. Results SCT promotes the telogen-to-anagen transition, hair thickening, and elongation of the vibrissae in mice; regulates dermal papilla cells and hair matrix cells through cysteine and methionine metabolism; and stimulates methylthioadenosine synthesis in hair matrix cells by activating the PI3K/AKT/mTOR signaling pathway. Clinical studies demonstrated that SCT increased human hair density and average hair diameter. Scalp physiological tests and subjective feedback indicated no related adverse reactions on the scalp or hair. Conclusions SCT promoted hair growth, thickening, and the hair follicle cycle via the PI3K/AKT/mTOR signaling pathway. This research provides a basis for the application of cell-free alternatives in hair care and hair loss prevention.
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.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025070
Schisandrin A (SchA), a bioactive lignan that was isolated from the dried fruit of Schisandra chinensis, has attracted much attention because of its diverse spectrum of pharmacological effects. The aim of this study is to clarify the function of SchA in diabetes-related fear memory impairment and its molecular mechanisms. Rats are randomly assigned to 4 groups: the control group (Con group), the DM group, the DM + SchA group, and the Con + SchA group. The results demonstrate that SchA treatment improves insulin sensitivity, reduces blood glucose, and significantly reduces memory impairment. SchA treatment also prevents histological damage, enhances synaptic protein production, and significantly decreases Aβ42 formation in the diabetic prefrontal cortex. Further research reveals that SchA therapy decreases microglial activation and the expression levels of variables linked to inflammation while increasing the phosphorylation of proteins implicated in the insulin resistance signaling pathway. Furthermore, in the prefrontal cortex of diabetic rats, SchA decreases ferroptosis by increasing the protein expressions of GPX4, SLC7A11, Nrf2, HO-1, and SIRT1. Overall, our findings suggest that SchA may lessen diabetes-associated fear memory impairment symptoms by, most likely, lowering ferroptosis and inflammatory responses in the prefrontal brain of diabetic rats. SchA may be a useful therapy for diabetes, including memory impairment.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025014
Ferroptosis is a novel form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxides. Recent research has suggested that ferroptosis in osteoblasts contributes to steroid-induced osteonecrosis of the femoral head (SONFH). However, the relationship between ferroptosis and SONFH remains unclear. In this study, in vitro experiments show that dexamethasone (Dex) treatment reduces the expressions of key ferroptosis regulators, SLC7A11 and GPX4, in MC3T3-E1 cells. This reduction leads to a decrease in intracellular glutathione (GSH) levels, accompanied by elevated levels of total iron, malondialdehyde (MDA), and reactive oxygen species (ROS). Importantly, the ferroptosis inhibitor ferrostatin-1 (Fer-1) effectively reverses Dex-induced ferroptosis in MC3T3-E1 cells. Furthermore, RNA-seq analysis reveals that the long noncoding RNA (lncRNA) XR_877193.1 is significantly upregulated in Dex-treated MC3T3-E1 cells. Functional studies demonstrate that the knockdown of lncRNA XR_877193.1 promotes osteogenic differentiation by inhibiting Dex-induced ferroptosis in MC3T3-E1 cells, whereas its overexpression exacerbates cell death via ferroptosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis reveals that the differentially expressed lncRNA XR_877193.1 is enriched in ferroptosis-related pathways, including the PI3K/AKT signaling pathway. Moreover, PI3K/AKT inhibitors reverse ferroptosis in MC3T3-E1 cells inhibited by lncRNA XR_877193.1 knockdown. Collectively, our findings indicate that lncRNA XR_877193.1 knockdown exerts anti-ferroptosis effects by stimulating the PI3K/AKT signaling pathway, suggesting a promising therapeutic strategy for attenuating SONFH.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023246
This corrigendum corrects the affiliation of the authors in the original article. The affiliation has been changed from 'Cancer Hospital Affiliated to Zhengzhou University' to 'The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital'.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025203
Immunotherapy, including cellular therapy, has emerged as a crucial pillar in cancer treatment, complementing established modalities such as surgery, chemotherapy and radiotherapy. The clinical observation that immunotherapy is effective in only a limited proportion of patients inspires mechanistic research on the complicated regulatory network within the tumor microenvironment (TME). Circadian regulation significantly affects immune cell behavior, including the activity of immune cells and cytokine production, and emerging evidence suggests the key role of circadian regulation in the TME, which subsequently affects the effectiveness of immunotherapy. Results from preclinical and clinical studies indicate that appropriate timing of adoptive cellular therapy and immune checkpoint blockade therapy improves their efficacy. Therefore, understanding the molecular mechanism of the circadian rhythm together with its role in immunotherapy is essential for optimizing cellular function, proliferation and persistence in the TME. Here, we review how circadian rhythms influence immunotherapy and the TME across different stages of tumor progression. Future clinical protocols may integrate concepts of circadian rhythm and immunotherapy to enhance treatment response.
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•2026•DOI: 10.3724/abbs.2026015
Diabetic nephropathy (DN) is a major cause of end-stage renal disease. While glomerular damage is a known aspect of its pathology, tubular epithelial cell necroptosis also plays a crucial role in disease progression. Epigenetic modifications, particularly histone acetylation, have garnered attention for their role in the regulation of kidney damage-related gene expression. This study explores whether the histone acetyltransferase P300 regulates KRT18 expression via histone H3 lysine 18 acetylation (H3K18ac), driving tubular epithelial cell necroptosis and accelerating DN progression. We establish an STZ-induced diabetic nephropathy mouse model and a high glucose-treated HK-2 cell model. Western blot analysis, qPCR, immunohistochemistry, and AO/PI staining are employed to assess the expression levels of P300, H3K18ac, KRT18, and necroptosis-related proteins (RIPK1 and MLKL). Functional validation of the P300-KRT18 axis is performed using shRNA interference, overexpression, and the small molecule inhibitor C646. Both in vivo and in vitro models show significant upregulation of P300, H3K18ac, and KRT18, coupled with RIPK1/MLKL pathway activation and increased cell death. P300 knockdown or C646 treatment effectively inhibits H3K18ac and KRT18 expression, reducing necroptosis; KRT18 knockdown also alleviates P300 overexpression-induced cell death. Co-transfection with P300 overexpression and KRT18 interference demonstrates that KRT18 is a key downstream effector of P300-mediated necroptosis. In conclusion, P300 upregulates KRT18 expression through H3K18 acetylation, subsequently activating the RIPK1/MLKL pathway and promoting tubular epithelial cell necroptosis. The P300-KRT18 axis may serve as a novel epigenetic therapeutic target for DN, suggesting that epigenetic regulation could be a viable intervention strategy to delay DN progression.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024102
Synovial inflammation plays a key role in osteoarthritis (OA) pathogenesis. Fibroblast-like synoviocytes (FLSs) represent a distinct cell subpopulation within the synovium, and their unique phenotypic alterations are considered significant contributors to inflammation and fibrotic responses. The underlying mechanism by which acetyl-11-keto-β-boswellic acid (AKBA) modulates FLS activation remains unclear. This study aims to assess the beneficial effects of AKBA through both in vitro and in vivo investigations. Network pharmacology evaluation is used to identify potential targets of AKBA in OA. We evaluate the effects of AKBA on FLSs activation in vitro and the regulatory role of AKBA on the Nrf2/HO-1 signaling pathway. ML385 (an Nrf2 inhibitor) is used to verify the binding of AKBA to its target in FLSs. We validate the in vivo efficacy of AKBA in alleviating OA using anterior cruciate ligament transection and destabilization of the medial meniscus (ACLT+DMM) in a rat model. Network pharmacological analysis reveals the potential effect of AKBA on OA. AKBA effectively attenuates lipopolysaccharide (LPS)-induced abnormal migration and invasion and the production of inflammatory mediators, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS) in FLSs, contributing to the restoration of the synovial microenvironment. After treatment with ML385, the effect of AKBA on FLSs is reversed. In vivo studies demonstrate that AKBA mitigates synovial inflammation and fibrotic responses induced by ACLT+DMM in rats via activation of the Nrf2/HO-1 axis. AKBA exhibits theoretical potential for alleviating OA progression through the Nrf2/HO-1 pathway and represents a viable therapeutic candidate for this patient population.
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.2025044
Pigs, as crucial economic livestock species, possess remarkable reproductive traits and thus play a highly significant role in promoting the progress of the livestock industry. With the advent and application of CRISPR/Cas9 technology, researchers have explored genetic editing techniques to increase swine reproductive performance, flavour profiles, and nutritional attributes. Additionally, with respect to anatomy, physiology, immunology, and genomics as well as other traits, pigs exhibit remarkable similarities to humans. Genetically edited pigs play crucial roles in human disease models, xenotransplantation, breed improvement, vaccine development, and drug assessment. Common methods deployed in the preparation of genetically edited pigs include somatic cell nuclear transfer (SCNT), microinjection and sperm-mediated approaches. For example, Shen et al. [1] successfully generated P53-knockout Diannan miniature pigs using transcription activator-like effector nucleases combined with SCNT, offering a valuable resource for preclinical oncology research. In 2019, Chen et al. [2] employed microinjection to deliver Cas9 messenger ribonucleic acid (mRNA) and single guide ribonucleic acid (sgRNA) into the cytoplasm of fertilized eggs. These authors successfully obtained both the albinism phenotype and the combined phenotype of albinism and immunodeficiency in Tibetan miniature pigs. More recently, Tenihara et al. [3] introduced the CRISPR/Cas9 protein into fertilized porcine eggs via electroporation, enabling a simple, micromanipulation-free approach for generating gene-edited pigs. Among these methods, SCNT has gained extensive interest among researchers because of its reliability. An essential aspect of SCNT is the preparation of embryonic fibroblasts to serve as donor cells. Previously, the CRISPR/Cas9 plasmid editing system served as the predominant technique to generate genetically edited embryonic fibroblasts (Figure 1A) [4]. This approach, which is distinguished by its relative simplicity, high stability, and low cost, was formerly widely utilized in the production of gene-edited pigs. However, plasmid editing is associated with several notable limitations. First, it introduces resistance genes, posing risks of inaccurate gene editing, drug resistance and biosafety concerns. Second, during the CRISPR/Cas9 editing process, there is a possibility of ongoing editing due to deoxyribonucleic acid (DNA) integration. This continuous editing can increase the likelihood of off-target effects, random mutations, and interference with DNA repair mechanisms. Third, the acquisition of positive cell lines via the plasmid editing system typically demands an extended period of in vitro cultivation (lasting 3–4 weeks), which increases the risk of apoptosis and chromosomal aberrations. Consequently, plasmid-based transfection is now largely supplanted by ribonucleoprotein (RNP) systems for gene editing. RNP systems bypass plasmids, delivering the Cas9 protein and sgRNA directly into cells, reducing off-target effects and cytotoxicity [5]. In 2022, Xu et al. [6] developed the reporter RNA-enriched dual-sgRNA CRISPR/Cas9 ribonucleoprotein (RE-DSRNP) method, a transgene-free approach using CRISPR/Cas9 RNPs enriched with ATTO550-tracrRNA (IDT, Iowa, USA) as a fluorescent RNA probe (Figure 1B). This method reduced the time needed to generate donor cells from 3-4 weeks to one week, resulting in high-efficiency WIP1 gene knockouts and the production of pigs with male reproductive disorders. However, owing to genetic diversity, not all target genes achieve 95% editing efficiency, as demonstrated by the RE-DSRNP method, with some falling below 90%. For example, DOCK8, which belongs to the DOCK family, is an atypical guanine nucleotide exchange factor that plays a crucial role in immune responses. DOCK8 deficiency syndrome, a rare hereditary disorder, often leads to combined immunodeficiency and is characterized by elevated serum immunoglobulin E levels, increased eosinophil
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024192
Clitoria ternatea L. flowers are used as traditional herbal medicines and are known for their advanced pharmacological activities. Flavonoids and anthocyanins reportedly contribute to the therapeutic properties of C. ternatea flowers; however, their potential anti-bladder cancer effects and molecular mechanisms remain unknown. In this study, flavonoid- and anthocyanin-rich samples from C. ternatea flowers (DDH) are prepared via macroporous resin-based extraction coupled with an efficient and reliable two-dimensional UPLC-DAD-MS/MS method. In vitro and in vivo studies reveal that DDH can inhibit bladder cancer cell growth and enhance the anti-bladder cancer activity of cisplatin. RNA-seq combined with KEGG analysis reveals that fatty acid synthesis is closely related to the anti-bladder cancer effect of DDH. Furthermore, DDH dose-dependently reduces cellular fatty acid levels in bladder cancer cells, and the addition of fatty acids significantly mitigates DDH-induced cell growth inhibition. Subsequent findings reveal that DDH downregulates sterol regulatory element-binding protein 1 (SREBP1), a key transcriptional regulator of de novo fatty acid synthesis in cancer cells, and its downstream targets (FASN, SCD1, and ACC). Additionally, this study demonstrates that gallic acid not only enhances the stability of DDH but also synergistically potentiates its anti-bladder cancer activity. Our study suggests that targeting the SREBP1 pathway is an effective strategy in bladder cancer therapy, and the ability of DDH to induce cell death by inhibiting the SREBP1 pathway and its good tolerance in mice make it a promising strategy for preventing and treating bladder cancer.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.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•2025•DOI: 10.3724/abbs.2024181
MicroRNAs (miRNAs) have emerged as essential regulators that play important roles in the development of multiple systems. Recent studies have identified significant roles for miRNAs in the progression of cardiac hypertrophy. This study aims to investigate the effects of miR-133b-3p on angiotensin II (Ang II)-induced cardiac hypertrophy and apoptosis, as well as explore its underlying mechanisms. Our experimental results reveal that miR-133b-3p expression is significantly decreased in both animal and cell models of cardiac hypertrophy induced by Ang II. Overexpression of miR-133b-3p reverses the hypertrophic manifestations and apoptosis induced by Ang II. Through bioinformatics analysis and dual-luciferase reporter assays, CDIP1 (cell death inducing p53 target 1) is identified as a direct target of miR-133b-3p, and the overexpression of miR-133b-3p reduces CDIP1 expression. Additionally, CDIP1 silencing suppresses cardiomyocyte hypertrophy and apoptosis induced by Ang II. In summary, these results suggest that miR-133b-3p may serve as a potential diagnostic marker for cardiac hypertrophy and that the upregulation of miR-133b-3p inhibits cardiac hypertrophy by targeting CDIP1.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.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•2025•DOI: 10.3724/abbs.2025096
Ferroptosis, a novel form of regulated necrosis, has drawn the attention of the scientific community. Nevertheless, few studies have focused on the impact of ferroptosis on MC3T3-E1 cells in the context of steroid-induced osteonecrosis of the femoral head (SONFH). In this study, we explore the relationship between the degree of ferroptosis induced by dexamethasone (Dex) and the expression of silent information regulatory protein 1 (Sirt1). The results indicate that the ferroptosis level induced by Dex is mediated by the downregulation of Sirt1. Overexpression of Sirt1 increases the levels of the ferroptosis-related proteins SLC7A11 and GPX4 in MC3T3-E1 cells following Dex exposure. Moreover, the effect of Dex on Sirt1 expression is regulated by hypermethylation of the Sirt1 promoter, which is catalyzed by DNA methyltransferase 3a (DNMT3a). In summary, this study reveals that Dex can trigger ferroptosis by promoting DNMT3a-mediated DNA methylation and downregulating Sirt1 expression. Our findings provide an additional new mechanism for Dex-induced ferroptosis in MC3T3-E1 cells.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024189
Osteoarthritis (OA) is a significant contributor to pain and disability worldwide. Pain is the main complaint of OA patients attending the clinic and has a large impact on their quality of life and economic standards. However, existing treatments for OA-related pain have not been shown to achieve good relief. The main focus is on preventing and slowing the progression of OA so that the problem of OA pain can be resolved. Pain caused by OA is complex, with the nature, location, duration, and intensity of pain changing as the disease progresses. Previous research has highlighted the role of various forms of cell death, such as apoptosis and necrosis, in the progression of pain in OA. Emerging studies have identified additional forms of novel cell death, such as pyroptosis, ferroptosis, and necroptosis that are linked to pain in OA. Different types of cell death contribute to tissue damage in OA by impacting inflammatory responses, reactive oxygen species (ROS) production, and calcium ion levels, ultimately leading to the development of pain. Evidence suggests that targeting novel types of cell death could help alleviate pain in OA patients. This review delves into the complex mechanisms of OA pain, explores the relationship between different modes of novel cell death and pain, and proposes novel cell death as a viable strategy for the treatment of these conditions, with the goal of providing scientific references for the development of future OA pain treatments and drugs.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024026
Adhesion molecules play critical roles in maintaining the structural integrity of the airway epithelium in airways under stress. Previously, we reported that catenin alpha-like 1 (CTNNAL1) is downregulated in an asthma animal model and upregulated at the edge of human bronchial epithelial cells (HBECs) after ozone stress. In this work, we explore the potential role of CTNNAL1 in the structural adhesion of HBECs and its possible mechanism. We construct a CTNNAL1‒/‒ mouse model with CTNNAL1-RNAi recombinant adeno-associated virus (AAV) in the lung and a CTNNAL1-silencing cell line stably transfected with CTNNAL1-siRNA recombinant plasmids. Hematoxylin and eosin (HE) staining reveals that CTNNAL1‒/‒ mice have denuded epithelial cells and structural damage to the airway. Silencing of CTNNAL1 in HBECs inhibits cell proliferation and weakens extracellular matrix adhesion and intercellular adhesion, possibly through the action of the cytoskeleton. We also find that the expressions of the structural adhesion-related molecules E-cadherin, integrin β1, and integrin β4 are significantly decreased in ozone-treated cells than in vector control cells. In addition, our results show that the expression levels of RhoA/ROCK1 are decreased after CTNNAL1 silencing. Treatment with Y27632, a ROCK inhibitor, abolished the expressions of adhesion molecules induced by ozone in CTNNAL1-overexpressing HBECs. Overall, the findings of the present study suggest that CTNNAL1 plays a critical role in maintaining the structural integrity of the airway epithelium under ozone challenge, and is associated with epithelial cytoskeleton dynamics and the expressions of adhesion-related molecules via the RhoA/ROCK1 pathway.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024015
Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database. Breast cancer-related genes are obtained from the GeneCards database. Major targets and pathways related to SYF treatment in breast cancer are identified by analyzing the above data. By conducting molecular docking analysis, we find that the active ingredients quercetin and luteolin bind well to the key targets KDR1, PPARG, SOD1, and VCAM1. In vitro experiments verify that SYF can reduce the proliferation, migration, and invasion ability of TNBC cells. Using a TNBC xenograft mouse model, we show that SYF could delay tumor growth and effectively inhibit the occurrence of breast cancer lung metastasis in vivo. PPARG, SOD1, KDR1, and VCAM1 are all regulated by SYF and may play important roles in SYF-mediated inhibition of TNBC recurrence and metastasis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04936-3
Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by immune-mediated platelet destruction and impaired production, leading to isolated thrombocytopenia. Abnormal CD4+ T cell-mediated immune responses are central to ITP progression. Ningxue Shengban Decoction (NXSBD) is clinically effective, but its mechanism remains obscure. This study investigates the role of exosomal miR-199a-5p derived from bone marrow mesenchymal stem cells (BMSCs) in immune homeostasis and evaluates the therapeutic potential of BMSC-derived exosomes (BMSCs-Exo) pretreated with NXSBD-containing serum on ITP. In vitro, CD4+ T cells were co-cultured with BMSCs or pretreated BMSCs-Exo, and proliferation and differentiation were assessed by CFSE staining and flow cytometry. In vivo, an active ITP murine model was used to evaluate therapeutic efficacy. Platelet counts, organ indices, serum autoantibody levels, splenic CD4+ T cell subsets, megakaryocyte number and morphology, and key cytokine levels were quantified. Results demonstrate that the immunomodulatory effect of BMSCs-Exo on CD4+ T cells is mediated by miR-199a-5p, and NXSBD-containing serum enhances this effect by increasing miR-199a-5p levels. BMSCs-Exo treatment significantly ameliorated ITP pathology, evidenced by increased peripheral platelet counts, reduced spleen and thymus indices, decreased autoantibodies, increased splenic Treg and Th2 cells, decreased Th17 and Th1 cells, enhanced mature megakaryocyte production, and rebalanced cytokine profiles. BMSCs-Exo pretreated with NXSBD-containing serum exhibited superior therapeutic efficacy compared to untreated BMSCs-Exo.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05044-y
Tooth loss remains a major unmet clinical challenge, and current prosthetic approaches cannot restore the biological complexity, sensory function, or regenerative capacity of natural teeth. Recent progress in stem cell biology, developmental engineering, and regenerative biomaterials has opened new possibilities for biological tooth regeneration. This review integrates advances across three major research domains that together define the current landscape of translational regenerative dentistry. First, we discuss stem cell-based, scaffold-guided strategies for tooth regeneration. These approaches combine dental and nondental stem cells, including DPSCs, SCAPs, PDLSCs, SHED, and iPSC-derived lineages, with bioactive materials such as HA/TCP ceramics, dentin-derived extracellular matrix scaffolds, and natural or synthetic polymers to promote odontogenic differentiation, vascularization, and periodontal attachment. Second, we summarize emerging tooth organoid and bioengineered tooth germ technologies that recapitulate epithelial–mesenchymal interactions and enable controlled reconstruction of dentin–pulp and periodontal compartments for modeling human odontogenesis. Third, we highlight molecular regulation-driven therapeutic strategies, focusing on the modulation of Wnt, BMP, FGF, TGF-β, and USAG-1 pathways to stimulate endogenous tooth regeneration and correct developmental defects. Despite marked progress, challenges remain, including stable neurovascular integration, optimization of stem cell–material crosstalk, precise control of spatiotemporal signaling, and long-term functional stability in vivo. Finally, we outline future directions involving smart biomaterials, gene- and protein-based molecular targeting, organoid-guided regeneration, and iPSC-enabled personalized therapies, which may further accelerate the clinical translation of stem cell-based tooth regeneration.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026015
Diabetic nephropathy (DN) is a major cause of end-stage renal disease. While glomerular damage is a known aspect of its pathology, tubular epithelial cell necroptosis also plays a crucial role in disease progression. Epigenetic modifications, particularly histone acetylation, have garnered attention for their role in the regulation of kidney damage-related gene expression. This study explores whether the histone acetyltransferase P300 regulates KRT18 expression via histone H3 lysine 18 acetylation (H3K18ac), driving tubular epithelial cell necroptosis and accelerating DN progression. We establish an STZ-induced diabetic nephropathy mouse model and a high glucose-treated HK-2 cell model. Western blot analysis, qPCR, immunohistochemistry, and AO/PI staining are employed to assess the expression levels of P300, H3K18ac, KRT18, and necroptosis-related proteins (RIPK1 and MLKL). Functional validation of the P300-KRT18 axis is performed using shRNA interference, overexpression, and the small molecule inhibitor C646. Both in vivo and in vitro models show significant upregulation of P300, H3K18ac, and KRT18, coupled with RIPK1/MLKL pathway activation and increased cell death. P300 knockdown or C646 treatment effectively inhibits H3K18ac and KRT18 expression, reducing necroptosis; KRT18 knockdown also alleviates P300 overexpression-induced cell death. Co-transfection with P300 overexpression and KRT18 interference demonstrates that KRT18 is a key downstream effector of P300-mediated necroptosis. In conclusion, P300 upregulates KRT18 expression through H3K18 acetylation, subsequently activating the RIPK1/MLKL pathway and promoting tubular epithelial cell necroptosis. The P300-KRT18 axis may serve as a novel epigenetic therapeutic target for DN, suggesting that epigenetic regulation could be a viable intervention strategy to delay DN progression.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21225
BACKGROUND: The crescent sign is a significant radiological feature in the progression of steroid-induced osteonecrosis of the femoral head (SIONFH), indicating the separation and defect of articular cartilage and subchondral bone. The appearance of the crescent sign is associated with the mid-to-late stages of the disease and poor prognosis. However, studies on the specific pathological characteristics and progression patterns of articular cartilage in SIONFH remain unclear. OBJECTIVE: To observe the pathological features of articular cartilage in specimens from different stages of SIONFH, explore the progression and pathological mechanisms, and elucidate the formation mechanism of the crescent sign, providing a theoretical basis for optimizing hip-preserving strategies. METHODS: Femoral head specimens were collected from patients with SIONFH who underwent total hip arthroplasty at the First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2021 to 2024. According to the ARCO staging, they were divided into mild, moderate, and severe collapse groups, with fresh femoral neck fracture specimens as controls. All specimens were cut coronally, and the folded cartilage surface in the necrotic area was taken; control group took corresponding area. Hematoxylin-eosin staining and Safranin O-fast green staining were used for morphological observation, immunohistochemistry and western blot for biomarker expression, and apoptosis kit for apoptosis level. RESULTS AND CONCLUSION: (1) Gross observation: The control group showed smooth cartilage surface without folds or hyperplasia, no separation or defect between articular cartilage and subchondral bone, and tough texture. In SIONFH specimens, obvious folds were visible on the cartilage surface, with separation and defects between articular cartilage and subchondral bone, and a loose sensation on pressing. (2) Pathological observation: In the control group, chondrocytes in each layer were arranged neatly, cartilage matrix stained uniformly, tidemark was intact and continuous, calcified cartilage layer and subchondral bone connection was clear and complete, and bone trabeculae were arranged neatly. In SIONFH specimens, chondrocytes were disorganized, empty lacunae increased, matrix staining loss of varying degrees, tidemark duplication and loss, calcified cartilage layer showed numerous cavities and sclerosis, with granulation tissue invasion into cavities, separation and defects between calcified cartilage and subchondral bone, and abundant proliferative granulation tissue in subchondral bone trabecular spaces. (3) Immunohistochemistry: In SIONFH specimens, positive staining of Runt-related transcription factor 2, matrix metalloproteinase 13, matrix metalloproteinase 3, and collagen type I alpha 2 chain increased in calcified cartilage layer and deep cartilage; vascular endothelial growth factor A, hypoxia-inducible factor 1 alpha, interleukin-1 beta, and tumor necrosis factor alpha positive staining increased in subchondral bone trabecular spaces and deep cartilage granulation and scar tissue. (4) Western blot results showed decreased expression of collagen type II alpha 1 chain and SOX9, and increased expression of Runt-related transcription factor 2, matrix metalloproteinase 13, hypoxia-inducible factor 1 alpha, and vascular endothelial growth factor A in SIONFH specimens. (5) Caspase3/7 activity in SIONFH samples was significantly higher than that in the control group, positively correlated with the degree of collapse. (6) These results indicate that articular cartilage lesions in SIONFH mainly concentrate in the deep cartilage and calcified cartilage around the necrotic area. Necrosis of subchondral bone leads to changes in local microenvironment and elastic modulus, causing sclerosis of calcified cartilage. With continued weight-bearing, stress concentration at the necrosis-sclerosis junction leads to brittle fracture, which is the starting point of fracture. Bone and cartilage fracture leads to destruction of the subchondral cortical bone barrier, and invasion of granulation tissue from subchondral bone trabecular spaces directly stimulates calcified cartilage and deep cartilage, resulting in terminal differentiation, apoptosis, matrix degradation, and cavity formation of chondrocytes, leading to decreased repair capacity of articular cartilage. The diseased cartilage cannot properly interlock with subchondral bone, and with disease progression, extensive separation and defects eventually appear between bone and cartilage, manifesting as the crescent sign on imaging.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21278
BACKGROUND: Previous studies have shown that knockdown of β-catenin can inhibit the osteogenic differentiation of human bone marrow mesenchymal stem cells and reduce the expression of TRIB3. Serum containing Compound Kidney-Invigorating Granules can promote the expression of β-catenin and TRIB3 in human bone marrow mesenchymal stem cells, and induce human bone marrow mesenchymal stem cells to differentiate into osteogenic cells. OBJECTIVE: To further explore the mechanism of Compound Kidney-Invigorating Granules in a mouse model of osteoporosis based on the TRIB3/β-catenin axis. METHODS: 8-week-old female C57BL/6 mice were randomly divided into the following experimental groups: blank control, sham operation, model, and low-, medium-, and high-dose Compound Kidney-Invigorating Granules groups, and positive drug group. Except for the blank control and sham operation groups, bilateral ovariectomy was performed to establish an osteoporosis mouse model. One week after modeling, mice in the low-, medium-, and high-dose groups were intragastrically administered 7.05, 14.1, and 28.2 g/kg Compound Kidney-Invigorating Granules, respectively; the blank control, sham operation, and model groups received an equal volume of normal saline once daily; the positive control group received 1.53 mg/kg alendronate sodium once weekly. After 12 weeks of administration, Micro-CT was used to detect changes in femoral bone microarchitecture; hematoxylin-eosin staining and Masson staining were used to detect pathological changes in the femur; Western blot was used to detect the expression levels of TRIB3, β-catenin, alkaline phosphatase, and osteopontin in bone tissue. RESULTS AND CONCLUSION: Compared with the blank control and sham operation groups, the model group showed sparse bone trabeculae and significantly increased empty lacunae; the protein expression levels of TRIB3, β-catenin, alkaline phosphatase, and osteopontin were significantly decreased (P < 0.05). Compared with the model group, the medium- and high-dose Compound Kidney-Invigorating Granules groups showed more complete and regular bone trabeculae, and the protein expression levels of TRIB3, β-catenin, alkaline phosphatase, and osteopontin were significantly upregulated (P < 0.05). These results indicate that Compound Kidney-Invigorating Granules exert a therapeutic effect on osteoporosis model mice, suggesting that the formula may act through the TRIB3/β-catenin axis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21253
BACKGROUND: Muscular atrophy is a pathological process characterized by the progressive decline in muscle mass and function, which severely affects patients' quality of life. In recent years, the role of mitophagy, as an important mitochondrial quality control mechanism for maintaining intracellular homeostasis, has attracted significant attention in the context of muscle atrophy. Drosophila, as a classical model organism, has become a crucial tool for studying the connection between muscle atrophy and mitophagy mechanism due to its conserved muscle functional structure and straightforward genetic manipulation. OBJECTIVE: To review the molecular mechanism of mitophagy dysfunction in muscular atrophy and to summarize the research progress of relevant Drosophila models in this field, with the aim of providing new insights and directions for the study of the pathological mechanism and the development of therapeutic strategies for muscular atrophy. METHODS: PubMed and China National Knowledge Infrastructure databases were searched using keywords including 'skeletal muscle, muscle regenerate, denervation muscle atrophy, muscle atrophy, sarcopenia, drosophila, drosophila melanogaster, mitophagy, mitochondrial dysfunction' and 'muscle atrophy, skeletal muscle, muscle regeneration, sarcopenia, denervation muscle atrophy, Drosophila, mitophagy, mitochondrial dysfunction'. The search period was from January 2001 to February 2025. After screening, 68 articles were included for review. RESULTS AND CONCLUSION: Studies using Drosophila models indicate that mitophagy plays a critical role in the development of muscle atrophy. Mitophagy dysfunction leads to the accumulation of damaged mitochondria in muscle cells, triggering oxidative stress, energy metabolism disorders, and inducing myocyte apoptosis, thereby exacerbating muscle atrophy. Furthermore, Drosophila models have shown great advantages in screening potential therapeutic targets and identifying intervention strategies, providing new avenues for mechanistic research and therapeutic development for muscle atrophy. By summarizing the findings from Drosophila models, this review emphasizes the strategy of treating muscle atrophy by modulating mitophagy mechanisms, highlights the unique advantages of Drosophila models in studying the molecular mechanisms of mitophagy and muscle atrophy, and suggests that future research should integrate translational medicine, high-throughput molecular screening, and multi-omics approaches to further explore unknown molecular mechanisms and new therapeutic targets.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21305
OBJECTIVE: Upper limb dysfunction after stroke is a common complication that seriously affects the quality of life and daily activity of patients. Virtual reality technology, as an emerging rehabilitation method, can effectively promote neural remodeling and functional recovery. This study will systematically evaluate the therapeutic effects of different virtual reality devices on upper limb motor dysfunction in patients with stroke. METHODS: The China National Knowledge Infrastructure (CNKI), WanFang Database, VIP website, PubMed, Web of Science, Embase, and the Cochrane Library were searched to retrieve relevant literature. Relevant data were extracted, and their quality was assessed. The control group received conventional rehabilitation treatment, while the experimental group received virtual reality rehabilitation training in addition to the treatment provided to the control group. Statistical analysis was performed using RevMan 5.4 and Stata 18.0 software. RESULTS: (1) A total of 12 articles and 571 patients were included in the meta-analysis. (2) Meta-analysis results showed that the Fugl-Meyer score of the upper limb in the virtual reality group was 7.29 times that of the conventional group (MD=7.29, 95%CI: 5.60-8.98, P < 0.05); the Action Research Arm Test score in the virtual reality group was 10.69 times that of the conventional group (MD=10.69, 95%CI: 4.96-16.43, P < 0.05); the modified Barthel index score in the virtual reality group was 8.25 times that of the conventional group (MD=8.25, 95%CI: 3.38-13.12, P < 0.05). (3) Subgroup analysis showed that patients aged 50-59 years had better improvement in upper limb Fugl-Meyer score; patients with disease duration within 3 months had better improvement; intervention duration ≥4 weeks had the best improvement. (4) Network meta-analysis showed that smart glove intervention [MD=-1.05, 95%CI(-1.85, -0.24), P < 0.05] was most effective for improving upper limb motor function; Armeo Spring intervention [MD=-1.19, 95%CI(-1.87, -0.51), P < 0.05] was most effective for improving upper limb coordination; Kinect intervention [MD=-0.59, 95%CI(-1.13, -0.06), P < 0.05] was most effective for improving hand dexterity; VREX intervention [MD=-0.76, 95%CI(-1.28, -0.23), P < 0.05] was most effective for improving activities of daily living. CONCLUSION: For improving upper limb motor function, the smart glove system is the first choice; for improving upper limb coordination, the Armeo Spring system is the first choice; for improving hand dexterity, the Kinect system is the first choice; for improving activities of daily living, the VREX system is the first choice. This study has certain limitations, and the above conclusions should be interpreted with caution.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21418
BACKGROUND: Clinically, due to the special anatomical characteristics and internal trabecular bone distribution of the scaphoid, the treatment effect of fractures is generally poor, often leading to nonunion and ischemic necrosis, which in turn causes wrist arthritis and loss of function. OBJECTIVE: To scan scaphoid specimens using Micro CT technology, analyze their internal microstructure characteristics, measure the trabecular bone microstructure parameters in each region, and discover regional differences in scaphoid trabecular bone, aiming to provide a scientific basis for the prevention, treatment, and fracture mechanism research of scaphoid fractures. METHODS: Bilateral scaphoid bones (10 cases) from 5 adult cadaver specimens were scanned by Micro CT. By selecting and reconstructing trabecular bone in three regions of interest (tubercle, waist, and body), the internal micromorphological characteristics of the scaphoid were observed in detail, and the differences in trabecular bone microstructure parameters among regions were measured and compared. RESULTS AND CONCLUSION: (1) Micro CT images showed that the cortical bone on the surface of the scaphoid was relatively thin, and the interior was filled with complex trabecular bone microstructure; the lamellar trabecular bone near the cortical bone was relatively dense, extending inward into rod-like trabecular bone. From sagittal, coronal, and transverse sections, the trabecular bone distribution in the waist was relatively sparse, while that in the body and tubercle was denser. (2) There were significant differences in bone volume fraction, bone surface area, bone surface area to tissue volume ratio, trabecular separation, trabecular number, trabecular connectivity, trabecular connection density, fractal dimension, bone mineral density, and bone mineral content of the scaphoid tubercle between left and right sides (P < 0.05). There were no significant differences in the trabecular bone microstructure parameters of the waist and body between left and right sides (P > 0.05). (3) There were significant differences in bone volume, bone volume fraction, bone surface area, bone surface area to tissue volume ratio, bone surface area to bone volume ratio, bone mineral density, and bone mineral content between the body and the tubercle/waist (P < 0.05). There was a significant difference in trabecular thickness between the body and the tubercle (P < 0.05). There were significant differences in trabecular separation and fractal dimension among the body, tubercle, and waist (P < 0.05). There were significant differences in trabecular number, trabecular connectivity, and trabecular connection density between the waist and the tubercle/body (P < 0.05). There were no significant differences in tissue volume and degree of anisotropy among the body, tubercle, and waist (P > 0.05). (4) The results showed that the trabecular bone microstructure parameters of the scaphoid had regional differences, among which the waist had lower bone density and strength, making it the most prone to fracture. This finding provides a theoretical basis for understanding the fracture mechanism of the scaphoid from the perspective of trabecular bone microstructure. At the same time, the trabecular bone structure characteristics of different parts of the scaphoid revealed in this study also provide a theoretical basis for designing targeted internal fixation instruments.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21327
BACKGROUND: Currently, the research on the fatigue elimination effect of hyperbaric oxygen therapy mainly involves two forms: single-session intervention and periodic multiple intervention, with the application research of single therapy being the main focus. However, the effectiveness of single-session hyperbaric oxygen therapy on exercise-induced fatigue remains controversial, affecting its application in sports training. OBJECTIVE: To summarize the intervention effect of a single hyperbaric oxygen therapy on exercise-induced fatigue from two aspects: the commonly used biochemical monitoring indicators and physiological monitoring indicators for exercise-induced fatigue, and proposes corresponding application strategies based on the current research status and training practice. METHODS: A literature search was conducted in Chinese databases (CNKI, Wanfang) and English databases (PubMed) using combinations of keywords such as 'hyperbaric oxygenation', 'micro-barometric oxygen', 'oxygen therapy', 'micro-hyperbaric oxygen' with 'exercise fatigue', 'high intensity exercise', 'heart rate', 'heart rate variability', 'rating of perceived exertion', 'blood urea', 'creatine kinase', 'testosterone', 'cortisol', 'white blood cell', 'hemoglobin'. The search period was from January 2001 to June 2025, and 62 articles were finally included for review. RESULTS AND CONCLUSION: (1) Single-session hyperbaric oxygen intervention can promote the elimination of exercise-induced fatigue, but its intervention effect on commonly used physiological monitoring indicators is better than that on biochemical indicators. The differences in fatigue type and fatigue degree (differences in fatigue induction protocols), insufficient dosage of hyperbaric oxygen, and metabolic characteristics of biochemical indicators in the body may be the main factors causing this issue. (2) In view of the current research status, it is recommended that future research should be conducted in the following directions: 'comprehensively comparing the advantages and disadvantages of different hyperbaric oxygen modes', 'deeply comparing the intervention effects of different hyperbaric oxygen intervention times on exercise-induced fatigue', 'clarifying the intervention effect of single-session hyperbaric oxygen therapy during non-acute exercise fatigue period', and 'establishing a comprehensive evaluation index system for the intervention effect of hyperbaric oxygen'.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21474
BACKGROUND: The tendon suturing technique for the hand has been continuously innovated with the development of biomechanics, minimally invasive techniques, and regenerative medicine. Over the past two decades, research has focused on optimizing traditional suturing techniques and the application of new repair materials, improving the effectiveness of tendon repair and the level of functional recovery in the hand. OBJECTIVE: To assess the global research status and development trends of hand tendon repair techniques over the past two decades through bibliometric analysis, identify research hotspots and their evolution. METHODS: Relevant literature was selected from the Web of Science database from 2005 to 2024, and bibliometric methods were employed for analysis. Data were organized using Microsoft Excel and analyzed for publication trends using the R language Bibliometrix package. VOSviewer was used to visualize keyword co-occurrence and collaboration networks, while CiteSpace was utilized to identify research hotspots and their temporal evolution. RESULTS AND CONCLUSION: Over the past two decades, research in the field of tendon suturing has shown a fluctuating growth trend. The United States, China, and Europe are the main contributing countries, with the United States occupying a central position in the global research network. Research on flexor tendon repair mainly focuses on biomechanics and the development of new repair materials, while extensor tendon research emphasizes postoperative functional recovery and complex injury repair. In recent years, biomaterials and regenerative medicine have gradually become research hotspots, promoting the application of precision medicine in tendon repair. In the future, interdisciplinary collaboration and the combination of advanced materials will further optimize hand tendon repair techniques.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21390
BACKGROUND: Lunge exercises are often used in strengthening programs for patellofemoral pain syndrome and have been shown to help strengthen the quadriceps. However, limited data exist to evaluate the effects of lunge exercises with medial or lateral resistance on patellofemoral joint stress and lower limb muscle activation. OBJECTIVE: To compare the effect of three lunge exercises (traditional lunge, lunge with hip adduction resistance, and lunge with hip abduction resistance) on lower limb muscle activation and patellofemoral joint stress in subjects with patellofemoral pain syndrome and health control group. METHODS: Totally 29 subjects with patellofemoral pain syndrome and 29 healthy subjects completed three different lunge exercises. Lower limb dynamics and electromyography data were simultaneously acquired using an infrared motion capture system, a three-dimensional force table, and a surface electromyography analyzer. A mixed-design analysis of variance was used to determine the effects of group and exercise on patellofemoral joint stress and lower limb muscle activation characteristics during different lunge exercises. RESULTS AND CONCLUSION: (1) During the squatting phase, the vastus lateralis muscle activation was significantly lower in both groups during the lunge exercises with hip adduction (P < 0.05), while the vastus medialis/vastus lateralis activation ratio was significantly increased in the healthy group (P < 0.05). In the patellofemoral pain syndrome group, the gluteus medius activation was significantly increased (P < 0.05) and the peak patellofemoral joint stress was significantly reduced (P < 0.05) during the lunge with hip abduction. (2) During the pushing phase, the vastus lateralis activation was significantly lower in both groups during the lunge with hip abduction (P < 0.05), and the patellofemoral pain syndrome group showed significantly reduced peak patellofemoral joint stress (P < 0.05) and enhanced gluteus medius activation (P < 0.05). In the healthy group, the vastus medialis/vastus lateralis activation ratio was significantly increased during the lunge with hip adduction (P < 0.05), and the patellofemoral pain syndrome group had significantly lower peak patellofemoral joint stress than the healthy group (P < 0.05). (3) These findings suggest that traditional lunge can be one of the preferred training methods for strengthening the quadriceps in the early rehabilitation of patellofemoral pain syndrome. Lunge exercises with lateral adduction/abduction resistance have advantages in improving vastus medialis/vastus lateralis activation imbalance, strengthening gluteus medius activation, and reducing patellofemoral joint stress during squatting, which may help rebuild neuromuscular control of the lower limb kinetic chain in the later rehabilitation stage. For patients with patellofemoral pain syndrome, lunge with lateral abduction resistance is more recommended to alleviate pain and improve function.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21387
BACKGROUND: The magnetic field mitochondrial regulation technology has been proven to enhance skeletal muscle function. Low-load blood flow restriction training can effectively induce adaptive growth of muscle strength through metabolic emergency mechanisms. Currently, both technologies have become hotspots in the application and research of skeletal muscle function improvement and treatment. However, the differences in their effects on muscle strength enhancement and whether their combined application can produce a synergistic effect remain unclear. OBJECTIVE: To observe the differences in the effects of low-frequency pulsed magnetic stimulation (1.5 mT, 3 300 Hz) and low-load blood flow restriction training on muscle strength enhancement and the impact of their combined intervention on lower limb muscle strength. METHODS: Fifty-six healthy subjects were recruited and randomly divided into magnetic stimulation group (high-load squat training + magnetic stimulation), blood flow restriction group (low-load blood flow restriction squat training), combined group (low-load blood flow restriction squat training + magnetic stimulation), and control group (high-load squat training). The trial lasted 4 weeks, with training three times per week, and low-frequency pulsed magnetic stimulation (1.5 mT, 3 300 Hz) was administered every 48 hours. After the trial, changes in maximal strength, explosive power, and strength endurance of the lower limb muscles were observed among groups. RESULTS AND CONCLUSION: Fifty subjects completed the trial and were included in the analysis. ① After 4 weeks of intervention, the maximal strength, explosive power, and strength endurance of the lower limbs in the magnetic stimulation, blood flow restriction, and combined groups significantly increased. ② In terms of maximal strength increase, blood flow restriction was superior to magnetic field mitochondrial regulation technology; low-load blood flow restriction also enhanced distal muscle strength, while magnetic field mitochondrial regulation technology had the advantage of improving maximal strength without fatigue accumulation. ③ In terms of explosive power increase, both technologies had similar effects; magnetic stimulation was more advantageous for explosive power in single-joint movements, while low-load blood flow restriction training was more advantageous for explosive power in multi-joint coordinated movements. ④ In terms of strength endurance increase, magnetic stimulation technology, due to its mitochondrial function regulation, effectively improved muscle fatigue resistance. The results suggest that the combined application of magnetic stimulation and low-load blood flow restriction can produce synergistic effects on maximal strength, explosive power, and strength endurance of the lower limbs. This technical approach may provide a novel and efficient auxiliary training protocol for lower limb muscle strength enhancement in postoperative rehabilitation and sports injury patients who cannot undergo high-intensity resistance training.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21450
BACKGROUND: Ginsenoside Rg3 has potential value in cartilage protection and repair, but its application is limited by poor water solubility, short half-life, and low bioavailability. To improve the pharmacokinetic properties of drugs, embedding drug-loaded liposomes into methylated gelatin, polysaccharide, or silk fibroin-based hydrogels has become a research hotspot in cartilage tissue engineering. OBJECTIVE: To prepare ginsenoside Rg3-loaded liposome methacrylated silk fibroin hydrogel and further analyze its effect on chondrogenic differentiation of mouse bone marrow mesenchymal stem cells. METHODS: (1) Ginsenoside Rg3 liposomes were prepared by thin-film dispersion method. Dil-labeled liposomes were co-cultured with mouse bone marrow mesenchymal stem cells, and phalloidin staining was used to detect cellular uptake of liposomes. Methacrylated silk fibroin (SilMA) was prepared. Ginsenoside Rg3 liposomes were mixed with SilMA and crosslinked by light to prepare composite hydrogel (SilMA@Lipo-Rg3). The microstructure, mechanical properties, rheological properties, swelling properties, and drug release properties of the hydrogel were evaluated. (2) Mouse bone marrow mesenchymal stem cells were cultured with different concentrations of SilMA hydrogel extract or SilMA@Lipo-Rg3 hydrogel extract. CCK-8 assay and live/dead cell staining were used to evaluate cytocompatibility. Cells were cultured with 1/8 concentration of SilMA hydrogel extract or SilMA@Lipo-Rg3 hydrogel extract. After chondrogenic induction, qPCR was used to detect mRNA expression of collagen type II, SOX9, and aggrecan. Alcian blue and safranin O staining were used to detect the expression of proteoglycans and glycosaminoglycans. RESULTS AND CONCLUSION: (1) Phalloidin staining showed that Dil-labeled liposomes could be successfully taken up by mouse bone marrow mesenchymal stem cells. Scanning electron microscopy showed that SilMA@Lipo-Rg3 hydrogel had a loose porous network structure. Compression and rheological tests showed that the compressive stiffness of SilMA@Lipo-Rg3 hydrogel was slightly lower than that of SilMA hydrogel; there was no significant difference in swelling properties between the two hydrogels. SilMA@Lipo-Rg3 hydrogel had good sustained release performance, releasing ginsenoside Rg3 for more than 14 days. (2) CCK-8 assay and live/dead cell staining showed that SilMA and SilMA@Lipo-Rg3 hydrogels had good cytocompatibility. qPCR showed that the mRNA expression of collagen type II, SOX9, and aggrecan in the SilMA@Lipo-Rg3 group was higher than that in the SilMA group (P < 0.05). Alcian blue and safranin O staining showed that the expression of proteoglycans and glycosaminoglycans in the SilMA@Lipo-Rg3 group was higher than that in the SilMA group. These results indicate that SilMA@Lipo-Rg3 hydrogel can promote chondrogenic differentiation of mouse bone marrow mesenchymal stem cells.
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: 10.12307/2026.21475
BACKGROUND: The pathogenesis of steroid-induced osteonecrosis of the femoral head remains unclear; however, it is closely associated with mitochondrial damage in osteoblasts. OBJECTIVE: To explore the impact of dexamethasone on mitochondrial dysfunction in osteoblasts following steroid-induced osteonecrosis of the femoral head and to analyze its regulatory roles in osteoblast apoptosis and autophagy. METHODS: MC3T3-E1 cells were cultured in vitro and divided into control group (no treatment) and dexamethasone group (1 μmol/L dexamethasone treatment for 24 hours). Osteoblast differentiation capacity was assessed by alizarin red staining and qRT-PCR. Mitochondrial morphology was examined using transmission electron microscopy, MitoTracker Red fluorescence staining, and flow cytometry. Mitochondrial membrane potential and energy metabolism were evaluated by JC-1 fluorescence staining and ATP content detection. Mitochondrial superoxide levels were measured using MitoSOX fluorescence probe and flow cytometry. Intracellular total reactive oxygen species and glutathione content were also measured to assess oxidative stress status. Additionally, Western blot and qRT-PCR were used to detect the expression of apoptosis-related proteins (Bax, Bcl-2) and autophagy markers (LC3B, p62), flow cytometry was used to analyze apoptosis rate, and autophagy flux was observed via mRFP-GFP-LC3 adenovirus transfection combined with confocal microscopy. RESULTS AND CONCLUSION: Compared with the control group, the dexamethasone group showed significantly reduced osteogenic differentiation capacity of MC3T3-E1 cells, abnormal mitochondrial structure (swelling, cristae disruption), decreased mitochondrial membrane potential, reduced ATP synthesis, increased mitochondrial superoxide and total reactive oxygen species levels, and increased glutathione consumption (P < 0.05). The dexamethasone group showed significantly upregulated pro-apoptotic protein Bax (P < 0.01), significantly downregulated anti-apoptotic protein Bcl-2 (P < 0.01), increased LC3B-II/I ratio (P < 0.01), and decreased p62 levels (P < 0.01); dexamethasone treatment significantly increased the apoptosis rate (P < 0.01). mRFP-GFP-LC3 adenovirus tracing revealed increased formation of autophagosomes and autolysosomes. These results indicate that dexamethasone induces mitochondrial dysfunction and oxidative stress, synergistically regulating apoptosis and autophagy in MC3T3-E1 cells, thereby impairing bone formation and repair function. This mechanism may be a key pathological basis for the pathogenesis of steroid-induced osteonecrosis of the femoral head.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21619
BACKGROUND: Intraoperative blood loss in hip hemiarthroplasty is reduced with the supercapsular percutaneously assisted total hip approach compared with the posterolateral approach, but the difference in hidden blood loss between the two approaches and the effect of tranexamic acid on it has not been fully investigated. OBJECTIVE: To investigate whether the supercapsular percutaneously assisted total hip approach reduces perioperative hidden blood loss in hip hemiarthroplasty for unstable femoral neck fractures in advanced age compared with the posterolateral approach and to analyze the effect of combined local and intravenous tranexamic acid on it. METHODS: This study retrospectively analyzed a total of 200 elderly unstable femoral neck fracture patients who underwent hip hemiarthroplasty in the Department of Orthopedics, First Affiliated Hospital, Soochow University from January 1, 2020 to December 31, 2024. They were divided into four groups (n=50 per group) according to the surgical approach and whether tranexamic acid was used in the perioperative period: (1) posterolateral approach group; (2) posterolateral approach + tranexamic acid group (combined local and intravenous tranexamic acid); (3) supercapsular percutaneously assisted total hip approach group; (4) supercapsular percutaneously assisted total hip approach + tranexamic acid group (combined local and intravenous tranexamic acid). General data including age, sex, height, weight, and surgical side, as well as preoperative hemoglobin, hematocrit, prothrombin time, activated partial thromboplastin time, and fibrinogen were collected. Hemoglobin and hematocrit were measured on postoperative day 3, and total blood loss and hidden blood loss were calculated. RESULTS AND CONCLUSION: (1) There were no statistically significant differences in preoperative general data among the four groups. (2) The total blood loss and hidden blood loss on postoperative day 3 in the supercapsular percutaneously assisted total hip approach group were significantly lower than those in the posterolateral approach group (P < 0.05). (3) The total blood loss and hidden blood loss in the posterolateral approach + tranexamic acid group were significantly lower than those in the posterolateral approach group without tranexamic acid (P < 0.05). (4) The total blood loss and hidden blood loss in the supercapsular percutaneously assisted total hip approach + tranexamic acid group were significantly lower than those in the supercapsular percutaneously assisted total hip approach group without tranexamic acid (P < 0.05). (5) The incidence of lower extremity venous thrombosis was very low in all groups, with no statistically significant difference among groups. (6) These findings suggest that compared with the traditional posterolateral approach, the supercapsular percutaneously assisted total hip approach for hip hemiarthroplasty in elderly patients with unstable femoral neck fractures can reduce perioperative total blood loss and hidden blood loss; combined local and intravenous tranexamic acid can reduce perioperative blood loss in both traditional and supercapsular percutaneously assisted total hip approaches without increasing the risk of thrombosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21593
BACKGROUND: Intervertebral disc degeneration is a core pathological mechanism of discogenic diseases, characterized by an imbalance in extracellular matrix metabolism. Tissue inhibitors of metalloproteinases, as endogenous antagonists of matrix metalloproteinases, play a crucial role in regulating extracellular matrix homeostasis, but the specific functions of subtypes, signaling pathway interactions, and epigenetic regulatory mechanisms have not been systematically clarified. OBJECTIVE: To review the expression changes, functional heterogeneity, and regulatory networks of tissue inhibitors of metalloproteinases in intervertebral disc degeneration, focusing on the molecular mechanisms and signaling pathways in oxidative stress, mechanical load, and inflammatory microenvironment, and to evaluate the translational potential of gene therapy strategies based on tissue inhibitors of metalloproteinases. METHODS: The first author searched PubMed, Web of Science, Embase, CNKI, Wanfang and other databases from inception to March 2025. Chinese search terms included '椎间盘退变，椎间盘退行性变，椎间盘退化，金属蛋白酶类组织抑制剂，信号通路', and English search terms included 'Tissue Inhibitor of Metalloproteinases, Tissue Inhibitor of Metalloproteinase, TIMPs, Intervertebral disc degeneration, Disc degeneration, Degenerative Disc Disease, Degenerative Intervertebral Discs'. Finally, 76 eligible articles were included for review. RESULTS AND CONCLUSION: (1) Subtype functions of tissue inhibitors of metalloproteinases: TIMP1 exhibits dual regulation (early protection/late depletion); TIMP2 maintains extracellular matrix homeostasis by inhibiting matrix metalloproteinase activity, and its abnormal expression can activate pro-apoptotic signaling pathways (e.g., miR-185-5p/MMP2 axis and inflammatory factor-mediated MMP/TIMP imbalance); TIMP3 exerts multi-dimensional protective effects by inhibiting matrix metalloproteinase activity, tumor necrosis factor-alpha converting enzyme/tumor necrosis factor-alpha axis, and angiogenesis; TIMP4 is regulated by miR-155-5p/fibroblast growth factor 2 and participates in extracellular matrix homeostasis. (2) Epigenetic reprogramming mechanisms: Abnormal mechanical stress degrades TIMP3 mRNA through the WTAP/YTHDF2-m6A axis, while miR-222 targets TIMP3 to synergistically accelerate extracellular matrix degradation. (3) Multi-modal therapeutic strategies: Photobiomodulation (wavelength-specific regulation of TIMP/MMP), stem cell exosomes (miR-199a/GREM1 axis), and irisin intervention can remodel matrix metabolic balance. This review summarizes the theoretical framework of 'functional network imbalance of tissue inhibitors of metalloproteinases', revealing its multi-level regulatory characteristics as a core driver of intervertebral disc degeneration, and providing a theoretical basis for developing precise therapies targeting epigenetic modifications and mechano-biological coupling interventions.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026028
ATP citrate lyase (ACLY) is involved in acetyl-coenzyme A synthesis and protein acetylation, thereby increasing lipid metabolism and altering protein metabolism to affect cellular metabolism. Additionally, ACLY is associated with various biological and pathological functions, especially regarding tumorigenesis. It facilitates the progression of various cancer types, including liver, lung, breast, prostate, and colorectal cancers. Mechanisms underlying ACLY-mediated carcinogenesis are under investigation and may not be limited to energy metabolism and biosynthesis. Acetylation modification of specific signaling molecules and transcription factors is considered a potential mechanism of ACLY-mediated tumorigenesis and offers novel insights and potential targets for the clinical treatment of tumors. Furthermore, the antitumor effect of pharmacological ACLY-inhibiting agents, including various small molecules or naturally active compounds, has been reported, albeit their practical application in clinical settings remains limited. This study aims to comprehensively review the oncogenic role of ACLY, with a focus on major collaborators and regulatory genes.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026035
Pulmonary fibrosis (PF) is a life-threatening interstitial lung disease characterized by scarring and inflammation in lung tissues. Aberrant activation of the JAK/STAT and NF-κB signaling pathways is critical in initiating and sustaining the inflammatory processes that drive fibrotic progression. In this study, we identify a novel small-molecule compound, T4015, a 4-indolyl-2-phenylaminopyrimidine derivative, as a dual-pathway inhibitor targeting both JAK/STAT and NF-κB signaling. Dual-luciferase reporter assays demonstrate the potent inhibitory activity of T4015 against these pathways. T4015 effectively suppresses the phosphorylation of STAT3, JAK1, and TYK2 induced by IL-6 and IFN-β, while suppressing LPS-induced NF-κB activation in macrophages. Transcriptome sequencing and pathway enrichment analyses further confirm that T4015 downregulates multiple inflammation-related signaling cascades, including the JAK/STAT, NF-κB, TNF, IL-17, and Toll-like receptor pathways. In a mouse model of bleomycin-induced PF, T4015 treatment significantly improves survival, attenuates collagen deposition, and reduces the expression of pro-inflammatory and profibrotic markers such as IL-6, CCL2, and COL1. Molecular docking and target prediction analyses suggest that T4015 exhibits strong binding affinity for multiple kinases within the JAK/STAT and NF-κB networks, including JAK1, TYK2, JAK2, JAK3, RIPK1, IRAK1/4, TAB1, and ZAP70. Collectively, these results highlight T4015 as a promising therapeutic candidate for PF through its simultaneous inhibition of the JAK/STAT and NF-κB signaling pathways.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025240
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options due to the absence of hormone receptors and HER2 amplification. Immune checkpoint blockade, particularly targeting PD-1/PD-L1, has emerged as a promising therapeutic strategy. However, the response rate of TNBC patients to this monotherapy remains low. This study explores the systemic effect of PD-1 blockade on the immune and hematopoietic systems in 4T1 TNBC mice and demonstrates its limited efficacy in reducing the tumor burden and changing the number of tumor-infiltrating immune cells. However, PD-1 blockade increases systemic immune activity, as demonstrated by increased T cells and DCs in the peripheral blood, which may be associated with inflammatory side effects of this treatment. In addition, PD-1 blockade does not rescue the hematopoietic damage caused by TNBC, highlighting a limitation in long-term response. Furthermore, PD-1 blockade in tumor-free mice leads to an increase in hematopoietic stem/progenitor cells, suggesting that PD-1 blockade may yield better benefits post-tumor resection.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025070
Diabetes mellitus (DM) is a metabolic and endocrine disorder with a projected global prevalence of 783 million by 2045. Individuals with type 2 diabetes face a 20–60% elevated risk of cognitive dysfunction, yet therapeutic options remain limited. This study investigates the efficacy of Schisandrin A (SchA), a bioactive lignan from Schisandra chinensis, in a streptozotocin-induced diabetic rat model. Rats were randomized into control, DM, DM+SchA, and Con+SchA groups. SchA treatment improved insulin sensitivity, reduced blood glucose, and significantly attenuated fear memory impairment. Histological analysis revealed decreased prefrontal cortex damage, enhanced synaptic protein expression, and reduced Aβ42 formation. Mechanistically, SchA suppressed microglial activation and inflammatory markers while increasing phosphorylation of insulin resistance pathway proteins. Furthermore, SchA mitigated ferroptosis by upregulating GPX4, SLC7A11, Nrf2, HO-1, and SIRT1 in the diabetic prefrontal cortex. These findings suggest that SchA alleviates diabetes-associated memory impairment by concurrently reducing neuroinflammation and ferroptosis, positioning SchA as a potential therapeutic agent for diabetes-related cognitive decline.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025044
The generation of genetically edited pigs via somatic cell nuclear transfer (SCNT) has historically relied on plasmid-based CRISPR/Cas9 systems, which introduce resistance genes, risk off-target effects from prolonged editing, and require 3–4 weeks of in vitro selection. This study presents a transgene-free, rapid strategy using the IRE-DSRNP method to edit monoclonal porcine fetal fibroblasts. Three IgA-knockout cell lines were obtained with large deletions in the CH1-CH3 region: 1044 bp (heterozygous), 1043 bp (homozygous), and 1039 bp (homozygous). These cells were pooled and used as donor nuclei for SCNT. From 880 fresh oocytes, 660 mature oocytes were selected, 500 underwent enucleation and nuclear transfer, yielding 400 fused cells; 300 embryos were transplanted into a surrogate sow. Pregnancy was confirmed at 28 days, and after 143 days of gestation, six F0 piglets were born. Genotyping revealed two heterozygotes (4010#, 4015#) and four homozygous knockouts, with two piglets per genotype (1044, 1043, 1039 bp deletions). This approach eliminates plasmid integration, reduces off-target risks, and shortens the timeline for producing IgA-deficient Bama pig models, offering a robust platform for disease modeling and xenotransplantation research.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025096
Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive bone disorder driven by prolonged glucocorticoid exposure, with limited therapeutic options. Ferroptosis, a regulated form of necrosis, has emerged as a potential contributor to SONFH pathogenesis, yet its mechanistic link to osteoblast dysfunction remains poorly defined. This study investigates the relationship between dexamethasone (Dex)-induced ferroptosis and silent information regulator 1 (Sirt1) in MC3T3-E1 osteoblastic cells. Dex treatment downregulated Sirt1 expression and increased ferroptosis markers, while Sirt1 overexpression elevated the ferroptosis-related proteins SLC7A11 and GPX4 following Dex exposure. Mechanistically, Dex promoted hypermethylation of the Sirt1 promoter via DNA methyltransferase 3a (DNMT3a), leading to Sirt1 suppression. These findings establish a novel epigenetic axis—DNMT3a-mediated Sirt1 promoter hypermethylation—that drives Dex-induced ferroptosis in osteoblasts. The study was conducted exclusively in vitro, and the pathophysiological relevance requires validation in animal models. Nevertheless, this work provides a foundation for understanding the epigenetic regulation of osteoblast ferroptosis and suggests potential therapeutic avenues for preventing SONFH.
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.