Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpbjnl/qzae037
This is a correction to: Feng Xu, Yifan Wang, Yunchao Ling, Chenfen Zhou, Haizhou Wang, Andrew E. Teschendorff, Yi Zhao, Haitao Zhao, Yungang He, Guoqing Zhang, Zhen Yang, dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms, Genomics, Proteomics & Bioinformatics, Volume 20, Issue 3, June 2022, Pages 446–454, https://doi.org/10.1016/j.gpb.2022.04.006. The published version of this manuscript contained errors in the author affiliation listings. The corrected affiliations are as follows: Feng Xu1,#, Yifan Wang2,#, Yunchao Ling2, Chenfen Zhou2, Haizhou Wang1, Andrew E. Teschendorff3, Yi Zhao4, Haitao Zhao5, Yungang He6,*, Guoqing Zhang2,*, Zhen Yang1,* 1 Center for Medical Research and Innovation of Pudong Hospital, Fudan University Pudong Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China 2 Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China 3 CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China 4 Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China 5 Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China 6 Shanghai Fifth People’s Hospital, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China These details have been corrected only in this correction notice to preserve the published version of record.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04549-2
Adipose-derived stem cells (ADSCs) are a specific type of mesenchymal stem cells (MSCs) obtained easily from adipose tissue (AT). Compared with MSCs, ADSCs are easier to obtain, have fewer ethical issues, and have a higher proliferative capacity, which makes them a promising type of stem cell in regenerative medicine. ADSCs possess impressive capabilities in cell regeneration as well as differentiation, making them promising candidates for injury repair, tissue regeneration and alleviation of inflamed tissues. At present, most clinical studies on ADSCs focus on the treatment of wounds, multiple sclerosis, soft tissue trauma, aging, diabetes, Parkinson’s disease, bone and cartilage regeneration, stroke, and spinal cord injury, while its clinical applications in the gastrointestinal tract are relatively few. Therefore, this review summarizes the findings of preclinical experiments, clinical trials, and areas that may require further development of ADSCs in the treatment of digestive disorders, including inflammatory bowel disease (IBD), colorectal cancer (CRC), colorectal fibrosis, hepatocellular carcinoma, hepatic fibrosis, gastric cancer (GC), gastrostomy closure and radiation-induced proctitis. The review is concluded by discussing the goals for improvement and future directions for ADSCs before large-scale clinical application.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04463-7
Background: Recent advances in clinical trials have involved the transplantation of induced retinal pigment epithelium (iRPE) cells from stem cells in creating a functional monolayer that mimics the characteristics of natural adult RPE cells. One method of achieving this goal is through the use of tissue engineering. In this research, decellularised femtosecond laser intrastromal lenticules (dfLEN) were employed as a scaffold for cultivating a bioengineered iRPE monolayer sheet. Methods: iRPE cells were obtained by differentiating induced pluripotent stem cells (iPSC). These cells were then seeded on decellularized FLI-lenticules (dfLEN). The functionality, characterization, and oxidative stress of iRPE cultured on dfLEN were compared with those cultured on plates (TCP) using various assays such as immunofluorescence (IF), Edu, CCK8, ELISA, DFCH-DA, and JC-1. Additionally, RNA-seq assays and electron microscope (SEM and TEM) were used to test the iRPE characteristic on engineered dfLEN. Finally, we evaluated the biocompatibility of iRPE-dfLEN sheets by transplanting them into the subretinal space of New Zealand white rabbits. Results: The iRPE cells cultured on dfLEN exhibited morphology and physiology similar to that of native RPE tissue. The dfLEN not only increased the resistance capacity of iRPE cells but also improved their functional properties compared to TCP. In addition, our results indicate that dfLEN enhances the expression of genes associated with cilium assembly, resulting in notable improvements in ciliogenesis in iRPE cells. Finally, the dfLEN-iRPE sheets demonstrated favorable biocompatibility and some viability when transplanted into the subretinal space of rabbits for a period of 14 days.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04245-1
Background Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral arterial disease (PAD). Mesenchymal stem cell (MSC) transplantation holds promise as a treatment for CLTI; however, the harsh local environment poses challenges to its effectiveness. Apoptotic vesicles (ApoVs) are extracellular vesicles produced by cells undergoing apoptosis, and they can carry various biomolecules from their parent cells, including proteins, RNA, DNA, lipids, ions, and gas neurotransmitters. ApoVs play significant roles in anti-inflammatory responses, anti-tumor activities, and tissue regeneration through intercellular communication, and they have demonstrated potential as drug carriers. In this study, we investigated the potential of bone marrow stem cell (BMSC)-derived ApoVs for treating CLTI. Methods In vivo, we explored the therapeutic effect of ApoVs on a hindlimb ischemia model through Laser Doppler, matrigel plug assay, and histological analysis. In vitro, we analyzed the effects of ApoVs on the proliferation, migration, and angiogenesis of HUVECs and explored the uptake process of ApoVs. In addition, Proteomic analysis, western blotting, quantitative real-time PCR, shRNA, and siRNA were used to analyze ApoVs-induced HUVECs activation and downstream signaling pathways. Results BMSCs transplantation showed improvement in a hind limb ischemia model, and this effect still exists after apoptosis of BMSCs. Subsequently, ApoVs of BMSCs were isolated and found to improve mouse hind limb ischemia in vivo. In vitro, ApoVs can be ingested by HUVECs through dynamin-, clathrin-, and caveolin-mediated endocytosis and promote its proliferation, migration, and angiogenesis. Mechanistically, ApoVs transferred NAMPT to HUVECs, therefore activating the NAMPT/SIRT1/FOXO1 axis, influencing the transcriptional activity of FOXO1, and promoting angiogenesis. Conclusions Our results demonstrate that the transplanted BMSCs can ameliorate hindlimb ischemia by releasing ApoVs during apoptosis. The main mechanism of this effect is promoting the proliferation, migration, and angiogenesis of endothelial cells via the NAMPT/SIRT1/FOXO1 axis.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04229-1
Background Despite numerous studies addressing the molecular mechanisms by which pluripotent stem cells (PSCs) maintain self-renewal and pluripotency under normal culture conditions, the fundamental question of how PSCs manage to survive stressful conditions remains largely unresolved. Post-transcriptional/translational regulation emerges to be vital for PSCs, but how PSCs coordinate and balance their survival and differentiation at translational level under extrinsic and intrinsic stress conditions is unclear. Methods The high-throughput sequencing of cross-linking immunoprecipitation cDNA library (HITS-CLIP) was employed to decipher the genome-wide OCT4-RNA interactome in human PSCs, a combined RNC-seq/RNA-seq analysis to assess the role of OCT4 in translational regulation of hypoxic PSCs, and an OCT4-protein interactome to search for OCT4 binding partners that regulate cap-independent translation initiation. By taking the Heterozygous Knocking In N-terminal Tags (HKINT) approach that specifically disrupts the 5'-UTR secondary structure and tagging its protein product of the mRNA from one allele while leaving that from the other allele intact, we examined the effect of disrupting the OCT4/5'-UTR interaction on translation of AKT1 mRNA. Results We revealed OCT4 as a bona fide RNA-binding protein (RBP) in human PSCs that bound to the 5'-UTR, 3'-UTR and CDS regions of mRNAs. Multiple known proteins participating in IRES-mediated translation initiation were detected in the OCT4-protein interactome, and a combined RNC-seq/RNA-seq analysis further confirmed a crucial role of OCT4 in translational regulation of PSCs in response to hypoxic stress. Remarkably, OCT4 bound to the GC-rich elements in the 5'-UTR of AKT1 and multiple PI3K/AKT-pathway-gene mRNAs, and promoted their translation initiation via IRES-mediated pathways under stress conditions. Specifically disrupting the AKT1 mRNA 5'-UTR structure and the OCT4/5'-UTR interaction by the HKINT approach significantly reduced the translation level of AKT1 that led to a higher susceptibility of PSCs to oxidative stress-induced apoptotic death and prioritized differentiation toward ectoderm and endoderm. Conclusions Our results reveal OCT4 as an anti-stress RBP for translational regulation that critically coordinates the survival and differentiation of PSCs in response to various stressors.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04751-2
Background Sepsis survivors frequently develop compromised humoral immunity, manifesting as prolonged immunosuppression that increases susceptibility to secondary infections with high associated mortality. While mesenchymal stromal cells (MSCs) have demonstrated efficacy in mitigating initial inflammatory responses and improving early survival rates in murine cecal ligation and puncture (CLP) models, they show limited effectiveness against subsequent secondary infections. Given that lymphopenia represents a primary driver of this infection vulnerability, we sought to investigate whether spleen-targeted MSC therapy could prevent lymphocyte depletion and enhance protection against secondary infections. Methods In this study, we developed CXCR5-overexpressing MSCs (MSCCXCR5) to enhance their targeted migration toward splenic CXCL13. Using a CLP mouse model followed by secondary Staphylococcus aureus (S. aureus) infection, we systematically evaluated the therapeutic potential of MSCCXCR5 in combating post-sepsis immunosuppression. Results MSCCXCR5 demonstrated enhanced splenic migration, specifically homing to CXCL13-rich B-cell zones, and conferred significant protection against both S. aureus secondary infection and sepsis-induced lymphopenia. Mechanistic investigations revealed that MSCCXCR5 treatment preserved follicular and germinal center B-cell populations, maintaining splenic architecture and potentiating antigen-specific B-cell responses to CLP challenge. These effects collectively contributed to markedly improved survival outcomes in CLP mice following secondary infection. Conclusion Our findings demonstrate that MSCCXCR5 confers dual-phase protection in sepsis, improving survival during both the initial hyperinflammatory phase and subsequent immunosuppressive period. This comprehensive
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04475-3
Background: Mitochondrial DNA (mtDNA) deletion and oxidative stress are key contributors to skin photoaging. Mitophagy helps mitigate oxidative stress. Human adipose-derived stem cell exosomes (hADSC-Exos) have been shown to counteract skin photoaging. This study aimed to explore the role and mechanism of hADSC-Exos in addressing skin photoaging. Methods: hADSC-Exos were isolated, and their surface markers were identified. Human dermal fibroblasts (HDFs) and nude mice were exposed to ultraviolet-B (UVB) irradiation, and treated with hADSC-Exos. Oxidative stress and photoaging were assessed through SA-β-gal staining, p21 expression, mtDNA deletion, reactive oxygen species (ROS) levels, and histological analysis. The PINK1, Parkin, LC3b, and p62 protein levels were measured to evaluate mitophagy. The PINK1 small-interfering RNA (siPINK1) was then used in HDFs to investigate the role of hADSC-Exos in mitophagy. Results: In UVB-exposed HDFs and nude mice, the number of SA-β-gal-positive cells, along with levels of p21, ROS, and mtDNA deletion, were significantly increased, but these effects were reduced by hADSC-Exos. Moreover, hADSC-Exos treatment significantly elevated PINK1 and Parkin levels, as well as the LC3bII/I ratio, while reducing p62 expression. In photoaged HDFs treated with hADSC-Exos, PINK1 knockout using siRNA decreased the LC3bII/I ratio and levels of PINK1 and Parkin, while increasing p62, ROS, and mtDNA deletion compared to the negative control (NC) group. Conclusion: hADSC-Exos can mitigate skin photoaging by promoting PINK1/Parkin-mediated mitophagy, thereby reducing mtDNA deletion and oxidative stress.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04788-3
End-stage liver disease (ESLD) is one of the predominant diseases contributing to high morbidity and mortality worldwide, with etiologies including alcoholic liver disease, viral hepatitis, non-alcoholic fatty liver disease, and metabolic-associated liver disease. Currently, liver transplantation remains the only effective treatment, however, its clinical application is significantly limited by donor shortages, immune rejection, and high medical costs. Among the five types of stem cells that have been experimentally applied to liver diseases, mesenchymal stem cells (MSCs) have emerged as the most extensively studied, with the largest number of experimental and clinical research platforms worldwide. This review compiles findings from 25 preclinical and clinical studies on MSCs in the treatment of ESLD, aiming to elucidate the core mechanisms of action and then outline both the challenges in MSC clinical translation and the novel opportunities arising from cutting-edge research.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04203-x
Background Mesenchymal stem cell (MSC) -derived exosomes, especially adipose-derived mesenchymal stem cell exosomes (ADSC-Exos), have emerged as a promising alternative for skin damage repair with anti-inflammatory, angiogenic and cell proliferation effects while overcoming some of the limitations of MSC. However, the mechanism by which ADSC-Exos regulates inflammatory cells during wound healing remains unclear. This study investigated how ADSC-Exos regulate macrophages to promote wound healing. Methods ADSC-Exos were isolated using ultracentrifugation, with subsequent quantification of exosomes particle number. To investigate their role in wound healing, the effects of ADSC-Exos on inflammation, angiogenesis, collagen deposition and macrophage polarization were evaluated through immunohistochemical staining, immunofluorescence and western blotting. Changes in gene expression associated with ADSC-Exos-induced macrophage polarization were analyzed using qPCR. RNA sequencing was performed to identify differentially expressed genes affected by ADSC-Exos. The critical role of IL-33 in the wound healing process was further confirmed using Il33−/− mice. Additionally, co-culture experiments were conducted to explore the effects of IL-33 on keratinocyte proliferation, collagen deposition and epithelialization. Results ADSC-Exos inhibited the expression of TNF-α and IL-6, induced M2 macrophage polarization, promoted collagen deposition and angiogenesis, and accelerated wound healing. RNA sequencing identified IL-33 as a key mediator in this process. In Il33−/− mice, impaired wound healing and decreased M2 macrophage polarization were observed. The co-culture experiments showed that IL-33 enhanced keratinocyte function through activation of the Wnt/β-catenin signaling pathway. These findings highlight the therapeutic potential of ADSC-Exos in wound healing by modulating IL-33. Conclusions ADSC-Exos promote wound healing by regulating macrophage polarization and enhancing IL-33 release which drives keratinocyte proliferation, collagen deposition and epithelialization via the Wnt/β-catenin
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04145-4
Background Asthma is a prevalent respiratory disease, and its management remains largely unsatisfactory. Mesenchymal stem cells (MSCs) have been demonstrated to be efficacious in reducing airway inflammation in experimental allergic diseases, representing a potential alternative treatment for asthma. Migrasomes are recently identified extracellular vesicles (EVs) generated in migrating cells and facilitate intercellular communication. The objective of this study was to investigate the therapeutic effects of migrasomes obtained from MSC in a model of asthma. Methods Migrasomes produced by human umbilical cord MSCs (hUCMSCs) were isolated by sequential centrifugation. Characterization of hUCMSC-derived migrasomes were carried out by transmission electron microscopy and western blot analysis. The therapeutic effects of migrasomes on airway inflammation in ovalbumin (OVA)-induced asthmatic mice were evaluated by hematoxylin-eosin (HE) and periodic-acid schiff (PAS) staining, and their mechanism were further testified by immunofluorescent staining, real-time PCR and flow cytometry. Results Here, we showed that inhibition of migrasomes’ production dramatically impaired the anti-inflammatory effects of hUCMSCs in OVA animals, as evidenced by a notable increase in both the infiltration of inflammatory cells and the number of epithelial goblet cells. We successfully isolated hUCMSC-migrasomes, which were morphologically intact and positive for the specific migrasomes markers. The administration of hUCMSC-migrasomes was observed to significantly ameliorate the symptoms of airway inflammation and mucus production in asthmatic mice. Additionally, the expression of Th2 cytokines (IL-4, IL-5 and IL-13) were found to be reduced, while the activation of dendritic cells (DCs) was inhibited. HUCMSC-migrasomes could possibly be delivered to lung region after injection, and were able to be taken in by DCs both in vivo and in vitro. Notably, in vitro, migraosmes decreased the capacity of
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03844-8
Background The leading cause of end-stage renal disease (ESRD) is diabetic nephropathy (DN). Podocyte damage is an early event in the development of DN. Currently, there is no effective treatment strategy that can slow the progression of DN or reverse its onset. The role of mesenchymal stem cells (MSCs) transplantation in diabetes and its complications has been extensively studied, and diabetic nephropathy has been a major focus. Irbesartan exerts reno-protective effects independent of lowering blood pressure, can reduce the incidence of proteinuria in rats, and is widely used clinically. However, it remains undetermined whether the combined utilization of the angiotensin II receptor antagonist irbesartan and MSCs could enhance efficacy in addressing DN. Methods A commonly used method for modeling type 2 diabetic nephropathy (T2DN) was established using a high-fat diet and a single low-dose injection of STZ (35 mg/kg). The animals were divided into the following 5 groups: (1) the control group (CON), (2) the diabetic nephropathy group (DN), (3) the mesenchymal stem cells treatment group (MSCs), (4) the irbesartan treatment group (Irb), and (5) the combined administration group (MSC+Irb). MSCs (2×10^6 cells/rat) were injected every 10 days through the tail vein for a total of three injections; irbesartan (30 mg/kg/d) was administered by gavage. Additionally, the safety and homing of mesenchymal stem cells were verified using positron emission tomography (PET) imaging. Results The combination treatment significantly reduced the UACR, kidney index, IGPTT, HOMA-IR, BUN, serum creatine, and related inflammatory factor levels and significantly improved renal function parameters and the expression of proteins related to glomerular podocyte injury in rats. Moreover, MSCs can homing target to damaged kidneys. Conclusions Compared to the administration of MSCs or irbesartan alone, the combination of MSCs and irbesartan exerted better protective effects on glomerular podocyte injury, providing new ideas for the clinical application of mesenchymal stem cells.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026054
The anti-inflammatory properties of the traditional herb Salvia miltiorrhiza Bunge are well-established, yet its precise mechanism of action in ulcerative colitis (UC) remains unclear. Herein, we evaluate the therapeutic potential of four major tanshinones–tanshinone IIA (Tan IIA), miltirone, neocryptotanshinone, and dihydrotanshinone I–in a murine dextran sulfate sodium (DSS)-induced colitis model. Our results show that tanshinones effectively alleviate disease severity, suppress systemic and local inflammation, and restore intestinal barrier integrity. Integrated multi-omics analysis reveals that the therapeutic efficacy originates from a comprehensive reprogramming of the gut microbiota-metabolite axis. Specifically, tanshinones reverse colitis-associated dysbiosis and rectify metabolic disturbances in linoleic acid metabolism, bile acid biosynthesis, and amino acid utilization. Correlation network analysis identifies key functional modules linking beneficial microbes (e.g., Akkermansia) to anti-inflammatory lipid mediators and associating pathobionts (e.g., Desulfovibrio) with disrupted bile acid metabolism. Notably, supplementation with Akkermansia muciniphila synergizes with Tan IIA to amplify barrier restoration and metabolic normalization. Our findings establish that tanshinones ameliorate UC through microbiota-driven metabolic reprogramming, wherein the restructured microbial community actively shapes a therapeutic metabolic output. This work elucidates a metabolite-mediated mechanism of action and positions tanshinones as promising microbiome-targeting therapeutics for inflammatory bowel disease.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025223
The clinical use of doxorubicin (DOX) as a chemotherapeutic agent is limited by its cardiotoxic effects. Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, has been increasingly recognized as an important regulator of cardiovascular disease. However, its role in doxorubicin-induced cardiotoxicity remains unknown. Therefore, the objective of this study is to investigate the role and mechanism of FGF13 in doxorubicin-induced cardiac injury. C57BL/6 mice are used to establish Dox-induced cardiotoxicity models. The results reveal that mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening are decreased in the DOX group. In contrast, Fgf13 deficiency mitigates doxorubicin-mediated cardiotoxicity, as indicated by increased mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening. Mechanistically, the protein expressions of bax and cleaved caspase 3 are elevated in the DOX-treated group, along with decreased JC-1 fluorescence intensity and bcl-2 expression, whereas Fgf13 knockout prevents these alterations. In addition, Parkin, but not p53, interacts with FGF13 and is upregulated in response to Fgf13 deficiency in a mouse model of doxorubicin-induced cardiotoxicity. Overall, Fgf13 knockout attenuates doxorubicin-induced cardiomyocyte apoptosis and mitochondrial damage through the modulation of Parkin, indicating that FGF13 may serve as a promising therapeutic target for DOX-induced cardiotoxicity.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024215
A better understanding of how sympathetic nerves impact pancreatic function is helpful for understanding diabetes. However, there is still uncertainty and controversy surrounding the roles of sympathetic nerves within the pancreas. To address this, we utilize high-resolution imaging and advanced three-dimensional (3D) reconstruction techniques to study the patterns of sympathetic innervation and morphology in the islets of adult wild-type (WT) and diabetic mice. Our data show that more than ~30% of α/β-cells are innervated by sympathetic nerves in both WT and diabetic mice. Additionally, sympathetic innervated α/β-cells are reduced in diet-induced obese (DIO) mice, whereas sympathetic innervated β-cells are increased in db/db mice. In addition, in situ chemical pancreatic sympathetic denervation (cPSD) improves glucose tolerance in WT and db/db mice but decreases glucose tolerance in DIO mice. In situ cPSD also enhances insulin sensitivity in diabetic mice without affecting WT mice. Overall, our findings advance our understanding of diabetes by highlighting the distinctive impact of pancreatic sympathetic innervation on glucose regulation.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025171
Obesity-induced metabolic inflammation is a key driver of chronic kidney disease (CKD), with immune dysregulation, particularly among lymphocytes, contributing to early disease pathology. To explore the role of apolipoprotein A4 (Apoa4) in regulating immune cell metabolism and function, we establish high-fat diet-induced obese (DIO) models using wild-type and Apoa4-knockout (KO) mice. KO mice exhibit exacerbated insulin resistance and renal lipid accumulation. Single-cell RNA sequencing reveals that Apoa4 deletion remodeled the renal immune-metabolic landscape. This remodeling broadly compromises the immune functions of T, NK, and B cells, even as it expands the proportions of cytotoxic Gzma+ NK cells and Derl3+ plasma cells. Mechanistically, Apoa4 deletion aggravates metabolic dysregulation and oxidative stress and downregulates the expression levels of key effector genes, including Ifng and Il1b. Furthermore, the regulatory network activities of key transcription factors, such as Lef1 and Runx3 in Cd8+ T cells; Irf8, T-bet, and Eomes in NK cells; and Tcf4, Lmo2, and Xbp1 in B cells, are perturbed. CellChat analysis predicts disruptions in pro-inflammatory (IFN-II and IL-1), immunoregulatory (FASLG), and metabolic regulatory (ENHO and ANGPTL) signaling, alongside enhanced IL-2-mediated suppression. These findings are corroborated by flow cytometry, immunofluorescence staining, and qPCR. Our results establish Apoa4 as a crucial regulator of lymphocyte metabolic and immune homeostasis in the early stages of obesity-associated CKD.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025233
This is a corrigendum to the article 'Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness by activating the TGF-β/Smad signaling pathway in breast cancer cells' published in Acta Biochim Biophys Sin 54: 1587–1598. The authors identified inaccuracies in the preparation of several figures (Figure 2D, 4A, and 5A) and have replaced them with corrected versions. The errors are strictly confined to figure presentation and do not impact the underlying data, statistical analysis, or main conclusions. The authors apologize for the oversight.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025121
Carfilzomib (Cfz) is a second-generation proteasome inhibitor approved for the treatment of relapsed/refractory multiple myeloma (RRMM). Previous studies have shown that Cfz is associated with a higher incidence of severe adverse cardiac effects than bortezomib (Btz); however, the underlying mechanisms remain to be elucidated. The aim of this study is to identify key regulators of cardiotoxicity induced by Cfz and to investigate the mechanisms by which these factors exert their effects. We establish a mouse model of cardiac toxicity induced by Cfz and confirm the phenotype through cardiac functional analysis, morphology assessment, myocardial fibrosis, and apoptosis analysis. We subsequently perform RNA sequencing to identify differentially expressed genes (DEGs) and further validate their functions and mechanisms. We find that Cfz induces myocardial hypertrophy and myocardial injury, along with the suppression of SENP1 expression in mouse heart tissues and in vitro cultured neonatal rat cardiomyocytes. Suppression of SENP1 exacerbates Cfz-induced injury and remodeling in cardiomyocytes by directly binding to and deconjugating the SUMO1-mediated SUMOylation of the RNA helicase DDX17. This process leads to a reduction in K-48 ubiquitin-linked polyubiquitination and degradation of DDX17, resulting in increased expressions of anti-apoptotic genes and maintenance of mitochondrial homeostasis. Therefore, the overexpression of SENP1 using AAV vectors alleviates Cfz-induced cardiotoxicity in mice. In summary, our findings reveal a previously unknown role of the SENP1-DDX17 axis in protecting against cardiotoxicity induced by Cfz, providing a potential foundation for developing therapeutic strategies to mitigate cardiac side effects in the clinical management of MM patients.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024208
Escherichia coli is widely used in industrial chemical synthesis but faces significant challenges due to bacteriophage contamination, which reduces product quality and yield. Therefore, developing an efficient antiphage system is essential. In this study, we develop a CRISPR-Cas9-based antiphage system (CAPS) targeting essential genes of the T7 phage (gene 5 and gene 19) with single gRNAs transformed into MG1655 strains expressing Cas9. While CAPS provides limited resistance, with plating efficiencies ranging from 10–5 to 10–1, further optimization is needed. To enhance efficacy, we design a double-site-targeting CRISPR-Cas9-based antiphage system (D-CAPS). D-CAPS demonstrates complete resistance, with no plaques observed even at a high multiplicity of infection (MOI of 2), and growth curve analysis reveals that antiphage E. coli strains grow normally, similar to the wild-type strain, even at a high multiplicity of infection. Furthermore, D-CAPS is effective against BL21(DE3) strains, showing strong resistance and demonstrating its versatility across different E. coli strains. Protein expression analysis via green fluorescent protein confirms that E. coli carrying D-CAPS could maintain normal protein expression levels even in the presence of phages, comparable to wild-type strains. Overall, D-CAPS offers a robust and versatile approach to enhancing E. coli resistance to phages, providing a practical solution for protecting industrial E. coli strains and improving fermentation processes.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025135
Despite the high efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL), approximately 10%–20% of patients develop drug resistance due to mutations in PML-RARα and other factors. Here, we find that inhibition of USP2 with ML364 or USP2 silencing reduces PML-RARα protein levels in both ATRA-sensitive and ATRA-resistant APL cells, and this effect is reversed by proteasome inhibition. Conversely, USP2 overexpression enhances PML-RARα stability. Mechanistically, USP2 interacts with and deubiquitinates PML-RARα, including its drug-resistant mutants. Consistent with PML-RARα degradation, ML364 treatment significantly induces apoptosis in APL cell lines and primary leukemia cells. In conclusion, this study identifies USP2 as a novel deubiquitinating enzyme for PML-RARα and highlights USP2 inhibition as a potential therapeutic strategy for APL with PML-RARα mutations.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025104
Non-viral episomal vectors offer a safe and attractive alternative to viral and integrated vectors by avoiding insertional mutagenesis and position effects, making them ideal expression vectors for gene therapy. The first non-viral episomal vector, pEPI-1, which is based on the full-length scaffold/matrix attachment region (S/MAR), was established by Piechaczek et al. The full-length S/MAR element interacts with the nuclear matrix via the matrix protein, e.g. SAF-A, thereby maintaining mitotic stability and transgene expression. Several strategies, including optimization of the vector backbone and promoter and incorporation of chromatin-modifying elements, have been used to increase expression levels and stability. In our previous work, we constructed the novel vector pEGFP-C1-M on the basis of S/MAR characteristic motifs (only 375 bp). This vector, which is shorter than the prototype episomal vector pEPI-1, resulted in relatively higher transgene expression. Building on the pEGFP-C1-M vector, we further constructed the episomal vector pEMEα with the EF-1α promoter and demonstrated that pEMEα maintained higher transgene expression, stability and copy number. The transgene expression levels of episomal vectors are correlated with gene copy number, that is, the number of plasmid episomes on the host cell chromosome. Previous studies have shown that the episomal maintenance of pEPI-1 vectors is mediated primarily by SAF-A. While the role of SAF-A in maintaining mammalian pEPI-1 episomal vectors has been well established, it remains unknown whether the overexpression of SAF-A promotes transgene expression and stability and whether the 375 bp MAR characteristic sequence retains its interaction with SAF-A. In the present study, we first evaluated whether transgene expression is positively correlated with the expression level of SAF-A. The non-viral episomal vector pEMEα was used as the gene of interest (GOI) vector and was subsequently transfected into CHO-K1 cells using the Lipofectamine 2000 reagent. The cells were cultured in medium containing 800 μg/mL geneticin (G418) 48 h post-transfection, and the G418 concentration was then reduced to 400 μg/mL to obtain monoclonal cell lines using the limiting dilution method. Five monoclonal cell clones were selected, and the eGFP expression levels, measured as the mean fluorescence intensity (MFI), were (6.5 ± 1.0) × 104, (6.8 ± 0.9) × 104, (7.0 ± 1.4) × 104, (23.5 ± 1.2) × 104 and (14.9 ± 0.17) × 104 for Clones 1–5, respectively. qPCR analysis of Clones 1–5 revealed that the relative mRNA levels of SAF-A and eGFP were 0.16 ± 0.13, 0.43 ± 0.11, 0.46 ± 0.23, 2.17 ± 0.41, 1.78 ± 0.15 and 0.51 ± 0.16, 0.71 ± 0.12, 1.05 ± 0.09, 2.47 ± 0.14, and 1.86 ± 0.10, respectively. Our results indicated that eGFP mRNA and protein expression levels are positively correlated with SAF-A mRNA level. To further verify the relationship between SAF-A expression and transgene expression, two shRNA plasmids targeting SAF-A (shRNA1: 5′-GCCACCTGTTGAAGAAGAAGA-3′, and shRNA2: 5′-GCTGGAGGAAGAGCTTCTTAT-3′) which were obtained from Shanghai GenePharma Co., Ltd. were designed and transfected into stable cell pools with the pEMEα vector. qPCR analysis revealed that the relative SAF-A mRNA levels in the shRNA1 and shRNA2 vectors were 0.47 ± 0.01 and 0.19 ± 0.02, respectively, indicating successful downregulation of SAF-A expression. Moreover, flow cytometry and qPCR revealed that, compared with those in the control group, the relative protein and mRNA levels of eGFP were reduced by 0.47- and 0.23-fold, and 0.47- and 0.40-fold in the pools of cells transfected with the shRNA1 and shRNA2 vectors, respectively. On the basis of the above results, the SAF-A overexpression vector pIRES-SAF-A was constructed and transfected into CHO-K1 cells, and the cells were cultured in blasticidin-containing medium 48 h after transfection to obtain stable cell pools. The stable cell pools overexpressing SAF-A were subsequently transfected with the pEMEα vector. Stable cell pools coexpressing SAF-A and GOI were selected, and the relative mRNA levels of SAF-A and eGFP were analyzed. qPCR analysis revealed that the relative mRNA levels of SAF-A and eGFP in the pools of cells overexpressing SAF-A were 2.69-fold and 2.05-fold higher than those in the control group, respectively. Flow cytometry also revealed a 2.07-fold increase in MFI in stable cell pools overexpressing SAF-A compared with the control group. To assess the long-term stability of transgene expression, we measured the MFI in st
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025251
Recombinant antibodies, primarily produced in Chinese hamster ovary (CHO) cells, are widely used to treat various diseases. For industrial production, a rapid and efficient method to screen stable, high-expressing clones is essential. However, conventional screening based on random integration is often cumbersome and labor intensive. This study establishes a novel strategy for generating stable, high-yielding clones by combining a MAR-based piggyBac (PB) transposon semitargeted integration system with blasticidin (BSD) selection. Compared to the random integrated vector pMAR-mAb, the MAR-PB system increases the titers (3.95- to 5.61-fold) and specific protein productivity (Qp; 4.28- to 6.07-fold) of four monoclonal antibodies in stable cell pools. When compared to PB-only vectors, the MAR-PB transposon system enhances the titers (by up to 2.50-fold) and Qp (1.96- to 2.77-fold), respectively. The increased antibody production correlates with elevated mRNA expression. Furthermore, this approach increases the proportion of high-expressing clones by more than 10-fold and significantly improves volumetric yield. Importantly, this approach promotes the long-term stability of recombinant mAb expression for over 60 generations. Transcriptome analysis reveals that the system modulates genes involved in DNA binding, transcriptional regulation, and protein binding. In conclusion, the MAR-based PB transposon system combined with BSD selection presents a significant improvement for efficiently generating high-yielding and stable CHO cell clones, offering a valuable tool for recombinant antibody production.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025196
Human embryonic kidney (HEK) 293 cells are widely used for recombinant protein production because of their efficient posttranslational modification capabilities. However, their large-scale culture is often limited by metabolic stress and early apoptosis, leading to insufficient protein yields. In this study, we aim to increase protein expression through the coordinated modulation of metabolic and apoptotic pathways. Using CRISPR/Cas9 technology, we target and knockout the genes of ornithine decarboxylase antizyme 1 (OAZ1), which regulates polyamine metabolism, and caspase 8-associated protein 2 (CASP8AP2), an apoptosis-related protein. We successfully construct an OAZ1/CASP8AP2 double-knockout HEK293 cell line. Following transfection with the knockout vector and screening of single-cell clones, multiple levels of validation confirm the successful gene knockout. The results show that the double-knockout cells exhibit significantly reduced apoptosis rates. Furthermore, the production of recombinant secreted alkaline phosphatase (SEAP) and vitronectin (VN) increases by 2.1 folds and 2.9 folds, respectively, compared with those in wild-type cells. Metabolic profiling reveals that the cell cycle is arrested in the G1/G0 phase, accompanied by increased specific consumption and production rates of key metabolites. This study demonstrates that concurrent inhibition of apoptosis and optimization of metabolism effectively enhances recombinant protein production in HEK293 cells, suggesting a novel strategy for improving HEK293 cell-based expression.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024088
Cloning short DNA fragments, such as shRNA and sgRNA, is a routine but time-consuming task in molecular biology. Traditional methods require annealing of complementary oligos or PCR amplification, which are labor-intensive and time-consuming. Here, we report a novel PCR-independent, annealing-free cloning method that enables the insertion of short DNA fragments using a single oligo. The method relies on T4 DNA ligase for ligation and host cell DNA polymerase for complementary strand synthesis. We demonstrate that adding T4 DNA polymerase and dNTPs to the ligation mixture significantly improves cloning efficiency. This approach simplifies the cloning process, reduces time to less than 1 hour, and is compatible with standard laboratory reagents. Our method provides a rapid and efficient alternative for cloning short DNA fragments, with broad applications in gene knockdown and genome editing.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024105
The glucose-fructose oxidoreductase/inositol dehydrogenase/rhizopine catabolism protein (Gfo/Idh/MocA) family includes a variety of oxidoreductases with a wide range of substrates that utilize NAD or NADP as redox cofactor. Human contains two members of this family, namely glucose-fructose oxidoreductase domain-containing protein 1 and 2 (GFOD1 and GFOD2). While GFOD1 exhibits low tissue specificity, it is notably expressed in the brain, potentially linked to psychiatric disorders and severe diseases. Nevertheless, the specific function, cofactor preference, and enzymatic activity of GFOD1 remain largely unknown. In this work, we find that GFOD1 does not bind to either NAD or NADP. Crystal structure analysis unveils that GFOD1 exists as a typical homodimer resembling other family members, but lacks essential residues required for cofactor binding, suggesting that it may function as a pseudoenzyme. Exploration of GFOD1-interacting partners in proteomic database identifies NF-κB inhibitor-interacting Ras-like 2 (NKIRAS2) as one potential candidate. Co-immunoprecipitation (co-IP) analysis indicates that GFOD1 interacts with both GTP- and GDP-bound forms of NKIRAS2. The predicted structural model of the GFOD1-NKIRAS2 complex is validated in cells using point mutants and shows that GFOD1 selectively recognizes the interswitch region of NKIRAS2. These findings reveal the distinct structural properties of GFOD1 and shed light on its potential functional role in cellular processes.
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.2025080
Macrophages are key players in the pathology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Existing studies and our previous studies have documented the role of CD206-positive M2 macrophages in the inflammatory process of AAV. Inflammasome activation is a critical pathway through which macrophages release inflammatory factors. In this study, we investigate the role of the inflammasome in macrophages in AAV and explore the role of CD206 in this process. We recruit newly diagnosed AAV patients and disease controls from our department. The expression and localization of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) and CD206 in the kidney are determined via immunofluorescence experiments. Myeloperoxidase (MPO)-ANCA immunoglobulin G (MPO-ANCA IgG) is purified from new-onset AAV patients with MPO-ANCA and used to treat lipopolysaccharide (LPS)-primed macrophages in vitro. Our findings reveal that NLRP3 expression is significantly elevated in the kidneys of active AAV patients, accompanied by increased cleaved caspase-1 and N-terminal gasdermin-D (GSDMD) levels in peripheral blood mononuclear cells (PBMCs). In vitro, MPO-ANCA IgG induces NLRP3 inflammasome activation and interleukin (IL)-1β production in macrophages, which is associated with increased MPO expression and JNK signaling pathway activation. Immunofluorescence analysis demonstrates partial colocalization of CD206 and NLRP3 in AAV kidneys. Furthermore, silencing of MRC1 gene, which encodes CD206, reduces inflammasome activation induced by MPO-ANCA IgG. In conclusion, our study provides evidence that MPO-ANCA IgG contributes to NLRP3 inflammasome activation and macrophage pyroptosis, with CD206 playing a critical role in this process. These findings elucidate the mechanisms underlying inflammation in AAV and suggest potential therapeutic targets.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025093
YY1 is a crucial transcription factor and plays significant roles in biological processes. However, the mechanisms of YY1 action in ischemia-reperfusion injury and its regulatory role in ferroptosis have not been extensively studied. This study aims to elucidate the molecular mechanism by which NEDD4L-mediated degradation of YY1 through ubiquitination suppresses SLC7A11 transcription, leading to the promotion of cellular ferroptosis and exacerbation of hepatic ischemia-reperfusion injury (IRI), via the integration of multiple omics sequencing datasets. An IRI-I/R mouse model is established, followed by proteomic sequencing to identify proteins that are differentially expressed during IRI. The altered expression of YY1 is validated, and in vivo and in vitro experiments are used to assess its impact on IRI damage. The E3 ligase NEDD4L, which regulates YY1 ubiquitination, is identified and validated via the UbiBrowser 2.0 database. The ubiquitination types of YY1 and its sites are screened and confirmed through in vitro experiments. Transcriptional sequencing of YY1-overexpressing cell lines is conducted to analyze the involvement of the downstream transcription factor SLC7A11 in IRI, followed by validation of its regulatory role. The results show that YY1 is downregulated in liver tissues during IRI and is expressed primarily in liver cells. YY1 overexpression alleviates liver tissue and liver cell IRI both in vitro and in vivo. Upregulation of E3 ligase expression during IRI promotes the K63-linked ubiquitination of YY1 at the K339 site, leading to proteasomal degradation of YY1. RNA-seq analysis and experimental validation demonstrate that YY1 suppresses IRI-induced ferroptosis via the transcriptional regulation of downstream target genes. YY1 positively regulates SLC7A11 transcription, inhibits IRI-induced ferroptosis and ameliorates liver injury. In summary, the E3 ubiquitin ligase NEDD4L facilitates YY1 protein degradation through ubiquitination, suppressing the transcription of the ferroptosis inhibitor SLC7A11, thus promoting IRI-related ferroptosis and exacerbating liver injury.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025217
Smurf1 is a member of the Nedd4 family of E3 ubiquitin ligases. Numerous lines of evidence indicate that the membrane localization of Smurf1 is essential for its activity. However, the underlying mechanisms that regulate the membrane localization of Smurf1 remain unclear. Type I phosphatidylinositol phosphate kinase (PIPKI) is a phosphatidylinositol kinase that generates phosphatidylinositol 4,5-bisphosphate (PIP2), which is located in the plasma membrane and regulates cellular processes, including ion channel activity and cell migration. In this study, we show that PIP2 and PIPKI regulate the membrane translocation of Smurf1. Importantly, the recruitment of Smurf1 to the cell membrane through the association of its C2 domain with PIPKI-produced PIP2 is essential for Smurf1-mediated E3 ligase activity and cell migration. Therefore, we identify a PIPKI-PIP2-Smurf1 signaling axis that regulates cell migration.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025024
Epithelial ovarian cancer (EOC) is a highly aggressive malignancy with a poor prognosis due to late-stage diagnosis and the lack of reliable biomarkers for early detection. Exosomes, small vesicles involved in intercellular communication, play a critical role in cancer progression by promoting migration, proliferation, and metastasis. This study investigates the role of exosomal proteins in EOC cell migration and identifies potential biomarkers. Exosomes are isolated from the ascites fluid of EOC patients (C-Exos) and benign ovarian disease patients (B-Exos), and mass spectrometry analysis of clinical samples reveals 185 differentially expressed proteins, with integrin alpha 3 (ITGA3) being strongly associated with poor prognosis. ITGA3 is transported via exosomes to recipient EOC cells, where it is released into the cytoplasm and translocated to the cell membrane. This localization enables ITGA3 to activate the intracellular signaling pathways that drive EOC migration. Immunoprecipitation mass spectrometry of clinical samples reveals that ITGA3 may influence EOC migration through the S100A7/p-ERK signaling pathway. Mechanistically, ITGA3 activates ERK signaling through S100A7, promoting cell migration. In vivo, exosomes enriched with ITGA3 facilitates tumor growth and migration, whereas ITGA3 knockdown reduces these effects. These findings suggest that exosomal ITGA3, via the S100A7/p-ERK signaling pathway, promotes EOC cell migration. ITGA3 could serve as a prognostic biomarker and therapeutic target in EOC. Targeting the ITGA3/S100A7 axis may help suppress migration, suggesting a promising strategy to improve EOC patient outcomes.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024174
Berberine (BBR) is used to treat diarrhea clinically. However, its reproductive toxicity is unclear. This study aims to investigate the impact of BBR on the male reproductive system. Intragastric BBR administration for 14 consecutive days results in a significant decrease in the serum testosterone concentration, epididymal sperm concentration, mating rate and fecundity of male mice. Testicular treatment with testosterone propionate (TP) partially reverses the damage caused by BBR to the male reproductive system. Mechanistically, the decrease in Muribaculaceae abundance in the gut microbiota of mice is the principal cause of the BBR-induced decrease in the sperm concentration. Both fecal microbiota transplantation (FMT) and polyethylene glycol (PEG) treatment demonstrate that Muribaculaceae is necessary for spermatogenesis. The intragastric administration of Muribaculaceae intestinale to BBR-treated mice restores the sperm concentration and testosterone levels. Metabolomic analysis reveals that BBR affects arginine and proline metabolism, of which ornithine level is downregulated. Combined analysis via 16S rRNA metagenomics sequencing and metabolomics shows that Muribaculaceae regulates ornithine level. The transcriptomic results of the testes indicate that the expressions of genes related to the low-density lipoprotein receptor (LDLR)-mediated testosterone synthesis pathway decrease after BBR administration. The transcriptional activity of the Ldlr gene in TM3 cells is increased with increased ornithine supplementation in the culture media, leading to increased testosterone synthesis. Overall, this study reveals an association between a BBR-induced decrease in Muribaculaceae abundance and defective spermatogenesis, providing a prospective therapeutic approach for addressing infertility-related decreases in serum testosterone triggered by changes in the gut microbiota composition.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025004
Atherosclerosis (AS) is a chronic inflammatory disease characterized by the accumulation of lipid-rich plaques in arterial walls, leading to cardiovascular events such as myocardial infarction and stroke. Macrophage pyroptosis, a form of programmed cell death driven by the NLRP3 inflammasome and caspase-1 activation, plays a critical role in the progression and destabilization of atherosclerotic plaques. This review explores the molecular mechanisms underlying macrophage pyroptosis and their significant contributions to AS pathogenesis. Recent advancements have highlighted the therapeutic potential of targeting key components of the pyroptotic pathway, including the use of nanotechnology to increase drug delivery specificity. These strategies are promising for reducing inflammation, stabilizing plaques, and mitigating the clinical impact of AS. Future studies should focus on translating these findings into clinical applications to develop effective treatments that can halt or reverse AS progression by modulating macrophage pyroptosis.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025241
The evolutionarily conserved nucleosome assembly protein 1 (NAP1) functions as a histone chaperone for H2A-H2B, regulating nucleosome assembly and maintaining chromatin integrity. However, the dynamic and variable nature of the interactions between acidic NAP1 and basic H2A-H2B has obscured the molecular basis of its chaperoning activity. Here, we report the crystal structures of Caenorhabditis elegans NAP1 (CeNAP1) in complex with Xenopus laevis H2A-H2B (XlH2A-H2B) and with C. elegans H2A.Z-H2B (CeH2A.Z-H2B) at 3.35 Å and 2.8 Å, respectively. In our structures, H2A/H2A.Z-H2B binds to the acidic concave surface of CeNAP1 in three distinct poses, with two in the CeNAP1-XlH2A-H2B complex and one in the CeNAP1-CeH2A.Z-H2B complex. These poses are different from the two poses observed in the previously reported CeNAP1-CeH2A/H2A.Z-H2B structures. The predominant interaction involves engagement of the acidic CeNAP1 α6-carboxy-terminal (C-terminal) tail by the basic H2A/H2A.Z αN–α1 region, stabilized by salt bridges and electrostatic interactions. A comparative analysis of all five known poses reveals that H2A/H2A.Z-H2B can shift approximately 20.7 Å along the α6-C-terminal tail-C′-terminal tail-α6′ axis. These findings demonstrate a sliding binding mode of H2A/H2A.Z-H2B on NAP1, providing new mechanistic insights into nucleosome assembly activity of histone chaperones.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025186
Bone remodeling represents a dynamic equilibrium orchestrated by mechanobiological and endocrine signals, with YAP/TAZ and ERα emerging as pivotal regulators of skeletal adaptation. YAP/TAZ functions as the central mechanotransduction hub of the Hippo pathway, converting biomechanical cues, including microenvironment matrix stiffness and shear stress, into osteogenic transcriptional programs. Concurrently, ERα integrates both mechanical stimuli and estradiol (E2) signaling to coordinate osteoblast-osteoclast coupling through the transcriptional regulation of RUNX2 activity and RANKL suppression. Although increasing evidence suggests that these two systems might engage in functional crosstalk, there is still no consensus on this issue. This review synthesizes the current understanding of YAP/TAZ-ERα interactions across three dimensions: (1) mechanohormonal integration in skeletal remodeling, (2) context-dependent reciprocity in breast carcinogenesis, and (3) tissue-specific regulatory paradigms in extra-skeletal systems. Key findings reveal that YAP/TAZ and ERα exhibit both synergistic cooperation (enhanced osteogenic differentiation via promoter co-occupancy) and pathway antagonism (competitive TEAD binding), with their interaction dynamics being critically shaped by the cellular microenvironmental context. Notably, mechanical potentiation of ERα transcriptional activity requires YAP/TAZ co-activation in bone mesenchymal stem cells, whereas estrogen signaling modulates YAP mechanosensitivity through cytoskeletal remodeling. These mechanistic insights indicate that the YAP/TAZ-ERα axis is a promising therapeutic target for osteoporotic bone loss, particularly in alveolar bone preservation. By bridging endocrine and mechanobiological perspectives, this work provides a conceptual framework for developing combinatorial therapies that simultaneously address hormonal imbalance and mechanical insufficiency in skeletal pathologies.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025117
Hepatocellular carcinoma (HCC) represents a significant global health challenge due to its aggressive malignancy. Abnormal glycosylation is a frequent phenomenon in tumor cells and manifests as alterations in key cancer biomarkers. This phenomenon is driven primarily by changes in the expressions of glycosyltransferases. Our study focuses on GALNT7, a member of the GALNT glycosyltransferase family, which catalyzes the initiation of O-linked glycan synthesis by transferring N-acetylgalactosamine (GalNAc) to serine or threonine residues on target proteins. We observe that GALNT7 expression is notably increased in HCC tissues and is correlated with increased tumor cell invasion, migration, and proliferation, alongside with reduced apoptosis, both in vivo and in vitro. Further molecular analyses indicate that GALNT7 specifically modifies the O-glycosylation pattern of MUC13, thereby influencing the activation of the PI3K/AKT signaling pathway. Additionally, elevated GALNT7 level enhances resistance to lenvatinib-based chemotherapy regimens. Thus, GALNT7 is a critical regulator of oncogenic processes in HCC. Targeting the GALNT7-MUC13-PI3K/AKT axis represents a novel therapeutic strategy for combating HCC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024129
Protein glycosylation is a type of protein post-translational modification. One specific example is the modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) and O-linked α-N-acetylgalactosamine (O-GalNAc). Enhanced levels of both O-GalNAc and O-GlcNAc in bladder cancer (BlCa) have been reported previously. However, the interplay between O-GalNAc and O-GlcNAc has yet to be explored. Herein, we find that the expression level of core1 β-1,3-galactosyltransferase (C1GalT1), which is responsible for extending and maturing mucin-type O-glycans, is increased in BlCa. This increase is accompanied by O-GlcNAc modification of C1GalT1. This modification stabilizes C1GalT1 expression and strengthens its interaction with its chaperone Cosmc. Mutation at Thr229 or Thr233 attenuates C1GalT1 stability and facilitates its degradation via the proteasome pathway. Furthermore, a decrease in C1GalT1 inhibits the pro-tumorigenic effect on bladder cancer cells by suppressing glycolysis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024197
The bulbs of Lycoris aurea Herb can produce unique alkaloids, which have been shown to have antiviral, anti-tumor, anti-malarial, and immunostimulatory properties and are effective in the symptomatic treatment of Alzheimer’s disease. As a consequence, the demand for Lycoris bulbs has dramatically increased, especially for L. aurea, which is native to southern China and is highly important for increasing bulb yield. Previous research in this area reported that the use of exogenous hormones is a way to optimize the artificial reproduction of their bulbs. Therefore, studying the molecular mechanism of bulb growth and development is highly important. Quantitative real-time PCR (qRT-PCR) is widely used in gene expression analysis to explore gene functions that regulate plant growth and development because of its high specificity, accuracy, sensitivity and efficiency, and selecting reference genes correctly is crucial for obtaining proper results and interpretations via qRT-PCR analysis. The selection and validation of reference genes of some Lycoris species in different floral development stages and tissues have been carried out, but under some abnormal conditions, including abiotic stress and hormone treatments, have not been assessed. In this study, we aimed to identify suitable reference genes for L. aurea under seven hormone treatments. A total of seven candidate reference genes were selected for investigation. The expressions of these candidate genes were measured by qRT-PCR. The expression stability of candidate genes was comprehensively evaluated by four different statistical algorithms, including geNorm, BestKeeper, NormFinder and RefFinder.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04919-4
Lung cancer remains the leading cause of cancer mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of diagnoses. Lung cancer stem-like cells (LCSCs) drive metastasis, recurrence, and therapeutic failure, yet effective targeting strategies remain elusive. Oxysterol-binding protein-like 2 (OSBPL2/ORP2) is a lipid transport protein that localizes to lipid droplets (LDs) and regulates cholesterol homeostasis, but its role in lung cancer stemness has not been defined. Here, we demonstrate that OSBPL2 reduces cellular cholesterol content, as quantified by HPLC-MS, and inhibits lipid droplet accumulation in lung cancer cells. OSBPL2-mediated lipid transportation significantly suppressed tumor sphere formation, stemness marker expression (ALDH1A1, CD133, Nanog), and in vivo tumorigenesis and metastasis. In peritoneal carcinomatosis models using BALB/c mice (n=10 per group) injected with L-Osbpl2 or L-Vector transduced LLC cells (5×10^6 cells/100µL), OSBPL2 overexpression reduced metastatic tumor burden. Clinical specimen analysis revealed that OSBPL2 represses LCSC marker expression and its level negatively correlates with tumor stage progression and lymph node metastasis. These findings establish OSBPL2 as a critical regulator of lung cancer stemness through lipid metabolic reprogramming, offering a potential therapeutic target for aggressive NSCLC.
Acta Hydrobiologica Sinica•2026•DOI: 10.3724/1000-3207.2026.2026.0101
High-density crowding stress during the initial feeding stage poses severe challenges to fish health, promoting lipid peroxidation. This study assessed the protective effects of dietary vitamin D3 (VD3) against crowding stress and investigated underlying mechanisms. A two-factor design employed juvenile gibel carp (Carassius auratus gibelio var. CAS V) (0.47±0.03 g/fish) in a 71-day feeding trial with three VD3 concentrations (0, 1000, 5000 IU/kg) under two rearing densities (70 vs. 210 fish/tank). Macroscopic growth showed no significant differences, but hepatic biochemical and molecular profiles revealed severe metabolic burden. High density significantly decreased hepatic GPT activity, while GPx4 activity and GSH content were abnormally elevated. Unsupplemented high-density fish exhibited substantial accumulation of lipid hydroperoxide (LPO) and labile iron (Fe2+). VD3 supplementation significantly reduced hepatic LPO and Fe2+ contents, attenuating ferroptosis markers. Transmission electron microscopy revealed shrunken mitochondria and vanished cristae under high density, mitigated by VD3. Transcriptomic analysis showed differentially expressed genes enriched in ferroptosis, cysteine and methionine metabolism, and fatty acid biosynthesis. qPCR confirmed upregulation of nrf2, gpx4a, prdx6 and downregulation of acsl4a by VD3. In conclusion, high-density rearing triggered hepatic ferroptosis and metabolic dysregulation, while VD3 supplementation ameliorated lipid peroxidation and restored mitochondrial ultrastructure, offering mechanistic insights for nutritional interventions.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026054
The anti-inflammatory properties of the traditional herb Salvia miltiorrhiza Bunge are well-established, yet its precise mechanism of action in ulcerative colitis (UC) remains unclear. Herein, we evaluate the therapeutic potential of four major tanshinones–tanshinone IIA (Tan IIA), miltirone, neocryptotanshinone, and dihydrotanshinone I–in a murine dextran sulfate sodium (DSS)-induced colitis model. Our results show that tanshinones effectively alleviate disease severity, suppress systemic and local inflammation, and restore intestinal barrier integrity. Integrated multi-omics analysis reveals that the therapeutic efficacy originates from a comprehensive reprogramming of the gut microbiota-metabolite axis. Specifically, tanshinones reverse colitis-associated dysbiosis and rectify metabolic disturbances in linoleic acid metabolism, bile acid biosynthesis, and amino acid utilization. Correlation network analysis identifies key functional modules linking beneficial microbes (e.g., Akkermansia) to anti-inflammatory lipid mediators and associating pathobionts (e.g., Desulfovibrio) with disrupted bile acid metabolism. Notably, supplementation with Akkermansia muciniphila synergizes with Tan IIA to amplify barrier restoration and metabolic normalization. Our findings establish that tanshinones ameliorate UC through microbiota-driven metabolic reprogramming, wherein the restructured microbial community actively shapes a therapeutic metabolic output. This work elucidates a metabolite-mediated mechanism of action and positions tanshinones as promising microbiome-targeting therapeutics for inflammatory bowel disease.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025223
The clinical use of doxorubicin (DOX) as a chemotherapeutic agent is limited by its cardiotoxic effects. Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, has been increasingly recognized as an important regulator of cardiovascular disease. However, its role in doxorubicin-induced cardiotoxicity remains unknown. Therefore, the objective of this study is to investigate the role and mechanism of FGF13 in doxorubicin-induced cardiac injury. C57BL/6 mice are used to establish Dox-induced cardiotoxicity models. The results reveal that mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening are decreased in the DOX group. In contrast, Fgf13 deficiency mitigates doxorubicin-mediated cardiotoxicity, as indicated by increased mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening. Mechanistically, the protein expressions of bax and cleaved caspase 3 are elevated in the DOX-treated group, along with decreased JC-1 fluorescence intensity and bcl-2 expression, whereas Fgf13 knockout prevents these alterations. In addition, Parkin, but not p53, interacts with FGF13 and is upregulated in response to Fgf13 deficiency in a mouse model of doxorubicin-induced cardiotoxicity. Overall, Fgf13 knockout attenuates doxorubicin-induced cardiomyocyte apoptosis and mitochondrial damage through the modulation of Parkin, indicating that FGF13 may serve as a promising therapeutic target for DOX-induced cardiotoxicity.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025251
Recombinant antibodies, primarily produced in Chinese hamster ovary (CHO) cells, are widely used to treat various diseases. For industrial production, a rapid and efficient method to screen stable, high-expressing clones is essential. However, conventional screening based on random integration is often cumbersome and labor intensive. This study establishes a novel strategy for generating stable, high-yielding clones by combining a MAR-based piggyBac (PB) transposon semitargeted integration system with blasticidin (BSD) selection. Compared to the random integrated vector pMAR-mAb, the MAR-PB system increases the titers (3.95- to 5.61-fold) and specific protein productivity (Qp; 4.28- to 6.07-fold) of four monoclonal antibodies in stable cell pools. When compared to PB-only vectors, the MAR-PB transposon system enhances the titers (by up to 2.50-fold) and Qp (1.96- to 2.77-fold), respectively. The increased antibody production correlates with elevated mRNA expression. Furthermore, this approach increases the proportion of high-expressing clones by more than 10-fold and significantly improves volumetric yield. Importantly, this approach promotes the long-term stability of recombinant mAb expression for over 60 generations. Transcriptome analysis reveals that the system modulates genes involved in DNA binding, transcriptional regulation, and protein binding. In conclusion, the MAR-based PB transposon system combined with BSD selection presents a significant improvement for efficiently generating high-yielding and stable CHO cell clones, offering a valuable tool for recombinant antibody production.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025196
Human embryonic kidney (HEK) 293 cells are widely used for recombinant protein production because of their efficient posttranslational modification capabilities. However, their large-scale culture is often limited by metabolic stress and early apoptosis, leading to insufficient protein yields. In this study, we aim to increase protein expression through the coordinated modulation of metabolic and apoptotic pathways. Using CRISPR/Cas9 technology, we target and knockout the genes of ornithine decarboxylase antizyme 1 (OAZ1), which regulates polyamine metabolism, and caspase 8-associated protein 2 (CASP8AP2), an apoptosis-related protein. We successfully construct an OAZ1/CASP8AP2 double-knockout HEK293 cell line. Following transfection with the knockout vector and screening of single-cell clones, multiple levels of validation confirm the successful gene knockout. The results show that the double-knockout cells exhibit significantly reduced apoptosis rates. Furthermore, the production of recombinant secreted alkaline phosphatase (SEAP) and vitronectin (VN) increases by 2.1 folds and 2.9 folds, respectively, compared with those in wild-type cells. Metabolic profiling reveals that the cell cycle is arrested in the G1/G0 phase, accompanied by increased specific consumption and production rates of key metabolites. This study demonstrates that concurrent inhibition of apoptosis and optimization of metabolism effectively enhances recombinant protein production in HEK293 cells, suggesting a novel strategy for improving HEK293 cell-based expression.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21203
BACKGROUND: Bisphosphonates, as the core drugs of anti-bone resorption therapy, are widely used in the treatment of metabolic bone diseases. However, long-term use can cause the complications of bisphosphonate related osteonecrosis of the jaw. The traditional pathogenesis focuses on the inhibitory effect of bisphosphonates on osteoclasts, but it is difficult to fully explain the pathological development of osteonecrosis. Compared with the relatively mature osteoclast research, there are fewer reports on the effects of bisphosphonates on the biological characteristics and functions of osteoblast-related cells, and there are differences between some reports. This difference may be due to the experimental system, drug concentration and cell source, highlighting the necessity of conducting systematic and standardized research.
OBJECTIVE: To investigate the effect of the third-generation bisphosphonate-zoledronic acid commonly used in clinical practice on the healing of tooth extraction sockets and the proliferation, migration and osteogenic differentiation of bone marrow mesenchymal stem cells derived from the jaw in mice.
METHODS: Sixteen male C57BL/6J mice were randomly divided into control and experimental groups. The experimental group received intraperitoneal injection of zoledronic acid combined with subcutaneous injection of dexamethasone, while the control group received an equal volume of PBS. After 2 weeks of injection, the left maxillary first molars of all mice were extracted, and after another 2 weeks of injection, the mice were sacrificed. The healing of extraction sockets was evaluated by gross observation, Micro CT imaging and three-dimensional reconstruction, and hematoxylin-eosin staining. Jaw bone marrow mesenchymal stem cells were isolated and cultured from both groups. After normal culture and osteogenic induction, cell proliferation, migration, and osteogenic differentiation were assessed by CCK-8 assay, qPCR, Western blot, alkaline phosphatase staining, and alizarin red staining.
RESULTS AND CONCLUSION: Compared with the control group, the experimental group showed poor healing of extraction sockets with more inflammatory cell infiltration. The proliferation and migration abilities of jaw bone marrow mesenchymal stem cells were significantly inhibited in the experimental group (P < 0.05). Alkaline phosphatase staining was weaker, calcium nodule formation was reduced, and the expression of osteogenic markers (alkaline phosphatase, integrin-binding sialoprotein, collagen type I alpha 1 chain, Runt-related transcription factor 2) was downregulated in the experimental group (P < 0.05). These results indicate that zoledronic acid can adversely affect extraction socket healing, possibly by inhibiting the proliferation, migration, and osteogenic differentiation of jaw bone marrow mesenchymal stem cells.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21261
BACKGROUND: The glycocalyx serves as a selective permeability barrier that enables the controlled exchange of substances and maintains fluid balance between within and outside the blood vessels. It is also involved in various pathological processes, including inflammation, thrombus formation, and microcirculation disorders, and is significantly associated with the development and progression of diseases such as atherosclerosis, diabetes, and cancer. OBJECTIVE: To correlate glycocalyx with exercise and disease. METHODS: A literature search was conducted across international databases (MedReading, PubMed, and Web of Science) and Chinese databases (CNKI, WanFang, and VIP) to identify academic articles. The search terms used were “glycocalyx, physical exercise, disease” in Chinese and “glycocalyx, physical exercise, exercises, physical activity, acute exercise, isometric exercises, aerobic exercise, resistance training, exercise training, disease, diseases” in English. A total of 81 publications were included in the final analysis. RESULTS AND CONCLUSION: As a biological barrier of the vascular endothelium, the glycocalyx plays a key role in regulating vascular permeability, mediating inflammatory responses, sensing blood shear stress, and facilitating anticoagulation. The integrity of the glycocalyx is essential for maintaining stable normal blood circulation and ensuring the physiological functions of various organs in the body. Shedding of the glycocalyx can induce structural changes in the endothelial barrier, leading to an abnormal increase in endothelial permeability and accelerating the pathological processes associated with atherosclerosis. Research has confirmed that the extensive thickening and shedding of the glycocalyx on the surface of cancer cells promote tumor proliferation, metastasis, and disease progression. In traumatic diseases, the severity can be assessed by measuring the levels of debris resulting from glycocalyx injury. The glycocalyx is influenced by factors such as the duration of exercise, changes in exercise mode, and exercise intensity. Acute exercise can induce microvascular changes and increase glycocalyx thickness. Aerobic exercise-induced shedding sensitivity of glycocalyx components varies by sex, age, and body mass index. Resistance exercise has positive acute effects on endothelial glycocalyx. Long-term exercise training can protect the glycocalyx. The glycocalyx serves as an intervention target for atherosclerosis, sepsis, cancer, and other diseases, providing theoretical support for developing non-pharmacological therapeutic strategies. However, clinical application of glycocalyx damage markers is not yet standardized, and the mechanisms among glycocalyx, exercise, and disease require further investigation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21302
BACKGROUND: The benefits of exercise as a classical intervention for aging have been widely recognized. The homeostatic balance of a wide range of microorganisms in the intestinal flora indirectly regulates aging, and the bidirectional association between exercise and the intestinal flora can collectively influence the process of aging. OBJECTIVE: To sort out the effects of exercise, intestinal flora and their interactions on aging, and to explore the specific physiological mechanisms involved. METHODS: A computer-based search in CNKI, WanFang, VIP, PubMed, MedReading, and Web of Science, with the time limit of 1976-01-01/2025-02-28, was conducted to collect the relevant studies on the effects of exercise and intestinal flora on aging. The search terms were “intestinal flora, gut microbiota, physical exercise, age, aerobic exercise, resistance exercise, low intensity exercise, moderate intensity exercise, high intensity exercise” in Chinese and English. RESULTS AND CONCLUSION: (1) Exercise and intestinal flora are both means to intervene in aging, and the combined benefits of exercise and gut microbiota in intervening in aging are even more pronounced. (2) Exercise changes the composition and function of intestinal flora, stimulates intestinal production of short-chain fatty acids, regulates host metabolism and immune function, reduces inflammatory response, and promotes the synthesis of vitamins and neurotransmitters. (3) The specific manifestations of aging, when the intestinal flora is regulated via different exercise modes, are different. (4) Different gut-organ axis regulated by exercise has different effects on aging.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21299
BACKGROUND: Neurogenic heterotopic ossification frequently occurs within 1 to 3 months following spinal cord injury or traumatic brain injury, characterized by abnormal bone formation in periarticular soft tissues. The precise pathogenesis remains unclear, underscoring the urgent need for systematic research to inform clinical management. OBJECTIVE: To summarize recent advances in animal models of neurogenic heterotopic ossification and elucidate its underlying mechanisms, with a particular focus on the pathological differentiation of osteogenic precursor cells, remodeling of the local tissue microenvironment, and the interplay between neural regulation and neurogenic heterotopic ossification formation. METHODS: PubMed, CNKI, and SinoMed were searched from inception to January 2025. Chinese search terms included 'neurogenic heterotopic ossification, spinal cord injury, traumatic brain injury, heterotopic ossification'; English search terms included 'Neurogenic Heterotopic Ossification, spinal cord injury, Traumatic brain injury, ossification, heterotopic, Central nervous system'. Literature related to animal models and mechanisms of neurogenic heterotopic ossification was included to summarize key pathogenic processes. RESULTS AND CONCLUSION: The recruitment and aberrant osteogenic differentiation of osteogenic precursor cells (mainly fibro-adipogenic progenitors) are regulated by local microenvironmental factors such as hypoxia, inflammation, and angiogenesis. Neurotrophic factors, calcitonin gene-related peptide, and substance P promote aberrant ossification through neuro-immune interactions. Future research should construct a systematic molecular map, explore core signaling pathways, and develop novel targeted interventions to achieve early identification and individualized treatment of neurogenic heterotopic ossification, thereby improving patient outcomes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21389
BACKGROUND: The scarcity of bone trabecular structures caused by osteoporosis is not enough to maintain screw holding power, which often leads to the failure of internal fixation surgery. The screw holding power is often increased by increasing the diameter and length of screws, changing the surface coating of screws, and reinforcing the nail track with bone cement. The cement reinforced cortical bone track nailing technique and the modified cortical bone track nailing technique using a new type of variable diameter screw have been proven to have good fixation effects, and now the related mechanical properties of the two need to be analyzed and compared.
OBJECTIVE: Finite element analysis was used to compare the mechanical properties of bone cement-strengthened cortical bone trajectory nailing technology, cortical bone trajectory nailing technology, and modified cortical bone trajectory nailing technology using a new variable-diameter total cortical bone thread screw in lumbar spine internal fixation surgery.
METHODS: Based on the CT scan data processing of three osteoporotic vertebrae, the L4 lumbar spine model was constructed, and the innovative variable-diameter all-cortical bone screw was applied in the modified cortical bone nailing technique, with the screw having a total length of 45 mm and a diameter varying from 5.5 to 4.3 mm. This was compared with the un-augmented cortical bone trajectory group (diameter 5.5 mm, length 40 mm) and the bone cement-augmented cortical bone trajectory group (diameter 5.5 mm, length 40 mm, central hole diameter 1 mm). The fixation strength of each group was compared by measuring axial pullout force, screw stability (load-displacement ratio in superior, inferior, left, and right directions), and vertebral range of motion.
RESULTS AND CONCLUSION: (1) Axial pullout force: augmented cortical bone trajectory group > modified cortical bone trajectory screw group (P=0.0246), and both augmented and modified groups were greater than the un-augmented cortical bone trajectory group (P=0.0001 and P=0.00264, respectively). (2) Screw stability: when load was applied inferiorly, the load-displacement ratios were augmented cortical bone trajectory group > un-augmented and modified groups (all P < 0.05), and modified group > un-augmented group (P < 0.05). (3) Vertebral range of motion: under five loading conditions, the augmented cortical bone trajectory group showed less motion than the modified group, but the differences were not statistically significant (P > 0.05), and both augmented and modified groups showed less motion than the un-augmented group. (4) Compared with the modified group, the augmented group showed improved mechanical properties in screw load-displacement ratio and lumbar range of motion, but the differences were not statistically significant (P > 0.05). (5) These findings suggest that the bone cement-augmented cortical bone trajectory technique has better biomechanical properties than the new variable-diameter all-cortical bone screw, and may be a more suitable screw placement option for internal fixation in patients with osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21379
BACKGROUND: Mitochondrial dysfunction is increasingly recognized as a key factor during intervertebral disc degeneration. Sirt3, a major mitochondrial deacetylase, mediates AMPK pathway activation by directly phosphorylating and inhibiting Drp1 activity while indirectly regulating mitochondrial function through downstream signaling. However, the specific mechanisms of Sirt3 and the AMPK/Drp1 pathway in nucleus pulposus cells during intervertebral disc degeneration remain unclear. OBJECTIVE: To investigate whether Sirt3 regulates mitochondrial dynamics balance in nucleus pulposus cells induced by tert-butyl hydroperoxide by mediating the AMPK/Drp1 pathway, thereby inhibiting cell apoptosis. METHODS: Human nucleus pulposus cells were cultured in vitro, and a degeneration model was established by oxidative damage with tert-butyl hydroperoxide. Cells were divided into the following groups: control, model, model + oe-NC, model + oe-Sirt3, model + oe-Sirt3 + Compound C (AMPK inhibitor), and Compound C alone. After 24 h of treatment, cell viability was assessed by CCK-8, apoptosis by flow cytometry, and expression of apoptosis-related proteins (Bax, Bcl2), disc degeneration-related proteins (aggrecan, collagen type II), Sirt3, mitochondrial fission proteins (Fis1, Mff), fusion proteins (Mfn1, Mfn2), and AMPK/Drp1 pathway proteins by western blot. ATP and reactive oxygen species levels were measured using kits, and mitochondrial DNA copy number was determined by RT-qPCR. RESULTS AND CONCLUSION: Compared with the control group, the model group showed significantly decreased cell viability and expression of Bcl2, aggrecan, collagen type II, and Sirt3, while apoptosis rate and Bax level were significantly increased (all P < 0.05), indicating successful establishment of the degeneration model. Additionally, ATP levels, mitochondrial membrane potential, mtDNA copy number, and Mfn1/Mfn2 expression were significantly reduced, while reactive oxygen species, Fis1, and Mff levels were elevated (all P < 0.05), indicating mitochondrial dynamics imbalance. Overexpression of Sirt3 in the model+oe-Sirt3 group inhibited TBHP-induced apoptosis, improved cell viability, restored mitochondrial dynamics balance, activated the AMPK/Drp1 pathway, and suppressed mitochondrial fission. However, the protective effects of Sirt3 overexpression were partially reversed by the AMPK inhibitor Compound C. These findings suggest that Sirt3 is a potential target for inhibiting nucleus pulposus cell apoptosis and may serve as a novel therapeutic direction for intervertebral disc degeneration.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21473
BACKGROUND: Photodynamic therapy, a novel tumor treatment, is limited by the hypoxic tumor microenvironment. Nanotechnology-based oxygen regulation strategies offer a novel approach to overcoming this bottleneck. OBJECTIVE: To systematically analyze the research status of nanotechnology in improving photodynamic therapy for hypoxic solid tumors using bibliometric methods, identify hotspots, and predict future directions. METHODS: Publications and reviews from 2016 to 2025 on nanotechnology for regulating tumor hypoxia and enhancing photodynamic therapy were retrieved from the Web of Science Core Collection. Excel, CiteSpace, VOSviewer, and Bibliometrix were used for visual analysis of categories, publication trends, countries, institutions, authors, co-cited references, and keywords. RESULTS AND CONCLUSION: A total of 1,879 articles were included, with 'nanoscience & nanotechnology' as the core category. From 2016 to 2022, publications increased steadily, with a slight decline in 2023 and a subsequent rise. China was the leading country, with the Chinese Academy of Sciences having the highest output, and Liu Zhuang from Soochow University being the most prolific author. The most cited paper was by Zhou ZJ et al. (2016) in Chemical Society Reviews. The field focuses on cancer treatment, particularly microenvironment-responsive optical therapeutic strategies using nanomaterials. Keywords 'Photodynamic therapy' and 'Nanoparticles' appeared most frequently. Bibliometric analysis indicates that nanotechnology offers advantages in enhancing photodynamic therapy for hypoxic tumors, with promising efficacy and safety. Future hotspots may focus on combination with immunotherapy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21503
OBJECTIVE: To systematically evaluate and quantify the effects of different doses of aquatic exercise on muscle strength in healthy older adults using a Bayesian model-based dose-response meta-analysis, thereby determining the optimal exercise regimen and providing evidence-based recommendations for precise exercise prescription. METHODS: A systematic search was conducted in both English and Chinese databases, including PubMed, Embase, Web of Science, CNKI, and WanFang, to identify randomized controlled trials published up to March 2025 that investigated the effects of aquatic exercise on muscle strength in older adults. Data analysis was performed using R 4.5.0. A conventional meta-analysis was first conducted to estimate the overall effect, followed by a Bayesian model-based dose-response meta-analysis to quantify the nonlinear relationships between different exercise dose dimensions (frequency, session duration, weekly total duration, period, and intensity) and muscle strength improvement. The standardized mean difference (SMD) with 95% confidence interval (CI) was used as the effect size. RESULTS: A total of 13 randomized controlled trials involving 531 participants were included. The overall meta-analysis showed that aquatic exercise significantly improved muscle strength in older adults compared with control (SMD=0.56, 95%CI 0.39-0.74, P < 0.0001). Dose-response analysis revealed cumulative trends for training period, frequency, and weekly total duration: the effect peaked at 24 weeks (SMD=0.65, 95%CI 0.40-0.66); significant gains were achieved at a frequency of twice per week (SMD=0.56, 95%CI 0.22-0.58), with a slight increase at three times (SMD=0.62, 95%CI 0.24-0.62); weekly cumulative duration showed significant effects at 100 minutes (SMD=0.58, 95%CI 0.34-0.60) and plateaued after 200 minutes. In contrast, session duration and intensity exhibited an inverted U-shaped relationship: the effect peaked at 40 minutes per session (SMD=0.62, 95%CI 0.32-0.82), with an optimal range of 30-45 minutes; the optimal intensity was Borg RPE 10-12 (SMD=0.45, 95%CI 0.18-0.46), with diminishing returns beyond this range. CONCLUSION: Aquatic exercise is an effective strategy for improving muscle strength in healthy older adults. It is recommended that older adults engage in aquatic exercise two to three times per week, with each session lasting approximately 40 minutes, at a moderate-to-vigorous intensity (Borg RPE 10-12), and as a long-term strategy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21476
BACKGROUND: Recent studies have found that immune cells play an important role in bone metabolism. Myeloid-derived suppressor cells, as a type of immunosuppressive cell, play a significant role in tumor development, but their role in primary osteoporosis remains unclear. OBJECTIVE: To investigate the osteoclastogenic potential of myeloid-derived suppressor cells in naturally aged and ovariectomy-induced osteoporosis mouse models. METHODS: (1) Myeloid-derived suppressor cells and bone marrow-derived macrophages were isolated from 6-8-week-old female C57BL/6 mice. Both cell types were induced for osteoclast differentiation. After 5 days of induction, osteoclast formation was detected by tartrate-resistant acid phosphatase staining. After 3 days of induction, mRNA expression of nuclear factor of activated T-cells 1 and osteoclast-associated immunoglobulin-like receptor was detected by qRT-PCR. (2) 6-8-week-old female C57BL/6 mice (young group, n=6) and 18-month-old female C57BL/6 mice (naturally aged group, n=6) were taken. Bone microstructure of the distal femur was analyzed by Micro-CT. Bone marrow cells were collected from both groups, and the proportion of myeloid-derived suppressor cells was detected by flow cytometry. Myeloid-derived suppressor cells were isolated and induced for osteoclast differentiation. After 5 days of induction, osteoclast formation was detected by tartrate-resistant acid phosphatase staining; after 3 days of induction, mRNA expression of nuclear factor of activated T-cells 1 and osteoclast-associated immunoglobulin-like receptor was detected by qRT-PCR. (3) 6-8-week-old female C57BL/6 mice were randomly divided into sham-operated group (n=6) and ovariectomy group (n=6). Eight weeks after ovariectomy, bone microstructure of the distal femur was analyzed by Micro-CT. Bone marrow cells were collected from both groups, and the proportion of myeloid-derived suppressor cells was detected by flow cytometry. Serum levels of tumor necrosis factor-alpha and interleukin-6 were measured by ELISA. Myeloid-derived suppressor cells were isolated and induced for osteoclast differentiation. After 5 days of induction, osteoclast formation was detected by tartrate-resistant acid phosphatase staining; after 3 days of induction, mRNA expression of nuclear factor of activated T-cells 1 and osteoclast-associated immunoglobulin-like receptor was detected by qRT-PCR. RESULTS AND CONCLUSION: (1) Tartrate-resistant acid phosphatase staining and qRT-PCR showed that the osteoclast differentiation ability of myeloid-derived suppressor cells was stronger than that of bone marrow-derived macrophages. (2) Micro-CT analysis showed that compared with the young group, the naturally aged group had lower bone mineral density, bone volume fraction, and trabecular number (P < 0.05), and increased trabecular separation (P < 0.05). The proportion of myeloid-derived suppressor cells in the naturally aged group was higher than that in the young group (P < 0.05). Tartrate-resistant acid phosphatase staining and qRT-PCR showed that the osteoclast differentiation ability of myeloid-derived suppressor cells in the naturally aged group was stronger than that in the young group. (3) Micro-CT analysis showed that compared with the sham-operated group, the ovariectomy group had lower bone mineral density, bone volume fraction, and trabecular number (P < 0.05), and increased trabecular separation (P < 0.05). The proportion of myeloid-derived suppressor cells and serum levels of tumor necrosis factor-alpha and interleukin-6 in the ovariectomy group were higher than those in the sham-operated group (P < 0.05). Tartrate-resistant acid phosphatase staining and qRT-PCR showed that the osteoclast differentiation ability of myeloid-derived suppressor cells in the ovariectomy group was stronger than that in the sham-operated group. (4) These results indicate that the proportion and osteoclastogenic ability of myeloid-derived suppressor cells increase under conditions of natural aging and estrogen deficiency, which may participate in the occurrence and development of osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21619
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: 10.12307/2026.21511
BACKGROUND: Currently, in clinical practice, the original internal fixation devices are often removed to perform revision surgery for failed vertebral fixation, which poses certain drawbacks and risks. The pedicle double-screw technique can preserve the original internal fixation devices, while the modified cortical bone trajectory technique offers excellent mechanical performance. Combining these two techniques for revision surgery can mitigate the conventional risks, although the mechanical performance of this new modified cortical bone trajectory technique in revision surgery is not yet well understood. OBJECTIVE: To analyze the mechanical performance of cortical bone trajectory (CBT) and modified cortical bone trajectory (MCBT) screw placement techniques combined with the double-screw technique in lumbar revision surgery using finite element analysis, and to explore the advantages of MCBT over CBT in revision surgery. METHODS: A three-dimensional model of L1-5 vertebrae, endplates, and intervertebral discs was established based on computed tomography data. Screws were placed following the traditional trajectory pedicle screw technique, and the models were divided into traditional trajectory initial group and loosening group based on different screw-bone contact forms. Revision was performed on the traditional trajectory loosening group using MCBT and CBT screws to re-fix the lumbar spine. Finite element analysis was used to evaluate the mechanical performance of MCBT and CBT in revision surgery. RESULTS AND CONCLUSION: (1) Under flexion, extension, lateral bending, and axial rotation, the CBT revision group showed reductions in range of motion (ROM) of 31.97%, 29.15%, 15.12%, and 29.63%, and reductions in intervertebral disc stress of 15.44%, 78.67%, 54.36%, and 40.55%, respectively, compared with the control group. (2) The MCBT revision group showed reductions in ROM of 32.16%, 29.33%, 15.47%, and 31.42%, and reductions in intervertebral disc stress of 16.25%, 83.00%, 64.82%, and 45.83%, respectively, compared with the control group. (3) Compared with the CBT revision group, the MCBT revision group showed reductions in ROM of 0.28%, 0.25%, 0.40%, and 2.54%, reductions in intervertebral disc stress of 0.96%, 20.25%, 22.91%, and 8.88%, reductions in vertebral body stress of 15.78%, 4.75%, 11.22%, and 7.42%, and reductions in screw-rod system stress of 0.15%, 9.80%, 1.04%, and 0.84%, respectively. (4) Both CBT and MCBT techniques effectively enhance the mechanical stability of the fixed segment in lumbar revision surgery, with MCBT showing superior overall performance, providing a new technical option for clinical lumbar revision.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21524
BACKGROUND: Research indicates that Buyang Huanwu Tang has positive therapeutic effects on the spinal cord injury symptoms and spinal cord function recovery, although its therapeutic mechanisms remain unclear. Spinal cord tissue contains numerous proteins and peptides that may serve as disease biomarkers. OBJECTIVE: To investigate the protective mechanism of Buyang Huanwu Tang in an acute spinal cord injury rat model by regulating proteomic- and transcriptomic-related pathways. METHODS: Thirty-six Sprague-Dawley rats were randomly divided into blank group, model group, and Buyang Huanwu Tang group. The latter two groups were used to establish acute spinal cord injury rat models using Allen's modified method. Motor function recovery was assessed by BBB score, pathological morphology was observed by Nissl staining, and differentially expressed proteins and genes were screened by isobaric tags for relative and absolute quantification (iTRAQ) proteomics and RNA-seq transcriptomics, followed by GO enrichment and KEGG pathway analyses. A PPI network was constructed using the STRING interaction database to identify key pathways, and core targets were validated by Western blot, immunohistochemistry, and RT-PCR. RESULTS AND CONCLUSION: (1) Motor function scores: Compared with the blank group, the model group showed significantly lower BBB scores (P < 0.001) and smaller inclined plane test angles (P < 0.001). Compared with the model group, the Buyang Huanwu Tang group showed higher BBB scores (P < 0.05) and larger inclined plane test angles (P < 0.001). Pathological morphology: The blank group showed relatively normal neuronal cells with intact structure, normal gaps, and clear nucleoli and nuclear membranes. The model group showed severe necrosis, disordered structure, pyknotic nuclei, disappearance of most nucleoli and nuclear membranes, numerous tissue cavities, and inflammatory cell infiltration. The Buyang Huanwu Tang group showed irregular but relatively intact neuronal cells with less swelling, reduced tissue cavities and cell necrosis. (2) GO functional annotation and KEGG pathway analysis revealed that differentially expressed proteins were mainly enriched in acute phase response, regulation of protein activation cascade, regulation of acute inflammatory response, platelet alpha granules, blood microparticles, vesicle lumen, serine-type endopeptidase inhibitor activity, and involved in pathways such as map04142 (lysosome), map04612 (antigen processing and presentation), map03013 (nucleocytoplasmic transport), map04964 (proximal tubule bicarbonate reclamation), map04610 (complement and coagulation cascades), map00511 (other glycan degradation), map03040 (spliceosome), map03410 (base excision repair), map00531 (glycosaminoglycan degradation), and coronavirus disease-COVID-19 pathway. Through PPI construction, 20 core differential proteins including FGG, FN1, FGB, HSP90B1, CASP3, and 20 core differential genes including FGG, FN1, FGB, CXCL1, CXCL13 were identified. (3) Western blot showed that Buyang Huanwu Tang inhibited the expression of myeloid differentiation factor 88 (MyD88) and P-IKBα in spinal cord tissue. Immunohistochemistry showed that Buyang Huanwu Tang inhibited the expression of BAX and Caspase-3, promoted BCL-2 expression, and inhibited apoptosis. RT-PCR results showed that Buyang Huanwu Tang inhibited the expression of MyD88 and CXCL1. These results suggest that Buyang Huanwu Tang may protect spinal cord tissue by inhibiting the Toll-like receptor 4/MyD88/nuclear factor-κB pathway to reduce inflammation, and by regulating the BAX/BCL-2 balance to inhibit Caspase-3 expression and prevent apoptosis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04919-4
Lung cancer is the first leading cause of cancer death worldwide. Oxysterol-binding protein-like 2 (OSBPL2) is a lipid transport protein regulating cholesterol homeostasis. Here, we clarified the previously unreported role of OSBPL2 in lung cancer stemness properties. We observed that OSBPL2 reduced cholesterol content by HPLC-MS. It inhibited the accumulation of lipid droplets (LDs) in lung cancer. OSBPL2-mediated lipid transportation significantly suppressed tumor sphere formation, stemness markers expression and in vivo tumorigenesis and tumor metastasis. In clinical specimens, we also demonstrated that OSBPL2 repressed the expression of Lung cancer stem-like cells (LCSCs) markers-ALDH1A1, CD133 and Nanog. The level of OSBPL2 was negatively correlated with malignant of lung cancer, such as tumor stage progression and lymph node metastasis. Taken together, these findings illustrated that OSBPL2-mediated lipid transportation inhibited the stemness and aggressiveness of lung cancer cells. OSBPL2 was a potential therapeutic target to develop novel cancer-preventive compound.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05049-7
Dental-derived stromal cells (DSCs), including periodontal ligament stem cells (PDLSCs), dental pulp stem cells (DPSCs), stem cells from the apical papilla (SCAP), and stem cells from human exfoliated deciduous teeth (SHED), are accessible and expandable candidates for oral and craniofacial regeneration. Their therapeutic performance remains inconsistent because conventionally expanded cells are poorly adapted to in vivo mechanical cues. This review presents mechanical preconditioning as a mechanomedicine-guided strategy for ex vivo functional priming of DSCs. It summarizes DSC responses to tensile and compressive forces, fluid shear stress, hydrostatic pressure, matrix stiffness, and surface topography, and discusses principal mechanotransduction pathways. Representative quantitative loading windows are outlined to support subtype-specific and indication-specific preconditioning design. Key translational barriers include stromal cell heterogeneity, donor variability, senescence, uncertain persistence of mechanically induced states, safety concerns, and the lack of standardized manufacturing workflows. Clinical translation will require a shift from descriptive mechanobiology toward parameter-defined, indication-specific, and good manufacturing practice-compatible preconditioning strategies for DSC-based regeneration.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04918-5
Intervertebral disc (IVD) degenerative disease is a prevalent and debilitating spinal condition. Current treatments provide only symptomatic relief and fail to halt disease progression or restore native biomechanical function. Regenerative medicine strategies, particularly those harnessing endogenous progenitor cells, offer a promising avenue for biological repair and functional homeostasis. The identification of intervertebral disc progenitor cells (IVD-PCs) has revealed a potential cellular reservoir for self-repair, given their demonstrated stemness attributes, including clonogenicity and multipotent differentiation. However, clinical translation of IVD-PCs is significantly hampered by an incomplete understanding of their inherent heterogeneity, hierarchical organization, and, most critically, the dynamic interplay with their unique microenvironment, which dictates their fate decisions. This review synthesizes recent advances in deciphering the molecular signatures and functional plasticity of IVD-PCs. We emphasize how key physicochemical, mechanical, and cellular cues within the IVD niche orchestrate progenitor cell behavior—ranging from maintenance and activation to aberrant differentiation—during both homeostasis and degeneration. Furthermore, we propose forward-looking insights to bridge critical knowledge gaps, aiming to propel the development of novel progenitor cell-based therapeutics for IVD degeneration.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05027-z
Retinal organoids (ROs) derived from human pluripotent stem cells are crucial for modeling retinal development and disease. However, the functional electrophysiological maturation of photoreceptors within ROs remains poorly characterized. This study aimed to define the functional maturation timeline of photoreceptors in human embryonic stem cell (hESC)-derived ROs. H9 hESC-derived ROs which included a CRX-tdTomato reporter line for specific photoreceptor identification were utilized. An integrated approach of RNA-sequencing analysis, immunofluorescence staining, and whole-cell patch-clamp recordings was employed to systematically assess photoreceptor maturation over 300 days of differentiation. Transcriptional and protein analysis revealed progressive upregulation of key ion channels. Patch-clamp recordings demonstrated stage-dependent maturation of membrane properties, which stabilized by D120–125. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated currents (Ih) increased progressively, peaking at D240, with amplitudes comparable to mature primate photoreceptors. Voltage-gated sodium (Nav) currents also showed significant developmental upregulation, reaching a maximum, stable plateau from D210–215 onward. Pharmacological blockade confirmed the identity of HCN and Nav currents. Critically, the capacity for action potential (AP) generation increased developmentally, with the proportion of photoreceptors capable of firing APs rising from 16.7% at D90–95 to a peak of 90.2% by D240–245. This study defines a comprehensive electrophysiological maturation timeline for photoreceptors in human ROs and establishes D240 as a key benchmark for functional maturity, characterized by peak Ih currents and AP generation capacity equivalent to mature native photoreceptors. These findings provide essential physiological criteria for standardizing RO quality control, enhancing their utility for modeling retinal degenerative diseases and developing cell replacement therapies.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026021
Macrophages play a pivotal role in bone regeneration, making their polarization a key target for immune regulation and therapeutic intervention. Modulating macrophage polarization represents a promising strategy for enhancing bone repair. Luteolin, a plant-derived flavonoid with well-documented anti-inflammatory properties, has been explored for its role in bone repair. However, its specific effects on macrophage polarization in bone repair remain unclear. This study investigates the role of luteolin in macrophage polarization and its underlying mechanisms. Our findings demonstrate that luteolin promotes M2 polarization while suppressing M1 polarization, as indicated by a reduction in the expression of pro-inflammatory markers, including IL-6 and iNOS, and an increase in the expression of anti-inflammatory factors, such as CD206, IL-10, and TGF-β. Mechanistically, luteolin inhibits STING oligomerization, thereby suppressing the STING-TBK1 pathway and mitigating downstream inflammatory responses. In vivo, in a mouse tibial bone defect model, luteolin effectively alleviates inflammation, facilitates angiogenesis, enhances collagen deposition, and improves bone density. Collectively, these findings highlight the potential of luteolin as a therapeutic agent for bone repair by modulating macrophage polarization and inhibiting STING-TBK1 signaling.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026117
SGLT2 inhibitor (SGLT2i)-induced diabetic hyperketonemia is a life-threatening acute complication of diabetes. While celastrol has been reported to have beneficial effects on obesity, its potential role in ketogenesis remains unclear. In this study, celastrol administration significantly attenuates the fasting-induced increase in blood β-hydroxybutyrate levels. Moreover, a 7-day course of celastrol (1 mg/kg/day) leads to reductions in body weight and fat mass. Mechanistically, celastrol specifically downregulates HMGCS2 expression and suppresses hepatic ketogenesis through the inhibition of PPARα expression in the short term (≤ 2 days). However, after prolonged treatment for 7 days, celastrol modulates both PPARα and serum free fatty acid (FFA) levels. Furthermore, the anti-ketogenic effect of celastrol is abolished in Pparα⁻/⁻ mice. Importantly, celastrol effectively ameliorates SGLT2i-induced hyperketonemia. In summary, celastrol curbs hepatic ketone overproduction in a PPARα-dependent manner, indicating its protective potential against SGLT2i-induced hyperketonemia.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025080
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening systemic autoimmune disease characterized by necrotizing small vessel vasculitis, with pauci-immune glomerulonephritis being the most severe manifestation. Macrophages, particularly CD206-positive M2 subsets, are central to AAV pathology, yet the mechanistic link between inflammasome activation and CD206 remains undefined. This study investigates NLRP3 inflammasome activity and pyroptosis in CD206+ macrophages exposed to myeloperoxidase (MPO)-ANCA immunoglobulin G (IgG). Newly diagnosed AAV patients and disease controls were recruited; renal NLRP3 and CD206 expression were assessed by immunofluorescence. MPO-ANCA IgG was purified from new-onset AAV patients and applied to lipopolysaccharide (LPS)-primed macrophages in vitro. Results demonstrate significantly elevated NLRP3 expression in active AAV kidneys, accompanied by increased cleaved caspase-1 and N-terminal gasdermin-D (GSDMD) in peripheral blood mononuclear cells (PBMCs). In vitro, MPO-ANCA IgG induces NLRP3 inflammasome activation and interleukin (IL)-1β production, associated with increased MPO expression and JNK signaling pathway activation. Immunofluorescence reveals partial colocalization of CD206 and NLRP3 in AAV kidneys. Silencing of MRC1, encoding CD206, reduces inflammasome activation induced by MPO-ANCA IgG. These findings establish that MPO-ANCA IgG contributes to NLRP3 inflammasome activation and macrophage pyroptosis, with CD206 playing a critical role. The study elucidates mechanisms underlying AAV inflammation and suggests potential therapeutic targets.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025233
This corrigendum addresses inaccuracies in three figure panels from the original article (Acta Biochim Biophys Sin 54: 1587–1598, doi: 10.3724/abbs.2022150). The authors identified that Figure 2D was mislabeled during preparation, Figure 4A contained an incorrect image due to a processing error, and Figure 5A was mistakenly replaced during final compilation. Corrected versions of these panels are provided. The authors confirm that these errors are confined to figure presentation and do not affect the underlying data, statistical analyses, or the main conclusions of the study. The original research demonstrated that caveolin-1 (CAV-1)-deficient fibroblasts promote migration, invasion, and stemness in breast cancer cells (BCCs) via activation of the TGF-β/Smad signaling pathway. Key experimental methods included Western blot for CAV-1 expression, scratch wound healing assays for migration, Transwell assays for migration and invasion, immunofluorescence and ELISA for TGF-β1 detection, and Western blot for EMT/stemness markers. Statistical significance was set at P < 0.05. This corrigendum ensures the accuracy of the scientific record and maintains the integrity of the reported findings.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025171
Obesity-induced metabolic inflammation drives chronic kidney disease (CKD), with lymphocyte dysregulation contributing to early pathology. We established high-fat diet-induced obese (DIO) models in wild-type and Apoa4-knockout (KO) mice to investigate apolipoprotein A4 (Apoa4) in immune-metabolic regulation. KO mice exhibited exacerbated insulin resistance and renal lipid accumulation. Single-cell RNA sequencing (scRNA-seq) of renal immune cells revealed that Apoa4 deletion remodeled the immune-metabolic landscape, compromising T, NK, and B cell functions while expanding cytotoxic Gzma+ NK cells and Derl3+ plasma cells. Mechanistically, Apoa4 deletion aggravated metabolic dysregulation and oxidative stress, downregulating effector genes including Ifng and Il1b. Transcription factor regulatory networks were perturbed: Lef1 and Runx3 in Cd8+ T cells; Irf8, T-bet, and Eomes in NK cells; and Tcf4, Lmo2, and Xbp1 in B cells. CellChat predicted disrupted pro-inflammatory (IFN-II, IL-1), immunoregulatory (FASLG), and metabolic (ENHO, ANGPTL) signaling, with enhanced IL-2-mediated suppression. Flow cytometry, immunofluorescence, and qPCR validated these findings. Sequencing depth averaged 278,276 reads/cell (WT) and 197,768 reads/cell (KO), ensuring robust detection of low-abundance transcripts despite modest cell capture. Apoa4 is a critical regulator of lymphocyte metabolic and immune homeostasis in early obesity-associated CKD.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025089
Cuproptosis, a copper-dependent cell death modality driven by acylated protein aggregation and mitochondrial proteotoxic stress, intersects with inflammatory signaling. Hexokinase domain-containing protein 1 (HKDC1), the fifth hexokinase, regulates mitochondrial function, yet its role in cuproptosis and LPS-induced macrophage inflammation remains undefined. Using THP-1-derived macrophages, we assessed plasticity via CCK8 viability and phagocytosis assays, quantified inflammatory factors and cuproptosis-related proteins by western blot and RT-qPCR, and mapped HKDC1 expression/localization through ChIP-qPCR and immunofluorescence. LPS elevated inflammatory cytokines, suppressed cuproptosis, activated glycolysis, and induced HKDC1 via TLR4. HKDC1 knockdown reversed these effects, inhibiting glycolysis and triggering cuproptosis. Mechanistically, LPS promoted Yin Yang 1 (YY1) binding to the HKDC1 promoter, driving transcription. HKDC1 interacted with HSCB and FDX1, increasing intracellular copper and cuproptosis. In vivo, HKDC1 knockdown alleviated acute sepsis by activating copper-dependent cell death. These findings establish HKDC1 as a central node linking LPS, glycolysis, and cuproptosis, proposing a cuproptosis-dependent anti-inflammatory strategy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025028
ISGylation is the post-translational modification of protein substrates covalently conjugated with the ubiquitin-like protein interferon-stimulated gene 15 (ISG15). Initially linked to antiviral immunity, recent evidence highlights important roles for ISGylation in various biological processes, such as maintaining genomic stability, promoting tumourigenesis, and being involved in other pathological conditions. In this review, we examine the molecular mechanisms underlying ISGylation, its interplay with other post-translational modifications, and its involvement in diverse biological and pathological processes. We propose future research directions to advance the field and discuss how ISGylation might be harnessed to ensure human health, particularly genome instability-associated diseases. The modification is catalyzed by an enzymatic cascade analogous to ubiquitination, involving the E1-activating enzyme UBA7 (Ube1L), E2-conjugating enzyme UbcH8, and E3 ligases such as HERC5, TRIM25, and RNF213. ISG15 is a 15 kDa protein comprising two tandem ubiquitin-like domains, initially synthesized as a 165-amino-acid precursor that undergoes processing by a human ortholog of yeast ubiquitin-specific protease Ubp1 to yield a mature 156-amino-acid protein. A conserved C-terminal motif (151-LRLRGG-156) is essential for target protein conjugation. ISGylation is reversed by the protease USP18 (UBP43). The modification is induced by type I interferons, lipopolysaccharide, DNA damage, and viral or bacterial infections. Beyond antiviral defense, ISGylation regulates DNA damage response, cell cycle progression, and immune signaling. Dysregulated ISGylation is implicated in cancer, inflammatory diseases, and viral pathogenesis. The review synthesizes current knowledge and outlines therapeutic opportunities targeting ISGylation for genome instability-associated diseases.