Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05059-5
Background Mitochondrial dysfunction contributes to poor embryo quality and recurrent assisted reproductive technology (ART) failure. Mitochondrial transplantation (MIT), which involves supplementing oocytes with exogenous mitochondria, has been proposed as a novel strategy to improve ART outcomes. However, both its clinical efficacy and safety remain unclear.
Methods In this single-center trial, 151 patients with a history of ≥ 2 failed ART cycles provided 1178 metaphase II (MII) oocytes. Sibling oocytes were randomized 1:1 to receive autologous bone marrow mesenchymal stem cells (BMSCs) mitochondria co-injection during intracytoplasmic sperm injection (ICSI) or standard ICSI. The primary outcome was the rate of day-3 good-quality embryos.
Results MIT significantly accelerated early embryonic cleavage at the 3-cell stage and 5-cell stage, but this morphokinetic alteration did not translate into improvements in good-quality embryo rate, clinical pregnancy rate, or live birth rate. Long-term follow-up of 23 live births revealed no adverse effects, with all offspring exhibiting normal growth and development. Exploratory analysis revealed that oocytes yielding ≥ 70% transferable embryos after MIT harbored an elevated higher burden of medium frequency (0.05–0.5) mtDNA point mutations.
Conclusions While autologous BMSCs-MIT transiently alters early cleavage kinetics, it does not demonstrate a clinical advantage in unselected patients with recurrent ART failure. Nevertheless, its observed safety profile and the identification of mtDNA mutation burden as a potential predictive biomarker provide a foundation for shifting future MIT research from a universal approach toward precision application in molecularly stratified populations.
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•2024•DOI: 10.1186/s13287-024-03838-6
Correction to: Stem Cell Research & Therapy (2023) 14:17. The authors note that during the preparation of the manuscript, the track plot included the expression trends of 14 genes (with Tk1 and Pclaf repeated twice), but only 13 gene symbols were labeled, resulting in a mismatch and repeat of the trackplot with the image on the right. This error occurred during the typesetting process of the original figures. The authors have corrected the annotations in Fig. 2C as shown ahead in this correction article, apologise for the error, and confirm that the overall results and conclusions are not affected by this change.
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.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04111-6
Background hucMSC-exosomes can be engineered to strengthen their therapeutic potential, and the present study aimed to explore whether hypoxic preconditioning can enhance the angiogenic potential of hucMSC-exosomes in an experimental model of POF. Methods Primary hucMSCs and ROMECs were isolated from fresh tissue samples and assessed through a series of experiments. Exosomes were isolated from hucMSCs under normoxic or hypoxic conditions (norm-Exos and hypo-Exos, respectively) and then characterized using classic experimental methods. Based on a series of angiogenesis-related assays, we found that hypo-Exos significantly promoted ROMEC proliferation, migration, and tube formation and increased angiogenesis-promoting molecules in vitro. Histology, immunohistochemistry, and immunofluorescence experiments in a rat model of POF demonstrated that hypoxia pretreatment strengthens the therapeutic angiogenic effect of hucMSC-exosomes in vivo. Subsequently, high-throughput miRNA sequencing, qRT-PCR analysis, and western blotting were employed to identify the potential molecular mechanism. Results We found that hypo-Exos enhance endothelial function and angiogenesis via the transfer of miR-205-5p in vitro and in vivo. Finally, based on the results of bioinformatics analysis, dual luciferase reporter assays, and gain- and loss-of-function studies, we found evidence indicating that exosomal miR-205-5p enhances angiogenesis by targeting the PTEN/PI3K/AKT/mTOR signalling pathway. These results indicated for the first time that exosomes derived from hypoxia-conditioned hucMSCs strongly enhance angiogenesis via the transfer of miR-205-5p by targeting the PTEN/PI3K/AKT/mTOR signalling pathway. Conclusions Our findings provide a theoretical basis and demonstrate the potential application of a novel cell-free approach with stem cell-derived products in the treatment of POF.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03781-6
Due to the advanced studies on stem cells in developmental biology, the roles of stem cells in the body and their phenotypes in related diseases have not been covered clearly. Meanwhile, with the intensive research on the mechanisms of stem cells in regulating various diseases, stem cell therapy is increasingly being attention because of its effectiveness and safety. As one of the most widely used stem cell in stem cell therapies, hematopoietic stem cell transplantation shows huge advantage in treatment of leukemia and other blood-malignant diseases. Besides, due to the effect of anti-inflammatory and immunomodulatory, mesenchymal stem cells could be a potential therapeutic strategy for variety infectious diseases. In this review, we summarized the effects of Staphylococcus aureus (S. aureus) and its components on different types of adult stem cells and their downstream signaling pathways. Also, we reviewed the roles of different kinds of stem cells in various disease models caused by S. aureus, providing new insights for applying stem cell therapy to treat infectious diseases.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026018
Doxorubicin (DOX) remains a cornerstone chemotherapeutic agent for malignancies, yet its clinical utility is severely limited by dose-dependent cardiotoxicity, which can lead to progressive left ventricular dysfunction and heart failure. Pleiotrophin (PTN), a heparin-binding growth factor with diverse physiological functions, regulates glucose and lipid metabolism and promotes oxidative energy pathways. However, whether PTN exerts protective effects against DOX-induced cardiotoxicity (DIC) remains unclear. In this study, we establish cellular and animal models of DIC. DOX administration induces pronounced myocardial injury in both models, characterized by impaired ventricular contractility, increased fibrotic remodeling, and reduced cell viability. Concurrently, PTN protein expression is significantly downregulated in cardiomyocytes under DOX treatment. Overexpression of PTN substantially alleviates these pathological changes. In vitro, PTN reduces mitochondrial oxidative stress and apoptosis while restoring energy production and cell viability. In vivo, PTN improves mitochondrial ultrastructure, decreases cardiomyocyte apoptosis, and enhances cardiac function. Mechanistically, PTN directly binds to SIRT1 and activates AMPK phosphorylation at Thr172, triggering a downstream cascade through the AMPK-PGC1α axis that reprograms mitochondrial energy metabolism and attenuates cardiotoxicity. In conclusion, the PTN-SIRT1 axis protects against DIC by reducing oxidative stress and promoting mitochondrial energy homeostasis via the AMPK/PGC1α pathway, highlighting its potential as a novel therapeutic target for preventing chemotherapy-related cardiac injury.
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.2025068
Lysine acetylation has been shown to be an abundant and vital post-translational modification (PTM) that utilizes acetyl phosphate (AcP) as one of the acetyl group donors in bacteria. The pyruvate dehydrogenase (PDH) complex catalyzes the conversion from pyruvate to acetyl coenzyme A (acetyl-CoA). Thus far, the connection between lysine acetylation and pyruvate metabolism has not been thoroughly investigated. In this study, we show that AcP could acetylate Escherichia coli pyruvate dehydrogenase (AceE) in vitro and in vivo, which could be reversed by protein lysine deacetylase (CobB). In vitro treatment of AceE with AcP also causes increased phosphorylation of the protein, whereas deleting ackA does not affect the phosphorylation of the protein. As a result, in vitro treatment of AceE by AcP leads to decreased enzymatic activity. In contrast, deleting ackA leads to increased acetylation and enzymatic activity of AceE, and deleting pta results in the decreased acetylation and enzymatic activity of AceE. As expected, deleting pta in E. coli causes pyruvate accumulation. Although deleting ackA also causes pyruvate accumulation, decreased expression of the two genes involved in pyruvate metabolism (ldhA and poxB) is observed in the mutant, indicating that AcP could affect pyruvate metabolism by other routes in addition to modulating the AceE activity. Thus, our results demonstrate that intracellular AcP could modulate pyruvate metabolism in E. coli. For the first time, a linkage between AcP-mediated protein lysine acetylation, pyruvate dehydrogenase activity, and pyruvate metabolism is established.
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•2026•DOI: 10.3724/abbs.2025146
Actin-bundling protein Fascin1 (FSCN1) is encoded by the Fscn1 gene and is crucial for cytoskeletal remodeling and cellular migration. Although a previous study linked Fscn1 deficiency to neonatal lethality in mice, the underlying metabolic mechanism remains unclear. In this study, we report that systemic knockout (KO) of Fscn1 leads to 52.2% mortality within 24 h post-birth, accompanied by severe hypoglycemia in KO pups compared with their littermates. Remarkably, this lethality is fully rescued by oral glucose administration, indicating a glucose supply-dependent survival mechanism. Surviving Fscn1-KO neonates display persistent developmental deficits, including growth retardation and depleted lipid stores, despite intact canonical insulin-regulated hepatic gluconeogenic pathways. Transcriptomic profiling of P0 livers reveals that Fscn1 loss predominantly disrupts metabolic pathways, with the glycerol phosphate shuttle being the most significantly downregulated module. Mechanistically, Fscn1-KO livers exhibit markedly reduced protein levels of glycerol-3-phosphate dehydrogenase isoforms (GPD1/GPD2), key enzymes bridging glycolysis and gluconeogenesis. Consistently, glycerol tolerance tests demonstrate impaired glycerol-to-glucose conversion in Fscn1-KO mice, confirming defective glycerol-driven gluconeogenesis. Our findings establish FSCN1 as a novel cytoskeletal-metabolic integrator essential for neonatal survival by sustaining hepatic glucose production from glycerol, thus revealing an unexpected role of actin dynamics in coordinating metabolic adaptation during early postnatal development.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024134
SUN5, a testis-specific gene, is associated with acephalic spermatozoa syndrome (ASS). Here, we demonstrate that SUN5 is involved in mRNA export. In Sun5-knockout mice (Sun5–/–), poly(A)+ RNA accumulates in the nuclei of germ cells, leading to reduced sperm counts, decreased sperm motility and disrupted sperm head-to-tail junctions. Additionally, in the GC-2 germ cell line with RNA interference of Sun5, heterogeneous nuclear ribonucleoproteins (hnRNPs) and poly (A)+ RNA (mainly mRNA) are retained in the nucleus. Further mechanistic studies reveal that SUN5 interacts with Nxf1 (nuclear RNA export factor 1) and nucleoporin 93 (Nup93). Interference with Nup93 inhibits mRNA export. Treatment with leptomycin B to block the CRM1 pathway indicates that Sun5 regulates mRNA export through an Nxf1-dependent pathway. In Sun5–/– mice, the binding of Nxf1 and Nup93 decreases due to loss of Sun5 function, and the process of submitting Nxf1-binding mRNPs to Nup93 is inhibited, resulting in abnormal spermatogenesis. Together, these data may elucidate a novel pathway for mRNA export in male germ cells.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024069
Cetuximab (CET), a human murine chimeric IgG monoclonal antibody and an inhibitor of epidermal growth factor receptor (EGFR), has been shown to be effective in treating various types of cancer. However, its use is hindered by limitations such as resistance development, variability in patient response, side effects, and challenges in biomarker identification. Therefore, CET is often combined with other targeted therapies or chemotherapies to enhance its effectiveness. In this study, we investigate the anticancer effects and underlying mechanisms of the combination of CET, an EGFR inhibitor, and STA9090, an inhibitor of heat shock protein 90 (Hsp90), in both in vitro and in vivo models of non-small cell lung cancer (NSCLC). The results demonstrate significantly stronger effects on NSCLC cells in response to combination therapy than to treatment with either agent alone, indicating that the combination of CET and STA9090 has potential synergistic effects. Additionally, the combination therapy inhibits tumor growth in a xenograft nude mouse model more effectively than treatment with either agent alone, suggesting improved efficacy when used together. Furthermore, the synergistic effects of the combination therapy are likely due to inactivation of the receptor tyrosine kinase (RTK) pathway, which is overly activated in cancer and contributes to tumor growth, angiogenesis, and metastasis. Consequently, our findings suggest that STA9090 has potent direct antitumor activity and synergizes with CET against NSCLC tumors. It is highly likely that these synergistic effects are mediated through RTK pathway inactivation caused by the combination. Therefore, our findings strongly and consistently support the potential synergistic effect of STA9090, an RTK inhibitor, in combination with EGFR-targeting agents.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024060
Medial arterial calcification (MAC) accompanying chronic kidney disease (CKD) leads to increased vessel wall stiffness, myocardial ischemia, heart failure, and increased cardiovascular morbidity and mortality. Unfortunately, there are currently no drugs available to treat MAC. The natural polyphenol epigallocatechin-3-gallate (EGCG) has been demonstrated to protect against cardiovascular disease; however, whether EGCG supplementation inhibits MAC in CKD remains unclear. In this study, we utilize a CKD-associated MAC model to investigate the effects of EGCG on vascular calcification and elucidate the underlying mechanisms involved. Our findings demonstrate that EGCG treatment significantly reduces calcium phosphate deposition and osteogenic differentiation of VSMCs in vivo and in vitro in a dose-dependent manner. In addition, through RNA sequencing (RNA-seq) analysis, we show a significant activation of the transcription factor JunB both in CKD mouse arteries and in osteoblast-like VSMCs. Notably, EGCG effectively suppresses CKD-associated MAC by inhibiting the activity of JunB. In addition, overexpression of JunB can abolish while knockdown of JunB can enhance the inhibitory effect of EGCG on the osteogenic differentiation of VSMCs. Furthermore, EGCG supplementation inhibits MAC in CKD via modulation of the JunB-dependent Ras/Raf/MEK/ERK signaling pathway. In conclusion, our study highlights the potential therapeutic value of EGCG for managing CKD-associated MAC, as it mitigates this pathological process through targeted inactivation of JunB.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024068
Transient receptor potential channel subfamily vanilloid 1 (TRPV1) is a member of the transient receptor potential family of nonselective cationic transmembrane channel proteins that are involved in the regulation of calcium homeostasis. It is expressed in various tumor types and has been implicated in the regulation of cancer growth, metastasis, apoptosis, and cancer-related pain. TRPV1 is highly expressed in triple-negative breast cancer (TNBC), and both its agonists and antagonists may exert anti-cancer effects. In this review, we provide an overview of the effect of TRPV1 on TNBC development and its influence on immunotherapy in an attempt to facilitate the development of future treatment strategies.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024231
Gastric cancer (GC) is an aggressive tumor type with an intricate pathogenesis and limited therapeutic options. Ubiquitin-specific protease 22 (USP22) is a protein implicated in cell proliferation, metastasis, and tumorigenesis. However, the regulatory mechanisms governing USP22 in GC are still not fully understood. In this study, we perform bioinformatics analysis to identify conserved miRNA recognition sites for miR-200b-5p within the 3′UTR of USP22. Validation via luciferase reporter assay confirms the transcriptional regulation of USP22 by miR-200b-5p. Overexpression of miR-200b-5p markedly inhibits the proliferation and migration of GC cells in vitro and suppresses tumor growth in vivo. Conversely, ectopic expression of USP22 reversed this effect by modulating the NF-κB signaling pathway. Additionally, qPCR analysis reveals an inverse correlation between the miR-200b-5p level and USP22 expression in GC. Collectively, our findings indicate that miR-200b-5p-mediated inhibition of USP22 attenuates cell proliferation by targeting the NF-κB signaling pathway in GC, suggesting that miR-200b-5p and USP22 could serve as potential diagnostic or therapeutic targets for gastric cancer and other related human diseases.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025156
CD19-directed chimeric antigen receptor T (CAR-T) cell therapy is promising for treating relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), yet its long-term efficacy remains limited by CAR-T-cell exhaustion. Given the broad immunomodulatory activities of vitamin D, we investigate whether its active form, 1α,25(OH)2D3, enhances CAR-T-cell functionality and improves therapeutic outcomes. We demonstrate that 1α,25(OH)2D3 treatment significantly mitigates exhaustion and enhances the antitumor activity of CD19 CAR-T cells derived from both healthy donors and DLBCL patients, which is further validated in xenograft mouse models. Mechanistically, we show that 1α,25(OH)2D3 upregulates the expression of the vitamin D receptor (VDR), promoting transcriptional reprogramming associated with memory-like differentiation and downregulation of exhaustion-related genes, thereby reshaping the functional heterogeneity of CAR-T cells under tumor stimulation. Our study highlights 1α,25(OH)2D3 supplementation as a safe and accessible approach to mitigate terminal differentiation and exhaustion of CAR-T cells, offering a promising strategy to enhance the clinical efficacy of CAR-T therapy in patients with R/R DLBCL.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025083
The urea cycle occurs mainly in the liver and undergoes changes during hepatocarcinogenesis. Argininosuccinate synthase 1 (ASS1) is a key enzyme in the urea cycle and is expressed at low levels in certain cancers. LM2I, a specific activator of ASS1, exhibits significant antitumor activity. However, the antitumor mechanism of LM2I in liver cancer remains unclear. In this study, we find that LM2I is more effective for liver cancer cells with low ASS1 expression. The results of the IP-LC/MS experiments reveal that ASS1 interacts with CAD. The expressions of ASS1 and CAD in liver cancer tissues and cells are negatively correlated. LM2I promotes the ubiquitination of CAD protein through ASS1. LM2I inhibits the proliferation of liver cancer cells in vivo and in vitro. However, its efficacy is weak in liver cancer cells stably overexpressing CAD. The H&E staining results reveal that LM2I has no toxicity in mice. In terms of metabolism, LM2I increases the urea content and decreases the pyrimidine content in liver cancer cells. Overexpression of CAD can reduce the inhibitory effect of LM2I on pyrimidine. Pyrimidine supplementation facilitates the proliferation of liver cancer cells, particularly when they are treated with LM2I. In summary, ASS1 interacts with CAD, and LM2I enhances CAD degradation through the activation of ASS1, consequently inhibiting pyrimidine synthesis and the progression of liver cancer.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024026
Adhesion molecules play critical roles in maintaining the structural integrity of the airway epithelium in airways under stress. Previously, we reported that catenin alpha-like 1 (CTNNAL1) is downregulated in an asthma animal model and upregulated at the edge of human bronchial epithelial cells (HBECs) after ozone stress. In this work, we explore the potential role of CTNNAL1 in the structural adhesion of HBECs and its possible mechanism. We construct a CTNNAL1‒/‒ mouse model with CTNNAL1-RNAi recombinant adeno-associated virus (AAV) in the lung and a CTNNAL1-silencing cell line stably transfected with CTNNAL1-siRNA recombinant plasmids. Hematoxylin and eosin (HE) staining reveals that CTNNAL1‒/‒ mice have denuded epithelial cells and structural damage to the airway. Silencing of CTNNAL1 in HBECs inhibits cell proliferation and weakens extracellular matrix adhesion and intercellular adhesion, possibly through the action of the cytoskeleton. We also find that the expressions of the structural adhesion-related molecules E-cadherin, integrin β1, and integrin β4 are significantly decreased in ozone-treated cells than in vector control cells. In addition, our results show that the expression levels of RhoA/ROCK1 are decreased after CTNNAL1 silencing. Treatment with Y27632, a ROCK inhibitor, abolished the expressions of adhesion molecules induced by ozone in CTNNAL1-overexpressing HBECs. Overall, the findings of the present study suggest that CTNNAL1 plays a critical role in maintaining the structural integrity of the airway epithelium under ozone challenge, and is associated with epithelial cytoskeleton dynamics and the expressions of adhesion-related molecules via the RhoA/ROCK1 pathway.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024110
Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of advanced/metastatic patients with lung cancer. However, only a small proportion of patients can benefit from ICIs, and clinical management of the treatment process remains challenging. Glycosylation has added a new dimension to advance our understanding of tumor immunity and immunotherapy. To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins, a series of serum samples from 12 patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, are firstly analyzed with mass-spectrometry-based label-free quantification method. Second, a stratification analysis is performed among anti-PD-1/PD-L1 responders and non-responders, with serum levels of glycopeptides correlated with treatment response. In addition, in an independent validation cohort, a large-scale site-specific profiling strategy based on chemical labeling is employed to confirm the unusual characteristics of IgG N-glycosylation associated with anti-PD-1/PD-L1 treatment. Unbiased label-free quantitative glycoproteomics reveals serum levels’ alterations related to anti-PD-1/PD-L1 treatment in 27 out of 337 quantified glycopeptides. The intact glycopeptide EEQFN177STYR (H3N4) corresponding to IgG4 is significantly increased during anti-PD-1/PD-L1 treatment (FC=2.65, P=0.0083) and has the highest increase in anti-PD-1/PD-L1 responders (FC=5.84, P=0.0190). Quantitative glycoproteomics based on protein purification and chemical labeling confirms this observation. Furthermore, obvious associations between the two intact glycopeptides (EEQFN177STYR (H3N4) of IgG4, EEQYN227STFR (H3N4F1) of IgG3) and response to treatment are observed, which may play a guiding role in cancer immunotherapy. Our findings could benefit future clinical disease management.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024015
Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database. Breast cancer-related genes are obtained from the GeneCards database. Major targets and pathways related to SYF treatment in breast cancer are identified by analyzing the above data. By conducting molecular docking analysis, we find that the active ingredients quercetin and luteolin bind well to the key targets KDR1, PPARG, SOD1, and VCAM1. In vitro experiments verify that SYF can reduce the proliferation, migration, and invasion ability of TNBC cells. Using a TNBC xenograft mouse model, we show that SYF could delay tumor growth and effectively inhibit the occurrence of breast cancer lung metastasis in vivo. PPARG, SOD1, KDR1, and VCAM1 are all regulated by SYF and may play important roles in SYF-mediated inhibition of TNBC recurrence and metastasis.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024062
Ubiquitin-conjugation enzyme E2C (UBE2C) is a crucial component of the ubiquitin-proteasome system that is involved in numerous cancers. In this study, we find that UBE2C expression is significantly increased in mouse embryos, a critical stage during skeletal muscle development. We further investigate the function of UBE2C in myogenesis. Knockdown of UBE2C inhibits C2C12 cell differentiation and decreases the expressions of MyoG and MyHC, while overexpression of UBE2C promotes C2C12 cell differentiation. Additionally, knockdown of UBE2C, specifically in the tibialis anterior muscle (TA), severely impedes muscle regeneration in vivo. Mechanistically, we show that UBE2C knockdown reduces the level of phosphorylated protein kinase B (p-Akt) and promotes the degradation of Akt. These findings suggest that UBE2C plays a critical role in myoblast differentiation and muscle regeneration and that UBE2C regulates myogenesis through the Akt signaling pathway.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261622
Dried flower buds or newly opened flowers of Lonicera macranthoides are used as Shanyinhua (Lonicerae Flos) for medicinal purposes. The Xianglei cultivar, developed from a natural mutant, exhibits a distinctive phenotype characterized by non-opening corolla and prolonged bud stage. This study aimed to elucidate the cellular and molecular mechanisms underlying this unique corolla phenotype. The flower of conventional cultivar (WT) and the Xianglei cultivar (XL) of L. macranthoides were used as materials. Corolla adaxial epidermal cells and longitudinal sections were observed using light microscopy. The expression patterns of xyloglucan endotransglucosylase/hydrolase genes (LmXTH6, LmXTH7, LmXTH33), expansin gene (LmEXP7), and pectin methylesterase genes (LmPME28, LmPME45) were analyzed by qRT-PCR. Protein-protein interaction networks were predicted using the STRING database. Ruthenium red staining coupled with Image J quantitative analysis was performed to assess the degree of pectin de-methylesterification in corolla cell walls. In the WT, the adaxial cells of corolla displayed a spatially sequential expansion, with the basal cells expanding first, followed by the middle cells. Moreover, the expansion rate of the adaxial cells is higher than that of the abaxial cells. In contrast, the expansion rate of adaxial cells in XL was significantly reduced, and the degree of cell expansion was not obvious. At the molecular level, LmXTH6, LmXTH7, and LmXTH33 were highly expressed in WT during the pre-anthesis and anthesis stages, but their expression was significantly inhibited in XL. LmEXP7 expression peaked before corolla opening in WT, while its expression was lower in XL during the same period. Ruthenium red staining results indicated that the overall degree of de-methylesterification in XL was higher than that in WT, consistent with the expression trends of LmPME28 and LmPME45. In conclusion, the non-opening corolla of the Xianglei cultivar is closely related to the inhibition of corolla cell expansion. The low expression of XTHs and EXP collectively leads to a decrease in the expansion capacity of Xianglei corolla cells, while the up-regulation of PMEs increases pectin de-methylesterification in the cell wall, potentially enhancing cell wall rigidity. The synergy of XTH/EXP-PME may be an important reason for the non-opening corolla of Xianglei, providing experimental evidence for the study of the regulatory mechanism of the excellent phenotype of Xianglei L. macranthoides and offering new insights into the cell wall regulatory mechanisms of plant floral organ morphogenesis.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261607
This study addresses the pharmacodynamic material basis of Houttuynia cordata volatile oil by integrating supramolecular "imprinting template" theory with matching frequency, total statistical moment, and factor rotation methods, coupled to in vitro antitumor activity. Fifty-eight batches (S1–S58) from different origins were fingerprinted by GC-MS. The matching frequency method reduced the imprinting template to 34 structural "material units" (A1–A34). Integration significantly decreased average peak count and information entropy (P < 0.01), while total zero-, first-, and second-order moments and information content remained unchanged. Factor rotation extracted eight common factors; comprehensive scores ranked S16 and S54 highest and S24 and S27 lowest. CCK-8 assays against human lung adenocarcinoma A549 cells yielded IC50 values from 73.6 to 269.9 nL/mL. Comprehensive scores negatively correlated with IC50 (r = −0.739, P < 0.01). High-contribution units A34, A31, and A7 were preliminarily identified as a potential pharmacodynamic component group. The model demonstrates utility for trend-level quality evaluation but does not provide one-to-one prediction of single-batch efficacy. Limitations include restriction to volatile constituents, single-cell-line validation, and lack of independent isolation and enrichment for the flagged units. The protocol offers a transferable statistical framework for linking chromatographic fingerprints to bioactivity in complex botanical oils.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05059-5
Background: Mitochondrial dysfunction contributes to poor embryo quality and recurrent assisted reproductive technology (ART) failure. Mitochondrial transplantation (MIT) has been proposed to improve ART outcomes, but its efficacy and safety remain unclear. Methods: In this single-center trial, 151 patients with ≥2 failed ART cycles provided 1178 metaphase II (MII) oocytes. Sibling oocytes were randomized 1:1 to receive autologous bone marrow mesenchymal stem cell (BMSC) mitochondria co-injection during intracytoplasmic sperm injection (ICSI) or standard ICSI. The primary outcome was day-3 good-quality embryo rate. Results: MIT significantly accelerated early cleavage at the 3-cell and 5-cell stages, but this did not translate into improved good-quality embryo rate, clinical pregnancy rate, or live birth rate. Long-term follow-up of 23 live births revealed no adverse effects, with normal growth and development. Exploratory analysis showed that oocytes yielding ≥70% transferable embryos after MIT harbored a higher burden of medium-frequency (0.05–0.5) mtDNA point mutations. Conclusions: Autologous BMSC-MIT transiently alters early cleavage kinetics but does not demonstrate clinical advantage in unselected patients with recurrent ART failure. Its safety profile and the identification of mtDNA mutation burden as a potential predictive biomarker support shifting future research toward precision application in molecularly stratified populations.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026018
Doxorubicin (DOX) remains a cornerstone chemotherapeutic agent for malignancies, yet its clinical utility is severely limited by dose-dependent cardiotoxicity, which can lead to progressive left ventricular dysfunction and heart failure. Pleiotrophin (PTN), a heparin-binding growth factor with diverse physiological functions, regulates glucose and lipid metabolism and promotes oxidative energy pathways. However, whether PTN exerts protective effects against DOX-induced cardiotoxicity (DIC) remains unclear. In this study, we establish cellular and animal models of DIC. DOX administration induces pronounced myocardial injury in both models, characterized by impaired ventricular contractility, increased fibrotic remodeling, and reduced cell viability. Concurrently, PTN protein expression is significantly downregulated in cardiomyocytes under DOX treatment. Overexpression of PTN substantially alleviates these pathological changes. In vitro, PTN reduces mitochondrial oxidative stress and apoptosis while restoring energy production and cell viability. In vivo, PTN improves mitochondrial ultrastructure, decreases cardiomyocyte apoptosis, and enhances cardiac function. Mechanistically, PTN directly binds to SIRT1 and activates AMPK phosphorylation at Thr172, triggering a downstream cascade through the AMPK-PGC1α axis that reprograms mitochondrial energy metabolism and attenuates cardiotoxicity. In conclusion, the PTN-SIRT1 axis protects against DIC by reducing oxidative stress and promoting mitochondrial energy homeostasis via the AMPK/PGC1α pathway, highlighting its potential as a novel therapeutic target for preventing chemotherapy-related cardiac injury.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21279
Objective: To systematically compare the acute effects of blood flow restriction combined with preconditioning (to induce post-activation performance enhancement) versus preconditioning alone or sitting, low-intensity preconditioning combined with blood flow restriction versus high-intensity preconditioning, and sitting combined with blood flow restriction versus sitting on sports performance using a multilevel meta-analysis. Methods: Following the PRISMA guidelines, Web of Science, PubMed, SPORTDiscus, and CNKI databases were systematically searched (from inception to May 24, 2025). Inclusion criteria: (1) healthy individuals who were at least physically active; (2) studies with at least one of the following four comparisons: preconditioning + blood flow restriction vs. preconditioning alone; preconditioning + blood flow restriction vs. sitting; low-intensity preconditioning + blood flow restriction vs. high-intensity preconditioning; sitting + blood flow restriction vs. sitting; (3) sports performance (e.g., jump, sprint, bench press throw) as the primary outcome; (4) randomized or non-randomized crossover/parallel designs; (5) published in peer-reviewed Chinese or English journals. Risk of bias was assessed using ROB-2, and evidence quality was evaluated with GRADE. Data were fitted using cluster robust variance estimation and a three-level mixed-effects model, with small-sample corrections. Subgroup analyses and meta-regression explored moderators and sources of heterogeneity. Results: Twelve studies (196 participants, 12 women, 184 men) were included. Main findings: (1) Preconditioning + blood flow restriction was more effective than preconditioning alone in enhancing sports performance (ES=0.21, 95%CI=0.01-0.40, GRADE=low), with the best effect at recovery times of 4-12 min and 50% arterial occlusion pressure (ES=1.49); (2) Preconditioning + blood flow restriction did not significantly differ from sitting (ES=0.52, 95%CI=-0.12-1.15, GRADE=very low), but preconditioning + 140 mmHg blood flow restriction was superior to preconditioning alone (ES=1.21, 95%CI=0.14-2.28); (3) Low-intensity preconditioning + blood flow restriction did not differ from high-intensity preconditioning (ES=-0.10, 95%CI=-0.84-0.64, GRADE=low); (4) Sitting + blood flow restriction did not significantly differ from sitting (ES=0.24, 95%CI=-0.03-0.52, GRADE=very low). Notably, the effects of the latter two comparisons significantly decreased with recovery time (β=-0.04, P < 0.01 and β=-0.04, P=0.02). Conclusion: Preconditioning combined with blood flow restriction is more effective than preconditioning alone in inducing post-activation performance enhancement, preliminarily suggesting the use of 50% arterial occlusion pressure and 4-12 min recovery time. However, preconditioning combined with blood flow restriction does not appear to be more effective than sitting, possibly due to insufficient number of included studies. Additionally, low-intensity preconditioning + blood flow restriction can achieve similar post-activation performance enhancement as high-intensity preconditioning, while the potential benefit of sitting + blood flow restriction on sports performance may diminish over time. Overall, it is preliminarily recommended to use low-intensity preconditioning (e.g., 30% one-repetition maximum squat or bodyweight training) combined with 50% arterial occlusion pressure or 140 mmHg blood flow restriction, with 4-12 min recovery before subsequent performance testing.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21272
BACKGROUND: Patients with cervical spondylosis often exhibit varying kinematic abnormalities due to degenerative structural changes and biomechanical imbalances in the cervical spine. Although previous studies have compared specific kinematic parameters between healthy individuals and cervical spondylosis patients, research on coupled motions and their associated ratios remains limited. OBJECTIVE: To investigate changes in kinematic parameters in cervical spondylosis patients before and after Feng's spinal manipulation therapy. METHODS: Thirty patients with cervical spondylosis and 30 healthy controls were enrolled. Participants completed three standardized motion tasks: lateral flexion, flexion-extension, and axial rotation. Three-dimensional cervical spine kinematics were quantified using stereophotogrammetry upon admission and discharge. The following kinematic parameters were analyzed: primary range of motion, coupled motion range, coupled motion patterns, motion symmetry, motion smoothness, and motion velocity. RESULTS AND CONCLUSION: Compared with healthy controls, patients with cervical spondylosis showed significantly reduced maximal angles in lateral flexion, flexion-extension, and axial rotation (P < 0.05), and significantly increased ratios of coupled flexion-extension during lateral flexion, coupled rotation during lateral flexion, coupled lateral flexion during extension, and coupled lateral flexion during rotation (P < 0.05). After treatment, patients showed significant improvements in visual analog scale score and cervical dysfunction index (P < 0.05). Significant differences were found in maximal lateral flexion angle, lateral flexion symmetry, maximum and average lateral flexion velocity, maximal flexion-extension angle, maximum and average flexion-extension velocity, maximal rotation angle, rotation symmetry, maximum rotation velocity, and average left rotation velocity before and after treatment (P < 0.05). No significant differences were observed in coupled motion patterns before and after treatment (P > 0.05). Significant differences were found in the ratios of coupled flexion-extension during right lateral flexion, coupled rotation during lateral flexion, coupled flexion-extension during right rotation, and coupled lateral flexion during rotation before and after treatment (P < 0.05). In conclusion, patients with cervical spondylosis exhibit increased ratios of some coupled motions relative to primary motions. Feng's spinal manipulation can significantly improve clinical symptoms and effectively restore cervical motor function.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21369
BACKGROUND: Oxidative stress, representing an imbalance between oxidative and antioxidant systems in the body, plays a crucial role in the pathogenesis of osteoporosis. However, a systematic analysis of the current research status and trends in the field of oxidative stress and osteoporosis is lacking. OBJECTIVE: To analyze the current research status, hot topics, and trends in the field of oxidative stress and osteoporosis using bibliometric methods. METHODS: The Web of Science core database was searched using “oxidative stress” and “osteoporosis” as search terms, with the language limited to “English” and the document type limited to “article” and “review article.” The search period was from January 1, 1999 to December 31, 2024. After screening the literature according to the inclusion and exclusion criteria, CiteSpace (6.3.R1) and VOSviewer (1.6.20) software were used for data analysis and visualization of publication volume, country, institution, author, journal, and keywords. RESULTS AND CONCLUSION: (1) Publication volume analysis: A total of 2 558 articles were retrieved, with 2 416 articles included. From 1999 to 2024, the number of publications in the field of oxidative stress and osteoporosis showed a significant increasing trend, especially after 2011, reflecting the gradual deepening and rising popularity of research in this field. (2) Country analysis: China ranked first with 1 088 publications, but the average citations per article were relatively low. The United States ranked second with 353 publications, but the average citations per article were as high as 74.62, demonstrating international influence in research quality. (3) Institution analysis: Chinese institutions dominated in publication volume, but the level of international cooperation needs improvement. Among them, Shanghai Jiao Tong University and Soochow University had extensive cooperation and high citation counts. (4) Author and co-cited author analysis: A few core authors such as Almeida and Manolagas had significant influence in this field, with extremely high citation counts and diverse collaboration models, dominated by international authors. (5) Journal analysis: American journals such as the Journal of Bone and Mineral Research occupied a core position in the field of osteoporosis and oxidative stress, with significant academic authority and influence. (6) Keyword analysis: The research core focused on the interaction mechanism between “osteoporosis” and “oxidative stress.” High-frequency keywords included “reactive oxygen species,” “inflammation,” “osteoblasts,” and “osteoclasts.” Keyword clustering analysis showed that research hotspots concentrated on inflammation, oxidative stress and bone metabolic imbalance, population and clinical studies, and the development and application of antioxidant therapy. (7) The field of oxidative stress and osteoporosis is growing rapidly. Although China occupies a dominant position, its international influence needs improvement. Future research should deeply analyze the oxidative stress signaling network, explore cross-disease interactions, develop novel antioxidants and therapeutic methods, promote precision medicine and multi-omics technology applications, and strengthen international cooperation and exchange, in order to provide more scientific and effective solutions for the prevention and treatment of osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21505
BACKGROUND: The Affiliated Hospital of Jiangxi University of Chinese Medicine has used traditional Chinese medicine (TCM) to treat children with cerebral palsy (CP) for over 20 years, but no analysis of medication patterns has been conducted. OBJECTIVE: To analyze TCM syndrome types and explore medication patterns for CP in children based on medical records and literature. METHODS: An evidence-based retrieval strategy was used to search and manage literature and medical records on TCM treatment for CP in children. Bibliometric methods were applied to mine and analyze data characteristics. VOSviewer software was used to create visual knowledge maps. IBM SPSS Modeler software was used for association rule analysis of TCM drugs. Radar chart method was used to analyze the four natures and five flavors of drugs. RESULTS AND CONCLUSION: A total of 503 medical records and 90 articles were included. Syndrome analysis showed that the main TCM syndrome type of CP in children was liver-kidney deficiency. Intervention analysis showed that external therapy was most frequently used, and among oral medications, drugs for nourishing liver and kidney were most common. Medication pattern analysis showed that among the top 20 drugs by frequency in both medical records and literature, 12 (60%) were the same. The drug pairs Shanyao (Rhizoma Dioscoreae) and Fuling (Poria), and Shudi (Radix Rehmanniae Preparata) and Fuling (Poria) had high support and confidence above 82.50%, indicating significant association. Among all TCM drugs for CP in children, the nature was mainly warm, followed by neutral and cold; the flavor was mainly sweet, followed by bitter and pungent; the meridian tropism was mainly liver and kidney meridians, followed by spleen, heart, and lung meridians. Most drugs in these formulas were non-toxic. The results indicate that CP in children is mainly characterized by liver-kidney deficiency, and the formulas used in clinical practice and related clinical research are mostly for nourishing liver and kidney, among which Liuwei Dihuang Pill and its derivative formulas appear most frequently. The drug pairs with the highest frequency and reliability are Shudi and Fuling, and Shanyao and Fuling. The nature and flavor of drugs are mainly warm, sweet, and attributed to liver and kidney meridians.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21497
BACKGROUND: Recent studies have demonstrated that mechanotransduction plays a critical role in the pathological processes of neurological disorders. PIEZO channels, as key mechanosensitive ion channels, serve as core mediators in sensing and transducing mechanical signals. However, a systematic review of their specific roles across various neurological diseases is relatively lacking. OBJECTIVE: To explore the roles and molecular mechanisms of PIEZO1 and PIEZO2 channels in central and peripheral nervous system diseases, and to evaluate their potential as therapeutic targets. METHODS: A literature search was conducted in PubMed, Web of Science, CNKI, WanFang, and VIP databases from January 2010 to May 2025. English search terms included 'central nervous system diseases', 'Central Nervous System Disorder', 'CNS Disease', 'CNS Diseases', 'Central Nervous System Disorders', 'neurodegenerative disease', 'Autonomic Nervous System Diseases', 'Brain Diseases', 'Central Nervous System Infections', 'High Pressure Neurological Syndrome', 'Spinal Cord Diseases', 'PIEZO1 Channel', 'PIEZO2 Channel', 'PIEZO Channel'; Chinese search terms included '神经系统疾病', '中枢神经系统疾病', 'PIEZO1', 'PIEZO2', 'PIEZO'. A combination of subject headings and free words was used. Based on inclusion and exclusion criteria, 60 English articles were finally included for systematic analysis and classified by disease type. RESULTS AND CONCLUSION: ①PIEZO1 is highly expressed in glioma and correlates with malignancy and poor prognosis; calcium influx promotes tumor proliferation and remodeling of microenvironment stiffness, driving tumor progression. ②In intracerebral hemorrhage, activation of neuronal PIEZO2 promotes iron transporter expression, increases intracellular iron accumulation, induces ferroptosis, and exacerbates secondary brain injury, while PIEZO1 dysfunction impairs cerebrovascular integrity and the blood-brain barrier. ③In traumatic brain injury, upregulation of PIEZO2 in neurons promotes neuronal death and pro-inflammatory cytokine release. ④Activation of PIEZO1 promotes fluid excretion in the brain, alleviating hydrocephalus. ⑤PIEZO1 dysfunction is involved in amyloid-beta toxicity, glial activation, vascular damage, and metabolic abnormalities in Alzheimer's disease. ⑥PIEZO1 activation inhibits myelination and modulates immune responses in multiple sclerosis. ⑦PIEZO1 mediates pulsatile pain characteristic of migraine induced by blood flow pulsation. ⑧Elevated intraocular pressure upregulates PIEZO1 and PIEZO2, leading to hyperexcitability and metabolic stress injury of retinal ganglion cells. ⑨PIEZO channels regulate neuronal excitability, proprioception, and baroreflex abnormalities in amyotrophic lateral sclerosis, and targeting PIEZO is a potential therapeutic strategy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21513
BACKGROUND: Schatzker IV tibial plateau fractures are highly challenging due to their involvement of the primary weight-bearing area and high rate of soft tissue complications. Although traditional double plating provides mechanical stability, it violates the minimally invasive principle and is associated with more postoperative complications, especially in elderly patients or those with high-energy trauma. Currently, there is a lack of an internal fixation strategy that can meet both mechanical stability and minimally invasive requirements.
OBJECTIVE: To establish a three-dimensional model of Schatzker IV tibial plateau fractures using the finite element method and compare the biomechanical stability of five fixation methods to provide an optimal surgical option for the treatment of Schatzker IV tibial plateau fractures.
METHODS: A healthy male volunteer underwent knee CT scanning, and a Schatzker IV tibial plateau fracture model was constructed using finite-element software. Five internal-fixation configurations were defined as Groups A, B, C, D, and E. Group A: isolated medial plate; Group B: medial plate plus two posteromedial tension screws; Group C: medial plate plus two lateral tension screws; Group D: posteromedial double plating; Group E: medial-lateral double plating. Under identical boundary and constraint conditions, finite-element analysis software was employed to evaluate the biomechanical performance of five internal fixation models.
RESULTS AND CONCLUSION: Finite element analysis showed that minimally invasive combinations (Groups B and C) had comparable overall biomechanical performance to traditional double plating. Group B was an ideal choice for elderly patients, as it had the lowest fracture fragment stress (9.0392 MPa), which could effectively prevent osteoporosis-related collapse, and the percutaneous screw technique reduced the risk of soft tissue complications. Group C showed potential in young patients, benefiting from the smallest implant displacement (4.388 mm), providing excellent stability, and the lateral tension screws avoided neurovascular injury associated with the posteromedial approach.
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.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026117
SGLT2 inhibitor (SGLT2i)-induced diabetic hyperketonemia is a life-threatening acute complication of diabetes. While celastrol has been reported to have beneficial effects on obesity, its potential role in ketogenesis remains unclear. In this study, celastrol administration significantly attenuates the fasting-induced increase in blood β-hydroxybutyrate levels. Moreover, a 7-day course of celastrol (1 mg/kg/day) leads to reductions in body weight and fat mass. Mechanistically, celastrol specifically downregulates HMGCS2 expression and suppresses hepatic ketogenesis through the inhibition of PPARα expression in the short term (≤ 2 days). However, after prolonged treatment for 7 days, celastrol modulates both PPARα and serum free fatty acid (FFA) levels. Furthermore, the anti-ketogenic effect of celastrol is abolished in Pparα⁻/⁻ mice. Importantly, celastrol effectively ameliorates SGLT2i-induced hyperketonemia. In summary, celastrol curbs hepatic ketone overproduction in a PPARα-dependent manner, indicating its protective potential against SGLT2i-induced hyperketonemia.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026035
Pulmonary fibrosis (PF) is a life-threatening interstitial lung disease characterized by scarring and inflammation in lung tissues. Aberrant activation of the JAK/STAT and NF-κB signaling pathways is critical in initiating and sustaining the inflammatory processes that drive fibrotic progression. In this study, we identify a novel small-molecule compound, T4015, a 4-indolyl-2-phenylaminopyrimidine derivative, as a dual-pathway inhibitor targeting both JAK/STAT and NF-κB signaling. Dual-luciferase reporter assays demonstrate the potent inhibitory activity of T4015 against these pathways. T4015 effectively suppresses the phosphorylation of STAT3, JAK1, and TYK2 induced by IL-6 and IFN-β, while suppressing LPS-induced NF-κB activation in macrophages. Transcriptome sequencing and pathway enrichment analyses further confirm that T4015 downregulates multiple inflammation-related signaling cascades, including the JAK/STAT, NF-κB, TNF, IL-17, and Toll-like receptor pathways. In a mouse model of bleomycin-induced PF, T4015 treatment significantly improves survival, attenuates collagen deposition, and reduces the expression of pro-inflammatory and profibrotic markers such as IL-6, CCL2, and COL1. Molecular docking and target prediction analyses suggest that T4015 exhibits strong binding affinity for multiple kinases within the JAK/STAT and NF-κB networks, including JAK1, TYK2, JAK2, JAK3, RIPK1, IRAK1/4, TAB1, and ZAP70. Collectively, these results highlight T4015 as a promising therapeutic candidate for PF through its simultaneous inhibition of the JAK/STAT and NF-κB signaling pathways.
Acta Biochimica et Biophysica Sinica•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.2025035
Primordial germ cell 7 (PGC7) is a maternal effect gene expressed in primordial germ cells and embryonic stem cells, serving as a pluripotency marker. Its role in regulating core pluripotency factors remains undefined. This study systematically evaluated the expression dynamics of PGC7 and pluripotency-associated proteins in F9 embryonal carcinoma (EC) cells using RT-qPCR and western blot analysis. Confocal immunofluorescence and co-immunoprecipitation assays established subcellular colocalization and molecular interactions. Results demonstrate that PGC7 is closely associated with the pluripotency status of F9 EC cells and counteracts the decrease in pluripotency induced by retinoic acid. Ectopic expression of PGC7 enhances Nanog translation. Mechanistically, PGC7 activates Y-box binding protein 1 (YBX1) phosphorylation by enhancing the interaction between YBX1 and AKT1. Subsequent phosphorylation of YBX1 reduces its binding to Nanog mRNA and promotes Nanog translation. These findings reveal a previously unknown role of PGC7 in supporting Nanog translation, providing insights into PGC7 function in F9 EC cells.