Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04718-3
Background Intestinal stem cells (ISCs) sustain epithelial homeostasis through rapid mitochondrial metabolism, however, how they sense nutrient signals to regulate mitochondrial function remains unclear. Methods We examined the role of L-glutamate (Glu) in regulating cell mitochondrial biosynthesis using in vivo piglets, ex vivo porcine intestinal organoids (IOs), and in vitro IPEC-J2 cells. Results Glu enhanced jejunal development in weaned piglets. Isobaric tags for relative and absolute quantitation (iTRAQ) analysis revealed the significant enrichment of mitochondrial functions and activation of EGFR-MEK-ERK-mTFB2 signaling pathway in the jejunum. In vitro, 5 mM Glu promotes mitochondrial biosynthesis and potentiates the EGFR-MEK-ERK-mTFB2 axis. Whereas inhibition of EGFR with Osimertinib and silencing EGFR abolished these effects in IOs and IPEC-J2 cells. Colocalization and biochemical studies demonstrated interaction between Glu and EGFR in IOs. Conclusions Glu promotes mitochondrial biogenesis and ISC expansion by activating the EGFR–MEK–ERK–mTFB2 axis, highlighting a nutrient-sensing mechanism that couples energy availability to ISC function.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04565-2
This correction article addresses an error in the scale of the control group image in Fig. 4E of the original article. The corrected image is provided. The original article can be found online at https://doi.org/10.1186/s13287-025-04468-2.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-023-03614-y
Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients’ quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin with a diameter of 30–150 nm, play a critical role in intercellular communication and have become an ideal vehicle for drug delivery. A growing body of evidence suggests that exosomes have great potential for repairing SCI. In this review, we introduce exosome preparation, functions, and administration routes. In addition, we summarize the effect and mechanism by which various exosomes repair SCI and review the efficacy of exosomes in combination with other strategies to repair SCI. Finally, the challenges and prospects of the use of exosomes to repair SCI are described.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024217
Ageing is an independent factor for cognitive dysfunction. Ageing-associated alterations in the gut microbiota also affect cognition. The present study is designed to investigate changes in the gut microbiota and their participation in ageing-associated cognitive impairment. Both 10-week-old and 18-month-old mice are used. Mouse cognition is examined by novel object recognition and T-maze tests. Mouse feces are collected for sequencing and transplantation. Protein expression in the mouse intestine and hippocampus is studied using immunohistochemistry and immunofluorescence staining. Senescent neurons are induced by hydrogen peroxide in vitro. The cell lysates are used for western blot analysis and adenosine triphosphate (ATP) measurement. Our results show that 18-month-old mice exhibit cognitive dysfunction compared with young mice. In aged mice, transplanting the microbiota of young mice increases the protein presence of synaptophysin in the hippocampus and partially restores cognition. The protein expressions of mucin-2 and E-cadherin in the intestine are reduced in aged mice but are increased by transplantation. Gut microbiota analyses reveal that the reduced abundance of the microbe Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus in aged mice is restored by transplantation. Fecal microbiota transplantation in young mice increases the serum level of acetic acid in aged mice. Hydrogen peroxide stimulation induces senescence and reduces the protein expression levels of synaptophysin and acetyl-coenzyme A synthetase member 2 (ACSS2) in primary neurons. Incubation with acetic acid upregulates the protein expressions of ACSS2 and synaptophysin and further increases ATP production in senescent neurons. In summary, gut microbiota transplantation increases the abundance of Lactobacillales, elevates serum acetic acid level, and improves cognitive function in aged mice. Gut microbiota transplantation has therapeutic importance for ageing-associated cognitive decline.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024183
Traumatic brain injury (TBI) is a recognized global public health problem. However, there are still limitations in the available therapeutic approaches and a lack of clinically effective drugs. Therefore, an in-depth exploration of the secondary pathological mechanism of TBI and the identification of new effective drugs are urgently needed. Cannabidiol (CBD), a component derived from the cannabis plant, has potential therapeutic effects on neurological diseases and has received increasing attention. However, few reports on CBD intervention in TBI patients exist. Here, we use the Feeney free-fall method to establish a rat TBI model. CBD significantly improves neurological deficit scores, neuronal damage and blood-brain barrier permeability in rats and significantly inhibits the expressions of the brain injury markers S-100β and NSE. Mechanistically, CBD attenuates TBI-induced astrocyte activation, reduces inflammation, and attenuates the expressions of inflammatory prostaglandin system indicators. The use of TG6-10-1 (EP2 inhibitor) and H-89 (PKA inhibitor) indicates that CBD attenuates TBI-induced neurological damage via the PGE2-EP2-cAMP-PKA signaling pathway. Overall, this research provides a novel drug candidate for the treatment of clinical brain trauma.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024182
Glycan-mediated recognition plays a critical role in facilitating cell-cell and cell-matrix interactions. Galectin-8 (Gal-8), classified as a ‘tandem-repeat’ type of galectin, binds to cell surface glycans to modulate various cellular functions, including cell adhesion, migration, apoptosis, pathogen recognition, autophagy, and immunomodulation. Despite the known function of Gal-8 in binding to various glycosylated proteins, only a few interactions have been reported to date. In this study, mass spectrometry is used to identify CD98hc as a novel binding partner for Gal-8. Both the N-terminal and C-terminal carbohydrate recognition domains (CRDs) of Gal-8 (Gal-8N and Gal-8C) bind to CD98hc, an interaction that is specifically inhibited by lactose but not sucrose, as confirmed by pull-down assays. The binding affinity between CD98hc and Gal-8 measured by microscale thermophoresis (MST) is 1.51 ± 0.17 μM. In addition, Gal-8N and Gal-8C have the binding affinities of 0.22 ± 0.03 μM and 10.68 ± 1.69 μM, respectively. Gal-8N and Gal-8C are both involved in the recognition and binding process of CD98hc. Furthermore, both full-length Gal-8 and its individual CRDs bind specifically to N-glycosylated glycans on CD98hc, as demonstrated by the use of tunicamycin to inhibit N-glycosylation in cells. In addition, Gal-8 and its individual CRDs can pull down glycosylated CD98hc-ED but not free CD98hc-ED in vitro, indicating that the binding of Gal-8 to glycosylated CD98hc-ED is N-glycosylation-dependent. Overall, our findings establish CD98hc as a novel binding partner for Gal-8 and provide insights for further exploration of the diverse biological functions of Gal-8.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024225
Arsenic is widely present in nature, and its compounds are extensively used in industrial, agricultural, and medical fields. Arsenic trioxide (As2O3) is specifically used as a therapeutic agent for acute promyelocytic leukemia because it induces cancer cell differentiation and apoptosis, significantly reduces the cancer cell count and has unique medical value. However, owing to its high toxicity and carcinogenicity, long-term use can induce cardiovascular diseases such as arrhythmia and myocardial contractile dysfunction. However, research on the treatment of arsenic-induced cardiotoxicity remains relatively scarce. Notably, artemisinin has anti-inflammatory and antioxidative effects on various heart diseases, effectively inhibiting reactive oxygen species (ROS) production, preventing myocardial damage and apoptosis caused by arsenic poisoning, and improving cardiac contractile and diastolic functions, thus enhancing cardiac function. This study aims to discuss the impact of artemisinin on the myocardium of arsenic-poisoned rats. Forty 12-week-old male SD rats were randomly divided into five groups: control, arsenic poisoning, drug control, low-dose artemisinin, and high-dose artemisinin. As2O3 was intraperitoneally injected at 5 mg/kg/day for 10 days in the arsenic poisoning, low-dose, and high-dose groups, whereas the control and drug control groups received equal volumes of physiological saline. Artemisinin was subsequently injected at corresponding doses for three weeks. Myocardial contrast echocardiography (MCE) was used to assess myocardial blood perfusion. Blood and myocardial tissue samples were collected for biochemical and histological analyses. Results showed that arsenic poisoning significantly decreased myocardial blood perfusion (AUC and WIS×PI) and increased CD31 expression, indicating microvascular damage and inflammation. Artemisinin intervention, especially at high dose, restored perfusion and reduced CD31 expression, suggesting a protective effect. Electron microscopy confirmed that artemisinin alleviated arsenic-induced myocardial structural damage. These findings suggest that artemisinin alleviates arsenic-induced myocardial injury by modulating oxidative stress and inflammatory responses.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024237
The interaction between TF binding and DNA methylation is increasingly recognized as a key player in the regulation of gene expression. However, the role of this interaction in regulating ICAM1 expression in breast cancer has not been elucidated. CpG methylation in the ICAM1 promoter is negatively correlated with ICAM1 expression, and ICAM1 expression is significantly positively correlated with DNMT and TET3 expression in breast cancer. TF binding attenuates ICAM1 promoter CpG methylation and promotes ICAM1 transcription. DNA methylation regulation enhances ICAM1 expression in breast cancer by promoting the transcription of transcription factors. In terms of mechanisms, RELA and STATs recruit TET3 to prevent DNMT-mediated DNA methylation, thereby maintaining CpG island hypomethylation in the ICAM1 promoter. Therefore, TF occupancy limits DNA methylation and affects ICAM1 expression in breast cancer.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025101
Abnormal proliferation and migration of endothelial cells are key contributors to tumor angiogenesis. Recent studies have shown that the crucial role of E3 ubiquitin ligase neuronal precursor cell expression developmentally downregulated 4-like (NEDD4L) in tumorigenesis. However, the precise mechanisms by which NEDD4L functions in endothelial cells remain unclear. In this study, we investigate the mechanisms by which NEDD4L influences the function of human umbilical vein endothelial cells (HUVECs) and its effect on tumor angiogenesis. Our results show that NEDD4L overexpression in HUVECs suppresses both cell proliferation and migration. Additionally, we find that the autophagic activity in NEDD4L-overexpressing cells is increased. Proteomic profiling and ubiquitination assays reveal that NEDD4L interacts with eEF1A1, promoting K48-linked ubiquitination-mediated degradation of eEF1A1. This post-translational modification is a key step in the NEDD4L-mediated regulation of autophagy and cellular function. Moreover, we find that loss of endothelial NEDD4L significantly enhances tumor growth and promotes angiogenesis in vivo. Overall, NEDD4L plays a crucial role in inhibiting tumor angiogenesis by regulating eEF1A1 ubiquitination and degradation, providing new insights into the NEDD4L-eEF1A1 axis and its potential as a therapeutic target.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024138
Chemoresistance is the primary reason for poor prognosis in patients with pancreatic cancer (PC). Recent studies have indicated that ferroptosis may improve chemoresistance, but the underlying mechanisms remain unclear. In this study, significant upregulation of heat shock protein 90α (Hsp90α) expression is detected in the peripheral blood and tissue samples of patients with chemoresistant PC. Further studies reveal that Hsp90α promotes the proliferation, migration, and invasion of a chemoresistant pancreatic cell line (Panc-1-gem) by suppressing ferroptosis. Hsp90α competitively binds to Kelch-like ECH-associated protein 1 (Keap1), liberating nuclear factor erythroid 2-related factor 2 (Nrf2) from Keap1 sequestration. Nrf2 subsequently translocates into the nucleus and activates the glutathione peroxidase 4 (GPX4) pathway, thereby suppressing ferroptosis. This process further worsens the chemoresistance of PC cells. This study provides valuable insight into potential molecular targets to overcome chemoresistance in PC. It sheds light on the intricate mechanisms linking Hsp90α and ferroptosis to chemoresistance in PC and provides a theoretical foundation for the development of novel therapeutic strategies.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261511
This study integrates network pharmacology, molecular docking, and in vitro experiments to elucidate the anti-gastric cancer mechanism of morin, an active flavonoid from Mori Ramulus. Network analysis identified 178 potential targets of Mori Ramulus and 13,100 gastric cancer-related targets, with 159 intersecting targets. Enrichment analysis highlighted the PI3K/Akt pathway as a key mediator. Molecular docking and dynamics simulations confirmed stable binding between morin and PIK3R1, which is significantly overexpressed in gastric cancer tissues. In vitro, morin (100–400 μmol/L) dose-dependently inhibited AGS cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis (P<0.05, 0.01). Western blotting revealed downregulation of PI3K/Akt pathway proteins (p85α, p110β, p-Akt) and cell cycle-related proteins (Bcl-2, CCND1, CDK4, CDK6), alongside upregulation of Bax and p21 (P<0.05, 0.01). Co-treatment with the PI3K agonist 740Y-P significantly reversed these effects (P<0.05, 0.01), confirming pathway dependence. These findings demonstrate that morin targets PIK3R1 to suppress PI3K/Akt signaling, thereby inhibiting proliferation and inducing apoptosis and cell cycle arrest in gastric cancer cells. The study underscores morin's potential as a natural, multi-target lead compound with low toxicity, though further validation in additional cell lines and gene-level manipulations is warranted.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21437
BACKGROUND: Osteonecrosis is a disabling and refractory disease with a high prevalence rate in China, necessitating the exploration of potential biomarkers for early prevention, diagnosis, and treatment. Metabolomic studies have demonstrated correlations between human metabolites and osteonecrosis; however, the causal relationship between plasma metabolites and osteonecrosis remains unclear. OBJECTIVE: To investigate the causal association between 1,400 plasma metabolites and osteonecrosis using Mendelian randomization and provide supporting evidence. METHODS: Public data on 1,400 plasma metabolites (exposure factors) and osteonecrosis (outcome factor) were collected. The plasma metabolite data were derived from a genome-wide association study (GWAS) on blood metabolites published in Nature Genetics in January 2023, which included 1,091 blood metabolites and 309 metabolite ratios from 8,299 individuals in the Canadian Longitudinal Study on Aging (CLSA) cohort. The single-nucleotide polymorphism data for osteonecrosis were obtained from the FinnGen public database R12 dataset, comprising 475,307 samples, including 2,043 osteonecrosis cases and 473,264 controls, all of European ancestry. Mendelian randomization analyses (inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode) were performed using Rstudio software, followed by heterogeneity tests, pleiotropy tests, and Steiger directionality tests to ensure robustness and reliability. RESULTS AND CONCLUSION: Three plasma metabolites showed significant causal associations with osteonecrosis (P < 0.05): adenosine monophosphate to valine ratio (OR=1.303, 95%CI=1.110-1.531, P=0.001, PFDR=0.07), oxidized cysteinylglycine level (OR=0.888, 95%CI=0.791-0.998, P=0.046, PFDR=0.05), and 3β,17β-androstenediol disulfate level (OR=1.121, 95%CI=1.020-1.231, P=0.018, PFDR=0.06). The adenosine monophosphate to valine ratio and 3β,17β-androstenediol disulfate level were risk factors for osteonecrosis, while oxidized cysteinylglycine level was a protective factor. These findings suggest causal relationships between three plasma metabolites and osteonecrosis, potentially serving as biomarkers for early diagnosis and targets for intervention. Although based on European population data, this study provides valuable reference for osteonecrosis research in China, and future domestic researchers may achieve early diagnosis and precise treatment by detecting and regulating metabolite levels.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21423
BACKGROUND: Current therapies for musculoskeletal degenerative diseases merely alleviate symptoms with significant adverse effects. As a traditional Chinese medicine, active ingredients of ginseng exhibit protective effects on bone and muscle through multi-target regulation of signaling pathways, and breakthroughs have been made in mechanism research in recent years. OBJECTIVE: To provide a systematical review of the latest molecular mechanisms of active ingredients of ginseng (ginsenosides, polysaccharides, and peptides) in preventing and treating musculoskeletal degenerative diseases via key signaling pathways, providing a basis for targeted drug development. METHODS: A systematic search was performed in multiple databases, including PubMed, Web of Science, Embase, CNKI, Wanfang, and VIP, with the search period from inception to April 2025. Chinese search terms included "musculoskeletal diseases, osteoporosis, osteoarthritis, intervertebral disc herniation, sarcopenia, ginsenosides, ginseng polysaccharides, ginseng peptides, signaling pathways"; English search terms included "musculoskeletal degenerative diseases, osteoporosis, osteoarthritis, intervertebral disc degeneration, sarcopenia, ginsenosides, ginseng polysaccharides, ginseng peptides, signaling pathways". Finally, 75 eligible articles were included. RESULTS AND CONCLUSION: (1) Ginsenosides (e.g., Rg3, Rh4, Rc): target the karyopherin α2-nuclear factor-κB axis to inhibit osteoclast differentiation and reduce bone resorption; activate the sirtuin 1 pathway to enhance mitochondrial biogenesis and delay sarcopenia; regulate Yes-associated protein 1/transcriptional coactivator and p38 mitogen-activated protein kinase to alleviate intervertebral disc degeneration. (2) Polysaccharides: processing techniques affect immunomodulatory activity, inhibiting inflammation via the mitogen-activated protein kinase/nuclear factor-κB pathway. (3) Peptides: activate the NAD+/sirtuin 1/peroxisome proliferator-activated receptor γ coactivator 1α axis to improve mitochondrial function. These findings suggest that ginseng exerts synergistic regulation of bone metabolism balance, inhibition of cartilage degradation, and delay of muscle aging through a "multi-component, multi-target" mechanism, but challenges remain regarding low bioavailability and lack of large-scale clinical trials for translation.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026078
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated clinical benefits in heart failure with preserved ejection fraction (HFpEF), yet the underlying mechanisms remain poorly defined. Given that mitochondrial dysfunction represents a central feature of HFpEF pathophysiology, we investigate whether modulation of mitochondrial homeostasis contributes to the cardioprotective effects of dapagliflozin. Using a Dahl salt-sensitive rat model of HFpEF, we find that dapagliflozin markedly improves diastolic function and attenuates cardiac hypertrophy, fibrosis, and apoptosis. These beneficial effects are accompanied by significant restoration of mitochondrial structure and function. Consistently, in an in vitro HFpEF model, dapagliflozin enhances mitochondrial respiratory capacity in cardiomyocytes, indicating a direct mitochondrial regulatory effect. Mechanistically, integrative transcriptomic and experimental analyses identify the SIRT1/PGC-1α/Mitofusin-2 (Mfn-2) signaling axis as a critical pathway suppressed in HFpEF but reactivated following dapagliflozin treatment. Activation of this pathway promotes mitochondrial biogenesis and improves mitochondrial dynamics, thereby preserving cardiomyocyte homeostasis. Collectively, our findings reveal that dapagliflozin exerts cardioprotective effects in HFpEF by restoring mitochondrial homeostasis through the SIRT1/PGC-1α/Mfn-2 axis, providing mechanistic insight into SGLT2i-mediated benefits and highlighting mitochondrial regulation as a potential therapeutic strategy for HFpEF.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026093
Transfer RNA (tRNA) acts not only as an indispensable adaptor in protein synthesis but also as a key contributor to tumorigenesis when its regulation is disrupted. This review systematically summarizes aberrant tRNA-related mechanisms in cancer, including altered tRNA expression profiles, abnormal post-transcriptional modifications, dysregulated aminoacylation, production of tRNA-derived small RNAs (tdRs), and defects in tRNA trafficking and translational fidelity. Notably, the metabolically abnormal tumor microenvironment actively shapes tRNA reprogramming to facilitate adaptive survival, while dysregulated tRNA elements, such as specific modifications and tdRs, further drive cancer stem cell properties and therapeutic resistance. Collectively, these alterations reprogram the oncoproteome and signaling networks, thereby promoting tumor cell proliferation, metastasis, immune evasion, and drug resistance. Targeting these mechanisms represents a promising strategy for developing novel cancer therapies. Potential approaches include the use of suppressor tRNAs to restore tumor suppressor gene function, the employment of tdRs to modulate oncogenic signaling pathways, or direct inhibition of enzymes involved in tRNA biogenesis. These strategies aim to remodel the dysfunctional tRNA network in cancer and offer new avenues for innovative treatments.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026033
Metabolic dysfunction-associated steatohepatitis (MASH) has become a global epidemic, and effective therapeutic strategies are urgently needed. Lonidamine (LND) has been reported to possess anti-inflammatory effects; however, few studies have investigated whether LND exerts a therapeutic effect on MASH. Therefore, in this study, we aim to explore the effects of LND on inflammatory responses and abnormal lipid metabolism in MASH mice. A mouse MASH model is established by feeding C57BL/6 mice a high-fat, high-cholesterol (CL) diet. The results show that LND attenuates CL-induced increases in body weight, serum glucose and lipid levels, inflammatory responses, and hepatocellular steatosis. In addition, the mitogen-activated protein kinase (MAPK) signaling pathway is inhibited, and the expression level of sterol regulatory element-binding protein 1 (SREBP1) protein is significantly reduced. Meanwhile, in vitro models of cellular inflammation and lipid metabolism are simulated, and molecular docking and biolayer interferometry (BLI) analysis are used to verify that LND and SREBP1 have a direct interaction and that LND promotes the degradation of SREBP1. Furthermore, specific knockdown of Srebp1 in AML12 cells is performed to further verify the effect of LND on MASH. The results confirm that LND exerts anti-inflammatory effects in MASH by inhibiting the activity of the MAPK signaling pathway and improves abnormal lipid metabolism through its interaction with SREBP1. Overall, LND holds promise as a potential therapeutic agent for the treatment of MASH.