International Journal of Biochemistry & Cell Biology最新文献

{"title":"Investigating the effects of post-exercise serum treatments on APP processing in iPSC-derived neurons and astrocytes","authors":"Richard J. Elsworthy ,&nbsp;Felicity S.E. Spencer ,&nbsp;Sophie Allen ,&nbsp;Connor Dunleavy ,&nbsp;Martin Whitham ,&nbsp;Samuel J.E. Lucas ,&nbsp;Eric J. Hill ,&nbsp;Sarah Aldred","doi":"10.1016/j.biocel.2026.106920","DOIUrl":"10.1016/j.biocel.2026.106920","url":null,"abstract":"<div><div>The number of people living with Alzheimer’s disease (AD) is increasing worldwide as populations age. A hallmark of AD is the accumulation of amyloid-β (Aβ) in the brain, and pathways regulating amyloid-β precursor protein (AβPP) processing are of major interest for disease-modifying and preventive strategies such as exercise. Regular exercise is associated with a reduced risk of AD, potentially through limiting Aβ accumulation, yet the underlying cellular mechanisms remain unclear. Acute bouts of exercise induce the release of circulating signalling molecules that may influence AβPP metabolism. To investigate the effects of exercise on AβPP processing, human induced pluripotent stem cell (iPSC)-derived neurons and astrocytes were treated with serum collected before and immediately after high-intensity exercise. Both healthy control and familial AD (PSEN1 A246E) neurons and astrocytes were independently exposed to 10 % pre- or post-exercise serum for 30 min, after which markers of AβPP processing were quantified. Post-exercise serum contained increased amounts of Lacate, BDNF, IL-6, sAβPPα, and Aβ₁–₄₂, and reduced neprilysin activity (p &lt; 0.05). Treatment with post-exercise serum acutely elevated ADAM10 activity in neurons, which was replicated by spiking lactate in pre-exercise serum. sAβPPα was also increased in PSEN1 neurons following post exercise serum treatment with increased Aβ₁–₄₂ secretion in both PSEN1 neurons and astrocytes (p &lt; 0.05). These findings demonstrate that human post-exercise serum can modulate AβPP processing in iPSC-derived neural cells. This supports the concept that circulating exercise-induced factors can influence neuronal pathways relevant to AD pathology.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"192 ","pages":"Article 106920"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulatory effects of exogenous estradiol during endotoxemia","authors":"Felix N. Tajanko,&nbsp;Cynthia R. Muller,&nbsp;Carlos Munoz,&nbsp;Pedro Cabrales","doi":"10.1016/j.biocel.2026.106919","DOIUrl":"10.1016/j.biocel.2026.106919","url":null,"abstract":"<div><div>This study explores the effects of exogenous estradiol on inflammatory, metabolic, and organ-function responses to lipopolysaccharide (LPS)-induced endotoxemia using a murine model. Male, female, and estradiol-supplemented female mice were administered equal dose of LPS injections and observed over a 6-hour period for systemic physiological changes, including blood pressure, glomerular filtration rate (GFR), blood gases, and temperature. Post-mortem analyses evaluated inflammatory pathway markers, biomarkers of organ injury, and targeted metabolomics from plasma samples. Estradiol supplementation was associated with attenuated early markers of hepatic and cardiac injury, reduced cardiac nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, and changes from baseline post-LPS on metabolite profiles compared with control female and male mice. These effects were organ- and endpoint-dependent, with renal functional differences emerging primarily at later time points. Metabolite changes involving <span>L</span>-carnitine, methionine sulfoxide, and octanoic acid were consistent with altered metabolic and redox responses, but do not directly demonstrate changes in mitochondrial or antioxidant function. Together, these findings indicate that elevated estradiol levels are associated with modulation of early inflammatory and metabolic responses during endotoxemia, rather than uniform protection across organs or sexes. This work highlights biological sex and hormonal status as important variables in endotoxemia models and provides hypothesis-generating evidence for future studies examining hormone-dependent regulation of immune–metabolic pathways during systemic inflammation.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"192 ","pages":"Article 106919"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xiaoyou decoction suppresses cervical precancerous lesions through the activation of cellular autophagy and the upregulation of p53 expression","authors":"Yang Li ,&nbsp;Jingjing Zhao ,&nbsp;Mubai Li ,&nbsp;Yinglong Cheng ,&nbsp;Li Liu","doi":"10.1016/j.biocel.2025.106894","DOIUrl":"10.1016/j.biocel.2025.106894","url":null,"abstract":"<div><h3>Background</h3><div>Persistent high-risk human papilloma virus (HR-HPV) infection is a key factor in the progression of cervical lesions to cervical cancer. This study explores the molecular mechanisms through which the traditional Chinese medicine Xiaoyou Decoction (XYD) inhibits cervical intraepithelial neoplasia (CIN) lesions, offering new insights into its potential therapeutic application.</div></div><div><h3>Materials and methods</h3><div>Network pharmacology analysis was employed to identify the potential active ingredients and key target genes of XYD in treating CIN. Functional enrichment analysis was utilized to pinpoint the critical biological pathways affected by XYD. Clinical randomized trials were performed to evaluate the clinical efficacy of XYD. In vitro experiments were conducted to explore the functional effects and underlying molecular mechanisms of XYD.</div></div><div><h3>Results</h3><div>A total of 209 potential target genes of XYD associated with CIN lesions were identified. In addition, the active ingredients of XYD exhibited a strong association with autophagy-related proteins. Clinical randomized trials demonstrated that XYD treatment effectively alleviated HR-HPV infection, and after a 6-month follow-up, 90.3 % of patients exhibited negative conversion, successfully reversing the progression of CIN lesions. In vitro experiments confirmed that XYD inhibited CIN cell proliferation by activating the autophagy pathway and upregulating p53 protein expression.</div></div><div><h3>Conclusion</h3><div>In conclusion, our study reveals that XYD effectively prevents the persistence of HR-HPV infection and reverses the progression of CIN lesions by activating the autophagy pathway and upregulating p53 expression. These findings provide preliminary insights into the biological effects and specific mechanisms of XYD in CIN, offering a novel perspective for treating persistent HR-HPV infections.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"191 ","pages":"Article 106894"},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of disruption methods to optimize the evaluation of mitochondrial enzymatic activities in human fibroblasts","authors":"María Alejandra Sánchez-Muñoz ,&nbsp;Adriana Castillo-Villanueva ,&nbsp;Marcia Rosario Pérez-Dosal ,&nbsp;Bertha Molina-Álvarez ,&nbsp;Salvador Uribe-Carvajal ,&nbsp;Diego González-Halphen ,&nbsp;Isabel Medina-Vera ,&nbsp;Horacio Reyes-Vivas ,&nbsp;Jesús Oria-Hernández","doi":"10.1016/j.biocel.2025.106896","DOIUrl":"10.1016/j.biocel.2025.106896","url":null,"abstract":"<div><div>Mitochondriopathies often lead to chronic degenerative pathology. Muscle biopsy is considered the gold standard for diagnosis; however, its invasiveness restricts the amount of tissue obtained, and issue that is limiting for prospective, longitudinal, and pharmacological studies. Primary human fibroblasts (HF) lines are a valid alternative to biochemically characterize mitochondrial syndromes. Cell disruption is essential for measuring mitochondrial enzyme activity, and yet, no systematic comparative study has evaluated the different existing methods. Using 17 different cell lysis procedures, we evaluated the activity preservation of two mitochondrial enzymes: complex IV or cytochrome <em>c</em> oxidase (CIV) and citrate synthase (CS), in normal HF samples from pediatric patients. Procedures were categorized as chemical, mechanical, physical, and enzymatic. Only the enzymatic disruption using Pronase leads to high activity values for both CIV and CS activities, exhibiting intra- and inter-sample consistency. We then measured the activities of all mitochondrial complexes (CI, CI+CIII, CII, CII+CIII) and CV (ATP hydrolysis) in Pronase-disrupted cells, finding proper reproducibility and values comparable to those in the literature. We propose Pronase cell disruption is an adequate method for evaluating mitochondrial activities in HF samples.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"191 ","pages":"Article 106896"},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145866194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal muscle stem cell-derived exosomes improve dexamethasone-induced muscle atrophy at the single muscle fiber level","authors":"Qing-Xin Wei ,&nbsp;Nasar Khan ,&nbsp;Xi-Jun Yin","doi":"10.1016/j.biocel.2025.106895","DOIUrl":"10.1016/j.biocel.2025.106895","url":null,"abstract":"<div><div>This study investigated the therapeutic potential of exosomes derived from fetal muscle stem cells (FMSC-Exos) in mitigating dexamethasone (DEX)-induced muscle atrophy in a mouse model. Kunming (KM) mice were utilized to visualize muscle atrophy at the single muscle fiber level through an optimized isolation technique. Following the induction of muscle atrophy by dexamethasone, mice were treated with FMSC-Exos via local intramuscular injection into the gastrocnemius muscle. Results demonstrated that exosome administration showed a trend towards improved body weight and significantly increased muscle ma<strong>ss</strong> and individual muscle fiber diameter compared to the dexamethasone-only group. Histological analysis confirmed that FMSC-Exos effectively alleviated muscle fiber atrophy and promoted regeneration. RT-PCR and Western blot analyses revealed differential expression of the muscle atrophy markers MuRF1 and MAFbx/Atrogin-1. The mRNA expression levels of these atrophy-related factors were significantly elevated in the DEX-treated group compared to the control. Although expression levels in the exosome treatment group remained higher than control, they were significantly lower than in the DEX group. Protein expression followed a similar trend, indicating that dexamethasone modulates MuRF1 and MAFbx at both transcriptional and translational levels, and that exosome treatment counteracts this effect, promoting a restoration towards normal muscle protein expression homeostasis.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"191 ","pages":"Article 106895"},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proton activated chloride channel and its regulation of insulin secretion in β cells","authors":"Yi Wu ,&nbsp;Fang Wang ,&nbsp;Fang-Lin Peng","doi":"10.1016/j.biocel.2025.106879","DOIUrl":"10.1016/j.biocel.2025.106879","url":null,"abstract":"<div><div>Type II diabetes is a prevalent chronic disease worldwide, yet no curative treatment currently exists. Compromised insulin release is one of the hallmarks of type II diabetes, to restore insulin release is one standard to screen candidates for therapy. Proton-activated chloride (PAC) channels are pH-sensitive chloride channels that open under acidic conditions, but their potential role in pancreatic β-cell physiology and diabetes has not been fully explored. In this study, we identified PAC on the membrane of pancreatic β-cells and found it to be closely associated with insulin secretory granules. Immunostaining and FRET imaging revealed that PAC is co-localized with Syntaxin 1 A and CaV1.2. Overexpression and knockdown of PAC increased and reduced L type calcium currents and steady capacitance jumps which reflect fast insulin secretion. Furthermore, manipulation of PAC expression significantly altered overall insulin release under high glucose conditions in vitro. Knockout of PAC channels in mice, however, affects body weight, fasting blood glucose levels, and serum insulin levels when constructing a type II diabetes model through high-fat diet feeding, compared to wild-type mice or <em>Pac</em> knockout mice fed a normal diet. Together, these findings reveal a previously unrecognized role for PAC in regulating both phases of insulin secretion and suggest that PAC channels could represent a novel therapeutic target for improving β-cell function and treating diabetes. Given the global burden of type II diabetes, understanding PAC channel function could open new avenues for targeted interventions to restore insulin secretion and improve disease outcomes.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106879"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mn2+ enhances phagocytosis of macrophages against Staphylococcus aureus by regulating autophagy","authors":"Jinzhu Ma ,&nbsp;Yixuan Ma ,&nbsp;Shuyu Wei ,&nbsp;Shuangshuang Wu ,&nbsp;Yazun Dong ,&nbsp;Kaiyue Liu ,&nbsp;Hongyan Liu ,&nbsp;Simiao Yu ,&nbsp;Liquan Yu ,&nbsp;Beiyan Wang ,&nbsp;Baifen Song","doi":"10.1016/j.biocel.2025.106875","DOIUrl":"10.1016/j.biocel.2025.106875","url":null,"abstract":"<div><div>Mn²⁺ is an important trace nutrient element in the body. Macrophages act a significant role on resisting <em>Staphylococcus aureus</em> (<em>S. aureus</em>). Nowadays, it remains unclear whether Mn²⁺ can regulate the phagocytosis of macrophages against <em>S. aureus</em> through autophagy. Here, after the RAW264.7 cells transfected with the p3 × Flag-CMV10-<em>ube2c</em> plasmids were treated with Mn²⁺, subsequently infected with <em>S. aureus</em>, then these cells manifested that the expression levels of LC3-II and p62 proteins were significantly increased, and autophagosome formation was enhanced, and the expression level of RhoB phagocytosis-related protein also was significantly increased, the phosphorylation levels of mTOR, p38 and JNK were obviously decreased, while phosphorylation level of ERK was enhanced, the production levels of IL-6 and IL-2, IFN-β, IFN-γ, CAT and NO were significantly elevated, especially the phagocytosis against <em>S. aureus</em> was become obviously stronger. The data indicated that Mn²⁺ could promote the early autophagy activation and inhibit the degradation of autophagolysosomes in the late stage of autophagy of RAW264.7 cells infected with <em>S. aureus</em> through Ube2C, thereby enhancing the phagocytosis of macrophages against <em>S. aureus</em>. These data provide an important basis for a deeper understanding of the molecular mechanism by which Mn²⁺ enhances the phagocytosis of macrophages.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106875"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of autophagy in intervertebral disc degeneration and the regulation mechanism of AP-2α on autophagy","authors":"Jichen He ,&nbsp;Wenhao Li ,&nbsp;Feng Chen,&nbsp;Guodong Yin,&nbsp;Lin Tang,&nbsp;Qie Fan","doi":"10.1016/j.biocel.2025.106876","DOIUrl":"10.1016/j.biocel.2025.106876","url":null,"abstract":"<div><div>Autophagy is a promising therapeutic target for intervertebral disc degeneration (IDD). Previous study has shown down-regulation of activator protein 2α (AP-2α) promoted proliferation and inhibited senescence and apoptosis of rat nucleus pulposus (NP) cells in IDD. This study aimed to investigate the involvement of autophagy in IDD and the regulatory mechanism of AP-2α on autophagy. Rat NP cells were exposed to varying concentrations of H₂O₂. A rat IDD model was constructed and injected with AP-2α low expression adeno-associated virus. To study the role of AP-2α and autophagy in IDD, we constructed an IDD cell model using H₂O₂ and treated NP cells with AP-2α low expression adeno-associated virus, autophagy activator rapamycin (RA) and autophagy inhibitor 3MA. <em>In vitro</em>, AP-2α (TFAP2A), LC3 (MAP1LC3A/B), Beclin-1 (BECN1), and p62 (Sequestosome 1, SQSTM1) levels were up-regulated after H₂O₂ treatment. <em>In vivo</em>, IDD increased the apoptosis degree of NP cells, but apoptosis was reduced after knockdown of AP-2α. Additionally, IDD increased AP-2α, LC3 II/I, Beclin-1, and p62 levels, but knockdown of AP-2α unblocked the autophagy flow. <em>In vitro</em>, H₂O₂ treatment increased AP-2α, LC3 II/I, Beclin-1, and p62 levels and NP cell apoptosis. Treatment with RA and its combined knockdown of AP-2α alleviated the dysfunction of autophagy flow and reduced the degree of apoptosis. Treatment with 3MA aggravated the dysfunction of autophagy flow and apoptosis, which can be alleviated by knockdown of AP-2α. Together, AP-2α regulated autophagy to participate in the development of IDD <em>in vivo</em> and rat NP cell model of IDD <em>in vitro</em>.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106876"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linoleic acid promotes osteogenic differentiation of bone marrow mesenchymal stem cells and ameliorates ovariectomy (OVX)-induced osteoporosis in mice through the PI3K/AKT pathway","authors":"Hao Liao ,&nbsp;Xiangping Luo ,&nbsp;Liqin Jiang","doi":"10.1016/j.biocel.2025.106878","DOIUrl":"10.1016/j.biocel.2025.106878","url":null,"abstract":"<div><div>Bone mineral density (BMD) reduction is heavily involved in osteoporosis. Bone marrow mesenchymal stem cells (BMSCs) are promising candidates in the implantation treatment of bone loss-related diseases. Traditional Chinese herbs and their active components are effective in osteoporosis therapy. The effects of linoleic acid on osteogenesis and osteoporosis have been investigated in this study, revealing multifaceted findings through several analyses and experiments. A total of 41 overlapping disease-drug target genes were obtained between differentially expressed genes in osteoporosis and linoleic acid potential targets. Linoleic acid was shown to enhance BMSC osteogenic differentiation and mineralization in <em>in vitro</em> assays. Additionally, linoleic acid significantly countered bone loss and improved bone microstructure in a mouse model of osteoporosis induced by ovarian varixectomy (OVX) operation. Molecular docking was used to predict the interaction between linoleic acid and the top ten Hub genes. The predicted binding energy of Retinoid X Receptor Alpha (RXRA) is the lowest. Moreover, linoleic acid stimulation increased the expression of RXRA in BMSCs. Functional enrichment and pathway analysis of the overlapping potential targets highlighted their involvement in crucial biological processes and signaling pathways, including the PI3K-AKT signaling. Linoleic acid promoted the phosphorylation of PI3K and AKT. Lastly, the siRNA for RXRA knockdown and PI3K/AKT inhibitor LY294002 exerted opposite effects on BMSCs to linoleic acid, and significantly attenuated the effects of linoleic acid on BMSC osteogenic differentiation and the PI3K/AKT signaling activation, suggesting that the functions of linoleic acid might be mediated by the PI3K/AKT signaling. Moreover, linoleic acid also inhibited osteoclastogenetic differentiation. Conclusively, linoleic acid, the main active compound of <em>Rehmanniae Radix Praeparata</em> (RR), could promote BMSC osteogenic differentiation by enhancing the PI3K/AKT signaling activation.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106878"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bielong Ruangan decoction inhibits tumor growth and improves immune response in a hepatocellular carcinoma mouse model through gut microbiota","authors":"Ruoyu Wang ,&nbsp;Dan Tang ,&nbsp;Lingyu Wu ,&nbsp;Longyun Ou ,&nbsp;Lin Ding ,&nbsp;Jiacheng Jiang ,&nbsp;Yunan Wu","doi":"10.1016/j.biocel.2025.106873","DOIUrl":"10.1016/j.biocel.2025.106873","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer fatality worldwide. It is closely linked to the gut-liver axis, which plays a crucial role in nutrient metabolism, immune responses, and the biotransformation of bacterial metabolites. Traditional Chinese Medicine (TCM), as an adjuvant treatment, is important in the treatment course of HCC. This study aimed to explore the effects of Bielong Ruangan decoction (BLRG) on HCC. It is a traditional Chinese medicine formula used for liver fibrosis and cancer. The study focuses on its impact on gut microbiota and associated mechanisms. An orthotopic liver transplantation model was established in mice in the presence or absence of BLRG treatment, and the therapeutic effects of BLRG were evaluated. BLRG significantly inhibited tumor growth in an orthotopic liver transplantation mouse model, by reducing tumor size, liver weight, volume, Ki-67, and serum AFP levels. It also enhanced intestinal barrier functions by lowering serum LPS levels, increasing intestinal mucus thickness, and boosting ZO-1 and occludin mRNA levels. Moreover, BLRG modulated immune responses, decreasing inflammatory cytokines (IL-10 and IL-1β) while increasing anti-tumor cytokines (IFN-α, IFN-γ, and IL-2). A notable shift in gut microbiota composition was observed, accompanied by a decrease in <em>Mucispirillum_sp.</em> and <em>Helicobacter_typhlonius</em> post-treatment. Serum metabolomic profiling confirmed these findings and revealed a positive correlation between <em>Mucispirillum</em> and triglycerides (TG). Fecal Microbiota Transplantation (FMT) experiments further highlighted the gut microbiota's role in mediating BLRG's anti-tumor effects, demonstrating decreased tumor metrics and improved serum AFP levels, intestinal permeability, and immune responses in recipient mice. These results underscore BLRG's potential as an adjunctive therapeutic agent in liver cancer, demonstrating its ability to modulate tumor growth, gut microbiota, and immune responses, thereby potentially reshaping the HCC therapeutic landscape.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106873"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}