Journal of Translational Medicine最新文献

{"title":"FGF21 maintains redox homeostasis and promotes neuronal survival after traumatic brain injury by targeting SLC25A39-mediated mitochondrial GSH transport.","authors":"Lekai Wang, Weiwei Li, Xun Wu, Qing Ouyang, Bing Sun, Jianing Luo, Heng Guo, Tao Yang, Yuan Ma","doi":"10.1186/s12967-025-06969-3","DOIUrl":"10.1186/s12967-025-06969-3","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) represents a critical form of acute brain injury, characterized by considerable mortality and morbidity. Recently, fibroblast growth factor 21 (FGF21), a multifaceted hormone predominantly synthesized in liver, has emerged as a promising neuroprotective agent. In the study, we aim to investigate whether FGF21 exerts protective effects against TBI and to further elucidate its underlying molecular mechanisms.</p><p><strong>Methods: </strong>To elucidate the role of FGF21 in regulating SLC25A39-dependent mitochondrial GSH transport and providing protection against TBI-induced neurological deficits, a series of cellular and molecular techniques, including western blot analysis, real-time polymerase chain reaction, immunohistochemistry, transmission electron microscope, and behavioral assays, were employed.</p><p><strong>Results: </strong>FGF21 knockout exacerbates neural apoptosis and brain edema, increases lesion volume, and worsens neurological deficits following TBI. Remarkably, these pathological alterations were substantially mitigated with subsequent administration of recombinant FGF21. Importantly, FGF21 was found to prevent mitochondrial damage and sustain redox homeostasis post-TBI. Mechanistically, we observed that FGF21 enhances the mitochondrial uptake of glutathione (GSH), an essential redox metabolite, by targeting SLC25A39, a recently identified mitochondrial GSH transporter. FGF21 does not influence the transcriptional production of SLC25A39 but enhances its protein expression by inhibiting degradation via the mitochondrial protease AFG3L2. Furthermore, in neuron-specific Slc25a39 knockout mice, FGF21 was unable to exert its neuroprotective effects.</p><p><strong>Conclusion: </strong>Our findings provide preliminary evidence that FGF21 confers protective effects against mitochondrial oxidative stress-related damage following TBI. Additionally, we elucidated a novel role for SLC25A39-dependent mitochondrial GSH transport in both the pathological processes subsequent to TBI and the physiological functions of FGF21.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1044"},"PeriodicalIF":7.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular mechanisms of mitochondrial dynamics and mitophagy and their complex association with cancer drug resistance.","authors":"Zhuo Zhao, Yuru Ren, Meijie Yuan, Guobin Liu, Jian Sun","doi":"10.1186/s12967-025-07078-x","DOIUrl":"10.1186/s12967-025-07078-x","url":null,"abstract":"<p><p>The development of drug resistance by cancer cells is among the main reasons for cancer treatment failure, greatly limiting the efficacy of chemotherapy, targeted therapy, and immunotherapy. Mitochondria, as the core organelles of cellular energy metabolism, play a key role in the cellular stress response. The dynamic changes in mitochondria, including fusion, fission, and mitophagy, not only regulate cellular energy metabolism and biosynthesis but also affect cell survival and death. Through mitochondrial fusion, fission, and mitophagy, a sufficient number of effective mitochondria are ensured to supply cellular energy, thereby increasing the tolerance of tumor cells to chemotherapeutic drugs and generating drug resistance. Recently, the role of mitochondrial dynamics and mitophagy in cancer drug resistance has gradually gained attention, but their complex structure and function and multiple roles in tumor biology pose challenges for the clinical application of cancer treatment strategies based on it. Therefore, targeting mitochondrial dynamics and mitophagy for cancer drug resistance has attracted increasing attention for various cancer types. In this study, we provide insights into the molecular mechanisms of mitochondrial fusion, fission, and mitophagy and summarize their complex associations with cancer drug resistance through a systematic review of the latest literature.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1047"},"PeriodicalIF":7.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VISTA expressed on tumor cells is regulated by m6A and influences immune microenvironment through STAT3/CCL22 in NSCLC.","authors":"Hao Xu, Kaikai Shen, Bei Jiang, Qiuli Xu, Bingbing Li, Zhangmin Ke, Qinpei Cheng, Suhua Zhu, Dong Wang, Yong Song, Tangfeng Lv","doi":"10.1186/s12967-025-06818-3","DOIUrl":"10.1186/s12967-025-06818-3","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy is playing an increasingly vital role in the treatment of non-small cell lung cancer (NSCLC), yet the challenge of immune evasion remains prevalent. Therefore, investigating the regulatory mechanisms of the tumor immune microenvironment could yield significant benefits.</p><p><strong>Methods: </strong>This study utilized differential expression analysis, WGCNA, and Lasso-Cox to analyze the GSE126044 dataset, identifying N6-methyladenosine (m6A)-related molecules that play significant roles in immunotherapy. The m6A modification of the molecule were validated through m6A dot blot, MeRIP, RNA pull-down and RNA stability assays. Their impact on the biological behavior of tumor cells (TCs) was evaluated by CCK-8 assays, wound healing assays, transwell assays, co-culture experiments and flow cytometry. Furthermore, RNA sequencing was conducted to uncover downstream pathways and cytokines, followed by subsequent validation. Lastly, validation was carried out in vivo.</p><p><strong>Results: </strong>Through bioinformatics analysis, we identified that V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) serves a crucial role in immunotherapy and that its expression is regulated by m6A. It was subsequently confirmed that METTL3 enhances the m6A modification levels of VISTA mRNA, which is recognized by YTHDF1. This interaction improved the stability of VISTA mRNA, leading to increased expression of VISTA proteins on the surface of TCs. The elevated expression of VISTA boosted the cytotoxic response of CD8 + T cells toward TCs. RNA sequencing analysis indicated that the JAK/STAT pathway significantly contributes to this process. Overexpression of VISTA on TCs decreased the phosphorylation of STAT3, which in turn reduced the expression and release of CCL22. This reduction alleviated immune suppression within the tumor microenvironment, resulting in increased enrichment and activity of CD8 + T cells and decreased enrichment of regulatory T cells (Tregs), ultimately enhancing their cytotoxic effects against TCs.</p><p><strong>Conclusion: </strong>We conduct a pioneering systematic study on the expression, function, and molecular mechanisms of the VISTA molecule on NSCLC TCs. We propose that in the tumor immune microenvironment, VISTA functions as both an immune checkpoint and a regulator of CD8 + T cell activation/recruitment and Treg recruitment via its expression on TCs.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1043"},"PeriodicalIF":7.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay of axon regeneration genes and immune infiltration in spinal cord injury.","authors":"Zimin Xiang, Dingxi Fang, Danping Gao, Qi Zhang, Yuxuan Zhang, Yuping Sun, Liyan Li, Xiaoqian Zhang, Jiaxin Li, Lingzhi Ding","doi":"10.1186/s12967-025-06915-3","DOIUrl":"10.1186/s12967-025-06915-3","url":null,"abstract":"<p><strong>Background: </strong>Spinal Cord Injury (SCI) impacts neural function and regeneration. This study aimed to identify key axon regeneration genes in SCI and their correlations with immune infiltration and SCI subtyping.</p><p><strong>Methods: </strong>Gene expression profiles of 30 sham-operated mice and 29 SCI mice were obtained from GSE5296, GSE47681, and GSE93561 datasets. A PPI network of axon regeneration genes was constructed. Consensus clustering classified SCI subtypes. Differential expression analysis identified genes associated with SCI and its subtypes. Immune infiltration was assessed. WGCNA identified key genes. Potential drugs targeting hub genes were explored. An SCI mouse model was established and subjected to HE staining to assess pathological changes. The dysregulation of five key axon regeneration-related genes was validated in mouse spinal cord tissues using qRT-PCR and Western blotting.</p><p><strong>Results: </strong>We identified 2,971 genes associated with SCI, including 19 axon regeneration-related genes, and 144 differentially expressed transcription factors, with Jun being highly interconnected. Significant alterations in immune cell abundance correlated with axon regeneration genes. Consensus clustering stratified SCI samples into two subtypes. WGCNA identified 21 hub genes associated with SCI subtypes. Drug-gene interaction analysis identified Itgam and Ptprc as potential therapeutic targets. Validation experiments showed significant upregulation of Fn1, Sdc1, and Cspg4, and downregulation of Col4a1 and Lamb1 in the SCI model group compared to controls.</p><p><strong>Conclusions: </strong>Our study elucidates the interplay among axon regeneration genes, immune infiltration, and transcriptional regulation in SCI. Validation experiments confirmed the dysregulation of key axon regeneration-related genes in SCI mice, supporting their role in SCI pathology.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1034"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tongue-coating microbiota as a predictive biomarker of washed microbiota transplantation efficacy in pediatric autism: integration with clinical features.","authors":"Chao Wu, Junran Lu, Yuzhuo Wang, Junwei Zong, Minghui Fan, Yanfei Yang, Shouyu Wang","doi":"10.1186/s12967-025-07001-4","DOIUrl":"10.1186/s12967-025-07001-4","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1037"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the role of MAG, PTEN, and NOTCH1 in axonal regeneration: a network analysis and molecular dynamics study of siRNA/drugs/nanocarriers interactions.","authors":"Alireza Salimi, Aysan Moeinafshar, Sima Rezvantalab, Mohammad Dabiri, Nima Rezaei, Nima Beheshtizadeh","doi":"10.1186/s12967-025-07042-9","DOIUrl":"10.1186/s12967-025-07042-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Axonal regeneration remains a critical yet challenging process in spinal cord injury (SCI) recovery, primarily due to the limited regenerative capacity of adult central nervous system (CNS) axons. Identifying key molecular targets and optimizing therapeutic delivery systems are promising strategies to enhance axonal regeneration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, we investigated the roles of three critical proteins-MAG, PTEN, and NOTCH1-in axonal regeneration through an integrative approach combining network analysis and molecular dynamics (MD) simulations. We compiled 361 regeneration-associated genes from the REGene database and a targeted PubMed literature review. Gene ontology enrichment analysis via DAVID identified key genes linked to axonal regeneration and oligodendrocyte differentiation. A protein-protein interaction (PPI) network was constructed to pinpoint hub genes, with Cytoscape used to assess degree, betweenness, and closeness centrality. The top-ranking genes across at least two centrality metrics were selected, and GeneMANIA validated their functional relevance, confirming MAG, PTEN, and NOTCH1 as negative regulators of regeneration. Using siDirect and siRNA Wizard, we designed siRNA molecules targeting these genes, while DGIdb and literature mining identified small-molecule drugs (e.g., GT1b for MAG, enzalutamide for PTEN). MD simulations explored their interactions with polymeric nanocarriers-PLGA, PEI, chitosan, and PEI-PEG-revealing distinct binding patterns.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;All proteins exhibited favorable binding with their respective drugs, with MAG-GT1b demonstrating the strongest affinity ( -146.07 ± 61.63 kJ/mol). Free energy landscape (FEL) analysis of the MAG/GT1b complex revealed a pronounced global energy minimum at 20.6 kJ/mol, reflecting high-affinity binding. Among nanocarriers, chitosan showed strong siRNA interactions, whereas PLGA and PEI exhibited superior drug-binding properties, particularly for GT1b, as evidenced by lower solvent-accessible surface area (SASA) values, indicating tighter encapsulation. Notably, PLGA-based systems displayed a broader radius of gyration (Rg) distribution, attributed to their amphiphilic nature, which promotes rapid self-assembly into multiple dispersed nanocarriers rather than consolidated structures. Additionally, PLGA chains exhibited reduced average SASA values (40-90 nm&lt;sup&gt;2&lt;/sup&gt;) compared to other polymers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The strongest siRNA interactions occurred between PTEN siRNA-enzalutamide and PLGA ( -107.31 kJ/mol) or PEI ( -87.15 kJ/mol), primarily driven by van der Waals forces. While these in silico findings are promising, preclinical validation is essential for clinical translation. This study highlights the potential of combining network analysis and MD simulations to decipher complex interactions among proteins, siRNA, drugs, and polymers, offering novel insights into therapeu","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1038"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastric microbiome in gastric cancer sequence depicts diverse microbial structures associated with cancer risk and prognosis.","authors":"Tsubasa Shimogama, Tomomitsu Tahara, Takuya Shijimaya, Jumpei Yamazaki, Sanshiro Kobayashi, Naohiro Nakamura, Yu Takahashi, Takashi Tomiyama, Yusuke Honzawa, Toshiro Fukui, Makoto Naganuma","doi":"10.1186/s12967-025-07046-5","DOIUrl":"10.1186/s12967-025-07046-5","url":null,"abstract":"<p><strong>Objective: </strong>Increasing evidence indicated substantial involvement of non-Helicobacter pylori microbiota in gastric tumorigenesis. We aimed to elucidate detailed relationship of microbiome dynamics between two different steps in gastric cancer (GC) such as cancer initiation and progression, and assessed their associations with clinicopathological and molecular changes.</p><p><strong>Methods: </strong>We systemically characterized gastric microbiome during GC initiation and progression using 944 biopsies from primary GC, non-cancerous gastric mucosa from both GC and non-cancer subjects. The association between specific microbial characteristics and GC risk, prognosis and molecular changes such as TP53 mutation, DNA methylation and telomere shortening were also evaluated.</p><p><strong>Results: </strong>Microbial α-diversity in the gastric mucosa was decreased in relation to the GC occurrence, while it increased in primary GC tissue. Such paradoxical change was also observed in specific groups of bacteria during GC occurrence and its progression. GC risk-related microbiome was associated with differentiated GC, severe intestinal metaplasia, associated DNA methylation and telomere shortening, while GC tissue-specific microbiome was associated with more aggressive features of GC and TP53 mutation status.</p><p><strong>Conclusions: </strong>Our findings suggested the different role of non-Helicobacter pylori microbiota in GC initiation and progression steps.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1039"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of therapeutic AGC2 modulators by combining docking, binding, and vesicle-based transport assays.","authors":"Lucas Cafferati Beltrame, Sabino Todisco, Anna Lucia Francavilla, Vincenzo Mangini, Elvira Bombino, Anna Giovanna Sciancalepore, Valeria Scaglione, Maria Noemi Sgobba, Lucia Trisolini, Luna Laera, Francesco Colella, Serena Spadone, Benny Danilo Belviso, Lorenzo Guerra, Anna De Grassi, Rocco Caliandro, Angelo De Stradis, Mariateresa Volpicella, Ciro Leonardo Pierri","doi":"10.1186/s12967-025-06961-x","DOIUrl":"10.1186/s12967-025-06961-x","url":null,"abstract":"<p><strong>Backgroud: </strong>The mitochondrial Aspartate/Glutamate Carrier 2 (AGC2), encoded by the SLC25A13 gene, plays a critical role in cellular metabolism and redox balance through the malate/aspartate shuttle. Dysregulation of AGC2 is implicated in rare genetic diseases and tumorigenesis, making it a promising therapeutic target.</p><p><strong>Methods: </strong>In this study, we developed the first integrative platform for the discovery and validation of high-affinity AGC2 modulators, combining in silico screening with biophysical and functional assays. Docking-based virtual screening of chemical libraries was employed to identify candidate inhibitors. Their binding and inhibitory activity were validated via a combination of thermal shift assays and isothermal titration calorimetry (ITC) performed on n-dodecyl-β-D-maltoside (DDM)-based vesicles reconstituted with AGC2, alongside functional transport assays using AGC2-containing proteoliposomes.</p><p><strong>Results: </strong>We identified two previously unreported AGC2 inhibitors, suramin and taurolithocholic acid 3-sulfate. Remarkably, we report the first successful application of ITC to AGC2, overcoming major experimental challenges associated with ITC assays on the SLC25A family members, and achieving greater stability and reproducibility compared to similar assays performed on other family members, such as the ADP/ATP carrier and uncoupling proteins. Additionally, we present the first transmission electron microscopy (TEM) characterization of proteoliposomes and DDM-based vesicles reconstituted with AGC2, providing direct structural insights into the systems used for biophysical analysis.</p><p><strong>Conclusions: </strong>This study establishes a reproducible, and scalable workflow that bridges high-throughput ligand identification with high-resolution kinetic characterization for targeting mitochondrial carriers.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1033"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between lymphatic system and synovial inflammatory cells in osteoarthritis: molecular mechanisms and potential cell-based therapies.","authors":"Wang Zeng, Jiangyu Xiang, Yang Liu, Shirong Chen, Hao Wang","doi":"10.1186/s12967-025-07080-3","DOIUrl":"10.1186/s12967-025-07080-3","url":null,"abstract":"<p><p>The lymphatic system plays a significant part in interstitial fluid balance and immune surveillance throughout the whole body. In addition, recent studies have elucidated the role of the lymphatic system in maintaining the normal function of joints, and its dysfunction is related to the pathogenesis of osteoarthritis (OA). In this review, we described the composition and function of the lymphatic system in the knee joints and summarized the research progress of lymphatic networks in the development of OA. The synovial lymphatic system (SLS) is the most well-characterized lymphatic network, and we elaborated the pathological changes of SLS which resulted in the disturbance of knee joint homeostasis and the progression of OA. We summarized the underlying molecular mechanisms of lymphatic disorders and focused on the crosstalk between the SLS and synovial inflammatory cells, especially the abnormal macrophage polarization and regulatory T cells dysfunction. Cell-based therapies have been proven to restore lymphatic function. This review proposed potential cell-based therapies to treat OA by targeting the SLS, and mesenchymal stem cells and Tregs based therapies are currently the most promising approaches to treat OA by restoring lymphatic flow.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1032"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into post-translational modifications in hepatic fibrosis: pathogenic roles and therapeutic potentials.","authors":"Xiwen Bai, Zhihan Liu, Xianbin Li, Ranran Sun, Zujiang Yu","doi":"10.1186/s12967-025-07037-6","DOIUrl":"10.1186/s12967-025-07037-6","url":null,"abstract":"<p><p>Hepatic fibrosis, a critical progression in liver disease, has been widely studied. While the activation of stellate cells and the accumulation of extracellular matrix components are recognized as key mechanisms, additional research is necessary to uncover further complexities. Recent investigations underscore the pivotal role of post-translational modifications (PTMs) in hepatic fibrosis. This study explores nine PTMs-methylation, acetylation, SUMOylation, Neddylation, phosphorylation, crotonylation, glycosylation, lactylation, and ubiquitination-each implicated in the pathogenesis of hepatic fibrosis. Furthermore, six classes of drugs-ACC inhibitors, ASK1 inhibitors, Akt activators, FXR agonists, PTP1B inhibitors, and HDAC inhibitors-are reviewed for their therapeutic potential in targeting PTMs to treat hepatic fibrosis.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1036"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}