International journal of molecular medicine最新文献

{"title":"[Expression of Concern] Anti‑metastatic and differential effects on protein expression of epigallocatechin‑3‑gallate in HCCLM6 hepatocellular carcinoma cells.","authors":"Yunjuan Zhang, Lawrence Owusu, Wei Duan, Tao Jiang, Shizhu Zang, Ayaz Ahmed, Yi Xin","doi":"10.3892/ijmm.2026.6014","DOIUrl":"10.3892/ijmm.2026.6014","url":null,"abstract":"<p><p>Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, for the cell invasion assay experiments shown in Fig. 2A on p. 962, panels 'b' and 'c' (showing treatment with 5 µg/ml or 10 µg/ml epigallocatechin‑3‑gallate respectively) contained an overlapping section of data, such that these data, which were intended to show the results from differently performed experiments, appeared to have been derived from the same original source. The authors have been contacted by the Editorial Office to offer an explanation for the apparently incorrect assembly of data in Fig. 2, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office conitnues to investigate this matter further. [International Journal of Molecular Medicine 32: 959‑964, 2013; DOI: 10.3892/ijmm.2013.1446].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 6","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Expression of Concern] Human ether‑à‑go‑go‑related gene mutation L539fs/47‑hERG leads to cell apoptosis through the endoplasmic reticulum stress pathway.","authors":"Shuting Ma, Yun Zhao, Miaomiao Cao, Chaofeng Sun","doi":"10.3892/ijmm.2026.5975","DOIUrl":"10.3892/ijmm.2026.5975","url":null,"abstract":"<p><p>Following the publication of the above paper, it has been drawn to the Editor's attention by an interested reader that, regarding the Hoechst‑stained images shown in Fig. 4 on p. 1258, the 'WT‑hERG+L539fs/47‑hERG' panel (top row, on the right) and the 'L539fs/47‑hERG+4‑PBA' panel (bottom row, middle panel) shared an overlapping section, such that data which were intended to show the results of differently performed experiments had apparently been derived from the same original source. Furthermore, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that the western blot data featured in Fig. 5A contained a number of potential anomalies: there appeared to be possible breaks in continuity in the gel showing the blots for cleaved caspase‑3 in this figure, and the backgrounds for the western blots in this figure also appeared to be rather heterogenous. Although the authors responded to this initial query concerning the incorrect assembly of data in Fig. 4, up to this time no response from them has been forthcoming concerning the western blots shown in Fig. 5. Owing to the time that has now elapsed, and given the fact that the Editorial Office has been made aware of potential problems associated with the scientific integrity of this study, we are issuing an Expression of Concern to notify readers of these issues while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine, 43:1253‑1262, 2019; DOI: 10.3892/ijmm.2019.4049].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 5","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of MALT1 inhibition by MI‑2 on the microglial phenotype switch, inflammatory cytokine secretion, neuronal loss and oxidative stress in Alzheimer's disease.","authors":"Yuanlong Li, Hua Fan, Xiong Han, Ming Ni, Xiaodan Hou, Hailan Xia, Yinzhu Shi, Lin Zhang, Jun Sun","doi":"10.3892/ijmm.2026.5973","DOIUrl":"10.3892/ijmm.2026.5973","url":null,"abstract":"<p><p>Mucosa‑associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a key paracaspase enzyme regulating immune responses, inflammation and oxidative stress. The present study aimed to investigate the effect of MALT1 inhibition on neuroinflammation, neuronal loss and oxidative stress in Alzheimer's disease (AD). A co‑culture system involving microglia and neuron cells under β‑amyloid (Aβ) intervention was used to establish AD cellular models using human microglia HMC3 cells and neuroblastoma SH‑SY5Y cells and mouse microglia BV‑2 and hippocampal neuron HT‑22 cells. The inhibition of MALT1 proteolytic activity was achieved by MALT1 inhibitor 2 (MI‑2) treatment, and the NF‑κB pathway was activated by phorbol 12‑myristate 13‑acetate (PMA) treatment in HMC3 and BV‑2 cells. Western blotting, ELISA, Cell Counting Kit‑8, EdU staining, reactive oxygen species (ROS) detection and reduced glutathione (GSH) assays were performed to evaluate molecular changes, inflammatory responses, neuronal viability and oxidative stress. MALT1 expression was upregulated following Aβ treatment in HMC3 and BV‑2 cells. MALT1 inhibition by MI‑2 suppressed the microglial M1 phenotype but enhanced the M2 phenotype, reduced the levels of the proinflammatory cytokines TNF‑α and IL‑1β and inactivated the NF‑κB pathway in HMC3 and BV‑2 cells. Moreover, microglial MALT1 inhibition elevated cell viability (verified by Cell Counting Kit‑8 and EdU assays), increased the level of reduced glutathione and decreased the levels of reactive oxygen species in SH‑SY5Y and HT‑22 cells. NF‑κB activation by PMA attenuated the effects of MALT1 inhibition on the microglial phenotype switch and proinflammatory cytokine secretion in HMC3 and BV‑2 cells, as well as cell viability and oxidative stress in SH‑SY5Y and HT‑22 cells. The present study reveals that MALT1 inhibition may suppress microglial M1 phenotype, neuroinflammation, neuronal loss and oxidative stress by inactivating the NF‑κB pathway in AD.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 5","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small extracellular vesicles in osteoarthritis: A double‑edged sword regulating inflammation and cartilage homeostasis (Review).","authors":"Yifan Yang, Jiachen Liang, Xiangyu Shi, Anqi Niu, Ruifang Gao, Xiuping Wu, Xiaojuan Guo, Xiaotong Shi, Kejie Cao, Bing Li, Ran Li","doi":"10.3892/ijmm.2026.5990","DOIUrl":"10.3892/ijmm.2026.5990","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a progressive degenerative joint disease and a leading cause of pain, disability and loss of joint function in older adults worldwide. Small extracellular vesicles (sEVs) are small vesicles secreted by cells and found in various body fluids. They carry a range of bioactive molecules, including nucleic acids, proteins and lipids, and participate in numerous cellular physiological activities, such as cell death, inflammation, immunity, proliferation, migration and differentiation. Depending on their cellular origin, sEVs can exert opposing effects on OA: They may either aggravate inflammation and cartilage damage or suppress inflammation and promote cartilage repair. Therefore, this review focuses on the preclinical research evidence regarding the dual mechanism of 'promoting or treating' by sEVs in the disease of OA, aiming to construct a theoretical framework to provide a theoretical basis for the development and translational application of OA treatment strategies based on sEVs.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 5","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal circular RNAs in the tumor immune microenvironment: From regulatory mechanisms to therapeutic opportunities and translational hurdles (Review).","authors":"Wenlong Zhang, Nuo Chen, Liya Gong, Yu Dong, Hui Shen, Xin Liu, Jie Sun, Luxuan Liu, Zhe Jin, Liaoyuan Wang, Xue Han, Bin Zhang, Shuixing Zhang","doi":"10.3892/ijmm.2026.5989","DOIUrl":"10.3892/ijmm.2026.5989","url":null,"abstract":"<p><p>Immune checkpoint inhibitors have changed cancer treatment, although durable benefit remains limited because malignant, immune and stromal cells sustain suppression within the tumor immune microenvironment. Extracellular vesicles (EVs), including small EVs, can transfer circular RNAs (circRNAs) between defined donor and recipient cells. The relevant steps extend from circRNA biogenesis and entry into EV populations to delivery, intracellular activity, immune phenotype and clinical use. Incomplete transfer experiments, tumor‑intrinsic circRNA activity and engineered RNA platforms differ from direct EV‑mediated transfer. Direct transfer has been linked to tumor‑associated macrophages, myeloid‑derived suppressor cells, natural killer cells, CD8+ T cells and regulatory T cells. Within recipient cells, circRNAs can regulate microRNA availability, assemble RNA‑binding protein complexes, alter protein or RNA stability and produce functional peptides. Donor state, recipient identity, tissue site, EV subpopulation and delivered dose can change the resulting phenotype. Cancer‑associated fibroblasts further connect EV‑associated circRNAs with matrix remodeling, immune‑cell access and treatment tolerance. Biological support is classified from E0 to E3, while EV methods are considered separately through source definition, separation, characterization, RNA protection, uptake controls and quantitative dose. Translation will require full‑length circRNA identification, absolute measurement in EVs and recipient cells, spatial localization, prospective treatment cohorts and repeated‑dose safety testing. These requirements distinguish circulating associations from transferred molecules and identify the experiments needed for biomarker or therapeutic development.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 5","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting integrated cell death networks in sepsis‑associated acute kidney injury: Shared regulatory nodes and diet‑related small molecule modulation (Review).","authors":"Lin Song, Aifeng He, Wei Jiang, Keran Shi, Jing Wang, Lu Xu, Jiangquan Yu, Ruiqiang Zheng","doi":"10.3892/ijmm.2026.5974","DOIUrl":"10.3892/ijmm.2026.5974","url":null,"abstract":"<p><p>Sepsis‑associated acute kidney injury (SA‑AKI) presents a significant challenge in critical care, largely due to the multifaceted nature of renal injury stemming from interconnected disturbances in inflammation, metabolism, microcirculation, mitochondrial function and programmed cell death, rather than arising from a singular dominant pathway. Increasing evidence indicates that apoptosis, pyroptosis, ferroptosis, necroptosis and autophagy‑related responses function as an integrated yet heterogeneous cell death network, characterized by extensive crosstalk, compensatory signaling and disease stage‑dependent regulation. The present review uses an integrated cell death network framework for SA‑AKI, rather than simply summarizing individual cell death pathways or sequentially cataloguing diet‑related small molecules. Current evidence was synthesized by organizing shared regulatory nodes according to their mechanistic roles, including upstream drivers, amplifiers or permissive states, context‑dependent modifiers, and terminal execution mechanisms. Focus is placed on mitochondrial dysfunction, redox‑iron imbalance, NF‑κB‑dependent inflammatory activation, inflammasome priming, failures in autophagy/mitophagy and immunometabolic stress. Furthermore, the present review explores how diet‑related small molecules may influence these shared injury conditions, differentiating between food‑derived phytochemicals, nutritional compounds, microbiota‑derived metabolites and intensive care unit‑based antioxidant or vitamin regimens. The potential efficacy of these compounds may derive less from their ability to selectively inhibit isolated death programs and more from their capacity to reshape common upstream environments that allow multiple death pathways to manifest. Finally, major translational barriers are discussed, including limited bioavailability, uncertainty surrounding active metabolites, altered pharmacokinetics during sepsis, disease‑stage specificity, renal target exposure and inter‑patient heterogeneity. An exposure‑aware and endotype‑guided framework is proposed for the future evaluation of diet‑related small molecules in the context of SA‑AKI.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 5","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sirt1 attenuates calcific aortic valve disease by inhibiting ferroptosis and enhancing mitochondrial function via the activation of the Nrf2/HO‑1/FTH1 axis.","authors":"Fei Yan, Lei Shi, Yuechan Wang, Ying Zhao, Yuanyuan Wu, Dubiao Xian, Yunheng Liang, Ning Wang, Hongwang Cui, Minni Zhang","doi":"10.3892/ijmm.2026.5993","DOIUrl":"10.3892/ijmm.2026.5993","url":null,"abstract":"<p><p>Calcific aortic valve disease (CAVD) is a progressive disorder characterized by valvular calcification and currently lacks effective pharmacological therapies. Sirtuin 1 (Sirt1) has emerged as a cardioprotective factor; however, its role in CAVD remains unclear. The present study aimed to investigate whether Sirt1 attenuates CAVD by regulating iron homeostasis, ferroptosis and mitochondrial function through the nuclear factor erythroid 2‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO‑1)/ferritin heavy chain 1 (FTH1) signaling axis. Sirt1 expression was evaluated in human calcified and non‑calcified aortic valves. Primary human aortic valve interstitial cells (hAVICs) were transfected with pcDNA3.1‑Sirt1 and subjected to osteogenic induction with or without the Nrf2 inhibitor, ML385, or the ferroptosis inducer, erastin. Osteogenic differentiation, mitochondrial function, ferroptosis and Nrf2/HO‑1/FTH1 signaling were analyzed. <i>In vivo</i>, apolipoprotein E‑deficient (Apoe‑/‑) mice fed a Western diet containing 21% fat and 0.15% cholesterol (w/w) were treated with the Sirt1 agonist, SRT2104, with or without AAV‑mediated HO‑1 or FTH1 silencing, to evaluate aortic valve calcification. The results revealed that Sirt1 expression was significantly reduced in calcified human valves and osteogenically induced hAVICs. Sirt1 overexpression inhibited osteogenic differentiation, reduced RUNX2 nuclear translocation, restored mitochondrial function and suppressed ferroptosis. Mechanistically, Sirt1 activated Nrf2/HO‑1 signaling, upregulated the downstream effector, FTH1, reduced intracellular Fe2+ accumulation and maintained iron homeostasis. These protective effects were abolished by treatment with ML385 or erastin. In Apoe‑/‑ mice, SRT2104 attenuated aortic valve calcification and pathological remodeling, whereas HO‑1 or FTH1 silencing partially reversed these benefits. Collectively, the present study demonstrates that Sirt1 protects against CAVD by activating the Nrf2/HO‑1 pathway, leading to the FTH1‑dependent maintenance of iron homeostasis, the suppression of ferroptosis, the preservation of mitochondrial function and the inhibition of osteogenic differentiation. These findings identify the Sirt1/Nrf2/HO‑1/FTH1 axis as a potential therapeutic target for CAVD.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 5","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel insights into the role of the renal interstitial microenvironment in Randall's plaque formation (Review).","authors":"Jialiang Wang, Zhangcheng Liao, Minghui Liu, Yizhou Wang, Yu Cui, Hequn Chen, Feng Zeng, Zewu Zhu","doi":"10.3892/ijmm.2026.6004","DOIUrl":"https://doi.org/10.3892/ijmm.2026.6004","url":null,"abstract":"<p><p>Randall's plaque (RP) consists of subepithelial hydroxyapatite (HAP) deposits within renal papillae and provides a well‑established attachment substrate for a subset of idiopathic calcium oxalate (CaOx) kidney stones. However, RP has traditionally been viewed as a passive mineral surface onto which crystals accrete, with comparatively less focus on the cellular and molecular events that build the plaque itself. The renal papillary interstitium has been indicated as a dynamic microenvironment that undergoes molecular remodeling during plaque‑associated mineralization. The present review aimed to organize the current evidence regarding interconnected processes that may overlap <i>in vivo</i> rather than occur in a fixed sequence. Physicochemical conditions in the inner medullary interstitium favor HAP nucleation and provide the foundation for plaque formation. Epithelial injury responses, regulated cell death, osteogenic‑like fibroblasts and immune remodeling may contribute to the development of a pro‑calcific microenvironment; however, the spatial relationship, temporal order and plaque specificity of these processes remain incompletely defined. Macrophage polarization may influence whether local crystal‑associated inflammation and mineralization are amplified or reduced. As interstitial HAP deposits enlarge and become exposed through focal disruption of the renal papillary epithelium, these deposits can interact with pelvic urine and support CaOx nucleation and overgrowth. Systemic metabolic abnormalities and urinary or gut microbiome alterations are associated with stone disease and may modify the papillary microenvironment; however, direct evidence that they alter human RP burden is lacking to date. Of note, available animal and cell models demonstrate selected aspects of mineralization or crystal injury but do not reproduce the chronic, progressive interstitial HAP plaque observed in humans. In conclusion, considering RP as an interstitial microenvironmental disorder may help identify potential biomarkers of early papillary remodeling and generate potential therapeutic strategies for stone prevention in the future.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 5","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"tRNA‑derived RNAs in hepatic diseases: From biological functions to clinical translation (Review).","authors":"Yaotian Cai, Yifei Chen, Fuji Yang, Yongmin Yan, Ting Jiang","doi":"10.3892/ijmm.2026.5987","DOIUrl":"10.3892/ijmm.2026.5987","url":null,"abstract":"<p><p>In recent years, with the deepening understanding of the significant role of small non‑coding RNAs in human health and diseases, transfer RNA‑derived RNAs (tsRNAs) have gradually become a research focus. Existing evidence shows that tsRNAs not only participate in the regulation of liver gene expression, translation and stress response, but may also act as signaling molecules to mediate inter‑organ communication. However, the specific pathological mechanism and clinical value in the occurrence and development of liver diseases remain unclear. Although tsRNAs show promising prospects as non‑invasive biomarkers and are expected to be used in the diagnosis of liver diseases, screening of therapeutic targets, drug delivery and regulation of enzyme activity, the methodological limitations at present and the differences in performance among different disease types and populations have significantly restricted their clinical translation. The present article systematically reviews the pathological roles of tsRNAs in various liver diseases, with a focus on elaborating their roles in tumor evolution, metabolic disorders and immune regulation. Their clinical application potential was also evaluated, methodological challenges were discussed, and future directions were proposed to advance tsRNA‑based clinical translation in hepatology.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 5","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketogenic diet attenuates Müller cell activation and retinal neuroinflammation in autoimmune glaucoma through acetylation‑mediated FOXO signalling.","authors":"Sisi Tan, Xiaochen Wang, Yunfan Zheng, Zhenni Mou, Lihong Zeng, Jingchang Yuan, Xiao Fan, Miao Wei, Yujia Huo, Ruotong Ouyang, Yanyu Pu, Junqin Lei, Xi Gao, Dangdang Wang, Yang Peng, Hong Li","doi":"10.3892/ijmm.2026.5992","DOIUrl":"10.3892/ijmm.2026.5992","url":null,"abstract":"<p><p>Glaucoma consists of a group of neurodegenerative diseases characterized by retinal ganglion cell degeneration, in which Müller cells are increasingly recognised as drivers of neuroinflammation. A ketogenic diet (KD) elevates circulating β‑hydroxybutyrate (BHB) and exhibits benefits in other neurodegenerative disorders; however, its role in glaucoma remains poorly understood. In the present study, an experimental autoimmune glaucoma (EAG) mouse model was established and primary Müller cells were cultured. Using spectrophotometry, optical coherence tomography and immunofluorescence, serum ketone body levels were found to be significantly lower in both patients with primary open‑angle glaucoma and EAG mice, independent of intraocular pressure. <i>In vitro</i> and <i>in vivo</i> experiments showed that KD increased BHB levels and ketone body metabolism, suppressed Müller cell activation and reduced retinal neuroinflammation. In addition, 4D data‑independent acquisition proteomic analysis and subsequent validation revealed that FOXO3A acetylation and FOXO3A and metallothionein 2A upregulation were regulated in the retina and Müller cells. These findings suggest that impaired ketone body metabolism occurs in glaucoma and that KD‑mediated neuroprotection is associated with altered FOXO3A acetylation. The present study highlighted an association between ketone metabolism and immune regulation in glaucoma, providing evidence for Müller cell phenotypic modulation and supported further investigation of KD as a potential neuroprotective adjunct therapy for glaucoma.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 5","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}