Molecular Medicine最新文献

{"title":"Epigenetic modulation elicits an NK cell-mediated immune response in urothelial carcinoma.","authors":"Himani Kumari, Ciao-Ni Chen, Hsin-An Shih, Chih-Chieh Yeh, Tsung-Yu Tseng, Hsing-Fen Tsai, Jie Ting Low, Chin Pui Chan, Guan-Ling Lin, Wan-Hong Huang, Chao-Ling Yao, Steven Lin, Cheng-Huang Shen, Michael W Y Chan","doi":"10.1186/s10020-025-01264-9","DOIUrl":"https://doi.org/10.1186/s10020-025-01264-9","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"247"},"PeriodicalIF":6.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoginkgetin protects chondrocytes and inhibits osteoarthritis through NF-κB and P21 signaling pathway.","authors":"Mengdai Xu, Xi Chen, Shasha Du, Huanhuan Xu, Changyu Liu","doi":"10.1186/s10020-025-01302-6","DOIUrl":"10.1186/s10020-025-01302-6","url":null,"abstract":"<p><strong>Objective: </strong>Osteoarthritis (OA) is the most prevalent chronic articular disease in adults. The degree of cartilage degradation and matrix depletion in OA have been substantially connected with chondrocyte inflammatory response. Consequently, pharmacological anti-inflammatory agents provide OA patients a new therapeutic option. Isoginkgetin (IGK), a bioactive bioflavonoid derived from the medicinal herb Ginkgo Biloba, defends against obesity-induced heart diastolic dysfunction and harmful remodeling. Whether IGK has a regulatory effect on OA remains unknown. This study investigated whether IGK could attenuate the progression of OA both in vivo and in vitro.</p><p><strong>Methods: </strong>Cell Counting Kit-8 (CCK8) was used to measure the vitality of chondrocytes. Mediators of inflammation, anabolism and catabolism were tested by Western blot and RT-PCR. Safranin-O staining, Hematoxylin-Eosin (H&E) staining, immunofluorescence, and Osteoarthritis Research Society International (OARSI) standards were used to assess the severity of OA and the degradation of articular cartilage. The phenotype of cartilage, NF-κB and P21 signaling pathway were measured by Western Blot. The mRNA sequencing was selected to find the differentially expressed genes and potential pathway. Pain of mice was measured by Von Frey hair mechanosensitivity. The senescence level of chondrocyte was SA-β-Gal staining.</p><p><strong>Results: </strong>IGK inhibited catabolism and promoted anabolism after stimulating by IL-1β in vitro. Following destabilization of the medial meniscus (DMM) surgery, administration of IGK significantly reduced OARSI scores and attenuated AGGRECAN and COLLAGEN2 loss, overexpression of MMP3 and articular cartilage deterioration. IGK relieved pain of mice after DMM. Besides, PI3K/AKT/NF-κB, P53, Autophagy, Ferroptosis pathway and reactive oxygen species (ROS), senescence of cartilage were changed after IGK treatment.</p><p><strong>Conclusion: </strong>IGK protects articular cartilage and reduces the progression of OA in a mouse model and shows promise as a potential therapeutic strategy for OA.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"246"},"PeriodicalIF":6.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy in orthodontic tooth movement: advances, challenges, and future perspectives.","authors":"Biao Li, Leilei Wang, Hong He","doi":"10.1186/s10020-025-01299-y","DOIUrl":"10.1186/s10020-025-01299-y","url":null,"abstract":"<p><p>Orthodontics aims to correct misaligned teeth by repositioning them into their proper three-dimensional positions through periodontal remodeling triggered by orthodontic forces. Orthodontic tooth movement (OTM) is an aseptic inflammation process characterized by osteoclast-mediated bone resorption on the compression side and osteoblast-induced bone deposition on the tension side. Orthodontic forces primarily include compressive force (CF), tensile force (TF), and flow shear stress (FSS), meanwhile, hypoxia is concomitantly induced during force application. Autophagy is a highly conserved catabolic mechanism mediating cellular degradation and recycling and is classified into three main types: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA), distinguished by their substrate delivery mechanisms to lysosomes. This review will first outline common autophagy classifications, describe the basic process of macroautophagy, and discuss autophagy regulators, as well as the theories of OTM mechanisms. Furthermore, it will systematically elucidate roles and mechanisms of autophagy in OTM across different cell types, with specific emphasis on hypoxia, CF, TF, and FSS. Additionally, mitophagy and CMA will be addressed. Hopefully, this comprehensive analysis aims to provide a theoretical foundation for accelerating OTM and mitigating orthodontically induced inflammatory root resorption through autophagy modulation.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"245"},"PeriodicalIF":6.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340274","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":"Effect of anti-CD4 mAb induced by inhibiting B cell disorder on immune reconstruction of HIV-infected immunological non-responders.","authors":"Yi Ouyang, Kang Wu, Lei Fu, Panpan Yi, Da Cheng, Xiaoyu Fu","doi":"10.1186/s10020-025-01286-3","DOIUrl":"10.1186/s10020-025-01286-3","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"244"},"PeriodicalIF":6.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336750","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":"Dehydrocostus lactone attenuates atherogenesis by promoting cholesterol efflux and inhibiting inflammation via TLR2/PPAR-γ/NF-κB signaling pathway.","authors":"Weitao Hong, Xiaojia Chen, Jiahai Xiao, Gengji Chen, Jiali Yang, Pengfei Zhang, Zhizhen Zhang","doi":"10.1186/s10020-025-01265-8","DOIUrl":"10.1186/s10020-025-01265-8","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"243"},"PeriodicalIF":6.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333527","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":"FCGR2B knockdown alleviates diabetes-induced cognitive dysfunction by altering neuronal excitability.","authors":"Yinmeng Qu, Xuan Chen, Peifan Wu, Yuhao Zhao","doi":"10.1186/s10020-025-01301-7","DOIUrl":"10.1186/s10020-025-01301-7","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM) patients with cognitive impairment seriously affect their quality of life. The onset and development of diabetes-induced cognitive dysfunction are associated with neuronal excitability. In this work, we aimed to reveal the pathogenesis of DM-induced cognitive impairment.</p><p><strong>Methods: </strong>DM mouse model was constructed by high-fat diet combined with streptozocin. Morris water maze test and novel object recognition was used to examine spatial learning and memory ability of mice. The protein expression levels of Fc gamma receptor 2b (FCGR2B), SHC1, p-PI3K and p-AKT were measured by Western blot. Neuronal markers c-Fos and GABAA were detected by Immunohistochemistry.</p><p><strong>Results: </strong>FCGR2B was highly expressed in hippocampus of DM mice, which was directly associated with Shc1. In vivo, DM mice exhibited decrease of spatial learning and memory ability and up-regulation of FCGR2B. FCGR2B knockdown improved spatial learning and memory ability of DM mice. Not only that, FCGR2B silencing increased the expression of SHC1, p-PI3K and p-AKT in hippocampus of DM mice. Excitatory neuron marker c-Fos was markedly increased and inhibitory neuron marker γ-aminobutyric acid type A (GABAA) receptor was markedly decreased in the hippocampus of DM mice with FCGR2B silencing.</p><p><strong>Conclusion: </strong>Knock-down FCGR2B within hippocampus of DM mice activated PI3K/AKT signaling pathway via SHC1 in DM mice and alleviated DM-induced cognition impairment. Knock-down FCGR2B alleviated DM-induced cognition impairment by regulating hippocampal neuronal excitability. Thus, this work suggested that FCGR2B may be a potential target for treatment of DM-induced cognitive dysfunction.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"242"},"PeriodicalIF":6.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333528","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":"Correction: F127-SE-tLAP thermosensitive hydrogel alleviates bleomycin-induced skin fibrosis via TGF-β/Smad pathway.","authors":"Zhiqin Cao, Keke Zhang, Jingruo Liu, Yu Pan, Jiayi Shi, Luxin Li, Xiaocan Sun, Shiqi Li, Xiaohuan Yuan, Dan Wu","doi":"10.1186/s10020-025-01291-6","DOIUrl":"10.1186/s10020-025-01291-6","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"241"},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326311","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":"4-Octyl itaconate alleviates endothelial cell inflammation and barrier dysfunction in LPS-induced sepsis via modulating TLR4/MAPK/NF-κB signaling : 4-Octyl itaconate alleviates endothelial dysfunction.","authors":"Rong Li, Yu Ma, Haoran Wu, Xiao Zhang, Nianhui Ding, Zhichao Li, Xin Hu, Jiajia Rao, Yiting Zhou, Liqun Wang, Ying Wan, Yan Yang, Jianbo Wu, Xiaoqin Zhang, Chunxiang Zhang","doi":"10.1186/s10020-025-01160-2","DOIUrl":"10.1186/s10020-025-01160-2","url":null,"abstract":"<p><strong>Aim: </strong>Sepsis-induced vascular injury is a major contributor to the high mortality rate of sepsis. However, effective treatments remain elusive due to limited knowledge regarding the underlying molecular mechanisms. Itaconic acid, an endogenous metabolite, involved in multiple inflammatory diseases, but its role in sepsis-induced vascular injury remains unclear. The current study investigates the effect of 4-octyl itaconate (4-OI), a cell-permeable derivative of itaconic acid, on sepsis-induced vascular injury and organ damage.</p><p><strong>Methods and results: </strong>An in vitro cell model was established by treating human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) revealed that 4-OI inhibited the LPS-induced increases in TNF-α, IL-6, and IL-1β levels. Cellular reactive oxygen species (ROS) levels, measured using the fluorescent probe DCFH-DA, mitochondrial ROS (mtROS) levels, measured by MitoSOX, and mitochondrial membrane potential (ΔΨ), detected by the fluorescent indicator JC-1, were all reduced following 4-OI treatment. Additionally, mtDNA release, detected by qRT-PCR, were decreased. Mitochondrial morphology, assessed by PK Mito Orange, was preserved by 4-OI treatment. Furthermore, 4-OI suppressed HUVECs apoptosis and pyroptosis, as detected by TUNEL staining and western blotting. 4-OI treatment also significantly inhibited LPS-induced cell adhesion, as shown in THP-1 attachment assay, by decreasing ICAM-1 and VCAM-1 expression. Cell permeability, determined by FITC-Dx-70 leakage, revealed that 4-OI effectively suppressed LPS-induced increases in cell permeability. Furthermore, 4-OI inhibited LPS-induced phosphorylation and internalization of VE-cadherin protein, preserving the adhesion junctions between endothelial cells. Network pharmacology and molecular docking analysis suggested the involvement of TLR4/MAPK/NF-κB signaling pathway as a key mechanism by which 4-OI ameliorated sepsis-induced vascular cell inflammation and injury, which was confirmed by western blotting. The in vitro results were subsequently verified in vivo in an LPS-induced sepsis mouse model. 4-OI pretreatment substantially decreased inflammatory cytokine levels in serum and lung tissues, inhibited pulmonary oedema and pulmonary vascular leakage, as evidenced by the wet-to-dry weight ratio and Evans blue staining of lung tissues, and alleviated tissue damage, as shown by histological analysis. Survival analysis indicated that 4-OI post-sepsis treatment improved the overall survival rate in LPS-induced ALI mice.</p><p><strong>Conclusion: </strong>4-OI protects against sepsis-induced vascular injury and tissue damage by suppressing endothelial inflammation, oxidative stress, and preserving endothelial barrier integrity.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"240"},"PeriodicalIF":6.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310216","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":"ALDOC and PGK1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancer.","authors":"Liyong Huang, Yixin Tong, Xu Li, Wei Wang, Zhen Wang, Bingchen Chen, Jifu E, Ruzhen Zhou, Hantao Wang, Jinghu He","doi":"10.1186/s10020-025-01252-z","DOIUrl":"10.1186/s10020-025-01252-z","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a significant health challenge globally, demanding a comprehensive understanding of its molecular underpinnings for effective management. In this study, we investigated the role of Aldolase C (ALDOC), a glycolytic enzyme, in CRC pathogenesis. Transcriptomic analysis of CRC tissues from The Cancer Genome Atlas (TCGA) revealed a substantial upregulation of ALDOC, correlating with adverse clinical outcomes. Immunohistochemical (IHC) staining of locally collected patient-derived tissues corroborated these findings, demonstrating elevated ALDOC expression in tumor tissues, particularly in advanced stages. Functional studies elucidated the regulatory role of ALDOC in CRC cell phenotypes. ALDOC knockdown significantly inhibited cell proliferation, induced apoptosis, arrested cell cycle progression, and suppressed cell migration in vitro. Moreover, in vivo studies using xenograft models confirmed that ALDOC knockdown attenuated tumor growth. Mechanistically, ALDOC was found to interact with hypoxia-inducible factor 1 alpha (HIF1A) and enhance its transcriptional activity on phosphoglycerate kinase 1 (PGK1), a key glycolytic enzyme. Dual-luciferase reporter assays and chromatin immunoprecipitation experiments validated the ALDOC-mediated transcriptional activation of PGK1. Further functional rescue experiments revealed a synergistic interplay between ALDOC and PGK1 in regulating CRC cell phenotypes. Additionally, ALDOC was implicated in promoting aerobic glycolysis in CRC cells, potentially through PGK1 regulation. Collectively, our findings unveil ALDOC as a critical regulator of CRC pathogenesis, offering insights into its potential as a therapeutic target and highlighting the ALDOC/PGK1 axis as a promising avenue for further investigation in CRC.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"239"},"PeriodicalIF":6.0,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302528","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":"Ubiquitin-specific protease 38 modulates atrial fibrillation susceptibility in chronic kidney disease via STRAP stabilization and activation of TGF-β/SMAD signaling.","authors":"Hong Meng, Zongze Qu, Zheng Xiao, Bin Kong, Hongjie Yang, Wei Shuai, He Huang","doi":"10.1186/s10020-025-01296-1","DOIUrl":"10.1186/s10020-025-01296-1","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to elucidate the role of the deubiquitinase USP38 in chronic kidney disease (CKD)-associated atrial fibrillation (AF) by investigating its impact on atrial structural and electrical remodeling and its interaction with STRAP and TGF-β/SMAD signaling.</p><p><strong>Methods: </strong>A murine CKD model was established using a two-stage 5/6 nephrectomy. Cardiomyocyte-specific USP38 knockout (USP38-CKO) and overexpression (USP38-TG) mice were generated. Atrial remodeling, electrophysiological parameters, and fibrosis markers were assessed by echocardiography, histology, and immunoblotting. In parallel, HL-1 cells were treated with indoxyl sulfate (100 μM) and subjected to adenoviral-mediated USP38 modulation. Molecular interactions between USP38 and STRAP were evaluated using immunofluorescence, co-immunoprecipitation, and ubiquitination assays. STRAP knockdown studies further validated the downstream effects of USP38.</p><p><strong>Results: </strong>CKD induced significant upregulation of USP38 in atrial tissue and HL-1 cells. USP38-CKO attenuated atrial fibrosis and reduced collagen I/III and α-SMA expression, whereas USP38-TG exacerbated these effects. Notably, USP38 modulation did not significantly alter atrial effective refractory period, suggesting its primary involvement in structural rather than direct electrical remodeling. Mechanistic studies revealed that USP38 stabilizes STRAP via deubiquitination, thereby enhancing TGF-β/SMAD signaling. STRAP knockdown reversed the pro-fibrotic and arrhythmogenic effects induced by USP38 overexpression.</p><p><strong>Conclusion: </strong>USP38 is a critical mediator of CKD-associated AF, promoting atrial fibrosis and electrical remodeling via STRAP stabilization and TGF-β/SMAD pathway activation. Targeting USP38 may represent a novel therapeutic strategy for CKD-associated AF.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"238"},"PeriodicalIF":6.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294125","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}