Molecular Medicine最新文献

{"title":"L-Phenylalanine promotes liver steatosis by inhibiting BNIP3-mediated mitophagy.","authors":"Ying Sun, Lingli Cai, Bowei Yu, Haojie Zhang, Ziteng Zhang, Xiaoqin Xu, Yuefeng Yu, Jiang Li, Chi Chen, Fangzhen Xia, Yingli Lu, Kun Zhang, Ningjian Wang","doi":"10.1186/s10020-025-01303-5","DOIUrl":"10.1186/s10020-025-01303-5","url":null,"abstract":"<p><strong>Background: </strong>L-Phenylalanine (L-Phe) levels are elevated in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, whether L-Phe induces liver steatosis and the underlying mechanism remain unknown. This study aimed to investigate the mechanism through which L-Phe promotes liver steatosis.</p><p><strong>Methods: </strong>We utilized human data from the UK Biobank and SPECT-China studies. Plasma/serum samples were collected for metabolomic testing to measure L-Phe levels. A rat model with L-Phe in the drinking water was established to investigate changes in hepatic lipid metabolism. In addition, BNIP3 was overexpressed both in vitro and in vivo to validate the role of L-Phe in BNIP3-mediated mitophagy associated with liver steatosis.</p><p><strong>Results: </strong>In both populations, elevated L-Phe quartiles were associated with increased body mass index, triglyceride, and transaminase levels and increased odds of MASLD (all p < 0.05). Rats exposed to L-Phe had increased hepatic lipid deposition and decreased mitophagy in the liver. Differentially expressed proteins were enriched in the PPARα and fatty acid β-oxidation signalling pathways, with downregulation of the mitophagy marker BNIP3. Mitophagy was activated by rapamycin and then inhibited by L-Phe, indicating that elevated L-Phe promoted lipid accumulation by suppressing mitophagy. BNIP3 overexpression effectively mitigated L-Phe-induced hepatic steatosis by restoring mitophagy. Moreover, L-Phe regulates the BNIP3-mediated PPARα and AMPK/mTOR signalling pathways to promote hepatic steatosis.</p><p><strong>Conclusions: </strong>Our study revealed the role of L-Phe in regulating lipid metabolism and promoting liver steatosis via BNIP3-mediated mitophagy. These findings provide novel insights into the link between L-Phe and liver steatosis, suggesting potential nutritional intervention strategies for preventing MASLD.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"250"},"PeriodicalIF":6.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528891","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 coniferaldehyde as an inhibitor of caseinolytic protease to combat Staphylococcus aureus infections.","authors":"Shufang Li, Yan Zhang, Jianfeng Wang, Hongfa Lv, Hongxia Ma, Lingcong Kong, Yonglin Zhou, Jingmin Gu, Wei Li, Qiaoling Zhang","doi":"10.1186/s10020-025-01306-2","DOIUrl":"10.1186/s10020-025-01306-2","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"249"},"PeriodicalIF":6.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528890","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: ITIH4 alleviates OVA-induced asthma by regulating lung-gut microbiota.","authors":"Yi-Hsuan Liu, Yueh-Lun Lee, Chia-Li Han, Yu-Chun Lo, Zih-An Liao, Yu-Syuan Shih, Yi-Wen Lin, Syue-Wei Peng, Kang-Yun Lee, Shu-Chuan Ho, Sheng-Ming Wu, Cheng-Wei Lin, Kian Fan Chung, Jer-Hwa Chang, Hsiao-Chi Chuang","doi":"10.1186/s10020-025-01293-4","DOIUrl":"10.1186/s10020-025-01293-4","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"248"},"PeriodicalIF":6.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497511","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":"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186328/pdf/","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":"OA","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182682/pdf/","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":"OA","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}