Molecular Medicine最新文献

{"title":"Reciprocal METTL3-PAX5 regulation in maintaining B-cell identity and promoting B-cell hyperreactivity in SLE.","authors":"Yiying Yang, Ying Zhang, Shasha Xie, Ke Liu, Meidong Liu, Yisha Li, Hui Luo, Xiaoxia Zuo, Huali Zhang, Muyao Guo","doi":"10.1186/s10020-025-01295-2","DOIUrl":"10.1186/s10020-025-01295-2","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"236"},"PeriodicalIF":6.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285515","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":"Cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in COPD but suppressed in non-COPD tobacco smokers.","authors":"Sarah D Yanik, Kaschin Jamal Jameel, Simon Rohde, Paul Bürger, Eike Bülthoff, Thomas Grunwald, Juliane Kronsbein, Andrea Koch, Michael R Edwards, Matthias Tenbusch, Jürgen Knobloch","doi":"10.1186/s10020-025-01277-4","DOIUrl":"10.1186/s10020-025-01277-4","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"237"},"PeriodicalIF":6.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285514","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":"PELI2 inhibits colorectal cancer development through MAPK signaling pathway.","authors":"Jialin Liu, Shengyun Hu, Liangbo Zhao, Yanmei Yang, Guanghua Wu, Yimeng Duan, Xinrui Ma, Peiwen Wang, Zhiyong Zhang, Hong Zong","doi":"10.1186/s10020-025-01294-3","DOIUrl":"10.1186/s10020-025-01294-3","url":null,"abstract":"<p><p>Colorectal cancer is one of the most common malignant tumors worldwide. Colorectal cancer has a poor survival rate because it tends to metastasise to the liver and other organs. PELI2, an E3 ubiquitin ligase, is down-expressed in a variety of tumors. However, the role of PELI2 in colorectal cancer has not been revealed. In the present study, we found that expression level of PELI2 were reduced significantly in colorectal tumors compared with normal tissues. Patients with low level of PELI2 expression tended to have poor prognosis. Moreover, PELI2 decreased the proliferation, migration and anti-apoptosis of colorectal cancer cells in vitro. We also constructed xenograft tumor model to verify colorectal tumor growth slowed down after PELI2 overexpression. Transcriptome analysis suggested that PELI2 suppressed colorectal cancer progression via the MAPK signaling pathway. In brief, our study shows that PELI2 inhibits colorectal cancer development by MAPK signaling pathway.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"235"},"PeriodicalIF":6.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275355","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":"AREG⁺ regulatory T cells mediating myocardial repair and neovascularization after myocardial infarction.","authors":"Yan Wang, Jiao Li, Yu Zhang, Pingping He, Weiwei Liu, Weirong Zeng, Chaofu Li, Yixuan Gao, Yongchao Zhao, Changyin Shen, Wenming Chen, Yunhang Li, Ranzun Zhao, Bei Shi","doi":"10.1186/s10020-025-01281-8","DOIUrl":"10.1186/s10020-025-01281-8","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"229"},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266685","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":"Bavachin ameliorates cisplatin-induced nephrotoxicity by enhancing mitochondrial β-oxidation and lipid metabolism through MFN2.","authors":"Shilu Luo, Ming Yang, Na Jiang, Chenrui Li, Yan Liu, Lin Sun","doi":"10.1186/s10020-025-01283-6","DOIUrl":"10.1186/s10020-025-01283-6","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin-induced nephrotoxicity is a critical adverse reaction that restricts the clinical utilization of cisplatin. Alterations in fatty acid metabolism have been associated with the pathogenesis of cisplatin-induced nephrotoxicity, yet the precise mechanisms remain unclear. Bavachin, a natural flavonoid, exhibits anti-inflammatory, antioxidant, and lipid metabolism-regulating properties, yet its role in mitigating cisplatin-induced nephrotoxicity via mitochondrial β-oxidation remains unexplored. Mitofusin-2 (MFN2), a mitochondrial fusion protein, has emerged as a critical regulator of fatty acid oxidation (FAO) and lipid homeostasis. However, its role in cisplatin-induced nephrotoxicity has not been fully explored.</p><p><strong>Methods: </strong>C57/6L mice were randomly divided into control, DMSO, cisplatin, and cisplatin + Bavachin groups. Blood urea nitrogen (BUN), serum creatinine (SCr), reactive-oxygen-species (ROS), lipid accumulation, and apoptosis were assessed. In vitro, the human proximal tubule epithelial cell line (HK-2) cells were treated with 20 µM cisplatin with or without bavachin. ROS production was detected by the DCFH-DA, lipid deposition was detected by oil red O staining, and MFN2, carnitine palmitoyltransferase 1a (CPT1a) were detected by Western blot (WB).</p><p><strong>Results: </strong>Compared with the cisplatin group, bavachin treatment reduced BUN (21.8%) and SCr (78.7%) in the cisplatin group, accompanied by improvements in renal pathological changes, lipid deposition, and apoptosis. In addition, bavachin up-regulated the expression of MFN2 and CPT1a, while decreasing the cisplatin-induced ROS overproduction. Similar results were found in vitro. Notably, the mitochondrial FAO has been increased in HK-2 cells treated with bavachin. Further, MFN2 siRNA partially reversed these protective effects, accompanied by decreased CPT1a expression and exacerbated lipid deposition.</p><p><strong>Conclusions: </strong>This study is the first to confirm MFN2 as a target for renal protection by bavachin. Mechanistically, Bavachin alleviated cisplatin-induced lipid accumulation and apoptosis by upregulating MFN2 expression, which activated CPT1a to promote mitochondrial FAO. These results will provide a new strategy for cisplatin-based cancer therapy and the reduction of its nephrotoxicity.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"234"},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275352","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":"Celastrol improves endothelial function in diet-induced obesity mice via attenuating endoplasmic reticulum stress through the activation of AMPK pathway.","authors":"Cheng Yu, Weihong Lin, Jing Yang, Qiong Jiang, Wenkun Liu, Hongjin Liu, Yong Lin, Litao Wang, Lei Chen, Yu Huang, Lianglong Chen","doi":"10.1186/s10020-025-01259-6","DOIUrl":"10.1186/s10020-025-01259-6","url":null,"abstract":"<p><strong>Background: </strong>Diet-induced obesity (DIO) is a significant factor in endothelial dysfunction. Celastrol, a potent anti-inflammatory and anti-oxidative pentacyclic triterpene, has shown promise as a protective agent against cardiovascular disease. However, the specific protective effects and mechanisms of celastrol in preventing endothelial dysfunction in diet-induced obesity are not yet fully understood.</p><p><strong>Methods and results: </strong>In this study, eight-week-old C57BL/6 mice were fed a normal or high-fat diet and treated with or without celastrol for 8 weeks. We measured acetylcholine-induced endothelium-dependent relaxation (EDR) in the aortae using a wire myograph. The results revealed that EDR was impaired in DIO mice, along with decreased AMPK phosphorylation, increased endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) in the aortae. These effects were reversed by celastrol treatment. Celastrol also reversed tunicamycin-induced ER stress, decreased nitric oxide (NO) production, and impaired EDR in mouse aortae. The protective effects of celastrol were negated by co-treatment with an AMPK inhibitor (Compound C). Furthermore, in AMPKα deficient mice, the beneficial effects of celastrol on EDR were significantly reduced.</p><p><strong>Conclusions: </strong>These findings suggest that celastrol improves endothelial function by inhibiting ER stress and increasing NO production through the activation of the AMPK pathway in DIO mice.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"233"},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275353","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":"ONECUT2 reprograms neuroendocrine fate and is an actionable therapeutic target in small cell lung cancer.","authors":"Mirian Gutiérrez, Irene Zamora, Raquel Iriarte, María José Pajares, Qian Yang, Chen Qian, Nerea Otegui, Joaquín Fernández-Irigoyen, Enrique Santamaría, Nicolas Alcala, Alexandra Sexton-Oates, Lynnette Fernández-Cuesta, Miguel Barajas, Alfonso Calvo, Luis M Montuenga, Beatrice Knudsen, Sungyong You, Michael R Freeman, Ignacio Encío, Mirja Rotinen","doi":"10.1186/s10020-025-01267-6","DOIUrl":"10.1186/s10020-025-01267-6","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) is a highly aggressive malignancy with extremely poor prognosis. SCLC cells exhibit high plasticity and can progress from neuroendocrine (NE) to non-NE phenotypes. This dynamic evolution promotes treatment resistance and relapses, representing a challenge for targeted therapies in this elusive disease. Here we identify the transcription factor ONECUT2 (OC2) as a driver of plasticity in SCLC, leading to non-NE transcriptional states. OC2 is highly expressed in SCLC tumors compared to normal lung tissue and its expression is associated with heightened clinical stage and lymph node metastasis. We show that OC2 is a repressor of ASCL1, the NE master regulator transcription factor. In addition, OC2 upregulates non-NE programs through activation of c-MYC and Notch signaling. We also demonstrate that OC2 is required for growth and survival of SCLC cells and that it can be targeted with a small molecule inhibitor that acts synergistically with the standard combination of cisplatin and etoposide, providing a novel therapeutic strategy for OC2 active SCLC tumors.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"232"},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275354","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":"Cellular imbalance in proximal and distal lung of CFTR^-/- sheep in utero and at birth.","authors":"Shih-Hsing Leir, Svyatoslav Tkachenko, Alekh Paranjapye, Arnaud J Van Wettere, Jenny L Kerschner, Iuri Viotti Perisse, Cheyenne M Marriott, Tayler Patrick, Ying Liu, Kenneth L White, Irina A Polejaeva, Ann Harris","doi":"10.1186/s10020-025-01266-7","DOIUrl":"10.1186/s10020-025-01266-7","url":null,"abstract":"<p><strong>Background: </strong>The Lung is the major focus of therapeutic approaches for the inherited disorder cystic fibrosis (CF) as without treatment lung disease is life-limiting. However, the initiating events that predispose the CF lung to cycles of infection, inflammation and resultant tissue damage are still unclear. Inflammation may occur in the CF lung prior to birth in human and several large animal models suggesting an in utero origin for the disease and encouraging further studies prior to birth.</p><p><strong>Methods: </strong>Here we used the sheep model of CF (CFTR^-/-) and age-matched wild-type (WT) sheep of the same breed to investigate the single cell transcriptomes of proximal and distal lung tissue at 80 days and 120 days of gestation and at term (147 days). Single cell RNA-seq was performed on tissues from 4 to 7 animals of each genotype (WT and CFTR^-/-) at each time point.</p><p><strong>Results: </strong>At term, FOXJ1-expressing ciliated cells are overrepresented in both lung regions from CFTR^-/- lambs, while secretory epithelial and basal cells are underrepresented in proximal lung, as are T cells and monocytes in distal lung. The imbalance in ciliated and basal cells was confirmed by immunohistochemistry. At 120 days of gestation, lymphoid cells are slightly more abundant in proximal and distal lung from CFTR^-/- animals compared to WT, consistent with the transient CF-associated inflammatory response in utero. At 80 days of gestation, T and B cells are underrepresented in both lung regions.</p><p><strong>Conclusions: </strong>The differences in epithelial cell abundance observed in the CFTR^-/- lambs at term may reflect sequelae from the loss of CFTR on lung development and differentiation in utero. These findings provide novel insights into the cellular mechanisms of pathology and may be relevant to the design of new therapeutic approaches for CF lung disease.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"231"},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266686","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":"Rescuing vascular dysfunction in dorsal pancreatic arteries prevents tacrolimus-induced glucose metabolism disorder in mice.","authors":"Lingyan Fei, Honghong Wang, Dongliang Zhao, Xiaohua Wang, Jizhen Ren, Lanyun Liu, Chun Tang, Yan Lei, Qingqing Wang, Yuanpeng Nie, Yang Liu, Na Li, Ming Zhong, Nan Xu, Jin Wei, Pontus B Persson, Andraes Patzak, Pratik H Khedkar, Zhihua Zheng, Shan Jiang","doi":"10.1186/s10020-025-01282-7","DOIUrl":"10.1186/s10020-025-01282-7","url":null,"abstract":"<p><p>Long-term adverse effects of the immunosuppressant tacrolimus (Tac), such as nephrotoxicity, hepatotoxicity and diabetes, have been widely reported. Up to 33.6% of solid organ transplantation patients receiving Tac treatment develop hyperglycemia; however, the underlying mechanisms remain poorly understood. Here, using a mouse model of Tac-induced hyperglycemia, we found that Tac-induced body-weight loss, hyperglycemia, hypoinsulinemia, glucose intolerance and insulin resistance were improved by valsartan, a renin-angiotensin system (RAS) inhibitor. Histological and immunofluorescence analysis of the pancreas showed reduced islet areas and β-cell mass in Tac-treated mice. Moreover, when compared to control mice, isolated islets from Tac-treated mice showed a downregulation of cell-proliferation markers (Ki67, Ccna2 and Ccnd1) while an upregulation of apoptotic markers (DNA fragmentation, Bax and Caspase3). Tac also upregulated hypoxia-related markers in the pancreas, including hypoxia-inducible factor-1α (HIF-1α) and its downstream factors (Adm, Hmox1 and Vegfa), CD31 and pimonidazole adducts. Furthermore, treatment with Tac led to vascular dysfunction in pancreatic arteries. All of these adverse effects could be partially or fully abrogated by valsartan. Tac also increased levels of renin in renal tissue (1.00 ± 0.06 vs 1.29 ± 0.04, p < 0.05) and serum (28.35 ± 4.29 ng/mL vs 51.99 ± 4.95 ng/mL, p < 0.05). Inhibition of RAS by valsartan protected against Tac-induced vascular dysfunction in renal interlobar arteries. Collectively, our data illustrate a previously undescribed mechanism, in which Tac-induced vascular dysfunction in renal interlobar arteries leads to RAS activation. Blocking RAS by valsartan alleviates vascular dysfunction in dorsal pancreatic arteries and hypoxia in islets, which in turn prevents Tac-induced β-cell dysfunction and glucose metabolism disorder.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"230"},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266690","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":"VILIP3 attenuates neuronal apoptosis and oxidative stress via Nrf2 activation in the pathogenesis of Alzheimer's disease.","authors":"Shasha Huangfu, Xiaoyu Sang, Shiyue Zhou, Haixia Liu, Dongqing Cui, Yansheng Du, Xinyue Xing, Wenyan Liu, Jianzhong Bi, Zhaohong Xie","doi":"10.1186/s10020-025-01280-9","DOIUrl":"10.1186/s10020-025-01280-9","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"227"},"PeriodicalIF":6.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266691","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}