Molecular Medicine最新文献

{"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":"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":"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}

{"title":"PIEZO1 promotes psoriasis-like skin inflammation in mice via NF-κB/IL-17 signaling pathway activation.","authors":"Wen Li, Kan Ze, Xufeng He, Lili Yang, Huimin Zhang, Weian Yuan, Wuqing Wang","doi":"10.1186/s10020-025-01279-2","DOIUrl":"10.1186/s10020-025-01279-2","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"225"},"PeriodicalIF":6.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266689","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":"Novel NIR fluorescent probe IR-546 inhibits melanoma through the AKT/GSK3β/β-catenin pathway.","authors":"Hongye Liao, Tong Xia, Ziyuan Zeng, Xun Yang, Simei Yang, Xia Xiong, Yuanmin He, Changzhen Sun, Na Hao, Li Liu","doi":"10.1186/s10020-025-01289-0","DOIUrl":"10.1186/s10020-025-01289-0","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"226"},"PeriodicalIF":6.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266687","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":"O-GlcNAcylation with ubiquitination stabilizes METTL3 to promoting HMGB1 degradation to inhibit ferroptosis and enhance gemcitabine resistance in pancreatic cancer.","authors":"Qiuhong Wang, Dong Wei, Chunman Li, Xiawei Yang, Kun Su, Tao Wang, Renchao Zou, Lianmin Wang, Dongyun Cun, Bo Tang, Tao Wu","doi":"10.1186/s10020-025-01285-4","DOIUrl":"10.1186/s10020-025-01285-4","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"228"},"PeriodicalIF":6.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266688","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":"Targeted destruction of follicle stimulating hormone receptor-positive cancer cells in vitro and in vivo by a lytic peptide Phor21-FSHβ conjugate.","authors":"Nafis A Rahman, Marcin Chrusciel, Donata Ponikwicka-Tyszko, Kamila Pulawska-Moon, Milena Doroszko, Joanna Stelmaszewska, Oliver J Keuzer, Adolfo Rivero-Muller, Piotr Bernaczyk, Grzegorz Zalewski, Peilan Guo, Jorma Toppari, Xiangdong Li, Adam J Ziecik, Slawomir Wolczynski, Ilpo Huhtaniemi","doi":"10.1186/s10020-025-01292-5","DOIUrl":"10.1186/s10020-025-01292-5","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"224"},"PeriodicalIF":6.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258590","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":"Nuclear VPS35 attenuates NHEJ repair by sequestering Ku protein.","authors":"Luping Zhang, Yonghong Nie, Tuo Tang, Yanji Lu, Wenlong Li, Xian Hong, Qiang Li, Aixue Zheng, Yongpei Li, Jianwen Zhou, Li Fan, Tao Wang, Zhihui Deng","doi":"10.1186/s10020-025-01288-1","DOIUrl":"10.1186/s10020-025-01288-1","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"222"},"PeriodicalIF":6.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248835","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":"Cross-talk between NLRP3 and AIM2 inflammasomes in macrophage activation by LPS and titanium ions.","authors":"Ana Belén Carrillo-Gálvez, José Antonio Guerra-Valverde, Miguel Padial-Molina, Andrea Martínez-Cuevas, Darío Abril-García, Allinson Olaechea, Natividad Martín-Morales, Francisco O'Valle, Pablo Galindo-Moreno, Federico Zurita","doi":"10.1186/s10020-025-01290-7","DOIUrl":"10.1186/s10020-025-01290-7","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"223"},"PeriodicalIF":6.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258589","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":"Dehydrodiisoeugenol targets NOD2 exerting dual effects against colitis and colorectal cancer: a double-edged sword.","authors":"Feiyang Yi, Nianzhi Chen, Maoyuan Zhao, Zhili Gu, Yun Yuan, Xuegui Tang, Fang Liu","doi":"10.1186/s10020-025-01193-7","DOIUrl":"10.1186/s10020-025-01193-7","url":null,"abstract":"<p><p>Dehydrodiisoeugenol (DEH) is a primary benzofuran-type neolignan isolated from the Chinese herbal medicine nutmeg, which is used in the treatment of gastrointestinal diseases. This study aims to observe the dual therapeutic effects of DEH on DSS-induced ulcerative colitis (UC) and colorectal cancer (CRC), with a focus on exploring the molecular mechanism by which DEH exerts anti-inflammatory effect in inflammatory cells and induces autophagy in CRC cells. An inflammatory cell model was established by LPS/IFNγ-stimulated RAW264.7 macrophages to observe the anti-inflammatory effect of DEH, while colon cancer cell lines were used to observe the anticancer activity of DEH. DSS-induced mice and subcutaneous tumor model in nude mice were also established to observe the bidirectional regulation of DEH. This study demonstrates that low concentrations of DEH exhibit anti-inflammatory effects in vitro. Importantly, DEH achieves significant inhibition of IκBα degradation and phosphorylation levels, as well as subsequent NF-κB nuclear translocation, while also suppressing the phosphorylation of the MAPK family members JNK, ERK, and p38, by reducing elevated NOD2 expression induced by LPS/IFNγ. In addition, oral administration of DEH improves colitis and colonic barrier damage in DSS-induced mice. Interestingly, at a high concentration of DEH significantly activates the NOD2 signaling pathway to promote autophagy and apoptosis in CRC cells, contributing to its anti-CRC effect. These findings suggest that different concentration of DEH shows bidirectional regulation by improve inflammatory responses in UC and simultaneously possess anti-CRC effects by targeting the NOD2. This highlights DEH as a promising candidate for clinical treatment of UC and CRC.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"221"},"PeriodicalIF":6.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225987","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}