Journal of Molecular Cell Biology最新文献

Increased serum β-hydroxybutyrate/acetoacetate ratio and aggravated histological liver inflammation in females with metabolic dysfunction-associated steatotic liver disease and polycystic ovary syndrome. 代谢功能障碍相关性脂肪性肝病和多囊卵巢综合征女性血清β-羟丁酸/乙酰乙酸比值升高，肝脏组织学炎症加重。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-05-22 DOI: 10.1093/jmcb/mjae048

Xiaopeng Zhu, Guligeina Aikebaier, Xilei Ban, Qingxia Huang, Hongmei Yan, Xinxia Chang, Xinyu Yang, Xiaoyang Sun, Huiru Tang, Hua Bian, Xin Gao, Mingfeng Xia

引用次数: 0

Low-dose quinine targets KCNH6 to potentiate glucose-induced insulin secretion. 低剂量奎宁靶向KCNH6，增强葡萄糖诱导的胰岛素分泌。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-05-22 DOI: 10.1093/jmcb/mjae051

Feng-Ran Xiong, Juan-Juan Zhu, Xiao-Rong Zhu, Jing Lu, Jin-Kui Yang

{"title":"Low-dose quinine targets KCNH6 to potentiate glucose-induced insulin secretion.","authors":"Feng-Ran Xiong, Juan-Juan Zhu, Xiao-Rong Zhu, Jing Lu, Jin-Kui Yang","doi":"10.1093/jmcb/mjae051","DOIUrl":"10.1093/jmcb/mjae051","url":null,"abstract":"Insulin secretion is mainly regulated by two electrophysiological events, depolarization initiated by the closure of adenosine triphosphate (ATP)-sensitive K+ (KATP) channels and repolarization mediated by K+ efflux. Quinine, a natural component commonly used for the treatment of malaria, has been reported to directly stimulate insulin release and lead to hypoglycemia in patients during treatment through inhibiting KATP channels. In this study, we verified the insulinotropic effect of quinine on the isolated mouse pancreatic islets. We also revealed that low-dose quinine (<20 μM) did not directly provoke Ca2+ spikes or insulin secretion under low-glucose conditions but potentiated Ca2+ influx and insulin secretion induced by high glucose, which cannot be explained by KATP inhibition. KCNH6 (hERG2) is a voltage-dependent K+ (Kv) channel that plays a critical role in the repolarization of pancreatic β cells. Patch clamp experiments showed that quinine inhibited hERG channels at low micromolar concentrations. However, whether quinine can target KCNH6 to potentiate glucose-induced insulin secretion remains unclear. Here, we showed that in vivo administration of low-dose quinine (25 mg/kg) improved glucose tolerance and increased glucose-induced insulin release in wild-type control mice but not in Kcnh6-β-cell-specific knockout (βKO) mice. Consistently, in vitro treatment of primary islet β cells with low-dose quinine (10 μM) prolonged action potential duration and augmented glucose-induced Ca2+ influx in the wild-type control group but not in the Kcnh6-βKO group. Our results demonstrate that KCNH6 plays an important role in low-dose quinine-potentiated insulin secretion and provide new insights into KCNH6-targeted drug development.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNAJC12 downregulation induces neuroblastoma progression via increased histone H4K5 lactylation. DNAJC12下调通过增加组蛋白H4K5乳酸化诱导神经母细胞瘤进展。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-05-22 DOI: 10.1093/jmcb/mjae056

Yaqi Yang, Jiejun Wen, Susu Lou, Yali Han, Yi Pan, Ying Zhong, Qiao He, Yinfeng Zhang, Xi Mo, Jing Ma, Nan Shen

{"title":"DNAJC12 downregulation induces neuroblastoma progression via increased histone H4K5 lactylation.","authors":"Yaqi Yang, Jiejun Wen, Susu Lou, Yali Han, Yi Pan, Ying Zhong, Qiao He, Yinfeng Zhang, Xi Mo, Jing Ma, Nan Shen","doi":"10.1093/jmcb/mjae056","DOIUrl":"10.1093/jmcb/mjae056","url":null,"abstract":"Neuroblastoma (NB) is the most common extracranial solid tumor in children. Despite treatment advances, the survival rates of high-risk NB patients remain low. This highlights the urgent need for a deeper understanding of the molecular mechanisms driving NB progression to support the development of new therapeutic strategies. In this study, we demonstrated that the reduced levels of DNAJC12, a protein involved in metabolic regulation, are associated with poor prognosis in NB patients. Our data indicate that low DNAJC12 expression activates glycolysis in NB cells, leading to increased lactic acid production and histone H4 lysine 5 lactylation (H4K5la). Elevated H4K5la upregulates the transcription of COL1A1, a gene implicated in cell metastasis. Immunohistochemistry staining of NB patient samples confirmed that high H4K5la levels correlate with poor clinical outcomes. Furthermore, we showed that inhibiting glycolysis, reducing H4K5la, or targeting COL1A1 can mitigate the invasive behavior of NB cells. These findings reveal a critical link between metabolic reprogramming and epigenetic modifications in the context of NB progression, suggesting that H4K5la could serve as a novel diagnostic and prognostic marker, and shed light on identifying new therapeutic targets within metabolic pathways for the treatment of this aggressive pediatric cancer.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Serum IL-27 and GDF15 levels in second trimester are associated with adverse pregnancy outcomes. 妊娠中期血清IL-27和GDF15水平与不良妊娠结局相关。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-05-22 DOI: 10.1093/jmcb/mjae053

Xue Li, Luping Liu, Li Jiang, Peihong Chen, Hua Jin, Enhao Li, Jiarong Dai, Jufen Yi, Xuemei Yu, Shan Zhang

引用次数: 0

Prospects for PARG inhibitors in cancer therapy. PARG 抑制剂在癌症治疗中的应用前景。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-05-22 DOI: 10.1093/jmcb/mjae050

Yangchan Hu, Yuxin Meng, Zirui Zhuang, Yuancong Li, Junjun Nan, Ning Xu, Zu Ye, Ji Jing

引用次数: 0

Structural insights into CRL2FEM1C ubiquitin ligase-mediated protein ubiquitination. CRL2FEM1C泛素连接酶介导的蛋白泛素化的结构见解。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-05-19 DOI: 10.1093/jmcb/mjaf016

Hualin Zhou, Mor Israel-Gueta, Xinyan Chen, Qiong Guo, Xing Liu, Itay Koren, Chao Xu

引用次数: 0

Modelling TIP60-YAP signalling in epithelial cell renewal using 3D gastric organoids. 利用三维胃类器官模拟TIP60-YAP信号在上皮细胞更新中的作用。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-05-16 DOI: 10.1093/jmcb/mjaf015

Hazrat Ismail, Zhen Dou, Dongmei Wang, Hengyi Shao, Xinjiao Gao, Chao Xu, Xing Liu, Chuanhai Fu, Xuebiao Yao, Xiaoyu Song

引用次数: 0

Targeting HPV for the prevention, diagnosis, and treatment of cervical cancer. 以 HPV 为目标，预防、诊断和治疗宫颈癌。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-05-02 DOI: 10.1093/jmcb/mjae046

Huiling Ni, Canhua Huang, Zhi Ran, Shan Li, Chunmei Kuang, Yu Zhang, Kai Yuan

{"title":"Targeting HPV for the prevention, diagnosis, and treatment of cervical cancer.","authors":"Huiling Ni, Canhua Huang, Zhi Ran, Shan Li, Chunmei Kuang, Yu Zhang, Kai Yuan","doi":"10.1093/jmcb/mjae046","DOIUrl":"10.1093/jmcb/mjae046","url":null,"abstract":"Despite advances in screening and prevention, cervical cancer (CC) remains an unresolved public health issue and poses a significant global challenge, particularly for women in low-income regions. Human papillomavirus (HPV) infection, especially with the high-risk strains, is a primary driver of cervical carcinogenesis. Emerging evidence indicates that integrating HPV testing with existing approaches, such as cervical cytology and visual inspection, offers enhanced sensitivity and specificity in CC screening. HPV infection-associated biomarkers, including HPV E6/E7 oncogenes, p16^INK4a, DNA methylation signatures, and non-coding RNAs, offer valuable insights into disease progression and the development of personalized interventions. Preventive and therapeutic vaccination against HPV, along with tertiary prevention strategies such as the use of antiviral and immune-modulating drugs for HPV-related lesions, show great clinical potential. At the mechanistic level, single-cell RNA sequencing analysis and the development of organoid models for HPV infection provide new cellular and molecular insights into HPV-related CC pathogenesis. This review focuses on the crucial roles of HPV in the prevention, diagnosis, and treatment of CC, with particular emphasis on the latest advancements in screening and disease intervention.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HDAC7 promotes cardiomyocyte proliferation by suppressing myocyte enhancer factor 2. HDAC7 通过抑制心肌细胞增强因子 2 促进心肌细胞增殖。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-05-02 DOI: 10.1093/jmcb/mjae044

Jihyun Jang, Mette Bentsen, Jin Bu, Ling Chen, Alexandre Rosa Campos, Mario Looso, Deqiang Li

{"title":"HDAC7 promotes cardiomyocyte proliferation by suppressing myocyte enhancer factor 2.","authors":"Jihyun Jang, Mette Bentsen, Jin Bu, Ling Chen, Alexandre Rosa Campos, Mario Looso, Deqiang Li","doi":"10.1093/jmcb/mjae044","DOIUrl":"10.1093/jmcb/mjae044","url":null,"abstract":"Postnatal mammalian cardiomyocytes (CMs) rapidly lose proliferative capacity and exit the cell cycle to undergo further differentiation and maturation. Cell cycle activation has been a major strategy to stimulate postnatal CM proliferation, albeit achieving modest effects. One impediment is that postnatal CMs may need to undergo dedifferentiation before proliferation, if not simultaneously. Here, we report that overexpression of Hdac7 in neonatal mouse CMs results in significant CM dedifferentiation and proliferation. Mechanistically, we show that histone deacetylase 7 (HDAC7)-mediated CM proliferation is contingent on dedifferentiation, which is accomplished by suppressing myocyte enhance factor 2 (MEF2). Hdac7 overexpression in CM shifts the chromatin state from binding with MEF2, which favors the transcriptional program toward differentiation, to binding with AP-1, which favors the transcriptional program toward proliferation. Furthermore, we found that HDAC7 interacts with minichromosome maintenance complex components to initiate cell cycle progression. Our findings reveal that HDAC7 promotes CM proliferation by its dual action on CM dedifferentiation and proliferation, uncovering a potential new strategy for heart regeneration/repair.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cohesin ring gates are specialized for meiotic cell division. 粘合素环门专门用于减数分裂的细胞分裂。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-05-02 DOI: 10.1093/jmcb/mjae047

Yuanyuan Liu, Bohan Liu, Ruirui Zhang, Zixuan Zhu, Li Zhao, Ruijie Jiang, Yinghao Wang, Feifei Qi, Ruoxi Wang, Huijie Zhao, Jun Zhou, Jinmin Gao

{"title":"Cohesin ring gates are specialized for meiotic cell division.","authors":"Yuanyuan Liu, Bohan Liu, Ruirui Zhang, Zixuan Zhu, Li Zhao, Ruijie Jiang, Yinghao Wang, Feifei Qi, Ruoxi Wang, Huijie Zhao, Jun Zhou, Jinmin Gao","doi":"10.1093/jmcb/mjae047","DOIUrl":"10.1093/jmcb/mjae047","url":null,"abstract":"Cohesin is a ring complex closed with structural maintenance of chromosome 1 (SMC-1), SMC-3, and a kleisin subunit, mediating sister chromatid cohesion in mitosis and meiosis. Kleisin N- and C-terminal domains interact with SMC-3 and SMC-1, forming two distinct cohesin gates. Whether these gates are specialized for mitosis and meiosis remains elusive. Here, we create Caenorhabditis elegans mutants that express chimeric proteins swapping N- and C-terminal domains between different kleisins to investigate how these gates are specialized for different cell division programs. Replacing the meiotic REC-8 N-terminus with that of a cell division-unrelated kleisin COH-1 or the mitotic kleisin sister chromatid cohesion protein 1 (SCC-1) disrupts inter-sister chromatid cohesion and causes severe meiotic defects. Swapping the REC-8 C-terminus with that of COH-1 or SCC-1 largely retains the meiotic functions of REC-8 but causes age-related chromosome abnormalities. A specialized C-terminus is also required for the functions of SCC-1. Furthermore, point mutations in the REC-8 C-terminus cause severe meiotic defects without impairing the SMC-1-kleisin interaction, suggesting an integrated SMC-1-kleisin gate. These findings suggest the requirements for specialized cohesin gates in different biological processes.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0