{"title":"Exosomes derived from mesenchymal stem cells ameliorate impaired glucose metabolism in myocardial Ischemia/reperfusion injury through miR-132-3p/PTEN/AKT pathway.","authors":"Hongkun Wu, Yongpeng Hui, Xingkai Qian, Xueting Wang, Jianwei Xu, Feng Wang, Sisi Pan, Kaiyuan Chen, Zhou Liu, Weilong Gao, Jue Bai, Guiyou Liang","doi":"10.1080/15384101.2025.2485834","DOIUrl":"https://doi.org/10.1080/15384101.2025.2485834","url":null,"abstract":"<p><p>Exosomes secreted by mesenchymal stem cells (MSCs) have been considered as a novel biological therapy for myocardial ischemia/reperfusion injury (MIRI). However, the underlying mechanism of exosomes has not been completely established, especially in the early stage of MIRI. In this study, we primarily investigated the protective effect of exosomes on MIRI from both in vitro and ex vivo perspectives. Bioinformatic analysis was conducted to identify exosomal miRNA associated with myocardial protection, Genes and proteins related to functional studies and myocardial energy metabolism were analyzed and evaluated using techniques such as Polymerase Chain Re-action (PCR), Western blotting, double luciferase biochemical techniques, flow cytometry assay, etc. It was discovered that exosomes ameliorated cardiomyocyte injury t by delivery of miR-132-3p.This process reduced the expression of Phosphatase and tensin homolog (PTEN) mRNA and protein, enhanced the expression of phosphorylated protein kinase (pAKT), regulated the insulin signaling pathway, facilitated intracellular Glucose transporter 4 (GLUT4) protein membrane translocation, and enhanced glucose uptake and Adenosine Triphosphate (ATP) production. This study confirmed, for the first time, that MSC-EXO can provide myocardial protection in the early stages of MIRI through miR-132/PTEN/AKT pathway. This research establishes a theoretical and experimental foundation for the clinical application of MSC-derived exosomes.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-20"},"PeriodicalIF":3.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell CyclePub Date : 2025-03-27DOI: 10.1080/15384101.2025.2484868
Mohamed El-Mesery, Franziska Rudolf, Yannick Heimann, Georg Häcker, Thomas Brunner
{"title":"Non-canonical functions of BCL-2 family members in energy metabolism and necrotic cell death regulation.","authors":"Mohamed El-Mesery, Franziska Rudolf, Yannick Heimann, Georg Häcker, Thomas Brunner","doi":"10.1080/15384101.2025.2484868","DOIUrl":"https://doi.org/10.1080/15384101.2025.2484868","url":null,"abstract":"<p><p>The large family of BCL-2 proteins plays a well-established role in the regulation of mitochondrial apoptosis pathway, and the crosstalk between death receptor signaling and mitochondrial apoptosis. Accumulating evidence suggests, however, that various BCL-2 family members are also involved in the regulation of apoptosis-unrelated necrotic forms of cell death, and even non-cell death processes. In this review, we discuss the emerging role of BCL-2 family members, and in particular BIM, in the regulation of mitochondrial dynamics, morphology and energy metabolism, and associated consequences for drug-inuced necrotic cell death.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-18"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell CyclePub Date : 2025-03-27DOI: 10.1080/15384101.2025.2463772
{"title":"Expression of Concern: ATM-dependent phosphorylation of heterogeneous nuclear ribonucleoprotein K promotes p53 transcriptional activation in response to DNA damage.","authors":"","doi":"10.1080/15384101.2025.2463772","DOIUrl":"https://doi.org/10.1080/15384101.2025.2463772","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell CyclePub Date : 2025-03-26DOI: 10.1080/15384101.2025.2460937
{"title":"Statement of Retraction: Fascin1 mediated release of pro-inflammatory cytokines and invasion/migration in rheumatoid arthritis via the STAT3 pathway.","authors":"","doi":"10.1080/15384101.2025.2460937","DOIUrl":"https://doi.org/10.1080/15384101.2025.2460937","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1"},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell CyclePub Date : 2024-11-24DOI: 10.1080/15384101.2024.2429968
Latifa Bakiri, Erwin F Wagner
{"title":"c-Jun and Fra-2 pair up to Myc-anistically drive HCC.","authors":"Latifa Bakiri, Erwin F Wagner","doi":"10.1080/15384101.2024.2429968","DOIUrl":"https://doi.org/10.1080/15384101.2024.2429968","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC), a leading cause of cancer-related death with limited therapies, is a complex disease developing in a background of Hepatitis Virus infection or systemic conditions, such as the metabolic syndrome. Investigating HCC pathogenesis in model organisms is therefore crucial for developing novel diagnostic and therapeutic tools. Genetically engineered mouse models (GEMMs) have been instrumental in recapitulating the local and systemic features of HCC. Early studies using GEMMs and patient material implicated members of the dimeric Activator Protein-1 (AP-1) transcription factor family, such as c-Jun and c-Fos, in HCC formation. In a recent report, we described how switchable, hepatocyte-restricted expression of a single-chain c-Jun~Fra-2 protein, functionally mimicking the c-Jun/Fra-2 AP-1 dimer, results in spontaneous and largely reversible liver tumors in GEMMs. Dysregulated cell cycle, inflammation, and dyslipidemia are observed at early stages and tumors display molecular HCC signatures. We demonstrate that increased c-Myc expression is an essential molecular determinant of tumor formation that can be therapeutically targeted using the BET inhibitor JQ1. Here, we discuss these findings with additional results illustrating how AP-1 GEMMs can foster preclinical research on liver diseases with novel perspectives offered by the constantly increasing wealth of HCC-related datasets.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-9"},"PeriodicalIF":3.4,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell CyclePub Date : 2024-09-27DOI: 10.1080/15384101.2024.2396717
{"title":"Expression of Concern: DDB2 association with PCNA is required for its degradation after UV-induced DNA damage.","authors":"","doi":"10.1080/15384101.2024.2396717","DOIUrl":"https://doi.org/10.1080/15384101.2024.2396717","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1"},"PeriodicalIF":3.4,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell CyclePub Date : 2024-09-19DOI: 10.1080/15384101.2024.2402191
Silvia G Vaena, Martin J Romeo, Mirna Mina-Abouda, Emma C Funk, George Fullbright, David T Long, Joe R Delaney
{"title":"Autophagy unrelated transcriptional mechanisms of hydroxychloroquine resistance revealed by integrated multi-omics of evolved cancer cells.","authors":"Silvia G Vaena, Martin J Romeo, Mirna Mina-Abouda, Emma C Funk, George Fullbright, David T Long, Joe R Delaney","doi":"10.1080/15384101.2024.2402191","DOIUrl":"10.1080/15384101.2024.2402191","url":null,"abstract":"<p><p>Hydroxychloroquine (HCQ) and chloroquine are repurposed drugs known to disrupt autophagy, a molecular recycling pathway essential for tumor cell survival, chemotherapeutic resistance, and stemness. We pursued a multi-omic strategy in OVCAR3 ovarian cancer and CCL218 colorectal cancer cells. Two genome-scale screens were performed. In the forward genetic screen, cell populations were passaged for 15 drug pulse-chases with HCQ or vehicle control. Evolved cells were collected and processed for bulk RNA-seq, exome-seq, and single-cell RNA-seq (scRNA-seq). In the reverse genetic screen, a pooled CRISPR-Cas9 library was used in cells over three pulse-chases of HCQ or vehicle control treatments. HCQ evolved cells displayed remarkably few mutational differences, but substantial transcriptional differences. Transcriptomes revealed multiple pathways associated with resistance to HCQ, including upregulation of glycolysis, exocytosis, and chromosome condensation/segregation, or downregulation of translation and apoptosis. The Cas9 screen identified only one autophagy gene. Chromosome condensation and segregation were confirmed to be disrupted by HCQ in live cells and organelle-free <i>in vitro</i> extracts. Transcriptional plasticity was the primary mechanism by which cells evolved resistance to HCQ. Neither autophagy nor the lysosome were substantive hits. Our analysis may serve as a model for how to better position repurposed drugs in oncology.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-21"},"PeriodicalIF":3.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Melatonin protects against defects induced by methoxychlor in porcine oocyte maturation.","authors":"Zhaojun Geng, Mingjun Zhang, Shuming Shi, Bing Hu, Liying Liu, Zhichao Chi, Linyi Qu, Yongxun Jin, Xianfeng Yu","doi":"10.1080/15384101.2024.2402190","DOIUrl":"https://doi.org/10.1080/15384101.2024.2402190","url":null,"abstract":"<p><p>Methoxychlor (MXC) is a widely used organochlorine pesticide primarily targeting pests. However, MXC has been found to negatively impact the reproductive system of both humans and animals, triggering oxidative stress and apoptosis. Melatonin (MLT), an endogenous hormone, possesses various benefits, including circadian rhythm regulation and anti-inflammatory and antioxidative stress effects. Moreover, MLT plays a crucial role in the development of animal germ cells and embryos. This study aimed to investigate the impact of MLT on porcine oocytes exposed to MXC. The experimental findings revealed that 200 μM MXC had detrimental effects on the maturation of porcine oocytes. However, the addition of 10<sup>-8</sup> M MLT mitigated the toxic effects of MXC. MXC induced oxidative stress in porcine oocytes, leading to an increase in reactive oxygen species and impairing mitochondrial function. Consequently, oocyte quality was affected, resulting in elevated levels of early apoptosis and DNA damage, ultimately negatively impacting subsequent embryonic development. However, the addition of MLT showed the potential to ameliorate the damage caused by MXC. In conclusion, our results suggest that MLT exhibits a protective effect against MXC-induced damage to porcine oocyte maturation.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-17"},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell CyclePub Date : 2024-09-16DOI: 10.1080/15384101.2024.2402192
Cristina Ros-Carrero, Mercè Gomar-Alba, J Carlos Igual
{"title":"Cell cycle regulated expression of the <i>WHI7</i> Start repressor gene.","authors":"Cristina Ros-Carrero, Mercè Gomar-Alba, J Carlos Igual","doi":"10.1080/15384101.2024.2402192","DOIUrl":"https://doi.org/10.1080/15384101.2024.2402192","url":null,"abstract":"<p><p>Periodic transcriptional waves along the cell cycle ensure the accurate progression of the different cell cycle phases through the timely regulated expression of cell cycle proteins. The G1/S transition (Start) consists in the activation of a transcriptional program by G1 CDKs through the inactivation of Start transcriptional repressors, Whi5 and Whi7 in yeast or Rb in mammals. Here, we provide a comprehensive characterization of the transcriptional regulation of the Start repressor Whi7 in budding yeast. We found that <i>WHI7</i> is a cell cycle regulated gene that shows periodic expression peaking in G1. Our results demonstrate that the three cell cycle transcriptional programs related to G1 and their corresponding transcription factors are involved in the transcriptional control of <i>WHI7</i>. Specifically, we identified that the transcriptional regulators Swi5 and Mcm1-Yox1, which are involved in late M and early G1 expression, and the transcription factors MBF and SBF, which are responsible for G1/S expression, are able to associate and regulate the <i>WHI7</i> gene. In summary, in this work, we provide new mechanisms for the regulation of the Start repressor Whi7, which highlights the precise and complex control of the cell cycle machinery governing the G1/S transition.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-17"},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}