Cellular & Molecular Biology Letters最新文献

{"title":"Endothelial activation during the diapedesis of cancer cells: between the kiss of death and therapeutic breakthrough.","authors":"Katarzyna Piwowarczyk, Zbigniew Madeja, Maciej Siedlar, Jarosław Czyż","doi":"10.1186/s11658-025-00797-5","DOIUrl":"10.1186/s11658-025-00797-5","url":null,"abstract":"<p><p>Cancer development is a complex process, initiated by the combination of epigenetic and genetic changes in normal cells. Selective microenvironmental pressure within the primary tumors prompts the microevolution of invasive cell lineages that efficiently penetrate circulation and lymphatic systems and extravasate in distant organs, initiating the formation of metastases. Extravasation (diapedesis), i.e., the multistep penetration of the endothelial layer by circulating cancer cells, is regarded as the decisive step and one of the bottlenecks of the metastatic cascade. It limits malignant cancer dissemination, while initiating the formation of metastases. The efficiency of extravasation depends equally on the properties of circulating cancer cells and the local functional status of the endothelium, which remains sensitive to paracrine, adhesive, and juxtacrine stimuli generated by cancer and immune cells. Here, we review the current state of knowledge on the significance of endothelial activation for the diapedesis of circulating cancer cells, with the emphasis on the intercellular communication pathways that mediate this process. We also address the potential and limitations of endothelial activation as the target for novel strategies of cancer treatment.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"122"},"PeriodicalIF":10.2,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12539140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analyses integration reveals a novel TRF2-miR-181a-5p-S100A10 regulatory axis in colon cancer.","authors":"Roberto Dinami, Eleonora Petti, Paola Ostano, Sara Iachettini, Angela Rizzo, Carmen Maresca, Pasquale Zizza, Serena Di Vito, Manuela Porru, Carmen D'Angelo, Pasquale Sibilio, Francesca De Nicola, Rosita Russo, Anna Di Benedetto, Aldo Palange, Maurizio Fanciulli, Angela Chambery, Eric Gilson, Annamaria Biroccio","doi":"10.1186/s11658-025-00813-8","DOIUrl":"10.1186/s11658-025-00813-8","url":null,"abstract":"<p><strong>Background: </strong>The Telomeric repeat-binding factor 2 (TRF2) binds to TTAGGG repeats located at chromosomes ends and ensures telomere protection together with the other members of shelterin. In addition to its well-known role in telomere maintenance, TRF2 can also bind to interstitial telomeric sequences and regulate the expression of specific genes with a consequent impact on tumor formation and progression. However, a comprehensive analysis of the impact of TRF2 on global gene expression of human cancer cells and of the underlying mechanisms is still lacking.</p><p><strong>Methods: </strong>The integration of omics technologies (RNA sequencing (RNA-seq), chromatin immunoprecipitation (ChIP-seq), interactomics, and microRNA (miRNA) profiling) was used to deeply investigate the extra-telomeric role of TRF2. Differential gene expression and binding sites of TRF2 were confirmed by qRT-PCR while the interaction of TRF2 with TATA-box binding protein associated factor 15 (TAF15) was validated by immunoprecipitation and proximity ligation assay. Finally, target specificity was assessed by luciferase assay and western blotting while biological effects were investigated by cell migration analysis (unpaired t tests was used to calculate statistical significance).</p><p><strong>Results: </strong>We found that TRF2 impinges on the expression of 717 genes involved in various cancer-related pathways. Unexpectedly, just a small portion of Differentially Regulated genes are directly bound by TRF2, suggesting the existence of alternative mechanisms of TRF2-mediated gene regulation. In particular, we found that TRF2 binds to various noncoding RNA regions and interacts with many RNA binding proteins, supporting TRF2's involvement in noncoding RNA-mediated mechanisms. Through the intersection of omics-analyses, we provided here experimental evidence of a multilayered mechanism of regulation where TRF2, interacting with TAF15, regulates miR-181A1 host gene and mature miR-181a-5p expression, which in turn targets S100A10, a known plasma membrane protein with oncogenic role.</p><p><strong>Conclusions: </strong>Our work shows, for the first time, a broad overview on the extra-telomeric role of TRF2 in human cancer, further revealing a new axis through which TRF2 contributes to cancer progression.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"121"},"PeriodicalIF":10.2,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Runx2 downregulates Lpl expression through super-silencer formation to alter lipid metabolism in Zhu Schwann cells after nerve injury.","authors":"Zhaowei Zhu, Rui Kuang, Shouwen Su, Yujing Zhang, Guanggeng Wu, Yi Zhang, Vincent Pang, Xiang Zhou, Yan Yang, Ge Li, Bo He, Yangbin Xu","doi":"10.1186/s11658-025-00796-6","DOIUrl":"10.1186/s11658-025-00796-6","url":null,"abstract":"<p><strong>Background: </strong>Phenotypic transformation of Schwann cells (SCs) plays a crucial role in nerve regeneration. Previous studies have demonstrated that Runx2 significantly influences the biological behavior of SCs. Nonetheless, the regulatory mechanisms that govern its epigenetic regulation are not yet fully elucidated.</p><p><strong>Methods: </strong>To facilitate this investigation, an adenovirus for the overexpression of Runx2 was constructed. Healthy adult Sprague-Dawley rats, weighing between 100 and 150 g and irrespective of sex, were randomly selected for the study. After establishing a model of sciatic nerve crush injury, tissue samples were harvested for histological analysis at both 4 and 7 days post-injury. In vitro, an Runx2-overexpressing SC line was established. Thorough analysis of transcriptome data, coupled with CUT&Tag sequencing of histones and transcription factors in SCs following Runx2 overexpression, was conducted. Additionally, single-cell RNA sequencing data from GSE216665 were incorporated to elucidate the mechanistic role of Runx2. The findings were subsequently validated through dual-luciferase assays.</p><p><strong>Results: </strong>Following nerve crush injury, Runx2-positive SCs were identified at the injury site. Through comprehensive multiomics analysis, we discovered that lipid metabolism was disrupted in Runx2-overexpressing SCs. Further investigation established a detailed super-silencer landscape in these cells, revealing that elevated Runx2 levels form a super-silencer within the transcriptional regulatory region of the Lpl gene, thereby downregulating Lpl expression.</p><p><strong>Conclusions: </strong>Runx2 can modulate the biological behavior of SCs by forming super-silencers that interfere with the expression of lipid metabolism genes, such as Lpl, thereby altering the metabolic capacity of SCs.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"120"},"PeriodicalIF":10.2,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP contributes to liver injury through mediating capillarization of liver sinusoidal endothelial cells via GATA6/eNOS signaling.","authors":"Junjun Wang, Zhenyang Shen, Guangwen Chen, Weiming Dai, Zhu Mei, Bo Shen, Yuecheng Guo, Jianxiang Wang, Hanjing Zhangdi, Qingqing Zhang, Jiaqi Gao, Qichao Ge, Hui Zhou, Hui Dong, Lungen Lu, Xiaobo Cai","doi":"10.1186/s11658-025-00798-4","DOIUrl":"10.1186/s11658-025-00798-4","url":null,"abstract":"<p><strong>Background: </strong>Capillarization of liver sinusoidal endothelial cells (LSECs) is a central event in response to liver injury. In this study, we investigated the role of Yes-associated protein 1 (YAP1, also known YAP) in LSEC capillarization and liver injury.</p><p><strong>Methods: </strong>YAP expression was assessed in liver samples from mice injured by CCl₄ injection and DDC diet. EC-specific Yap1 conditional knockout mice (Yap1^∆end) were generated by breeding Yap1^fl/fl mice with Cdh5-Cre^ERT2 mice. HA-PEI/siYap1 nanoparticles were applied to specifically inhibit YAP expression in LSECs.</p><p><strong>Results: </strong>YAP was primarily expressed in LSECs, and its expression was elevated during liver fibrosis. EC-specific Yap1 deficiency significantly increased the fenestrae in LSECs and mitigated hepatocyte death and liver fibrosis. Overexpression of YAP in EC aggravated capillarization, hepatocyte death, and liver fibrosis. Mechanistically, YAP inhibited Gata6 transcription via binding to its promoter and thus resulted in LSEC capillarization. Overexpression of GATA6 in EC alleviated capillarization and liver fibrosis by activating Nos3 transcription. Moreover, specific delivery of HA-PEI-siYap1 nanoparticles to LSEC alleviated liver injury in mice.</p><p><strong>Conclusions: </strong>YAP-GATA6/eNOS signaling is essential in LSEC capillarization and subsequent hepatocyte death. Interventions targeting YAP in LSECs offer a promising strategy for the treatment of liver fibrosis.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"119"},"PeriodicalIF":10.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of DHHC9-mediated CD36 palmitoylation lessens high-fat diet (HFD)-induced impairment of pubertal mammary gland development through the JNK-ERK pathway.","authors":"Yiming Fu, Fenglin Zhang, Limin Lang, Shuyi Liang, Junfeng Wang, Shilei Zhang, Kaixin Deng, Jinhao Liu, Lilin Cai, Yue Zhang, Lidong Yan, Guo Ren, Haoyan Kang, Lina Wang, Canjun Zhu, Ruifan Wu, Gang Shu, Qingyan Jiang, Songbo Wang","doi":"10.1186/s11658-025-00799-3","DOIUrl":"10.1186/s11658-025-00799-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;CD36, a vital fatty acid translocase, has been reported to participate in multiple physiological functions through palmitoylation mediated by zinc finger Asp-His-His-Cys-type palmitoyltransferases (DHHCs). This study aimed to investigate the possible involvement of DHHC-mediated CD36 palmitoylation in high-fat diet (HFD)-induced impairment of pubertal mammary gland development and explore the underlying mechanisms involved.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Palmitic acid (PA)-treated HC11 cells were used as the in vitro high-fat model, and the cell proliferation was examined by 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assay. The palmitoylation of CD36 was determined by the acyl-biotin exchange (ABE) method. The expression of CD36, proliferative genes, and signaling molecules was detected by immunoblotting. The cellular localization of CD36 was determined by immunofluorescence. The bindings of CD36 with zinc finger DHHC-type palmitoyltransferases 9 (DHHC9) or Fyn/Lyn were detected by co-immunoprecipitation (Co-IP). The palmitoylation inhibitor 2-bromopalmitate (2BP), DHHC9 knockdown, and point mutation of CD36 cysteine residues were applied to construct a CD36 palmitoylation deficiency model in vitro to investigate the effects of CD36 palmitoylation on HC11 proliferation. In vivo, the pubertal mice were treated with HFD and/or 2BP. Mammary gland morphology was determined by whole mount staining, and the underlying mechanisms were verified by the methods used in the in vitro system.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In vitro, the palmitoylation inhibitor 2BP eliminated PA-inhibited HC11 proliferation and inhibited CD36 palmitoylation and localization on the plasma membrane. Meanwhile, the binding of DHHC9 and CD36 in PA-treated HC11 cells was repressed by 2BP. In addition, both knockdown of DHHC9 and point mutation of CD36 cysteine residues suppressed the membrane palmitoylation and localization of CD36 and stimulated the proliferation of PA-treated HC11 cells. Furthermore, in PA-treated HC11 cells, the inhibition of CD36 palmitoylation, the knockdown of DHHC9, and the mutation of CD36 cysteine residues resulted in decreased formation of the CD36/Fyn/Lyn complex. Correspondingly, the downstream c-jun n-terminal kinase 1 (JNK1) pathway was inhibited, and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway was activated. Moreover, inhibition of the JNK pathway with SP600125 promoted the proliferation of PA-treated HC11 cells via activation of the ERK1/2 pathway. In vivo, the palmitoylation inhibitor 2BP ameliorated HFD-induced impairment of mammary gland development in pubertal female mice, which was associated with a decrease in DHHC9-mediated CD36 palmitoylation in the plasma membrane, a reduction in the CD36/Fyn/Lyn complex, inhibition of the JNK1 pathway, and activation of the ERK1/2 pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study revealed that inhibition of DHHC9-mediated CD36 palmitoylation mi","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"117"},"PeriodicalIF":10.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AXL activation governs the liver microenvironment to protect ischemia-reperfusion injury by suppressing NLRP3 inflammasome.","authors":"Deng Liu, Mengting Zhan, Lei Yao, Xingyun Liu, Ruixin Zhang, Lixia Zha, Xiaolu Zhang, Yaru Xu, Qi Fang, Haijian Cai, Qi Yan, Weizhi Wang, Jian Du, Lijian Chen","doi":"10.1186/s11658-025-00795-7","DOIUrl":"10.1186/s11658-025-00795-7","url":null,"abstract":"<p><strong>Background: </strong>Ischemia-reperfusion (I/R) injury frequently arises during liver surgery and significantly contributes to postoperative liver failure and graft dysfunction. Macrophage-mediated pyroptosis cascade plays a crucial effect in liver I/R injury. The attribution of pyroptosis in macrophage reprogramming and hepatic microenvironment during liver I/R remain unclear. Here, we identify AXL as a hepatic macrophage-enriched gene that regulates pyroptosis in I/R injury.</p><p><strong>Methods: </strong>We collected liver grafts to test the relationship between phosphorylated AXL (p-AXL) and degree of hepatic injury. We isolated primary mouse hepatocytes and macrophages for hypoxia/reoxygenation (H/R) treatment and coculture, and used macrophage depletion mice to reveal the unique function of AXL in hepatic macrophages. Mice were treated with activators and inhibitors of AXL, NLRP3, and XBP1, and subjected to liver I/R to determine the mechanism underlying AXL-mediated modulation of the hepatic microenvironment.</p><p><strong>Results: </strong>We found that AXL inhibition and NLRP3-induced pyroptosis was strongly associated with the degree of liver I/R injury. Further analysis revealed that AXL activation in macrophages suppressed hepatic I/R-induced pyroptosis. AXL activation with Gas6, a high-affinity ligand for AXL, significantly attenuated liver I/R injury and improved the hepatic microenvironment. Mechanistically, AXL activation impeded the IRE1-XBP1s axis to suppress NLRP3 inflammasome activation, which promoted hepatic macrophages to an alternative-like polarization, thereby enhancing the hepatic immune environment to attenuate liver I/R injury.</p><p><strong>Conclusions: </strong>This study not only elucidates how AXL reprograms macrophages but also suggests a therapeutic target for mitigating liver I/R injury.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"118"},"PeriodicalIF":10.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitranscriptomic modifications in programmed cell death: mechanistic insights and implications for liver diseases.","authors":"Lulu Chen, Yajuan Lu, Aoli Deng, Jinghao Cao, Feifan Jin, Hangqi Huang, Feifan Pan, Yingchao Liu, Yanchun Li, Xiangmin Tong, Hongfeng Yao, Jing Du","doi":"10.1186/s11658-025-00794-8","DOIUrl":"10.1186/s11658-025-00794-8","url":null,"abstract":"<p><p>Epitranscriptomic modifications, as a dynamic and reversible system of chemical modifications, have emerged as a key regulatory hub for programmed cell death (PCD) by finely modulating the RNA metabolic network. During the pathological progression of liver diseases, aberrant alterations in epitranscriptomic modifications can disrupt the dynamic equilibrium of PCD signaling pathways, leading to excessive cell death or abnormal survival of hepatocytes, thereby driving the development of metabolic dysfunction-associated steatotic liver disease (MASLD), viral hepatitis, alcohol-associated liver disease (ALD), hepatic fibrosis, and hepatocellular carcinoma (HCC). A thorough investigation into the molecular mechanisms of epitranscriptomic modifications in PCD pathways and their roles in liver diseases not only aids in elucidating the pathogenesis of liver disorders but also holds the potential to provide new biomarkers and therapeutic targets for the diagnosis, prognosis, and treatment of liver diseases. This review systematically summarizes the molecular mechanisms of epitranscriptomic modifications, delves into the complex regulatory networks between epitranscriptomic modifications and PCD, elaborates on their roles in liver diseases, and provides a comprehensive overview of current drugs targeting epitranscriptomic modifications. These insights offer new treatment ideas for liver diseases and new directions for precision medicine research.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"116"},"PeriodicalIF":10.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA-like MMP14 RNA facilitates colorectal cancer metastasis by suppressing H3K27cr at the STARD13 promoter region.","authors":"Mengting Li, Ying Gao, Xiaolin Sun, Wendan Zheng, Mengzhen Zhang, Chenlong Wang, Weiwei Chu, Xuemei Yang, Lin Wang, Maojin Zheng, Wenzhi Xue, Fuxing Dong, Dongsheng Pei, Meijian Liao","doi":"10.1186/s11658-025-00791-x","DOIUrl":"10.1186/s11658-025-00791-x","url":null,"abstract":"<p><strong>Background: </strong>MMP14 protein has been recognized to promote tumor metastasis through protease activity, yet drugs targeting the protein fail to improve survival rates, suggesting the presence of non-protein regulatory mechanisms. This study aims to explore the roles and mechanisms by which MMP14 RNA facilitates colorectal cancer (CRC) metastasis.</p><p><strong>Methods: </strong>Transwell assays and animal experiments utilizing loss-of-function and gain-of-function approaches were employed to assess the roles of MMP14 RNA in facilitating CRC metastasis. A combination of immunoprecipitation assays, scRNA-seq analysis, and western blotting was conducted to elucidate the underlying mechanisms by which MMP14 RNA promoted CRC metastasis.</p><p><strong>Results: </strong>Our study revealed that MMP14 RNA was highly expressed in CRC tissues and correlated with poor prognosis. The overexpression of MMP14 RNA facilitated metastasis both in vitro and in vivo. Mechanistically, MMP14 RNA interacted with the distal promoter of STARD13 and bound to the N-terminal of SIRT3, facilitating its recruitment to the promoter region. This cascade of events reduced H3K27cr levels at the STARD13 promoter, thereby inhibiting STARD13 transcription and ultimately promoting CRC metastasis. Furthermore, we proved that silencing MMP14 RNA had a more significant inhibitory effect on tumor metastasis compared with inhibiting the MMP14 protein.</p><p><strong>Conclusions: </strong>The study elucidated an lncRNA-like mechanism by which MMP14 RNA facilitated CRC metastasis via RNA-directed chromatin remodeling.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"115"},"PeriodicalIF":10.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous cardiac catecholaminergic systems in cardiac development, physiology, and pathophysiology.","authors":"Yuqing Zheng, Rina Yue Ren, Xingyue Wu, Fuzhi Qu, Alexander Grassam-Rowe, Tianyi Sun, Xianhong Ou, Xiaoqiu Tan, Minghe Huang, Ming Lei","doi":"10.1186/s11658-025-00778-8","DOIUrl":"10.1186/s11658-025-00778-8","url":null,"abstract":"<p><p>Catecholamines, canonically associated with the sympathetic nerves and the adrenal medulla, are also produced by neuroparacrine cells within the heart. Despite their putative importance, the precise functions of these neuroparacrine cells in the heart are not well understood and their clinical implications remain to be defined. In this review, we first explore the historical context and recent advances in research on intrinsic cardiac adrenergic (ICA) cells, focusing on their unique characteristics, distributions, and progenitor-like potential during cardiac development. We then examine their contributions to both physiological and pathological cardiac states. We further discuss a recently identified population of catecholaminergic cardiomyocytes; we discuss their involvement in cardiac development, maturation, and their potential interaction with sympathetic innervation during development. By reviewing these findings, we provide new insights into the endogenous production of catecholamines within the heart and its relevance to cardiac development, physiology and disease, and its potential clinical implications.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"114"},"PeriodicalIF":10.2,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.","authors":"Simona S Ghanem, Tara Al-Barazenji, Rehab Badi, Essam M Abdelalim","doi":"10.1186/s11658-025-00790-y","DOIUrl":"10.1186/s11658-025-00790-y","url":null,"abstract":"<p><p>Diabetes mellitus is a complex metabolic disorder characterized by hyperglycemia due to impaired insulin production, action, or both. The Pancreas and Liver play central roles in glucose regulation, and their dysfunction is critical to the onset and progression of specific types of diabetes, including type 2 diabetes and certain forms of monogenic diabetes. While these organs have distinct physiological roles, they originate from the foregut endoderm and share key developmental regulators and signaling pathways. This review explores the overlapping transcription factors and genes that are essential for both pancreatic and hepatic development and function. These dual-role genes not only govern early organogenesis but are also implicated in diabetes pathogenesis, underscoring their significance in metabolic homeostasis. We highlight how interorgan signaling, particularly between hepatokines and pancreatic islet cells, contributes to the maintenance or disruption of glucose metabolism. Furthermore, we discuss the clinical implications of these shared pathways, emphasizing how insights from developmental biology can inform precision diagnostics and therapeutic strategies for diabetes. Finally, we consider how emerging tools, such as pluripotent stem cell-based disease models and gene editing and multi-omics approaches, are transforming our understanding of gene function and disease progression. By bridging the developmental and metabolic landscapes of the pancreas and liver, this review provides a comprehensive framework for uncovering novel regulators of diabetes and paves the way toward targeted, personalized treatment strategies.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"113"},"PeriodicalIF":10.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}