Journal of Cellular and Molecular Medicine最新文献_第7页

Advances in CRISPR Base Editing: From Molecular Evolution to Therapeutic Applications in Genomic Medicine. CRISPR碱基编辑的进展：从分子进化到基因组医学的治疗应用。

IF 4.2 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2026-04-01 DOI: 10.1111/jcmm.71159

Melike Aliciaslan, Ezgi Erbasan, Fulya Erendor, Salih Sanlioglu

{"title":"Advances in CRISPR Base Editing: From Molecular Evolution to Therapeutic Applications in Genomic Medicine.","authors":"Melike Aliciaslan, Ezgi Erbasan, Fulya Erendor, Salih Sanlioglu","doi":"10.1111/jcmm.71159","DOIUrl":"10.1111/jcmm.71159","url":null,"abstract":"CRISPR-Cas9 systems revolutionized gene editing, but inherent drawbacks, namely DNA double-strand breaks (DSBs) and the difficulty of achieving precise repairs (due to low HDR efficiency), led researchers to invent new, more accurate gene editing tools. Base editing represents a significant leap forward, enabling targeted single-nucleotide conversions directly on the DNA without DSBs or donor templates. The core technology involves fusing catalytically dead or nickase Cas proteins to DNA deaminase enzymes. Cytosine base editors (CBEs) convert C•G to T•A pairs, while adenine base editors (ABEs) change A•T to G•C. These editors exploit the deaminase function within the R-loop structure formed by Cas binding and co-opt endogenous DNA repair mechanisms for precision. While offering improved efficiency and editing precision, base editing faces persistent challenges, such as off-target effects, bystander edits, delivery and ethical concerns. Continuous engineering efforts have refined these tools, enhancing accuracy, expanding targetability and reducing unwanted edits. The base editing arsenal has also broadened to include C-to-G base editors (CGBEs), dual A&C editors and versions targeting organelles. Successful preclinical studies demonstrating the correction of mutations responsible for the disease have paved the way for clinical trials, which are now testing therapies for conditions like sickle cell disease, β-thalassaemia and hypercholesterolemia using various delivery systems. This review explores CRISPR base editing's origins, mechanisms of action, potential therapies and current restrictions, pointing to its broadening impact on medical genetics.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71159"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772654","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}

引用次数: 0

Capsaicin Receptor TRPV1 Delays Aortic Aging in Atherosclerotic Mice by Inhibiting the ISG15-p53 Pathway. 辣椒素受体TRPV1通过抑制ISG15-p53通路延缓动脉粥样硬化小鼠主动脉老化

IF 4.2 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2026-04-01 DOI: 10.1111/jcmm.71157

Duo Zhang, Jishuang Liu, Te Liu, Jiulin Chen, ZhiHua Yu, Yun Gu, Fangfang Dou

{"title":"Capsaicin Receptor TRPV1 Delays Aortic Aging in Atherosclerotic Mice by Inhibiting the ISG15-p53 Pathway.","authors":"Duo Zhang, Jishuang Liu, Te Liu, Jiulin Chen, ZhiHua Yu, Yun Gu, Fangfang Dou","doi":"10.1111/jcmm.71157","DOIUrl":"10.1111/jcmm.71157","url":null,"abstract":"Vascular aging constitutes a significant pathological basis for the aging of various organs and systems within the human body. This study employed a murine model of atherosclerosis (AS) and Transient Receptor Potential Vanilloid 1 (TRPV1)-deficient AS mice to ascertain whether TRPV1 exerts an influence on AS by modulating aortic aging. Furthermore, the study sought to expand upon the molecular mechanisms by which TRPV1 regulates aortic aging. TRPV1 expression was examined in aortic tissue of Apoe-/- mice, and its expression level was significantly reduced in comparison with that of control mice. Apoe-/-Trpv1-/- mice were subjected to a high-fat diet, after which a significant increase in aortic sinus senescent cell area, senescence-associated secretory phenotypes (SASP) and expression of senescence-associated proteins was observed, accompanied by an increase in plaque area and instability. Transcriptome sequencing ascertained that the deletion of TRPV1 led to a substantial augmentation in the expression of ubiquitin-like protein 15 (ISG15) within the aortic tissue. It then demonstrated that TRPV1 deletion promotes ISG15-induced aortic senescence using Apoe-/-Trpv1-/- high-fat dietary mice, as well as cellular experiments. Studies utilising PPI analysis and in vitro cultured EA.hy926 cells have demonstrated that ISG15 promotes vascular endothelial cell senescence by facilitating the expression and phosphorylation of p53 and p21, and by impeding the phosphorylation of retinoblastoma (Rb). Aortic TRPV1 deficiency promotes aortic senescence by promoting upregulation of ISG15 expression, which in turn promotes p53 and p21 phosphorylation and inhibits Rb phosphorylation.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71157"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772743","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}

引用次数: 0

Correction to "Inhibition of STAT3 by S3I-201 Suppress Peritoneal Fibroblast Phenotype Conversion and Alleviate Peritoneal Fibrosis". 更正“sgi -201抑制STAT3抑制腹膜成纤维细胞表型转化和减轻腹膜纤维化”。

IF 4.2 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2026-04-01 DOI: 10.1111/jcmm.71115

引用次数: 0

RNA-Sequencing Reveals Two Subgroups of Eccrine Porocarcinomas and Poromas. rna测序揭示了两个亚群的内分泌porcrine癌和Poromas。

IF 4.2 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2026-04-01 DOI: 10.1111/jcmm.71140

Maya Puttonen, Sami Kilpinen, Maria von Willebrand, Kalle Ojala, Tom Böhling, Virve Koljonen, Harri Sihto

{"title":"RNA-Sequencing Reveals Two Subgroups of Eccrine Porocarcinomas and Poromas.","authors":"Maya Puttonen, Sami Kilpinen, Maria von Willebrand, Kalle Ojala, Tom Böhling, Virve Koljonen, Harri Sihto","doi":"10.1111/jcmm.71140","DOIUrl":"10.1111/jcmm.71140","url":null,"abstract":"Eccrine porocarcinoma (EPC), a rare malignant eccrine gland tumour, remains molecularly understudied. Transcriptomic studies of EPC and benign eccrine poroma (EP) have identified recurrent fusions and expression changes, but differences distinguishing malignant EPC from benign EP are unclear. RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) samples (13 EPCs and 49 EPs) from Helsinki Biobank and Finnish Clinical Biobank Tampere. RNA sequencing characterized transcriptomic profiles. Histopathological features were assessed on haematoxylin-eosin-stained sections, and fusion genes were evaluated by NUT and YAP1 immunohistochemistry. EPCs and EPs clustered into two transcriptomic groups regardless of tumour subtype, primarily distinguished by differential expression of genes involved in skin metabolism. The metabolism-high group showed higher expression of genes associated with immune-related processes, mesothelin, and Ras-MAPK signalling. The metabolism-low group contained a subgroup enriched for Hedgehog pathway-associated genes, such as GLI1, GLI2, HHIP, LRP2, and PTCH2. All samples with the YAP1-NUTM1 fusion pattern belonged to the metabolism-low group and showed elevated NUTM1 expression in the heatmap. RNA sequencing revealed transcriptomic subgroups in EPC/EP partly linked to fusions. The results underscore the necessity for further investigation into the disrupted signalling pathways, which may facilitate the development of targeted therapies.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71140"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690345","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}

引用次数: 0

Correction to "ALKBH5-Mediated m6A Modification of lncRNA KCNQ1OT1 Triggers the Development of LSCC via Upregulation of HOXA9". 更正“alkbh5介导的m6A修饰lncRNA kcnq10t1通过上调HOXA9触发LSCC的发展”。

IF 4.2 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2026-04-01 DOI: 10.1111/jcmm.71091

引用次数: 0

Correction to "Sprouty2 Suppresses Progression and Correlates to Favourable Prognosis of Intrahepatic Cholangiocarcinoma via Antagonizing FGFR2 Signalling". 更正“Sprouty2通过拮抗FGFR2信号抑制肝内胆管癌的进展并与良好预后相关”。

IF 4.2 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2026-04-01 DOI: 10.1111/jcmm.71149

引用次数: 0

Bioinformatics and Immunohistochemistry Reveal the Diagnostic and Mechanistic Role of the Cuproptosis-Related Genes SMOC2/THY1 in Liver Fibrosis. 生物信息学和免疫组织化学揭示铜纤维化相关基因SMOC2/THY1在肝纤维化中的诊断和机制作用。

IF 4.2 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2026-04-01 DOI: 10.1111/jcmm.71144

Ranyan Gao, Hongliang Chen, Jiaxin Wang, Lingyi Xu, Fengchun Li, Xinyu Jiang, Xinyu Geng, Ning Li, Ram Prasad Chaulagain, Babalola Deborah Oluwaseun, Wanwei Li, Shizhu Jin

{"title":"Bioinformatics and Immunohistochemistry Reveal the Diagnostic and Mechanistic Role of the Cuproptosis-Related Genes SMOC2/THY1 in Liver Fibrosis.","authors":"Ranyan Gao, Hongliang Chen, Jiaxin Wang, Lingyi Xu, Fengchun Li, Xinyu Jiang, Xinyu Geng, Ning Li, Ram Prasad Chaulagain, Babalola Deborah Oluwaseun, Wanwei Li, Shizhu Jin","doi":"10.1111/jcmm.71144","DOIUrl":"10.1111/jcmm.71144","url":null,"abstract":"Cuproptosis, a newly identified form of programmed cell death, inhibits liver fibrosis in hepatic stellate cells. However, how cuproptosis influences liver fibrosis in other cells remains to be determined. We aimed to develop a diagnostic model for cuproptosis and to further investigate its role in liver fibrosis. We obtained datasets of patients with metabolic dysfunction-associated fatty liver disease from the Gene Expression Omnibus. A diagnostic model was established using WGCNA and machine learning, and the model demonstrated a satisfied accuracy in the training and validation sets. Single-cell RNA (scRNA) confirmed that cuproptosis is highly likely to occur in hepatocytes and likely promotes liver fibrosis through communication with macrophages and dendritic cells. Immunohistochemistry analyses revealed that THY1 localized to fibroblast membranes and SMOC2 localized to hepatocytes. Molecular docking and molecular dynamics were used to identify the most suitable therapeutic drugs and suggested that breviscapine may target THY1, which may have a therapeutic effect on liver fibrosis. These findings establish a diagnostic model based on cuproptosis-related genes for liver fibrosis, identify THY1 and SMOC2 as key diagnostic biomarkers, and propose a model in which the expression of these markers in hepatocyte are associated with fibrosis progression, potentially through immune-mediated mechanisms.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71144"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716753","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}

引用次数: 0

ARIH2 Ubiquitination Regulates NUPR1 to Inhibit Ferroptosis in Bladder Cancer. ARIH2泛素化调控NUPR1抑制膀胱癌铁下垂。

IF 4.2 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2026-04-01 DOI: 10.1111/jcmm.71147

Hannuo Deng, Yuanyuan Mi, Lei Zhang, Yuchen Tan, Guangming He, Zebin Shi, Shenglin Gao, Lifeng Zhang, Li Zuo, Jie Peng

{"title":"ARIH2 Ubiquitination Regulates NUPR1 to Inhibit Ferroptosis in Bladder Cancer.","authors":"Hannuo Deng, Yuanyuan Mi, Lei Zhang, Yuchen Tan, Guangming He, Zebin Shi, Shenglin Gao, Lifeng Zhang, Li Zuo, Jie Peng","doi":"10.1111/jcmm.71147","DOIUrl":"10.1111/jcmm.71147","url":null,"abstract":"NUPR1 is a pro-tumorigenic factor in bladder cancer (BLCA), but the mechanisms governing its protein stability remain poorly defined. Here, we identified ARIH2 as an E3 ubiquitin ligase that interacts with NUPR1 in BLCA cells through immunoprecipitation-mass spectrometry (IP-MS), co-immunoprecipitation (Co-IP), and immunofluorescence analyses. ARIH2 overexpression reduced NUPR1 abundance and inhibited BLCA cell proliferation and migration while enhancing apoptosis, whereas ARIH2 knockdown increased NUPR1 expression and promoted malignant phenotypes. Mechanistically, ARIH2 depletion prolonged NUPR1 protein stability and reduced its ubiquitination, indicating that ARIH2 negatively regulates NUPR1 through ubiquitin-mediated degradation. Moreover, NUPR1 overexpression suppressed ferroptosis, as reflected by increased GPX4 and SLC7A11, decreased ACSL4, reduced lipid peroxidation, and diminished Fe2+ accumulation, while NUPR1 knockdown exerted the opposite effects. ARIH2 knockdown mimicked the ferroptosis-resistant phenotype induced by NUPR1 upregulation, supporting that ARIH2 modulates ferroptosis through NUPR1. Bioinformatic and experimental analyses further showed that NUPR1 was associated with immunosuppressive infiltration and promoted M2 macrophage polarization. Together, our findings uncover an ARIH2-NUPR1 regulatory axis that drives BLCA progression by suppressing ferroptosis and favouring an immunosuppressive microenvironment, highlighting this pathway as a potential therapeutic target in BLCA.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71147"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716772","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}

引用次数: 0

A Novel Long Noncoding RNA-LNC000133 Associated With Steroid-Induced Osteonecrosis of the Femoral Head Promotes Osteoblast Differentiation Through Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Pathway: A Bioinformatics Validation and Detailed Mechanistic Study. 一种与类固醇诱导的股骨头骨坏死相关的新型长链非编码RNA-LNC000133通过骨髓间充质干细胞衍生外体途径促进成骨细胞分化：生物信息学验证和详细的机制研究。

IF 4.2 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2026-04-01 DOI: 10.1111/jcmm.71135

Chengbin Yang, Tixiong Xia, Xi Li, Tong Chen, Yingxing Xu

{"title":"A Novel Long Noncoding RNA-LNC000133 Associated With Steroid-Induced Osteonecrosis of the Femoral Head Promotes Osteoblast Differentiation Through Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Pathway: A Bioinformatics Validation and Detailed Mechanistic Study.","authors":"Chengbin Yang, Tixiong Xia, Xi Li, Tong Chen, Yingxing Xu","doi":"10.1111/jcmm.71135","DOIUrl":"10.1111/jcmm.71135","url":null,"abstract":"Steroid-induced osteonecrosis of the femoral head (SONFH) is a debilitating disease caused by glucocorticoid abuse, characterized by complex pathogenesis and unclear molecular mechanisms. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) and their exosome-mediated signalling is a key contributor to SONFH, although the precise mechanisms remain to be elucidated. In this study, the differential expression profiles of long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs) in exosomes derived from human BMSCs (hBMSCs) obtained from patients with SONFH compared to controls with femoral neck fractures were identified. Through next-generation sequencing, a novel lncRNA, LNC000133, associated with SONFH was discovered. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and competing endogenous RNA (ceRNA) network construction, the LNC000133/miR-362-5p/TGF-β3/SMAD3/BMP2 signalling axis was established. The definitive expression, localization and full-length sequence of LNC000133 in BMSCs were subsequently validated by Northern blot, quantitative real-time polymerase chain reaction (qRT-PCR), fluorescence in situ hybridization (FISH) and rapid amplification of cDNA ends (RACE). Most notably, mechanistic studies demonstrated that LNC000133-modified BMSCs-derived exosomes were efficiently taken up by osteoblasts, which promoted proliferation and osteogenic differentiation by targeting the miR-362-5p/TGF-β3/SMAD3/BMP2 signalling pathway.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71135"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716811","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}

引用次数: 0

Dysregulated Sheddase Signalling as a Molecular Driver of Plaque Instability Revealed by Integrative Transcriptomics. 整合转录组学揭示了失调的Sheddase信号作为斑块不稳定的分子驱动因素。

IF 4.2 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2026-04-01 DOI: 10.1111/jcmm.71136

Alaa G Alahmadi, Hind A Alkhatabi, Reem M Alotibi, Wedad M Albeshri, Mohammed El-Mezgueldi, Ammar Al-Farga, Peter Natesan Pushparaj

{"title":"Dysregulated Sheddase Signalling as a Molecular Driver of Plaque Instability Revealed by Integrative Transcriptomics.","authors":"Alaa G Alahmadi, Hind A Alkhatabi, Reem M Alotibi, Wedad M Albeshri, Mohammed El-Mezgueldi, Ammar Al-Farga, Peter Natesan Pushparaj","doi":"10.1111/jcmm.71136","DOIUrl":"10.1111/jcmm.71136","url":null,"abstract":"Atherosclerosis is a major cause of mortality due to chronic and progressive low-grade inflammation and fibroproliferative remodelling of the intima of arteries. Comprehensive understanding of the interplay between plaque biology and the mechanisms underlying plaque vulnerability and rupture is essential. Here, we aimed to investigate the transcriptomic profiles of stable and unstable atherosclerotic plaques using RNA sequencing data from human carotid atherosclerotic plaque samples based on next-generation knowledge discovery (NGKD) methods. High-throughput RNA-seq data from plaques dissected in stable and unstable regions of four patients were obtained from the Gene Expression Omnibus (GEO) database. GEO RNA-seq Experiments Interactive Navigator (GREIN) software was used to obtain raw gene-level counts and filtered metadata for this dataset. The data were further filtered and normalized using Express analyst to derive differentially expressed genes (DEGs) in unstable plaques compared to stable plaques. The DEGs were further analysed using WebGestalt, STRING DB, preranked gene set enrichment analysis (GSEA), and Ingenuity Pathway Analysis (IPA) software. We identified 4792 DEGs in unstable plaques based on a p-value cutoff of < 0.05. NGKD analysis revealed that the sheddase pathway, collagen degradation, activation of matrix metalloproteinases (MMPs), and extracellular matrix (ECM) degradation ranked among the top five upregulated pathways, whereas the inhibition of MMPs and smooth muscle contraction pathways were identified as the most prominent downregulated pathways in unstable plaques. We found that the sheddase pathway was one of the most significantly upregulated canonical pathways in unstable plaques and this finding opens new avenues for potential therapeutic interventions in patients with atherosclerosis.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 8","pages":"e71136"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772746","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}

引用次数: 0