JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Inhibition of METTL3 Attenuates Renal Fibrosis by Upregulating ABCG2 m6A Modifications via IGF2BP2-Dependent Mechanisms in Hyperuricemic Nephropathy","authors":"Tong Zu,&nbsp;Hang Yang,&nbsp;Jie Wang,&nbsp;Shuangjian Li,&nbsp;Yue Yu,&nbsp;Kuo Zhang,&nbsp;Xiuxiu Song,&nbsp;Jie Ying,&nbsp;Yaru Yang,&nbsp;Xian Wang,&nbsp;Juan Jin","doi":"10.1111/jcmm.70468","DOIUrl":"https://doi.org/10.1111/jcmm.70468","url":null,"abstract":"<p>Hyperuricemia has been linked to kidney problems including hyperuricemic nephropathy (HN), which is characterised by inflammation and fibrosis in the kidneys. HN is frequently observed in patients with chronic gout. However, the causes of HN are not fully understood and effective treatments are limited. The status of RNA m6A, expression, and location of METTL3 in the kidney was evaluated in mice with HN. The mechanism of the METTL3-associated ABCG2 downregulation was further studied in mTEC cells and a potassium oxazinate + adenine-induced mice model and adeno-associated virus 9 (AAV9)-mediated METTL3 silencing mice. Expressions of ABCG2, α-SMA, collagen-1, TGF-β1, IL-1β, IL-6, and TNF-α were analysed using real-time PCR and western blotting. Hyperuricemia led to elevated m6A levels and METTL3 expression in mouse kidneys. METTL3 was mainly located in mTEC cells. METTL3-specific inhibitor STM2457 alleviated uric acid-induced inflammatory and fibrotic responses in mTEC cells. Mechanistically, ABCG2 was identified as a target of METTL3 by RNA sequencing. The stability of ABCG2 was decreased through the binding of IGF2BP2 (insulin-like growth factor 2 binding protein 2) to its m6A-modified stop codon regions. Silencing or inhibition of METTL3 significantly reduced uric acid-induced cell injury and increased ABCG2 expression, leading to uric acid excretion. In vivo data showed that AAV9-mediated METTL3 silencing significantly alleviated renal dysfunction and fibrosis in HN mice. Our study provides the first evidence that METTL3 regulates uric acid excretion by controlling the m6A levels of ABCG2 through the binding of IGF2BP2, and inhibiting METTL3 can effectively alleviate kidney damage caused by hyperuricemia, showing potential as a therapy for HN.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Norwogonin Attenuates Inflammatory Osteolysis and Collagen-Induced Arthritis via Modulating Redox Signalling and Calcium Oscillations","authors":"Haojue Wang,&nbsp;Tao Yuan,&nbsp;Xiao Yu,&nbsp;Yi Wang,&nbsp;Changxing Liu,&nbsp;Ziqing Li,&nbsp;Shui Sun","doi":"10.1111/jcmm.70492","DOIUrl":"https://doi.org/10.1111/jcmm.70492","url":null,"abstract":"<p>Norwogonin is a flavonoid extraction derived from <i>Scutellaria baicalensis</i>. However, its potential mechanisms in the context of rheumatoid arthritis (RA) are unclear. This study investigates the specific effects and associated targets of Norwogonin in RA-related inflammatory osteolysis. Network pharmacology was conducted to analyse the core targets and signalling pathways of Norwogonin in RA. In vitro experiments were carried out to explore the actual effects of Norwogonin on osteoclast behaviours and related signalling mechanisms. In vivo studies further validated the therapeutic effect of Norwogonin in collagen-induced arthritis (CIA) mice. The network pharmacological analysis identified 18 shared targets between Norwogonin and RA, indicating a connection with inflammatory response and oxidoreductase activity. For biological validations, the results of in vitro experiments revealed 160 μM of Norwogonin inhibited LPS-driven osteoclast differentiation and function. The qPCR assay and Western blot analysis also disclosed consistently diminished changes to osteoclastic marker genes and proteins due to Norwogonin treatment, including those for osteoclast differentiation (Traf6, Tnfrsf11a and Nfatc1), fusion (Atp6v0d2, Dcstamp and Ocstamp) and function (Mmp9, Ctsk and Acp5). Further mechanism study revealed Norwogonin suppressed LPS-driven ROS production and calcium (Ca²⁺) oscillations. Also, intraperitoneal injection of 30 mg/kg Norwogonin every other day successfully mitigated clinical arthritis progression and attenuated bone destruction in the CIA model. Our study scrutinises Norwogonin's therapeutic prospects in treating RA and illustrates its inhibitory effects and potential mechanism within LPS-induced osteoclastogenesis and CIA mice, providing a basis for further translational research on Norwogonin in the treatment of RA-related inflammatory osteolysis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70492","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABARAPL1 Exerts Regulatory Effects on Hypoxia-Induced Pyroptosis in the Pathogenesis of Myocardial Infarction","authors":"Chunying Liu,&nbsp;Chenghui Yan,&nbsp;Dan Liu,&nbsp;Haixu Song,&nbsp;Yaling Han","doi":"10.1111/jcmm.70469","DOIUrl":"https://doi.org/10.1111/jcmm.70469","url":null,"abstract":"<p>Myocardial infarction (MI) is a major health threat, with high incidence and poor prognosis. This study aims to discover novel biomarkers and therapeutic targets to reduce myocardial damage and improve patient survival. A comprehensive bioinformatics analysis of MI datasets was conducted to identify pivotal genes related to pyroptosis and autophagy. These genes underwent protein–protein interaction (PPI) analysis, functional enrichment analysis, and immune infiltration analysis. Receiver operating characteristic (ROC) curves and nomograms were used to pinpoint the most diagnostic hub genes. Western blotting and qRT-PCR were performed to evaluate their expression and mechanisms. Drug prediction and molecular docking identified potential therapeutic agents targeting hub genes, with validation of their effects on hypoxia-induced pyroptosis both in vivo and in vitro. In conclusion, GABARAPL1 was identified as a hub gene, and PIK90 emerged as a promising therapeutic candidate drug. GABARAPL1 expression was significantly upregulated in heart tissue following MI and in endothelial cells subjected to hypoxic conditions. Silencing GABARAPL1 aggravated hypoxia-induced pyroptosis in endothelial cells. In vivo, PIK90 improved survival, reduced cardiac dysfunction, and alleviated myocardial fibrosis induced by MI. In vitro, PIK90 inhibited hypoxia-induced pyroptosis in endothelial cells. Consequently, <i>GABARAPL1</i> may represent a promising therapeutic target for the treatment of MI.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p16INK4a Deletion Alleviated Obesity-Associated Kidney Fibrosis by Regulating Metabolic Reprogramming and the Inflammasome Pathway","authors":"Qian Liu,&nbsp;Fen Wang,&nbsp;Yuan Du,&nbsp;Yankui Liu,&nbsp;Zhixuan Zhang,&nbsp;Xiaodong Zhang,&nbsp;Jianwei Li,&nbsp;Guangyi Huang,&nbsp;Fengqi Liu,&nbsp;Biahong Li,&nbsp;Wang Xiao,&nbsp;Chenyan Sui,&nbsp;Neng Bao,&nbsp;Ruijuan Zhuang,&nbsp;Changzheng Gao,&nbsp;Xiaoyan Wang,&nbsp;Xin Gu","doi":"10.1111/jcmm.70444","DOIUrl":"https://doi.org/10.1111/jcmm.70444","url":null,"abstract":"<p>Recent research has revealed a close association between obesity and various metabolic disorders, including renal metabolic diseases, but the mechanism is still unknown. This study explored the role of p16INK4a in obesity-related kidney fibrosis and evaluated its potential as a therapeutic target. Using wild-type (WT) mice and p16 KO mice, we fed both groups a high-fat diet (HFD) for 6 months. Our results showed that an HFD led to significant weight gain and increased p16INK4a expression in WT mouse kidneys. Notably, p16 KO mice presented reduced fibrosis, as indicated by decreased levels of profibrotic proteins (α-SMA and collagen I) and improved histological outcomes, including reduced fibrosis in the glomeruli and renal tubules. P16 KO also suppressed the levels of several proinflammatory biomarkers (MMP1, MMP3, IL-1β, TNF-α and IL-6) and inhibited the NLRP3 inflammasome pathway. The administration of ABT263 further validated these findings by decreasing fibrosis and inflammation in HFD-fed mice, suggesting that p16INK4a contributes to both fibrotic and inflammatory processes. Metabolomic analyses revealed that p16 knockout influenced various metabolic pathways, including linoleic acid and pyrimidine metabolism, in HFD-induced kidneys. Additionally, p16INK4a over-expression was observed in the kidneys of chronic kidney disease patients with long-term hyperlipidaemia. These results highlight the critical role of p16INK4a in obesity-induced kidney damage and suggest that targeting p16INK4a may be a promising approach for treating obesity-related kidney fibrosis and inflammation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenomedullin Inhibits the Efficacy of Combined Immunotherapy and Targeted Therapy in Biliary Tract Cancer by Disrupting Endothelial Cell Functions","authors":"Zhengfeng Xuan,&nbsp;Haoran Hu,&nbsp;Jian Xu,&nbsp;Xiaowei Ling,&nbsp;Long Zhang,&nbsp;Wenzhu Li,&nbsp;Junda Li,&nbsp;Chan Zhu,&nbsp;Yunjie Song,&nbsp;Xing Zhang,&nbsp;Jianhua Rao,&nbsp;Yong Wang,&nbsp;Feng Cheng","doi":"10.1111/jcmm.70460","DOIUrl":"https://doi.org/10.1111/jcmm.70460","url":null,"abstract":"<p>The global incidence of biliary tract cancer (BTC) is on the rise, presenting a substantial healthcare challenge. The integration of immune checkpoint inhibitors (ICIs) with molecularly targeted therapies is emerging as a strategy to enhance immune responses. However, the efficacy and underlying mechanisms of these treatments in BTC are still largely unexplored. In this study, tissue samples from 19 BTC patients treated with camrelizumab and apatinib were analysed using the NanoString 289-panel to identify key molecular biomarkers. Comparative analyses and subsequent experimental validations, including cell-based assays and histopathological examinations, identified adrenomedullin (ADM) as a critical molecular marker associated with treatment efficacy and poor prognosis. ADM has been shown to promote BTC cell proliferation, migration and angiogenesis, primarily by interacting with vascular endothelial growth factor (VEGF) and increasing AKT phosphorylation. Furthermore, ADM disrupts endothelial cell barrier function via the calcitonin receptor-like receptor (CRLR) and vascular endothelial (VE)-cadherin signalling pathway. Preclinical inhibition of ADM or CRLR resulted in suppressed tumour growth. Additionally, elevated ADM expression was correlated with increased tumour-infiltrating immune cells and higher immune checkpoint expression. These findings suggest that ADM plays a pivotal role in resistance to immunotherapy and anti-angiogenic treatment in BTC, and thus, targeting ADM may offer a promising therapeutic approach to enhance treatment efficacy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Pathogenic Role of Novel CPLANE1 Compound Heterozygous Variants in Joubert Syndrome: Insights Into mRNA Stability and NMD Pathway","authors":"Zhidan Hong,&nbsp;Sheng Xiang,&nbsp;Zhiying Chen,&nbsp;Xueping Qiu,&nbsp;Li Zhang,&nbsp;Ling Ma,&nbsp;Mei Wang","doi":"10.1111/jcmm.70484","DOIUrl":"https://doi.org/10.1111/jcmm.70484","url":null,"abstract":"<p>Joubert syndrome (JS) is a rare neurodevelopmental disorder associated with mutations in genes involved in ciliary function. Germline variants in <i>CPLANE1</i> have been implicated in JS. In this study, we investigated a family with three adverse pregnancies characterised by fetal malformations consistent with JS. Whole-exome sequencing (WES) identified compound heterozygous variants in <i>CPLANE1</i>: c.8893C&gt;T (p.Gln2965*) and c.203C&gt;T (p.Thr68Ile). Sanger sequencing confirmed the variants in the family. Bioinformatics analysis predicted that the c.203C&gt;T variant affects mRNA splicing and protein function. Functional studies using PBMCs demonstrated that the c.203C&gt;T variant causes exon 3 skipping, resulting in a frameshift and premature termination codon, leading to potential nonsense-mediated mRNA degradation (NMD). The mRNA transcription and translation inhibition experiment, by treatment with actinomycin D and puromycin, indicated that the c.203C&gt;T variant leads to accelerated mRNA degradation. Notably, the inhibition of SMG1, a key marker of the NMD pathway, partially rescued mRNA expression in mutated cells, providing further evidence of NMD activation. Based on these findings and ACMG guidelines, the c.203C&gt;T variant was reclassified from a variant of uncertain significance (VUS) to likely pathogenic. This is the first report of novel <i>CPLANE1</i> compound heterozygous variants contributing to JS in this family. Our study expands the known pathogenic variant spectrum of <i>CPLANE1</i> in JS and provides new insights into the molecular mechanisms of this ciliopathy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70484","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAM17/PTGS2 Facilitates Pulmonary Fibrosis by Regulating Ferroptosis","authors":"Suyan Yan,&nbsp;Yaqi Zhao,&nbsp;Wei Xu,&nbsp;Jin Zhang,&nbsp;Ying Zhang,&nbsp;Baocheng Liu,&nbsp;Xinya Li,&nbsp;Zhenzhen Ma,&nbsp;Qingrui Yang","doi":"10.1111/jcmm.70466","DOIUrl":"https://doi.org/10.1111/jcmm.70466","url":null,"abstract":"<p>Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease characterised by excessive deposition of extracellular matrix (ECM), resulting in high mortality rates. In this study, we provide evidence that ADAM17/PTGS2 plays a crucial role in inducing ferroptosis in fibroblasts, promoting PF. Initially, an assessment was made of ADAM17 protein levels in patients diagnosed with connective tissue diseases–interstitial lung diseases (CTD-ILD), using ELISA assays. Confirmation of the relationship between ADAM17 and fibrosis was achieved by stimulating cells with PMA or TAPI-1 (the ADAM17 inhibitor), in conjunction with the fibrosis-inducing factor, TGFβ1. To further explore the major downstream proteins of ADAM17 contributing to altered PF, we employed mRNA transcriptomics. To further investigate the role of ADAM17/PTGS2 in promoting ferroptosis and fibrosis, we employed western blot assays, immunofluorescence and transmission electron microscopy (TEM). Furthermore, the effects of the ADAM17/PTGS2/ferroptosis pathway in PF were verified using Adeno-associated virus (AAV)-mediated ADAM17 gene knockdown in mice. In CTD-ILD patients, ADAM17 expression was significantly elevated. Upon PMA stimulation, lung fibroblasts exhibited increased fibrosis-related proteins, and the combined stimulation of PMA and TGFβ1 synergistically promoted cellular fibrosis. Conversely, TAPI-1 alleviated fibrotic stimulation induced by TGFβ1. Transcriptomic analysis of lung fibroblast specimens overexpressing ADAM17 revealed significantly elevated PTGS2 expression levels. Knockdown and ferroptosis inhibition assays demonstrated that ADAM17 regulates ferroptosis in lung fibroblasts via PTGS2, ultimately inducing fibrosis. Furthermore, the deficiency of ADAM17 alleviated bleomycin-induced PF and inflammation in mice. These findings first verified that ADAM17/PTGS2/ferroptosis is a novel mechanism for regulating PF; it provides a new theoretical basis for further exploring the treatment of PF.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding Alzheimer's Disease With Depression: Molecular Insights and Therapeutic Target","authors":"Zekun Li,&nbsp;Hongmin Guo,&nbsp;Yihao Ge,&nbsp;Xiaohan Li,&nbsp;Fang Dong,&nbsp;Feng Zhang","doi":"10.1111/jcmm.70454","DOIUrl":"https://doi.org/10.1111/jcmm.70454","url":null,"abstract":"<p>The purpose of this study was to recognise predictive biomarkers and explore the promising therapeutic targets of AD with depression. We confirmed a positive correlation between AD and depression through MR Analysis. Through WGCNA analysis, we identified 1569 genes containing two modules, which were most related to AD. In addition, 1629 depressive DEGs were also identified. In these genes, 84 genes were shared by both AD and depression, which were screened by the Degree algorithm, MCC algorithm, and four machine learning algorithms. Two genes (ITGB5 and SPCS1) were confirmed as predictive biomarkers with AUC &gt; 0.7. Furthermore, the nomogram indicated that ITGB5 and SPCS1 are good biomarkers in diagnosing AD with depression. Four drugs targeted at ITGB5 were determined by the DGIdb website. In conclusion, we identified two predictive biomarkers for AD with depression, thus providing promising therapeutic targets for AD with depression.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Disulfidptosis-Related Diagnostic Gene Signature and Differential Expression Validation in Ischaemic Cardiomyopathy","authors":"Xin Tan,&nbsp;Shuai Xu,&nbsp;Yiyao Zeng,&nbsp;Fengyi Yu,&nbsp;Zhen Qin,&nbsp;Ge Zhang,&nbsp;Jili Fan,&nbsp;Xiaohong Bo,&nbsp;Junnan Tang,&nbsp;Huimin Fan,&nbsp;Yafeng Zhou","doi":"10.1111/jcmm.70475","DOIUrl":"https://doi.org/10.1111/jcmm.70475","url":null,"abstract":"<p>Ischaemic cardiomyopathy (IC) predominantly arises from prolonged deprivation of oxygen in the coronary arteries, resulting in compromised cardiac contractility or relaxation. This study investigates the role of disulfidptosis-associated genes (DiGs) in IC. Through the analysis of datasets GSE5406 and GSE57338, we explored the association between DiGs and immune characteristics to identify crucial genes contributing to IC development. The support vector machine model emerged as the most effective, identifying key genes such as MYH9, NUBPL, MYL6, MYH10 and NCKAP1. Validation with independent datasets GSE57345, GSE48166 and single-cell GSE145154 further supported these findings, demonstrating high predictive accuracy. Experimental validation in an IC mouse model, using Western blot, immunohistochemistry and RT-qPCR, confirmed the altered expression of these core genes in myocardial ischaemic regions. This research not only elucidates the significance of DiGs in IC but also underscores the diagnostic potential of identified core genes.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Development of Unclassified Myeloid Lineage Acute Leukaemia With Trisomy 6 and U2AF1 Mutation","authors":"Miroslaw Markiewicz,&nbsp;Agnieszka Kopacz,&nbsp;Beata Blajer-Olszewska,&nbsp;Malwina Mazur,&nbsp;Katarzyna Warzybok,&nbsp;Marta Szarawarska,&nbsp;Marzena Wojtaszewska,&nbsp;Monika Moskwa,&nbsp;Dominika Dudycz,&nbsp;Ewa Schwarz,&nbsp;Katarzyna Kosior,&nbsp;Krzysztof Lewandowski","doi":"10.1111/jcmm.70461","DOIUrl":"https://doi.org/10.1111/jcmm.70461","url":null,"abstract":"<p>We present a case of acute clonal bone marrow 98% infiltration of atypical myeloid cells with borderline hypogranular/agranular promyelocytes/myelocytes and occasional blast cells maturity, which also formed extramedullary tumours in the chest wall, with isolated trisomy of chromosome 6 and pathogenic variant <i>U2AF1</i> (S34F) that escapes established acute myeloid leukaemia (AML) diagnostic criteria according to the World Health Organization (WHO) classification. Following standard daunorubicin and cytarabine induction therapy, the disease progressed with the appearance of a previously undetected clone of leukaemic cells with a distinct immunophenotype demonstrating monocytoid differentiation and clonal evolution to a hypo-tetraploid karyotype with an average number of 84 chromosomes and new pathogenic <i>NRAS</i> and <i>ZRSR2</i> mutations. The patient reactivated refractory disseminated intravascular coagulation (DIC) leading to a progressive supratentorial hematoma and finally cardiac arrest. In conclusion, our report shows that atypical clonal myelocytes can massively infiltrate the bone marrow and form extramedullary tumours, justifying the diagnosis and treatment of acute leukaemia, although they did not fit the current classification.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}