JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Can Gene Expression Differentiate Patients With Heart Failure due to Coronary Heart Disease From Patients With Coronary Disease Without Heart Failure?","authors":"Józefa Dąbek,&nbsp;Joanna Głogowska-Ligus,&nbsp;Mieczysław Piechota","doi":"10.1111/jcmm.70727","DOIUrl":"https://doi.org/10.1111/jcmm.70727","url":null,"abstract":"<p>The aim of the study was to analyse and compare the transcriptional activity of the TGF-β1 gene and its receptors in patients with heart failure based on coronary artery disease and patients with coronary artery disease without heart failure, taking into account the presence of individual risk factors, the stage of heart failure and the number of diseased coronary arteries. The study included 105 patients with advanced heart failure (NYHA III–IV) and 52 patients with coronary artery disease without heart failure. The study was performed using the QRT-PCR technique. The transcriptional activity of the TGF-β1 gene and its type III receptor was significantly lower in patients with advanced heart failure. In this group of patients with risk factors such as previous myocardial infarction, family history, overweight/obesity and arterial hypertension, a statistically significant reduction in TGF-β1 gene expression was demonstrated. In patients with heart failure, changes in the transcriptional activity of all receptor's genes were found when these patients were burdened with risk factors. The reduced transcriptional activity of TGF-β1 and its type III receptor demonstrated in patients with heart failure may be a useful marker in clinical practice for assessing the progression of coronary artery disease towards the development of heart failure, as well as its decompensation and compensation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70727","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929531","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":"Pharmacological Targeting of DHHC9-Mediated STRN4 Palmitoylation to Suppress YAP-Driven Cancer Metastasis","authors":"Yang Tian,&nbsp;Wei Li,&nbsp;Qing Zhai,&nbsp;Ying Yu,&nbsp;Jiaxin Yuan,&nbsp;Yan Ma,&nbsp;Jingjing Yang,&nbsp;Mingyue Li,&nbsp;Wenwen Chang,&nbsp;Wenjing Li,&nbsp;Keke Huang,&nbsp;Chongran Sun,&nbsp;Chen Zeng,&nbsp;Yingdi Sun,&nbsp;Jiabao Gu,&nbsp;Huilin Zhang,&nbsp;Dameng Li,&nbsp;Yanan Yu,&nbsp;Lu Hu,&nbsp;Peng Zhang,&nbsp;Bo Ma,&nbsp;Junnian Zheng,&nbsp;Pan Li,&nbsp;Feng Guo,&nbsp;Yang Sun","doi":"10.1111/jcmm.70815","DOIUrl":"https://doi.org/10.1111/jcmm.70815","url":null,"abstract":"<p>Protein S-palmitoylation, a dynamic and reversible post-translational modification involving the attachment of palmitate to cysteine residues, is a key regulator of protein functionality and cellular signalling. Dysregulation of this modification has emerged as a critical driver of cancer progression. Among the 23 DHHC palmitoyl transferases responsible for catalysing S-palmitoylation, aberrant expression of specific members is linked to tumorigenesis and development, underscoring their potential as promising therapeutic targets. However, the cancer-specific roles and substrates of individual DHHC enzymes remain poorly characterised. In this study, we identified DHHC9 as a crucial regulator of adenocarcinoma progression, including colorectal and lung cancers. Functional studies demonstrated that DHHC9 knockdown profoundly inhibited cell migration in vitro and tumour metastasis in vivo. Proteomic and functional analyses revealed that STRN4, a core component of the STRIPAK complex, was palmitoylated by DHHC9 at cysteine 701. The STRN4 palmitoylation reduced YAP phosphorylation, promoted nuclear translocation of YAP and activated downstream Hippo pathway transcriptional targets—including CCN1, CCN2 and ANKRD1—thereby driving cancer cell migration. Notably, we discovered two small molecules, Treprostinil and 10-HCPT, as potent DHHC9 inhibitors that effectively suppressed adenocarcinoma cell migration. Our findings define the DHHC9-STRN4-YAP axis as a novel mechanism linking palmitoylation to phosphatase regulation and Hippo pathway dysregulation, unveiling DHHC9 as a highly promising therapeutic target in cancer treatment.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70815","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934928","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":"Epigenomic Profiling Positions ATF7 as a Core Regulator of Colonic Inflammation","authors":"Fang Liu,&nbsp;Yidong Chen,&nbsp;Jiamin Li,&nbsp;Junrong Li,&nbsp;Qi Yu,&nbsp;Xiaopeng Zhang,&nbsp;Liangru Zhu","doi":"10.1111/jcmm.70831","DOIUrl":"https://doi.org/10.1111/jcmm.70831","url":null,"abstract":"<p>Mitochondrial dysfunction plays a central role in epithelial damage and persistent inflammation in ulcerative colitis (UC), but the transcriptional mechanisms that govern mitochondrial quality control in the intestinal epithelium remain poorly defined. Here, we identify Activating Transcription Factor 7 (ATF7) as a key regulator of mitophagy in colonic epithelial cells. Integrative transcriptomic and epigenomic analyses of patient-derived mucosal samples revealed marked ATF7 downregulation and widespread activation of inflammatory pathways. Chromatin immunoprecipitation and luciferase reporter assays demonstrated that ATF7 directly binds to and activates the promoter of PINK1, a master regulator of mitophagy. Genetic ablation of ATF7 or PINK1 in human epithelial cells impaired mitophagy, disrupted mitochondrial membrane potential, and increased reactive oxygen species. In vivo, intestinal epithelial cell-specific knockout of ATF7 or PINK1 exacerbated dextran sulfate sodium-induced colitis, with greater epithelial injury, elevated cytokine production, and transcriptional activation of TNF, NF-kappaB, and inflammatory bowel disease signalling pathways. These results establish ATF7 as a critical transcriptional regulator linking mitochondrial homeostasis to epithelial resilience in the inflamed colon.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70831","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934926","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":"β-Sitosterol as an Anti-Tumour Active Component of Herba Sarcandrae Inhibits Colorectal Cancer Progression Through Up-Regulation of TBX20","authors":"Haixiao Yuan,&nbsp;Weiqing Feng,&nbsp;Shaohua Yang,&nbsp;Hao Yin,&nbsp;Shaoyong Ouyang,&nbsp;Hong Xie,&nbsp;Hongmei Tang,&nbsp;Xiaowei Ou,&nbsp;Xianling Gong,&nbsp;Jie Yuan","doi":"10.1111/jcmm.70809","DOIUrl":"https://doi.org/10.1111/jcmm.70809","url":null,"abstract":"<p>Colorectal cancer (CRC) is a common malignant tumor of the digestive tract with a high incidence rate. <i>Herba Sarcandrae</i> (HS) is an antipyretic and has been reported to have anti-cancer effects. This study explored the impacts of β-sitosterol on the sensitivity of CRC to 5-fluorouracil (5-FU) and oxaliplatin and the stability of TBX20 protein in CRC cells. There were 41 HS active ingredients and 265 corresponding potential targets, and 48 potential targets of HS were enriched in CRC. Then, 206 differentially expressed genes (DEGs) related to TBX20 overexpression were screened based on the TCGA database, some of which were associated with TMN stages of COAD patients. Epimedin C, rutin, and β-sitosterol, which could be combined with TBX20, were screened and validated in CRC cells. Functionally, β-sitosterol could suppress proliferation and induce apoptosis of CRC cells. β-sitosterol could also enhance the sensitivity of CRC to 5-FU and oxaliplatin. In xenograft models, both HS and β-sitosterol treatments inhibited tumor growth and upregulated TBX20 protein expression, with β-sitosterol demonstrating a stronger effect. Mechanistically, β-sitosterol may stabilize TBX20 by inhibiting its ubiquitin-mediated degradation. In conclusion, β-sitosterol, as an anti-tumor active component of HS, prevents CRC cell proliferation, and accelerates apoptosis by upregulating TBX20.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70809","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927438","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":"Wnt Signalling-Activated EN2 Promotes the Progression of Glioblastoma by Upregulating Fatty Acid Synthesis Metabolism","authors":"Junjun Zhang,&nbsp;Shengjun Zhou,&nbsp;Zifeng Dai,&nbsp;Fanyong Gong,&nbsp;Jianfei Zhang","doi":"10.1111/jcmm.70726","DOIUrl":"https://doi.org/10.1111/jcmm.70726","url":null,"abstract":"<p>Glioblastoma (GBM) is the most aggressive primary brain tumour, with limited treatment options and a propensity for rapid development of resistance to therapies. Previous studies have indicated that fatty acid metabolic reprogramming is a critical marker of tumour progression and plays a significant role in the proliferation and migration of cancer cells. However, research on fatty acid synthesis metabolism in GBM is relatively limited, and the underlying mechanisms warrant further investigation. In this study, we identified a significant correlation between the expression of Engrailed 2 (EN2) and poor prognosis in GBM patients. Both in vivo and in vitro experiments demonstrated that EN2 promotes GBM progression and facilitates fatty acid metabolic reprogramming. Mechanistically, EN2 activates the expression of Sterol Regulatory Element-Binding Protein 1 (SREBP1), thereby enhancing the fatty acid synthesis metabolic pathway and contributing to tumour resistance. Furthermore, we found that EN2 is primarily regulated by the Wnt signalling pathway and T-cell factor 4 (TCF4). Targeting EN2 enhances the efficacy of chemotherapy in GBM and prolongs survival in mouse models. Overall, our findings suggest that EN2 represents a potential therapeutic target for GBM and underscores its role in promoting fatty acid synthesis metabolism in GBM cells.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927653","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":"Butyrate Reducing Bone Mass Loss by Regulating the Expression of m6A Methyltransferase METTL3 in Implant-Associated Staphylococcus aureus Osteomyelitis","authors":"Chongkai Sun,&nbsp;Yuan Xu,&nbsp;Ziyue Peng,&nbsp;Xuyou Zhou,&nbsp;Zixuan Wang,&nbsp;Haoyang Wan,&nbsp;Bin Yu","doi":"10.1111/jcmm.70683","DOIUrl":"https://doi.org/10.1111/jcmm.70683","url":null,"abstract":"<p><i>Staphylococcus aureus</i> (<i>S. aureus</i>) has been identified as a hindrance to osteoblast differentiation, thereby contributing significantly to the development of osteomyelitis. Consequently, exploring pharmaceutical interventions targeting osteoblast differentiation mediated by <i>S. aureus</i> may present a novel approach for treating osteomyelitis. It has been reported that N6-methyladenosine (m6A) methylation is highly associated with infection. Moreover, studies continue to validate that short-chain fatty acids play an important role in transcriptional modification and have been considered as a potential treatment for <i>S. aureus</i> infection. Our research aimed to examine the impact and underlying mechanism of butyrate, a short-chain fatty acid, in reducing the inhibitory influence exerted by <i>S. aureus</i> on osteoblast differentiation. The concentration of butyrate beneficial to MC3T3-E1 cell viability was screened by Cell Counting Kit-8 (CCK8) assay. Reverse transcription-quantitative PCR (RT-qPCR), Western blotting, and alkaline phosphatase (ALP)staining were used to verify the osteogenic indexes and the expression levels of m6A methylation-related proteins in MC3T3-E1 cells infected with <i>S. aureus</i> at different time points. Besides, the same methods were used to verify the effects of butyrate stimulation and METTL3 knockdown on the osteogenic ability of MC3T3-E1 cells. H&amp;E staining, Goldner staining, and immunohistochemical staining were used to verify the effect of butyrate on mice with endo-plant associated <i>S. aureus</i> osteomyelitis. The potential mechanisms of METTL3 and autophagy in MC3T3-E1 cells were studied by Western blotting. In vitro experiments, we found that butyrate significantly enhanced the expression of osteogenic-related genes down-regulated by infection in MC3T3-E1 cells induced by <i>S. aureus</i>, including RUNX2, OCN, and ALP. In addition, METTL3, an important m6A methyltransferase, was significantly up-regulated in <i>S. aureus</i>-infected MC3T3-E1 cells, but its expression could be down-regulated by butyrate. Inhibiting the expression of METTL3 by siRNA could effectively rescue the osteogenic markers down-regulated by <i>S. aureus</i> infection in MC3T3-E1 cells, which was similar to the results of butyrate treatment. In vivo experiments had shown that butyrate could alleviate inflammation and osteogenic activity in implant-associated osteomyelitis. The construction of bone marrow METTL3 low-expression mice using siRNA also showed similar effects on osteogenic activity. Additionally, Western blotting confirmed that knocking down METTL3 rescued the autophagy imbalance caused by <i>S. aureus</i> infection in MC3T3-E1 cells. In general, our research demonstrated that butyrate effectively alleviated the hindrance of osteoblast activity induced by <i>S. aureus</i> infection by suppressing the expression of METTL3, suggesting that butyrate may be a novel treatment for <i>S. aureus</i> ost","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927342","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":"Monitoring SARS-CoV-2 Dissemination in Wastewater and Virus Isolation in Cell Cultures: An Integrated Approach for Pathogen Detection and Surveillance","authors":"Elena Radu,&nbsp;Tudor Emanuel Fertig,&nbsp;Laura Denisa Dragu,&nbsp;Ioana Mădălina Pitică,&nbsp;Marius Surleac,&nbsp;Ana Iulia Neagu,&nbsp;Lavinia Pană,&nbsp;Alexandra Păiş,&nbsp;Lilia Matei,&nbsp;Ionut-Lucian Antone-Iordache,&nbsp;Daciana Silvia Marta,&nbsp;Victor-Eduard Peteu,&nbsp;Mihai Niţă-Lazăr,&nbsp;Cătălina Stoica,&nbsp;Cornel Popescu,&nbsp;Camelia Mădălina Sultana,&nbsp;Anca Botezatu,&nbsp;Iulia Virginia Iancu,&nbsp;Mihaela Chivu-Economescu,&nbsp;Leontina Banică,&nbsp;Ana Sorinica Petre,&nbsp;Simona Paraschiv,&nbsp;Mihaela Gherghiceanu,&nbsp;Simona Maria Ruta,&nbsp;Norbert Kreuzinger,&nbsp;Carmen Cristina Diaconu,&nbsp;Coralia Bleotu","doi":"10.1111/jcmm.70805","DOIUrl":"https://doi.org/10.1111/jcmm.70805","url":null,"abstract":"<p>Our study presents wastewater (WW) monitoring data, focusing on determining the infectivity of SARS-CoV-2 in the collected samples. Additionally, a panel of different viruses has been tested in the WW samples. The untreated WW monitoring campaign took place over 1 year in Bucharest, with approximately 300 samples being collected twice a week at the wastewater treatment plant (WWTP) and an infectious diseases hospital. Our data indicated that SARS-CoV-2 concentrations in WW preceded the increase in the number of clinical cases by nearly 2 weeks. Differences between locations were notable, with higher raw concentrations in WW samples from the hospital than those from the WWTP. However, after normalising to population equivalent, the hospital samples concentrations dropped significantly, suggesting that WW monitoring at the urban level provides a more complete and epidemiologically relevant picture than data obtained only from hospitals. Only a few isolates could demonstrate SARS-CoV-2 persistence during in vitro passages. Although the success rate was low, the technique remains crucial for validating the viability of viruses. Adenovirus, Bocavirus and Reovirus were the most abundant ones in both urban and hospital wastewater. WW monitoring remains the most effective approach for tracking the dissemination of various pathogens and supporting public health authorities.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927347","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":"Imipramine Inhibits Osteosarcoma Invasion via Src Inactivation and Caspase-Dependent Apoptosis","authors":"Yu-Chang Liu,&nbsp;Chi-Jung Fang,&nbsp;Li-Cho Hsu,&nbsp;Fei-Ting Hsu,&nbsp;Ming-Hsien Hu","doi":"10.1111/jcmm.70761","DOIUrl":"https://doi.org/10.1111/jcmm.70761","url":null,"abstract":"<p>Osteosarcoma (OS) is an aggressive malignancy characterised by high metastatic potential and poor prognosis. Imipramine, a tricyclic antidepressant, has shown potential anticancer effects. This study evaluates the cytotoxic, pro-apoptotic and anti-invasion effects of imipramine on OS cells in vitro and in vivo, as well as its underlying mechanisms. Imipramine significantly reduced U-2 OS and MG 63 cell viability in a time- and dose-dependent manner, confirmed through MTT and colony formation assays. It induced apoptosis via caspase-dependent pathways, as evidenced by increased cleaved caspase-3, -8 and -9 levels and reduced expression of anti-apoptotic proteins such as MCL-1. Imipramine activated both extrinsic and intrinsic apoptosis pathways in vitro and in vivo, increasing Fas, Fas-L, BAX and BAK while suppressing anti-apoptotic factors like BCL-2 and XIAP. Transwell assays showed dose-dependent inhibition of cell migration and invasion, supported by suppressed Src phosphorylation and downregulation of EMT markers (Snail-1 and Slug). In U-2 OS xenograft-bearing mice, imipramine significantly inhibited tumour growth in a dose-dependent manner, with the 30 mg/kg group showing the smallest tumour volume and slowest growth rate (<i>p</i> = 0.0098). Tumour weights were significantly reduced without impacting body weight or liver and kidney function markers (AST, ALT, γ-GT and CREA). Histopathological analyses revealed no significant abnormalities in vital organs. Imipramine exerts potent anti-OS effects by suppressing Src-mediated invasion and enhancing caspase-dependent apoptosis through extrinsic and intrinsic pathways. It inhibits tumour progression without inducing systemic toxicity, demonstrating its potential as a therapeutic candidate for OS.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70761","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927343","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 Unified Hybrid Model for Cardiovascular Risk Prediction: Merging Statistical, Kernel-Based and Neural Approaches","authors":"Mudassir Khan,&nbsp;Rupali A. Mahajan,&nbsp;Nithya Rekha Sivakumar,&nbsp;Monali Gulhane,&nbsp;Nitin Rakesh,&nbsp;Rajesh Dey,&nbsp;Md. Salah Uddin,&nbsp;Shakila Basheer","doi":"10.1111/jcmm.70797","DOIUrl":"https://doi.org/10.1111/jcmm.70797","url":null,"abstract":"<p>Cardiovascular diseases (CVDs) are still the leading cause of death in the worldwide. Traditional machine learning models often have difficulty in determine how to capture the complex links between disease risk factors and disease occurrence. This article discusses a hybrid machine learning approach for cardiovascular risk prediction (HMLCRP) to address this problem. This approach combines logistic regression (LR), support vector machines (SVMs) and neural networks (NNs) to make predictions more correct and reliable. The proposed model looks at important coronary heart sickness risk factors, including excessive blood pressure, a record of coronary heart disorder within the family, pressure, age, sex, levels of cholesterol, body mass index (BMI) and poor dwelling choices. The hybrid technique makes use of the nice functions of LR for clean understanding, SVM for dealing with large amounts of facts and NNs for finding developments. By integrating these models together, the HMLCRP makes positive that type is correct and that danger predictions are accurate. In this study, benchmark datasets used, which include the cardio statistics set, heart ailment dataset and Framingham heart examination dataset, are used to train and test the version. Popular parameter measures, such as accuracy, precision, recall and the F1-score, are used to determine overall performance. The results of the experiments indicate that the HMLCRP is better at predicting effects than individual models. The suggested combination model is a major step forward in personalised healthcare because it allows proactive risk management and early intervention methods to stop CVD.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70797","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910437","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":"Mechanisms of Resistance to PARPi in Pancreatic Ductal Adenocarcinoma","authors":"Jojanneke Stoof,&nbsp;Charlotte Andrieu,&nbsp;Fiona O'Connell,&nbsp;Jacintha O'Sullivan,&nbsp;Maeve A. Lowery,&nbsp;Naomi Walsh","doi":"10.1111/jcmm.70816","DOIUrl":"https://doi.org/10.1111/jcmm.70816","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited treatment options. PARP inhibitors (PARPi) have shown promise in treating PDAC with homologous recombination deficiency (HRD), but rapid acquisition of resistance limits their efficacy. Our objective is to investigate mechanisms of resistance to PARPi in <i>BRCA2</i>-mutant PDAC cells and identify potential therapeutic targets to modulate this resistance. We developed olaparib- and talazoparib-resistant Capan-1 cell lines and characterised their resistance profiles using viability assays, RNA sequencing and metabolomic profiling. We also developed a cisplatin-resistant Capan-1 cell line to compare resistance mechanisms between PARPi and platinum agents. Both olaparib- and talazoparib-resistant cells showed cross-resistance to other PARPi and oxaliplatin, but not to gemcitabine or 5-FU. Talazoparib-resistant cells exhibited a similar resistance profile to cisplatin-resistant cells, including decreased PARP1 expression and altered metabolomic profiles. RNA sequencing and metabolomic profiling revealed significant enrichment of metabolic pathways, including oxidative phosphorylation and glycolysis, in resistant cells. Our study highlights the complexity of resistance mechanisms to PARPi in PDAC and identifies potential therapeutic targets in metabolism. The differences in the resistance profiles between olaparib and talazoparib suggest that PARP-trapping potency may play a role in resistance development. Further research is needed to validate these findings and explore novel therapeutic strategies to overcome resistance to PARPi in PDAC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70816","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910434","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}