Current medicinal chemistry最新文献

{"title":"Elucidating the Significance of Zonulin in the Pathogenesis of Chronic Inflammatory Disorders: Emphasis on Intestinal Barrier Function and Tight Junction Regulation","authors":"Marziyeh Mohammadi-kordkhayli, Mohammad Javad Mousavi, Carlos R Camara-Lemarroy, Farshid Noorbakhsh, Ali Akbar Saboor-Yaraghi","doi":"10.2174/0109298673335863240829060545","DOIUrl":"https://doi.org/10.2174/0109298673335863240829060545","url":null,"abstract":": The intestinal barrier, a critical component of the body's defense system, plays a vital role in maintaining homeostasis by preventing the translocation of harmful substances from the gut lumen into the bloodstream. Disruptions in this barrier, often characterized by increased intestinal permeability, are increasingly recognized as contributors to the development and progression of various Chronic Inflammatory Disorders (CIDs). Zonulin, a key regulator of intestinal Tight Junctions (TJs), has emerged as a pivotal player in this process. Dysregulation of zonulin, leading to increased intestinal permeability, has been implicated in the pathogenesis of a wide range of CIDs, including Inflammatory Bowel Disease (IBD), celiac disease, and Multiple Sclerosis (MS). This review examines the intricate relationship between zonulin and intestinal permeability, emphasizing its role in regulating TJ integrity and its association with various CIDs. Recent research has demonstrated the therapeutic potential of targeting zonulin, specifically through the use of larazotide acetate, a zonulin antagonist. Preclinical and clinical studies have shown promising results in improving gut barrier integrity and reducing inflammation in patients with CIDs. These findings underscore the significance of zonulin as a potential biomarker for intestinal barrier function and a promising therapeutic target for managing CIDs. Further research is needed to elucidate the precise mechanisms of action of zonulin antagonists and evaluate their efficacy and safety in clinical trials. A deeper understanding of the complex interplay among zonulin, intestinal permeability, and CIDs is crucial, paving the way for novel therapeutic strategies and personalized approaches to patient care.","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"To Elucidate the Effective Role of Small Molecule Regulated lncRNAs in the Tumour Microenvironment in Immunotherapy","authors":"Ahmed Saad Abdullah Al-Qaysi, Ayşe Hale Alkan, İbrahim Gadashli, Demet Cansaran-Duman","doi":"10.2174/0109298673318929240829065611","DOIUrl":"https://doi.org/10.2174/0109298673318929240829065611","url":null,"abstract":"The tumour microenvironment is a complex ecosystem comprising tumour cells, and cancer stem cells, and support cells that facilitate cancer growth and escape from treatment. Cancer immunotherapy focuses on immunological pathways such as PD-1/PD-L1 and CTLA-4 to target cancer stem cells via immune cells. Small molecules, immune checkpoint inhibitors, are employed to impede tumour growth by targeting cellular mediators in the cell cycle and tumour microenvironment. Long non-coding RNAs (lncRNAs) affect the growth, development, motility, and differentiation of cancer cells by regulating gene expression and are therefore considered important biomarkers. Small molecules demonstrate their effects on gene expression and behaviour of cancer cells by inducing lncRNAs. This relationship between lncRNAs and small molecules is of great importance in terms of their impact on cancer and the tumour microenvironment. The evaluation of this communication in clinical trials is of critical importance for the development of therapeutic strategies. This review provides a detailed description of the role of lncRNAs and small molecules in the tumour microenvironment and their relationship with cancer stem cells. Thus, the potential of controlling lncRNAs and using anti-cancer small molecules in TME to improve the efficacy of cancer therapy was evaluated.","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role and Therapeutic Potential of P2X7 Receptor in Lung Cancer Progression","authors":"Yahui Cao, Yanan Du, Wei Song, Qingqing Yu, Xin Wang, Ronglan Zhao, Xiaoxiang Peng","doi":"10.2174/0109298673331527240829080249","DOIUrl":"https://doi.org/10.2174/0109298673331527240829080249","url":null,"abstract":"Lung cancer is the second malignant tumor in the world and is the most prevalent malignant tumor of the respiratory system. In lung cancer, the P2X7 receptor (P2X7R) is an important purinergic receptor. P2X7R is a class of ionotropic adenosine triphosphate (ATP)-gated receptors, which exists in many kinds of immune tissues and cells and is involved in tumorigenesis and progression. P2X7R is closely related to lung cancer and is expressed at higher levels in lung cancer than in normal lung tissue. P2X7R plays a critical regulatory function in lung cancer invasion and migration through multiple mechanisms of action and affects the proliferation and apoptosis of cancer cells in the lung. Antagonists of P2X7R can block its function, which in turn has a significant inhibitory effect on lung cancer cell development and progression. This paper details a comprehensive overview of the structure and function of P2X7R. It focuses on the impact and treatment potential of P2X7R in lung cancer invasion, migration, proliferation, and apoptosis, providing new ideas and a new basis for clinical lung cancer treatment and prognosis.","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANGPTL4-the Link Binding Lipid Metabolism and Inflammation","authors":"Yueqi Zhang, Jingwen liang, Lei Dai, Yuyue Zuo, Zhi Li","doi":"10.2174/0109298673320024240829070906","DOIUrl":"https://doi.org/10.2174/0109298673320024240829070906","url":null,"abstract":"Background: Angiopoietin-like 4 (ANGPTL4) belongs to the family of angiopoietin- like proteins. The involvement of ANGPTL4 in various aspects of lipid metabolism and inflammation has become an important area of research. Methods: A thorough search on PubMed related to ANGPTL4, lipid metabolism, and inflammation was performed. Results: Over the past two decades, the recognition of ANGPTL4 as a potent regulator of lipid metabolism has substantially increased. As part of the senescence-associated secretory phenotype, ANGPTL4 also serves as an inflammatory mediator. Considering the advancements in ANGPTL4 research, we have highlighted that ANGPTL4 acts as a key node linking lipid metabolism and inflammation. ANGPTL4 impacts inflammation by regulating lipid metabolism. It affects critical enzymes (lipoprotein lipase, hepatic lipase, endothelial lipase, and acetyl-CoA carboxylase), regulatory factors (AMPK, cAMP, SLC7A11, GPX4, and mTOR), and receptors (LepR, CD36, and PPARγ) of lipid oxidation, synthesis, and peroxidation, thereby affecting immune cells and inflammatory pathways. Conclusion: Understanding the potential association and the therapeutic value of ANGPTL4 for regulating lipid metabolism and inflammation could contribute to drug discovery and therapeutic development.","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression Profile and Prognostic Values of IRX Family Members in Lung Adenocarcinoma.","authors":"Jieli Zhang, Yanqiu Zhou, Xiaoli Li, Shufang Wang, Peng Zhang, Dongbing Li, Yunzhi Zhou","doi":"10.2174/0109298673320965240829065919","DOIUrl":"https://doi.org/10.2174/0109298673320965240829065919","url":null,"abstract":"<p><strong>Background: </strong>The potential role of the iroquois homeobox (IRX) genes in tumorigenesis is a subject of interest, yet their specific involvement in lung adenocarcinoma (LUAD) has not been extensively examined.</p><p><strong>Objective: </strong>This research endeavored to explore the impact of the IRX genes on the onset and progression of LUAD.</p><p><strong>Methods: </strong>Utilizing data from The Cancer Genome Atlas (TCGA), samples of LUAD were selected for analysis. The influence of the IRX genes was scrutinized through various tools, including Kaplan-Meier Plotter, cBioPortal, and the R programming language (version 3.6.3), with gene expression levels being confirmed in cellular models via quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>It was observed that the levels of IRX1/2/3/6 were notably diminished in LUAD tissues when juxtaposed with healthy lung tissue. Conversely, the expression of IRX4 was found to be elevated in LUAD. Correlations were identified between IRX gene expression and several clinical parameters such as T stage, smoking history quantified in pack-years, lymph node involvement, patient gender, initial treatment responses, and smoking status. The diminished expression of IRX2/5 emerged as a significant indicator of an unfavorable prognosis in LUAD. The study also highlighted the potential of various IRX genes as diagnostic indicators for LUAD. These genes were implicated in the facilitation of LUAD's growth and spread through a range of biological pathways, encompassing the Ras signaling and more. Additionally, a pronounced link was discovered between the infiltration of immune cells and the expression patterns of the IRX genes. IRX genes were abnormally expressed in LUAD cell lines.</p><p><strong>Conclusion: </strong>IRX gene family could serve not only as indicators of LUAD prognosis but also as therapeutic targets for LUAD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of a PANoptosis-related Prognostic Signature for Predicting Prognosis, Tumor Microenvironment, and Immune Response in Ovarian Cancer.","authors":"Yonghong Li, Guizhen Lyu","doi":"10.2174/0109298673314864240829064622","DOIUrl":"https://doi.org/10.2174/0109298673314864240829064622","url":null,"abstract":"<p><strong>Background: </strong>The PANoptosis pathway is a recently identified mechanism of cellular death that involves the interaction and synchronization among cellular pyroptosis, apoptosis, and necrosis. More and more evidence suggests that PANoptosis is involved in the development and treatment of cancer. However, a comprehensive understanding of the influence of PANoptosis genes on prognostic value, tumor microenvironment characteristics, and therapeutic outcomes in patients with ovarian cancer (OC) remains incomplete.</p><p><strong>Objective: </strong>The present work was designed to devise a PANoptosis signature for OC prognosis and explore its potential molecular function.</p><p><strong>Methods: </strong>For this study, we obtained RNA sequencing and clinical data for ovarian cancer from the Cancer Genome Atlas (TCGA) and the GSE32062 cohort. Somatic variants of PANoptosis-related genes (PRGs) in OC were analyzed using GSCA. TCGA-OC and GSE32062 were used to construct training and validation cohorts for the model. Differential expression and correlation analyses were performed following the screening of genes with prognostic ability using univariate Cox analysis. Least Absolute Shrinkage and Selection Operator (LASSO) regression was performed to construct PRG signature based on genes that were differentially expressed and correlated with prognosis. CIBERSORT and ESTIMATE were used to analyze the relationship between the PRGs signature and immune infiltration. TIDE was used to analyze the relationship between the PRG signature and immune checkpoint genes. OncoPredict was used to analyze the relationship between the PRG signature and the drug sensitivity. Quantitative real-time PCR (qRT-PCR) was used to validate the expression of PRGs in OC.</p><p><strong>Results: </strong>The PRG signature was constructed using three prognostic genes (AIM2, APAF1, and ZBP1) in both TCGA-OC. The results showed that the PRGs signature had an AUC of 0.521, 0.546, and 0.598 in TCGA-OC and 0.620, 0.586, and 0.579 in GSE32062 to predict to predict OS at 1-, 3-, and 5-year intervals. Furthermore, a higher PRG signature risk score was significantly associated with shorter OS (HR = 1.693, 95% CI: 1.303 - 2.202, p = 8.34 × 10^-5 in TCGA-OC and HR = 1.63, 95% CI: 1.13 - 2.35, p = 0.009 in GSE32062). The risk score was identified as the independent prognostic factor for OC. Patients categorized according to their risk score exhibited notable variations in immune status, response to immunotherapy, and sensitivity to drugs. AIM2, APAF1, and ZBP1 were significantly aberrantly expressed in OC cell lines.</p><p><strong>Conclusion: </strong>The PRG signature has the potential to serve as a prognostic predictor for OC and to provide new insights into OC treatment.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics Analysis Screening and Identification of Key Biomarkers and Drug Targets in Human Glioblastoma.","authors":"Chunlei Wang, Ozal Beylerli, Yan Gu, Shancai Xu, Zhiyong Ji, Tatiana Ilyasova, Ilgiz Gareev, Vladimir Chekhonin","doi":"10.2174/0109298673316883240829073901","DOIUrl":"https://doi.org/10.2174/0109298673316883240829073901","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma is the most common type of brain cancer, with a prognosis that is unfortunately poor. Despite considerable progress in the field, the intricate molecular basis of this cancer remains elusive.</p><p><strong>Aim: </strong>The aim of this study was to identify genetic indicators of glioblastoma and reveal the processes behind its development.</p><p><strong>Objective: </strong>The advent and integration of supercomputing technology have led to a significant advancement in gene expression analysis platforms. Microarray analysis has gained recognition for its pivotal role in oncology, crucial for the molecular categorization of tumors, diagnosis, prognosis, stratification of patients, forecasting tumor responses, and pinpointing new targets for drug discovery. Numerous databases dedicated to cancer research, including the Gene Expression Omnibus (GEO) database, have been established. Identifying differentially expressed genes (DEGs) and key genes deepens our understanding of the initiation of glioblastoma, potentially unveiling novel markers for diagnosis and prognosis, as well as targets for the treatment of glioblastoma.</p><p><strong>Methods: </strong>This research sought to discover genes implicated in the development and progression of glioblastoma by analyzing microarray datasets GSE13276, GSE14805, and GSE109857 from the GEO database. DEGs were identified, and a function enrichment analysis was performed. Additionally, a protein-protein interaction network (PPI) was constructed, followed by module analysis using the tools STRING and Cytoscape.</p><p><strong>Results: </strong>The analysis yielded 88 DEGs, consisting of 66 upregulated and 22 downregulated genes. These genes' functions and pathways primarily involved microtubule activity, mitotic cytokinesis, cerebral cortex development, localization of proteins to the kinetochore, and the condensation of chromosomes during mitosis. A group of 27 pivotal genes was pinpointed, with biological process analysis indicating significant enrichment in activities, such as division of the nucleus during mitosis, cell division, maintaining cohesion between sister chromatids, segregation of sister chromatids during mitosis, and cytokinesis. The survival analysis indicated that certain genes, including PCNA clamp-associated factor (PCLAF), ribonucleoside- diphosphate reductase subunit M2 (RRM2), nucleolar and spindle-associated protein 1 (NUSAP1), and kinesin family member 23 (KIF23), could be instrumental in the development, invasion, or recurrence of glioblastoma.</p><p><strong>Conclusion: </strong>The identification of DEGs and key genes in this study advances our comprehension of the molecular pathways that contribute to the oncogenesis and progression of glioblastoma. This research provides valuable insights into potential diagnostic and therapeutic targets for glioblastoma.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Review and Meta-analysis Indicating Curcumin to Enhance the Synergistic Potential of Paclitaxel and Reduce Cell Viability, Tumor Volume, and Drug Resistance in Different Cancers.","authors":"Yasmin Fatima, Agneesh Pratim Das, Gaurab Kumar Jha, Subhash Mohan Agarwal","doi":"10.2174/0109298673313858240826105305","DOIUrl":"https://doi.org/10.2174/0109298673313858240826105305","url":null,"abstract":"<p><strong>Background: </strong>To treat diseases like cancer, conventional Paclitaxel (PTX)- based monotherapy treatment regimens are becoming less effective due to the development of resistance. In this aspect, the phytomolecule curcumin (Cur), having ethnopharmacological importance in traditional South Asian remedies, like Ayurveda and Chinese traditional medicine, has been studied as a promising chemo-sensitizing and synergistic partner of PTX.</p><p><strong>Aim: </strong>This study aimed to evaluate the combined effect of PTX and Cur compared to PTX therapy alone in the in vitro and in vivo environments.</p><p><strong>Material and methods: </strong>An extensive PubMed search was performed wherein 169 papers were shortlisted and screened to identify 30 studies that have reported the effect of PTX and Cur either in vitro, in vivo, or both. The pooled Odds Ratio (OR) was calculated at a 95% Confidence Interval (CI) for determining the effect of combination therapy.</p><p><strong>Results: </strong>The meta-analysis has indicated PTX and Cur combination therapy to be associated with a significant decrease in cell viability (OR: 0.37, 95% CI: 0.27-0.51; p < 0.01) and tumor volume (OR: 0.32, 95% CI: 0.15-0.71; p = 0.01). Additionally, the effect of this combination on drug-resistant cell lines has exhibited a significant decrease in the odds of cell viability (OR: 0.45, 95% CI: 0.35-0.57; p < 0.01).</p><p><strong>Conclusion: </strong>Overall, the current meta-analysis has shown PTX and Cur combination to effectively inhibit the viability of cancer cells, reduce tumor volume, and diminish the growth of drug-resistant cancer cells.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay between Pro-inflammatory Mediators and Oxidative Stressinvolved Recurrent Chronic Heart Failure in Elderly Patients with Coronary Stents.","authors":"Xia Li, Yongjuan Zhao, Hualan Zhou, Youdong Hu, Ying Chen, Dianxuan Guo","doi":"10.2174/0109298673309995240829060533","DOIUrl":"https://doi.org/10.2174/0109298673309995240829060533","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Inflammation and oxidative stress are related to congestive heart failure in patients with coronary heart disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Chronic congestive heart failure is a serious stage of coronary artery disease and is mainly a disease of elderly people over the age of 65. Elderly heart failure patients are characterized by myocardial ischemia, and post-ischemic myocardial dysfunction. Oxidative Stress, inflammation, and immune response play important roles in the development of heart failure. We tried to examine the mutual triggering of oxidative stress (malondialdehyde), inflammatory cytokines (tumor necrosis factor-α and soluble tumor necrosis factor receptor-1/2), immune response (toll-like receptors 2,3,4), and high sensitivity C-reactive protein expression in elderly patients with recurrent congestive heart failure after coronary stenting and investigated the effect of interplay of these changes on onset and progression of recurrent congestive heart failure in elderly patients underwent coronary stent implantation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 726 patients were enrolled in this study. We determined the levels of malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF- α), soluble tumor necrosis factor receptor-1 and 2 (sTNFR-1/2) and toll-like receptor 2,3,4 (TLR2/3/4) in elderly patients with recurrent congestive heart failure after coronary artery stent implantation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Levels of MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4 were remarkably increased (p&lt;0.01) in elderly patients with recurrent congestive heart failure after coronary artery stenting. The results indicated that these markers were closely correlated to each other and showed that these markers were associated with increased New York Heart Association functional classification and low left ventricular ejection fractions. Further analysis confirmed that the independent clinical risk factors for recurrent congestive heart failure were MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4. The interplay of oxidative stress, inflammatory cytokines and toll-like receptors, and hs-CRP expression levels was an important factor involved in recurrent congestive heart failure of elderly patients after coronary stenting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;High levels of MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4 had an important implication for recurrent heart failure with increased New York Heart Association functional classification and low left ventricular ejection fractions. These eight factors amplified each other's positive effects and this interaction may be a key element of their roles in recurrent heart failure. The eight risk factors were inter-dependent and occurred simultaneously, and exerted detrimental effects forming a vicious circle. MDA may trigger the over-expressions of pro-inflammatory risk factors (hs-CR","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Subtypes Based on Mitochondrial Oxidative Stress-related Gene Signature and Tumor Microenvironment Infiltration Characterization of Colon Adenocarcinoma.","authors":"Peijia Cong, Ruixue Xu, Ziru Tan, Xiaolin Wu, Haifeng Lian, Dan Li","doi":"10.2174/0109298673318692240829053543","DOIUrl":"https://doi.org/10.2174/0109298673318692240829053543","url":null,"abstract":"<p><strong>Background: </strong>As the most common subtype of colorectal cancer, colorectal adenocarcinoma (COAD) still needs better prognostic stratification methods and new intervention targets. The mitochondrial stress response, linked to mitochondrial homeostasis and cancer metabolism, warrants further investigation.</p><p><strong>Methods: </strong>We identified mitochondrial oxidative stress-related genes (MOS) associated with COAD prognosis through the TCGA and GEO databases. Molecular subtype characteristics were identified based on MOS gene signatures, and an MOS scoring system was established to comprehensively evaluate its clinical value. Additionally, the effect of one of the screened genes, NDRG1, was investigated through a series of in vitro experiments, including Western blot, qRT-PCR, CCK8 assay, clone formation, and Transwell assay, to explore its impact on COAD proliferation and migration ability.</p><p><strong>Results: </strong>Our analysis revealed that MOS gene signatures effectively distinguished molecular subtypes of COAD, and the MOS scoring system was found to be independent in predicting prognosis. Evaluation of microenvironment infiltration characteristics, mutation characteristics, immunotherapy response, and drug sensitivity analysis further suggested the potential clinical utility of this study. in vitro experimental results showed that NDRG1 significantly affected the proliferation and migration of COAD cells, partially verifying the reliability of our bioinformatics analysis.</p><p><strong>Conclusion: </strong>This study provides a novel perspective on the role of mitochondrial oxidative stress in COAD, proposing innovative prognostic evaluation methods and potential therapeutic targets, thus offering new directions for the clinical treatment of COAD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}