Current medicinal chemistry最新文献

{"title":"From Proteomics to Diagnosis: Biomarker Discovery in Tuberculosis Research.","authors":"Jiarong Yang, Jianhua Zheng","doi":"10.2174/0109298673346264241008110105","DOIUrl":"https://doi.org/10.2174/0109298673346264241008110105","url":null,"abstract":"<p><p>Tuberculosis (TB) is a leading cause of death from a single infectious disease worldwide. Early and accurate diagnosis is advantageous for timely detection and prompt treatment, thereby reducing the risk of disease transmission, which is essential for effective TB control. Biomarkers provide a valuable resource for TB diagnosis. Proteomic technologies have emerged as a powerful tool in biomarker discovery. In this perspective, we explore how proteomic technologies contribute to the discovery of TB diagnostic biomarkers. We also address the challenges and discuss prospective methods to augment the performance of biomarkers in diagnosing TB.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460072","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":"FOXN3-AS1: A Candidate Prognostic Marker and Epigenetic Target with Immunotherapeutic Implications in Acute Myeloid Leukemia.","authors":"Fangfang Ge, Yulu Wang, Peng Chen, Amit Sharma, Xiaoli Huang, Tikam Chand Dakal, Zifeng Wang, Ulrich Jaehde, Markus Essler, Matthias Schmid, Ingo G H Schmidt-Wolf","doi":"10.2174/0109298673311108240926062214","DOIUrl":"https://doi.org/10.2174/0109298673311108240926062214","url":null,"abstract":"<p><strong>Aim: </strong>We focused on the FOXN3 gene and selected its antisense transcripts (FOXN3-AS1) to investigate its potential involvement in acute myeloid leukemia (AML).</p><p><strong>Background: </strong>Several integrated multi-omics datasets have expanded the horizons of the cancer landscape. With the emergence of new high-throughput technologies, a large number of non-coding RNAs have been confirmed to be involved in the pathogenesis of different types of hematological malignancies.</p><p><strong>Methods: </strong>We conducted experimental validation using quantitative polymerase chain reaction (qPCR) with bone marrow specimens from AML patients. Then, Kaplan-Meier (KM) and Receiver Operating Characteristic (ROC) curves were used to substantiate the prognostic association between FOXN3-AS1 and AML patients within the TCGA database. Correlation between FOXN3-AS1 expression and gene mutation, immune, and immune function using Spearman correlation analysis. To explore the physical and functional interaction between FOXN3-AS1 and the DNMT1 protein, we utilized the RPISeq web tool from Iowa State University. Subsequently, we performed qPCR experiments to test the effect of 5AzaC (DNMT1 inhibitor) on FOXN3-AS1 expression AML cell lines (THP1 and OCI-AML3). We leveraged the \"OncoPredict\" R package in conjunction with the Genomics of Drug Sensitivity (GDSC) database to predict drug response in AML patients expressing FOXN3-AS1.</p><p><strong>Results: </strong>We observed a significant upregulation of FOXN3-AS1 expression in AML patients compared to healthy controls using clinical samples. The TCGA database revealed an association between high FOXN3-AS1 expression and adverse prognosis. In our subsequent analysis, genes with poor prognostic implications in AML patients were exclusively identified in the FOXN3-AS1 high-expression group, further corroborating this relationship. AML patients with higher FOXN3-AS1 expression levels may respond less optimally to immunotherapy than patients with lower levels. Besides, we computationally predicted the interaction of FOXN3- AS1 and DNMT1 protein and experimentally confirmed that DNMT1i (GSK-3484862) affects the expression level of FOXN3-AS1. We also found that the chemotherapy drugs (5-Fluorouralic, Cisplatin, Dactolisib, Sapitinib, Temozolomide, Ulixertinib, Vinorelbine, Ruxolitinib, Osimertinib and Cisplatin) showed favorable responses in AML patients with high FOXN3-AS1 expression levels.</p><p><strong>Conclusion: </strong>Our candidate approach identifies FOXN3-AS1 as a prognostic indicator of survival in AML with a potential immune-related role. The preliminary observations we made on FOXN3-AS1/DNMT1 crosstalk warrant more in-depth invested immunotherapeutic approaches in AML.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460071","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":"Implementation of an Automated System Using Machine Learning Models to Accelerate the Process of In Silico Identification of Small Molecules As Drug Candidates.","authors":"Tuba Sevimoglu","doi":"10.2174/0109298673334173241003060139","DOIUrl":"https://doi.org/10.2174/0109298673334173241003060139","url":null,"abstract":"<p><p>Drugs are commonly utilized to diagnose, cure, or prevent the occurrence of diseases, as well as to restore, alter, or change organic functions. Drug discovery is a time-consuming, costly, difficult, and inefficient process that yields very few medicinal breakthroughs. Drug research and design involves the capturing of structural information for biological targets and small molecules as well as various in silico methods, such as molecular docking and molecular dynamic simulation. This article proposes the idea of expediting computational drug development through a collaboration of scientists and universities, similar to the Human Genome Project using machine learning (ML) strategies. We envision an automated system where readily available or novel small molecules (chemical or plant-derived), as well as their biological targets, are uploaded to an online database, which is constantly updated. For this system to function, machine learning strategies have to be implemented, and high-quality datasets and high quality assurance of the ML models will be required. ML can be applied to all computational drug discovery fields, including hit discovery, target validation, lead optimization, drug repurposing, and data mining of small compounds and biomolecule structures. Researchers from various disciplines, such as bioengineers, bioinformaticians, geneticists, chemists, computer and software engineers, and pharmacists, are expected to collaborate to establish a solid workflow and certain parameters as well as constraints for a successful outcome. This automated system may help speed up the drug discovery process while also lowering the number of unsuccessful drug candidates. Additionally, this system will decrease the workload, especially in computational studies, and expedite the process of drug design. As a result, a drug may be manufactured in a relatively short time.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399698","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":"Discovery of 5-(Substituted Phenyl)-2-aryl Benzimidazole Derivatives as SIRT1 Activators: Their Design, in silico Studies, Synthesis, and in vitro Evaluation.","authors":"Shilpi Chauhan, Ashwani Kumar, Rajnish Kumar, Deepika Saini","doi":"10.2174/0109298673330534240924104941","DOIUrl":"https://doi.org/10.2174/0109298673330534240924104941","url":null,"abstract":"<p><strong>Aim: </strong>Silent information regulator two homologue one (SIRT1) is an emerging target for managing metabolic disorders. This study aimed to synthesize novel 5-(- substituted phenyl)-2-aryl benzimidazole derivatives and evaluate them for SIRT1 activation.</p><p><strong>Methods: </strong>The compounds were designed according to the findings of the QSAR models framed in our previous studies. Molecular docking and dynamics studies were also performed to explore the interactions of designed compounds with the active site of the SIRT1 enzyme using AutoDock Vina and Schrödinger Maestro version 11.8.012, respectively. Compounds with good binding affinity were synthesized by Suzuki-Miyaura cross-coupling and spectrally characterized. The molecules were evaluated for their in vitro SIRT1 activation properties using a fluorescent screening kit. Based on the results of in vitro assay, a structure-activity relationship was established. SwissADME was employed to calculate the pharmacokinetics characteristics of the synthesized molecules.</p><p><strong>Results: </strong>The molecular docking studies revealed that all the activators were effectively docked in the catalytic active site. All compounds demonstrated interactions with important amino acids like Glu230 and Arg446. In molecular dynamics simulations, the root mean square deviation (RMSD) of compound 5m and protein SIRT1 remained stable, i.e., below 3mm. Compound 5m, 4-(2-(3,4-dihydroxy-5-nitrophenyl)-1H-benzo[d]imidazol- 5-yl)benzaldehyde, was the most potent compound with an EC50 value of 0.006 mM (±0.001) and maximum activation of 240.5%. All the synthesized compounds had acceptable theoretical ADME profiles, and drug-likeness properties complied with Lipinski's rule.</p><p><strong>Conclusion: </strong>According to the findings, synthesized compounds may be viable leads for SIRT1 activators and may be used to advance preclinical in vivo research utilizing animal models.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399697","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":"Anticancer Drug Discovery from Natural Compounds Targeting PI3K/AKT/mTOR Signaling Pathway.","authors":"Manuele Figueiredo da Silva, Arestides Alves Lins, Midiane Correia Gomes, Washley Phyama de Jesus Marinho, Rodrigo Santos Aquino de Araújo, Ricardo Olimpio de Moura, Peng Zhan, Igor José Dos Santos Nascimento, Edeildo Ferreira da Silva-Júnior","doi":"10.2174/0109298673325229240928040758","DOIUrl":"https://doi.org/10.2174/0109298673325229240928040758","url":null,"abstract":"<p><p>The term cancer is used to describe a complex pathology characterized by the uncontrollable proliferation of cells, which displays a fast metastatic spread, being a disease with difficult treatment. In this context, Phosphatidylinositol 3-kinase (PI3K) represents a promising pathway to be inhibited, aiming to develop anticancer agents, since it performs a pivotal role in regulating essential cellular processes, including cell proliferation, growth, autophagy, and apoptosis. In parallel, natural compounds can effectively represent a therapeutic strategy to fight against malignant cells. Then, compounds derived from various plant sources, such as flavonoids, terpenoids, alkaloids, coumarins, and lignans, have exhibited remarkable in vitro and in vivo anticancer properties. This review focused in the exploration of natural products targeting the PI3K/AKT/m-TOR signaling pathway, demonstrating that these compounds could even further investigated to reveal novel and effective anticancer drugs in the future.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399685","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":"Multi-Target Mechanisms of Si-Ni-San on Anxious Insomnia: An Example of Network-pharmacology and Molecular Docking Analysis.","authors":"Chih Ting Lin, Hsin Yi Lin, Wen Huang Peng, Lung Yuan Wu","doi":"10.2174/0109298673299665240924090617","DOIUrl":"https://doi.org/10.2174/0109298673299665240924090617","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Based on comprehensive network-pharmacology and molecular docking analysis, this study was intended to unveil the multiple mechanisms of Si-Ni-San (SNS) in treating anxious insomnia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The compounds of SNS were meticulously analyzed, selected and standardized with references to their pharmacological attributes. The components included chaihu (Bupleurum chinense DC.), baishao (Paeonia lactiflora Pall.), zhishi (Citrus aurantium L.) and gancao (Glycyrrhiza uralensis Fisch. ex DC.). We used the Traditional Chinese Medicine System Pharmacology (TCMSP) Database, Traditional Chinese Medicines Integrated Database (TCMID), GeneCards database, therapeutic target database (TTD) and comparative toxicogenomic database (CTD) to construct the components-compounds-targets networks and used Cytoscape 3.9.1 software to visualize the outcome. Afterwards, the STRING database and Cytoscape 3.9.1 software were utilized to construct and visualize the protein-protein interaction (PPI) network analysis. In addition, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were also conducted through the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The molecular docking program was carried out using AutoDock 4.2 software to understand interactions between target receptors and compound ligands selected for study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We thoroughly sorted and filtered 31 pharmacologically active compounds from SNS. Subsequently, several potential target genes were predicted, of which there were 59 target genes distinctly associated with anxious insomnia. The PPI analysis indicated that the core target proteins included AKT1, IL6, TNF, SLC6A4, MAOA and GABRA2. The results of our study indicated that SNS potentially remediates anxious insomnia by reducing inflammation, neurodegeneration, and cell apoptosis of neurons. In addition, GO and KEGG enrichment analysis results indicated that SNS could modulate multiple aspects of anxious insomnia through mechanisms related to pathways of neuroactive ligand-receptor interaction. These pathways include various kinds of synaptic transmission pathways, and anti-inflammatory activity associated with response pathways. When we compared the components-compounds-targets networks and the compounds-targets-synaptic pathways networks, the five active compounds, including beta-Sitosterol, Kaempferol, Tetramethoxyluteolin, Isorhamnetin and Shinpterocarpin, were selected to conduct molecular docking experiments. Eleven target proteins, (AKT1, SLC6A4, ADRB2, MAOA, ACHE, ESR1, CYP3A4, CHRNA7, GABRA2, HTR2A and NOS3), which also play significant roles in regulating serotonergic, cholinergic, dopaminergic and GABAergic systems in the PPI network, were selected to act as receptors in molecular docking trials. The results showed that docking pairs isorhamnetin-AKT1, isorhamnetin-SLC6A4, β-sito","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460079","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 of Ferroptosis in ALD: Focusing on Hepcidin and Besides Hepcidin.","authors":"Leijie Chen, Hejun Zhou, Zongyong Cheng, Deliang Liu, Yuyong Tan","doi":"10.2174/0109298673317526240924050651","DOIUrl":"https://doi.org/10.2174/0109298673317526240924050651","url":null,"abstract":"<p><p>Ascending incidence and poor outcomes make Alcoholic Liver Disease (ALD) a considerable public health concern. This review concluded the iron metabolism under physiology conditions and alcohol disturbance (leading to ferroptosis in ALD) and summarized the novel treatment, diagnosis, and prognosis of ferroptosis for ALD. ALD is characterized by alcohol-induced chronic metabolism disorder, peroxidation damage, and dysfunction of the anti-oxidant system. Current animal experiments and clinical studies identified ferroptosis as a new form of regulated cell death involved in ALD. One strong evidence is that the key iron regulatory hormone, hepcidin, is downgraded in ALD through NF-κB/IL-6/STAT3, BMP/SMAD, and Jak/STAT3 pathways, which would impair iron hemostasis and induce ferroptosis in ALD. Also, imbalance metabolism and other pathological responses in ALD induce and regulate ferroptosis, which proves ferroptosis participates in the pathophysiology of ALD via oxidative stress, steatosis, and fibrosis. Inhibition of ferroptosis via regulating hepcidin expression and metabolism impairment may provide new therapies for ALD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460083","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":"Lipidomics in Periodontal Disease Research: A Systematic Review.","authors":"Carolina Silva, Francisco Peixoto, Isabel Dias, Rosário Domingues, Carlos Viegas","doi":"10.2174/0109298673323591240923051742","DOIUrl":"https://doi.org/10.2174/0109298673323591240923051742","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Periodontal disease is a highly prevalent oral pathology in the human population, which has a significant local and systemic impact. Currently, multi-omics analyses, including lipidomics, are fundamental to obtaining an in-depth molecular understanding of the individual. Lipidomics is dedicated to the study of lipid species and their interactions in various health contexts. This specific multi-omics analysis is important for understanding the alteration of metabolism and signaling in disease, identifying biochemical markers, and potential therapeutic targets. This study aimed to carry out a systematic review of the existing scientific literature on lipidomics in periodontal disease and thus determine which molecules have already been analyzed and their potential in this specific disease.</p><p><strong>Methods: </strong>This study followed the recommendations of the PRISMA 2020 methodology. The inclusion criteria used were articles published in indexed journals between 2000 and 2023, written in English, and establishing an exclusive relationship about lipidomics in human periodontal disease. The articles were searched in three different databases.</p><p><strong>Results: </strong>Considering the criteria defined, only six articles were selected and zed individually in detail. In four of the six studies, differences in the lipidome of individuals with periodontal disease were identified. Furthermore, phosphoethanolamine ceramide was found to have potential as a diagnostic biomarker. Finally, the therapeutic potential of a lipoxin A4 analogue was also identified.</p><p><strong>Conclusion: </strong>These results reinforce the need for future research in this area so that the consequences of this disease on the lipidome can be identified.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388778","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":"Unveiling the Power of Mitochondrial Fission and Fusion: A Five-Gene Signature for Personalized Prognosis in Gastric Cancer.","authors":"Bin Zhou, Ping Tie, Dongbing Li, You Lu, Yuanhua Liu","doi":"10.2174/0109298673339515240930053412","DOIUrl":"https://doi.org/10.2174/0109298673339515240930053412","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial fission and fusion play important roles in tumorigenesis, progression and therapy. Dysregulation of these processes may lead to tumor progression, and regulation of these processes may provide novel strategies for cancer therapy. The involvement of genes related to mitochondrial fission and fusion (MD) in gastric cancer (GC) remains poorly understood.</p><p><strong>Objective: </strong>The aim of this study was to establish an MD gene signature for GC patients and to investigate its association with prognosis, tumor microenvironment and treatment response in GC.</p><p><strong>Methods: </strong>We use the TCGA-GC database as the cohort, focusing specifically on genes associated with MD. We conducted identification and consistency clustering analysis of differentially expressed genes in MD, conducted MD gene mutation and copy number variation analysis, as well as correlation and functional enrichment analysis between MD gene cluster classification and immune infiltration. TCGA-GC and GSE15459 were used to construct training and validation cohorts for the model. We used various statistical methods, including Cox and Lasso regression, to develop the model. We validated the model using bulk transcriptome and single- cell transcriptome datasets (GSE13861, GSE26901, GSE66229, and GSE13450). We used GSEA enrichment, CIBERSORT algorithm, ESTIMATE, and TIDE to gain insight into the annotation of MD signature and the characterization of the tumor microenvironment. OncoPredict was used to analyze the relationship between the PRG signature and the drug sensitivity. We validated the expression of several key genes in MD signature on GC cell lines using quantitative real-time PCR (qRT-PCR).</p><p><strong>Results: </strong>These MDs-related subtypes exhibited different prognosis and immune filtration patterns. A five-gene signature, comprising AGT, HCFC1, KIFC3, NOX4, and RIN1, was developed. There was a clear distinction in overall survival between low- and high-risk patients. The analyses showed further confirmation of the independent prognostic value of the gene signature. There was a notable correlation between the MD signature, immune infiltration and drug susceptibility. The expression levels of AGT, HCFC1, KIFC3, NOX4 and RIN1 mRNA were all increased in these GC cells.</p><p><strong>Conclusion: </strong>The MD signature has the capacity to significantly contribute to the prediction of personalized outcomes and the advancement of novel therapeutic strategies tailored for GC patients.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388781","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":"Development of a Mitochondrial Membrane Permeability Transition Prognosis System in Colon Adenocarcinoma: Risk Stratification and Therapeutic Target Identification.","authors":"Bomiao Zhang, Mingyu Xia, Shihui Zhao, Yien Li, Chenfeng Yu, Liqiang Song, Shaoke Wang, Binbin Cui","doi":"10.2174/0109298673335900240920070746","DOIUrl":"https://doi.org/10.2174/0109298673335900240920070746","url":null,"abstract":"<p><strong>Aims: </strong>Explore the role of mitochondrial membrane permeability transition (MPT) in colon adenocarcinoma (COAD).</p><p><strong>Background: </strong>Further exploration of risk stratification for COAD prognostic assessment has important clinical value. MPT-related pathways play a key role in the pathogenesis of many human diseases, including tumorigenesis. Its impact on COAD is still unknown.</p><p><strong>Objective: </strong>Bioinformatics analysis was conducted by analyzing the GEO database and TCGA database, and the bioinformatics results were verified by in vitro experiments.</p><p><strong>Method: </strong>Through the analysis of the transcriptome data of 1008 COAD samples in the GEO database and TCGA database, the differential expressions of MPT-related genes in COAD were explored, followed by molecular subtype analysis based on MPT characteristics by univariate Cox algorithm analysis and the consensus clustering algorithm. The gene signature associated with MPT molecular subtypes was further identified and the MPT scoring system was established by the LASSO-univariate Cox analysis algorithm. After evaluating the prognostic value of the MPT scoring system in COAD patients via nomogram establishment, the clinical value of the MPT scoring system was comprehensively analyzed through somatic mutation characteristics analysis, immunotherapy response analysis, immunoinfiltration analysis, and drug sensitivity analysis. CCK-8, WB, PCR, colony formation method, and Transwell method were used to verify the effect of the screened target on the proliferation and invasion of COAD cells.</p><p><strong>Result: </strong>We successfully established a scoring system related to MPT and validated the prognostic value of COAD patients. The potential clinical value of the MPT scoring system was also analyzed. VSIG4 was selected for further in vitro experiments to verify the effect of the screened targets on the proliferation and invasion ability of COAD cells.</p><p><strong>Conclusions: </strong>We established an MPT scoring system for effective risk stratification of COAD patients, demonstrating the impact of MPT on the development of COAD and its potential value as an intervention factor.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388768","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}