{"title":"Transfer Learning for Automated Two-class Classification of Pulmonary Tuberculosis in Chest X-Ray Images.","authors":"Akansha Nayyar, Rahul Shrivastava, Shruti Jain","doi":"10.2174/0109298673375085250704061619","DOIUrl":"https://doi.org/10.2174/0109298673375085250704061619","url":null,"abstract":"<p><strong>Aim: </strong>Early and precise diagnosis is essential for effectively treating and managing pulmonary tuberculosis. The purpose of this research is to leverage artificial intelligence (AI), specifically convolutional neural networks (CNNs), to expedite the diagnosis of tuberculosis (TB) using chest X-ray (CXR) images.</p><p><strong>Background: </strong>Mycobacterium tuberculosis, an aerobic bacterium, is the causative agent of TB. The disease remains a global health challenge, particularly in densely populated countries. Early detection via chest X-rays is crucial, but limited medical expertise hampers timely diagnosis.</p><p><strong>Objective: </strong>This study explores the application of CNNs, a highly efficient method, for automated TB detection, especially in areas with limited medical expertise.</p><p><strong>Methods: </strong>Previously trained models, specifically VGG-16, VGG-19, ResNet 50, and Inception v3, were used to validate the data. Effective feature extraction and classification in medical image analysis, especially in TB diagnosis, is facilitated by the distinct design and capabilities that each model offers. VGG-16 and VGG-19 are very good at identifying minute distinctions and hierarchical characteristics from CXR images; on the other hand, ResNet 50 avoids overfitting while retaining both low and high-level features. The inception v3 model is quite useful for examining various complex patterns in a CXR image with its capacity to extract multi-scale features.</p><p><strong>Results: </strong>Inception v3 outperformed other models, attaining 97.60% accuracy without pre-processing and 98.78% with pre-processing.</p><p><strong>Conclusion: </strong>The proposed model shows promising results as a tool for improving TB diagnosis, and reducing the global impact of the disease, but further validation with larger and more diverse datasets is needed.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689461","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}
Min Li, Yang Yang, Ran Wang, Wufu Zhu, Yuanbiao Tu, Pengwu Zheng, LinXiao Wang
{"title":"Machine Learning, Virtual Screening and Bioactivity Evaluation to Identify AJ-292/12941271 as an Anti-proliferative Agent and Target mTOR Protein.","authors":"Min Li, Yang Yang, Ran Wang, Wufu Zhu, Yuanbiao Tu, Pengwu Zheng, LinXiao Wang","doi":"10.2174/0109298673362945250628044807","DOIUrl":"https://doi.org/10.2174/0109298673362945250628044807","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this study is to obtain inhibitors against mTOR targets with virtual screening, dynamic simulation and bioactivity assessment. This pursuit aims to obtain a rapid and accurate method for the discovery of new mTOR inhibitors.</p><p><strong>Methods: </strong>Firstly, the researchers obtained nearly 9000 compounds by using ROC-guided machine learning from a library of over 200000 compounds. Secondly, virtual screening was used to evaluate the affinity of 45 compounds. Further analysis was performed to identify 6 hit compounds. Simultaneously, MTT antitumor activity evaluation and kinase inhibition assays are conducted for the active compounds to discern the most promising candidates. Furthermore, AO staining and JC-1 assays are performed for the selected compounds. Simultaneously, MTT antitumor activity evaluation and kinase inhibition assays are conducted for the active compounds to discern the most promising candidates. Furthermore, AO staining, JC-1 and hemolytic toxicity evaluation assays are performed for the selected compounds.</p><p><strong>Results: </strong>The kinase assay demonstrates that these 6 compounds display greater sensitivity to mTOR than to PI3K. Among them, compounds AJ-292/12941271 and AG-205/12550019 show better activity against mTOR target than PI3K, with an IC50 of 2.55 and 4.48 μM, respectively. Additionally, the anti-proliferative activity of the six hit compounds was also considered. Compound AJ-292/12941271 shows the best anticancer activity against A549 cell lines with an IC50 value of 4.3 μM. Further analysis reveals that compound AJ-292/12941271 induces apoptosis in the A549 cell line in a concentration- dependent or time-dependent manner. Hemolytic toxicity evaluation suggests that the compound AJ-292/12941271 is safe for further in vivo study.</p><p><strong>Conclusion: </strong>This research proposes that the fused method of ROC-based machine learning, virtual screening, and bioactivity evaluation could be used to discover novel mTOR inhibitors quickly and precisely.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682142","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":"NPLOC4 constructs tumor immunosuppressive microenvironment in pan-cancer and hepatocellular carcinoma.","authors":"Wanli Zhang, Chengdong Liu, Xiaohan Zhou","doi":"10.2174/0109298673344143250604061421","DOIUrl":"https://doi.org/10.2174/0109298673344143250604061421","url":null,"abstract":"<p><strong>Introduction: </strong>NPLOC4 (nuclear protein localization 4 homolog) is mainly involved in DNA damage, cell cycle, and ubiquitination promotion. Nonetheless, the role of NPLOC4 in the tumor immune microenvironment (TIME) and its potential as a promising tumor therapeutic target remains unclear.</p><p><strong>Methods: </strong>Therefore, analyses of NPLOC4 mRNA and protein expression, RNA subcellular localization, and patient prognosis associated with NPLOC4 expression were conducted across multiple tumor types. Additionally, the correlations between NPLOC4 and immune cells, non-immune cells, and immune molecules within the tumor immune microenvironment (TIME) were investigated. These analyses utilized data from various public resources, including the Genotype-Tissue Expression (GTEx) project, The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), The Human Protein Atlas (HPA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), TIMER2.0, KM-Plotter, The University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), and Tumor Immune Single-cell Hub 2 (TISCH2). Subsequently, we utilized hepatocellular carcinoma (HCC) patients' cancer and adjacent tissues plus tumor cell lines to verify the differential RNA and protein expression of NPLOC4 via qRT-PCR and immunohistochemistry (IHC). Then, the relationship of NPLOC4 expression level with immune infiltration score, infiltration of effector immune cells, suppressive immune cells, and several vital immune checkpoints was analyzed in HCC immune microenvironment. Furthermore, the distribution of expression of NPLOC4 in various cells in the HCC microenvironment was determined through single-cell sequencing analysis.</p><p><strong>Results: </strong>We discovered that NPLOC4 was up-regulated in a variety of tumors and was correlated with poor prognosis. NPLOC4 not only had the potential as a tumor prognostic marker and therapeutic target but also was strongly linked to immune cells, immune checkpoints, and immune-related molecules and pathways in HCC immune microenvironment.</p><p><strong>Conclusion: </strong>In summary, NPLOC4 may serve as a promising target for immunotherapy.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674067","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":"Drug-Resistant Infections: A Global Challenge for the Future.","authors":"Parul Grover","doi":"10.2174/0109298673427964250715043856","DOIUrl":"https://doi.org/10.2174/0109298673427964250715043856","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658663","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":"Novel Combination Therapy and Personalized Therapeutic Strategies in Cancer: From Comprehensive Treatment to Precision Treatment.","authors":"Shigao Huang","doi":"10.2174/0109298673429318250715094048","DOIUrl":"https://doi.org/10.2174/0109298673429318250715094048","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658603","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}
Mingjun Tang, Xi Su, Zipin Zhao, Jun Ma, Ning Zhang
{"title":"Identification of Critical Genes Related to Breast Cancer with Brain Metastasis Through Bioinformatics Analysis.","authors":"Mingjun Tang, Xi Su, Zipin Zhao, Jun Ma, Ning Zhang","doi":"10.2174/0109298673397130250708114435","DOIUrl":"https://doi.org/10.2174/0109298673397130250708114435","url":null,"abstract":"<p><strong>Introduction: </strong>Distant metastasis accounts for the majority of Breast Cancer (BC)-related mortality. The brain is one of the most common regions of metastasis. However, the underlying molecular mechanisms remain uncertain.</p><p><strong>Methods: </strong>In this study, gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. Datasets GSE100534 and GSE52604, containing 16 primary brain tumor samples and 38 breast cancer brain metastasis samples, were used to identify the Differentially Expressed Genes (DEGs). The Metascape database was used to analyze enriched Gene Ontology (GO) entries and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway entries in DEGs. The STRING database was then used to construct a Protein-Protein Interaction (PPI) network, and the Cytoscape platform was employed to visualize the network. Furthermore, the Kaplan-Meier curve was used to analyze the Relapse-Free Survival (RFS) among the hub genes. Finally, the iRegulon plugin was used to construct a regulatory network to find the transcription factors (TFs) that regulate the expression of the hub genes.</p><p><strong>Results: </strong>A total of 344 DEGs, including 182 up-regulated and 162 down-regulated genes, were identified by using the limma package in R. A module with 18 nodes and 9 hub genes was selected from the PPI network by using the plugins MCODE and Cyto- Hubba, respectively. KEGG pathway analysis demonstrated that brain metastasis in BC was closely related to the oocyte cell cycle. The Kaplan-Meier curve showed that high expression of these 9 hub genes was associated with poor RFS in BC patients. TFs' analysis showed that E2F4, SIN3A, FOXM1, and TFDP1 interacted with these hub genes.</p><p><strong>Discussion: </strong>This study revealed that Breast Cancer Brain Metastasis (BCBM) may have a promoting effect on the cell cycle of oocytes and affect the maturation and division of oocytes through the KEGG and GO analyses of 344 DEGs. The selected 9 hub genes (ASPM, BUB1, BUB1B, CCNA2, CCNB1, CDK1, NDC80, NCAPG, and TOP2A) and 4 transcription factors (E2F4, SIN3A, FOXM1, TFDP1) may play a critical role in brain metastasis of BC.</p><p><strong>Conclusion: </strong>The results of this study may aid in the early diagnosis and suggest potential targets for the treatment of BCBM.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658664","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":"Inflammatory Biomarkers in Hypertension.","authors":"Panagiotis Tsioufis, Panagiotis Theofilis, Kyriakos Dimitriadis, Panayotis K Vlachakis, Panayotis Iliakis, Dimitrios Tsiachris, Konstantinos Tsioufis, Dimitris Tousoulis","doi":"10.2174/0109298673348789250604113545","DOIUrl":"https://doi.org/10.2174/0109298673348789250604113545","url":null,"abstract":"<p><p>Hypertension remains a leading modifiable risk factor for cardiovascular diseases, yet its underlying mechanisms are not fully understood. Emerging evidence suggests that inflammation plays a central role in the pathogenesis and progression of hypertension. This review explores the association between inflammatory biomarkers, such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and hypertension. These biomarkers are not only indicators of inflammation but also active participants in the processes that elevate blood pressure, including endothelial dysfunction, oxidative stress, and immune system activation. Cytokines play a pivotal role in vascular remodeling and renal dysfunction, underscoring the inflammatory underpinnings of hypertension. Additionally, novel composite biomarkers like the monocyte-to-high-density lipoprotein ratio (MHR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII) have been identified as valuable tools for assessing the inflammatory state in hypertensive patients. While renal denervation has emerged as a promising treatment for resistant hypertension, its impact on inflammatory biomarkers remains inconclusive, highlighting the need for further research.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648732","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}
Leping Liu, Haixia Zhang, Phoebe Abonyo Ouru, Pan Chen, Minghua Yang
{"title":"Exploring the Role of Cuproptosis-related Genes in Acute Myeloid Leukemia Through WGCNA, Single-cell Sequencing and Experiments.","authors":"Leping Liu, Haixia Zhang, Phoebe Abonyo Ouru, Pan Chen, Minghua Yang","doi":"10.2174/0109298673363210250618120652","DOIUrl":"https://doi.org/10.2174/0109298673363210250618120652","url":null,"abstract":"<p><strong>Background: </strong>Cuproptosis, a newly discovered form of programmed cell death, has potential implications for tumorigenesis and cancer progression. This study investigates the role of cuproptosis in Acute Myeloid Leukemia (AML) and identifies associated biomarkers using bulk and single-cell RNA sequencing. Despite recent advances, the mechanisms of cuproptosis in AML remain unclear, and its relationship with immune cell infiltration could reveal novel therapeutic targets.</p><p><strong>Methods: </strong>RNA-seq data from 151 AML patients and 70 healthy controls were obtained from TCGA and GTEx databases, and single-cell RNA-seq data from 10 AML patients (GEO) were used for validation. Differential expression of Cuproptosis-Related Genes (CRGs) was analyzed via RCircos and correlation analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA. WGCNA identified key genes for AML and cuproptosis subtypes, which were validated with single-cell data. Intercellular communication was analyzed through ligand-receptor interactions. RNA interference experiments validated TLR4 and NCF2, with gene expression measured through RT-qPCR. Apoptosis and CCK-8 assays assessed cell viability.</p><p><strong>Results: </strong>We identified 18 CRGs with differential expression between AML subtypes linked to immune cell infiltration. Subtype analysis classified AML patients into C1 and C2 subgroups enriched in biosynthesis and metabolism pathways. WGCNA identified 2701 genes associated with AML and 92 with cuproptosis, leading to 15 intersecting genes. RETN was highlighted as key in intercellular communication. Experimental validation showed that elesclomol-induced cell death in THP-1 cells is reversible by TTM. Knockout of TLR4 and NCF2 promoted cuproptosis.</p><p><strong>Conclusion: </strong>These findings offer new insights into the role of cuproptosis in AML, highlighting novel biomarkers, such as TLR4 and NCF2, which may provide promising targets for the development of future therapeutic strategies in AML treatment.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648731","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}
Md Sadique Hussain, M Arockia Babu, Muhammad Afzal, R Roopashree, Madan Lal, A Rekha, Brian G Oliver, Ronan MacLoughlin, Amlan Chakraborty, Kamal Dua, Haider Ali, Moyad Shahwan, Gaurav Gupta
{"title":"Targeted Protein Degradation in Lung Cancer: The Emerging Role of PROTAC Technology and E3 Ligases.","authors":"Md Sadique Hussain, M Arockia Babu, Muhammad Afzal, R Roopashree, Madan Lal, A Rekha, Brian G Oliver, Ronan MacLoughlin, Amlan Chakraborty, Kamal Dua, Haider Ali, Moyad Shahwan, Gaurav Gupta","doi":"10.2174/0109298673382742250619055201","DOIUrl":"https://doi.org/10.2174/0109298673382742250619055201","url":null,"abstract":"<p><p>Lung cancer remains one of the most prevalent and lethal malignancies, with poor drug response and high mortality rates. Proteolysis-targeting chimeras (PROTACs) are emerging as a novel therapeutic strategy, leveraging E3 ligases to degrade oncogenic proteins selectively via the ubiquitin-proteasome pathway. These degraders offer higher selectivity and bioavailability compared to traditional inhibitors. This review explores how PROTACs eliminate oncogenic proteins in lung cancer and examines the role of E3 ligases in this process. Commonly utilized ligases include Cereblon (CRBN) and Von Hippel-Lindau (VHL), while newer ones, such as MDM2 and Kelch-like ECH-associated protein 1 (KEAP1), are being investigated for therapeutic potential. We discuss key factors in PROTAC design, including ligand selection, linker optimization, and pharmacokinetic properties, which influence tumor specificity and efficacy while minimizing off- target effects. Additionally, we highlight targetable oncogenic drivers in lung cancer, such as KRAS, EGFR, and ALK fusion proteins, and evaluate preclinical and clinical studies that demonstrate PROTACs' potential for overcoming drug resistance. The challenges associated with clinical translation, tumor microenvironment interactions, and E3 ligase selection are also discussed. Finally, we present future perspectives, including expanding the range of E3 ligases, developing multitargeting strategies, and integrating next-generation molecular glue degraders. By offering a comparative analysis of E3 ligase- specific PROTACs, this review underscores the potential of PROTAC technology to advance precision oncology in lung cancer.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648797","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}