Combinatorial chemistry & high throughput screening最新文献

{"title":"Identification of DNA Replication Stress-Related Genes as Prognostic Biomarkers for Bladder Cancer.","authors":"Fei Zhang, Shuai Li, Zhijie Zhang, Jiulong Li, Huiqin Liu, Xudong Ma, Zhigang Yang","doi":"10.2174/0113862073396305250526102508","DOIUrl":"https://doi.org/10.2174/0113862073396305250526102508","url":null,"abstract":"<p><strong>Introduction: </strong>Bladder cancer (BLCA) is a highly aggressive malignancy with poor prognosis. DNA replication stress-related genes (DRSGs) hold prognostic significance in multiple cancers, and their expression patterns in BLCA may reveal novel biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>This study was designed using a public database and the Cancer Genome Atlas (TCGA). Genes associated with DNA replication stress in BLCA were discovered by analyzing data from the TCGA and GEO databases using bioinformatics tools. The prognostic gene expression profiles in BLCA cell lines were analyzed using Western blotting (WB). The motility capacity of BLCA cells was evaluated using the wound healing and Transwell migration assays, while cell growth was ascertained with the CCK-8 assay.</p><p><strong>Results: </strong>Five DRSGs with prognostic significance were identified, and a risk score model was constructed using univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm. Kaplan-Meier (KM) analysis showed worse Overall Survival (OS) in the high-risk group (P < 0.05). Gene Set Enrichment Analysis (GSEA) indicated involvement in tumor-related pathways. The nomogram effectively predicted OS in both training and validation cohorts. WB and functional assays confirmed gene expression and effects on BLCA cell proliferation and migration.</p><p><strong>Discussion: </strong>This study first validates DRSGs' prognostic value in bladder cancer, highlighting potential biomarkers and targets. Limitations include reliance on public data and in vitro tests. Future research should use multicenter cohorts and animal models to confirm clinical relevance.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636381","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":"The Potential Mechanisms of Banxia Xiexin Decoction in Treating Chronic Colitis: Insights from UPLC-Q-TOF-MS/MS and Network Pharmacology Studies.","authors":"Xinyao Pan, Ruyun Zhang, Mengyuan Wang, Chunjuan Yang, Jinhui Wang, Chunli Gan","doi":"10.2174/0113862073350796250305225907","DOIUrl":"https://doi.org/10.2174/0113862073350796250305225907","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Banxia Xiexin Decoction (BXD)is commonly used to treat a variety of gastrointestinal disorders, including Chronic Colitis (CC), due to its anti-inflammatory, antibacterial, and intestinal flora-regulating effects. However, CC is a chronic intestinal immunologic disease whose exact pathogenesis is unknown. Thus, more studies are needed to clarify the mechanism of action of BXD for CC treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The common components of BXD were validated by combining ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) analysis. Then, the mechanism of BXD for CC treatment was investigated using network pharmacology, including potential therapeutic CC phytochemicals, potential targets, and related signaling pathways. Molecular docking analysis was performed to investigate the protein-ligand interactions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Firstly, the chemical composition of BXD was determined by UPLC-QTOF- MS/MS technique and combined with TCMSP and HERB databases to determine the possible active ingredients in the formula, and the Uniprot database was used to find the targets corresponding to the ingredients; the disease targets related to CC were obtained by using GeneCards and Dis- GeNET databases. The intersection of component targets and disease targets was taken and imported into the STRING database for analysis, and then by Cytoscape 3.9.1 software, a protein-protein interaction network diagram (PPI) was constructed and the multi-level network of TCM-compoundtarget- disease was visualized, and DAVID database was used for GO and KEGG enrichment analysis of core genes. Finally, PyRx, AutoDockTools 1.5.6, PyMol 2.5.0, and Open Babel 2.4.1 were used for molecular docking, virtual computation, and visualization analyses of core components and key targets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;UPLC-Q-TOF-MS/MS detected 482 components of BXD, Among the main components of BXD are flavonoids, triterpenoid saponins, alkaloids, glycosides, etc., and comprehensive analysis and screening yielded 165 active ingredients, including quercetin, kaempferol, baicalein, naringenin, etc. There were 283 targets related to BXD's treatment of CC, of which the core targets included AKT1, IL-6, TP53, ALB, etc. GO enrichment analysis yielded relevant entries including molecular function 60 entries, 257 entries of biological processes, and 31 entries of cellular composition, and KEGG enrichment analysis identified 150 entries involving IL-17, TNF, PI3K-Akt, and other pathways. The molecular docking results demonstrated that the core components exhibited better binding activities with the key targets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Quercetin, kaempferol, baicalein, and naringenin, the main active ingredients in BXD, may play roles in anti-inflammatory, antimicrobial, and regulating intestinal microbiota to achieve the therapeutic purpose of CC treatmen","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636382","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":"The Genus Stauntonia DC.: Botany, Phytochemistry, Bioactivity, and Application.","authors":"Ming-San Miao, Shuo Tian, Wen-Min Liu, Qin-Ge Ma, Rong-Rui Wei, Zhi-Hui Zhang","doi":"10.2174/0113862073390090250625111201","DOIUrl":"https://doi.org/10.2174/0113862073390090250625111201","url":null,"abstract":"<p><strong>Background: </strong>The plants of genus Stauntonia DC. are important Chinese medicines. To better develop and utilize the edible and medicinal values of Stauntonia DC., the botany, phytochemistry, bioactivity, and application of genus Stauntonia DC. plants were summarized in this review.</p><p><strong>Methods: </strong>The references of genus Stauntonia DC. were obtained from multiple databases, including ScienceDirect, Web of Science, Elsevier, SciFinder, PubMed, Willy, Baidu Scholar, Google Scholar, Scopus, SciHub, CNKI, and ancient classics on Chinese herbal medicine. The Latin names presented in the review are retrieved by the World Flora Online (http://www.worldfloraonline.org/) and the updated version of \"The Plant List\".</p><p><strong>Results: </strong>A total number of 267 compounds were isolated from the plants of genus Stauntonia DC., which were classified as pentacyclic triterpenoids and their glycosides, methylated pentacyclic triterpenoids and their glycosides, phenylpropanoids, flavonoids, and so on. The bioactivities of genus Stauntonia DC. plants are diverse, including analgesic, anti-inflammatory, anti-cancer, hyperphilidemic, anti-oxidant, and other activities. The fruits from plants of genus Stauntonia DC. are edible, and seeds can be used for oil extraction.</p><p><strong>Conclusion: </strong>This review analysized and summarized the contents of botany, phytochemistry, bioactivity, application of genus Stauntonia DC. plants, which provided a comprehensive information resource for development and utilization of genus Stauntonia DC. plants.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599593","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":"Formononetin Alleviates MNNG-Triggered Chronic Atrophic Gastritis: Its Potential Mechanisms.","authors":"Yuling Wei, Wenhui Wu, Min Duan, Ting Li, Mei Liu, Jinyan Li","doi":"10.2174/0113862073409559250618212035","DOIUrl":"https://doi.org/10.2174/0113862073409559250618212035","url":null,"abstract":"<p><strong>Background: </strong>Chronic atrophic gastritis (CAG) is the initial phase in the carcinogenesis of gastric cancer (GC). Therefore, effective treatment for CAG is important in reducing the risk of GC progression. As an isoflavone compound, formononetin (FMN) has been identified as a potential therapeutic agent for acute gastric ulcers and GC. However, no study has reported the protective effect of FMN against CAG and its underlying mechanism.</p><p><strong>Objective: </strong>This study aimed to explore the therapeutic effects of FMN on CAG and its underlying mechanisms in vitro.</p><p><strong>Methods: </strong>Network pharmacology was applied to predict the core targets of FMN therapy in CAG. The CAG cell model was developed using N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-triggered human gastric epithelial cells (GES-1). The CCK-8 assay was applied to estimate cellular viability. The expression of inflammatory cytokines in cell supernatant was detected by ELISA. The protein levels and localization of nuclear receptor coactivator 1 (NCOA1), c-Jun, and c-Fos were evaluated using western blotting and immunofluorescence staining. Cell apoptosis was measured using flow cytometry.</p><p><strong>Results: </strong>Network pharmacology analysis identified c-Jun as the core target of FMN in the treatment of CAG, with biological processes primarily involving the regulation of apoptosis and inflammation. In vitro, MNNG exposure reduced GES-1 cell viability as well as increased inflammation and cellular apoptosis, and these effects were reversed by FMN treatment. In detail, FMN decreased the protein levels of NCOA1, c-Jun, and c-Fos in MNNG-triggered GES-1 cells. The activator protein-1 (AP-1) inhibitor T-5224 enhanced the effects of FMN treatment on cell viability, inflammatory response, and apoptosis in MNNG-triggered GES-1 cells.</p><p><strong>Conclusion: </strong>FMN ameliorated the cell damage that MNNG triggered in GES-1 cells. The mechanism involved the anti-inflammatory and anti-apoptotic effects of FMN via modulation of the NCOA1/AP-1 signaling axis. The present preliminary study found FMN to exhibit a potential therapeutic effect against CAG.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574960","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":"Network Pharmacology and Experimental Validation of the Anti-Inflammatory Effect of Modified Qianzheng Powder in Atherosclerosis.","authors":"Nianpei Yin, Hui Luo, Jie Feng, Weisheng Zhan, Zheng Zhou, Ying Yang","doi":"10.2174/0113862073376112250602092950","DOIUrl":"https://doi.org/10.2174/0113862073376112250602092950","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to validate the hypothesis that Modified Qianzheng Powder (MQZP) exerts a protective effect on atherosclerosis (AS) by targeting macrophageassociated inflammatory pathways through a multi-target approach. The objective is to identify the bioactive components of MQZP, assess its therapeutic potential, and uncover its molecular mechanisms in AS.</p><p><strong>Materials and methods: </strong>Herein, 124 effective components and 417 potential therapeutic targets were identified through network pharmacological analysis. Among them, cyclo(D)-Pro-(D)-Phe, aurantiamide, beauverilide a, and ecdysone were the key active components of MQZP against AS, whereas the core therapeutic targets included TP53, SRC, STAT3, and AKT1. Furthermore, GO and KEGG enrichment analyses identified 3417 biological components and 238 pathways.</p><p><strong>Results: </strong>Molecular docking analysis revealed that the primary targets were capable of forming stable bonds with their respective compounds. Finally, macrophages were used to create an ox- LDL-induced foam cell model of AS, upon which the levels of inflammatory factors, related proteins, and mRNA were assessed using Oil Red O staining, ELISA, western blotting, and RTqPCR.</p><p><strong>Conclusions: </strong>According to the results, MQZP could alleviate inflammation and improve AS by suppressing the IL-6/STAT3 pathway. Besides a theoretical foundation and experimental data for understanding how MQZP potentially acts to treat AS, this study also offers essential insights and novel research directions regarding the anti-atherosclerotic properties of traditional Chinese medicine (TCM)-derived compounds and extracts.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574962","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":"Juanbi Lijieqing Decoction Inhibits TLR4/NF-κB Signaling Pathway by Promoting PPARγ Expression to Relieve Acute Gouty Arthritis.","authors":"Chengyin Lu, Fangxiao Zhu, Zhiqiang Luo, Hui Xiong, Yuxing Guo","doi":"10.2174/0113862073378606250616114958","DOIUrl":"https://doi.org/10.2174/0113862073378606250616114958","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to explore the mechanism by which Juanbi Lijieqing Decoction (JLD) alleviates acute gouty arthritis (AGA) by promoting PPARγ expression to inhibit the TLR4/NF-κB signaling pathway.</p><p><strong>Methods: </strong>A total of 84 male SD rats were divided into 7 groups of 12 rats. One group was randomly selected as the normal control group (Group A), while the remaining 72 rats were used to establish an acute gouty arthritis model through intraperitoneal injection of potassium oxonate combined with MSU ankle joint injection. These rats were randomly assigned to the model group (Group B), high-dose Juanbi Lijieqing Decoction group (Group C), medium-dose group (Group D), low-dose group (Group E), etoricoxib group (Group F), and pioglitazone group (Group G), with 12 rats per group. The acute gouty arthritis model was established by intraperitoneal injection of potassium oxonate combined with monosodium urate (MSU) injection in the ankle joint, followed by pharmacological intervention in each group. The ankle swelling index, pain threshold changes, and serum uric acid levels in each group of rats were observed. The pathological state of synovial tissue in each group was evaluated by hematoxylin-eosin (HE) staining. The levels of TNF-α, IL-6, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression of TLR4, NF-κB, and PPARγ in vivo and in vitro were detected by Western blot.</p><p><strong>Results: </strong>JLD effectively reduced local swelling, relieved pain, and lowered serum uric acid levels in rats with AGA. (2) Both in vivo and in vitro experiments demonstrated that the Chinese medicine groups showed a significant reduction in TNF-α, IL-1β, and IL-6 levels. Moreover, in in vivo experiments, the expression of PPARγ protein was significantly upregulated in the JLD and pioglitazone groups, while TLR4 and NF-κB p65 protein expressions were significantly downregulated, a pattern not observed in the etoricoxib group. In vitro experiments showed significant increases in PPARγ protein expression in the pioglitazone and medicated serum groups, with significant decreases in TLR4 protein expression. Meanwhile, the NF-κB inhibitor group only exhibited a downregulation of TLR4 protein expression.</p><p><strong>Conclusion: </strong>This study demonstrates that JLD alleviates acute gouty arthritis symptoms by promoting the expression of PPARγ, which, in turn, inhibits the TLR4/NF-κB signaling pathway. This molecular mechanism results in reduced inflammation, lower serum uric acid levels, and decreased joint swelling. These findings provide valuable insight into the therapeutic effects of JLD in managing gout and suggest that it may serve as a promising adjunct to current treatment strategies. However, further studies are needed to fully elucidate its long-term effects and the precise molecular targets involved, paving the way for future clinical applications.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574961","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":"Luohuazizhu Granules Alleviate Symptoms of Ulcerative Colitis via Changes in Bile Acid Metabolism and Gut Microbiota.","authors":"Mo Liu, Leyi Huang, Longhai Shen, Danwei Ouyang, Tong Wu","doi":"10.2174/0113862073405852250625170230","DOIUrl":"https://doi.org/10.2174/0113862073405852250625170230","url":null,"abstract":"<p><strong>Introduction: </strong>Luohuazizhu granules (LHZZG) are made of Callicarpa nudiflora Hook. (CN), which is used to treat ulcerative colitis (UC). The anti-inflammatory effects of CN on UC have been previously reported. However, the biological effects of LHZZG on bile acids (BAs) in UC and the underlying mechanisms remain unexplored.</p><p><strong>Methods: </strong>Integrated metabolomics were used to explore the regulatory mechanisms of LHZZG for BA metabolism in UC mice. Both 16S rDNA sequencing and flow cytometry analyses were combined to comprehensively assess gut microbiota (GM) and immune responses.</p><p><strong>Results: </strong>Twenty-five differential biomarkers were identified in the untargeted metabolomic analysis, most of which were correlated with BA metabolism. UC signs were significantly alleviated after LHZZG treatment. The targeted metabolomics analysis revealed BA metabolic disorders to be significantly improved following LHZZG treatment. Additionally, the imbalances in the GM and immune cells related to BA metabolism were restored.</p><p><strong>Discussion: </strong>This study not only confirmed significant dose-dependent protective effects of LHZZG in UC mice, but also performed the first investigation into the underlying mechanisms related to BA metabolism and immune function. Nevertheless, the limitations precluded a definitive mechanistic explanation for the observed changes. Consequently, in-depth mechanistic investigations will be prioritized in subsequent research to experimentally validate this hypothesis.</p><p><strong>Conclusion: </strong>BAs could serve as biomarkers for evaluating the therapeutic effects of LHZZG on UC. This study has provided the first detailed explanation of the mechanism underlying the effects of LHZZG from a BA metabolic perspective, providing a foundation for their clinical application in UC.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559430","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":"Improved Visualization Method of DNA Sequences and its Application in Phylogenetic Analysis.","authors":"Li Dong, Xinyang Jiang, Yong Liu, Yunlong Gao, Yan Yang","doi":"10.2174/0113862073379972250612103433","DOIUrl":"https://doi.org/10.2174/0113862073379972250612103433","url":null,"abstract":"<p><strong>Introduction: </strong>With a large number of species' genomes assembled, sequence comparison has become an effective method for further studying biological classification and evolution. Traditional sequence alignment relies on predefined scoring functions, but it is computationally intensive and lacks molecular justification for scoring the differences between sequences. Therefore, we have developed a graphical representation method for DNA sequences to facilitate better sequence comparison and evolutionary analysis.</p><p><strong>Method: </strong>In this article, we introduce a novel method for representing DNA sequences using three-dimensional (3D) graphics. This method possesses two significant properties: (1) the graphical representation is acyclic; (2) each DNA sequence maintains a bijective relationship with its graphical representation.</p><p><strong>Result: </strong>Leveraging this proposed visualization method, we computed the corresponding ALE index for any DNA sequence by converting it into an L/L matrix and constructed a 12-dimensional feature vector.</p><p><strong>Conclusion: </strong>The feasibility of our proposed method has been validated through the construction of phylogenetic trees in four test sets: terrestrial vertebrates, hantavirus, fish and Japanese encephalitis virus.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552458","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":"Mechanisms and Therapeutic Implications of ncRNAs in Regulating the PD-1/PD-L1 Axis Across Cancers.","authors":"Huilin Jian, Xitai Li, Xiaoyong Lei, Shengsong Tang, Xiaoyan Yang","doi":"10.2174/0113862073384743250617062430","DOIUrl":"https://doi.org/10.2174/0113862073384743250617062430","url":null,"abstract":"<p><p>Cancer remains one of the most challenging health issues worldwide. Thus, there is an urgent need to discover effective treatments for cancer. Immune checkpoint blockade targeting the PD-1/PD-L1 axis has revolutionized cancer therapy, yet resistance and limited clinical efficacy remain significant challenges. Emerging evidence highlights ncRNAs as upstream regulators of PD-1/PD-L1, offering novel therapeutic opportunities. This review systematically examines the role of miRNAs, lncRNAs, and circRNAs in modulating PD-1/PD-L1 signaling across diverse cancers, emphasizing their mechanisms and clinical implications. We further discuss the potential of ncRNAs as biomarkers and therapeutic targets to overcome immune evasion and enhance immunotherapy efficacy.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539293","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":"Profiles of Circulating Exosomal microRNAs in Female College Students with Qi Stagnation and Balanced Constitutions by High-Throughput Sequencing.","authors":"Yunan Zhang, Yali Zhou, Pengfei Zhao, Yuxiu Sun, Yini Li, Lichun Tian, Jianhua Zhen, Guangrui Huang","doi":"10.2174/0113862073399668250612045822","DOIUrl":"https://doi.org/10.2174/0113862073399668250612045822","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Individual constitutions are classified into nine types in traditional Chinese medical theory, and qi stagnation constitution (QSC) manifests as disrupted Qi circulation and increased susceptibility to emotional disorders and cancers. However, as a pre-disease state mainly affecting women, the biological basis of QSC and its susceptible mechanism to related diseases are still unclear. Exosomal microRNAs (miRNAs) are the stable regulators of gene expression and intercellular communication, and analysis of miRNAs enables us to understand the QSC better. This study profiles plasma exosomal miRNAs in QSC and balanced constitution (BC) females via high-throughput sequencing, aiming to identify the potential biomarkers of QSC and reveal its biological basis and the mechanism of its susceptible disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this cross-sectional observation, female college students were recruited according to the criterion of QSC and BC in Classification and Determination of Constitution in TCM. Exosomal miRNAs were isolated from blood plasma and then profiled using high-throughput sequencing. Differentially expressed miRNAs (DEMs) were identified with fold change &gt; 2 and P &lt; 0.05, and screened as biomarkers to construct the receiver operating characteristic (ROC) curve. The diagnostic values of these biomarkers in different types of cancers were also validated based on the published data. KEGG and GO functional analysis were explored based on the predicted target genes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Subjects with QSC showed significantly higher concentrations of albumin (ALB) and alkaline phosphatase (ALP) compared to those with BC, while there was no significant difference in baseline information and other clinical indicators between groups. A total of 54 DEMs were identified, including 30 30 up-regulated and 24 down-regulated miRNAs in the QSC group. The area under the ROC curve (AUC) for 7 specific up-regulated DEMs was 1.0, as well as the AUCs for therein 6 DEMs in various cancers were all above 0.9. The enriched KEGG pathways included \"signal transduction,\" \"infectious disease,\" and \"cancers\", and the most associating systems included immune, endocrine, and nervous systems, while the GO function was mainly enriched in \"protein binding,\" \"nucleus\" and \"transcription, DNA-templated\".&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;These 7 potential biomarkers of QSC have been confirmed to regulate oncogenic processes through epithelial-mesenchymal transition modulation and metabolic reprogramming, as well as therein 1 can also improve depression by lowering the expression of 5-hydroxytryptamine 1A receptor. The results of this study deepen the understanding of the traditional Chinese medicine constitutions. However, the small single-sex sample limits the application of the conclusion, and a large-scale clinical cohort including both sexes is still needed in future.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The expression","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504980","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}