Combinatorial chemistry & high throughput screening最新文献

筛选
英文 中文
Exploring the Blueprint of Life: The Innovation in Antibody and Protein Design. 探索生命的蓝图:抗体和蛋白质设计的创新。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-02-20 DOI: 10.2174/0113862073189534250217114015
Zhiwei Yang, Gerald H Lushington
{"title":"Exploring the Blueprint of Life: The Innovation in Antibody and Protein Design.","authors":"Zhiwei Yang, Gerald H Lushington","doi":"10.2174/0113862073189534250217114015","DOIUrl":"https://doi.org/10.2174/0113862073189534250217114015","url":null,"abstract":"<p><p>The innovation in antibody and protein design highlights the transformation from empirical approaches to sophisticated strategies integrating computational methods and artificial intelligence (AI). Key principles, such as combinatorial, structure-based, consensus, and computational designs, have been pivotal in predicting structures from sequences (in silico design). Advances in tools, like AlphaFold and Rosetta suite, enable accurate structure prediction, facilitating the development of functional proteins and antibodies. However, challenges remain, including improving prediction accuracy, modeling flexible regions, understanding structural dynamics, and designing catalytic and binding sites. Despite these, the field promises groundbreaking advancements in biomedical sciences, enriching our understanding and serving human health and scientific discovery.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466942","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}
引用次数: 0
Investigation of LncRNA Expression Profiles and Analysis of Immune-Related lncRNA-miRNA-mRNA Networks in Neovascular Age-Related Macular Degeneration. 新生血管性年龄相关性黄斑变性中LncRNA表达谱研究及免疫相关LncRNA - mirna - mrna网络分析
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-02-12 DOI: 10.2174/0113862073342212250102042734
Liying Qin, Xiang Gao, Xiuhai Lu, Wencai Liu, Jingyi Tian, Gongqiang Yuan
{"title":"Investigation of LncRNA Expression Profiles and Analysis of Immune-Related lncRNA-miRNA-mRNA Networks in Neovascular Age-Related Macular Degeneration.","authors":"Liying Qin, Xiang Gao, Xiuhai Lu, Wencai Liu, Jingyi Tian, Gongqiang Yuan","doi":"10.2174/0113862073342212250102042734","DOIUrl":"https://doi.org/10.2174/0113862073342212250102042734","url":null,"abstract":"<p><strong>Introduction: </strong>Age-related Macular Degeneration (AMD) is a predominant cause of blindness in the elderly. The present study is the first to investigate the alteration of lncRNAs and mRNAs in neovascular AMD.</p><p><strong>Methods: </strong>Nine patients with neovascular AMD were included in the study. The control group comprised seven patients with epiretinal membranes. RNA sequencing was performed to obtain the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs). Then, the DElncRNA-DEmRNA co-expression network, ceRNA network, and immune-related ceRNA subnetwork were constructed. Functional annotation of DEmRNAs between the two groups and DEmRNAs in networks was conducted. The immune cell distribution in neovascular AMD was also evaluated. Real-time qPCR (RT-qPCR) was used to validate the expression levels of key markers.</p><p><strong>Results: </strong>A total of 342 DEmRNAs and 157 DElncRNAs were obtained in neovascular AMD. Functional annotation indicated that these DEmRNAs significantly enriched immune systemrelated processes, such as positive regulation of B cell activation, immunoglobulin receptor binding, complement activation, and classical pathway. The DElncRNA-DEmRNA co-expression network, including 185 DElncRNA-DEmRNA co-expression pairs, and the ceRNA (DElncRNA-miRNA-DEmRNA) network, containing 45 lncRNA-miRNA pairs and 73 miRNAmRNA pairs, were constructed. The immune-related ceRNA subnetwork, including 2 lncRNAs, 5 miRNAs, and 3 mRNAs, was constructed. In addition, the distribution of immune cells was slightly different between the neovascular AMD group and the control group. RT-qPCR validation indicated the consistency between the RT-qPCR results and RNA sequencing results.</p><p><strong>Conclusion: </strong>In conclusion, STC1, S100A1, MEG3, MEG3-hsa-miR-608-S100A1, and MEG3- hsa-miR-130b-3p/hsa-miR-149-3p-STC1 may be related to the occurrence and development of neovascular AMD.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406187","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}
引用次数: 0
Therapeutic Potential of Desert Truffles in the Management of Eye Infections: Demystifying the Fact. 沙漠松露治疗眼部感染的潜力:揭开事实的神秘面纱。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-02-10 DOI: 10.2174/0113862073356481250128045428
Md Abul Barkat
{"title":"Therapeutic Potential of Desert Truffles in the Management of Eye Infections: Demystifying the Fact.","authors":"Md Abul Barkat","doi":"10.2174/0113862073356481250128045428","DOIUrl":"https://doi.org/10.2174/0113862073356481250128045428","url":null,"abstract":"<p><p>Truffle, an ascomycetous, hypogeous macrofungi, has long been recognized and valued for its therapeutic and dietary properties. Of late, a range of medicinal compounds, such as ergosterol, tuberoside anandamide, polysaccharides, and phenolics exhibiting anti-inflammatory, immunomodulatory, anticancer, antibacterial, and aphrodisiac properties have been identified in truffles. This review provides an update on contemporary truffle research with a focus on antimicrobial potentials and aims to draw the attention of researchers to exploit the therapeutic potential of truffles in the management of eye infections. The scholarly literature pertaining to the utilization of desert truffles in the management of ocular infections was systematically summarized and reviewed from multiple databases, including Scopus, Web of Science Core Collection, PubMed, and others. The essence of truffle is used as a remedy for trachoma and as an antiinflammatory agent for ocular problems. The most probable inhibitory constituents are the fungal lectins, polysaccharides, and laccases. Truffle lectins possess the ability to identify and remove bacterial exopolysaccharides. In addition, the fungal polysaccharides affect the bacterial defensive systems. Conversely, laccases facilitate the process of oxidizing phenols, resulting in the release of superoxide anion radicals and the production of hydrogen peroxide. The application of desert truffles in addressing ocular issues has been clinically observed to be satisfactory. The existing literature clearly indicates a pressing need for further investigation into the translation of the antimicrobial properties of crude truffle extract into truffle-based pharmaceutical formulations for clinical application.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390444","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}
引用次数: 0
Identification of NR4A2 as a Potential Predictive Biomarker for Atherosclerosis. 鉴定NR4A2作为动脉粥样硬化潜在的预测性生物标志物。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-02-10 DOI: 10.2174/0113862073357411250127080814
Lebin Yuan, Ruru Bai, Xinhao Han, Jiajia Xiang
{"title":"Identification of NR4A2 as a Potential Predictive Biomarker for Atherosclerosis.","authors":"Lebin Yuan, Ruru Bai, Xinhao Han, Jiajia Xiang","doi":"10.2174/0113862073357411250127080814","DOIUrl":"https://doi.org/10.2174/0113862073357411250127080814","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis, a leading cause of death globally, is characterized by the buildup of immune cells and lipids in medium to large-sized arteries. However, its precise mechanism remains unclear.</p><p><strong>Objective: </strong>The purpose of this study is to explore innovative and reliable biomarkers as a viable approach for the identification and management of atherosclerosis.</p><p><strong>Methods: </strong>The atherosclerosis-related datasets GSE100927 and GSE66360 were retrieved from the Gene Expression Omnibus (GEO) database. The Limma package in the R programming language was utilized, applying the criteria of |logFC| > 1 and P < 0.05. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the 127 identified DEGs using R. Machine learning techniques were then applied to these data to explore and pinpoint potential biomarkers. The diagnostic potential of these markers was assessed via Receiver Operating Characteristic (ROC) curve analysis. Finally, Western Blot, real-time quantitative PCR (qRT-PCR), and immunohistochemistry (IHC) were employed to confirm the key biomarkers.</p><p><strong>Results: </strong>Our research indicated that a total of 127 DEGs linked to atherosclerosis were successfully identified. Through the application of machine learning methods, eight critical genes were highlighted. Among these, Nuclear Receptor Subfamily 4 Group A Member-2 (NR4A2) emerged as the most promising marker for further investigation. CIBERSORT analysis revealed that NR4A2 expression levels were significantly correlated with multiple immune cell types, including B cells, plasma cells, and macrophages. Additional validation experiments confirmed that NR4A2 expression was indeed elevated in atherosclerotic plaques, supporting its potential as a biomarker for atherosclerosis.</p><p><strong>Conclusion: </strong>Our study identified NR4A2 as a potential immune-related biomarker for the diagnosis and treatment of atherosclerosis.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390402","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}
引用次数: 0
The Role of Jianpi Jiedu Recipe in Modulating the CRC Microenvironment. 健脾解毒方对CRC微环境的调节作用。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-02-07 DOI: 10.2174/0113862073339913241214051331
Mengyao Li, Dongming Hua, Yuanyuan Feng, Zhiyan Wang, Xueqing Hu, Yan Wang
{"title":"The Role of Jianpi Jiedu Recipe in Modulating the CRC Microenvironment.","authors":"Mengyao Li, Dongming Hua, Yuanyuan Feng, Zhiyan Wang, Xueqing Hu, Yan Wang","doi":"10.2174/0113862073339913241214051331","DOIUrl":"https://doi.org/10.2174/0113862073339913241214051331","url":null,"abstract":"<p><strong>Background: </strong>The anti-tumor effects of Traditional Chinese Medicine has been recognized in regulating the tumor microenvironment. Jianpi Jiedu Recipe (JPJDR) is clinically effective in enhancing the chemotherapy efficacy in Colorectal Cancer (CRC) treatment and significantly improved the quality of life of CRC patients. However, its therapeutic mechanism remains to be investigated.</p><p><strong>Material and methods: </strong>The active compounds of each herb in JPJDR were obtained from the HIT2.0 and HERB databases supported by evidence in literature. Single-cell RNA sequencing data of CRC were obtained from published studies (PMID: 32451460, 32103181, and 32561858). Pathway enrichment was analyzed using the reactome database, and gene correlation analysis was performed using the corrplot R software package. Gene expression regulated by JPJDR was verified by RT-qPCR.</p><p><strong>Results: </strong>Ye Pu Tao Teng, Ba Yue Zha, Huang Qi, Bai Zhu, Yi Yi Ren and Dang Shen contained 4,7, 18, 26,3 and 30 compounds, respectively, and they target to 38, 7, 262, 309, 50, 54 genes, respectively. JPJDR is involved in a range of immune-related biological processes, including cytokine signaling, cell proliferation, apoptosis and cellular senescence. JPJDR regulates various cell types in the CRC microenvironment, including malignant CRC cells, immune cells (including CD4+ T cell, CD8+ T cell, B cell, plasma cell, mast cell, and myeloid cell), and stromal cells (including fibroblast, pericyte, enteric glial cell, and endothelial cell). We confirmed that JPJDR significantly downregulated the expression of HMGB1 and MT2A in CRC.</p><p><strong>Conclusions: </strong>JPJDR regulates a range of cell types in the CRC microenvironment, including malignant CRC, immune cells and stromal cells. Downregulation of HMGB1 and MT2A might be the important mediators for JPJDR to modulate the CRC microenvironment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390405","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}
引用次数: 0
Adaptability of Thermotoga Maritima's Glycolysis Pathway in Both Oxic and Anoxic Environments. 海洋热藓糖酵解途径在缺氧和缺氧环境下的适应性
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-02-06 DOI: 10.2174/0113862073357899250126032044
Raja Lakhal, Manaf AlMatar, Tahani Alkalaf
{"title":"Adaptability of Thermotoga Maritima's Glycolysis Pathway in Both Oxic and Anoxic Environments.","authors":"Raja Lakhal, Manaf AlMatar, Tahani Alkalaf","doi":"10.2174/0113862073357899250126032044","DOIUrl":"https://doi.org/10.2174/0113862073357899250126032044","url":null,"abstract":"<p><strong>Background: </strong>The phylum Thermotogae is composed of five families: Fervidobacteriaceae, Thermatogaceae, Kosmotogaceae, Petrotogaceae, and Mesoaciditogaceae; one class: Thermotogae; and four orders: Kosmotogales, Petrotogales, and Mesoaciditogales.</p><p><strong>Method: </strong>There are thirteen genera in all. The physical and metabolic characteristics of the Thermotogae species reflect the extreme heat from which they were separated. Thermotogae members have a broad spectrum of metabolic capacities, resulting in a pool of valuable chemicals with potential uses in many different sectors.</p><p><strong>Result: </strong>Based on NMR analysis, our findings demonstrate that T. maritima uses the EM route to metabolize 90% of glucose in anoxia and the ED pathway for 10%. On the other hand, T. maritima continues to employ the EM and ED glycolysis routes concurrently when exposed to extended oxidative stress; however, the ED pathway's contribution drops from 10% to around 5%.</p><p><strong>Conclusion: </strong>Compared to the EM route, the ED pathway has more strongly repressed transcripts that encode its unique enzymes.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398179","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}
引用次数: 0
Causal Mediation Analysis of the Effect of Dietary Habits on Sleep Apnea Risk. 饮食习惯对睡眠呼吸暂停风险影响的因果中介分析
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-02-06 DOI: 10.2174/0113862073348527250124113458
Yingying-Li, Liang Wu, Wenbo-Chen
{"title":"Causal Mediation Analysis of the Effect of Dietary Habits on Sleep Apnea Risk.","authors":"Yingying-Li, Liang Wu, Wenbo-Chen","doi":"10.2174/0113862073348527250124113458","DOIUrl":"https://doi.org/10.2174/0113862073348527250124113458","url":null,"abstract":"<p><strong>Objective: </strong>Diet is a modifiable factor that influences several chronic diseases, making lifelong dietary interventions critically important for reducing disease risk. Hence, this study aims to assess the potential causal relationship between diet and sleep apnea (SA).</p><p><strong>Methods: </strong>We analyzed genome-wide association study (GWAS) data from approximately 450,000 individuals, focusing on 8 dietary intakes and GWAS statistics for 249 metabolites from the UK Biobank. Sleep apnea-related phenotypic data from 16,761 participants were sourced from the FinnGen Biobank. Furthermore, we conducted a series of two-sample Mendelian Randomization (two-sample MR) to explore the causality between diet and SA. Sensitivity analyses were conducted to assess the robustness of the two-sample MR results, and reverse MR analysis was performed to examine potential reverse causality. Multivariate MR (MVMR) analysis and mediation effect estimation were employed to evaluate the mediating roles of metabolites.</p><p><strong>Results: </strong>Two-sample MR analyses revealed significant causal associations between bread intake (OR=0.56, 95% CI 0.35-0.89, P =0.014), cheese intake (OR=0.67, 95% CI 0.50-0.89, P =0.006), and dried fruit intake (OR=0.61, 95% CI 0.39-0.95, P =0.029) with SA. Reverse MR analysis indicated a causal effect of SA on dried fruit intake (P < 0.05). Univariate MR analyses further identified significant causal effects of bread and cheese intakes on 2 and 32 metabolites, respectively (P < 0.05). Subsequent MVMR analysis demonstrated direct causal effects of bread and cheese intake on SA, independent of metabolite mediation (P < 0.05). Furthermore, the mediating effect of cheese intake on SA through glucose was estimated at 0.023 (90% CI 0.01- 0.046), whereas other modeled mediation effects were not statistically significant.</p><p><strong>Conclusion: </strong>The MR analysis in this study offers genetic evidence indicating that heightened genetic susceptibility to cheese and bread intake potentially reduces SA risk. These findings underscore and validate the significance of diet in preventing SA.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398262","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}
引用次数: 0
Bingqing Gao Facilitates the Healing Process of Full-Thickness Skin Defects in Rat Wounds by Activating the PI3K/AKT Pathway. 激活PI3K/AKT通路促进大鼠创面全层皮肤缺损愈合
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-02-04 DOI: 10.2174/0113862073311259240918081737
Hong'e Ma, Rui Hu, Jiajun Guo, Xinfu Wang, Xin Liu, Ning Zhang, Ruilong Ren, Danyang Wang, Wenxian Zhang
{"title":"Bingqing Gao Facilitates the Healing Process of Full-Thickness Skin Defects in Rat Wounds by Activating the PI3K/AKT Pathway.","authors":"Hong'e Ma, Rui Hu, Jiajun Guo, Xinfu Wang, Xin Liu, Ning Zhang, Ruilong Ren, Danyang Wang, Wenxian Zhang","doi":"10.2174/0113862073311259240918081737","DOIUrl":"https://doi.org/10.2174/0113862073311259240918081737","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Trauma, resulting from mechanical factors, entails damage to human tissues or organs. Whether occurring during times of war or peace, trauma is prevalent, particularly skin defects arising from surgery or external injuries. The development and design of effective wound dressings have become paramount. Bingqing Gao (BQG), rooted in Chinese folk medicine, is employed explicitly in trauma treatment based on Traditional Chinese Medicine (TCM) theory. This study aims to elucidate how BQG facilitates full-thickness skin wound healing in Sprague Dawley (SD) rats.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data collection commenced using two approaches: retrieval from TCM system pharmacology databases (TCMSP) and literature mining to compile the practical chemical components and targets of BQG. A drugtarget network was constructed. Subsequently, disease targets related to wound healing were collected to select core targets and pathways, building a drug-disease target protein-protein interaction (PPI) network using the ClusterONE algorithm to identify core genes. Gene Ontology (GO) and KEGG enrichment analyses were conducted based on the Metascape database. Finally, molecular docking validation was performed on the screened core targets and core components. In terms of in vivo experimentation, an SD rat full-thickness skin defect model was established, and varying doses of BQG were applied. Healing area, HE staining, Masson staining, ELISA, PCR, and other methods were employed to validate cytokines, differential proteins, and pathways. The study collectively discusses the mechanism and targets by which BQG promotes full-thickness skin wound healing in SD rats.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Through network pharmacology screening, we identified various active components, including resveratrol, Lithospermic acid B, sanguiinH-2, asernestioside A_qt, kaempferol, daidzein, quercetin, apigenin, and Medicarpin. The core targets encompass Interleukin-6 (IL-6), Protein Kinase B (AKT1), Vascular Endothelial Growth Factor A (VEGFA), Interleukin-1 beta (IL-1β), Tumor Protein 53 (TP53), Epidermal Growth Factor Receptor (EGFR), Tumor Necrosis Factor (TNF), Albumin (ALB), among others. Potential signaling pathways include Phosphoinositide 3-kinase (PI3K)/AKT, Tumor Necrosis Factor (TNF), Hypoxia-Inducible Factor-1 (HIF-1), and more. Molecular docking studies suggest a robust binding interaction between the active components of BQG and disease targets, indicating a potential regulation of cytokines through the PI3K/AKTsignaling pathway, thereby promoting wound healing. The results of the in vivo experiment revealed that, in comparison to the model group, both the rhb-FGF group and BQG-H group exhibit a noteworthy increase in the expression levels of PI3K and AKT genes. Concurrently, there is a significant decrease in the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Additionally, there is a substantial increase in the levels of Transf","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363945","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}
引用次数: 0
CD4+ Effector Memory T Cells Related Marker Gene Signatures in Osteoporosis and Aging: Insight From Single-Cell Analysis and Mendelian Randomization. CD4+效应记忆T细胞在骨质疏松和衰老中的相关标记基因特征:来自单细胞分析和孟德尔随机化的见解。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-02-04 DOI: 10.2174/0113862073353509241205065221
Xiangwen Shi, Linmeng Tang, Mingjun Li, Yipeng Wu, Yongqing Xu
{"title":"CD4+ Effector Memory T Cells Related Marker Gene Signatures in Osteoporosis and Aging: Insight From Single-Cell Analysis and Mendelian Randomization.","authors":"Xiangwen Shi, Linmeng Tang, Mingjun Li, Yipeng Wu, Yongqing Xu","doi":"10.2174/0113862073353509241205065221","DOIUrl":"https://doi.org/10.2174/0113862073353509241205065221","url":null,"abstract":"<p><strong>Objective: </strong>With the accelerated aging of the population, aging has emerged as a major risk factor for osteoporosis (OP). This study aims to investigate the relationship and shared molecular mechanisms between OP and aging through various genetic approaches.</p><p><strong>Methods: </strong>Single-cell data from the peripheral blood of osteoporosis patients, aging individuals, and healthy controls were integrated to analyze characteristic changes in cell subpopulations. Differentially expressed genes (DEGs) were then identified within core subpopulations, and Mendelian Randomization (MR) analysis was employed to explore potential causal links between key genes and OP. Additionally, an OP model was established in rats, and mRNA levels of key genes were measured using RT-qPCR.</p><p><strong>Results: </strong>Through the integration, filtering, and analysis of scRNA-seq data, an increased proportion of CD4+ effector memory T (CD4+ TEM) cells were identified in OP and aging samples, marking them as a core subpopulation. Differential expression analysis identified 49 DEGs, and further analysis through Mendelian Randomization (MR) identified three key genes (KLRB1, NR4A2, and S100A4) significantly associated with OP. Notably, the upregulation of KLRB1 and S100A4 may enhance the interactions within T cells and with other cell subgroups. At the same time, the downregulation of NR4A2 could impede communication between T cells and other cell subpopulations. The RT-qPCR results indicated that NR4A2 was significantly downregulated in the OP group.</p><p><strong>Conclusion: </strong>This study conducted a comprehensive analysis of the potential link between OP and aging, identifying CD4+ TEM cells as the core cell subgroup in OP and aging samples. It further revealed the causal relationship between KLRB1, NR4A2, and S100A4 and the occurrence of OP. The upregulation of KLRB1 and S100A4 may contribute to OP pathogenesis by promoting interactions between CD4+ TEM cells and other cell subgroups, providing new insights for molecular targeting and immunotherapy of OP.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363998","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}
引用次数: 0
Effects of Inhaled Corticosteroids/Long-Acting Beta-Agonists (ICS/LABA) on Airway Microbial Diversity and IL-8/IL-10 Cytokine Levels in Stable COPD. 吸入皮质类固醇/长效β激动剂(ICS/LABA)对稳定型COPD患者气道微生物多样性和IL-8/IL-10细胞因子水平的影响
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-02-04 DOI: 10.2174/0113862073349683241226100233
Aili Fang, Buwu Li, Sheng Chen
{"title":"Effects of Inhaled Corticosteroids/Long-Acting Beta-Agonists (ICS/LABA) on Airway Microbial Diversity and IL-8/IL-10 Cytokine Levels in Stable COPD.","authors":"Aili Fang, Buwu Li, Sheng Chen","doi":"10.2174/0113862073349683241226100233","DOIUrl":"https://doi.org/10.2174/0113862073349683241226100233","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic Obstructive Pulmonary Disease (COPD) is a severe respiratory system disorder. In recent years, the combined therapy of inhaled corticosteroids/long-acting beta-agonists (ICS/LABA) has become the primary treatment for stable COPD patients. This study aimed to investigate the effects of ICS/LABA treatment on the airway microbiota and inflammatory profiles in COPD patients.</p><p><strong>Materials and methods: </strong>Respiratory samples were collected from 18 individuals, including 2 healthy controls, 4 COPD patients, and 12 COPD patients receiving ICS/LABA treatment. Microbial diversity sequencing was employed to analyze the respiratory microbiota, with both diversity and functional predictions performed. Inflammatory factor levels were assessed using enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>The COPD group exhibited a dysregulated respiratory microbiota compared to the control group. Compared to the COPD group, patients in the ICS/LABA treatment group showed a trend toward decreased α-diversity of bacterial communities in the respiratory tract, while the α- diversity of fungi significantly increased. Post-treatment, the abundance of Streptococcus and Fusicolla decreased, whereas the abundance of Moraxella and Candida increased in the respiratory tract. These findings suggest that ICS/LABA treatment may help maintain a balanced respiratory microbiota. Furthermore, patients in the treatment group exhibited a significant decrease in IL-8 levels and a notable increase in IL-10 levels, indicating that ICS/LABA therapy may modulate cytokine levels by suppressing inflammatory responses and promoting anti-inflammatory reactions.</p><p><strong>Conclusion: </strong>The combined therapy of inhaled corticosteroids/long-acting beta-agonists (ICS/LABA) appears to regulate the gene functions of respiratory tract microbiota and IL-8/IL- 10 levels in stable COPD patients. These findings offer new insights into personalized COPD treatment and microbial interventions.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363999","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信