Combinatorial chemistry & high throughput screening最新文献

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miR-507 Acts as a Tumor Suppressor in Renal Cell Carcinoma Cells by Targeting STEAP3. miR-507通过靶向STEAP3在肾细胞癌细胞中起抑瘤作用
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-01-09 DOI: 10.2174/0113862073353340241108053733
Gong Xiaobo, Huang Jian, Guo Linjie, Tang Zhe, Zhong Guangjun, Feng Ye
{"title":"miR-507 Acts as a Tumor Suppressor in Renal Cell Carcinoma Cells by Targeting STEAP3.","authors":"Gong Xiaobo, Huang Jian, Guo Linjie, Tang Zhe, Zhong Guangjun, Feng Ye","doi":"10.2174/0113862073353340241108053733","DOIUrl":"https://doi.org/10.2174/0113862073353340241108053733","url":null,"abstract":"<p><strong>Introduction: </strong>In recent years, there has been a rise in the incidence of renal cell carcinoma (RCC), with metastatic RCC being a prevalent and significant contributor to mortality. While a regulatory role for microRNAs (miRNAs) in the development and progression of RCC has been recognized, their precise functions, molecular mechanisms, and potential clinical implications remain inadequately elucidated. Hence, this study aimed to explore the role of miR-507 in RCC and identify STEAP3 as a downstream target of miR-507.</p><p><strong>Methods: </strong>Bioinformatics analysis was used to analyze the expression of miR-507 and STEAP3 in RCC specimens. CCK-8, Transwell, and flow cytometry assays were used to assess the function of miR-507 in RCC cells. The connection between miR-507 and STEAP3 was confirmed through a luciferase reporter assay. The expression level of STEAP3, p53, and xCT was analyzed by western blotting.</p><p><strong>Results: </strong>Bioinformatics analysis showed that miR-507 was expressed at low levels in RCC tissues and was linked to poor overall survival. STEAP3 was found to be significantly upregulated in RCC. Further, STEAP3 was shown to be targeted by miR-507. High levels of miR-507 reduced the expression of STEAP3, leading to stagnant cell viability, apoptosis, and migrative capacity. Whereas miR-507 knockdown reverted such a tendency. The study also discovered that miR-507 exerted its inhibitory effect through the op53/xCT pathway.</p><p><strong>Conclusion: </strong>Within RCC, miR-507 modulates the expression of SETAP3/p53/xCT axis, exhibiting a tumor suppressive effect. These discoveries offer present prospective biomarkers for both surveillance and treatment of RCC.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977954","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 Association between Arm Fat, Left Leg Fat, and Trunk Fat Masses and Risk of Polycystic Ovarian Syndrome: A Mendelian Randomization Study. 手臂脂肪、左腿脂肪和躯干脂肪块与多囊卵巢综合征风险的因果关系:一项孟德尔随机研究。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-01-09 DOI: 10.2174/0113862073325251241101054306
Yuhan Zhang, Wei Zhou, Qiong Su, Qi Chen
{"title":"Causal Association between Arm Fat, Left Leg Fat, and Trunk Fat Masses and Risk of Polycystic Ovarian Syndrome: A Mendelian Randomization Study.","authors":"Yuhan Zhang, Wei Zhou, Qiong Su, Qi Chen","doi":"10.2174/0113862073325251241101054306","DOIUrl":"https://doi.org/10.2174/0113862073325251241101054306","url":null,"abstract":"<p><strong>Background: </strong>Observational studies have reported that arm fat, left leg fat, and trunk fat masses have different effects on polycystic ovarian syndrome (PCOS). However, the causal relationship between them remains unknown.</p><p><strong>Materials and methods: </strong>A two-sample Mendelian randomization (MR) study was conducted by utilizing pooled data from the largest Genome-Wide Association Study (GWAS). Random effect inverse variance weighted (IVW) method, weighted median (WM), and MR-Egger regression analysis were the main statistical methods utilized. Finally, a sensitivity assessment was conducted. Cochran's Q test was used to analyze heterogeneity, whereas MR-Egger regression (intercept term) was used to analyze horizontal pleiotropy. The leave-one-out analysis was performed to assess if MR estimates were impacted by a single nucleotide polymorphism (SNP) exhibiting significant horizontal pleiotropy.</p><p><strong>Results: </strong>This study discovered a significant positive correlation between left leg fat mass, arm fat mass, and trunk fat mass and genetic factors of PCOS (odds ratio (OR): 4.452, confidence interval (CI): 2.740-7.232, p < 0.001, OR: 3.321, CI: 2.248-4.907, p < 0.001, and OR: 2.518, CI: 1.722-3.682, p < 0.001, respectively).</p><p><strong>Conclusion: </strong>This study indicates that arm fat, left leg fat, and trunk fat masses may be genetically correlated with PCOS.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977947","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
Combinatorial Synthesis of Tetrasubstituted Alkenes and Related Compounds with Potential Anticancer Activity. 具有潜在抗癌活性的四取代烯烃及其相关化合物的组合合成。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-01-09 DOI: 10.2174/0113862073347827241104062749
Kateřina Nováčková, Ladislav Drož, Marek Kořínek, David Sedlák, Petr Bartůněk, Václav Eigner, Miroslav Havránek
{"title":"Combinatorial Synthesis of Tetrasubstituted Alkenes and Related Compounds with Potential Anticancer Activity.","authors":"Kateřina Nováčková, Ladislav Drož, Marek Kořínek, David Sedlák, Petr Bartůněk, Václav Eigner, Miroslav Havránek","doi":"10.2174/0113862073347827241104062749","DOIUrl":"https://doi.org/10.2174/0113862073347827241104062749","url":null,"abstract":"<p><strong>Objective: </strong>In search of efficient anticancer agents, we aimed at the design and synthesis of a library of tetrasubstituted alkenes. These are structural analogues of tamoxifen, one of the widely used anticancer therapeutics.</p><p><strong>Methods: </strong>Our small organic compound library was prepared via a chemical synthesis in the solution using the Larock three-component coupling reaction, which is known to tolerate diverse functional groups. Further, we have integrated this synthetic approach to four- and fivecomponent alkene assembly by using Sonogashira coupling, A3 and AHA reactions. The final products were isolated through preparative LC/MS station and characterized by NMR, MS, and X-ray crystallography. The biological activity of all novel compounds was tested by luciferase reporter assays against estrogen receptor (ER) and androgen receptor (AR).</p><p><strong>Results and discussion: </strong>Our combinatorial synthetic approach was based on structurally diverse internal alkynes, arylboronic acids and aryl halides. After experiment optimization a \"one-pot\" single synthetic procedure was developed. This allowed us to prepare a small-sized screening library of novel tetrasubstituted alkenes quickly and efficiently without laborious intermediate isolation. In most cases, we isolated the final product as a single isomer, and in selected cases, we confirmed their chemical structure via X-ray crystallography. High throughput screening of the novel tetrasubstituted alkenes revealed a dozen hits with predominant agonistic ERα- and antagonistic AR-activity in the micromolar range.</p><p><strong>Conclusion: </strong>The proposed combinatorial approach is applicable for the synthesis of diversified organic compound libraries and for the discovery of new tamoxifen analogues with an improved therapeutic profile.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977951","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
Establishment of a Prognostic Necroptosis-Related lncRNA Signature in Ovarian Cancer. 卵巢癌预后坏死相关lncRNA信号的建立。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-01-07 DOI: 10.2174/0113862073339602241028095015
Hui Xu, Meng Li, Wen-Lan Qiao, Tian Hua
{"title":"Establishment of a Prognostic Necroptosis-Related lncRNA Signature in Ovarian Cancer.","authors":"Hui Xu, Meng Li, Wen-Lan Qiao, Tian Hua","doi":"10.2174/0113862073339602241028095015","DOIUrl":"https://doi.org/10.2174/0113862073339602241028095015","url":null,"abstract":"<p><strong>Introduction: </strong>Ovarian Cancer (OC) was known for its high mortality rate among gynecological malignancies, often resulting in a poor prognosis. This study sought to identify prognostic necroptosis-related long non-coding RNAs (lncRNAs) (NRlncRNAs) with prognostic potential and to construct a reliable risk prediction model for OC patients.</p><p><strong>Method: </strong>The transcriptome and clinic data were sourced from TCGA and GTEx databases. Initially, NRlncRNAs were discovered by assessing gene correlations and evaluating differences in gene expression. Subsequently, Cox regression and LASSO methods were employed to develop the NRlncRNAs risk model, which was further validated through survival analysis, ROC curves, Cox regression, and nomograms across both the test and entire datasets.</p><p><strong>Results: </strong>Multivariate Cox analysis revealed that the risk score based on 14 NRlncRNAs can independently predict the prognosis of OC. The low-risk group demonstrated significantly higher immune cell infiltration scores and lower tumor immune dysfunction, exclusion, and TIDE scores, as well as an increased number of neoantigens and higher TMB. Notably, the low-risk group also exhibited an elevated HRD score.</p><p><strong>Conclusion: </strong>The model's predictive accuracy was further substantiated through ROC analysis, showing superior performance compared to many existing models.Finally, the expression levels of 14 NRlncRNAs were confirmed using the qRT-PCR in two OC cell lines. These findings suggested that the NRlncRNAs risk model could serve as a more precise indicator for forecasting immune response and outcomes of targeted treatments in OC.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945891","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 and Validation of Potential Biomarkers and Therapeutic Targets of COVID-19-related Depression. covid -19相关抑郁症潜在生物标志物和治疗靶点的鉴定与验证
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-01-07 DOI: 10.2174/0113862073322931241030104813
Peng Qi, Mengjie Huang, Haiyan Zhu
{"title":"Identification and Validation of Potential Biomarkers and Therapeutic Targets of COVID-19-related Depression.","authors":"Peng Qi, Mengjie Huang, Haiyan Zhu","doi":"10.2174/0113862073322931241030104813","DOIUrl":"https://doi.org/10.2174/0113862073322931241030104813","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of depression in COVID-19 patients is notably high, disrupting daily life routines and compounding the burden of other chronic health conditions. In addition, to elucidate the connection between COVID-19 and depression, we conducted an analysis of commonly differentially expressed genes [co-DEGs], uncovering potential biomarkers and therapeutic avenues specific to COVID-19-related depression.</p><p><strong>Methods: </strong>We obtained gene expression profiles from the Gene Expression Omnibus [GEO] database with strategic keyword searches [\"COVID-19\", \"depression,\" and \"SARS\"]. We used functional enrichment analysis of the co-DEGs to decipher their likely biological roles. Then, we utilized protein-protein interaction [PPI] network analysis to identify hub genes among the co- DEGs. These findings were validated via an independent third-party dataset.</p><p><strong>Results: </strong>Our analysis of blood samples from COVID-19 patients revealed 10,716 upregulated genes and 10,319 downregulated genes. In addition, by applying the same approach to depression samples, we identified 571 upregulated and 847 downregulated genes. Furthermore, by intersecting these datasets, we extracted 121 upregulated and 175 downregulated co-DEGs. Through PPI network construction and hub gene selection, we identified MPO, ARG1, CD163, FCGR1A, ELANE, LCN2, and CR1 as co-upregulated hub genes and MRPL13, RPS23, and MRPL1 as co-downregulated hub genes. The incorporation of third-party datasets revealed that these hub genes are specific targets of SARS-CoV-2, not generic viral response mechanisms.</p><p><strong>Conclusion: </strong>The identification of potential biomarkers represents a groundbreaking strategy for assessing and treating depression in the context of COVID-19, with the potential to reduce its prevalence among these patients. However, to fully harness this potential, additional clinical research is paramount.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945899","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
Paederia Foetida Linn (Rubiaceae): Chemical Diversity, Phytopharmacological Potential, Quantitative Analysis and Clinical Approaches. 小檗(茜草科):化学多样性、植物药理学潜力、定量分析和临床方法。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-01-07 DOI: 10.2174/0113862073314773241115100620
Jyotsana Dwivedi, Pranay Wal, Vijay D Wagh, Pranjal Sachan, Neha Shukla Joshi, Swapnil Goyal, Arpan Kumar Tripathi
{"title":"Paederia Foetida Linn (Rubiaceae): Chemical Diversity, Phytopharmacological Potential, Quantitative Analysis and Clinical Approaches.","authors":"Jyotsana Dwivedi, Pranay Wal, Vijay D Wagh, Pranjal Sachan, Neha Shukla Joshi, Swapnil Goyal, Arpan Kumar Tripathi","doi":"10.2174/0113862073314773241115100620","DOIUrl":"https://doi.org/10.2174/0113862073314773241115100620","url":null,"abstract":"<p><p>The discovery of novel counteractive pharmaceuticals, which have recently generated much interest, has played a significant role in the development of drugs derived from herbal medicines or botanical sources. Paederia foetida (P. foetida) is one such example of a role in both traditional and traditional medicine. Owing to its popularity in folk medicine, it has been the subject of intense pharmacological and chemical studies for the last 30 years. They are locally known as \"Gandhavadulia\" or \"GandhaPrasarini\" (English name \"skunkvine\") and belong to the family Rubiaceae. This plant has a broad range of applications in the treatment of several illnesses, including anti-inflammatory, antinociceptive, antitussive, thrombolytic, antidiabetic, antihyperlipidaemic, antioxidant, nephroprotective, anti-inflammatory, hepatoprotective, anthelmintic, and antidiarrheal effects. Additionally, it contains a variety of phytochemicals, such as asperuloside, paederosidic acid, sitosterols, campesterol, lignans, alkaloids, volatile oils, iridoids, methylindooxy substances, stigmasterol, tannins, triterpenoids, ellagic acid, ursolic acid, epifriedelinol, and phenolic compounds. Recently, mounting data on numerous active ingredients have indicated that they may be beneficial for spermatogenesis, wound healing, inflammatory illnesses, and cancer. This review describes the phytochemistry and mechanisms of action of these pharmacological effects and provides insights into potential pharmacological targets. These results highlight the need for additional studies on this medicinal plant and the investigation of new counteractive medications to determine their mode of action before use in healthcare.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945643","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
A Novel Prognostic Risk Model Based on Oxidative Stress to Predict Survival and Improve Treatment Strategies in Stomach Adenocarcinoma. 基于氧化应激的新型预后风险模型预测胃腺癌患者的生存并改进治疗策略。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-01-07 DOI: 10.2174/0113862073353612241030061241
Nuo Yao, Kexin Lin, Xiaodong Qu, Xuezhi Li, Xingyu Zhao, Songbo Li, Jie Zhang, Yongquan Shi
{"title":"A Novel Prognostic Risk Model Based on Oxidative Stress to Predict Survival and Improve Treatment Strategies in Stomach Adenocarcinoma.","authors":"Nuo Yao, Kexin Lin, Xiaodong Qu, Xuezhi Li, Xingyu Zhao, Songbo Li, Jie Zhang, Yongquan Shi","doi":"10.2174/0113862073353612241030061241","DOIUrl":"https://doi.org/10.2174/0113862073353612241030061241","url":null,"abstract":"<p><strong>Background: </strong>Stomach adenocarcinoma (STAD) is the fifth most common tumor worldwide, imposing a significant disease burden on populations, particularly in Asia. Oxidative stress is well-known to play an essential role in the occurrence and progression of malignancies. Our study aimed to construct a prediction model by exploring the correlation between oxidative stress-related genes and the prognosis of patients with STAD.</p><p><strong>Method: </strong>STAD data from TCGA were used to identify the differentially expressed oxidative stress-related genes (OSGs), with data from GEO serving as the validation cohort. Univariate Cox and LASSO regression analyses were performed to select prognosis-related genes for the risk model, which was then integrated with clinical features into a nomogram. The physiological functions and pathways of these identified genes were explored using GO and KEGG analyses. After evaluating the prediction value of the prognostic model in the GEO cohort, drug sensitivity and immune infiltration were comprehensively analyzed using R. Expression levels of the prognostic genes were verified by quantitative real-time PCR in gastric cancer and paired normal tissues.</p><p><strong>Results: </strong>Cox regression and LASSO regression analysis identified SERPINE1, VHL, CD36, NOS3, ANXA5, ADCYAP1, POLRMT and GPX3 as the signature genes from 160 differentially expressed OSGs. Both Kaplan-Meier survival analysis and ROC curve at 5 years in the TCGA and the GEO cohort exhibited great predictive ability of the prognostic model, with the AUC >0.7 in TCGA. Validated as an independent risk factor, the model was integrated with clinicopathological variables (including age, stage, and gender) to build a nomogram for more accurate risk stratification. Moreover, therapy sensitivity analysis between the low- and high-risk categories showed that those who scored higher would benefit more from BEZ235, Dasatinib, Pazopanib, and Saracatinib. Meanwhile, differences in the tumor environment, immune infiltration and response to immunotherapy between the two groups were noted. Finally, qRT-PCR validated the differential expression of these genes in STAD and paired normal tissues.</p><p><strong>Conclusion: </strong>Our study has effectively established an oxidative stress-related prognostic model, providing a promising tool for personalized clinical strategies and improved STAD patient outcomes.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945861","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
Exploration of the Mechanism of Tanre Qing Injection in Treating Acute Respiratory Distress Syndrome through Network Pharmacology, Molecular Docking, and Animal Experiments. 网络药理学、分子对接及动物实验探讨痰热清注射液治疗急性呼吸窘迫综合征的机制
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-01-07 DOI: 10.2174/0113862073331156241029074305
Liang Wang, Ganqun Lu, Tianyu Cheng, Shuangquan Wen, Wenxiang Ma, Yixuan Li
{"title":"Exploration of the Mechanism of Tanre Qing Injection in Treating Acute Respiratory Distress Syndrome through Network Pharmacology, Molecular Docking, and Animal Experiments.","authors":"Liang Wang, Ganqun Lu, Tianyu Cheng, Shuangquan Wen, Wenxiang Ma, Yixuan Li","doi":"10.2174/0113862073331156241029074305","DOIUrl":"https://doi.org/10.2174/0113862073331156241029074305","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the active components and potential mechanism of Tanre Qing Injection (TRQI) in the treatment of Acute Respiratory Distress Syndrome (ARDS) using network pharmacology, molecular docking, and animal experiments.</p><p><strong>Methods: </strong>The targets of active ingredients were identified using the TCMSP and Swiss Target Prediction databases. The targets associated with ARDS were obtained from the GeneCards database, Mala card database, and Open Targets Platform. A Protein-protein Interaction network (PPI) was constructed, and the core targets were subjected to Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, molecular docking technology and a mouse model of lipopolysaccharide-induced acute lung injury validated the experimental results.</p><p><strong>Results: </strong>The results of network pharmacology showed the active components of TRQI in the treatment of ARDS to be baicalin, chenodeoxycholic acid, oroxylin-A, and ursodeoxycholic acid, and the core targets to be TP53, ESR1, AKT1, JUN, and SRC. KEGG analysis showed 181 signaling pathways, primarily including the IL-17 signaling pathway, endocrine resistance, lipid metabolism, and atherosclerosis. Molecular docking results demonstrated that baicalin, chenodeoxycholic acid, oroxylin-A, and ursodeoxycholic acid in TRQI exhibited the strongest affinity for TP53, ESR1, and SRC. Furthermore, the results of animal experiments have indicated TRQI to have a significant inhibitory effect on inflammatory factors TNF-α, IL-1β, and IL-6, and effectively alleviate the pathological damage of ARDS to lung tissue.</p><p><strong>Conclusion: </strong>TRQI may exert its therapeutic effects on ARDS through multiple targets and pathways, providing a research basis for its clinical application and further development.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945894","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
Integrated Network Pharmacology and Transcriptomics Analysis to Elucidate the Mechanism of Huoxue Tongluo Qiwei Decoction in the Treatment of Erectile Dysfunction in Spontaneously Hypertensive Rats through Angii-Activated Pkcε Pathway. 综合网络药理学和转录组学分析:活血通络七味汤通过血管激活Pkcε通路治疗自发性高血压大鼠勃起功能障碍的机制
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-01-07 DOI: 10.2174/0113862073330086241016115236
Junlong Feng, Sheng Deng, Bin Wang, Cong Zhao, Kali Zou, Haisong Li, Jisheng Wang
{"title":"Integrated Network Pharmacology and Transcriptomics Analysis to Elucidate the Mechanism of Huoxue Tongluo Qiwei Decoction in the Treatment of Erectile Dysfunction in Spontaneously Hypertensive Rats through Angii-Activated Pkcε Pathway.","authors":"Junlong Feng, Sheng Deng, Bin Wang, Cong Zhao, Kali Zou, Haisong Li, Jisheng Wang","doi":"10.2174/0113862073330086241016115236","DOIUrl":"https://doi.org/10.2174/0113862073330086241016115236","url":null,"abstract":"<p><strong>Background and aim: </strong>As a classical formula to invigorate blood circulation, Huoxue Tongluo Qiwei Decoction (HTQD) can effectively treat hypertensive erectile dysfunction (ED), but its exact mechanism of action is not yet clear. The goal of this research was to explore the potential mechanism of HTQD in improving hypertensive erectile dysfunction in rats through transcriptomics, network pharmacology, and associated animal experimentations.</p><p><strong>Methods: </strong>The HTQD chemical constituents were screened using high-performance liquid chromatography- tandem mass spectrometry (HPLC-MS/MS). Furthermore, transcriptomics analysis was performed via mRNA sequencing to identify significantly differentially expressed proteins. Moreover, the key target proteins of HTQD in the treatment of hypertensive ED were screened by network pharmacology and transcriptomics. In addition, the endothelial cells of the corpus cavernosum were assessed using hematoxylin-eosin staining. The transcript and protein expressions were evaluated via western blotting and Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>The network pharmacology and transcriptome mRNA sequencing revealed that KCNE1 may be the target protein of HTQD in improving hypertensive ED. After HTQD treatment, the systolic and diastolic blood pressure (BP) of hypertensive rats decreased, the number of erections increased, and the pathological structure of the penis was improved. Moreover, HTQD downregulated the protein and mRNA expression of AngII, AT1R, DAG, and PKCε, whereas it upregulated the transcript and protein expression of KCNE1.</p><p><strong>Conclusion: </strong>HTQD may activate the PKCε pathway through AngII, inhibit the expression of KCNE1 protein, relax vascular smooth muscles, and improve erectile function.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945901","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 Bioactivities and Chemical Composition Analysis of Rhizome Oleoresin of Hedychium coronarium Collected from Uttarakhand, India. 印度北阿坎德邦姜花根茎油树脂的生物活性及化学成分分析。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-01-07 DOI: 10.2174/0113862073327439241119113953
Sushila Arya, Ravendra Kumar, Om Prakash, Mamta Latwal, Ganesh Pandey, Satya Kumar, R M Srivastava, Suraj N Mali
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