Combinatorial chemistry & high throughput screening最新文献

{"title":"Constipation and Psychiatric Disorders: A Bidirectional Mendelian Randomization Study.","authors":"Xu Yang, Jie Kang, Xuan Zhang, Nan Sui","doi":"10.2174/0113862073378253250428071105","DOIUrl":"https://doi.org/10.2174/0113862073378253250428071105","url":null,"abstract":"<p><strong>Background: </strong>Observational studies have shown a link between constipation (CN) and psychiatric disorders, including Schizophrenia (SP), Bipolar disorder (BD), Schizoaffective disorder (SD), and Parkinson's disease (PD). However, it is still unknown whether CN affects the occurrence and development of psychiatric disorders or whether psychiatric disorders cause the occurrence and development of CN. Therefore, this study used Mendelian randomization (MR) analysis to evaluate the relationship between CN and psychiatric disorders.</p><p><strong>Method: </strong>We used genome-wide association studies (GWAS) to assess the relationship between constipation (N = 411, 623) and four psychiatric disorders, including SP ( N = 77, 096), BD (N = 51, 710), SD ( N = 210, 962), PD (N = 482, 730 ), using bidirectional MR analysis. Inverse variance weighting (IVW), MR Egger (ME) and Weighted median (WM) were used as causal analysis methods. Cochran's Q test, funnel plot, MR Egger intercept test and Leave-one-out analysis were used to detect sensitivity. Confounding factors were analyzed and eliminated by LDtrait to avoid influencing the final MR Analysis result.</p><p><strong>Results: </strong>The results of positive MR analysis indicated that there was no evidence of influence of constipation on SP ( OR 1.043, 95%CI 0.946 - 1.149, P value = 0.398), BD (OR 1.114, 95%CI 0.995 - 1.248, P value = 0.062), SD (OR 0.934, 95%CI 0.674 - 1.294, P value = 0.682) and PD (OR 1.118, 95%CI 0.918 - 1.361, P value = 0.269) under gene prediction. Reverse MR analysis suggested that SP (OR 1.030, 95% CI 1.001-1.060, P value = 0.042) had a causal relationship with constipation. BD (OR 0.993, 95% CI 0.962-1.025, P value = 0.664), SD (OR 1.021, 95% CI 0.984-1.059, P value = 0.265) and PD (OR 1.004, 95% CI 0.974-1.035, P value = 0.790) were not associated with CN.</p><p><strong>Conclusion: </strong>There was a positive association between SP and CN. CN may have no exact causal relationship with BD, SD and PD, and the interaction mechanism between these diseases needs to be further explored.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076431","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":"An Analysis of Effective Components of Pulsatillae radix Using UHPLC-QTOF-MS/MS and Network Pharmacology to Investigate its Effects on Ulcerative Colitis.","authors":"Jiaojiao Zhang, Xing Chen, Yuman Li, Xue Ma, Nuo Xu, Tuanjie Wang, Yun Shi, Kunming Qin","doi":"10.2174/0113862073358579250428103652","DOIUrl":"https://doi.org/10.2174/0113862073358579250428103652","url":null,"abstract":"<p><strong>Background: </strong>Pulsatillae radix (PR), a medicinal root plant and a well-known Chinese herbal remedy, is primarily used for its heat-clearing, detoxifying, blood-cooling, and antiinflammatory properties. This study aimed to investigate the underlying mechanisms by which PR exerts therapeutic effects on ulcerative colitis (UC) through an integrated approach, combining ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS), network pharmacology, and molecular docking.</p><p><strong>Methods: </strong>The constituents of PR were systematically analyzed using UHPLC-Q-TOF-MS/MS. Potential targets of active components were identified via the SwissTargetPrediction and PharmMapper databases, while UC-related disease targets were retrieved from GeneCard, OMIM, and other relevant databases. Overlapping targets between PR and UC were determined using Venn analysis. Cytoscape software facilitated the construction of the compound-disease-target network. The STRING database was employed to generate a protein-protein interaction (PPI) network for the intersecting targets, and core targets were identified using the CytoNCA plugin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the DAVID platform. Lastly, molecular docking of key components with target proteins was carried out using PyMOL.</p><p><strong>Results: </strong>A total of 27 active compounds, 237 drug targets, and 4622 disease targets were identified. Intersection analysis revealed 141 shared targets, while the PPI network identified 10 hub targets. GO and KEGG enrichment analyses indicated that the hub targets were primarily associated with phosphorylation, cytoplasmic functions, nuclear receptor activity, as well as pathways related to the advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling, T cell receptor (TCR) signaling, lipid and cholesterol metabolism, and various cancer-related pathways. Molecular docking experiments demonstrated that (+)- pinoresinol, cichoric acid, β-ecdysone, pulsatilla saponin D, 23-HBA, and AB4 exhibited stable binding to PIK3R1, TLR4, and ESR1, with AB4 forming the most stable complex with ESR1.</p><p><strong>Conclusion: </strong>This study established a rapid and effective UHPLC-Q-TOF-MS/MS method for characterizing the main chemical components of PR. Using network pharmacology and molecular docking, the active components and potential mechanisms of PR involved in the UC treatment were investigated, providing a foundation for future experimental studies on pharmacodynamics and the underlying mechanisms.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076330","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":"KLHL17 as a Prognostic Indicator and Therapeutic Target in Cervical Cancer: A Comprehensive Analysis.","authors":"Guizhen Lyu, Jinyuan Li, Dongbing Li","doi":"10.2174/0113862073378446250417123724","DOIUrl":"https://doi.org/10.2174/0113862073378446250417123724","url":null,"abstract":"<p><strong>Background: </strong>The role of kelch like family member 17 (KLHL17) in cervical cancer (CESC) is unclear.</p><p><strong>Objective: </strong>To clarify this uncertainty, our research employed bioinformatics analysis coupled with experimental corroboration.</p><p><strong>Methods: </strong>We utilized the Cancer Genome Atlas (TCGA) database to assess the expression of KLHL17 in various cancers, specifically CESC, and to explore its association with clinical characteristics, diagnostic utility, and prognostic significance in CESC. The current investigation delved into the potential regulatory pathways related to KLHL17, examining its connection with the infiltration of immune cells, the expression of immune checkpoint genes, the status of microsatellite instability (MSI), and the efficacy of diverse therapeutic agents in CESC. The research analyzed KLHL17 expression patterns using single-cell sequencing data from CESC samples and investigated the genetic variations of KLHL17 within this context. KLHL17 expression was validated using GSE145372. The presence and levels of KLHL17 in different cell lines were validated through quantitative real-time PCR (qRT-PCR) assays.</p><p><strong>Results: </strong>KLHL17 exhibited irregular expression profiles across various cancer types, including CESC. Furthermore, increased KLHL17 levels in CESC patients were significantly associated with a lower progression-free survival (PFS) rate (hazard ratio: 1.62; 95% confidence interval: 1.01-2.60, p = 0.044). Moreover, KLHL17 expression emerged as a distinct prognostic indicator for CESC patients (p = 0.031). It has been associated with various biological pathways, such as cytokine-cytokine receptor interaction, primary immunodeficiency, cell adhesion molecules (CAMs), chemokine signaling pathway, steroid hormone biosynthesis, and others. The expression levels of KLHL17 were found to correlate with the presence of immune cells, the expression of immune checkpoint genes, and the status of MSI within CESC. Furthermore, KLHL17 expression exhibited a significant and inverse correlation with XMD15-27, rTRAIL, Paclitaxel, tp4ek, and tp4ek-k6. Furthermore, KLHL17 was found to be significantly positively regulated in CESC cell lines.</p><p><strong>Conclusion: </strong>KLHL17 is a promising prognostic marker and potential therapeutic target in CESC.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076436","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":"A Study on the Anti-Inflammatory and Antibacterial Effects of Huanglian Jiedu Decoction in the Treatment of Pressure Injuries.","authors":"Jing Gao, Dingxi Bai, Wenting Ji, Lin Zhu, Xianying Lu, Wei Wang, Chaoming Hou","doi":"10.2174/0113862073240207250424192712","DOIUrl":"https://doi.org/10.2174/0113862073240207250424192712","url":null,"abstract":"<p><strong>Objective: </strong>Pressure Injuries (PIs) severely affect the quality of life of patients. Infection and inflammation are key factors contributing to the progression of pressure injuries; therefore, their inhibition plays a crucial role in preventing the worsening of the condition. Huanglian Jiedu Decoction (HLJDD), as a typical traditional Chinese medicine with heat-clearing and detoxicating effects, has good broad-spectrum antibacterial and anti-inflammatory effects. It is commonly used in the treatment of clinically infected external wounds. However, the therapeutic effects of HLJDD on PI remains unclear.</p><p><strong>Methods: </strong>The extract of HLJDD was prepared using the water extraction and alcohol precipitation method. Sixty male SD rats were randomly divided into five groups (n = 12/group): control group, model group, normal saline group (negative control group), iodophor group (positive control group), and HLJDD group (test group). Except for the control group, magnet clamping and the Staphylococcus aureus inoculation method were used to construct the model of stage 3 PI infection wound in the other groups. After irrigating the wound, the healing rate, bacterial concentration, concentrations of IL-1, IL-6, and TNFα, and the protein expression levels of TLR2, MyD88, and NF-Bp65 were examined. Skin and ocular mucosal irritation tests were conducted to evaluate the safety of the topical application of HLJDD.</p><p><strong>Results: </strong>Rats treated with HLJDD exhibited an improved wound healing rate, along with reduced bacterial concentration on the wound surface and a significant decrease in the content of inflammatory cytokines (IL-1β, IL-6, and TNF-α). The protein expression levels of TLR2, MyD88, and NF-κBp65 were down-regulated after the administration of HLJDD. The prepared HLJDD did not cause any irritation.</p><p><strong>Conclusion: </strong>HLJDD can promote the healing of PI wounds and has a protective effect on PI through its anti-inflammatory and anti-bacterial properties.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075883","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":"Expression, Prognostic Significance, and Immune-Related Roles of ABCA Family Genes in Gastric Cancer: A Comprehensive Analysis.","authors":"Yongli Hu, Tianxiang Liu, Yan Du, Zhisheng Qiu, Mingxu Da, Pengxue Mao","doi":"10.2174/0113862073356415250423045501","DOIUrl":"https://doi.org/10.2174/0113862073356415250423045501","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have demonstrated that ABCA family proteins play a critical role in cholesterol transport. Cholesterol, as a major component of the cell membrane, can influence numerous physiological and pathological processes, including cell migration, cancer progression, and metastasis. Therefore, ABCA family proteins may impact cancer progression; however, their specific roles in gastric cancer remain poorly understood. Methods：In this study, we systematically assessed the expression, prognostic significance, and immune-related implications of ABCA family genes in gastric cancer (GC). Utilizing data from The Cancer Genome Atlas (TCGA) database, we compared ABCA expression profiles between GC and normal gastric mucosa. We conducted Kaplan-Meier analysis, Cox regression, and logistic regression to investigate associations with clinical characteristics, constructed ROC curves and nomograms for diagnostic evaluation, and single sample gene set enrichment analysis (ssGSEA) algorithm assessed ABCA relationships with immune cell infiltration, immune-related genes, immune checkpoint genes, the tumor immune dysfunction and exclusion (TIDE) predicts response to immuno-check inhibitor therapy, \"oncoPredict\" function for chemotherapy drug resistance analysis. We also employed Gene Set Enrichment Analysis (GSEA) to evaluate relevant signaling pathways. To validate our findings, we performed PCR to confirm ABCA expression in gastric cancer and normal gastric mucosal cells.</p><p><strong>Results: </strong>Our results demonstrate significant differential expression of most ABCA family members in GC tissues compared to normal tissues, with associations to clinicopathological parameters. Cellular experiments revealed distinct expression patterns of ABCA genes in GC cell lines, with some aligning with TCGA data and others showing variability. Differentially expressed transcripts correlated with overall survival, making ABCAs independent risk factors for GC patient survival. A validated nomogram predicted overall survival. ABCAs exhibited correlations with immune cell infiltration, co-expression with immune-associated and checkpoint genes, and implications for resistance to common therapies and immunotherapy. Enrichment analysis highlighted pathways involving the extracellular matrix, cell motility, cell death, and tumor development.</p><p><strong>Conclusion: </strong>In conclusion, ABCA family genes hold promise as prognostic biomarkers and potential immunotherapeutic targets due to their relevance in the tumor microenvironment, particularly in relation to immune cell infiltration.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076433","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":"Identification of Selected Genes Associated With the Prediction of Prognosis in Bladder Cancer.","authors":"Xiao-Dong Li, Jun-Ming Zhu, Qi You, Xiao-Hui Wu, Qi Huang, Hai Cai, Yong Wei, Yun-Zhi Lin, Xiong-Lin Sun, Ning Xu, Xue-Yi Xue, Qing-Shui Zheng","doi":"10.2174/0113862073352389250407104347","DOIUrl":"https://doi.org/10.2174/0113862073352389250407104347","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BC) is one of the most common urological malignancies, ranking as the eleventh most common cause of cancer-related deaths worldwide. The lack of specific and sensitive prognostic biomarkers presents a significant challenge in the early diagnosis and treatment of BC.</p><p><strong>Methods: </strong>We used the Gene Expression Omnibus (GEO) dataset GSE13507 and the Cancer Genome Atlas (TCGA) database to screen differentially expressed genes related to BC. By using Weighted Gene Co-expression Network Analysis (WGCNA), two modules associated with BC were investigated in GSE13507 and TCGA. Hub genes were identified through Protein-Protein Interaction (PPI) network analysis and their functions were validated through multiple approaches, including Gene Expression Profiling Interactive Analysis (GEPIA), Western Blotting (WB) assay, Human Protein Atlas (HPA), Oncomine analysis, and quantitative Real-Time PCR (qRTPCR) analysis. Additionally, miRNAs associated with hub gene expression were identified using various databases to predict the progression and prognosis of BC.</p><p><strong>Results: </strong>WCGNA and differential gene expression analysis identified 171 common genes as target genes. Ten genes (MYH11, ACTA2, TPM2, ACTG2, CALD1, MYL9, TPM1, MYLK, SORBS1, and LMOD1) were identified using the PPI tool and the CytoHubba plugin of Cytoscape. The CALD1 and MYLK genes showed a significant prognostic value for overall survival and diseasefree survival in patients with BC. According to the HPA and Oncomine databases, CALD1 and MYLK expression levels were significantly lower in BC tissues than in normal tissues. Additionally, qRT-PCR analysis, WB assay, and immunohistochemical analysis confirmed CALD1 and MYLK as tumor suppressor genes in BC. Furthermore, miR-155 showed a significant positive correlation with MYLK.</p><p><strong>Conclusion: </strong>This study established MYLK as a direct target gene of miR-155, functioning as an actionable survival-related gene correlated with BC development.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076434","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":"State-of-the-Art Computational Investigation of Long-release Hydrochlorothiazide Formulation for Myocardial Infarction Prevention.","authors":"Rahul Maheshwari, Mayank Sharma, Sankha Bhattacharya","doi":"10.2174/0113862073376522250421022308","DOIUrl":"https://doi.org/10.2174/0113862073376522250421022308","url":null,"abstract":"<p><strong>Aim: </strong>The present investigation aims to employ a quality-by-design (QbD) approach to prioritize critical factors for the drug formulation and, thus, the number of experimental runs to be performed for the identification of critical quality attributes (CQA) while maintaining an adequate risk profile.</p><p><strong>Background: </strong>Hydrochlorothiazide (HCT), a diuretic class of drug, is often recommended with antihypertensives to prevent the problem of early morning heart attack (myocardial infarction).</p><p><strong>Method: </strong>Prior knowledge was systematically applied during the early development phase of risk assessment using the fishbone diagram and qualitative risk assessment, resulting in 17 factors that may influence the final quality of long-action hydrochlorothiazide tablets. A quantitative evaluation using Failure Mode Effect and Criticality Analysis (FMECA) was conducted on 11 preselected variables with medium and high risk, employing the Plackett-Burman (PB) design.</p><p><strong>Results: </strong>Utilizing logical reasoning, literature review, and preliminary data analysis, we minimized the number of experiments to a manageable level and further streamlined them using FMECA. Plackett-Burman design findings revealed that only three critical factors impacted selected quality attributes.</p><p><strong>Conclusion: </strong>The quality risk management tool has successfully helped to identify critical variables affecting critical quality attributes and reduce the number of experimental runs to a manageable level.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978583","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":"Metabolomics and Network Pharmacology Analyses Reveal the Mechanism of Moxibustion in Knee Osteoarthritis.","authors":"Yaqiong Su, Minfeng Fang, Ziyao Qiao, Na Zheng, Yun Yang, Jingjing Li, Weijian Zhao, Yaning Zhang, Hong Zhang, Ye Li, Chunliu Wang","doi":"10.2174/0113862073365403250423070858","DOIUrl":"https://doi.org/10.2174/0113862073365403250423070858","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to explore the mechanism of moxibustion in the knee by combining osteoarthritis metabolomics and network pharmacology.</p><p><strong>Methods: </strong>A rat knee osteoarthritis (KOA) model was established by intra-articular injection of papain. The efficacy of moxibustion in KOA rats was evaluated by swelling degree, pathological progress, and mobility loss of knee joint. On this basis, the metabolic mechanism of moxibustion in relieving knee osteoarthritis was analyzed by metabolomics analysis.</p><p><strong>Results: </strong>Moxibustion significantly reduced joint swelling and inflammation in the knee joint of KOA rats. Sixteen metabolites and nine metabolic pathways were found to be associated with the mechanism of action of moxibustion in metabolomics analysis results. According to network pharmacology, 3186 KOA disease targets, 158 drug targets, and 89 intersecting targets were obtained. The key targets included MAPK-3, AKT-1, RELA, MAPK-8, MAPK-14, etc. Signal pathways were found to be involved in mechanisms of moxibustion in knee osteoarthritis, such as alanine, aspartate, and glutamate metabolism, cysteine and methionine metabolism, and arginine and proline metabolism.</p><p><strong>Conclusion: </strong>The mechanism of moxibustion in knee osteoarthritis may involve alanine, aspartate, and glutamate metabolism, cysteine and methionine metabolism, arginine and proline metabolism, amino tRNA biosynthesis, and D-glutamine and D-glutamate metabolism signaling pathways with MAPK-3, AKT-1, RELA, MAPK-8, and MAPK-14 as core targets. More precise mechanisms need to be verified by further systematic molecular biology experiments.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982840","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":"Liuwei Dihuang Prevents Human Umbilical Vein Endothelial Cells Senescence via the JPX-STING-IRF3 Pathway","authors":"Chao Xu, Tiantian Cai, Xinghai Du","doi":"10.2174/1386207326666230901163717","DOIUrl":"10.2174/1386207326666230901163717","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence plays a crucial role in age-related diseases. Endothelial senescence is closely associated with age-related vascular disorders. This study aimed to reveal the role of traditional Chinese medicine Liuwei Dihuang (LWDH) in anti-endothelial cell senescence.</p><p><strong>Methods: </strong>Human umbilical vein endothelial cells (HUVECs) were exposed to LPS treatment to induce senescence. Senescence-associated β-galactosidase (SA-β-gal) positive staining, p53 and p16 expression, BrdU staining, and relative telomere length (RTL) experiments were conducted to estimate LPS-induced cellular senescence of HUVECs. Real-time qPCR analysis was performed to identify differentially expressed lncRNAs in LPS-induced senescent HUVECs before and after treatment with LWDH. Bioinformatics analysis and ChIP assay were conducted to explore the mechanism of JPX in the anti-endothelial cell aging effect of LWDH.</p><p><strong>Results: </strong>We first discovered that lncRNA JPX and STING-IRF3 pathways are involved in the process of anti-endothelial senescence of LWDH. Mechanistically, LWDH could reverse abnormally elevated JPX induced by LPS and inhibit the activation of STING, as well as the interaction between JPX and STING.</p><p><strong>Conclusion: </strong>Overall, our study explores the potential therapeutic value of LWDH and provides key insights into the potential avenues for preventing and treating HUVECs senescence.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10181934","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":"Circulating Inflammatory Proteins and Age-related Macular Degeneration: New Insights from Mendelian Randomization.","authors":"Yujin Guo, Jing Zhao, Zhiqing Chen","doi":"10.2174/0113862073373085250418113858","DOIUrl":"https://doi.org/10.2174/0113862073373085250418113858","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is a key mechanism underlying age-related macular degeneration (AMD); however, the specific circulating inflammatory proteins involved remain unclear. This study investigated the causal relationship between 91 circulating inflammatory proteins and AMD using a two-sample Mendelian randomization (MR) approach.</p><p><strong>Methods: </strong>We conducted a two-sample magnetic resonance imaging MR analysis using genomewide association study (GWAS) data. Five MR methodologies were applied, with inverse variance weighting (IVW) as the primary approach. We applied false discovery rate (FDR) correction to mitigate false positives. Sensitivity analyses were performed to assess horizontal pleiotropy and heterogeneity. Additionally, Steiger's test, reverse MR analysis, and linkage disequilibrium score regression (LDSC) were used to validate the results.</p><p><strong>Results: </strong>Five inflammatory proteins demonstrated significant associations with overall AMD, including three associated with wet AMD and one associated with dry AMD. LDSC analysis indicated that, except for fibroblast growth factor-19, no genetic correlation confounded the causal relationships. Additionally, the expression of the identified proteins was unaffected by the genetic prediction of AMD.</p><p><strong>Conclusion: </strong>This study highlights the causal relationship between specific inflammatory proteins and AMD, emphasizing their potential roles in AMD pathogenesis and potential therapeutic targets.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986167","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}