Combinatorial chemistry & high throughput screening最新文献

{"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}

{"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}

{"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}

{"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}

{"title":"Study on the Mechanism of Anti-Atopic Dermatitis by Herba Siegesbeckiae Based on Metabolomics.","authors":"YingYue Wang, Xiaowei Chen, Lingling Zhang, Yuting Chen, Yubin Xu, Chunxue You, Xuetao Lu","doi":"10.2174/0113862073345094241226112758","DOIUrl":"https://doi.org/10.2174/0113862073345094241226112758","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis is a common inflammatory skin disease worldwide that is characterized by skin barrier dysfunction, itching, and a reduced quality of life.</p><p><strong>Objective: </strong>The research at hand aimed to delve into the anti-atopic dermatitis mechanism of Herba Siegesbeckiae, a traditional medicinal herb, using a metabolomic approach.</p><p><strong>Methods: </strong>The molecular mechanism by which Herba Siegesbeckiae acts against atopic dermatitis was investigated by establishing a mouse model of atopic dermatitis while conducting a metabolomics analysis on its metabolites.</p><p><strong>Results: </strong>Interleukin IL-13, IL-17A, IL-3, IL-31, IL-33, IL4, IL-5, TSLP, IgE, and histamine levels in serum, participating in inhibiting itching and regulating immunity signaling were found to be restored to varying degrees in AD treating with HS. A total of 31 differential metabolites were selected from metabolomics results, among which N-acetyl-L-alanine (VIP = 1.62), Nacetyl- L-methionine (VIP = 1.5), uracil (VIP = 1.47), and prostaglandin E2 (VIP = 1.4) play important roles in the anti-AD regulatory mechanisms of HS and can be used as biomarkers. In addition, the mechanisms of HS anti-AD have been shown to be associated with seven metabolic pathways, including β-alanine metabolism, glycerophospholipid metabolism, histidine metabolism, and so on.</p><p><strong>Conclusion: </strong>In conclusion, HS demonstrated properties that counteract Atopic Dermatitis by suppressing itchiness and boosting the immune system, subsequently controlling the concentrations of related metabolites.</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":"143364002","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":"Systems Biology Approach to Unraveling Transcriptomic Mechanisms of Ganfule Capsules in Ameliorating Nonalcoholic Fatty Liver Disease.","authors":"Yu Pan, Yunkun Zhang, Suren R R Sooranna, Xiaonan Yang, Yaqin Zhou, Lu Chen, Fei Xu, Danna Huang","doi":"10.2174/0113862073335295241216152011","DOIUrl":"https://doi.org/10.2174/0113862073335295241216152011","url":null,"abstract":"<p><strong>Aims: </strong>The primary objective of this study is to explore the impact of Ganfule (GFL), a traditional Chinese medicine, on differentially expressed genes (DEGs) linked to nonalcoholic fatty liver disease (NAFLD). By identifying potential biomarkers, we seek to enhance GFL's clinical efficacy through targeted pharmaceutical design.</p><p><strong>Background: </strong>NAFLD a prevalent liver disorder, is often associated with obesity and metabolic syndrome. While GFL has demonstrated clinical efficacy in treating NAFLD, its precise targets and mechanisms of action remain elusive. Understanding these mechanisms could pave the way for more effective treatments.</p><p><strong>Objectives: </strong>GFL, a long-standing traditional Chinese medicine (TCM), has demonstrated clinical effectiveness in treating NAFLD. However, its precise targets and mechanism of action remain elusive. In this study, we aim to explore GFL's impact on differentially expressed genes, which could potentially serve as biomarkers for developing targeted therapies. This approach is intended to enhance GFL's clinical efficacy by identifying key genes that respond to its treatment.</p><p><strong>Methods: </strong>To induce NAFLD, 23 Sprague-Dawley rats were fed a high-fat diet. These rats were then categorized into three groups: normal diet (NOR), high-fat diet model (HFD), and those treated with GFL. Highthroughput sequencing was employed to identify DEGs in their livers. Utilizing the STRING and DAVID databases, we analyzed potential protein interactions expressed by these genes. Furthermore, the KEGG, Reactome, and Wiki databases aided in determining their biological roles and signaling pathways. Key DEGs' mRNA expression levels and corresponding proteins were further screened and confirmed through haematoxylin- eosin staining (HE), immunohistochemistry (IHC), Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR), and western blotting.</p><p><strong>Results: </strong>Significant variations in DEGs were observed across the three groups, with 19 intersecting genes identified within a cluster of 90 NAFLD-related genes. GFL was found to adjust the expression of nine core DEGs, including Abcg1, Igfgb1, Lepr, Pdk4, Socs3, and Stat3. These genes-related proteins are tied to proteins such as FABP4, LEPR, SCD1, SOCS3, and STAT3, which are intimately connected to adipocytokine and adipogenesis pathways. Our study reveals that GFL modifies the expression of IGFBP1, LEPR, PDK4, SCD1, and SOCS3, thereby regulating the adipocytokine, JAK-STAT, leptin-insulin signaling, and adipogenesis metabolic pathways, respectively.</p><p><strong>Conclusions: </strong>This study enhances understanding of GFL's efficacy and identifies potential biomarkers for NAFLD treatment. Optimizing GFL's efficacy and elucidating its mechanism provides a methodological reference for traditional Chinese medicine exploration.</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":"143364012","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":"Yueju Pill Inhibits Apoptosis by Regulating the SCF/c-Kit/PI3K/AKT Signaling Pathway to Ameliorate Functional Dyspepsia.","authors":"Yaru Gu, Yaning Biao, Chenxu Liu, Yufang Zhang, Ya Gao, Yucong Xue, Yixin Zhang","doi":"10.2174/0113862073344555241120103257","DOIUrl":"https://doi.org/10.2174/0113862073344555241120103257","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the therapeutic effect of Yueju Pill (YJP) on functional dyspepsia (FD) rats and its mechanism of promoting gastrointestinal motility.</p><p><strong>Methods: </strong>We replicated FD rat models using classical tail pinching and irregular feeding for 14 days. After 28 days of YJP treatment, we measured the gastric emptying rate and intestinal propulsion rate of the rats. Hematoxylin-eosin (H&E) staining was used to observe the pathological damage in the gastric antrum. The serum levels of related brain-gut peptides (BGPs) were determined using the enzyme-linked immunosorbent assay (ELISA). Furthermore, we detected the expression of proteins related to the SCF/c-Kit/PI3K/AKT signaling pathway through Western blot and immunohistochemistry. Finally, we assessed the levels of apoptosis using the TUNEL assay.</p><p><strong>Results: </strong>YJP improved gastric emptying and small intestine propulsion rates while reducing gastric tissue injury in FD rats. Moreover, YJP increased the levels of gastrin (GAS) and ghrelin (Ghrelin) and decreased the levels of cholecystokinin (CCK) and vasoactive intestinal peptide (VIP). YJP also elevated the levels of SCF, c-kit and Bcl-2, promoted the phosphorylation of PI3K and AKT, and inhibited the expression of Bax.</p><p><strong>Conclusion: </strong>YJP achieved the effect of FD treatment by regulating the SCF/c-Kit/PI3K/AKT pathway, providing a theoretical basis for the clinical treatment of FD.</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":"143364019","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 Anti-lung Cancer Mechanism of Qingzao Jiufei Decoction was Studied based on Network Pharmacology, Molecular Docking, and Experimental Verification.","authors":"Xiaoli Wen, Fangyan Cai, Min Tan, Ge Zhang, Xiang Zhang, Lihua Xie, Ziheng Yao, Hongning Liu","doi":"10.2174/0113862073347396241227122956","DOIUrl":"https://doi.org/10.2174/0113862073347396241227122956","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Lung cancer (LC) is one of the most common cancers in the world, with both its incidence and mortality rates ranking at the top position among all types of cancers, posing a serious threat to human health. Qingzao Jiufei Decoction (QD) has been used clinically to treat lung cancer, but its mechanism of action remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to elucidate the potential pharmacological mechanisms of QD in treating LC through network pharmacology, molecular docking, molecular dynamics simulation (MDS), and animal experiment validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Active components of QD were screened utilizing the TCMSP and HREB databases, and potential targets were predicted using network pharmacology methods. Relevant targets for LC were identified from the Genecards, OMIM, and TTD databases. Intersecting targets between QD and LC were imported into the STRING 12.0 database and Cytoscape 3.10.0 software to create proteinprotein interaction (PPI) network diagrams, and Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted through using the DAVID database to identify core active components and key targets. Molecular docking was employed to assess the binding affinity of core active components with key targets in lung cancer, and MDS was used to evaluate the stability of the target-active component complexes. An in vivo lung cancer model was used to verify the therapeutic effects of QD, and Western blot analysis was used to confirm the pharmacological mechanisms of QD in treating lung cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Network pharmacology analysis has identified 9 core components and 9 key targets. GO and KEGG analyses have revealed a total of 185 signaling pathways, with the PI3K-Akt signaling pathway and MAPK signaling pathway being the two most significantly enriched pathways. Molecular docking results showed that all 9 core components and 9 key targets exhibited significant binding activity (binding energy &lt; -5 kcal/mol). MDS study further simulated and confirmed strong and stable interactions between targets and active components. In an in vivo lung cancer model, QD significantly inhibited tumor growth, while Western blot analysis demonstrated that QD exerted its therapeutic effects on lung cancer by inhibiting the phosphorylation of ERK, JNK, and p38 in the MAPK signaling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This experimental study found that QD can significantly inhibit the growth of lung cancer through a multifaceted approach involving various components, targets, and pathways, providing a foundation for the development and clinical application of new drugs targeting lung cancer for QD. Furthermore, it offers valuable insights into anti-tumor research with Traditional Chinese Medicine (TCM) and facilitates a more comprehensive interpretation of TCM principles through the lens of modern ","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":"143364014","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":"Isolation, Characterization, and Evaluation of the Mucilage from Pedalium murex Linn. Leaves.","authors":"Leema Rose Mary Devasahayam, Marie Arockianathan Pushpam, Lawrance Antonysamy, Senthamizhselvan Anbazhagan","doi":"10.2174/0113862073345969241129043350","DOIUrl":"https://doi.org/10.2174/0113862073345969241129043350","url":null,"abstract":"<p><strong>Background: </strong>Many plant-derived compounds have been used as pharmaceutical excipients due to their various functional properties. One such plant product is mucilage, which has created great interest among researchers to be explored for numerous biological applications.</p><p><strong>Objectives: </strong>The objective of the present study was to isolate mucilage from the leaves of Pedalium murex Linn. (family; Pedaliaceae). The obtained mucilage was characterized physiochemically and evaluated for its antioxidant and anticancer properties.</p><p><strong>Methods: </strong>The obtained mucilage was screened for its phytochemicals and characterized physiochemically using FTIR, XRD, DSC, and SEM. Its antioxidant property was analyzed using DPPH and FRAP assays. The anticancer activity of the mucilage was evaluated against colon and cervical cancer cell lines using an MTT assay.</p><p><strong>Results: </strong>The phytochemical screening of the mucilage demonstrated the ability to reduce sugars, flavonoids, amino acids, tannins, saponins, and steroids. The yield percentage of mucilage was 24%, and it has a swelling index of 10. It was found to be soluble in warm water and showed a pH of 9. The FTIR spectra of mucilage showed characteristic peaks of its functional groups. The SEM image showed a porous and rough morphological surface of mucilage. The obtained mucilage demonstrated antioxidant activity by DPPH and FRAP assays and exhibited anticancer activity against cervical and colon cancer cell lines using the MTT assay.</p><p><strong>Conclusion: </strong>Mucilage contains many phytochemicals with various functional properties like antioxidant and anti-cancer activities. Thus, the isolated mucilage from Pedalium murex Linn. showed promising characteristics that could be tailor-made for various biological applications.</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":"143364000","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":"Role of Cellular Mechanisms in Dengue Pathogenesis: Focus on Immune Cells Interactions.","authors":"Rituraj Niranjan, Khashpatika Ganesh","doi":"10.2174/0113862073349558241216040511","DOIUrl":"https://doi.org/10.2174/0113862073349558241216040511","url":null,"abstract":"<p><p>Dengue is an arbovirus mosquito-borne disease that occurs after an infection with dengue virus. Dengue virus releases E-proteins, which act as binding proteins and enter the host cell after infection. It triggers several cellular reactions and activates the immune system; however, the mechanisms are still poorly understood. Our goal is to find out how these cellular interactions participate in the activation of immune cells and participate in dengue pathogenesis. Once dengue infects the host cell, it follows these steps: (1) dengue virus releases M- protein into the skin of the host, and it infects the Langerhans cells of the skin, which is a dendritic cell which acts as antigen representing cells. (2) After infection with dendritic cells, the virus enters into the blood cells white blood cells (monocytes, lymphocytes, neutrophils, eosinophils, basophils, and macrophages), red blood cells (erythrocytes), and platelets. After blood cell infection, it targets monocytes or macrophage cells and starts replication. Once replication is done, it circulates in all parts of the organ as well as its cells like endothelium (Endotheliocytes), liver (Hepatocytes, Kupffer), tissue macrophages, Bone marrow (Stromal cells) and enhances endothelial permeability possibly by overproducing matrix metalloproteinases (MMPs) and other cellular mediators. (3) Once all monocytes cell of blood gets infected, it activates NK cell, IFNγ and TNF-α response. For the execution of this mechanism, various pattern recognition receptors, such as Toll-like Receptor 3 (in endosome), play a role in pathogen recognition and activation of innate immunity. (4) MDA5 (melanoma differentiation-associated protein 5) MDA5 protein can function as a cytosolic sensor that recognizes viral double-strand RNA and then triggers the transcription of genes encoding type I interferon (IFN) and RIG-I (retinoic acidinducible gene-I) is an intracellular molecule that responds to viral nucleic acids and activates downstream signalling, resulting in the induction of members of the type I interferon (IFN) family. Non-structural part of the virus secretes NS protein, which disrupts the endothelial glycocalyx layer (EGL) by enkindling the upregulation of 3 of the 4 endothelial sialidases (cytosolic (Neu 2), plasma membrane (Neu 3), and lysosomal (Neu 1). These sialidases translocate to the plasma membrane and lead to the hydrolysis of the endothelial glycocalyx layer expressed sialic acid residues, which disrupts the endothelial layer, and as an end result, it increases the pathogenesis of dengue fever. Collectively, the various molecules of the dengue virus activate different cellular components of immune cells, leading to immune dysfunctions and causing severe dengue pathogenesis.</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":"143398267","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}