Combinatorial chemistry & high throughput screening最新文献

{"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":"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":"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":"Therapeutic Mechanism of Zhishi Decoction Regulating P38/MAPK Signaling Pathway on Functional Constipation (FC).","authors":"Jie Kang, Xu Yang, Nan Sui","doi":"10.2174/0113862073332162241126105559","DOIUrl":"https://doi.org/10.2174/0113862073332162241126105559","url":null,"abstract":"<p><strong>Background: </strong>Zhishi decoction (ZSD) is one of the most common herb decoctions in traditional Chinese medicine (TCM), and it is used for the treatment of FC. However, its main therapeutic mechanism is not yet clear. This study aims to explore the possible pharmacodynamic material basis and potential molecular mechanism from network pharmacology and molecular docking and verify them through animal experiments.</p><p><strong>Methods: </strong>Firstly, the effective ingredients, potential targets, and key targets of ZSD in the treatment of FC were screened through network pharmacology. Go and KEGG analyses were performed for potential targets. Secondly, molecular docking was used to link the main active components of ZSD with target genes to predict their possible molecular mechanisms. Finally, 30 male BALB/c mice (20±2 g) were randomly divided into five groups (n=6), including the blank group, ZSD groups with two dosages (7.15, 14.3 g/kg), FC model group, and positive group (lactulose group). All the mice were given difenoxate tablets for 14 days to establish FC model except the blank group. Moreover, the mice in the blank group were given the same volume of normal saline. After admination for 14 days, the whole colon tissues were obtained for the analysis of small intestinal propulsion rate, and the expression of P38MAPK in colon tissues of mice was observed via immunohistochemistry and WesterBlot.</p><p><strong>Results: </strong>In this study, 43 active ingredients in ZSD were identified. Four hundred and thirty potential therapeutic targets were selected, among which AKT1, MAPK12, and MAPK14 were key targets. 164 GO biological processes and 123 KEGG signaling pathways were identified after analysis， such as MAPK signaling pathway, TNF signaling pathway etc. The molecular docking results showed that Prangenin, 4-Hydroxyhomopterocarpin, isoponcimarin, and AKT1, MAPK12, MAPK14 had good binding degree. Additionally, ZSD could relieve the symptoms of FC in mice significantly. Compared with the model group, p38/MAPK positive expression cells and protein expression levels in the colon tissues of ZSD groups significantly increased in a dose-dependent manner (p<0.01).</p><p><strong>Conclusion: </strong>This study confirmed that ZSD could act on AKT1, MAPK12, and MAPK14 targets to activate the p38/MAPK signaling pathway to relieve FC induced by defenoxate tablets. The further development of ZSD provided a theoretical basis.</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":"143364017","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}

{"title":"Study on the Mechanism of the Leaves of Dimocarpus longan Lour. in the Management of Type 2 Diabetes based on Metabolomics.","authors":"Jie Liang, Piaoxue Zheng, Jue Hu, Xianfu Liu, Kuikui Chen, Yupin Cao, Yanli Liang, Chunlian Lu, Jingjing Xie, Yuming Ma, Jiawen Peng, Zujie Qin","doi":"10.2174/0113862073335304241023153906","DOIUrl":"https://doi.org/10.2174/0113862073335304241023153906","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM) is a chronic metabolic disease. The leaves of Dimocarpus longan Lour. (LYY), a well-known traditional Chinese medicine (TCM) with Guangxi national characteristics often used in simple recipes to treat DM has attracted increasing attention. In this study, we investigated the therapeutic effects of LYY in diabetic rats from a metabolomic perspective.</p><p><strong>Methods: </strong>The type 2 diabetes (T2DM) rat model was induced by a high-sugar and high-fat diet (HSFD) combined with 40 mg/kg streptozotocin (STZ). After oral administration of LYY (10.7 g/kg) for 28 d, their weight, fasted blood glucose (FBG), blood lipid levels, and inflammatory factors were assessed. The feces, urine, and serum samples of the rats were collected, and proton nuclear magnetic resonance (1H-NMR) technology was used to explore the changes in the sample's metabolism spectrum and analyze the relevant targeted metabolic pathways.</p><p><strong>Results: </strong>Compared with the diabetes group, LYY rats significantly delayed the reduction of body weight and decreased the FBG level (P <0.01); the levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C), IL-6, and TNF-α in serum significantly reduced (P < 0.05, 0.01), and the level of high-density lipoprotein-cholesterol (HDL-C) significantly increased (P < 0.01). 2 candidate biomarkers were identified from feces samples, and 4 associated metabolic pathways were discovered. 13 potential biomarkers were screened from urine samples, leading to the identification of 16 related metabolic pathways. Similarly, 5 potential biomarkers were screened from serum samples, and 11 related metabolic pathways were found.</p><p><strong>Conclusion: </strong>LYY can regulate the metabolic disorder caused by T2DM by regulating amino acid metabolism, amino acid synthesis, and tricarboxylic acid cycle, which provides a specific reference for the clinical treatment of T2DM.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122210","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 Comparative Chemoinformatics Analysis of Compounds Extracted from Nyctanthes Arbor-tristis","authors":"Nandini Kotharkar, Sanket Bapat, Renu Vyas, Pranav Pathak","doi":"10.2174/1386207326666230417085141","DOIUrl":"10.2174/1386207326666230417085141","url":null,"abstract":"<p><strong>Introduction: </strong>Natural products are a rich source of diverse chemical compounds with interesting therapeutic properties. There is a need for in-depth investigation of this reservoir with in-silico tools to assert the molecular diversity with respect to clinical significance. Although studies have been reported on plants such as Nyctanthes arbor-tristis(NAT) and its medicinal importance. A comprehensive study on comparative analysis of all phyto-onstituents has not been carried out.</p><p><strong>Aim: </strong>In the present work, we have carried out a comparative study of compounds obtained from the ethanolic extracts of various parts such as calyx, corolla, leaf, and bark of the NAT plant. Methods: The extracted compounds were characterized by LCMS and GCMS studies. This was further corroborated by the network analysis, docking, and dynamic simulation studies with validated anti-arthritic targets.</p><p><strong>Methods: </strong>The extracted compounds were characterized by LCMS and GCMS studies. This was further corroborated by the network analysis, docking, and dynamic simulation studies with validated anti-arthritic targets.</p><p><strong>Results: </strong>The most significant observation from LCMS and GCMS was that the compounds from calyx and corolla were closer in chemical space to the anti-arthritic compounds. To further expand and explore chemical space, the common scaffolds were seeded to enumerate a virtual library. The virtual molecules were prioritized based on the drug-like, leadlike scores and docked against anti-arthritic targets to reveal identical interactions in the pocket region.</p><p><strong>Conclusion: </strong>The comprehensive study will be of immense value to medicinal chemists for the rational synthesis of molecules as well as bioinformatics professionals for getting useful insight into identifying rich diverse molecules from plant sources.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9562781","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":"Hsa_circ_0030568 Promotes the Proliferation and Migration of Prostate Cancer Cells via the miR-141-3p-BRD4 Axis.","authors":"Xiaoxiao Sun, Congming Xiang, Yuwei Wu, Dongsheng Ge, Chengwen Sun","doi":"10.2174/0113862073341224241228054703","DOIUrl":"https://doi.org/10.2174/0113862073341224241228054703","url":null,"abstract":"<p><strong>Introduction: </strong>Numerous studies have indicated that circular RNAs (circRNAs) play an important role in diverse cancers. However, the specific molecular mechanism of circRNAs in prostate cancer (PCa) remains largely unclear.</p><p><strong>Method: </strong>In this study, we performed western blotting, real-time quantitative polymerase chain reaction, CCK-8 assay, cell scratch wound assay, and RNA immunoprecipitation assay.</p><p><strong>Results: </strong>These results showed that the expression of hsa_circ_0030568 was remarkably increased in PCa cells by using quantitative real-time PCR combined with dataset analysis. Mechanistically, circ_0030568 could physically bind to miR-141-3p and elevate the expression of BRD4 via sponging miR-141-3p in PCa cells, then accelerating the progression of PCa. Upregulation of hsa_circ_0030568 induces tumor progression through the miR-141-3p-BRD4 axis.</p><p><strong>Conclusion: </strong>Taken together, these findings suggested that hsa_circ_0030568 may act as a potential biomarker of PCa and a promising target for PCa treatment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122206","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}