Combinatorial chemistry & high throughput screening最新文献

{"title":"Network Pharmacology Combined with Animal Models to Investigate the Mechanism of ChangPu YuJin Tang in the Treatment of Tourette Syndrome.","authors":"Man-Qi Lu, Zheng-Gang Shi, Jing Shang, Lei Gao, Wei-Jiao Gao, Lu Gao","doi":"10.2174/0113862073295447240430113053","DOIUrl":"10.2174/0113862073295447240430113053","url":null,"abstract":"<p><strong>Background: </strong>ChangPu YuJin Tang (CPYJT) is a Chinese herbal formula that has been shown to be an effective therapeutic strategy for pediatric patients with Tourette Syndrome (TS). Using an integrated strategy of network pharmacology and animal model, the aim of this study was to investigate the mechanism of CPYJT in the treatment of TS.</p><p><strong>Methods: </strong>Compound libraries of CPYJT were established using databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The TCMSP database and Swiss Target Prediction database were used to predict the targets. The above results were constructed into a CPYJT-Drug-Component-Target network. Moreover, TS targets were predicted using GeneCards and other databases. The targets corresponding to the potential ingredients in CPYJT and the targets corresponding to TS were taken as the intersections to construct the CPYJT-TS network. The target network was analysed by PPI using the string database. GO and KEGG enrichment analyses were performed on the target network. The whole process was performed using Cytoscape 3.7.2 to make visual network diagrams of the results. CPYJT was characterised by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS). Transmission Electron Microscopy (TEM) was used to observe the structural changes of CPYJT on the neuronal cells of the IDPN model rats. RT-PCR and Western Blot were used to analyse the changes in the mRNA and protein expression levels of BDNF, TrkB, PI3K, and AKT in the cortex, striatum, and thalamus brain regions after CPYJT administration in IDPN model rats.</p><p><strong>Results: </strong>Network pharmacology and UHPLC-MS studies revealed that CPYJT acted on the TS through multiple neurotransmitters and the BDNF/TrkB and PI3K/AKT signalling pathways. CPYJT ameliorated neurocellular structural damage in the cortex, striatum, and thalamus of TS model rats. Additionally, CPYJT up-regulated the levels of BDNF, TrkB, PI3k, and AKT in the cortex, striatum, and thalamus of TS model rats.</p><p><strong>Conclusion: </strong>It was found that CPYJT protected neuronal cells from structural damage in multiple brain regions and affected the expression levels of BDNF, TrkB, PI3K, and Akt in the cortex, striatum, and thalamus during TS treatment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":"166-184"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Network Pharmacology and <i>In-silico</i> Approaches to Decipher the Pharmacological Mechanism of <i>Dioscorea septemloba</i> Thunb in Treating Gout and Its Complications.","authors":"Wen-Bin Liu, Jie Dai, Xuan Chen, Ning Du, Jian Hu","doi":"10.2174/0113862073258523231025095117","DOIUrl":"10.2174/0113862073258523231025095117","url":null,"abstract":"<p><strong>Background: </strong>Dioscorea septemloba Thunb. (DST) has demonstrated therapeutic potential in the treatment of gout and its associated complications. However, the underlying mechanisms of DST's pharmacological activity remain unclear. This study aims to investigate the pharmacological substances and network regulatory mechanisms of DST in treating gout and its complications using network pharmacology.</p><p><strong>Methods: </strong>According to ultra-high performance liquid chromatography coupled with hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) data and Lipinski's rule of five, 24 bioactive phytochemicals from DST were identified. The targets of gout were retrieved from Gene Expression Omnibus (GEO), GeneCards, and DisGeNET databases, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG pathway) enrichment analysis. The Cytoscape network analysis was used to identify the primary pathological pathways and key targets. Finally, LeDock was used for molecular docking to verify the active components of DST and their core target proteins.</p><p><strong>Results: </strong>DST contains several core active ingredients, such as tetrahydroimidazo[1,2-a]pyridine- 2,5-dione, diosgenin, beta-sitosterol, dioscorol B, montroumarin and 9,10-dihydro-5,7- dimethoxy-3,4-phenanthrenediol. Moreover, these active components were found to strongly bind to the key targets for treating gout and its complications, including HSP90AA1, STAT3, PTGS2, PPARG, MTOR, HIF1A, MMP9, ESR1, and TLR4. As a result, DST alleviates gout and its complications by inhibiting xanthine dehydrogenase (XDH) to reduce uric acid levels and regulating the HIF-1α, EZH2/STAT3, and COX-2/PPAR-γ pathways to reduce inflammation. Additionally, it also plays an analgesic role by regulating the neuroactive ligand-receptor interaction pathway and calcium ion signaling pathway.</p><p><strong>Conclusion: </strong>This study has provided insights into the underlying mechanisms of DST in the treatment of gout and its complications, which could serve as a scientific foundation for its clinical translation.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":"74-88"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92153010","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":"Inhibition of Taurine-upregulated Gene 1 Upregulates MiR-34a-5p to Protect against Myocardial Ischemia/Reperfusion <i>via</i> Autophagy Regulation.","authors":"Qunjun Duan, Aiqiang Dong, Haifeng Cheng, Shufen Zhang, Wei Chen, Weijun Yang","doi":"10.2174/0113862073267559231106074309","DOIUrl":"10.2174/0113862073267559231106074309","url":null,"abstract":"<p><strong>Background: </strong>Taurine upregulated gene 1 (TUG1) has been identified on long noncoding RNA (lncRNA); however, its function in myocardial cells following ischemia/ reperfusion (I/R) injury has not been explored. This study aimed to investigate the role of LncTUG1 in I/R injury by focusing on its relationship with autophagy induction by regulating miR-34a-5p expression.</p><p><strong>Methods: </strong>We established a myocardial I/R model and H9C2 hypoxia-ischemic and reoxygenation (HI/R) conditions to induce I/R injury. TTC, Western blot, CCK-8 assay, quantitative reverse transcription PCR, flow cytometry, and confocal microscopy were used to assess the size of myocardial infarct, level of some apoptotic-related and autophagy-associated proteins, cell viability, the level of LncRNA TUG1, apoptosis, and autophagy, respectively.</p><p><strong>Results: </strong>The results revealed that a TUG1 knockdown protected against I/R-induced myocardial injury by decreasing the impairment in cardiac function. LncRNA TUG1 expression was increased in a myocardial I/R model and HI/R in H9C2 cells. Moreover, inhibition of LncTUG1 enhanced H9C2 cell viability and protected the cells from HI/R-induced apoptosis. Silencing LncRNA TUG1 promoted HI/R-induced autophagy. Furthermore, TUG1 siRNA upregulated the level of miR-34a-5p compared to the HI/R group. The protective effect of LncRNA TUG1 inhibition on H9C2 cells following HI/R was eliminated by blocking autophagy with an miR-34a-5p inhibitor.</p><p><strong>Conclusion: </strong>These findings indicated that inhibiting TUG1 may reduce the extent of myocardial I/R injury by regulating miR-34a-5p. Taken together, these results suggest that LncRNA TUG1 may represent a novel therapeutic target for myocardial I/R injury.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":"110-121"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650387","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":"<i>Fructus mori</i>: An Updated Review on Botany, Phytonutrient, Detection, Bioactivity, Quality Marker, and Application.","authors":"Ling-Na Li","doi":"10.2174/0113862073270666231206093528","DOIUrl":"10.2174/0113862073270666231206093528","url":null,"abstract":"<p><strong>Background: </strong><i>Fructus mori</i> (mulberry) is not only a delicious fruit with rich phytonutrients and health functions but also a medicinal plant with many clinical therapeutic values for tonifying kidneys and consolidating essence, making hair black and eyes bright.</p><p><strong>Methods: </strong>The related references about <i>F. mori</i> in this review from 1996 to 2022 had been collected from both online and offline databases, including PubMed, Elsevier, SciFinder, Willy, SciHub, Scopus, Web of Science, ScienceDirect, SpringerLink, Google Scholar, Baidu Scholar, ACS publications, and CNKI. The other information was acquired from ancient books and classical works about <i>F. mori</i>.</p><p><strong>Results: </strong>An updated summary of phytonutrients from <i>F. mori</i> was listed as fellows: flavonoids (1-20) (23.5%), phenolic acids (21-34) 16.5%), alkaloids (35-75) (48.2%), polysaccharides (76- 78) (3.5%), other compounds (79-85) (8.3%). The above chemical components were detected by TLC, UV-Vis, HPLC, GC-MS, and AAS methods for their quality standards. The various bioactivities (hepatoprotective, immunomodulatory, anti-oxidant, hypoglycemic, anti-cancer, and other activities) of mulberry are summarized and discussed in this review, which laid an important basis for analyzing their mechanisms and quality markers. This review summarized its applications for vinegar, wine, yogurt, drink, jelly, and sweetmeat in food fields, and the existing problems and future development directions are also discussed in this review.</p><p><strong>Conclusions: </strong>This review made a comprehensive description of <i>F. mori</i>, including botany, phytonutrient, detection, bioactivity, quality marker, and application. It will not only provide some important clues for further studying <i>F. mori,</i> but also provide some valuable suggestions for in-depth research and development of <i>F. mori</i>.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":"12-32"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139566893","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":"Jeduxiaoliu Formula can Induce Apoptosis of Lymphoma Cells <i>In Vitro</i> and <i>In Vivo</i>.","authors":"XiaoWei Feng, Ming Hu, Cong Ming Wei, Hong Yu Zhang, Wen Wen Jiang, Qi Hu","doi":"10.2174/0113862073271687231122064637","DOIUrl":"10.2174/0113862073271687231122064637","url":null,"abstract":"<p><strong>Objective: </strong>Lymphoma is the most common malignancy of the haematological system. Jeduxiaoliu formula (JDXLF) exerts good therapeutic effects against lymphoma, however, the mechanisms underlying these effects remain unclear. Therefore, this study aimed to investigate the mechanism of action of JDXLF.</p><p><strong>Methods: </strong>RNA-Seq was performed to examine the molecular mechanisms underlying the therapeutic effects of JDXLF against lymphoma. CCK-8 assay was performed to examine the effects of JDXLF on the proliferation of lymphoma cells. Electron microscopy was performed to examine the morphology of lymphoma cells. Flow cytometry was performed to examine the apoptosis and cell cycle of lymphoma cells. qPCR and Western blotting were performed to detect the expression of apoptotic genes and proteins. <i>In vivo</i>, the tumour-suppressive effect of JDXLF on lymphoma transplanted tumours was examined by establishing a subcutaneous transplantation tumour model in nude mice, and the expression of apoptotic proteins in tumour tissues was analysed via immunohistochemical staining.</p><p><strong>Results: </strong>RNA-Seq revealed 71, 350 and 620 differentially expressed genes (DEGs) in the 1 mg/mL, 4 mg/mL and 8 mg/mL JDXLF treatment groups, respectively. KEGG pathway analysis showed that the DEGs were significantly associated with apoptosis, TNF signalling and NF-κB signalling. <i>In vitro</i> experiments revealed that JDXLF inhibited the proliferation of lymphoma (Raji and Jeko-1) cells in a dose-dependent manner, induced apoptosis and upregulated the expression of Bax/Bcl2 and caspase3. <i>In vivo</i> experiments revealed that JDXLF had a significant tumourshrinking effect on mice and increased the expression of the apoptosis-related proteins caspase3 and Bax/Bcl2.</p><p><strong>Cconclusions: </strong>This study indicates that JDXLF can induce apoptosis in lymphoma cells <i>in vitro</i> and <i>in vivo</i>. We suggest this may provide a direction for further research into lymphoma therapy.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":"319-338"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416486","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":"Scutellaria Baicalensis Georgi Stem and Leaf Flavonoids Ameliorate the Learning and Memory Impairment in Rats Induced by Okadaic Acid.","authors":"Shuai Ma, Cong-Cong Xu, Yong-Cai Dong, Cai-Xia Li, Ya-Zhen Shang","doi":"10.2174/0113862073265060231127054325","DOIUrl":"10.2174/0113862073265060231127054325","url":null,"abstract":"<p><strong>Aim: </strong>The objective of this study is to explore the impact and underlying mechanism of S. baicalensis Georgi stem and leaf flavonoids (SSFs) on cognitive impairment caused by intracerebroventricular injection of okadaic acid (OA) in rats.</p><p><strong>Methods: </strong>An experimental model of Alzheimer's disease (AD) was induced in rats by intracerebroventricular injection of OA, resulting in memory impairment. The Morris water maze test was employed to confirm the successful establishment of the memory impairment model. The rats that exhibited significant memory impairment were randomly divided into different groups, including a model group, three SSFs dose groups (25, 50, and 100 mg/kg), and a positive control group treated with Ginkgo biloba tablets (GLT) at a dose of 200 mg/kg. To evaluate the learning and memory abilities of the rats, the Morris water maze test was conducted. Hematoxylin-eosin (HE) staining was used to observe any morphological changes in neurons. Immunohistochemistry (IHC) was performed to measure the expression of choline acetyltransferase (ChAT) protein. Western blotting (WB) was utilized to assess the phosphorylation levels of tau protein at Ser262 and Ser396. The activities of inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS) were quantified using ultraviolet spectrophotometry. The levels of inflammatory factors, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were measured using ELISA.</p><p><strong>Results: </strong>In rats, the administration of OA via intracerebroventricular injection resulted in cognitive impairment, neuropathological changes, and alterations in protein expression and activity levels. Specifically, the protein expression of ChAT was significantly reduced (P<0.01), while the phosphorylation levels of tau protein at Ser262 and Ser396 were significantly increased (P<0.01). Moreover, iNOS activity in the hippocampus and cerebral cortex exhibited a significant increase (P<0.01), whereas cNOS activity showed a decrease (P<0.05). Furthermore, the levels of IL-1β and TNF-α in the cerebral cortex were elevated (P<0.01), while the level of IL-6 was decreased (P<0.05). The administration of three doses of SSFs and GLT to rats exhibited varying degrees of improvement in the aforementioned pathological alterations induced by OA.</p><p><strong>Conclusion: </strong>SSFs demonstrated the ability to enhance cognitive function and mitigate memory deficits in rats following intracerebroventricular injection of OA. This beneficial effect may be attributed to the modulation of ChAT protein expression, tau hyperphosphorylation, NOS activity, and inflammatory cytokine levels by SSFs.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":"263-277"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416489","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":"Network Pharmacology and Experimental Validation to Elucidate the Pharmacological Mechanisms of Luteolin Against Chondrocyte Senescence.","authors":"Ling Long, Xiaokai Tang, Yi Wang, Jiaxiang Gu, Jiachao Xiong, Hao Luo, Hao Lv, Faxin Zhou, Kai Cao, Sijian Lin","doi":"10.2174/0113862073273675231114112804","DOIUrl":"10.2174/0113862073273675231114112804","url":null,"abstract":"<p><strong>Background: </strong>Luteolin, a flavonoid found in various medicinal plants, has shown promising antioxidant, anti-inflammatory, and anti-aging properties. The cartilaginous endplate (CEP) represents a crucial constituent of the intervertebral disc (IVD), assuming a pivotal responsibility in upholding both the structural and functional stability of the IVD.</p><p><strong>Objective: </strong>Exploring the precise mechanism underlying the protective effects of luteolin against senescence and degeneration of endplate chondrocytes (EPCs).</p><p><strong>Methods: </strong>Relevant targets associated with luteolin and aging were obtained from publicly available databases. To ascertain cellular functions and signaling pathways, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed. Core genes were identified through the construction of a protein-protein interaction (PPI) network. Molecular docking (MD) was utilized to assess the binding affinity of luteolin to these core genes. Finally, the impact of luteolin on the senescence and degeneration of EPCs was evaluated in an in vitro cellular senescence model induced by tert-butyl hydroperoxide (TBHP).</p><p><strong>Results: </strong>There are 145 overlapping targets between luteolin and senescence. Analysis using GO revealed that these targets primarily participate in cellular response to oxidative stress and reactive oxygen species. KEGG analysis demonstrated that these markers mainly associate with signaling pathways such as p53 and PI3K-Akt. MD simulations exhibited luteolin's binding affinity to P53, Cyclin-dependent kinase (CDK)2, and CDK4. Cell cycle, cell proliferation, and β- galactosidase assays confirmed that luteolin mitigated senescence in SW1353 cells. Western blot assays exhibited that luteolin significantly suppressed the expression of Matrix Metallopeptidase (MMP) 13, P53, and P21, while concurrently promoting CDK2, CDK4, and Collagen Type II Alpha 1 (COL2A1) expression.</p><p><strong>Conclusion: </strong>In summary, luteolin demonstrated beneficial properties against aging and degeneration in EPCs, offering novel insights to mitigate the progression of intervertebral disc degeneration (IVDD).</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":"291-305"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650390","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":"Drug-containing Serum of Quyoufang Promotes Apoptosis of Ectocervical H8 Cells through an E6/p53-related Pathway.","authors":"Shan Huang, Xiaofeng Chen, Yuanjie Qi, Jing Xiao","doi":"10.2174/0113862073263350231107105959","DOIUrl":"10.2174/0113862073263350231107105959","url":null,"abstract":"<p><strong>Background: </strong>Persistent human papillomavirus (HPV) infection is a causative agent for the majority of cervical cancer cases. The traditional Chinese medicine formula Quyoufang (QYF), a herbal oral decoction therapy, has been widely applied in the treatment of various diseases caused by HPV infection, but the molecular mechanism of QYF in the treatment of HPV infection remains unclear. This study aimed to investigate the effect of drug-containing serum of QYF on the apoptosis of HPV16-positive cervical immortalized epithelial cell line H8 <i>in vitro</i>.</p><p><strong>Methods: </strong>Different concentrations of medicated serum were obtained by feeding QYF into the stomachs of rats. The effects of medicated serum on H8 cell proliferation and apoptosis were detected using the cell counting kit-8 assay (CCK-8) method, flow cytometry, and Hoechst 33342/PI apoptosis assays. The different expressions of E6, E7, p53, and pRb among H8 cells were detected by RT-PCR and Western Blot.</p><p><strong>Results: </strong>The results firstly indicated that the drug-containing serum of QYF induced apoptosis and suppressed the proliferation of H8 cells in a concentration-dependent manner. RT-PCR and Western Blot unveiled that in contrast to the control group, the QYF groups could markedly elevate the mRNA expression of P53 and pRb as well as promote the expression of p53 and pRb protein levels. The QYF groups suppressed the expression of E6 mRNA and inhibited the expression of E6 protein.</p><p><strong>Conclusion: </strong>The drug-containing serum of QYF could effectively inhibit the proliferation of H8 cells and induce their apoptosis, possibly through the E6/p53-related pathway.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":"122-131"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451116","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":"Combinatorial Paths to the Future: A Preface.","authors":"Gerald H Lushington","doi":"10.2174/138620732801240822152502","DOIUrl":"https://doi.org/10.2174/138620732801240822152502","url":null,"abstract":"","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":"28 1","pages":"1-2"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432433","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 Novel Hub Genes Associated with Inflammation and Autophagy in Astragaloside Membranaceus ameliorates Lupus Nephritis by Bioinformatics Analysis and Molecular Dynamics Simulation.","authors":"Kaili Kong, Xiaomei Qiao, Ting Liu, Xiaoxia Wang, Rui Li, Jingai Fang, Xiaodong Zhang","doi":"10.2174/0113862073255980231113071412","DOIUrl":"10.2174/0113862073255980231113071412","url":null,"abstract":"<p><strong>Background: </strong>Lupus nephritis is an autoimmune disease, and its pathogenesis involves inflammation and autophagy disorders. Studies have demonstrated that Astragalus membranaceus can effectively suppress the progression of LN, but the underlying therapeutic target is still unclear.</p><p><strong>Objection: </strong>This study aimed to investigate the therapeutic target whereby AM ameliorates LN.</p><p><strong>Method: </strong>We downloaded AM and LN-related chips from the TCMSP and GEO databases, respectively. We selected the two compound targets for the subsequent analysis via WGCNA, and constructed protein interaction networks of compound targets and determined the core targets. GO, KEGG analyses were conducted on compound targets to identify enriched functional and genomic pathways. The core genes were further validated in clinical and external datasets. Molecular docking of AS with the core targets was performed using the AutoDock software, and molecular dynamics simulation was conducted for the optimal core protein ligand obtained by molecular docking by Gromacs 2020.6 software.</p><p><strong>Result: </strong>We obtained 10 core targets, namely IL-1β, EGF, CCND1, CASP3, STAT1, PTGS2, PPARγ, AR, CXCL10, and KDR, from the 24 compound targets identified. The results of the GO enrichment analysis mainly included cell growth regulation. The results of the KEGG enrichment analysis showed that 7 out of 23 valid targets were significantly enriched in the mitogen-activated protein kinase pathway (p < 0.01). Combined with the clinical datasets, we found that IL-1β, EGF, CCND1, CASP3, STAT1, PTGS2, and PPARγ have high diagnostic values for LN. In the validation dataset, all the core targets were significantly differentially expressed, except for EGF deletion. The molecular docking and molecular dynamics simulation results showed that AM and IL- 1β, CASP3, STAT1, and PPARγ all had binding energies < -5 kJ·mol-1 and good binding properties.</p><p><strong>Conclusion: </strong>IL-1β, CASP3, STAT1, and PPARγ could be potential biomarkers and therapeutic targets in AM ameliorates LN.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":"306-318"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650386","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}