Combinatorial chemistry & high throughput screening最新文献

{"title":"Angelicin Inhibits NSCLC Tumor Growth via the Inhibition of Cancer-Associated Fibroblasts.","authors":"Binbin Ding, Hang Yin, Shuo Cao, Kai Cheng, Luna Ge","doi":"10.2174/0113862073366593250109093910","DOIUrl":"https://doi.org/10.2174/0113862073366593250109093910","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the effect of angelicin on the NSCLC tumor growth.</p><p><strong>Background: </strong>Accumulating evidence shows that cancer-associated fibroblasts (CAFs) play an important role in tumor progression and metastasis, making CAFs an increasingly attractive target for therapeutic intervention. Targeted therapies against CAFs have been considered to have the potential to significantly improve cancer treatment outcomes, overcome resistance, and improve immune evasion. Angelicin (Ang), an active ingredient isolated from the Chinese herbal medicine Psoralea corylifolia Linn., has been reported to inhibit tumor progression. Due to its natural origin, angelicin has good clinical safety and low toxicity. Further clinical studies and exploration of its role as a CAF inhibitor in difficult-to-treat tumors like as NSCLC are expected to offer up a new channel for cancer treatment. Furthermore, angelicin's low cost and good biocompatibility make it have important application potential in cancer combination therapy, especially when used in combination with traditional therapies such as chemotherapy and immunotherapy, which may significantly improve treatment outcomes and reduce side effects. However, the mechanism of its anti-tumor effect remains poorly defined. The aim of this study was to investigate whether ANG modulates CAF activity to inhibit NSCLC progression.</p><p><strong>Methods: </strong>NIH3T3 cells are a mouse fibroblast cell line, and the use of NIH3T3 cells as a model for CAFs is mainly due to their natural fibroblast phenotype, ease of culture, good response to stimuli, and ability to simulate the functions of fibroblasts in the tumor microenvironment. NIH3T3 was treated with TGF-β (4ug/ml) and H2O2 (10μM). A conditioned medium was used to study the effect of Ang on tumor growth, invasion, and migration by regulating CAFs.Ang concentrations were set at 12.5, 25, and 50μM for cell cycle experiments and 0, 20, and 40μM for cell migration and invasion experiments. Subcutaneous tumors were established by mixing LLC and NIH3T3 cells to observe the effect of Ang on tumor progression and microenvironment. Fibroblast activity during Ang intervention was monitored by fluorescence-labeled FAPI-04 and 18F-labeled FAPI-04. The molecular pharmacological mechanism of Ang was investigated by RNA sequencing and network pharmacology.</p><p><strong>Results: </strong>The result showed that Ang significantly inhibited TGF-β and H2O2-induced NIH3T3 transformation, as evidenced by reduced expression of markers such as FAPα and α-SMA. Ang inhibited proliferation, invasion and migration of LLC cells induced by CAFs-conditioned medium. In vivo Experiments showed that Ang greatly inhibited tumor growth in Lewis's lung cancer caused by CAFs. Molecular pharmacological analysis showed that Ang could modulate CAFs activity through multiple targets. These data indicate that Ang has a great potential to reduce CAF ac","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032511","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":"Predicting Polymerase Chain Reaction Success: Integrating the K-Word Order Model, Physicochemical Properties Modeling of Double Bases, and Support Vector Machine.","authors":"Long Yan, Yong Liu, Yan Yang","doi":"10.2174/0113862073351071250102100221","DOIUrl":"https://doi.org/10.2174/0113862073351071250102100221","url":null,"abstract":"<p><strong>Introduction: </strong>Polymerase Chain Reaction (PCR) has been a pivotal scientific technique since the twentieth century, and it is widely applied across various domains. Despite its ubiquity, challenges persist in efficiently amplifying specific DNA templates.</p><p><strong>Method: </strong>While PCR experimental procedures have garnered significant attention, the analysis of the DNA template, which is the experiment's focal point, has been notably overlooked. This study addresses the uncertainty surrounding the amplification of DNA fragments using conventional Taq DNA polymerase-based PCR protocols. The imperative need to characterize DNA templates and devise a reliable method for predicting PCR success is underscored.</p><p><strong>Result: </strong>In this study, we formulate a 72-dimensional feature vector representing a DNA template through the utilization of k-word order and modeling of physicochemical properties of double bases. Subsequently, a Support Vector Machine (SVM) model is employed to assess PCR results.</p><p><strong>Conclusion: </strong>A jackknife cross-validation test is used to evaluate the anticipated success rates, resulting in an overall accuracy of 95.77%. Sensitivity, specificity, and Matthew's Correlation Coefficient (MCC) stand at 95.75%, 95.79%, and 0.915, respectively.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032513","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":"Exploring the Mechanism of Shi-San-Wei-He-Zhong-Wan in the Treatment of Functional Dyspepsia Based on Network Pharmacology and Experimental Validation.","authors":"Xiao Min Li, Jing Wei Zhu, Kui Wu Li, Xiao Yu Han, Jing Ru Ruan, Hao Ran Chu","doi":"10.2174/0113862073358956241203101815","DOIUrl":"https://doi.org/10.2174/0113862073358956241203101815","url":null,"abstract":"<p><strong>Purpose: </strong>The incidence of Functional Dyspepsia (FD) is gradually increasing, yet there are currently no effective treatment methods available. This study explored the effective components, potential targets, and pathways of Shi-San-Wei-He-Zhong-Wan (SSWHZW) in the treatment of FD, aiming to provide new insights into its treatment.</p><p><strong>Methods: </strong>First, the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and GeneCards databases were utilized to identify the major active components of SSWHZW and potential therapeutic targets of FD. Subsequently, functional enrichment analyses were performed to elucidate the mechanisms of SSWHZW on FD. Molecular docking simulations were then conducted to assess the binding affinity of key targets and major active components. Next, an FD animal model was established, and the therapeutic effects of SSWHZW were validated using Hematoxylin and Eosin (HE) staining and Enzyme-linked Immunosorbent Assay (ELISA). Finally, Western blot analysis was performed to validate the involvement of key signaling pathways.</p><p><strong>Results: </strong>A total of 229 active ingredients and 283 putative targets were identified from SSWHZW, of which 173 overlapped with the targets of FD and were considered potential therapeutic targets. Key ingredients, such as quercetin, kaempferol, wogonin, and baicalein, were identified as pivotal components of SSWHZW, potentially acting on the 173 overlapping targets and influencing FD through related signaling pathways. Functional enrichment analysis revealed that the PI3K-Akt signaling pathway, VEGF signaling pathway, and NF-kappa B signaling pathway may be involved in the mechanism of SSWHZW in treating FD. Molecular docking predicted that all five ingredients could firmly bind with the top-ranked target TP53 in the Protein- protein Interaction (PPI) network. Further experiments demonstrated that SSWHZW protected the intestinal tissues of FD rats from inflammatory damage by inhibiting the PI3K/AKT signaling pathway.</p><p><strong>Conclusion: </strong>Based on network pharmacology, this study explored the multi-component, multitarget, and multi-pathway characteristics of SSWHZW in treating FD. The findings suggest that SSWHZW exerts its anti-FD effects by inhibiting the expression of the PI3K/AKT signaling pathway, providing new insights and methods for further research on the mechanism of SSWHZW in treating FD.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032512","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":"Resveratrol Reduces Cisplatin-induced Cochlear Hair Cell Pyroptosis by Inhibiting the mtROS/TXNIP/NLRP3 Pathway.","authors":"Andi Peng, Jiahui Peng, Ruosha Lai, Wei Liu, Xubo Chen, Bing Hu, Yingying Xu, Lihua Li","doi":"10.2174/0113862073354456241219065512","DOIUrl":"https://doi.org/10.2174/0113862073354456241219065512","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin is an effective anti-cancer drug with limited clinical applications due to ototoxicity. Resveratrol, known for its antioxidant and anti-inflammatory properties, has been reported to mitigate these adverse effects, although the underlying mechanism remains under-researched.</p><p><strong>Objective: </strong>This study aimed to investigate the effects and underlying mechanisms of resveratrol on cisplatin-induced ototoxicity.</p><p><strong>Methods: </strong>Ototoxicity was modeled in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells by cisplatin exposure, followed by interventions using thioredoxin-interacting protein (TXNIP) siRNA transfection, MitoQ, or resveratrol. Apoptosis and proliferation were quantitatively assessed using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and Ki67 immunostaining. Quantitative real-time PCR (qRT-PCR) and western blotting were used to measure the changes in mRNA and protein levels. Flow cytometry and enzyme- linked immunosorbent assay (ELISA) were used to analyze pyroptotic cells and inflammatory responses. Reactive oxygen species (ROS) production was tracked using 2', 7'- dichlorofluorescein diacetate (DCFH-DA) staining and flow cytometry. Mitochondrial Membrane Potential (MMP) and mitochondrial permeability transition pore (MPTP) opening levels were analyzed through tetramethylrhodamine ethyl ester (TMRE) staining and specific reagent kits, respectively. Lastly, immunofluorescence staining and co-immunoprecipitation were employed to investigate the co-localization and interactions between TXNIP and thioredoxin (TRX)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) proteins.</p><p><strong>Results: </strong>Cisplatin exacerbated apoptosis, suppressed cell proliferation, and upregulated NLRP3, pro-Caspase-1, cleaved Caspase-1, Gasdermin D (GSDMD), GSDMD-N, and TXNIP expression. Concurrently, cisplatin resulted in increased pyroptotic cells and increased interleukin-6 (IL-6), IL-18, IL-1β, and tumor necrosis factor-α (TNF-α) levels. These effects were mitigated by TXNIP knockdown. Furthermore, cisplatin led to elevated cellular ROS and mitochondrial ROS (mtROS), decreased MMP, and inhibited MPTP opening. Cisplatin reduced the colocalization and interaction between TRX and TXNIP while enhancing those between TXNIP and NLRP3. These changes were attenuated by MitoQ. Resveratrol displayed effects similar to those of TXNIP knockdown and MitoQ treatment.</p><p><strong>Conclusion: </strong>Resveratrol alleviated the toxic effects of cisplatin on cochlear hair cells by inhibiting cell pyroptosis process mediated by the mtROS/TXNIP/NLRP3 pathway.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022475","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":"Investigation of the Mechanism of Pachyman against Gout Arthritis with Network Pharmacology Analysis and Verification In Vivo.","authors":"Qing-Xin Kong, Wei-Ping Xu, Cheng Fan, Bi-Lin Liu, Li-Ping Reng, Qiao Ruan","doi":"10.2174/0113862073330896241211155436","DOIUrl":"https://doi.org/10.2174/0113862073330896241211155436","url":null,"abstract":"<p><strong>Purpose: </strong>Pachyman, derived from Poria cocos, has been used to treat gouty arthritis (GA) for thousands of years, although its precise role and mechanisms remain unclear. Herein, we investigate the therapeutic effects of pachyman on GA and explore their underlying mechanisms.</p><p><strong>Methods: </strong>Network pharmacology and experimental methods were employed to investigate the therapeutic mechanisms of pachyman against GA. The protein-protein interaction network of shared targets between pachyman and gout was constructed. Furthermore, we elucidated the functions and mechanisms of pachyman against GA. Subsequently, we validated the predicted mechanisms from an experiment on rats.</p><p><strong>Results: </strong>The treatment of GA with pachyman primarily related to tumor necrosis factor (TNF), matrix metalloproteinases (MMP), and relaxation factor signaling pathways. In the experimental validation, pachyman were found to regulate the expression of IL-1β, TNF-α, TGF-β, superoxide dismutase, and glutathione peroxidase of hyperuricemic rats.</p><p><strong>Conclusion: </strong>These collective findings suggest that pachyman holds promise as an alternative treatment for GA.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022348","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":"Cellulose and Cellulose Nanomaterials: Recent Research and Applications in Medical Field.","authors":"Murtaza Ahmad Khanday, Danish Ahmad Shergujri, Aisha Noor, Shahid Fayaz, Syed Naiem Raza, Reyaz Hassan Mir, Nisar Ahmad Khan","doi":"10.2174/0113862073334330241105095235","DOIUrl":"https://doi.org/10.2174/0113862073334330241105095235","url":null,"abstract":"<p><p>Cellulose, the most prevalent biopolymer in the world, is comprehensively reviewed. Cellulose occurs in fibrillar patterns with alternating crystalline and amorphous regions. The non-toxic and -friendly nature of cellulose has made it beneficial in many fields, such as pharmaceuticals, biomedical, nanotechnology, etc. Numerous sources, including the plant cell wall and wood, some types of bacteria, algae, and tunicates can provide cellulose. This polysaccharide is composed of a straight chain of d-glucose units attached by β (1 → 4) that extend in number from several hundred to thousands. This review details the recent progress in the synthesis of cellulose nanofibers or nanofibrillated cellulose, cellulose nanocrystals, commonly referred to as nanocellulose, and bacterial cellulose. The methodologies and procedures for evaluating the morphology, purity, crystallinity, mechanical, rheological, and other characteristics of cellulose micro/nanomaterials are covered in this review. The current study also discusses several ways to functionalize CNFs, CNCs, and BC. Finally, a guide to the synthesis of cellulose nanocomposites is provided, along with possible uses in the biomedical field, such as wound healing, bone tissue engineering, and artificial blood vessel production. Additionally, applications related to the pharmaceutical industry are also highlighted.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022347","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":"Ir-Catalyzed Intermolecular Arylthiocyanation of Alkenes.","authors":"Jie Xu, Jing Leng, Hao Huang, Yanan Li, Ying Qi Chen","doi":"10.2174/0113862073347918241209052708","DOIUrl":"https://doi.org/10.2174/0113862073347918241209052708","url":null,"abstract":"<p><strong>Aims: </strong>Organic thiocyanates are important pharmaceutical intermediates. This study aimed to develop a selective and efficient approach for synthesizing organic thiocyanates.</p><p><strong>Methods: </strong>Under mild reaction conditions, an array of alkenes, KSCN, and diaryliodonium salts are considered good substrates, providing various aryl-substituted alkylthiocyanates with modest to excellent yield. Radical trapping and nucleophilic trapping experiments were carried out to explore the mechanistic pathways. The experiments indicated the involvement of free-radical and carbenium ion intermediate processes. Diaryliodonium salts were used as the radical arylating reagent, and KSCN was the electrophilic cyanating reagent. Under irradiation, the excited photocatalyst reduced aryldiazonium salt to aryl radical. Then, the radical was added to olefin to generate a new radical. Finally, the generated radical was further oxidized and arrested by SCN anion.</p><p><strong>Conclusion: </strong>This coupling reaction provides a straightforward and practical route to construct various aryl-substituted alkylthiocyanates.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022416","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":"Mechanisms of the Compound of Magnoliae Flos and Xanthii Fructus Essential Oils for the Treatment of Allergic Rhinitis based on the Integration of Network Pharmacology, Molecular Docking, and Animal Experiment.","authors":"Tao Lu, Yuqin Yang, Zhenlin Yang, Ziyi Liu, Miao Li, Ziman Lu, Ting Gong, Jincheng Zhang","doi":"10.2174/0113862073333657241216040227","DOIUrl":"https://doi.org/10.2174/0113862073333657241216040227","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aim and objective: &lt;/strong&gt;Magnoliae Flos (Chinese name: Xin-Yi) and Xanthii Fructus (Chinese name: Cang-Er-Zi) are Chinese herbal medicines and have been used to treat allergic rhinitis (AR). However, the therapeutic effect, active ingredients, and probable processes of a compound of Magnoliae Flos and Xanthii Fructus in the form of essential oils (CMFXFEO) in treating AR have not been reported. This study aims to determine the efficacy of the CMFXFEO on ovalbumin (OVA)-induced AR in a rat model and to use network pharmacology and molecular docking to reveal the hub genes, biological functions, and signaling pathways of CMFXFEO against AR.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Animal experiments were applied to validate the role of CMFXFEO in the treatment of AR. 20 rats were randomly divided into four groups: control group (CON, n=5), positive control group (AR, n=5), CMFXFEO-treated group (AR+CMFXFEO, n=5), and budesonide-treated group (AR+Budesonide, n=5). Rats were stimulated with OVA to induce AR. Symptom scores assessment and histo-pathomorphological evaluation was performed. The serum level of OVA-specific immunoglobulin (Ig) E was measured. Gas Chromatograph-Mass Spectrometer analysis (GC-MS) was used to identify the monomer chemical composition of CMFXFEO. The target genes of CMFXFEO were obtained by using PubChem and SwissTargetPrediction databases. The target genes of AR were screened using GeneCards, DisGeNET, and OMIM databases. The target genes were intersected using the venny2.1 website to obtain the potential therapeutic targets of CMFXFEO for treating AR and to construct the PPI network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to reveal associated signaling pathways. The Sybyl tool was used to dock the CMFXFEO with key therapeutic targets molecularly.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Intranasal CMFXFEO administration significantly suppressed the allergic symptoms, reduced the inflammatory cell infiltration, and the serum level of OVA-specific immunoglobulin (Ig) E. The main components of CMFXFEO obtained through the GC-MS analysis, listed as γ-terpinene (9.4908%), limonene (7.2693%), menthol (7.1821%), β-pinene (7.1190%), β-caryophyllene (7.0396%), eucalyptol (6.1367%), linalool(5.9686%), eugenol (5.0776%). A total of 398 CMFXFEO targets and 488 AR-related targets were screened, of which 42 were common targets. The GO and KEGG pathway analyses unveiled that CMFXFEO were strongly associated with several signaling pathways, including the AGE-RAGE signaling pathway, TNF signaling pathway, and Chemokine signaling pathway. PPI network construction screened six hub genes as therapeutic targets, including STAT3, IL1B, TLR4, PTGS2, ICAM1, and VCAM1. The molecular docking verification indicated that CMFXFEO have good binding activity with therapeutic targets, and β-Pinene's docking ability with TLR4 is particularly prominent.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The anti-infl","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022474","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":"Mechanism of HJ11 Decoction in the Treatment of Atherosclerosis Based on Network Pharmacology and Experimental Validation.","authors":"Fei Lu, Jiaxi Zou, Weiming Xu, Fangyuan Zhang, Wenyi Nie, Yue Zhao, Lijie Jiang, Lizhe Liang, Jingqing Hu","doi":"10.2174/0113862073356770241218065012","DOIUrl":"https://doi.org/10.2174/0113862073356770241218065012","url":null,"abstract":"<p><strong>Background: </strong>HJ11 (HJ11 decoction), which is based on the traditional prescription Si-Miao-Yong-An decoction, has exerted a remarkable effect on atherosclerosis (AS). Nevertheless, the main components and underlying mechanisms of HJ11 for treating AS remain unclear.</p><p><strong>Aim of the study: </strong>This study was designed to elucidate the mechanism of HJ11 in the treatment of AS through network pharmacology and in vivo experimental validation.</p><p><strong>Methods: </strong>Network pharmacology was employed to explore the primary bioactive components and targets of HJ11. AS-related genes were obtained from the GeneCards and DisGeNET databases and screened for intersections with HJ11. A herb-compound-target interaction network was constructed by Cytoscape 3.9.1, and molecular docking analyses were constructed on key targets. By using a mouse model, the mechanism of action of HJ11 was further confirmed.</p><p><strong>Results: </strong>A total of 231 active components of HJ11, 1681 AS-related genes, and 156 common targets were identified. Through the establishment of numerous networks, it was discovered that the main association of the mechanism of HJ11 in AS therapy pertained to anti-inflammation. Important substances included quercetin, kaempferol, and luteolin, while TNF-α, AKT1, IL-6, and VEGFA were the main targets. Molecular docking demonstrated that there were favorable binding interactions between active drugs (quercetin, kaempferol, and luteolin) and targets (TNF-α, AKT1, IL-6, and VEGFA). In the in vivo study, HJ11 reduced the expression of TNF-α, AKT1, IL-6, and VEGFA at both the mRNA and protein levels, inhibited atherosclerotic lesions in AS mouse models, and retarded the development of retroarterioid sclerosis.</p><p><strong>Conclusions: </strong>HJ11 can inhibit inflammation and the progression of AS, and the mechanism might involve downregulating the expression of TNF-α, AKT1, IL-6, and VEGFA.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022418","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":"FOLR1 Regulates the Malignant Progression of Glioblastoma through the SRC/ERK1/2 Axis.","authors":"Xueshan Jia, Weihang Liang, Junya Yang, Xuejiao Chen, Yi Bin, Zhikun Cao, Qingfeng Tian","doi":"10.2174/0113862073335351241226070841","DOIUrl":"https://doi.org/10.2174/0113862073335351241226070841","url":null,"abstract":"<p><strong>Background: </strong>GBM is an aggressive brain tumor with limited treatment options. Prior research has indicated FOLR1 as a pivotal gene involved in cancer pathogenesis.</p><p><strong>Aim: </strong>This study aimed to explore the involvement of folate receptor alpha (FOLR1) in glioblastoma (GBM) and evaluate its potential as a therapeutic target.</p><p><strong>Objective: </strong>This study investigated the expression pattern of FOLR1 in GBM, its impact on patient prognosis, and its role in GBM cell growth and the SRC/ERK1/2 signaling axis.</p><p><strong>Methods: </strong>Initially, we conducted an expression analysis of FOLR1 based on public databases and examined its expression pattern in GBM and its impact on patient prognosis. Subsequently, cell experiments were carried out to evaluate the regulation of GBM cells by differential FOLR1 expression. We then downloaded 100 FOLR1 co-expressed genes from the Linkedomics data repository and performed an enrichment analysis. Finally, the role of FOLR1 and SRC/ERK1/2 axis in GBM was analyzed again by cell experiments.</p><p><strong>Results: </strong>FOLR1 was found to be substantially expressed in GBM patients and was linked to a poor prognosis. Cell experiments showed that overexpression of FOLR1 promoted GBM cell growth, while low expression of FOLR1 inhibited cell growth. Additionally, genes related to FOLR1 were enriched in the lysosome, toxoplasmosis, and other pathways. This study further indicated that FOLR1 facilitates the activation of the SRC/ERK1/2 signaling pathway in GBM cells, and the attenuation of these pathways can effectively impede the malignancy-promoting effects triggered by FOLR1 in GBM cells.</p><p><strong>Conclusions: </strong>We revealed that FOLR1 orchestrates the malignant advancement of GBM by stimulating the SRC/ERK1/2 signaling axis, underscoring its pivotal role in the pathogenesis of GBM.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001389","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}