Combinatorial chemistry & high throughput screening最新文献

{"title":"Pinoresinol Diglucoside Potentiates α-lipoic Acid-mediated Attenuation of ROS-induced Cell Injury by Affecting Oxidative and ER Stress in NIH-3T3 Fibroblasts.","authors":"Yan Zhang, Lian Yang, Han Wang, Ximao Cui, Dawei Deng, Yili Yang, Xin Xu","doi":"10.2174/0113862073426908251206001610","DOIUrl":"https://doi.org/10.2174/0113862073426908251206001610","url":null,"abstract":"<p><strong>Introduction: </strong>A Large amount of ROS generated by radiotherapy leads to radiationinduced skin injury (RISI), but drugs that can treat RISI are still limited in the clinic.</p><p><strong>Methods: </strong>An oxidative-stress model was established by inducing NIH-3T3 cells with H2O2, and the protective effects of α-lipoic acid (α-LA) combined with pinoresinol diglucoside (PDG) on H2O2-induced cell injury were evaluated. Cell viability was assessed by the CCK-8 assay. Oxidative stress was evaluated by detecting the expressions of oxidative and antioxidant factors. Endoplasmic reticulum (ER) stress was evaluated by detecting ER stress-associated biomarkers. A Western blot was performed to assess the expression of the indicated proteins.</p><p><strong>Results: </strong>Co-administration of α-LA and PDG significantly abolished H2O2-induced cell death and oxidative stress in NIH-3T3 fibroblasts, including changes in cell viability, ROS generation, and the expressions of oxidative and antioxidant factors. Mechanistically, PDG enhanced the ability of α-LA to suppress H2O2-induced JNK activation and PARP cleavage. PDG also potentiated α-LA-mediated upregulation of AKT activation, as well as the expression of Nrf2 in H2O2- treated NIH-3T3 fibroblasts. Moreover, PDG strengthened the inhibitory effect of α-LA on H2O2-induced ER stress in these cells.</p><p><strong>Discussion: </strong>The present study investigated the protective effects of α-LA and PDG against ROSinduced injury in NIH-3T3 fibroblasts, and further investigations using in vivo models of RISI will be performed in future studies.</p><p><strong>Conclusion: </strong>This study revealed that co-administration of α-LA and PDG exerted the protective effects on H2O2-induced cell injury by reducing oxidative stress and ER stress, suggesting a promising therapeutic strategy for the treatment of RISI in the future.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590702","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":"Shenling Baizhu San Ameliorates MASH and Associated Depression-like Behavior in Mice by Impacting Gut Microbiota and Carbohydrate Enzymes.","authors":"Aiping Wu, Wanyi Ou, Dongliang Chen, Yuanfei Wang, Guiru Lin, Jianmei Yang, Yanyan Hong, Minhui Li, Qinhe Yang, Chenli Lin, Yinji Liang","doi":"10.2174/0113862073446908260305080457","DOIUrl":"https://doi.org/10.2174/0113862073446908260305080457","url":null,"abstract":"<p><strong>Introduction: </strong>A major clinical concern of Metabolic Dysfunction-Associated Steatohepatitis (MASH) is its potential to progress to cirrhosis and hepatocellular carcinoma. Although Shenling BaiZhu San (SLBZS) has shown potential in managing MASH, its underlying therapeutic mechanisms remain unclear. This study sought to explore how SLBZS ameliorate MASH, particularly its regulatory effects on gut microbiota and carbohydrate enzymes (CAZymes).</p><p><strong>Methods: </strong>15 male C57BL/6 mice were assigned to three groups: control (normal diet, ND), MASH (Western diet combined with CCl₁, WDC), and treatment (WDC plus daily SLBZS, WDC-SLBZS). After 12 weeks, the physiological, biochemical, pathological and behavioral indicators of the mice were assessed, and 16S rRNA gene sequencing was conducted, along with characterization of CAZymes in fecal samples from all experimental groups.</p><p><strong>Result: </strong>The treated mice showed reduced hepatic steatosis and fibrosis, with significantly lower liver lipids (TC and TG), serum enzymes (AST and ALT), and pro-inflammatory cytokines (IL6, IL-1β, and MCP-1), accompanied by alleviation of depression-like behavior. 16S rRNA gene analysis revealed that beneficial bacteria (Muribaculum, Rikenellaceae, and Prevotellaceae) were significantly decreased in the MASH mice, whereas potentially harmful taxa (Klebsiella, Corynebacterium, and Faecalibaculum) were increased; these trends were reversed in the treatment group, especially for Rikenellaceae (P < 0.05). CAZymes, markedly diminished in MASH (P < 0.05), were partially restored after treatment. Correlation analysis showed that declines in Rikenellaceae and increases in Corynebacterium both positively correlated with depression-like behavior (r ≥ 0.7, P < 0.05).</p><p><strong>Discussion: </strong>The benefits of SLBZS against MASH and associated depression are not simply in rebuilding the gut microbiota, but in reshaping carbohydrate metabolism through regulated CAZymes, which restores the intestinal barrier and energy balance, thereby attenuating liver lipid accretion and the inflammatory cascade. Although efficacy has been validated, the \"microbiotaCAZyme-host metabolism\" causal chain at finer taxonomic and functional levels needs further analysis.</p><p><strong>Conclusion: </strong>SLBZS may relieve liver lipid accumulation, inflammatory damage, and associated depression-like behavior in MASH by partially restoring beneficial bacteria (e.g., Rikenellaceae) and related CAZymes.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142986","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":"Multi-Component Analysis by Chemometric Techniques: Advances and Applications for Solid Dosage Form.","authors":"Shilpa Sahu, Shiv Shankar Shukla, Ravindra Kumar Pandey, Bina Gidwani","doi":"10.2174/0113862073415336251124162649","DOIUrl":"https://doi.org/10.2174/0113862073415336251124162649","url":null,"abstract":"<p><strong>Introduction: </strong>Chemometric multivariate techniques are statistical and mathematical methods used in chemistry and related sciences to extract relevant information from complex data sets. These techniques are essential in analyzing multivariate data where multiple variables are measured simultaneously, as is common in spectroscopic, chromatographic, or process-monitoring data.</p><p><strong>Method: </strong>The article was prepared by collecting data from various sources like books, journals, websites, databases from e-resources, including Springer, Elsevier, Bentham, Taylor and Francis, etc A literature survey on 150 articles (research and review) on the relevant topic was conducted to conclude our findings. Chemometric multivariate methods offer an efficient and robust solution by utilizing mathematical and statistical techniques to analyze complex data.</p><p><strong>Result: </strong>Chemometric methods overcome the limitations of traditional univariate approaches by enabling accurate, precise, and non-destructive analysis without the need for extensive sample separation or prior information about the analytes. In multicomponent formulations, overlapping UV absorption spectra of APIs hinder accurate quantification using conventional methods like absorbance ratio, derivative spectroscopy, or classical least squares without calibration. Discussion - This work highlights the potential of chemometric techniques to improve quality control and streamline pharmaceutical analysis workflows. It is more straightforward in use, cost-effective, necessitates minimal sample handling, and yields trustworthy analytical results compared to alternatives. It is an exceptionally versatile instrument for pharmaceutical analysis across all tiers.</p><p><strong>Conclusion: </strong>The efficacies of the proposed methods were demonstrated using UV-Vis spectroscopy and chromatographic data, with results showing high predictive ability and minimal interference from excipients.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142954","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 Relationship between Antibody-mediated Immune Responses and Four Types of Neurodegenerative Diseases: A Mendelian Randomization Analysis.","authors":"Jinjian Li, Chunshu Rong, Zhen Wei, Xu Wang, Dexi Zhao","doi":"10.2174/0113862073448107260325213324","DOIUrl":"https://doi.org/10.2174/0113862073448107260325213324","url":null,"abstract":"<p><strong>Introduction: </strong>Recognizing the risk factors associated with neurodegenerative diseases is essential for their prevention. Currently, no studies are exploring the causal link between antibody-mediated immune responses and neurodegenerative diseases. This Mendelian randomization (MR) study further examines whether a causal relationship exists between antibodymediated immune responses and neurodegenerative diseases, and offers evidence supporting causality.</p><p><strong>Method: </strong>Data on antibody-mediated immune responses came from this study, which selected 9,724 subjects as the subgroup research participants and collected their serum samples for microbiological serological analysis. The large artery atherosclerotic stroke data includes 4,373 patients. The multiple sclerosis consists of 1,683 cases. Parkinson's disease comprises 37,688 cases. Alzheimer's disease includes 17,008 cases. MR analysis was conducted to estimate the associations between antibody-mediated immune responses(exposure) and neurodegenerative diseases(outcome) risk.</p><p><strong>Result: </strong>The IVW analysis revealed that 9 antibody-mediated immune responses were associated with 4 neurodegenerative diseases, including anti-varicella-zoster virus and Epstein-Barr virus antibodies, and others.</p><p><strong>Discussion: </strong>This study systematically investigates, for the first time through Mendelian randomization analysis, the potential relationships between antibody-mediated immune responses and various neurodegenerative diseases. The results indicate that a total of 9 antibody-mediated immune responses are significantly associated with the risk of four neurodegenerative diseases: Conclusion: These antibody-mediated immune responses serve as potential markers for predicting the occurrence and development of neurodegenerative diseases. Our genetic analysis suggests that antibodies against antigens may be involved in the pathological process of neurodegenerative diseases, which provides a new direction for future exploration of their specific mechanisms.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142951","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":"Hexosamine Biosynthesis Pathway in Colorectal Cancer: Current Insights and Therapeutic Opportunities.","authors":"Yi Zou, Xin Chen, Xinwen Ma, Yanbo Zhang, Haoyue Wang, Haotian Cui, Junkai Wen, Xueqing Hu, Wanli Deng","doi":"10.2174/0113862073443622260330054300","DOIUrl":"https://doi.org/10.2174/0113862073443622260330054300","url":null,"abstract":"<p><p>Colorectal Cancer (CRC) is a prevalent malignancy characterized by significant metabolic alterations that drive tumor progression and therapy resistance. The Hexosamine Biosynthetic Pathway (HBP) functions as a critical nutrient-sensing hub by integrating fluxes from glucose, glutamine, fatty acids, and uridine to control protein O-GlcNAcylation. Dysregulation of this pathway contributes to CRC oncogenesis through the modulation of oncogenic signaling cascades and metabolic plasticity. This review elucidates the distinct roles of key enzymes, including GFAT, PGM3, UAP1, and the O-GlcNAc cycling enzymes OGT and OGA, in exerting oncogenic roles. We detail how aberrant pathway flux and downstream O-GlcNAcylation orchestrate critical malignant phenotypes such as epithelial-to-mesenchymal transition, maintenance of cancer stemness, and DNA repair mechanisms that confer chemoresistance. Furthermore, we highlight emerging evidence linking dysregulation of the HBP to Tumor Microenvironment (TME) remodeling, specifically its role in promoting immune evasion via macrophage polarization and immune checkpoint stabilization. Beyond mechanistic insights, this article critically evaluates current therapeutic strategies targeting the pathway, ranging from novel inhibitors and interventions guided by biomarkers to combination therapies that synergize with conventional chemotherapy or immunotherapy. We also analyze the major hurdles hindering clinical translation. By framing both the biological complexity and therapeutic opportunities of this metabolic nexus, this work aims to provide a translational roadmap for developing precise and effective metabolic interventions to improve the clinical management of refractory CRC.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143028","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":"Morus alba L.: Bioactive Constituents, Pharmacological Activities, and Therapeutic Potential.","authors":"Xue Hu, Zhao Wang, Shengzhi Liu, Mohamed El-Shazly, Wei Zhu, Kefeng Zhai, Jingkui Tian, Yan Yan","doi":"10.2174/0113862073469823260410172135","DOIUrl":"https://doi.org/10.2174/0113862073469823260410172135","url":null,"abstract":"<p><p>Morus alba L. (mulberry) is a traditional medicinal plant originating from China and has long been used in herbal practice. In recent years, it has attracted renewed research interest because different parts of the plant contain a wide range of bioactive constituents. The leaves, fruits, root bark, and twigs are known to be rich in flavonoids, alkaloids, polysaccharides, and related compounds, which underlie their multiple biological activities. Experimental and pharmacological studies have reported effects on glucose and lipid metabolism, inflammatory responses, oxidative stress, as well as neural and microbial regulation. Importantly, the biological functions vary across plant tissues: leaves and twigs are mainly associated with metabolic and cardiovascular regulation, the root bark shows pronounced neuroprotective and antitumor activity, and the fruits exhibit additional benefits related to renal protection and immune function. Owing to this tissue-specific activity profile and its generally low toxicity, M. alba is considered a valuable source for exploring therapeutic strategies against metabolic, inflammatory, malignant, and renal disorders.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143003","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":"Profiling of the TNBC Tumor Microenvironment's Functional Heterogeneity by CITE-seq to Guide Personalized Medicine.","authors":"Zhang Yiping, Zhang Xin, Tian Jinqiang","doi":"10.2174/0113862073455902260410110103","DOIUrl":"https://doi.org/10.2174/0113862073455902260410110103","url":null,"abstract":"<p><p>Introduction / Objective: Triple-negative breast cancer (TNBC) is an aggressive subtype with few effective treatments and frequent resistance to immune checkpoint inhibitors. The heterogeneous and plastic tumor microenvironment (TME) is a dynamic, complex ecosystem. This study aims to deconstruct the TNBC immune ecosystem and generate a cellular atlas of its tumor microenvironment.</p><p><strong>Methods: </strong>In this study, we apply three CITE-seq datasets from murine TNBC tumors, totaling 2,356 cells. After correcting for technical batch effects, we perform clustering to identify major cell types, followed by focused sub-clustering of tumor-associated macrophages (TAMs) and T cells to analysis their functional states and potential differentiation trajectories.</p><p><strong>Results: </strong>Batch-corrected analysis resolves six primary cell populations within the TNBC microenvironment. TAMs segregate into three distinct subpopulations: a classical antigen-presenting subset, a metabolically active subset enriched for mitochondrial gene expression, and a unique subset with an erythroid-like gene signature consistent with active erythrophagocytosis. T-cell analysis reveals five major states. Furthermore, we identify several therapeutic targets.</p><p><strong>Discussion: </strong>These findings reveal substantial functional diversity within key immune compartments of TNBC, particularly TAMs and T cells, including metabolically specialized and erythrophagocytic TAMs, as well as distinct T cells. Besides, we also identify several potential drug targets for targeted treatment.</p><p><strong>Conclusion: </strong>This work provides a detailed single-cell atlas of the TNBC tumor microenvironment and uncovers functional heterogeneity in its immune cells. The resulting map offers a foundation for precision medicine, facilitating patient stratification and the design of tailored therapies that target the specific cellular ecosystems driving TNBC progression.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142995","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 Influence of Circadian Rhythm Disorders in Metabolic Syndrome through Gut Microbiota.","authors":"Jia-Min Wang, Rong-Qin Wang, Yan Wang, Xiao-Yun Gao, Si-Yu Liu, Su-Wen Qi, Guan-Lan Hu, Dong-Li Li, Yan Zhang, Xiao-Kang Xu, Hui-Ling Feng","doi":"10.2174/0113862073482277260412133043","DOIUrl":"https://doi.org/10.2174/0113862073482277260412133043","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic syndrome (MetS) is a chronic metabolic disorder whose global prevalence continues to rise, imposing a significant burden on public health. With the development of round-the-clock societies, shift work has become increasingly commonplace. A growing body of epidemiological evidence indicates that circadian rhythm disruption constitutes a predictable risk factor for MetS; however, the precise mechanisms underlying this relationship remain inadequately understood. This study employed golden hamsters as a model to investigate the effects of circadian rhythm disruption simulated by cyclic light (CL) exposure on MetS.</p><p><strong>Methods: </strong>Thirty-three male golden hamsters (7 weeks old, body weight 120-160 g) were randomly assigned to four groups for a 6-week intervention: the Control group (normal light + normal diet, ND), the high-fat diet group (normal light + HFD, to induce a MetS model), the cyclic light group (CL + normal diet, CL), and the CL + HFD group (CL + HFD). Outcome measures included metabolic indicators, hepatic histopathology, and gut microbiota (analyzed via 16S rDNA sequencing).</p><p><strong>Results: </strong>The stability of the MetS model was assessed through measurements of body weight, fasting blood glucose, and total cholesterol levels. The results indicated that CL exposure may further aggravate metabolic disorders associated with MetS. Furthermore, it was observed that CL exposure intensified MetS-related disturbances in gut microbiota, evidenced by an increase in α-diversity and distinct separation in β-diversity. CL exposure in the MetS model golden hamsters resulted in a reduced abundance of Bacteroidetes and Weissella, alongside an overgrowth of Helicobacter.</p><p><strong>Discussion: </strong>Circadian rhythm disruption is an independent risk factor for MetS. It further exacerbates metabolic indicators by inducing gut microbiota dysbiosis and promoting the growth of harmful bacteria. Future research should integrate functional metabolomics with faecal microbiota transplantation studies to validate causal mechanisms and explore clinical translational value.</p><p><strong>Conclusion: </strong>Circadian rhythm disruption is an independent risk factor for MetS. It exacerbates the pathological progression of MetS by reducing beneficial bacteria and promoting the growth of harmful bacteria, thereby further damaging its metabolic indicators.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143008","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 and Regulation of Common Key Genes in COPD and AD.","authors":"Huajun Yang, Yunfei Li","doi":"10.2174/0113862073456087260329192856","DOIUrl":"https://doi.org/10.2174/0113862073456087260329192856","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic obstructive pulmonary disease (COPD) is a prevalent comorbidity in Alzheimer's disease (AD) patients. Despite their potential links, the shared pathology of AD and COPD is unclear. This study used bioinformatics to identify key genes involved in both diseases.</p><p><strong>Methods: </strong>Transcriptome data of AD and COPD were obtained from the Gene Expression Omnibus (GEO) database, and common differentially expressed genes (DEGs) of the two diseases were screened by differential expression analysis. Hub genes were identified using topological analysis algorithms in the protein-protein interaction (PPI) network. Receiver operating characteristic (ROC) curve analysis, gene set enrichment analysis (GSEA), as well as the prediction of regulatory transcription factors (TFs) and microRNAs (miRNAs) were performed for these hub genes.</p><p><strong>Results: </strong>Thirty common DEGs were identified, with enrichment analysis linking them to neurodegeneration pathways. From the PPI network, five key genes (PDP1, SERPINI1, PPP3CA, ATP2B1, and VSNL1) were found to have significant diagnostic value (area under the curve > 0.6). GSEA revealed their functional roles, and a regulatory network suggested that TFs (e.g., ZNF76, KLF8) regulate these genes. Finally, a disease-miRNA-mRNA network was constructed, linking AD/COPD, four mRNAs, and seven miRNAs (e.g., hsa-miR-206).</p><p><strong>Discussion: </strong>This study preliminarily elucidated the cross-regulatory relationship between COPD and AD via bioinformatics, laying a theoretical foundation for investigating their comorbidity mechanism. However, all findings are based on bioinformatics analyses and require further experimental validation.</p><p><strong>Conclusion: </strong>This study identified five key genes linking AD and COPD, providing insights into their shared pathogenesis and potential diagnostic biomarkers for this comorbidity.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142945","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":"Mume Fructus Total Flavonoids Modulate miR-145-3p Expression to Inhibit Lipopolysaccharide-induced Inflammatory Cytokine Production in BV2 Cells.","authors":"Chunling Wang, Lian Gu, Zhengwei Yang, Jinli Su, Xiaodong Wen","doi":"10.2174/0113862073447531260414195911","DOIUrl":"https://doi.org/10.2174/0113862073447531260414195911","url":null,"abstract":"<p><strong>Introduction: </strong>The inhibition of microglia-mediated inflammatory responses is of great importance for the treatment of neurodegenerative diseases. Mume Fructus total flavonoids (MFTF) are one of the major bioactive components of Mume Fructus, a traditional food and medicinal herb in China. This study aimed to clarify the anti-inflammatory effect of MFTF on lipopolysaccharide (LPS)-induced microglial inflammation and to elucidate its underlying mechanism.</p><p><strong>Methods: </strong>Ultra-high-performance liquid chromatography coupled with Quadrupole Time-offlight mass spectrometry was used to analyze the chemical composition of MFTF. BV2 cells were stimulated with LPS (100 ng/mL) for 24 h to establish an in vitro inflammatory model. Cell viability was tested by the Cell Counting Kit-8 assay. Cell proliferation was assessed by the 5- Ethynyl-2'-deoxyuridine assay. Cell polarization and miR-145-3p expression were analysed by real-time quantitative PCR. The expression of apoptosis- and inflammation-related proteins was analyzed by Western Blotting. RNA sequencing was used to explore the potential mechanisms by which MFTF regulates the inflammation of BV2.</p><p><strong>Results: </strong>A total of 379 compounds have been identified in MFTF. MFTF promoted the proliferation, downregulated the expression of pro-inflammatory markers (iNOS, IL-1β, and CD86), and upregulated the expression of anti-inflammatory markers (Arg-1, IL-10, and CD206) of BV2 cells following LPS stimulation. In addition, MFTF inhibited the expression of pro-apoptotic protein Bad and inflammatory mediators COX-2 and iNOS, while promoting the anti-apoptotic protein Bcl-2. Further, MFTF unregulated miR-145-3p expression in LPS-stimulated BV2 cells, and inhibition of miR-145-3p partially abolished the anti-inflammatory, anti-apoptotic, and proproliferative effects of MFTF. RNA sequencing results showed MFTF may inhibit the inflammation in BV2 cells by regulating the Toll-like receptor signalling pathway, NOD-like receptor signalling pathway, and NF-κB signalling pathway.</p><p><strong>Discussion: </strong>Our findings demonstrated that MFTF inhibited pro-inflammatory polarization (M1) while promoting proliferation and anti-inflammatory polarization (M2) of microglia, potentially through the upregulation of miR-145-3p. These results indicated that MFTF could attenuate microglial inflammation, thereby supporting our hypothesis that MFTF may have therapeutic potential in alleviating neurodegenerative diseases.</p><p><strong>Conclusion: </strong>These results uncovered a potential mechanism underlying the antineuroinflammatory effects of MFTF and provide a theoretical basis for its therapeutic application in neuroinflammatory disorders.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142998","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}