Combinatorial chemistry & high throughput screening最新文献

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The Gut Microbiome and Metabolomics Profiles of Dust-exposed Rats. 暴露于粉尘的大鼠的肠道微生物组和代谢组学特征
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-04-07 DOI: 10.2174/0113862073354023250314050225
Xi Shen, Miaomiao Wang, Shasha Pei, Shuyu Xiao, Kun Xiao, Jinlong Li, Xiaoming Li, Qingan Xia, Heliang Liu, Fuhai Shen
{"title":"The Gut Microbiome and Metabolomics Profiles of Dust-exposed Rats.","authors":"Xi Shen, Miaomiao Wang, Shasha Pei, Shuyu Xiao, Kun Xiao, Jinlong Li, Xiaoming Li, Qingan Xia, Heliang Liu, Fuhai Shen","doi":"10.2174/0113862073354023250314050225","DOIUrl":"https://doi.org/10.2174/0113862073354023250314050225","url":null,"abstract":"<p><strong>Background: </strong>Limited treatments for silicosis necessitate further study of pneumoconiosis characteristics and pathophysiology. This study employs metabolomics to investigate metabolite changes and identify biomarkers for understanding pneumoconiosis pathogenesis.</p><p><strong>Methods: </strong>We explored pneumoconiosis pathogenesis through the lens of intestinal flora, using 18 healthy SPF male SD rats divided into three groups: control, coal dust, and silica. After dust exposure, metabolite changes were analyzed to identify metabolic markers and pathways. We assessed the relationship between intestinal flora and silicosis, aiming to provide early diagnostic evidence. Rats were exposed to coal dust, silica, or sterile saline for 8 weeks, after which blood, lung tissue, and feces were collected. Lung pathology was assessed, and inflammatory factors (IL-6, IL-11) were measured. 16S rDNA sequencing and UHPLC-QTOFMS metabolomics were used to analyze intestinal flora and fecal metabolites.</p><p><strong>Results: </strong>After 8 weeks of dust exposure, silica-exposed rats showed significantly reduced weight and elevated serum IL-6 and IL-11 levels compared to controls (P < 0.05). Lung tissue pathology revealed normal alveolar structure in controls, whereas silica group rats exhibited lung damage, intensified inflammation, and silicon nodule formation. Coal dust group rats showed lung tissue changes with fibroblast aggregation. α diversity analysis showed a decreased Shannon index and increased Simpson index in the coal dust group, and a decreased Simpson index in the silica group, suggesting altered intestinal flora. β diversity analysis confirmed significant differences in gut microbiota between dust-exposed groups and controls. Metabolomics identified 11 differential metabolites in rat feces, meeting criteria of Fold change > 2, VIP > 1, and P < 0.05, indicating metabolic changes post-exposure.</p><p><strong>Conclusion: </strong>Dust exposure disrupts intestinal flora and metabolic state, with potential metabolic markers identified in both coal dust and silica groups, implicating fructose and mannose metabolism in coal dust exposure and sphingolipid metabolism in silica exposure. This study provides new insights into the pathogenesis of pneumoconiosis and potential biomarkers for early diagnosis.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802794","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}
引用次数: 0
Curcumin Regulating Primordial Follicle Initiation by Restoring the Oxidative-antioxidant Balance.
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-04-07 DOI: 10.2174/0113862073368250250319001421
Wanjing Li, Jinbang Xu, Dan Shi, Jingyi Wang, Tao Liu, Juan Yang, Disi Deng
{"title":"Curcumin Regulating Primordial Follicle Initiation by Restoring the Oxidative-antioxidant Balance.","authors":"Wanjing Li, Jinbang Xu, Dan Shi, Jingyi Wang, Tao Liu, Juan Yang, Disi Deng","doi":"10.2174/0113862073368250250319001421","DOIUrl":"https://doi.org/10.2174/0113862073368250250319001421","url":null,"abstract":"<p><strong>Background: </strong>Diminished ovarian reserve (DOR) is accompanied by abnormal initiation and development of primordial follicles. Reporting that curcumin can protect the ovarian reserve, we used rats as a model to explore the regulatory mechanism of curcumin on primordial follicle priming.</p><p><strong>Objective: </strong>Curcumin restores the ovarian microenvironment of DOR model rats by AMPK/ SIRT 1 signaling pathway, thus regulating the initiation of primordial follicles.</p><p><strong>Methods: </strong>The study used the ovaries of 3-day-old female rats, after replicating the DOR model by triptolide (TP), then used curcumin intervention for 3 days. Histomorphological analysis was counted by H & E staining; ELISA test was used to count ovarian hormone [follicle stimulating hormone (FSH) / luteinizing hormone (LH) ratio and estradiol (E2)] concentration in the culture supernatant. Spectrophotometric measurement was used to count of superoxide dismutase (SOD) and the malondialdehyde (MDA). The protein and mRNA expression of the pathway and key indicators for follicle initiation were determined by Western Blot and Q-PCR (AMPK, SIRT 1, PTEN, PGC-1 α, and AMH).</p><p><strong>Results: </strong>After curcumin treatment, the number of growing follicles increased (P < 0.05). FSH/LH ratio decreased but the content and expression of E2 and AMH increased (P < 0.05). The protein and mRNA expression of characteristic indicators of inhibiting primordial follicle initiation (PTEN) was decreased (P < 0.05). Oxidation-reduction-related SOD activity increased and the content of MDA decreased (P < 0.05), while the protein and mRNA expression of PGC- 1α increased (P < 0.05). The protein and mRNA expression of the pathway (AMPK, SIRT 1) were increased (P < 0.05).</p><p><strong>Conclusion: </strong>Curcumin restored the ovarian local oxidant-antioxidant balance and promoted primordial follicle priming through AMPK/SIRT 1 signaling pathway in the DOR model rats.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802793","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}
引用次数: 0
The Regulatory Effects of Electroacupuncture on the Intestinal Flora of Mice with Ulcerative Colitis.
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-04-07 DOI: 10.2174/0113862073357858250219050156
Xinyu Gao, Enfan Xiao, Shaohui Geng, Haixu Jiang, Hesong Wang, Yuxin Zhao, Jiaxin Xie, Guangrui Huang, Wenrui Jia
{"title":"The Regulatory Effects of Electroacupuncture on the Intestinal Flora of Mice with Ulcerative Colitis.","authors":"Xinyu Gao, Enfan Xiao, Shaohui Geng, Haixu Jiang, Hesong Wang, Yuxin Zhao, Jiaxin Xie, Guangrui Huang, Wenrui Jia","doi":"10.2174/0113862073357858250219050156","DOIUrl":"https://doi.org/10.2174/0113862073357858250219050156","url":null,"abstract":"<p><strong>Objective: </strong>The primary objective of this study was to investigate the modulation of intestinal flora composition in a murine model of ulcerative colitis (UC) through the application of electroacupuncture. This study also aimed to analyze the role of specific microbial taxa and to identify the key regulatory targets and pathways involved in this modulation.</p><p><strong>Methods: </strong>A UC model was established in mice through the administration of a 5% dextran sodium sulfate (DSS) solution. Subsequently, UC mice underwent electroacupuncture treatment, with mesalazine serving as a positive control. The electroacupuncture group received treatment at the bilateral \"Shangjuxu\" acupuncture points, while the mesalazine group was administered mesalazine at a dosage of 0.5 g/kg via gavage. Interventions were conducted from days 5 to 9 of the experimental period. The weight, disease activity index (DAI) scores, and colon lengths of the mice across all groups were compared. Hematoxylin-eosin (HE) staining was utilized to assess the morphological characteristics of colon tissue, thereby validating the efficacy of electroacupuncture in the UC model. Additionally, 16S rDNA high-throughput sequencing was employed to analyze alterations in the intestinal flora present in the feces of the UC model mice.</p><p><strong>Results: </strong>Compared to the model group, the DAI scores of mice in the electroacupuncture group were significantly reduced on days 7 and 9 of the experiment (P < 0.05; P < 0.01). HE staining revealed a marked reduction in morphological disruption and inflammatory infiltration within the colon tissue of the electroacupuncture group relative to both the model and mesalazine groups. Results from linear discriminant analysis effect size and Wilcoxon rank-sum test demonstrated a significant increase in the abundance of genera, such as Roseburia, in the electroacupuncture group. Furthermore, the alpha diversity of the intestinal flora exhibited an increase. Predictions regarding intestinal microbial function indicated that pathways, such as RNA transport and glycerophospholipid metabolism, were significantly diminished in the model group compared to the control group (P < 0.05), while these pathways were significantly enhanced in the electroacupuncture group relative to the model group (P < 0.01).</p><p><strong>Conclusion: </strong>Electroacupuncture effectively regulated both the structure and function of intestinal flora in UC mice. The genus Roseburia may serve as a critical therapeutic target for electroacupuncture in the modulation of intestinal flora in UC. Additionally, lipid metabolism and RNA transport may represent key pathways through which electroacupuncture exerts its regulatory effects on intestinal flora.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802795","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}
引用次数: 0
Sanggenol L Activates Caspase and Inhibits the NF-кB/JNK/ERK Signaling Pathway to Promote Apoptotic Cell Death in Colorectal Cancer Cells.
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-04-03 DOI: 10.2174/0113862073369624250131053853
Zhiyi Tang, Ye Li, Jie Shu, Annamalai Vijayalakshmi, Ran Luo
{"title":"Sanggenol L Activates Caspase and Inhibits the NF-кB/JNK/ERK Signaling Pathway to Promote Apoptotic Cell Death in Colorectal Cancer Cells.","authors":"Zhiyi Tang, Ye Li, Jie Shu, Annamalai Vijayalakshmi, Ran Luo","doi":"10.2174/0113862073369624250131053853","DOIUrl":"https://doi.org/10.2174/0113862073369624250131053853","url":null,"abstract":"<p><strong>Background: </strong>In Western nations, colorectal cancer is the most prevalent type of cancer. Recent research has revealed that Western habits are influencing Asian countries, thus significantly contributing to the rapidly increasing rate of cancer. A naturally occurring flavonoid called sanggenol L found in the root bark of Morus alba possesses anti-cancer properties against colorectal malignant cells. The cellular and molecular mechanisms underlying the effects of sanggenol L on human colorectal cancer cells are still unknown.</p><p><strong>Objective: </strong>The current study explored whether sanggenol L enhances apoptosis through the inhibition of the NF-кB/JNK/ERK signaling pathway in colorectal human cancer cells.</p><p><strong>Materials and methods: </strong>The effects of sanggenol L were determined based on the observed cytotoxic activity, fluorescent staining for apoptotic cells using AO/EB, DCFH-DA, Rh-123, DAPI, ROS, and MMP, as well as the analysis of cell proliferation, inflammatory and apoptotic markers through western blot analysis.</p><p><strong>Results: </strong>Colorectal cancer cells exposed to sanggenol L (20 and 30 μM/ml) mediated apoptosis of Bax, Bcl-2, and TNF-α and reduced cell growth by down-regulating p-ERK, p-JNK, and pp38 via mediation of p-NF-кB.</p><p><strong>Conclusion: </strong>The study results indicate that sanggenol L triggers caspase-induced apoptosis in colorectal cancer cells. Lastly, it was proposed that sanggenol L could help prevent colon cancer.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779342","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}
引用次数: 0
Metformin Inhibits the Development of Lung Adenocarcinoma by Regulating the Expression of CCNA2 via E2F1.
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-04-03 DOI: 10.2174/0113862073348968241101112455
Luyao Wang, Yinlong Huang, Mei Tian, Mengling Hu, Kai Zhang, Chaoqun Lian, Xiaojing Wang, Jing Zhang
{"title":"Metformin Inhibits the Development of Lung Adenocarcinoma by Regulating the Expression of CCNA2 via E2F1.","authors":"Luyao Wang, Yinlong Huang, Mei Tian, Mengling Hu, Kai Zhang, Chaoqun Lian, Xiaojing Wang, Jing Zhang","doi":"10.2174/0113862073348968241101112455","DOIUrl":"https://doi.org/10.2174/0113862073348968241101112455","url":null,"abstract":"<p><strong>Background: </strong>The incidence and mortality rates of lung cancer in China have significantly increased in recent years, and lung adenocarcinoma (LUAD) accounts for about 40% of all lung cancers. Metformin (MET) has been used as a therapeutic drug for type 2 diabetes, and a recent study revealed that MET can play an anti-tumor role by inhibiting cell proliferation, but its specific mechanism of action in LUAD is still unclear.</p><p><strong>Methods: </strong>The key genes and signaling pathways of MET acting on LUAD were screened by bioinformatics, and the effects of MET on LUAD cell proliferation, invasion, migration, and apoptosis were detected. We then constructed small interfering RNAs for CCNA2 and combined them with MET to verify whether MET inhibits LUAD cell growth by affecting the expression of CCNA2. The binding ability of MET to E2F1 was predicted by molecular docking, and the correlation between E2F1 and CCNA2 was analyzed by bioinformatics. Finally, it was verified by interfering with the expression of E2F1 whether MET down-regulated the expression of CCNA2 by regulating E2F1, thus exerting anti-tumor effects.</p><p><strong>Results: </strong>MET can inhibit the proliferation of LUAD cells and induce apoptosis, exerting its anticancer activity. Moreover, MET reduced the expression of CCNA2 in LUAD cells, and when the expression of CCNA2 was down-regulated, the anti-tumor cell activity of MET was promoted. In addition, MET had a good binding ability with E2F1, and MET down-regulated the expression of E2F1 in LUAD. Down-regulating the expression of E2F1 could reduce the expression of CCNA2 and enhance the inhibitory effect of MET on the proliferation of LUAD cells.</p><p><strong>Conclusion: </strong>In conclusion, our findings revealed a novel mechanism for LUAD treatment in which MET can down-regulate CCNA2 expression via E2F1 and thus exert its anti-tumor effects.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779340","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}
引用次数: 0
Paeonol Inhibits the MAPK Signaling Pathway by Targeting SIRT1 in AGE-Induced HUVECs Injury.
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-03-27 DOI: 10.2174/0113862073359192250311081427
Dingkun Liu, Hongrui Gao, Xiaochun Wu, Yulin Mo, Xiaobin Jia, Liang Feng, Minghua Zhang
{"title":"Paeonol Inhibits the MAPK Signaling Pathway by Targeting SIRT1 in AGE-Induced HUVECs Injury.","authors":"Dingkun Liu, Hongrui Gao, Xiaochun Wu, Yulin Mo, Xiaobin Jia, Liang Feng, Minghua Zhang","doi":"10.2174/0113862073359192250311081427","DOIUrl":"https://doi.org/10.2174/0113862073359192250311081427","url":null,"abstract":"<p><strong>Background: </strong>Chronic hyperglycemia in diabetes is a significant contributor to endothelial injury through the induction of oxidative stress. Paeonol is anticipated to address oxidative stress with the aim of ameliorating endothelial injury. Our study delved into the effects of paeonol on endothelial damage induced by diabetes and elucidated the underlying mechanisms.</p><p><strong>Methods: </strong>This research presented a novel endothelial injury model employing advanced glycation end products (AGEs) in human umbilical vein endothelial cells (HUVECs). Additionally, a network analysis was carried out to pinpoint the targets influenced by paeonol, with pivotal targets substantiated via polymerase chain reaction (PCR), western blot analysis, and immunofluorescence staining. Ultimately, the introduction of small interfering RNA transfection validated the involvement of SIRT1 in AGEs-induced HUVECs injury.</p><p><strong>Results: </strong>Twelve metabolites of paeonol were conclusively detected in vivo. Paeonol demonstrated substantial efficacy in ameliorating and diminishing levels of various cytokines and biochemical indicators, including AGEs, Col IV, ET-1, E-selectin, FN, hs-CRP, ICAM-1, MMP2, and sVCAM-1. Notably, network analysis accentuated the pivotal role of the MAPK signaling pathway. Furthermore, paeonol exhibited significantly elevated mRNA and protein levels of SIRT1 and ERK across varying dosage regimens compared to the model group while displaying relatively decreased mRNA expression levels of p38MAPK.</p><p><strong>Conclusion: </strong>This research revealed that paeonol inhibited the activation of p38 and ERK within the MAPK signaling pathway. Moreover, the regulatory influence of paeonol over p38 and ERK was compromised subsequent to the silencing of SIRT1, indicating a SIRT1-dependent suppressive action of paeonol on the MAPK pathway. The potential therapeutic utility of SIRT1 in mitigating diabetic endothelial impairment and its concomitant cardiovascular ramifications is underscored by these findings.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729144","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}
引用次数: 0
Exploring Mechanisms of Ephx2 in Treating Atherosclerosis Using Independent Cascade Model and Adverse Outcome Pathways.
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-03-27 DOI: 10.2174/0113862073345542250220051427
Caiyuzhen Zhang, Yuanwen Dai, Yong Chen, Bo Cao, Jinbing An, Wei Pang
{"title":"Exploring Mechanisms of Ephx2 in Treating Atherosclerosis Using Independent Cascade Model and Adverse Outcome Pathways.","authors":"Caiyuzhen Zhang, Yuanwen Dai, Yong Chen, Bo Cao, Jinbing An, Wei Pang","doi":"10.2174/0113862073345542250220051427","DOIUrl":"https://doi.org/10.2174/0113862073345542250220051427","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis (AS) is a leading cause of cardiovascular diseases, characterized by lipid accumulation in arterial walls. The enzyme Ephx2 (soluble epoxide hydrolase, sEH) is implicated in AS development, but its precise mechanisms and therapeutic potential are not fully understood.</p><p><strong>Objectives: </strong>This study aimed to analyze gene expression data from low-density lipoprotein receptor knockout (LDLR⁸/⁸) and LDLR⁸/⁸sEH⁸/⁸ mice to identify significant genes associated with AS.</p><p><strong>Methods: </strong>A directed compound-protein interaction network was constructed based on these genes and related pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In the end, through resistance distance (RD) between any two nodes in this network, the Independent Cascade (IC) model was applied to explore Ephx2 mechanisms in AS, such as important Adverse Outcome Pathways (AOPs).</p><p><strong>Results: </strong>Several AOPs were identified as critical in AS treatment via Ephx2. The key AOPs included inflammatory response and cytokine release, cholesterol deposition and oxidation, disruption of plaque stability, smooth muscle cell proliferation and migration, and platelet activation and coagulation. Within the top AOPs of inflammatory response and cytokine release, potential target genes were identified, such as Mapk3, PiK3cd, Gnai2, Mapk10, Arnt, and RhoA. Critical paths from Ephx2 to these target genes were established, suggesting mechanisms by which Ephx2 may influence AS pathogenesis.</p><p><strong>Conclusion: </strong>By defining the AS network and corresponding RD, this study elucidated potential mechanisms by which Ephx2 affects AS through specific KEGG pathways, AOPs, and target genes. These findings enhanced the understanding of AS pathogenesis and highlighted potential targets like Mapk3 for developing therapeutic strategies in AS prevention and treatment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729142","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}
引用次数: 0
Astragalosides Promote MH7A Cell Apoptosis by Suppressing WTAP-mediated m6A Methylation of TRAIL-DR4.
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-03-25 DOI: 10.2174/0113862073363967250308084008
Xiaoya Cui, Linhui Zhang, Huimei Chen, Hui Jiang
{"title":"Astragalosides Promote MH7A Cell Apoptosis by Suppressing WTAP-mediated m6A Methylation of TRAIL-DR4.","authors":"Xiaoya Cui, Linhui Zhang, Huimei Chen, Hui Jiang","doi":"10.2174/0113862073363967250308084008","DOIUrl":"https://doi.org/10.2174/0113862073363967250308084008","url":null,"abstract":"<p><strong>Background: </strong>Astragaloside (AST), a natural saponin extracted from Astragalus membranaceus (Fisch.) Bunge., has been consistently utilized in the treatment of rheumatoid arthritis (RA). N6-methyladenosine (m6A), the most prevalent modification of mRNA, is associated with the progression of various diseases, including RA. Nonetheless, the effects of AST on m6A modification in RA remain to be elucidated.</p><p><strong>Methods: </strong>The MH7A cell model was established through induction with TNF-α. The effects of AST on the expression levels of WTAP, BAX, BCL2, and TRAIL-DR4 were evaluated utilizing immunofluorescence, RT-qPCR, and Western blot analysis. Furthermore, CCK-8 and flow cytometry were used to assess MH7A cell viability, cell cycle, apoptosis, and proliferation. Then, the m6A modification of TRAIL-DR4 was elucidated via MeRIP-qPCR.</p><p><strong>Results: </strong>The optimal dose administration time was 50 μg/mL at 48 h. AST not only reduced the expression levels of WTAP, BCL2, BAX, TRAIL-DR4, and the m6A modification level of TRAIL-DR4 but also significantly enhanced apoptosis in MH7A cell, while inhibiting cell viability and proliferation. Furthermore, AST was capable of reversing the effect on MH7A cell proliferation and apoptosis induced by WTAP overexpression.</p><p><strong>Conclusion: </strong>This study elucidates the protective role of AST on MH7A cells by attenuating m6A/WTAP-mediated apoptosis, offering novel insights into the mechanisms of AST.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718269","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}
引用次数: 0
Solving Minimum Spanning Tree Problems Based on DNA Chemical Reaction Networks.
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-03-18 DOI: 10.2174/0113862073360358250128094601
Jing Yang, Yawen Zheng, Zhixiang Yin, Xianya Geng, Zhen Tang
{"title":"Solving Minimum Spanning Tree Problems Based on DNA Chemical Reaction Networks.","authors":"Jing Yang, Yawen Zheng, Zhixiang Yin, Xianya Geng, Zhen Tang","doi":"10.2174/0113862073360358250128094601","DOIUrl":"https://doi.org/10.2174/0113862073360358250128094601","url":null,"abstract":"<p><strong>Introduction: </strong>DNA strand displacement reactions are emerging as a promising biocomputing tool. The minimum spanning tree problem is fundamental in graph theory. This paper explores the use of DNA strand displacement reaction networks for addressing the minimum spanning tree problem. We also present a computing model that is based on DNA strand displacement reactions.</p><p><strong>Method: </strong>The model effectively solves the minimum spanning tree problem by intelligently integrating the three reaction modules of weighted, threshold, and sum. Thus, initially, we encoded the edges in the graph using distinct DNA sequences and effectively assigned the edges their respective weights. Afterwards, the threshold module applied a filter to the weighted edges based on the fluorescence intensity. Ultimately, the sum module gathered the filtered edges to calculate the overall weight of the minimum spanning tree. In order to verify the effectiveness of the proposed method, we conducted simulation experiments using visual DSD software.</p><p><strong>Result: </strong>The results of the simulations showed the viability and precision of this DNA computing model in resolving intricate problems.</p><p><strong>Conclusion: </strong>Furthermore, this study not only confirms the capability of DNA computing in solving problems related to graph theory, but also offers significant theoretical backing and experimental foundation for the future advancement of DNA-based computer systems and biocomputing applications.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662685","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}
引用次数: 0
Synthesis, QSAR Study and Pharmacological Evaluation of Novel Triazolidine-2-thione Analogues as Antimicrobial, Anti-inflammatory and Antioxidant Agents 作为抗菌、消炎和抗氧化剂的新型三唑烷-2-硫酮类似物的合成、QSAR 研究和药理评估。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2025-03-11 DOI: 10.2174/1386207326666230302101657
Abhishek Sharma, Rubina Bhutani, Akanksha Gupta, Manni Dutta
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