Combinatorial chemistry & high throughput screening最新文献

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"Synthesis, QSAR Study and Pharmacological Evaluation of Novel Triazolidine-2-thione Analogues as Antimicrobial, Anti-inflammatory and Antioxidant Agents","authors":"Abhishek Sharma, Rubina Bhutani, Akanksha Gupta, Manni Dutta","doi":"10.2174/1386207326666230302101657","DOIUrl":"10.2174/1386207326666230302101657","url":null,"abstract":"<p><strong>Background: </strong>The triazole analogues are molecules of immense attraction because of their wide pharmacological applications.</p><p><strong>Methods: </strong>Present research deals with the synthesis of triazole-2-thione analogues and their QSAR study. The synthesized analogs are also evaluated for their antimicrobial, anti-inflammatory, and antioxidant effect.</p><p><strong>Results: </strong>It was revealed that the benzamide analogues (3a, 3d) and triazolidine analogue (4b) were found to be most active against P. aeruginosa and E. coli with pMIC values of 1.69, 1.69 and 1.72, respectively. The antioxidant study of the derivatives showed that 4b was the most active antioxidant with 79% protein denaturation inhibition. The highest anti-inflammatory activity was shown by 3f, 4a and 4f.</p><p><strong>Conclusion: </strong>This study provides certain potent leads for further development of more potential anti- inflammatory, antioxidant and antimicrobial agents.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9380189","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":"Jiawei Danggui Buxue Decoction Reduces Apoptosis and EMT of Renal Interstitial Fibrosis by Regulating JAK2/STAT3 Signaling Pathway.","authors":"Xin Jiang, Yinghang Wang, Saiyue Qiu, Lu Tang, Meixiu Luo, Zhi Pan","doi":"10.2174/0113862073355322250226050458","DOIUrl":"https://doi.org/10.2174/0113862073355322250226050458","url":null,"abstract":"<p><strong>Background: </strong>Renal interstitial fibrosis (RIF) is the primary pathological progression in chronic kidney disease (CKD). Given the constraints related to cost and adverse effects of current treatments, it is crucial to explore novel and efficacious therapeutic strategies. The purpose of this study was to elucidate the potential of Jiawei Danggui Buxue Decoction (JDBD) to reduce apoptosis and epithelial-mesenchymal transition (EMT) in RIF by regulating the Janus kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) pathway.</p><p><strong>Methods: </strong>An angiotensin II (Ang II)-induced HK-2 cells model and a unilateral ureteral obstruction (UUO) animal model were employed to replicate the RIF model. A total of 48 male Wistar rats (weighing 200-220g) were acclimated for 1 week and then randomly divided into 6 groups (sham operation, UUO, Losartan potassium tablets, and three JDBD dosage groups: high, medium, and low, n=8). After the acclimatization period, UUO models were established in 40 rats through surgery, excluding the sham operation group. Each group received the corresponding drug via gavage for 2 weeks. After 2 weeks, rats were anesthetized, and tissues were collected for subsequent analysis. Renal function tests and histological stains were used to evaluate renal damage and histopathological alterations in rats. Cell viability was examined using the CCK-8 assay. Apoptosis was identified through the utilization of flow cytometry and assessment of mitochondrial membrane potential, along with other techniques. We identified and examined the expression of EMT and extracellular matrix (ECM)-related factors, as well as the JAK2/STAT3 pathway.</p><p><strong>Results: </strong>In vivo experiments indicated that JDBD effectively reduced renal dysfunction in UUO rats, ameliorated pathological changes in renal tissues, and significantly modulated the JAK2/STAT3 signaling pathway to inhibit EMT and apoptosis, thereby reducing ECM deposition. Furthermore, JDBD markedly increased the survival rate of Ang II-treated HK-2 cells and reduced apoptosis. The in vitro experimental results further confirmed that JDBD ameliorates RIF by regulating the JAK2/STAT3 pathway.</p><p><strong>Conclusion: </strong>JDBD exhibits anti-apoptotic and EMT-inhibiting functions in RIF, potentially mediated by targeting and inhibiting JAK2/STAT3 signaling transduction.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Anti-PEDV Effects and Mechanisms of Forsythia Essential Oil Based on Network Pharmacology and Experimental Validation.","authors":"Ruiping Liang, Jianbo Guo, Kai Li, Xuan Wang, Xiaoxiao Ge, Jinhui Wang, Jing Sun, Chongbo Zhao, Huanxian Shi, Rongxia Qiao, Hongqing Zheng, Xiaofei Zhang","doi":"10.2174/0113862073358217250225052414","DOIUrl":"https://doi.org/10.2174/0113862073358217250225052414","url":null,"abstract":"<p><strong>Objective: </strong>Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae, is responsible for acute diarrhea, vomiting, and dehydration, which can lead to high mortality in neonatal piglets. Previous research has indicated the antiviral potential of forsythia essential oil (FEO); however, its active components and mechanisms of action remain inadequately defined. This study aims to investigate the antiviral effects of FEO and elucidate its potential mechanisms for treating PEDV.</p><p><strong>Methods: </strong>The primary components of FEO were identified using gas chromatography-mass spectrometry (GC/MS) in conjunction with the National Institute of Standards and Technology Standard Spectrum (NIST) Database. Network pharmacology and weighting coefficients were employed to determine the key signaling pathways associated with PEDV-related diseases. Molecular docking simulations were conducted to explore the interactions between the active ingredients and their corresponding targets. The safety profile of FEO was assessed through cell viability assays utilizing the CCK8 method. Subsequently, immunofluorescence assays (IFA) and reverse transcription-quantitative polymerase chain reaction (RT-Q-PCR) were performed to provide evidence of the anti-PEDV effects. Additionally, the viral replication cycle was analyzed to identify the stages at which FEO exerts its antiviral effects. Finally, key targets were validated through RT-Q-PCR to further investigate the anti-PEDV mechanisms of FEO.</p><p><strong>Results: </strong>The IL-17 signaling pathway was identified as a critical pathway for the treatment of PEDV with FEO based on network pharmacology and weighting coefficient analyses. Furthermore, results from RT-Q-PCR and IFA demonstrated that FEO influenced the replication of PEDV during the attachment and internalization phases. Specifically, during the viral attachment phase, FEO significantly upregulated the expression of HSP90AA1 while downregulating MAPK14 expression, leading to a reduction in associated inflammatory factors. At the high dose of FEO, the expression of HSP90AA1 was higher than that of the model group by about 5-fold, and the expression of MAPK14 was lower than that of the model group by about 2-fold. Cell viability assay showed no significant cytotoxicity of FEO at 0.63 μL/mL, thus confirming its safety.</p><p><strong>Conclusion: </strong>The findings of this study suggest that FEO possesses potential antiviral properties against PEDV. Its novel mechanisms of action warrant further investigation, which may contribute to the development of effective therapeutic strategies for managing PEDV infections.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603857","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":"GLI3 is Inhibited by miR-143-3p and Attenuates Septic-induced Lung Injury and Inflammation by Targeting SFRP1.","authors":"Minqing Ma, Haixia Han, Xiaoya Luo, Jiakai Lin, Bin Sun","doi":"10.2174/0113862073354161250220121414","DOIUrl":"https://doi.org/10.2174/0113862073354161250220121414","url":null,"abstract":"<p><strong>Objectives: </strong>Transcription factors (TF) are the central regulatory hubs of signaling pathways in eukaryotic cells. Here, we explored the abnormal expression of TF in septic-induced lung injury by sequencing.</p><p><strong>Methods: </strong>The levels of target proteins were detected using Western Blot and Elisa. Cell function was evaluated using CCK8 and transwell assays. A double luciferase reporter assay was performed to detect interactions between target molecules.</p><p><strong>Results: </strong>We found that TF glioma-associated oncogene (GLI) family zinc finger 3 (GLI3) was abnormally low expressed in a lipopolysaccharide (LPS) induced acute lung injury (ALI) cell model. In an in vitro model, GLI3 overexpression promoted the proliferation and migration and inhibited apoptosis of lung epithelial cells in LPS-induced inflammatory environment. Importantly, GLI3 overexpression inhibited the secretion of inflammatory factors IL-1β, IL-6, and TNF-α. Additionally, miR-143-3p inhibited the expression of GLI3. MiR-143-3p inhibitor alleviated the cell damage caused by LPS, while knocking down GLI3 counteracted this effect, indicating that miR-143-3p downregulated GLI3 and inhibited its anti-inflammatory effect. Secreted frizzled related protein-1 (SFRP1) was upregulated in LPS-treated cells and SFRP1 promoter interacted with GLI3, suggesting that SFRP1 was a target of TF GLI3. Co-transfection with GLI3 knockdown and SFRP1 overexpression plasmids attenuated the secretion of inflammatory factors IL- 1β, IL-6, and TNF-α caused by GLI3 knockdown in LPS-treated cells, indicating that SFRP1 plays an anti-inflammatory role as a GLI3 target in the ALI cell model.</p><p><strong>Conclusions: </strong>miR-143-3p caused degradation of GLI3 mRNA and thus inhibited the transcription of SFRP1, leading to decreased proliferation and increased levels of inflammatory factors, providing new potential targets for the clinical diagnosis and treatment of ALI.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603849","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}