Combinatorial chemistry & high throughput screening最新文献

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ZFC3H1 as an Indicator of Poor Prognosis in Hepatocellular Carcinoma: Bioinformatic Analysis and Experimental Verification. 作为肝细胞癌不良预后指标的 ZFC3H1:生物信息学分析与实验验证
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2024-08-02 DOI: 10.2174/0113862073317938240729055626
Jiaxin Zhao, Cheng Wang, Rui Wu, Zheyu Fang, Rui Dong, Jie Zhou, Zhenhua Hu
{"title":"ZFC3H1 as an Indicator of Poor Prognosis in Hepatocellular Carcinoma: Bioinformatic Analysis and Experimental Verification.","authors":"Jiaxin Zhao, Cheng Wang, Rui Wu, Zheyu Fang, Rui Dong, Jie Zhou, Zhenhua Hu","doi":"10.2174/0113862073317938240729055626","DOIUrl":"https://doi.org/10.2174/0113862073317938240729055626","url":null,"abstract":"<p><strong>Background: </strong>Zinc finger C3H1-type containing (ZFC3H1) might regulate RNA processes. However, research lacks the prognostic value of ZFC3H1 in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>The study analyzed ZFC3H1 expression in HCC cells and its correlation with patient prognosis using transcriptomics, immunohistochemistry, and quantitative real-time reverse transcription PCR, as well as single-cell RNA expression data. Additionally, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to investigate the potential ZFC3H1-related cellular functions and signaling pathways. The impact of ZFC3H1 expression on the tumor microenvironment and tumor mutational burden (TMB) was assessed using the ESTIMATE algorithm. Cell-based assays, including cell counting kit 8, proliferation, colony formation, cell cycle, wound healing, and Transwell assays, were conducted to evaluate the influence of ZFC3H1 on hepatocellular carcinoma proliferation and migration.</p><p><strong>Results: </strong>ZFC3H1 is upregulated in HCC and linked to tumor progression. High ZFC3H1 expression is a prognostic risk factor for HCC, according to Kaplan-Meier and Cox regression analyses. ESTIMATE analysis suggested that ZFC3H1 reduces immune cell infiltration and increases the TMB. Patients with low ZFC3H1 expression might respond better to immunotherapy. High ZFC3H1 expression is associated with increased half-maximal inhibitory concentration (IC50) of sorafenib. Functional experiments demonstrated that reducing ZFC3H1 expression inhibited HCC cell proliferation and migration.</p><p><strong>Conclusion: </strong>ZFC3H1 is upregulated in HCC, promoting the proliferation and migration of liver cancer cells, impacting the prognosis of HCC patients and the effectiveness of immunotherapy. ZFC3H1 might serve as a therapeutic target and biomarker for HCC.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896964","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
Ballota acetabulosa (L). Bentham: A First-Time GC-MS Analysis and Antioxidant Potential of its Essential Oil. Ballota acetabulosa (L).本瑟姆:首次 GC-MS 分析及其精油的抗氧化潜力。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2024-07-31 DOI: 10.2174/0113862073319327240614113859
Ayse Nur Yazgan-Ekici, Filiz Bakar-Ates, Sinem Aslan Erdem, Betul Sever-Yilmaz
{"title":"Ballota acetabulosa (L). Bentham: A First-Time GC-MS Analysis and Antioxidant Potential of its Essential Oil.","authors":"Ayse Nur Yazgan-Ekici, Filiz Bakar-Ates, Sinem Aslan Erdem, Betul Sever-Yilmaz","doi":"10.2174/0113862073319327240614113859","DOIUrl":"https://doi.org/10.2174/0113862073319327240614113859","url":null,"abstract":"<p><strong>Background: </strong>Ballota acetabulosa native to the Mediterranean region, belonging to the Lamiaceae family, holds significance in folk medicine. Externally, it is applied for treating cuts and burns, while internally, it is utilized to alleviate inflammation, suppress cough, and address gastrointestinal issues.</p><p><strong>Methods: </strong>This study aimed to investigate the chemical composition of the essential oil of Ballota acetabulosa and to evaluate the antioxidant capacity of the essential oil, as well as the aqueous and ethanolic extracts of the plant. Essential oil analysis was performed using Gas Chromatography- Mass Spectrometry (GC-MS), while 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and inhibition of lipid peroxidation assays were applied to the essential oil, water, and ethanol extracts of the plant.</p><p><strong>Results: </strong>Spathulenol was found to be the predominant constituent of the essential oil, comprising 25.03% of the oil. Compared to the control group (Propyl gallate for DPPH, IC50 0.109; BHT for inhibition of lipid peroxidation, IC50 0.133), the essential oil was found to have insignificant antioxidant activity (IC50 value 10.395 mg/mL for DPPH, 1.051 mg/mL for inhibition of lipid peroxidation). Moreover, ethanolic extract (IC50 value 1.583 mg/mL for DPPH, 0.029 mg/mL for inhibition of lipid peroxidation) exerted more antioxidant activity than aqueous extract (IC50 value 1.9017 mg/mL for DPPH, 0.161 mg/mL for inhibition of lipid peroxidation).</p><p><strong>Conclusion: </strong>Hitherto, this is the earliest report on the composition and activity of the essential oil Ballota acetabulosa. However, further investigation of different antioxidant capacity assays is suggested to highlight potential variations in mechanisms of action and subsequent results. Everything considered, this study advances the comprehension of the chemical composition and possible therapeutic uses of Ballota acetabulosa, highlighting the need for more research into its uses.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874366","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
Effect and Mechanism of 6-Gingerol against Precancerous Lesions of Gastric Cancer Based on Network Pharmacology and In Vitro Experiment. 基于网络药理学和体外实验的 6-姜酚对胃癌癌前病变的作用和机制
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2024-07-29 DOI: 10.2174/0113862073303380240722112207
Jingyu Xu, Cian Zhang, Ling Wang, Meiling Wang, JIayu Liang, Yanlong Yang, Xuan Zhang
{"title":"Effect and Mechanism of 6-Gingerol against Precancerous Lesions of Gastric Cancer Based on Network Pharmacology and In Vitro Experiment.","authors":"Jingyu Xu, Cian Zhang, Ling Wang, Meiling Wang, JIayu Liang, Yanlong Yang, Xuan Zhang","doi":"10.2174/0113862073303380240722112207","DOIUrl":"https://doi.org/10.2174/0113862073303380240722112207","url":null,"abstract":"<p><strong>Background: </strong>Precancerous Lesions of Gastric Cancer (PLGC) are critical in the secondary prevention of gastric cancer. Despite the notable effects of natural products on PLGC, the specific mechanisms by which compounds, like 6-gingerol, influence these lesions are not fully understood.</p><p><strong>Aims: </strong>This study aimed to confirm the effect and mechanism of 6-gingerol in the treatment of precancerous lesions of gastric cancer (PLGC).</p><p><strong>Objective: </strong>The objective of this study was to elucidate the effects and mechanisms of 6-gingerol against PLGC using network pharmacology and in vitro experiments.</p><p><strong>Methods: </strong>We employed network pharmacology to identify potential targets and pathways influenced by 6-gingerol, followed by validation through in vitro experiments using a PLGC cell model.</p><p><strong>Results: </strong>Network pharmacology analysis highlighted the PI3K/Akt signaling pathway as significantly influenced by 6-gingerol. In vitro experiments confirmed that 6-gingerol effectively inhibited proliferation, invasion, and metastasis of MC cells, promoted apoptosis, and induced cell cycle arrest, primarily through modulation of the PI3K/Akt pathway. Statistical analysis revealed significant inhibition (p < 0.05) across these cellular processes in a dose-dependent manner.</p><p><strong>Conclusion: </strong>This study demonstrated that 6-gingerol acts as an effective agent against PLGC, with clear dose-dependent effects that pave the way for further experimental and clinical exploration.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792167","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
Knockdown of Anoikis-Associated Gene OCIAD2 Reduces Proliferation and Migration of Glioblastoma Cell Lines. 敲除 Anoikis 相关基因 OCIAD2 可减少胶质母细胞瘤细胞株的增殖和迁移。
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2024-07-29 DOI: 10.2174/0113862073305357240719070044
Danna Huang, Lu Chen, Yu Liu, Wuwei Wu, Yingying Liu, Yu Pan
{"title":"Knockdown of Anoikis-Associated Gene OCIAD2 Reduces Proliferation and Migration of Glioblastoma Cell Lines.","authors":"Danna Huang, Lu Chen, Yu Liu, Wuwei Wu, Yingying Liu, Yu Pan","doi":"10.2174/0113862073305357240719070044","DOIUrl":"https://doi.org/10.2174/0113862073305357240719070044","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) severely disrupts the quality of life of patients. Anoikis represents a significant mechanism in cancer invasion and metastasis. Our study focused on the prognostic relationship between the anoikis-associated gene and GBM and its effect on GBM cell progression.</p><p><strong>Methods: </strong>We downloaded 656 and 979 GBM sample data from TCGA and CGGA cohort datasets, respectively. Fifteen anoikis-associated genes were obtained from the GeneCards database and were subsequently clustered to identify differential genes associated with them. After LAASO screening, the expression values of the 5 differential genes were the sum of LASSO regression coefficients. Survival analysis and ROC curve analysis of anoikis scores were performed using the TCGA training and CGGA validation sets. The prognostic factors were analyzed using Cox regression analysis in GBM. Moreover, CCK-8, colony formation, wound healing, and transwell assay were used to evaluate GBM cell proliferation and migration.</p><p><strong>Results: </strong>Significant differences were observed in the 5-year survival of GBM patients between the two subgroups. Then, our analysis demonstrated that high OCIAD2, FTLP3, IGFBP2, and H19 levels were associated with lower 5-year GBM survival rates, whereas high SFRP2 levels were associated with higher survival rates. Univariate Cox analysis indicated that GBM risk was linked to both anoikis score and grade, while multivariate Cox analysis indicated that GBM risk was associated with both anoikis score and age. Additionally, OCIAD2 was highly expressed in U251MG and T98G cells. Moreover, OCIAD2 silencing inhibited GBM cell proliferation and migration.</p><p><strong>Conclusion: </strong>This study demonstrated the potential of the anoikis-associated gene OCIAD2 as a prognostic biomarker for GBM. Furthermore, we validated in vitro that OCIAD2 promoted GBM cell progression.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792168","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
Corrigendum to: B2M is a Biomarker Associated With Immune Infiltration In High Altitude Pulmonary Edema. 更正:B2M是与高海拔肺水肿中免疫渗透相关的生物标志物
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2024-07-23 DOI: 10.2174/1386207327999240723122132
Mu Yuan, Xueting Hu, Wei Xing, Xiaofeng Wu, Chengxiu Pu, Wei Guo, Xiyan Zhu, Mengwei Yao, Luoquan Ao, Zhan Li, Xiang Xu
{"title":"Corrigendum to: B2M is a Biomarker Associated With Immune Infiltration In High Altitude Pulmonary Edema.","authors":"Mu Yuan, Xueting Hu, Wei Xing, Xiaofeng Wu, Chengxiu Pu, Wei Guo, Xiyan Zhu, Mengwei Yao, Luoquan Ao, Zhan Li, Xiang Xu","doi":"10.2174/1386207327999240723122132","DOIUrl":"https://doi.org/10.2174/1386207327999240723122132","url":null,"abstract":"<p><p>The funding details have been incorporated upon author's request in the funding section of this article titled \"B2M is a Biomarker Associated With Immune Infiltration In High Altitude Pulmonary Edema ,\" 2024, 27(1), 168-185 [1]. Details of the error and a correction are provided here. Original: This work was supported by grants from the Chongqing Natural Science Gene General Project (No. YWRYPYG). Corrected: This work was supported by General Project of Chongqing Natural Science Foundation cstc2020jcyj-msxmX0227. We regret the error and apologize to the readers. The original article can be found online at www.eurekaselect.com/article/131669.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003783","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
Integrating Molecular Biology and Network Pharmacology to Analyze the Antidepressant Mechanism of Glycyrrhizaglabra. 结合分子生物学和网络药理学分析甘草的抗抑郁机制
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2024-07-22 DOI: 10.2174/0113862073295662240715070530
Liting Liang, Yongmei Jiang, Linghan Kuang, Xingxin Liu, Jingjing Luo, Jiaji Ling, Wenjing Wu
{"title":"Integrating Molecular Biology and Network Pharmacology to Analyze the Antidepressant Mechanism of Glycyrrhizaglabra.","authors":"Liting Liang, Yongmei Jiang, Linghan Kuang, Xingxin Liu, Jingjing Luo, Jiaji Ling, Wenjing Wu","doi":"10.2174/0113862073295662240715070530","DOIUrl":"https://doi.org/10.2174/0113862073295662240715070530","url":null,"abstract":"<p><strong>Introduction: </strong>Antidepressants have adverse effects and induce drug resistance when used excessively or frequently. Therefore, adjuvants are needed to reduce the use of antidepressants during treatment. Traditional Chinese medicine (TCM) is an important adjunctive approach to depression with safety, environmental protection, and low toxicity. Glycyrrhizaglabra (licorice, GG) is a plant commonly used in various herbal remedies.</p><p><strong>Method: </strong>We investigated the antidepressant activity of GG, its active constituents, and potential depression-related targets. We combined animal behavioral and molecular biological assays with network pharmacology to analyze the antidepressant mechanism of GG. GG extracts reversed lipopolysaccharide (LPS)-induced depression-like behavior in behavioral tests. We selected 56 active compounds and 695 target compounds of licorice from TCMSP. The PPI network screened 80 core targets for enrichment analysis. It shows that GG significantly affected neurodegeneration pathways, neuroactive ligand-receptor interaction, cAMP signaling pathway, serotonergic synapse, dopaminergic synapse, and MAPK signaling pathway.</p><p><strong>Result: </strong>Mechanistic studies showed that GG reduced IL-1β, IL-6, and TNF-α levels, 5-HTRA1 expression, and GSK3β phosphorylation in mouse hippocampus. It also increased BDNF and DRD1 expression and CREB and ERK1/2 phosphorylation.</p><p><strong>Conclusion: </strong>It shows that GG acted on these proteins to affect multiple pathways that mediate the pathogenesis of depression.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747648","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
ADAMTS16 Suppression by MicroRNA-25 Leads to Oncogenic Properties in Renal Cell Carcinoma. MicroRNA-25抑制ADAMTS16导致肾细胞癌的致癌特性
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2024-07-22 DOI: 10.2174/0113862073321326240718063755
Jian Huang, Zhe Tang, Guangjun Zhong, Linjie Guo, Ye Feng
{"title":"ADAMTS16 Suppression by MicroRNA-25 Leads to Oncogenic Properties in Renal Cell Carcinoma.","authors":"Jian Huang, Zhe Tang, Guangjun Zhong, Linjie Guo, Ye Feng","doi":"10.2174/0113862073321326240718063755","DOIUrl":"https://doi.org/10.2174/0113862073321326240718063755","url":null,"abstract":"<p><strong>Introduction: </strong>Increasing evidence indicates that microRNAs (miRNAs) play a crucial role in modulating tumor growth. This study is centered on investigating the contribution of miR-25 to the progression of Renal Cell Carcinoma (RCC).</p><p><strong>Methods: </strong>The investigators examined the expression levels of miR-25 and ADAMTS16 in RCC samples and cell lines. The association between miR-25 and ADAMTS16 was validated via a luciferase reporter assay. Cell viability, apoptosis, migration, and invasion were evaluated utilizing CCK-8 and flow cytometry techniques, while the expression levels of ADAMTS16, β-catenin, GSK-3β, and p-GSK-3β were assessed through western blot analysis.</p><p><strong>Results: </strong>The investigation revealed elevated expression levels of miR-25 in RCC tissues. Subsequently, ADAMTS16 was identified as a target of miR-25. Increased miR-25 levels were associated with decreased expression of ADAMTS16, resulting in enhanced cell viability and diminished apoptosis. Conversely, inhibition of miR-25 led to decreased cell viability, proliferation, and migration. Additionally, the researchers observed that miR-25 triggered the phosphorylation of GSK-3β and β-catenin while leaving the total GSK-3β level unaffected.</p><p><strong>Conclusion: </strong>This study suggests that miR-25 regulates the expression of ADAMTS16 through the Wnt/β-catenin signaling pathway, providing new insights into the cause and potential treatment of RCC.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747646","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
Promoter Hypermethylation Downregulates MiR-125b-5p and MiR-199b-5p Targeting of ΔNp63, Resulting in PI3K/AKT/mTOR Pathway Activation and Keratinocyte Differentiation. Promoter Hypermethylation Downregulates MiR-125b-5p and MiR-199b-5p Targeting of ΔNp63, Resulting in PI3K/AKT/mTOR Pathway Activation and Keratinocyte Differentiation.
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2024-07-22 DOI: 10.2174/0113862073314510240612101052
Yi Ding, Shi-Qi Ma, Min Li, Long Chen, Shu-Mei Feng
{"title":"Promoter Hypermethylation Downregulates MiR-125b-5p and MiR-199b-5p Targeting of ΔNp63, Resulting in PI3K/AKT/mTOR Pathway Activation and Keratinocyte Differentiation.","authors":"Yi Ding, Shi-Qi Ma, Min Li, Long Chen, Shu-Mei Feng","doi":"10.2174/0113862073314510240612101052","DOIUrl":"https://doi.org/10.2174/0113862073314510240612101052","url":null,"abstract":"<p><strong>Background: </strong>Normal keratinocyte differentiation is important for epidermal wound healing. ΔNp63 is a major gene regulating epidermal formation and differentiation. We identified miRNAs targeting ΔNp63 and studied the association between the miRNAs and DNA methylation in keratinocyte differentiation.</p><p><strong>Aims: </strong>This study aimed to explore the mechanisms regulating ΔNp63 expression during keratinocyte differentiation.</p><p><strong>Methods: </strong>Bioinformatics analysis was performed to screen the miRNAs targeting ΔNp63 and uncover potential pathway mechanisms. The differentiation model of keratinocytes was established by CaCl2 treatment. Furthermore, the effects of the miRNA transgenic technique on Δ Np63 and keratinocyte differentiation were studied. In addition, the RNA FISH experiment was conducted to detect the location of different miRNAs. A double luciferase reporter experiment was carried out to verify the potential bindings between the miRNAs and ΔNp63. A rescue experiment was also performed to assess the effects of different miRNAs targeting ΔNp63 on keratinocyte differentiation. We analyzed the methylation patterns of the promoter regions of miRNAs using keratinocytes treated with 5-Aza-2'-deoxycytidine. Finally, we designed a methylation rescue experiment to verify the effects of miRNA promoter methylation on keratinocyte differentiation.</p><p><strong>Results: </strong>Bioinformatics analysis showed that the miR-125b-5p and miR-199b-5p binding to the ΔNp63 3'UTR region decreased during skin development. Moreover, such binding may downregulate the PI3K/AKT/mTOR pathway. The expression levels of CK10, Inv, TG1, ΔNp63, and PI3K/AKT/mTOR were all significantly increased during keratinocyte differentiation. Both miR- 125b-5p and miR-199b-5p were localized in the cytoplasm. Luciferase assay results showed that both miR-125b-5p and miR-199b-5p can bind to the 3'UTR region of ΔNp63. Overexpression of ΔNp63 can significantly counteract the inhibitory effect of miRNA mimics on keratinocyte differentiation. Moreover, the promoter regions of both miR-125b-5p and miR-199b-5p had methylation sites, and the methylation levels in those promoter regions were significantly increased during keratinocyte differentiation. 5-Aza-2'-Deoxycytidine treatment increased the expression of miR- 125b-5p and miR-199b-5p and inhibited the differentiation of keratinocytes. Finally, miRNA inhibitors reversed the inhibitory effects of 5-Aza-2'-deoxycytidine on keratinocyte differentiation.</p><p><strong>Conclusion: </strong>Promoter hypermethylation in miR-125b-5p and miR-199b-5p seem to promote keratinocyte differentiation via upregulation of ΔNp63 expression and the activation of the PI3K/AKT/mTOR pathway. The findings of this study are helpful for future research on skin development and clinical scar-free healing.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747649","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
HRAS Induces Ferroptosis through Upregulating HSPB1 in Hepatocellular Carcinoma. HRAS 通过上调肝细胞癌中的 HSPB1 诱导铁变态反应
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2024-07-22 DOI: 10.2174/0113862073306462240710174817
Wei Chen, Xiang Zhang, Bin Zhang, Minhui Chi, Qi Zheng
{"title":"HRAS Induces Ferroptosis through Upregulating HSPB1 in Hepatocellular Carcinoma.","authors":"Wei Chen, Xiang Zhang, Bin Zhang, Minhui Chi, Qi Zheng","doi":"10.2174/0113862073306462240710174817","DOIUrl":"https://doi.org/10.2174/0113862073306462240710174817","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study is to explore the mechanism of HRAS and HSPB1 in ferroptosis. Primary liver cancer is the third leading cause of tumor death worldwide. Hepatocellular carcinoma (HCC) constitutes 75%-85% of cases of primary liver cancer. HRAS and HSPB1 co-express in multiple cells and participate in tumor progression regulation. However, their expression regulation and role in HCC have not been reported.</p><p><strong>Methods: </strong>We investigated the effects of HRAS and HSPB1 on ferroptosis in in vitro experiments. Here, the role and mechanism of HRAS and HSPB1 on ferroptosis were investigated by transfecting the specific siRNA or overexpressing plasmids in HCC cells.</p><p><strong>Results: </strong>Bioinformatics analysis proved that HRAS and HSPB1 were highly expressed in HCC tissues and associated with poor prognosis of patients with HCC. In vitro, HRAS overexpression reduced the level of intracellular iron, ROS, and MDA production in HCC cells. Mechanistically, HRAS increased GPX4 expression and decreased the levels of ACSL4 and P53. HRAS also increased HSPB1 expression, and HRAS knockdown downregulated HSPB1 levels in HCC cells. Importantly, overexpression of HSPB1 reversed HRAS-increased concentration of iron, MDA, and ROS and eliminated HRAS-induced ferroptosis. Moreover, HRAS enhanced the proliferation and invasion by targeting HSPB1.</p><p><strong>Conclusion: </strong>The regulation of HSPB1 by HRAS enhanced the resistance of HCC cells to ferroptosis. HRAS promoted proliferation and invasion by upregulating HSPB1. This research provides a new potential strategy for HCC treatment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747647","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
Bushen Zhuyun Decoction Improves Endometrial Receptivity by Inhibiting NF-κB/NLRP3 Signaling Pathway. 蒲参竹茹汤通过抑制NF-κB/NLRP3信号通路改善子宫内膜的受孕能力
IF 1.6 4区 医学
Combinatorial chemistry & high throughput screening Pub Date : 2024-07-15 DOI: 10.2174/0113862073309790240711110744
Xiaolan Wang, Yun Tong, Haidong Zhang, Yeting Zou, Yinyin Ding, Bei Liu, Weiye Zhou, Jinjun Shan, Jianjian Ji, Wenren Su, Yinyin Liu, Huifang ZHou
{"title":"Bushen Zhuyun Decoction Improves Endometrial Receptivity by Inhibiting NF-κB/NLRP3 Signaling Pathway.","authors":"Xiaolan Wang, Yun Tong, Haidong Zhang, Yeting Zou, Yinyin Ding, Bei Liu, Weiye Zhou, Jinjun Shan, Jianjian Ji, Wenren Su, Yinyin Liu, Huifang ZHou","doi":"10.2174/0113862073309790240711110744","DOIUrl":"https://doi.org/10.2174/0113862073309790240711110744","url":null,"abstract":"<p><strong>Objective: </strong>Bushen Zhuyun Decoction (BSZY), a traditional Chinese herbal prescription has shown promising effects on gynecological infertility, but the mechanism for endometrial receptivity is still unclear. This study aimed to investigate the regulatory effects of BSZY on endometrial receptivity, which plays a key role in colonization of embryo, and its regulatory mechanisms associated with NF- κB/NLRP3 pathway.</p><p><strong>Methods: </strong>SD rats at reproductive age with affected endometrial receptivity was established using mifepristone (RU486), and the regulatory effects of BSZY on endometrial receptivity were evaluated by H&E staining, and changes in sex hormones by ELISA and Western blot. Moreover, human endometrial RL95-2 cells were treated with H2O2, and inflammatory cytokines in rats and RL95-2 cells were analyzed by ELISA. The activation of NF-κB/NLRP3 signaling pathway in RL95-2 cells were characterized using immunofluorescence and Western blot. Mitochondrial morphology and function in RL95-2 cells were observed by transmission electron microscope and cell mitochondrial stress test.</p><p><strong>Results: </strong>BSZY increased uterine endometrial thickness and attenuate histopathological changes induced by RU486. BSZY can regulate endometrial estrogen receptor and progesterone receptor, and the levels of sex hormones and inflammatory cytokines in pregnant rats. BSZY-containing serum also showed strong anti-inflammatory and cytoprotective effects in vitro. In addition, BSZY-containing serum inhibited the activation of NF-κB/NLRP3 signaling pathway, and improve mitochondrial morphology and function in RL95-2 cells.</p><p><strong>Conclusion: </strong>BSZY can improve endometrial receptivity, potentially by improving mitochondrial morphology and function to inhibit the activation of NF-κB/NLRP3 signaling pathway in endometrial cells, thus regulate inflammation to improve endometrial receptivity.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632883","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}
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