Molecular and Cellular Probes最新文献

{"title":"Cancer-associated fibroblasts secret extracellular vesicles to support cell proliferation and epithelial-mesenchymal transition in laryngeal squamous cell carcinoma","authors":"Tingting Li ,&nbsp;Linli Tian ,&nbsp;Jing Cao ,&nbsp;Ming Liu","doi":"10.1016/j.mcp.2023.101934","DOIUrl":"10.1016/j.mcp.2023.101934","url":null,"abstract":"<div><p>As the critical components of tumor microenvironment, cancer-associated fibroblasts (CAFs) support the development of various type of cancers, including laryngeal squamous cell carcinoma (LSCC), but the detailed molecular mechanisms by which cancer-associated fibroblasts interact with LSCC cells to facilitate its progression have not been fully uncovered. In the present study, by analyzing the contents from normal fibroblasts (NFs) and cancer-associated fibroblasts-derived extracellular vesicles (EVs) with Real-Time qPCR analysis, we found that the tumor-initiating LncRNA TUC338 was significantly upregulated in the cancer-associated fibroblasts-derived extracellular vesicles, compared to the normal fibroblasts-secreted extracellular vesicles. Further experiments confirmed that cancer-associated fibroblasts-derived extracellular vesicles promoted cell proliferation, colony formation abilities, epithelial-mesenchymal transition (EMT) and tumorigenesis of LSCC cells via delivering LncRNA TUC338. The mechanical experiments verified that LncRNA TUC338 was stabilized by METTL3/YTHDF1-mediated N6-methyladenosine (m6A) modifications, and elevated LncRNA TUC338 sponged miR-8485 to upregulate chromobox homolog 2 (CBX2) in LSCC cells in a competing endogenous RNA mechanisms-dependent manner. Moreover, our rescue experiments evidenced that cancer-associated fibroblasts-derived LncRNA TUC338-containing extracellular vesicles-induced supportive effects in LSCC aggressiveness were all abrogated by overexpressing miR-8485 and silencing CBX2. Collectively, this study is the first to identify a novel m6A/LncRNA TUC338/miR-8485/CBX2 axis in CAFs-EVs-mediated LSCC development, and to show its potential as a diagnostic biomarker for LSCC.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41162493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC02253 promote the malignant phenotype of Colon adenocarcinoma cells by up-regulating WWP1-mediated SMAD3 ubiquitination","authors":"Jinfeng Wu ,&nbsp;Xianhong Lu ,&nbsp;Jinzhong Yu ,&nbsp;Pan Li ,&nbsp;Xiqiu Yu","doi":"10.1016/j.mcp.2023.101928","DOIUrl":"10.1016/j.mcp.2023.101928","url":null,"abstract":"<div><h3>Objectives</h3><p>Colon adenocarcinoma (COAD) represents a type of common malignant tumor originating in the digestive tract. Long non-coding RNAs (lncRNAs) have been identified to engage in regulating the initiation and development of COAD. LncRNA LINC02253 has been reported abnormal expressed in COAD, but the underlying mechanism has not been discussed so far. This study aimed to determine the role and the molecular biology mechanism of LINC02253 in COAD progression and unearthed its specific molecular mechanism.</p></div><div><h3>Materials and results</h3><p>RT-qPCR and Western blot assays were conducted to detect gene expression. Function assays were performed to evaluate the effect of gene expression on COAD cell phenotype. Mechanism analyses were done to verify the association among genes after bioinformatics analysis. The obtained data revealed that LINC02253 demonstrated a high expression in COAD tissues and cells. This gene served as an oncogene, permitting to stimulate proliferation and suppress apoptosis of COAD cells. Mechanically, it was found that LINC02253 recruited FUS to stabilize WWP1 mRNA and WWP1 could mediate SMAD3 ubiquitination, thereby promoting the malignant phenotype formation of COAD cells.</p></div><div><h3>Conclusions</h3><p>LINC02253 was uncovered to exert an oncogenic role, enhancing the proliferation of COAD cells and repressing the cell apoptosis by recruiting FUS and encouraging WWP1-mediated SMAD3 ubiquitination.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10025075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-coding RNA profile for natural killer cell activity","authors":"Soudeh Ghafouri-Fard ,&nbsp;Arian Askari ,&nbsp;Alireza Zangooie ,&nbsp;Hamed Shoorei ,&nbsp;Hasan Pourmoshtagh ,&nbsp;Mohammad Taheri","doi":"10.1016/j.mcp.2023.101935","DOIUrl":"10.1016/j.mcp.2023.101935","url":null,"abstract":"<div><p>Natural killer cells (NK cells) are a type of cytotoxic lymphocytes which are involved in innate immunity, alongside with assisting with adaptive immune response. Since they have cytotoxic effects, disruptions in their functionality and development leads to a variety of conditions, whether malignant or non-malignant. The profile and interaction of these non-coding RNAs and NK cells in different conditions is extensively studied, and it is now approved that if dysregulated, non-coding RNAs have detrimental effects on NK cell activity and can contribute to the pathogenesis of diverse disorders. In this review, we aim at a thorough inspection on the role of different non-coding RNAs on the activity and development of NK cells, in a broad spectrum of conditions, including blood-related disorders, viral infections, neurological diseases, gastrointestinal disorders, lung disorders, reproductive system conditions and other types of maladies, alongside with providing insight to the future non-coding RNA-NK cell studies.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41174150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of hub genes and potential inhibitory compounds in the process of liver transplantation through transcriptome sequencing","authors":"Chujun Duan ,&nbsp;Xiaojun Zhao ,&nbsp;Xiao Li ,&nbsp;Jiangang Xie ,&nbsp;Yi Si ,&nbsp;Linxiao Wang ,&nbsp;Dan Wu ,&nbsp;Yifan Wang ,&nbsp;Shanshou Liu ,&nbsp;Qianmei Wang ,&nbsp;Ran Zhuang ,&nbsp;Wen Yin ,&nbsp;Junjie Li","doi":"10.1016/j.mcp.2023.101936","DOIUrl":"10.1016/j.mcp.2023.101936","url":null,"abstract":"<div><p>Liver transplantation (LT) is the best choice for patients with end-stage liver diseases. In order to better understand pathophysiological alterations in LT, we aimed to identify potential hub genes and inhibitory compounds involved in the LT process. Four pairs of peripheral blood mononuclear cell (PBMC) samples of the LT recipients before and after surgery were collected and taken for transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the screened differentially expressed genes (DEGs) between pre- and post-operation groups. Common DEGs were obtained from GO and KEGG enriched pathways, followed by protein-protein interaction (PPI) network construction, hub gene identification, module analysis, and structure-based virtual screening process (SBVS). Compared to the pre-operation stage, 4745 genes were down-regulated and 798 up-regulated after LT. GO analysis showed that the DEGs were enriched in ribosome-related translation regulation, and KEGG analysis indicated that infection and immune-related pathways and diseases were largely enriched. A large number of down-regulated DEGs were not only associated with ribosome-related pathways but also with the alterations of epigenetic modifications, in particular ubiquitination. Moreover, through the PPI network of 29 common genes from GO and KEGG-enriched pathways, 7 hub genes were identified, including PTEN, MYC, EIF2S1, EIF4EBP1, HSP90AB1, TP53, and HSPA8, which were mainly involved in the PI3K-AKT signaling pathway. SBVS of the seed molecule PTEN (PDB code: <span>1D5R</span><svg><path></path></svg>) predicted top hits compounds that may serve as potential inhibitors of PTEN, of which the compound ZINC4235331 had the lowest binding affinity of -10 kcal/mol. The significance of screened hub genes and potential inhibitors involved in the process of LT provides novel therapeutic strategies for improving the outcomes of LT recipients during surgery.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41166673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood exosome marker miRNA-30d-5p: Role and regulation mechanism in cell stemness and gemcitabine resistance of hepatocellular carcinoma","authors":"Biao Tang,&nbsp;Longhui Xie,&nbsp;Xin Tang,&nbsp;Junjie Tian,&nbsp;Shaofei Xiao","doi":"10.1016/j.mcp.2023.101924","DOIUrl":"10.1016/j.mcp.2023.101924","url":null,"abstract":"<div><h3>Background</h3><p>Cancer stem cells (CSCs) are different from regular cancer cells because of their self-renewal feature and differentiation potential, which establishes the backbone of the vital role of CSCs in the progress and drug resistance of hepatocellular carcinoma (HCC). The objective of this study was to evaluate the effects of blood exosome-derived miRNA-30d-5p on the stemness and gemcitabine resistance of HCC cells and the underlying mechanisms.</p></div><div><h3>Methods</h3><p>The expression data of HCC-related miRNAs and mRNAs were downloaded from TCGA database and analyzed for differences. Employing the databases of starBase, TargetScan, miRDB, and mirDIP, we conducted target gene prediction upstream of mRNA. The expression of miRNA-30d-5p and SOCS3 mRNA was assayed by qRT-PCR, and the binding between them was validated by dual luciferase assay. CCK-8 was employed to evaluate cell viability and the IC₅₀ value of gemcitabine. Cells were subjected to a sphere-forming assay to assess their ability to form spheres. Western blot was applied to evaluate the levels of cell surface marker proteins (Nanog, CD133, and Oct4) and exosome markers (CD9, CD81, and FLOT1).</p></div><div><h3>Results</h3><p>Bioinformatics analysis found that SOCS3 expression was down-regulated in HCC. qRT-PCR showed that SOCS3 expression was notably lower in HCC cell lines than in normal liver cell WRL68. At the cellular functional level, SOCS3 overexpression inhibited the viability, sphere-forming ability, stemness, and gemcitabine resistance of HCC cells. Bioinformatics analysis demonstrated that miRNA-30d-5p was the upstream regulator of SOCS3 and highly expressed in HCC tissues and cells. Dual luciferase assay demonstrated that miRNA-30d-5p could bind SOCS3. Rescue experiments showed that upregulating SOCS3 could reverse the effects of miRNA-30d-5p overexpression on the viability, sphere-forming ability, and gemcitabine sensitivity of HCC cells.</p></div><div><h3>Conclusions</h3><p>Blood exosome-derived miRNA-30d-5p promoted the stemness and gemcitabine resistance of HCC cells by repressing SOCS3 expression. Hence, the miRNA-30d-5p/SOCS3 axis might be a therapeutic target for chemotherapy resistance and a feasible marker for the prognosis of HCC patients.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10333821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"16S full-length gene sequencing analysis of intestinal flora in breast cancer patients in Hainan Province","authors":"Yonglan Jiang ,&nbsp;Wei Gong ,&nbsp;Zhenyong Xian ,&nbsp;Weihua Xu ,&nbsp;Junjie Hu ,&nbsp;Zhichao Ma ,&nbsp;Huaying Dong ,&nbsp;Chong Lin ,&nbsp;Shengmiao Fu ,&nbsp;Xinping Chen","doi":"10.1016/j.mcp.2023.101927","DOIUrl":"10.1016/j.mcp.2023.101927","url":null,"abstract":"<div><p>Breast cancer has become the number one cancer in the world, and intestinal flora may be closely linked to it. Geographic location also has an important impact on human intestinal flora. We conducted the first study on the intestinal flora of breast cancer patients and non-breast cancer patients in a tropical region - Hainan Province in China. At the same time, Pacbio platform based on third-generation sequencing was used for the first time to conduct 16S full-length sequencing of fecal microorganism DNA. We completed the species diversity analysis and differential species analysis of the intestinal flora between the two groups, inferred their functional genetic composition and performed functional difference analysis. There were statistically significant differences in alpha diversity between the two groups in Hainan Province. By species composition difference analysis, at the phylum level, Bacteroidales (P = 0.006) and Firmicutes (P = 0.002) was differed between the two groups, and at the genus level, 17 breast cancer-related differential species such as Bacteroides were screened. According to the five grouping methods including ER level, PR level, HER2 status, Ki67 index and histological grade of breast cancer patients, 4, 1, 9, 6, 5 differential microbiota were screened out respectively, which were in total 25 (P &lt; 0.05 for all subgroups) . The functional prediction and difference analysis revealed two functional metabolisms with significant differences between the two groups of microbes (P &lt; 0.05). These results suggest that breast cancer is associated with changes in the composition and function of intestinal flora. These microflora and functional differences may become biomarkers or new targets for diagnosis and treatment of breast cancer.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10282808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formin-related protein 1 facilitates proliferation and aggressive phenotype of clear cell renal cell carcinoma through MAPK/MMP2 pathway","authors":"Gui Ma ,&nbsp;Bin Zhang ,&nbsp;Shengjun Fu ,&nbsp;Jianzhong Lu ,&nbsp;Lili Zhang ,&nbsp;Panfeng Shang ,&nbsp;Zhongjin Yue","doi":"10.1016/j.mcp.2023.101921","DOIUrl":"10.1016/j.mcp.2023.101921","url":null,"abstract":"<div><h3>Background</h3><p>Formin-related protein-1(FRL1) has reportedly been overexpressed in a variety of malignancies, such as clear cell renal cell carcinoma (ccRCC). However, the clinical value and molecular mechanisms underlying ccRCC tumorigenesis and progression in association with FRL1 remain poorly understood.</p></div><div><h3>Methods</h3><p>Immunohistochemical analysis was performed on 119 paraffin-embedded RCC tissue samples to detect FRL1 expression and analyze its prognostic value. Colony formation, the CCK-8 assay, flow cytometry, and <em>in vivo</em> nude mice subcutaneous experiments were used to identify the effects of FRL1 on growth and proliferation. In vitro tests for wound healing, migration, and invasion were used to assess the involvement of FRL1 in invasion and metastatic potential. The process of epithelial-mesenchymal transition process (EMT) and the MMP2 expression were detected in stably transfected RCC cells via western blotting, as well as in tumor tissue paraffin sections from xenograft model.</p></div><div><h3>Results</h3><p>Both FRL1 mRNA and protein levels were noticeably elevated in ccRCC cell lines and samples. Aberrant overexpression of FRL1 was associated with unfavorable clinicopathological features of ccRCC and indicated poor prognosis. Ectopic overexpression of FRL1 increased the growth-promoting traits of ccRCC cells as well as the migratory and invasive capacity of RCC cells, whereas FRL1-silencing caused the opposite results<em>.</em> In addition, FRL1 promoted epithelial-mesenchymal transition (EMT) and upregulated the expression of matrix metalloproteinase 2 (MMP2). Finally, overexpression of FRL1 upregulated phosphorylation level of ERK1/2 with no effect on total level of ERK1/2 in the RCC cells. MAPK/ERK inhibitor reversed the promotional effects of FRL1.</p></div><div><h3>Conclusion</h3><p>FRL1 was overexpressed in ccRCC tissues and predicted poor prognosis. FRL1 contributes to invasion and aggressive phenotype of ccRCC by facilitating EMT through MAPK/MMP2 axis.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10628495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COTE-1 promotes the proliferation and invasion of small cell lung cancer by regulating autophagy activity via the AMPK/mTOR signaling pathway","authors":"Yuhui Ma ,&nbsp;Huijing Feng ,&nbsp;Yuxuan Wang ,&nbsp;Lina Hu ,&nbsp;Xuan Su ,&nbsp;Nan Li ,&nbsp;Xu Li","doi":"10.1016/j.mcp.2023.101918","DOIUrl":"10.1016/j.mcp.2023.101918","url":null,"abstract":"<div><h3>Background</h3><p>COTE-1 has been found to promote the proliferation and invasion of non-small cell lung cancer. However, the mechanism of COTE-1 in SCLC is still unclear. Exploring the role of COTE-1 in SCLC is expected to provide a potential target for the prognosis and treatment of SCLC.</p></div><div><h3>Methods</h3><p>The expression of COTE-1 and ki-67 was detected by immunohistochemical staining. PCR detected COTE-1 expression level. Cell proliferation activity was detected by CCK8 assay. A wound healing test detected cell migrative ability. Transwell invasion assay detected cell invasive ability. The numbers of autophagosomes were observed by transmission electron microscopy. WB detected the expression levels of autophagy-related proteins and AMPK/mTOR pathway-related proteins. The effect of COTE-1 expression level on the proliferation of SCLC tumor tissues was investigated by establishing a mouse SCLC xenograft tumor model.</p></div><div><h3>Results</h3><p>The expression of COTE-1 in SCLC tissues and cells was higher than that in normal tissues and cells. In SCLC cells with high COTE-1 expression, the expression level of autophagy proteins was notably increased, the number of intracellular autophagosomes increased, and the proliferative activity, migration and invasion abilities were enhanced. COTE-1 promotes autophagy, proliferation, and invasion of SCLC cells under nutrient deprivation by activating the AMPK/mTOR signaling pathway. Activation of autophagy by COTE-1 promotes the proliferation and development of xenograft tumors in a mouse model of SCLC.</p></div><div><h3>Conclusion</h3><p>COTE-1 promotes the proliferation, migration and invasion of small cell lung cancer by mediating autophagy based on the AMPK/mTOR pathway.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10628494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathway","authors":"Yingying Zhao ,&nbsp;Rui Ma ,&nbsp;Chuyue Wang ,&nbsp;Rong Hu ,&nbsp;Weili Wu ,&nbsp;Xiang Sun ,&nbsp;Baotao Chen ,&nbsp;Wen Zhang ,&nbsp;You Chen ,&nbsp;Jiajian Zhou ,&nbsp;Ping Yuan","doi":"10.1016/j.mcp.2023.101919","DOIUrl":"10.1016/j.mcp.2023.101919","url":null,"abstract":"<div><h3>Purpose</h3><p>Given the high incidence and mortality rates of colorectal cancer (CRC) and the inadequacy of existing treatments for many patients, this study aimed to explore the potential of Capping Actin Protein (CAPG), a protein involved in actin-related movements, as a novel therapeutic target for CRC.</p></div><div><h3>Methods</h3><p>Bioinformatic analysis of gene expression was conducted using the UALCAN website. Cell proliferation was measured using the CCK-8 kit. Cell cycle, apoptosis, and ferroptosis were analyzed using flow cytometry. Tumorigenesis was evaluated by the subcutaneous inoculation of CRC cells into BALB/c nude female mice. Differentially expressed genes and signaling pathways were identified using RNA sequencing.</p></div><div><h3>Results</h3><p>CAPG was significantly overexpressed in human CRC tissues and its upregulation was correlated with poor overall survival. CAPG knockdown led to notable inhibition of CRC cells <em>in vitro</em> and <em>in vivo</em>. Interference with CAPG blocked the cell cycle at the G1 phase and triggered apoptosis and ferroptosis by upregulating the P53 pathway in CRC cells.</p></div><div><h3>Conclusion</h3><p>CRC patients with higher CAPG levels have a poorer prognosis. CAPG inhibits apoptosis and ferroptosis, while promoting CRC cell proliferation by repressing the P53 pathway. Our study suggests that CAPG may be a potential therapeutic target for CRC prognosis and treatment.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10280914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A network pharmacology-based approach to explore the effect of dihydromyricetin on non-alcoholic fatty liver rats via regulating PPARG and CASP3","authors":"Lu Liu ,&nbsp;Sen Sun ,&nbsp;Xiaohua Li","doi":"10.1016/j.mcp.2023.101926","DOIUrl":"10.1016/j.mcp.2023.101926","url":null,"abstract":"<div><h3>Background</h3><p>Non-alcohol fatty liver disease (NAFLD) is the most prevalent hepatopathy in China, with few effective cures currently. This work aimed to confirm the effect of DHM <em>in vivo</em>/vitro and explore the potential mechanism based on a network pharmacology-based approach.</p></div><div><h3>Methods</h3><p>The rats were fed using a high-fat diet (HFD) to accumulate lipid. DHM at different concentrations was used to treat the HFD rats. The serum total cholesterol (TC), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected using ELISA kits. The target genes of DHM against NAFLD were screened by online databases. Then, the cytotoxicity of DHM in primary hepatocytes and HepG2 cells was determined by MTT reagent. qRT-PCR was used to quantify the expression level of <em>PPAGR</em> and <em>CASP3</em> mRNA. Cell apoptosis and intracellular triglyceride (TG) were detected.</p></div><div><h3>Results</h3><p>HFD diet increased rat liver weight/body weight ratio, serum TC, ALT, and AST. But DHM treatment can reduce these elevated indicators. DHM targeted 14 potential genes in NAFLD. PPARG and CASP3 were two hub genes for DHM against NAFLD, with score factor coefficients of −7.1 and −6.8 kcal/mol. DHM reduced the increased PPARG mRNA level and intracellular TG induced by palmitic acid. DHM can reduce the increased CASP3 mRNA level and cell apoptosis induced by palmitic acid.</p></div><div><h3>Conclusion</h3><p>This work demonstrates a mechanism of DHM that alleviates lipid metabolism disorder and cell apoptosis for the treatment of NAFLD, evidencing the potential application of DHM in NAFLD.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10284559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}