南方医科大学学报杂志最新文献

{"title":"[High expression of LINC00467 promotes proliferation and metastasis of lung adenocarcinoma cells by suppressing autophagy <i>via</i> inhibiting the AMPK/mTOR pathway].","authors":"Y Li, X Xi, M Zhang, X Wu, X Wang","doi":"10.12122/j.issn.1673-4254.2024.10.08","DOIUrl":"10.12122/j.issn.1673-4254.2024.10.08","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the regulatory effects of LINC00467 on proliferation and metastasis of lung adenocarcinoma cells and the involvement of autophagy in its regulatory mechanism.</p><p><strong>Methods: </strong>LINC00467 expression levels in lung adenocarcinoma tissues and their correlation with the patients' survival outcomes were analyzed using data from TCGA database. LINC00467 expression was also examined using qRT-PCR in human bronchial epithelial cells 16HBE and lung adenocarcinoma cell lines A549 and H1299. In A549 and H1299 cells transfected with a short hairpin RNA targeting LINC00467 (shLINC00467), the effects of 3-methyladenine (3-MA, an autophagy inhibitor) and BML-275 (an AMPK inhibitor) treatment on cell proliferation, migration, and expressions of LC3 and the AMPK/mTOR pathway proteins were tested using colony formation assay, wound-healing and Transwell assays, immunofluorescence staining and Western blotting. GSEA enrichment analysis was conducted to analyze the correlation between LINC00467 and the autophagy pathway.</p><p><strong>Results: </strong>The expression level of LINC00467 was significantly higher in lung adenocarcinoma tissues than in the adjacent tissues (<i>P</i> < 0.001) and increased progressively with the clinical stage (<i>P</i> < 0.05), and its high expression was associated with a poor overall survival (<i>P</i>= 0.049) and a high first progression rate (<i>P</i>=0.026) of the patients. LINC00467 expression was also significantly higher in A549 and H1299 cells than in 16HBE cells. In A549 and H1299 cells, LINC00467 knockdown significantly decreased colony-forming, migration and invasion abilities of the cells, lowered p-mTOR/mTOR and p62 expressions, and increased p-AMPK/AMPK expressions and LC3Ⅱ/Ⅰ ratio, and these effects were strongly attenuated by application of either 3-MA or BML-275. GSEA analysis suggested an inhibitory effect on LINC00467 on the autophagy pathway (|NES| > 1, <i>P</i> < 0.05, FDR < 0.25).</p><p><strong>Conclusion: </strong>High expressions of LINC00467 promote proliferation and metastasis of lung adenocarcinoma cells possibly by inhibiting cell autophagy mediated by the AMPK/mTOR signaling pathway.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":"44 10","pages":"1898-1909"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Expansion and identification of primary rat aortic vascular stem cells <i>in vitro</i>].","authors":"H Ma, Y Huang, Y Yang, H Liu, Y Tang, W Cong","doi":"10.12122/j.issn.1673-4254.2024.10.06","DOIUrl":"10.12122/j.issn.1673-4254.2024.10.06","url":null,"abstract":"<p><strong>Objective: </strong>To culture and expand primary rat aortic vascular stem cells in vitro and evaluate their characteristics as mesenchymal stem cells.</p><p><strong>Methods: </strong>The thoracic and abdominal aortas isolated from 2- to 3-week-old Sprague-Dawley rats were cut into vascular segments 2.0 mm in length and cultured in culture flasks till adhesion and solidification of the outer membranes. The primary cells were further cultured to 80%-90% confluence before passaging. The morphology and growth characteristics of the cells were observed under a microscope, and the expressions of surface marker CD molecules on the cells was analyzed using flow cytometry. Adipogenic and osteogenic differentiation assays were performed to assess the capacity of the cells for multilineage differentiation.</p><p><strong>Results: </strong>After 3 days of culture, a small number of spindle, star-shaped or polygonal cells migrated out from the peripheral of the vascular segments. At 5-6 days, island-like cell clusters occurred and the cells began to proliferate rapidly. The cell clusters expanded radially and showed signs of cell cloning. At 7-8 days, the cells fused into sheets and displayed a vortex-like distribution. The cells in the third passage presented with a uniform morphology, showing a typical fibroblast-like arrangement. Flow cytometry showed that the cells expressed predominantly CD44 (80.3%), CD73 (62.2%) and CD90 (46.8%) with low expressions of CD34 (1.1%), CD45 (0.2%) and CD11b/c (0.2%). Adipogenic and osteogenic differentiation experiments demonstrated that the cells were capable of lipogenic and osteogenic differentiation <i>in vitro</i>.</p><p><strong>Conclusion: </strong>Rat aortic vascular stem cells with mesenchymal stem cell characteristics can be successfully isolated and cultured by adherent culture of the segmented outer membrane.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":"44 10","pages":"1881-1886"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Inhibiting Yes-associated protein alleviates CCl₄ liver fibrosis in mice by reducing epithelial mesenchymal transition].","authors":"W Zhao, H Ruan, S Wang, Y Cheng, M Lei, J Zhao, C Liu","doi":"10.12122/j.issn.1673-4254.2024.10.01","DOIUrl":"10.12122/j.issn.1673-4254.2024.10.01","url":null,"abstract":"<p><strong>Objective: </strong>To explore whether Yes-associated protein (YAP) affects occurrence and progression of liver fibrosis by regulating epithelial-mesenchymal transition (EMT).</p><p><strong>Methods: </strong>In a 8-week-old C57BL/6 mouse model of CCl₄-induced liver fibrosis, the effect of verteporfin (a YAP inhibitor) intervention was assessed with HE staining and by detecting liver biochemistry and expressions of YAP and EMT-related genes using immunohistochemistry and Western blotting. Transcriptome and proteomic sequencing and informatics analysis were used to investigate the main downstream pathways of YAP in liver fibrosis. Serum levels of YAP, N-cadherin, vimentin and Twist were examined in 60 healthy individuals, 60 patients with chronic hepatitis B (CHB), and 60 patients with HBV-related liver cirrhosis. In another 24 C57BL/6 mice, the effects of Twist inhibitor alone or in combination with harmine (a YAP activator) on CCl₄-induced liver fibrosis were evaluated by histopathological examination and Western blotting.</p><p><strong>Results: </strong>The mouse models of liver fibrosis showed obvious structural damages of the liver lobes with formation of pseudolobules, and verteporfin treatment significantly improved these pathologies and lowered plasma ALT and AST levels of the mice. Transcriptome and proteomic sequencing and informatics analysis suggested that N-cadherin and Twist were differentially expressed in liver fibrosis in close correlation with YAP. Inhibition of YAP obviously downregulated hepatic N-cadherin and Twist protein expressions in the mice with liver fibrosis. In patients with CHB and liver cirrhosis, serum levels of YAP elevated obviously with the severity of liver fibrosis and were significantly correlated with N-cadherin, vimentin and Twist levels. In mice with liver fibrosis, inhibiting Twist effectively improved liver inflammation and fibrosis, while the combined treatment with YAP activator worsened hepatic collagen fiber deposition and increased hepatic YAP and <i>α</i>-SMA expressions.</p><p><strong>Conclusion: </strong>EMT is an important pathogenic mechanism of liver fibrosis, and inhibiting YAP can alleviate liver fibrosis by reducing EMT.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":"44 10","pages":"1839-1849"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Nlrp6 overexpression inhibits lipid synthesis to suppress proliferation of hepatocellular carcinoma cells by regulating the AMPK-Srebp1c axis].","authors":"C Huang, Y Sun, W Li, L Liu, W Wang, J Zhang","doi":"10.12122/j.issn.1673-4254.2024.10.09","DOIUrl":"10.12122/j.issn.1673-4254.2024.10.09","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the mechanism of Nlrp6 for regulating hepatocellular carcinoma (HCC) progression in light of lipid synthesis regulation.</p><p><strong>Methods: </strong>Nlrp6 expression level in HCC tissues of different pathological grades was investigated using RNA-seq data from The Cancer Genome Atlas (TCGA) database, and its correlation with the patients' survival was analyzed with Kaplan-Meier survival analysis. HepG2 cells with adenovirus-mediated Nlrp6 overexpression or knockdown were treated with palmitic acid (PA), and the changes in lipid deposition and cell proliferation were evaluated using Oil Red O staining, CCK-8 assay, EdU staining, and colony formation assay. RT-qPCR and Western blotting were used to detect the changes in expression of lipid synthesis-related genes and the proteins in the AMPK-Srebp1c axis. In a mouse model of hepatic steatosis established in liver-specific Nlrp6 knockout mice by high-fat diet feeding for 24 weeks, liver fibrosis was examined with histological staining, and the changes in expressions of HCC markers and the AMPK-Srebp1c signaling pathway were detected.</p><p><strong>Results: </strong>Nlrp6 expression was significantly reduced in HCC tissues with negative correlations with the pathological grades and the patients' survival (<i>P</i> < 0.0001). In HepG2 cells, Nlrp6 overexpression significantly inhibited lipid deposition and cell proliferation, whereas Nlrp6 knockdown produced the opposite effects. Nlrp6 overexpression strongly suppressed the expression of lipid synthesis-related genes, promoted AMPK phosphorylation, and inhibited Srebp1c expression. The mice with liver-specific Nlrp6 knockout and high-fat feeding showed increased hepatic steatosis, collagen deposition, and AFP expression with reduced AMPK phosphorylation and increased Srebp1c expression.</p><p><strong>Conclusion: </strong>Nlrp6 overexpression inhibits lipid synthesis in HCC cells by regulating the AMPK-Srebp1c axis, which might be a key pathway for suppressing HCC cell proliferation.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":"44 10","pages":"1910-1917"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Modification with IL-21 and CCL19 enhances killing efficiency and tumor infiltration of NKP30 CAR-T cells in lung cancer].","authors":"Z Zhou, S Liu, J Li, M Chen, H Lin, Y Chen, W Chen, J Lin, H Zhou, Q Zheng","doi":"10.12122/j.issn.1673-4254.2024.10.11","DOIUrl":"10.12122/j.issn.1673-4254.2024.10.11","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether modification with IL-21 and CCL19 enhances killing and tumor-infiltrating efficiency of NKP30 CAR-T cells in lung cancer.</p><p><strong>Methods: </strong>The modified IL-21-CCL19 NKP30 CAR-T cells expressing IL-21 and CCL19 fusion gene was constructed based on NKP30 CAR-T cells and stimulated with CD3CD28 antibodies and IL-2. The immunophenotype and migration of the cells in the presence of IL-21 were investigated using flow cytometry and migration experiments. Lactate dehydrogenase (LDH) release and sphere formation assays were used to assess the killing and infiltration capabilities of CAR-T cells, and the secretion levels of IFN-γ, IL-21 and CCL19 were determined with enzyme-linked immunospot assay (ELISPOT) and ELISA. A zebrafish model bearing HCG-27 cell xenograft was established by microinjection of the tumor cells into the yolk sac followed 24 h later by injection of the immune cells at the same site, and the fluorescence signals were captured using a fluorescent microscopy.</p><p><strong>Results: </strong>The NKP30 ligand B7H6, which was almost undetectable in normal tissues and blood cells, was highly expressed (over 90%) in lung cancer cells. Compared with NKP30 CAR-T cells and conventional T cells, IL-21-CCL19 NKP30 CAR-T cells exhibited stronger proliferative and migration capabilities with the formation of central memory T cells. The reduced expressions of CTLA4 and PD1 in the constructed cells resulted in enhanced killing efficiency against lung cancer cells accompanied by significantly increased production of IFN-γ, IL-21 and CCL19. In the zebrafish models, CAR-T cells exhibited stronger cytotoxicity and proliferative abilities than typical T cells, but these differences were not statistically significant between the two CAR-T cells.</p><p><strong>Conclusion: </strong>Modification of NKP30 CAR-T cells with IL-21 and CCL19 facilitates their access into solid tumors for more effective tumor cell killing while producing a large number of memory T cells.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":"44 10","pages":"1926-1936"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[<i>Euphorbia helioscopia</i> inhibits proliferation, invasion, and migration and promotes apoptosis of non-small cell lung cancer cells].","authors":"X Liu, Y Yang, W Liu, Z Zhang, X Zhou, W Xie, L Shen, M Zhang, X Li, J Zang, S Li","doi":"10.12122/j.issn.1673-4254.2024.10.10","DOIUrl":"10.12122/j.issn.1673-4254.2024.10.10","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effect of <i>Euphorbia helioscopia</i> on biological behaviors of non-small cell lung cancer (NSCLC) cells.</p><p><strong>Methods: </strong>NSCLC cell lines PC-9 and A549 treated with different concentrations of <i>Euphorbia helioscopia</i> preparations were examined for changes in proliferation, apoptosis, invasion and migration using CCK-8 assay, colony formation assay, flow cytometry, wound healing assay and Transwell assay. Western blotting was performed to detect the changes in protein expressions of Bax, Bcl-2, E-cadherin, vimentin, MMP2, and MMP9 in the treated cells. PC-9 cells were injected subcutaneously into BALB/C nude mice to establish a nude mouse subcutaneous tumor model. According to the growth of subcutaneous tumors, mice were randomly divided into control group: gavaged daily with saline; <i>Euphorbia helioscopia</i>-treated group: gavaged daily with <i>Euphorbia helioscopia</i> 65 mg/mL, and <i>Euphorbia helioscopia</i> granules were dissolved in saline; cisplatin-treated group: injected intraperitoneally with cisplatin 4 mg/kg every 5 days, 6 mice per group. The subcutaneous tumor volume and mass changes of mice were measured, and the toxic effects of <i>Euphorbia helioscopia</i> on heart, liver, spleen, lung and kidney as well as the therapeutic effects of <i>Euphorbia helioscopia</i> were observed in the mice bearing tumor.</p><p><strong>Results: </strong><i>Euphorbia helioscopia</i> granules concentration-dependently inhibited the proliferation and survival of PC-9 and A549 cells, significantly promoted cell apoptosis, suppressed invasion and migration abilities of the cells, up-regulated the expression levels of E-cadherin and Bax, and down-regulated the expressions of Bcl-2, vimentin, MMP2, and MMP9. In the tumor-bearing mice, treatment with <i>Euphorbia helioscopia</i> significantly inhibited tumor growth without producing obvious toxicity in the vital organs.</p><p><strong>Conclusion: </strong><i>Euphorbia helioscopia</i> can inhibit proliferation, invasion, and migration and induces apoptosis of NSCLC cells <i>in vitro</i>.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":"44 10","pages":"1918-1925"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[<i>Tongsai</i> Granules inhibit autophagy and macrophage-mediated inflammatory response to improve acute exacerbations of chronic obstructive pulmonary disease in rats].","authors":"M Cheng, X Liu, Y Wei, X Xing, L Liu, N Xin, P Zhao","doi":"10.12122/j.issn.1673-4254.2024.10.18","DOIUrl":"10.12122/j.issn.1673-4254.2024.10.18","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the inhibitory effect of <i>Tongsai</i> Granules (TSG) on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in rats and explore the underlying mechanism.</p><p><strong>Methods: </strong>Twenty-four rats were divided into control group, AECOPD model group, TSG treatment group, and moxifloxacin+salbutamol (MXF+STL) treatment group. In the rat models of COPD, AECOPD was induced by nasal instillation of <i>Klebsiella pneumoniae</i> on day 3 of week 9 after modeling, and saline, TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9. After the treatments, lung tissues were collected for examining for pathologies and expressions of inflammatory markers, MMP2, and MMP9. In cultured macrophage MH-S cells with LPS stimulation, the effect of TSG-medicated serum on IL-1β, IL-6, TNF-α, COX-2, and iNOS expressions and phosphorylation levels of p38, p-p62, LC3, FoxO3a, and mTOR were evaluated.</p><p><strong>Results: </strong>TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept, increasing alveolar numbers, and reducing pulmonary expression of IL-1β, IL-6, TNF- α, MMP2 and MMP9. In MH-S cells, TSG significantly suppressed LPS-induced expressions of inflammatory cytokines, COX-2 and iNOS. Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum, and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin, which regulate the MAPK, mTOR, FoxO, and autophagy pathways. In MH-S cells, luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38, FoxO3a, mTOR, p-p62 and LC3.</p><p><strong>Conclusion: </strong>TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38, mTOR, and FoxO3a pathways and inhibiting autophagy.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":"44 10","pages":"1995-2003"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Colorectal fibroblasts promote malignant phenotype of colorectal cancer cells by activating the ERK signaling pathway].","authors":"X Xi, T Deng, B DU","doi":"10.12122/j.issn.1673-4254.2024.10.04","DOIUrl":"10.12122/j.issn.1673-4254.2024.10.04","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effect of human colorectal fibroblast (CCD-18Co)-conditioned medium (CCD18-Co-CM) on biological behaviors of colorectal cancer (CRC) cells and explore the possible molecular mechanisms.</p><p><strong>Methods: </strong>Real-time cellular analysis (RTCA), clone formation assay and wound healing assay were used to analyze the changes in proliferation, clone formation, and migration abilities of CRC cell lines HCT116 and Caco-2 treated with CCD18-Co-CM. Western blotting was used to detect the changes in ATK, ERK and STAT3 signaling pathways in the CRC cells activated by CCD18-Co-CM. The effect of CCD18-Co-CM on spheroidization ability of the cells was assessed with sphere-formation assay, and the changes in expressions of CRC stemness markers were detected using RT-PCR.</p><p><strong>Results: </strong>CCD-18Co-CM significantly promoted proliferation, colony formation, and migration of HCT116 and Caco-2 cells, enhanced sphere-forming ability and expressions of CRC stemness markers, and increased ERK phosphorylation in the cells. Treatment with SCH772984 effectively inhibited CCD-18Co-CM-induced ERK signaling pathway activation, suppressed the malignant phenotype, and lowered the sphere-forming ability and expression of stemness markers of the two CRC cells.</p><p><strong>Conclusion: </strong>Colorectal fibroblasts promote malignant phenotype of CRC cells by activating the ERK signaling pathway.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":"44 10","pages":"1866-1873"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Quercetin suppresses pyroptosis in mouse fibroblasts by inhibiting the NLRP3/caspase-1/GSDMD pathway].","authors":"P Shu, M Yuan, K Yang, W He, L Liu","doi":"10.12122/j.issn.1673-4254.2024.10.05","DOIUrl":"10.12122/j.issn.1673-4254.2024.10.05","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether quercetin inhibits pyroptosis of mouse fibroblast NIH-3T3 cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway.</p><p><strong>Methods: </strong>NIH-3T3 cells were treated with quercetin or MCC950 (a specific inhibitor of NLRP3) before stimulation with lipopolysaccharide (LPS) and ATP to induce cell pyroptosis. The optimal quercetin concentration and duration were screened using the CCK-8assay after testing various concentrations and times. Morphological changes of the treated cells was observed, and the levels of IL-18 and IL-1β in the cell culture supernatant were detected with ELISA; the protein expressions of NLRP3, cleaved caspase-1, and GSDMD-N and the mRNA levels of NLRP3, caspase-1 and GSDMD were detected using Western blotting and qRT-PCR. The changes in cell pyroptosis were examined with TUNEL staining and LDH release assay.</p><p><strong>Results: </strong>The CCK-8 assay indicated that 24-hour treatment with 20 μmol/L quercetin yielded the most favorable results. LPS and ATP stimulation of NIH-3T3 cells induced obvious swelling, cell membrane rupture and leakage of cell contents, significantly increased IL-18 and IL-1β levels, and enhanced protein expressions of NLRP3, cleaved caspase-1 and GSDMD-N and mRNA levels of NLRP3, caspase-1 and GSDMD. LPS and ATP stimulation also caused a significant increment of TUNEL-positive cell counts and LDH release in NIH-3T3 cells. Treatment with quercetin or MCC950 significantly reduced cell pyroptosis induced by LPS and ATP, lowered the concentrations of IL-18 and IL-1β, decreased the expression levels of NLRP3, caspase-1/cleaved caspase-1, GSDMD/GSDMD-N, and reduced the number of TUNEL-positive cells and LDH release.</p><p><strong>Conclusion: </strong>Quercetin suppresses pyroptosis of mouse fibroblasts stimulated with LPS and ATP and reduces secretion of inflammatory cytokines by inhibiting the NLRP3/caspase-1/GSDMD pathway.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":"44 10","pages":"1874-1880"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[LncRNA MAGI2-AS3 enhances cisplatin sensitivity of non-small cell lung cancer cells by regulating the miR-1269a/PTEN/AKT pathway].","authors":"X Fan, Z Qi, Y Deng, Z Yang, L Sun, G Li, J Liang, F Wu, L Yuan","doi":"10.12122/j.issn.1673-4254.2024.10.22","DOIUrl":"10.12122/j.issn.1673-4254.2024.10.22","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines (A549 and H1299) and their resistant counterparts (A549/DDP and H1299/DDP). In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3, the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay, colony formation assay, flow cytometry and Western blotting, and the changes in epithelial-mesenchymal transition (EMT) were assessed with wound healing and Transwell assays. The interaction between MAGI2-AS3, miR-1269a and PTEN was predicted using GEPIA, StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation (RIP) assay. A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.</p><p><strong>Results: </strong>MAGI2-AS3 expression was significantly downregulated in lung cancer tissues (<i>P</i> < 0.05) in association with a poor prognosis (<i>P</i> < 0.05). In the two DDP-resistant lung cancer cell lines, MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells. Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment, and also decreased DDP-induced apoptosis of the cells. In A549/DDP and H1299/DDP cells, MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis. Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3 '-UTR domain of PTEN. The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation, thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.</p><p><strong>Conclusion: </strong>MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":"44 10","pages":"2033-2043"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}