Résumé
Resumo Fundamento O infarto do miocárdio com elevação do segmento ST (IAMCSST) é uma das principais causas de doenças cardiovasculares fatais, que têm sido a principal causa de mortalidade em todo o mundo. O diagnóstico na fase inicial beneficiaria a intervenção clínica e o prognóstico, mas ainda falta a exploração dos biomarcadores do IAMCSST. Objetivos Neste estudo, conduzimos uma análise bioinformática para identificar potenciais biomarcadores cruciais no progresso do IAMCSST. Métodos Obtivemos GSE59867 para pacientes com IAMCSST e doença arterial coronariana estável (DACE). Genes diferencialmente expressos (GDEs) foram selecionados com o limiar de -log2fold change- > 0,5 e p < 0,05. Com base nesses genes, conduzimos análises de enriquecimento para explorar a relevância potencial entre genes e para rastrear genes centrais. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Resultados 133 GDEs entre DACE e IAMCSST foram obtidos. Em seguida, a rede PPI de GDEs foi construída usando String e Cytoscape, e análises posteriores determinaram genes centrais e 6 complexos moleculares. A análise de enriquecimento funcional dos GDEs sugere que as vias relacionadas à inflamação, metabolismo e imunidade desempenham um papel fundamental na progressão de DACE para IAMCSST. Além disso, foram previstos miRNAs relacionados, has-miR-124, has-miR-130a/b e has-miR-301a/b regularam a expressão do maior número de genes. Enquanto isso, a análise dos fatores de transcrição indica que EVI1, AML1, GATA1 e PPARG são os genes mais enriquecidos. Finalmente, as curvas ROC demonstram que MS4A3, KLRC4, KLRD1, AQP9 e CD14 exibem alta sensibilidade e especificidade na previsão de IAMCSST. Conclusões Este estudo revelou que imunidade, metabolismo e inflamação estão envolvidos no desenvolvimento de IAMCSST derivado de DACE, e 6 genes, incluindo MS4A3, KLRC4, KLRD1, AQP9, CD14 e CCR1, poderiam ser empregados como candidatos a biomarcadores para IAMCSST.
Abstract Background ST-segment elevation myocardial infarction (STEMI) is one of the leading causes of fatal cardiovascular diseases, which have been the prime cause of mortality worldwide. Diagnosis in the early phase would benefit clinical intervention and prognosis, but the exploration of the biomarkers of STEMI is still lacking. Objectives In this study, we conducted a bioinformatics analysis to identify potential crucial biomarkers in the progress of STEMI. Methods We obtained GSE59867 for STEMI and stable coronary artery disease (SCAD) patients. Differentially expressed genes (DEGs) were screened with the threshold of -log2fold change- > 0.5 and p <0.05. Based on these genes, we conducted enrichment analysis to explore the potential relevance between genes and to screen hub genes. Subsequently, hub genes were analyzed to detect related miRNAs and DAVID to detect transcription factors for further analysis. Finally, GSE62646 was utilized to assess DEGs specificity, with genes demonstrating AUC results exceeding 75%, indicating their potential as candidate biomarkers. Results 133 DEGs between SCAD and STEMI were obtained. Then, the PPI network of DEGs was constructed using String and Cytoscape, and further analysis determined hub genes and 6 molecular complexes. Functional enrichment analysis of the DEGs suggests that pathways related to inflammation, metabolism, and immunity play a pivotal role in the progression from SCAD to STEMI. Besides, related-miRNAs were predicted, has-miR-124, has-miR-130a/b, and has-miR-301a/b regulated the expression of the largest number of genes. Meanwhile, Transcription factors analysis indicate that EVI1, AML1, GATA1, and PPARG are the most enriched gene. Finally, ROC curves demonstrate that MS4A3, KLRC4, KLRD1, AQP9, and CD14 exhibit both high sensitivity and specificity in predicting STEMI. Conclusions This study revealed that immunity, metabolism, and inflammation are involved in the development of STEMI derived from SCAD, and 6 genes, including MS4A3, KLRC4, KLRD1, AQP9, CD14, and CCR1, could be employed as candidate biomarkers to STEMI.
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Objective @#To systematically evaluate the detection of Legionella pneumophila in central air-conditioning systems of public places in China, so as to provide insights into the management of L. pneumophila contamination.@*Methods@#The publications pertaining to L. pneumophila contamination in central air-conditioning systems of public places in China were searched in international and national databases, including CNKI, Wanfang Data, CBM, PubMed and Web of Science from January 1, 2010 to December 31, 2022. The publication quality was evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology. A meta-analysis was performed using the software Stata version 16.0. The pooled detection of L. pneumophila and its 95%CI were estimated. The publication bias was evaluated using Begg's test, and sensitivity analysis was performed with the leave-one-out evaluation for assessment of the robustness of the outcomes.@*Results@#A total of 742 publications were initially searched, and 29 publications were finally included, all of which were cross-sectional studies. The publications included 10 high-quality and 19 moderate-quality studies covering 6 160 samples, and the pooled detection of L. pneumophila was 17.20% (95%CI: 12.80%-21.90%). Subgroup analysis showed a higher detection rate of L. pneumophila in cooling water (21.80%) than in condensed water (5.50%) (P<0.01). According to the criteria defined in Hygienic Specification of Central Air-conditioning Ventilation System in Public Buildings (2006 version), the detection of L. pneumophila was 23.30%, which was higher than the detection (13.20%) according to the Hygienic Specification of Central Air-conditioning Ventilation System in Public Buildings (WS 394-2012) (P<0.05). The detection of L. pneumophila did not vary in place, region or sample (P>0.05). Begg's test showed no significant publication bias, and sensitivity analysis showed robustness of the results. @*Conclusions@#The detection of L. pneumophila ranges from 12.80% to 21.90% in central air-conditioning systems of public places in China. Health and environmental protection sectors need to improve the monitoring of L. pneumophila contamination in central air-conditioning systems of public places.
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Objective To investigate the effect of mTORC1/2 inhibitor AZD2014 induced autophagy on cell proliferation in HCCLM3 cell lines in vitro. Methods HCCLM3 cells were cultured in the presence or absence of AZD2014 (100 nmol/L) or rapamycin (100 nmol/L) or 3-methyladenine (10 nmol/L). To detect autophagy vacuoles, HCCLM3 cells were divided into the control group, rapamycin group, AZD2014 group, control+3-MA group, rapamycin+3-MA group, and AZD2014+3-MA group, and auto-fluorescent dye monodansylcadaverine (MDC) was used to monitor autophagy vacuoles. To semi-quantify the expression of autophagy-related proteins, HCCLM3 cells were divided into the control group, rapamycin group, and AZD2014 group, and Western blotting analysis was carried out to detect the expression of autophagy-related proteins, LC3B-II and Beclin-1. To evaluate the effect of autophagy induced by AZD2014 on cell proliferation, HCCLM3 cells were divided into the control group, 3-MA group, AZD2014 group, and AZD2014+3-MA group, Cell Counting Kit-8 was used. Results AZD2014-treated HCC cells showed an increase in the number of MDC-labeled vacuoles as well as in their size. AZD2014 treatment increased the levels of LC3B-II and Beclin-1 (P<0.05). CCK-8 assay revealed that suppression of cell proliferation elicited by AZD2014 in HCCLM3 was partly attenuated by 3-MA (autophagy inhibitor). Conclusion Dual mTORC1/2 inhibitor AZD2014 suppressed cell proliferation in the HCCLM3 cell line with increased autophagy, in vitro. This study provides a potential basis for further investigation of AZD2014 as a clinical molecular targeted agent for HCC treatment.
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Recent studies suggested that the prostate cancer may arise from prostate cancer stem cells that share some same characteristics with normal stem cells.The purpose of this study was to detect the differences of Nanog expression between PC3 prostate cancer cell line and its tumor stem cells,and fhe relationship was preliminarily examined between Nanog and prostate cancer and its tumor stem cells.By using magnetic active cell sorting (MACS),we isolated a population of CD44+/CD133+ prostate cancer cells that display stem cell characteristics from PC3 cell line.lmmunohistochemistry revealed positive expressions of CD44,C D 133 and α2β1-integin in the isolated cells.CCK-8 analysis showed that isolated cells had a strong proliferafive ability.The formation of the cell spheres in serum-free medium and holoclones in serum-supplied medium showed that the cells were capable of self-renewing,indicating that the isolated cells were a population of cancer stem-like cells derived from PC3 cell line.Western blotting exhibited that the isolated cells had higher experession of Nanog,an embryonic stem marker,as compared with PC3 cells.Our study showed that Nanog might be helpful in sustaining the self-renewal and fhe undifferentiation of prostate cancer stem cells,and may serve as a marker for prostate cancer stem cells for isolation and identification.