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BACKGROUND: To investigate the involvement of LINC02605 in the progression of paediatric Mycoplasma pneumoniae pneumonia (MPP). METHODS: One hundred and thirty-two children with MPP (90 simple MPP and 42 MPP + diarrhoea) were enrolled, and their plasma was collected for detection of LINC026505 expression. CCK-8 kit and commercial apoptosis kit were introduced to determine cell growth and apoptosis. In silico prediction analyses were conducted to predict the downstream miRNA for LINC02605, following verification by dual luciferase reporter assay. The lipid-associated membrane proteins (LAMPs) were used to treat A549 and Coca-2 cells. RESULTS: LIN02605 was highly expressed in the MPP, especially in MPP complicated with diarrhoea. LINC02605 downregulation in A549 cells correlated with significant suppression of cell apoptosis rate and growth inhibition rate in vitro. Introduction of miR-539-5p inhibited luciferase activity in a reporter system containing the wild-type LINC02605 and CXCL1. After stimulation with LAMPs, overexpression of LINC02605 and CXCL1 and inhibition of miR-539-5p were found. miR-539-5p and CXCL1 knockdown resulted in a rescue effect on the LINC02605-inhibited cell apoptosis. LAMPs induced IL-1ß in intestinal epithelial cells and IL-1ß induced LINC02605 expression in A549 cells. CONCLUSIONS: LINC02605 was upregulated in MPP and miR-539-5p was a target for LINC02605. LINC02605 may be involved in the crosstalk between the gastrointestinal tract and the respiratory tract.
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Apoptosis , Quimiocina CXCL1 , Diarrea , MicroARNs , Neumonía por Mycoplasma , ARN Largo no Codificante , Humanos , MicroARNs/metabolismo , MicroARNs/genética , Neumonía por Mycoplasma/genética , Apoptosis/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Masculino , Diarrea/genética , Femenino , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/genética , Células A549 , Preescolar , Niño , Regulación hacia AbajoRESUMEN
Epigenetic dysregulation emerges as a critical hallmark and driving force of aging. Although still an evolving field with much to explore, it has rapidly gained significance by providing valuable insights into the mechanisms of aging and potential therapeutic opportunities for age-related diseases. Recent years have witnessed remarkable strides in our understanding of the epigenetic landscape of aging, encompassing pivotal elements, such as DNA methylation, histone modifications, RNA modifications, and noncoding (nc) RNAs. Here, we review the latest discoveries that shed light on new epigenetic mechanisms and critical targets for predicting and intervening in aging and related disorders. Furthermore, we explore burgeoning interventions and exemplary clinical trials explicitly designed to foster healthy aging, while contemplating the potential ramifications of epigenetic influences.
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Metilación de ADN , Epigénesis Genética , Humanos , Envejecimiento/genética , Procesamiento Proteico-PostraduccionalRESUMEN
The summer Eurasian westerly jet is reported to become weaker and wavier, thus promoting the frequent weather extremes. However, the primary driver of the changing jet stream remains in debate, mainly due to the regionality and seasonality of the Eurasian jet. Here we report a sharp increase, by approximately 140%, in the interannual variability of the summertime East Asian jet (EAJ) since the end of twentieth century. Such interdecadal change induces considerable changes in the large-scale circulation pattern across Eurasia, and consequently weather and climate extremes including heatwaves, droughts, and Asian monsoonal rainfall regime shifts. The trigger mainly emerges from preceding February North Atlantic seesaw called Scandinavian pattern (contributing to 81.1 ± 2.9% of the enhanced EAJ variability), which harnesses the "cross-seasonal-coupled oceanic-atmospheric bridge" to exert a delayed impact on EAJ and thus aids relevant predictions five months in advance. However, projections from state-of-the-art models with prescribed anthropogenic forcing exhibit no similar circulation changes. This sheds light on that, at the interannual timescale, a substantial portion of recently increasing variability in the East Asian sector of the Eurasian westerly jet arises from unforced natural variability.
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Sirtuins are pro-longevity genes with chromatin modulation potential, but how these properties are connected is not well understood. Here, we generated a panel of isogeneic human stem cell lines with SIRT1-SIRT7 knockouts and found that any sirtuin deficiency leads to accelerated cellular senescence. Through large-scale epigenomic analyses, we show how sirtuin deficiency alters genome organization and that genomic regions sensitive to sirtuin deficiency are preferentially enriched in active enhancers, thereby promoting interactions within topologically associated domains and the formation of de novo enhancer-promoter loops. In all sirtuin-deficient human stem cell lines, we found that chromatin contacts are rewired to promote aberrant activation of the placenta-specific gene PAPPA, which controls the pro-senescence effects associated with sirtuin deficiency and serves as a potential aging biomarker. Based on our survey of the 3D chromatin architecture, we established connections between sirtuins and potential target genes, thereby informing the development of strategies for aging interventions.
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Senescencia Celular , Cromatina , Placenta , Sirtuinas , Humanos , Senescencia Celular/genética , Placenta/metabolismo , Sirtuinas/metabolismo , Sirtuinas/genética , Femenino , Embarazo , Cromatina/metabolismo , Cromatina/genética , Sirtuina 1/metabolismo , Sirtuina 1/genética , Regiones Promotoras Genéticas/genética , Línea CelularRESUMEN
Objective: Considering that there are no effective biomarkers for the screening of cardia gastric cancer (CGC), we developed a noninvasive diagnostic approach, employing data-independent acquisition (DIA) proteomics to identify candidate protein markers. Methods: Plasma samples were obtained from 40 subjects, 10 each for CGC, cardia high-grade dysplasia (CHGD), cardia low-grade dysplasia (CLGD), and healthy controls. Proteomic profiles were obtained through liquid chromatography-mass spectrometry (LC-MS/MS-based DIA proteomics. Candidate plasma proteins were identified by weighted gene co-expression network analysis (WGCNA) combined with machine learning and further validated by the Human Protein Atlas (HPA) database. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the biomarker panel. Results: There was a clear distinction in proteomic features among CGC, CHGD, CLGD, and the healthy controls. According to the WGCNA, we found 42 positively associated and 164 inversely associated proteins related to CGC progression and demonstrated several canonical cancer-associated pathways. Combined with the results from random forests, LASSO regression, and immunohistochemical results from the HPA database, we identified three candidate proteins (GSTP1, CSRP1, and LY6G6F) that could together distinguish CLGD (AUC = 0.91), CHGD (AUC = 0.99) and CGC (AUC = 0.98) from healthy controls with excellent accuracy. Conclusions: The panel of protein biomarkers showed promising diagnostic potential for CGC and precancerous lesions. Further validation and a larger-scale study are warranted to assess its potential clinical applications, suggesting a potential avenue for CGC prevention in the future.