Aging has been attributed to oxidative stress and inflammatory response, in which NF-κB and Nrf2-ARE signaling pathways play significant roles. Senescence accelerated mouse prone 8 (SAMP8) is generally used an animal model for aging studies. Here, we investigated the NF-κB and Nrf2-ARE signaling pathways in SAMP8 brains at different ages and their responses to SS31 peptide treatment. Thirty six SAMP8 mice were separated into aging groups and SS31-treatment groups. The hippocampus from each mouse was dissected for RNA and protein extraction. Cytokines and ROS levels were measured using ELISA and standardised method. Gene expressions of NF-κB, Nrf2 and HO-1 were measured by RT-qPCR. Total protein amount of NF-κB and HO-1, as well as the concentrations of nuclear and cytoplasmic Nrf2 were measured using Western blots. Our data showed that aging could activate both NF-κB and Nrf2-ARE signaling pathways, which could be suppressed and activated by SS31 treatment respectively. Regression analysis revealed that NF-κB gene expression was the most important parameter predicting aging process and SS31 treatment effects in SAMP8. Our findings suggested that SS31 treatment may modulate the inflammatory and oxidative stress status of the aged brains and exert protective effects during brain aging.
Introduction: MI is defined by the presence of myocardial necrosis, which is caused by acute and persistent ischemia and hypoxia of the coronary artery. In recent years, its incidence rate has been on the rise in China. Methods: GSE34198, GSE97320 and GSE141512 datasets were download for DEG analysis. KEGG pathway analysis, GO analysis, GSEA and PPI network construction were performed. Later, target genes of candidate miRNAs were predicted. Next, echocardiography was conducted to detect the effects of miR-29 on left ventricular structure and cardiac function in vivo , and H&E staining was adopted to study the effects of miR-29 on angiogenesis and fibrosis in vivo . Furthermore, Western blotting was employed to investigate the effects of miR-29 inhibition on the expressions of proteins related to the PI3K\mTOR\ HIF-1α\VEGF pathway. Results: There were 162 DEGs involved in MI. GO analysis revealed that inflammatory responses, negative regulation of apoptosis and innate immune response were the main enriched biological processes. KEGG analysis manifested that DEGs were mainly enriched in the PI3K/Akt signaling pathway, and GSEA demonstrated that they were mainly enriched in the PI3K/Akt/mTOR, HIF and VEGF pathways. Moreover, target gene prediction showed that miR-29 was lowly expressed in MI. According to Masson's trichrome staining, miR-29 inhibition promoted angiogenesis, reduced fibrosis, and increased the protein expressions of p-PI3K, p-mTOR, HIF-1α, and VEGF. Conclusions: MiR-29 may play an important role in the growth and development of MI. After inhibition of miR-29, the PI3K/mTOR/HIF-1α/VEGF pathway is activated to alleviate MI.
Background Few studies have reported on the use of intravoxel incoherent motion (IVIM) for renal tumors. Purpose To investigate the value of IVIM for distinguishing renal tumors. Material and Methods Thirty-one patients with clear cell renal cell carcinomas (CCRCCs), 13 patients with renal angiomyolipomas with minimal fat (RAMFs), eight patients with chromophobe renal cell carcinomas (ChRCCs), and ten patients with papillary renal cell carcinomas (PRCCs) were examined. The tissue diffusivity (D), pseudodiffusivity (D*), and perfusion fraction (f) were calculated. Results The D and f values were highest for CCRCCs, lowest for PRCCs, and intermediate for ChRCCs and RAMFs ( P < 0.05). The D values of CCRCCs differed significantly from those of ChRCCs and PRCCs ( P < 0.05). The D* values were highest for RAMFs, lowest for ChRCCs, and intermediate for CCRCCs and PRCCs ( P < 0.05). Statistically significant differences were observed between the D* values of CCRCCs and RAMFs ( P < 0.05). The D* values of the CCRCCs differed significantly from the D* values of the ChRCCs ( P < 0.05). Using the D and f values of 1.10 and 0.41, respectively, as the threshold values for differentiating CCRCCs from RAMFs, ChRCCs, and PRCCs, the best results had sensitivities of 81.0% and 66.8% and specificities of 85.7% and 81.0%, respectively. Using the D* value of 0.038 as the threshold value for differentiating RAMFs from CCRCCs, ChRCCs, and PRCCs, the best result obtained had a sensitivity of 90.5% and specificity of 76.2%. Conclusion IVIM may provide information for differentiating renal tumor types.
Fundamento: Os resultados de estudos anteriores sobre a relação entre ácido úrico sérico (AUS) e o risco de doença cardiovascular (DCV) até agora são inconsistentes devido aos fatores de confusão causados por outros fatores de risco cardiovascular conhecidos. Objetivos: Este estudo tem o objetivo de avaliar a relação entre o AUS e as DCV incidentes em chineses de meiaidade e idosos, que foram estratificados de acordo com o índice de massa corporal (IMC). Métodos: Recrutamos 5.721 participantes com idades entre 40 e 75 anos que não tinham diagnóstico de DCV na linha de base, e que foram monitorados de 2008 a 2017. Os participantes foram categorizados em quintis de AUS. A regressão de Cox e a análise de sobrevivência de Kaplan-Meier foram utilizadas para comparar a incidência de DCV entre os grupos de AUS. As correlações entre AUS e a incidência de DCV em grupos com IMC e circunferência de cintura (CC) variados também foram analisadas. Um P valor <0,05 foi considerado estatisticamente significativo. Resultados: Durante um período médio de monitoramento de 7,6 anos, a incidência de DCV aumentou com o AUS (teste de Log-rank p<0,001). Em comparação com o primeiro quintil, as razões de risco padronizadas (intervalos de confiança de 95%) para p desenvolvimento de DCV foram 1,08 (0,78-1,65), 1,17 (0,88-1,77), 1,47 (1,12-2,21), e 1,68 (1,28-2,44) para o segundo, terceiro, quarto e quinto quintis, respectivamente. Essa relação ficou mais clara em participantes com IMC e CC normais. A razão de risco ajustada para cada aumento de 100 μmol/L de AUS foi de 1,13 (intervalo de confiança de 95%: 1,02-1,39) para eventos de DCV. Conclusões: O AUS alto é um fator de risco de DCV independente em pessoas de meia-idade e idosas do norte da China. Esse efeito é mantido mesmo depois da estratificação de acordo com medidas de magreza/obesidade. Palavras-chave: Hiperuricemia; Ácido Úrico; Doenças Cardiovasculares/incidência; Fatores de Risco; Peso Corporal.
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