Background and purpose: Perivascular adipose tissue (PVAT) attenuates vascular contraction, but the mechanisms remain largely unknown. The possible involvement of endothelium (E) and hydrogen peroxide (H 2 O 2 ) was investigated. Experimental approach: Aortic rings from Wistar rats were prepared with both PVAT and E intact (PVAT þ E þ ), with either PVAT or E removed (PVAT-E þ , or PVAT þ E-), or with both removed (PVAT-E-) for functional studies. Nitric oxide (NO) production was measured. Key results: Contraction to phenylephrine and 5-HT respectively was highest in PVAT-E-, lowest in PVAT þ E þ , and intermediate in PVAT þ E-or PVAT-E þ . In bioassay experiments, transferring bathing solution incubated with a PVAT þ ring (donor) to a PVAT-ring (recipient) induced relaxation in the recipient. This relaxation was abolished by E removal, NO synthase inhibition, scavenging of NO, high extracellular K þ , or blockade of calcium-dependent K þ channels (K Ca ). The solution stimulated NO production in isolated endothelial cells and in PVAT-E þ rings. In E-rings, the contraction to phenylephrine of PVAT þ rings but not PVAT-rings was enhanced by catalase or soluble guanylyl cyclase (sGC) inhibitor, but reduced by superoxide dismutase and tiron. In PVAT-E-rings, H 2 O 2 attenuated phenylephrine-induced contraction. This effect was counteracted by sGC inhibition. NO donor and H 2 O 2 exhibited additive inhibition of the contraction to phenylephrine in PVAT-E-rings. Conclusion: PVAT exerts its anti-contractile effects through two distinct mechanisms: (1) by releasing a transferable relaxing factor which induces endothelium-dependent relaxation through NO release and subsequent K Ca channel activation, and (2) by an endothelium-independent mechanism involving H 2 O 2 and subsequent activation of sGC.

BackgroundNovel diagnostic predictors and drug targets are needed for LUAD (lung adenocarcinoma). We aimed to build a specific SVM (support vector machine) classifier for diagnosis of LUAD and identify molecular markers with prognostic value for LUAD.MethodsThe expression differences of miRNAs, lncRNAs and mRNAs between LUAD and normal samples were compared using data from TCGA (The Cancer Genome Atlas) database. A LUAD related miRNA-lncRNA-mRNA network was constructed, based on which feature genes were selected for the construction of LUAD specific SVM classifier. The robustness and transferability of SVM classifier were validated using gene expression profile datasets GSE43458 and GSE10072. Prognostic markers were identified from the network. A set of LUAD-related differentially expressed miRNAs, lncRNAs and miRNAs were identified and a LUAD related miRNA-lncRNA-mRNA network was obtained. The LUAD specific SVM classifier constructed on the basis of the network was robust and efficient for classification of samples from TCGA dataset and two independent validation datasets.ResultsEight RNAs with prognostic value were identified, including hsa-miR-96, hsa-miR-204, PGM5P2 (phosphoglucomutase 5 pseudogene 2), SFTA1P (surfactant associated 1), RGS20 (regulator of G protein signaling 20), RGS9BP (RGS9-binding protein), FGB (fibrinogen beta chain) and INA (alpha-internexin). Among them, RGS20 and INA were regulated by hsa-miR-96. RGS20 was also regulated by hsa-miR-204, which was a potential target of SFTA1P.ConclusionThe LUAD specific SVM classifier may serve as a novel diagnostic predictor. hsa-miR-96, hsa-miR-204, PGM5P2, SFTA1P, RGS20, RGS9BP, FGB and INA may serve as prognostic markers in clinical practice.

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Nonalcoholic fatty liver disease (NAFLD) is reported to affect 20-30% of adults and is accompanied by various metabolic comorbidities, where the economic and clinical burden of NAFLD is attributed to the progression of liver disease as well as the presence of extrahepatic diseases. Chronic kidney disease (CKD), which has a high incidence rate, high morbidity and mortality rates, and high medical costs, has been linked to NAFLD. CKD is associated with some metabolism-related risk factors that overlap with metabolic comorbidities of NAFLD. Therefore, to investigate the potential factors that influence CKD occurrence, the association between NAFLD and CKD should be clarified. Some studies have confirmed that NAFLD influences the occurrence and severity of CKD, whereas some studies have indicated that there is no correlation. In this review, the results of a few studies have been discussed, the potential risk factors for CKD in NAFLD are explored, and the respective biological mechanisms are elaborated to help clinicians identify CKD in patients much earlier than it is diagnosed now and thus help in reducing the incidence of liver and kidney transplants.

We conclude that in rat lung, acidosis causes an increase in pulmonary vascular resistance at normal and elevated tone conditions. Furthermore, the response is limited primarily to the small arteries, and is not mediated by nitric oxide. Alkalosis tends to cause the opposite effects. The effects of acidosis and alkalosis were abolished when vascular tone was elevated with a low dose of KCl, suggesting that vascular response to pH may involve changes in membrane potential.