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Objective: Non-alcoholic fatty liver disease (NAFLD) is an aberrant lipid metabolism disease. Hypoxia inducible factor-1 (HIF-1α) is a transcription factor which plays an important part in adapting lower oxygen condition. Here, we aimed to clarify the relationship between HIF-1α and NAFLD., Methods: HepG2 cells was stimulated by oleic acid (OA) and palmitic acid (PA) to establish in vitro model of NAFLD. The expression of lipid metabolism-related genes, the binding of PPARα to HIF-1α promoter, the lipid deposition, and oxidative stress were detected by qRT-PCR, western blot, Chip assay, Oil Red O staining and ELISA assays, respectively., Results: HIF-1α silence promoted lipid accumulation in NAFLD cells, accompanying by the significantly increased contents of TG (triglyceride) and ApoB (apolipoprotein B). In HepG2 cells treated with OA/PA, the expression of lipid metabolism-related genes and proteins, including APOE, A2m, TNFRSF11B, LDLr, and SREBP2, and the intracellular lipid deposition were up-regulated and further aggravated after silencing HIF-1α. In addition, the loss of HIF-1α could remarkably elevate MDA contents while inhibit the activities of beneficial antioxidant enzymes SOD and GSH-Px to activate oxidative stress, and promote the secretion of pro-inflammatory IL-6 and TNF-α to aggravate inflammation in NDFLD cells. PPARα positively bound to HIF-1α promoter. The silence of PPARα aggravated lipid deposition under normal or hypoxic environment in NAFLD cells. In addition, PPAR-α silence could decrease the expression of HIF-1α and ANGPTL4 in NAFLD cell model; moreover, the expression of APOE, A2m and TNFRSF11B and the production of TG and MDA were increased by PPAR-α suppression., Conclusion: HIF-1α plays a crucial role in the regulation of lipid metabolism through activating PPAR-α/ANGPTL4 signaling pathway in NAFLD., (Copyright © 2020. Publicado por Elsevier España, S.L.U.)

Introduction: To assess the risk factors of Gleason sum upgrading between biopsy and radical prostatectomy (RP) and update the nomogram for the prediction of Gleason sum upgrading., Methods: The study cohort consisted of 237 Chinese prostate adenocarcinoma patients who underwent 10-core prostate biopsy and subsequently received RP in Huashan Hospital from February 2011 to May 2015. The main outcome of our study was Gleason sum upgrading between biopsy and RP pathology. Univariate and multivariate logistic regression models were conducted to explore the potential predictors, and ultimately to build the nomograms. The prediction model was further evaluated for its ability to predict significant upgrading in patients with biopsy Gleason sum<8., Results: In the main cohort of all the patients, Gleason sum upgrading was observed in 62 (26.16%) patients. The pre-operative prostate-specific antigen (PSA) level, biopsy Gleason sum, and digital rectal examination were used in building the nomogram, which was validated internally with a bootstrap-corrected concordance index of 0.787. In the sub-cohort of 115 patients with standardized biopsy details, Gleason sum upgrading was observed in 31 (26.96%) patients. The pre-operative PSA level, biopsy Gleason sum, and number of positive cores were used in the nomogram, which was also validated internally with a bootstrap-corrected concordance index of 0.833. These two nomograms both demonstrated satisfactory statistical performance for predicting significant upgrading., Conclusions: Updated nomograms to predict Gleason sum upgrading in Chinese population between biopsy and RP were developed, demonstrating good statistical performance upon internal validation., (Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)