Comparative Tandem Mass Tag-Based Quantitative Proteomics Analysis of Liver Against Chronic Hypoxia: Molecular Insights Into Metabolism in Rats.

Xu, Jin, Shenhan Gao, Mingyuan Xin, Wenjie Chen, Kaikun Wang, Wenjing Liu, Xinzong Yan, Sinan Peng, and Yanming Ren. Comparative tandem mass tag-based quantitative proteomics analysis of liver against chronic hypoxia: molecular insights into metabolism in rats. High Alt Med Biol. 24:49-58, 2023. Objective: Using a metabolomic approach, we uncovered key regulators in metabolism from tandem mass tag (TMT)-based proteomic analysis in animals chronically exposed to hypoxia. Methods: Sixteen Sprague-Dawley rats (n = 8 per group) were exposed to chronic normoxia or hypoxia (380 mmHg corresponding to a simulated altitude of 5,500 m) for 35 consecutive days. Hypoxia-induced alterations in metabolic pathways were analyzed from TMT-based proteomic analysis, complemented by western blot validation of key regulators. Results: We profiled biochemical parameters and serum lipids, found that serum alanine aminotransferase and blood glucose were not significantly changed due to chronic hypoxia. However, serum triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL) were significantly affected by chronic hypoxia. And the levels of LDL nearly doubled (p < 0.05) after hypoxia exposure for 35 days. Through Kyoto Encyclopedia of Genes and Genomes classification, we found several metabolic pathways were enriched, including lipid metabolism, cofactor and vitamin metabolism, amino acids metabolism, carbohydrate metabolism, and energy metabolism. To explore the potential functions of proteins in metabolic pathways that become a coordinated shift under chronic hypoxic conditions, Gene Ontology and pathway analysis were carried out on differentially expressed proteins. As the co-expression network shown in Figure, we identified the most significant differentially expressed proteins after chronic hypoxic changes in the livers of rats. Furthermore, we validated the gene expression profiles at the protein level using western blot. Results of western blot were in accordance with our quantitative polymerase chain reaction findings. The levels of fatty acid synthase and aquaporin 1 were significantly downregulated after 35 days and the levels of ATP citrate lyase, 2'-5'-oligoadenylate synthetase 1A, aldehyde dehydrogenase 2, and Ras-related protein Rap-1A were significantly upregulated after 35 days. Conclusions: Although this study cannot completely account for all the molecular mechanisms in rats, we provide a good analysis of protein expression and profiling of rats under chronic hypoxia conditions.

Effects of ai-assisted colonoscopy on adenoma miss rate/adenoma detection rate: A protocol for systematic review and meta-analysis.

BACKGROUND: Colonoscopy can detect colorectal adenomas and reduce the incidence of colorectal cancer, but there are still many missing diagnoses. Artificial intelligence-assisted colonoscopy (AIAC) can effectively reduce the rate of missed diagnosis and improve the detection rate of adenoma, but its clinical application is still unclear. This systematic review and meta-analysis assessed the adenoma missed detection rate (AMR) and the adenoma detection rate (ADR) by artificial colonoscopy. METHODS: Conduct a comprehensive literature search using the PubMed, Medline database, Embase, and the Cochrane Library. This meta-analysis followed the direction of the preferred reporting items for systematic reviews and meta-analyses, the preferred reporting item for systematic review and meta-analysis. The random effect model was used for meta-analysis. RESULTS: A total of 12 articles were eventually included in the study. Computer aided detection (CADe) significantly decreased AMR compared with the control group (137/1039, 13.2% vs 304/1054, 28.8%; OR,0.39; 95% CI, 0.26-0.59; P < .05). Similarly, there was statistically significant difference in ADR between the CADe group and control group, respectively (1835/5041, 36.4% vs 1309/4553, 28.7%; OR, 1.54; 95% CI, 1.39-1.71; P < .05). The advanced adenomas missed rate and detection rate in CADe group was not statistically significant when compared with the control group. CONCLUSIONS: AIAC can effectively reduce AMR and improve ADR, especially small adenomas. Therefore, this method is worthy of clinical application. However, due to the limitations of the number and quality of the included studies, more in-depth studies are needed in the field of AIAC in the future.

Profiles of transcriptome and metabolic pathways after hypobaric hypoxia exposure.

BACKGROUND: Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. However, a detailed understanding of the metabolic genes and pathways involved remains elusive. METHODS: In vivo experiments were designed to analyze body weight and lipid metabolism changes of rats under hypoxia. After this, we combined microarray analysis and gene overexpression experiments to validate the core mechanisms involved in the response to hypoxia. RESULTS: The hypobaric hypoxia treated rats exhibited significantly increased serum triglycerides (TG) (p < 0.05), despite no significant changes in serum alanine aminotransferase (ALT) and blood glucose (BG) were observed. In addition, serum high-density lipoprotein cholesterol (HDL-C) greatly increased after 3 days and then returned to normal level at 30 days. Interestingly, serum low-density lipoprotein cholesterol (LDL-C) showed an opposite pattern. Transcriptome analysis, qRT-PCR, ICC revealed that the genes PPARA, ANGPTL4, CPT-I, ACC and LPL play a crucial role in response to hypobaric hypoxia. IPA pathway analysis further confirmed that PPARA-mediated regulation of ANGPTL4 participated in TG clearance and lipoprotein metabolism. Finally, the PPARA-ANGPTL4 pathway was validated in rats and HL 7702 cells treated with Fenofibrate, a PPARA specific agonist. CONCLUSIONS: Our study showed this pathway plays an important role on lipid metabolism caused by hypobaric hypoxia and the potential target genes associated with oxygen-dependent lipid homeostasis in the liver.