Angiopoietin-like protein 4 (ANGPTL4) plays a crucial role in processes such as angiogenesis, inflammation, and metabolism. Despite numerous studies suggesting its involvement in cancer, a definitive Show more
Angiopoietin-like protein 4 (ANGPTL4) plays a crucial role in processes such as angiogenesis, inflammation, and metabolism. Despite numerous studies suggesting its involvement in cancer, a definitive role remains unclear. We introduce the first comprehensive meta-analysis and pan-cancer bioinformatics study on ANGPTL4, aiming to unravel its implications across various cancer types. Moderate-to high-quality observational studies were retrieved from PubMed, Scopus, and Embase. A meta-analysis was conducted using the R package "meta." Survival analysis was performed using GEPIA2 and TIMER2.0. Immune infiltration, mutational burden, and drug resistance analyses was done via GSCAlite. Co-expression and gene set enrichment analyses (GSEA) were carried out using cBioportal and enrichr, respectively. Increased ANGPTL4 expression was linked to worse tumor grade (OR = 1.51, P = 0.023), stage (OR = 2.42, P < 0.001), lymph node metastasis (OR = 1.76, P = 0.012), vascular invasion (OR = 2.16, P = 0.01), and lymphatic invasion (OR = 2.20, P < 0.001). Furthermore, ANGPTL4 expression was linked to worse OS (HR = 1.40, 95% CI: 1.29,1.50, P = 0.0001). Single gene level analysis revealed that ANGPTL4 upregulated epithelial-to-mesenchymal transition (EMT) in 23 different cancers. Immune infiltration varied between cancer types, but increased infiltration of cancer-associated fibroblasts was observed in most cancers. Mutation analysis revealed increased alterations in TP53 and CDKN2A in cohorts with ANGPTL4 alterations. GSEA of co-expressed genes revealed involvement in hypoxia, EMT, VEGF-A complex, TGF-B pathways, and extracellular matrix organization. ANGPTL4 plays a significant role in tumor progression via its positive regulation of EMT and angiogenesis, while possibly harboring a TGF-B dependent role in systemic metastasis. Therefore, ANGPTL4 is a suitable target for future drug development. Show less
Equine metabolic syndrome (EMS) is a steadily growing endocrine disorder representing a real challenge in veterinary practice. As a multifactorial condition, EMS is characterized by three main metabol Show more
Equine metabolic syndrome (EMS) is a steadily growing endocrine disorder representing a real challenge in veterinary practice. As a multifactorial condition, EMS is characterized by three main metabolic abnormalities including insulin resistance, increased adiposity or obesity and hoof laminitis. Adipose tissue dysfunction is recognized as a core pathophysiological determinant of EMS, as it strongly participates to lipotoxicity and systemic metaflammation, both of which have been closely linked to the development of generalized insulin resistance. Besides, sex hormone binding globulin (SHBG) is an important sex steroids transporters that has been recently proposed as an important metabolic mediator. Therefore, the aim of this study was to verify whether SHBG treatment may ameliorate subcutaneous adipose tissue metabolic failure under EMS condition in terms of lipidome homeostasis, lipid metabolism programs, insulin signalling and local inflammation. Subcutaneous adipose tissue (SAT) biopsies were collected post-mortem from healthy ( Show less