The rising global prevalence of obesity and its impact on health and economy make finding available safe treatment an urgent need. Ketogenic diet represents trendy dietary intervention, while underlyi Show more
The rising global prevalence of obesity and its impact on health and economy make finding available safe treatment an urgent need. Ketogenic diet represents trendy dietary intervention, while underlying molecular mechanisms remains unclear. Twenty-four male Sprague-Dawley rats were randomized into three groups: Control (maintained on conventional chow diet for 24 weeks), HFD (fed High-fat diet (HFD) for 24 weeks), keto (fed HFD for 12 weeks, then ketogenic diet for additional 12 weeks). Effect of ketogenic diet on serum metabolomics using Ultra Performance Liquid Chromatography coupled with Liquid Chromatography on both positive and negative modes; hepatic tissue using histopathological examination, enzyme-linked immunosorbent assay (ELISA), Real time Polymerase Chain Reaction, proteome array detection; intestinal tissue using histopathological examination, ELISA and adipose tissue using histopathological examination were evaluated. The ketogenic diet reduced rat weight, food intake, epididymal fat mass, and blood glucose level compared to HFD group. Furthermore, it resulted in a decrease in serum methionine, linolenic acid, Lyso Phosphatidylcholine (PC) (15.0:0.0), Lyso PC (18.0:0.0) with hepatic repression of fibroblast growth factor 21 (FGF21), and type II cell surface protein/ Dipeptidyl peptidase 4, Intercellular Adhesion Molecule 1, Insulin growth factor-1, Lipocalin-2, Serpin E1, tissue inhibitor of matrix metalloproteinase-1, receptor for advanced glycation end products and induction of Farnesoid X receptor (FXR), hepatocyte growth factor (HGF) which leads to hepatic antioxidant effects and histopathological amelioration. In addition, the ketogenic diet caused intestinal induction of melanocortin-4 receptors/ glucagon-like peptide 1 pathway, which causes intestinal antioxidant effects and histopathological amelioration. Thus, ketogenic diet stated potential anti-obesity effect that mitigates HFD-induced organ damage through the modulation of key metabolic and signaling networks. Show less
The current study evaluated the impact of lysophospholipid emulsifiers' (LPLs) dietary incorporation on ameliorating the negative impacts of oxidative stress in broilers. A total of 270 2-week-old mal Show more
The current study evaluated the impact of lysophospholipid emulsifiers' (LPLs) dietary incorporation on ameliorating the negative impacts of oxidative stress in broilers. A total of 270 2-week-old male Avian 48 chicks were randomly divided into six experimental groups. The first group fed a basal diet (BD) only, while the second group (+DEX) received BD containing 2 mg/kg dexamethasone. The third and fourth groups consisted of birds fed a BD containing 0.5 and 1 g of LPLSs/kg, respectively. The fifth and sixth groups, received BD containing 1 mg/kg dexamethasone and were supplemented with 0.5 and 1 g of LPLs, respectively. Separate supplementation of LPLs significantly improved the broilers' growth as confirmed by increasing final weight, body gain, and FI with improved feed conversion ratio (FCR) ( Dietary supplementation of LPLs at 0.5g level could effectively mitigate the adverse effects of oxidative stress in broilers, improving the growth performance, immune response, intestinal health, and meat quality of broiler chickens under normal and stressful conditions. Show less
Colorectal cancer is a major health concern as it ranks third in incidence and second major cause of cancer-related deaths worldwide. A leading cause of treatment failure has been attributed to cancer Show more
Colorectal cancer is a major health concern as it ranks third in incidence and second major cause of cancer-related deaths worldwide. A leading cause of treatment failure has been attributed to cancer stem cells that can invariably resist existing chemotherapeutic regimens. Notch signaling pathway has been involved in the maintenance of stem cells besides being crucial in cell fate decision and embryonic development. This pathway has also been implicated in several human malignancies including colorectal cancer. We investigated mRNA expression of four Notch receptors (Notch1-4), five ligands (Jag1, Jag2, Dll1, Dll3, and Dll4), and four target genes (Hes1, Hes5, Hey1, and Hey2) using highly specific TaqMan gene expression assays in colorectal adenomas and cancers. Upregulated expression of Notch receptors ranged between 29 and 73% in colorectal cancers and between 11 and 56% in adenomas. Expression of Notch3 and Notch4 receptors was significantly higher in colorectal cancers compared to normal and adenoma tissues. The Jagged and Delta-like ligands were overexpressed between 25 and 52% in colorectal cancers, while in adenomas, it ranged between 0 and 33%. Combining the data for upregulation of receptors and ligands suggests that 86% colorectal cancers and 56% adenomas exhibited overexpression of Notch pathway genes in our cohort. Notch target genes were upregulated between 24 and 33% in colorectal cancers and between 11 and 22% in adenomas. Collating upregulation of Notch receptors and ligands with the target genes showed concordance in 58% colorectal tumors. Additionally, we evaluated expression of Notch receptors, ligands, and target genes with prognosis using the TCGA mRNA expression dataset. Patients overexpressing Notch3, Notch4, and Hey1 had significantly poorer overall survival relative to those having lower levels of these genes. Taken together, Notch signaling components are aberrantly overexpressed in colorectal tumors, and development of therapeutics targeting the Notch pathway may prove to be beneficial in the management of colorectal cancers. Show less