👤 Rober Abdo

Dyslipidemia is a major risk factor for the development of NAFLD, atherosclerosis and cardiovascular diseases. Rosuvastatin (ROS) is a lipid-lowering drug that protects against the development of NAFLD and atherosclerosis. However, the mechanism of this protection remains obscure. Therefore, the current study aims to explore the mechanism by which ROS-loaded glycerosomes (ROS-GLY) protect against NAFLD and atherosclerosis. Hence, for this purpose, hepatic lncRNA-H19/miR-130a/PPAR-γ and aortic PPAR-γ/LXRα/ABCA1 signaling pathways were assessed. In addition, these target pathways were predicted using molecular docking analysis. Thirty-five male Sprague Dawley rats were separated into control, dyslipidemic (poloxamer 407 (P 407)), P 407+ROS-GLY, P 407+NC, and P 407+ROS-GLY+NC groups. ROS-GLY improved lipid profile, hepatic MDA, SOD, catalase and total antioxidant capacity (TAC) in compared to P 407 group. In the dyslipidemic group, ROS-GLY downregulated hepatic lncRNA-H19 expression which leads to an upregulate of the miR-130a level and subsequent reduction of the PPAR-γ level. Consequently, the hepatic expression level of lipogenic genes such as, ACC-1, FASN and SCD-1 was significantly downregulated in the ROS-GLY group than the dyslipidemic one. Aortic PPAR-γ/LXRα/ABCA1 signaling pathway was significantly upregulated in the ROS-GLY group compared to the dyslipidemic group. Furthermore, ROS-GLY modulated IL-6 and IL-10 immunoprotein expression in hepatic and aortic tissues. Interestingly, ROS showed a substantial binding affinity with PPAR-γ, LXR-α, and FASN, according to a molecular docking study. The current study indicated that ROS-GLY protected against the progression of NAFLD and atherosclerosis in dyslipidemic rats via modulation of lipid profile, oxidative stress, pro-/anti-inflammatory cytokines, hepatic lncRNA-H19/miR-130a/PPAR-γ, and aortic PPAR-γ/LXRα/ABCA1 signaling pathways. Show less

Brain metastasis occurs in up to 40% of patients with non-small cell lung cancer (NSCLC). Considerable genomic heterogeneity exists between the primary lung tumor and respective brain metastasis; however, the identity of the genes capable of driving brain metastasis is incompletely understood. Here, we carried out an in vivo genome-wide CRISPR activation screen to identify molecular drivers of brain metastasis from an orthotopic xenograft model derived from a patient with NSCLC. We found that activating expression of the Alzheimer's disease-associated beta-secretase 1 (BACE1) led to a substantial increase in brain metastases. Furthermore, genetic and pharmacological inhibition of BACE1 blocked NSCLC brain metastasis. Mechanistically, we identified that BACE1 acts through epidermal growth factor receptor to drive this metastatic phenotype. Together, our data highlight the power of in vivo CRISPR activation screening to unveil molecular drivers and potential therapeutic targets of NSCLC brain metastasis. Show less

A major factor in the propagation of an infectious disease is host genetics. In this study, 180 dairy cows (90 of each breed: Holstein and Montbéliarde) were used. Each breed's tested dairy cows were divided into two groups of comparable size (45 cows each), mastitis-free and mastitis-affected groups. Each cow's jugular vein was punctured to obtain blood samples for DNA and RNA extraction. In the examined Holstein and Montbéliarde dairy cows, single nucleotide polymorphisms (SNPs) related with mastitis resistance/susceptibility were found in the Show less