Mathew OP, Ranganna K, Milton SG
The Evolving Role of PD-L1 Testing in Patients With Metastatic Urothelial Carcinoma
Of these, Siamese Crocodile oil has been the most extensively studied, likely due to easier sample availability and broader investigation of its pharmacological mechanisms
Introduction Sepsis has an annual prevalence of 49 million and a mortality of 11 million, making it one of the most unmet medical needs of today ( Recent evidence highlights a significant role of metabolic dysregulation in sepsis pathogenesis, which is characterized by tachycardia, fever, tachypnoea, immune activation, complement and coagulation activation, and the acute phase response (APR) ( We recently published that hepatocyte nuclear factor 4 (HNF4) is a major protective factor and one of the top upstream regulators in acute murine septic peritonitis, as well as in pigs and in mice with a humanized liver ( Ppara expression by binding to the DR1 element within its gene promoter but also facilitates GR binding to its liver-specific elements by promoting chromatin opening ( An interesting nuclear receptor, whose expression is mainly regulated by HNF4 and has barely been investigated in sepsis, is the constitutive androstane receptor (CAR), encoded by the Nr1i3 gene ( In contrast to other nuclear receptors, which comprise an N-terminal A/B domain with activation function-1 (AF1), a DNA-binding domain, a hinge region, a ligand-binding domain with activation function-2 (AF2) and a C-terminal F domain, CAR lacks an A/B domain with AF1 and can exert ligand-independent activity by mimicking an active AF2 conformation ( in vivo or in primary hepatocytes ( It has already been shown that hepatic Nr1i3 mRNA is downregulated starting 4h after LPS injection in mice, associated with reduced expression of CAR target gene Cyp2b10 ( We use the cecal ligation and puncture (CLP) mouse model, which is considered the gold standard for polymicrobial sepsis, to study hepatic CAR function during sepsis
