doi: 10.1080/08820130801967809
The Evolving Role of PD-L1 Testing in Patients With Metastatic Urothelial Carcinoma
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
& Mingarro, I
When the detoxification system is compromised, it leads to an accumulation of toxins that trigger an autoimmune response, potentially contributing to the onset or progression of vitiligo
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