14 As highlighted in this paper, MICA might play a role in UC pathogenesis via the dysfunctional activation of NK and T cells. Like most NKG2D ligands, MICA is inducible on epithelial cells by many different types of stress, including viral, bacterial, and physical, which leads those stressed cells to become targets for immune recognition.18 If this pathway is less responsive in UC patients
because MICA is a less effective NKG2D ligand (weak binder), immune targeting of stressed gut epithelial cells in these patients would be impaired. MICA is an intriguing functional candidate for UC providing a logical pathway for disease development, which is compatible with the current hypothesis of a dysfunctional immune system. Although there have been conflicting data regarding genetic DNA Damage inhibitor associations, several functional studies have provided interesting evidence which suggests a role for MICA or other NKG2D ligands in disease development. Further functional studies are required buy Bortezomib to explore this role in greater detail, as well as additional genetic studies in large, well-characterized, ethnically-diverse UC populations to consider other
key genes in this pathway. “
“The global obesity epidemic is linked to an increased incidence of a number of metabolic disorders, including type 2 diabetes mellitus, the metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). The term NAFLD Phosphoprotein phosphatase encompasses a number of pathological conditions ranging
from hepatic steatosis (fatty liver), which is thought to be a largely benign condition, to more aggressive disease states, including nonalcoholic steatohepatitis (NASH) and cirrhosis; a number of patients may ultimately progress from cirrhosis to hepatic failure and hepatocellular carcinoma.1 Surveys suggest that the occurrence of NAFLD in the general population may be as high as 30%-35%,2 but this incidence may rise significantly in obese individuals. ER, endoplasmic reticulum; FFA, free fatty acid; HFE, hemochromatosis gene; IR, insulin resistance; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; UPR, uncoupled protein response; SREBP, sterol-response element binding protein. The incidence of NAFLD is closely associated with insulin resistance (IR) and the metabolic syndrome.3 The development of NAFLD is often considered to be a two-stage process.4 Stage one arises from lipid accumulation in the liver; this could occur for a number of reasons, including increased uptake of fat (derived, for example, from either dietary sources or from the flow of free fatty acids [FFAs] released from the adipose tissue as a result of IR), increased lipid synthesis, or decreased hepatic lipid secretion.