Inhibition of histone deacetylase (HDAC) suppresses inflammation of pancreatic islets and apoptosis of β-cells. However, the underlying molecular mechanism is unclear. In the present study, we demonstrate that MGCD0103 (MGCD), an HDAC inhibitor, protects the pancreas from streptozotocin (STZ)-induced oxidative stress and cell death. Sprague-Dawley rats were intraperitoneally injected with STZ (40 mg/kg) to induce type I diabetes. MGCD (10 μg/day) was infused with osmotic mini-pump for 4 weeks. Pancreatic insulin and macrophage infiltration were analyzed by immunohistochemistry. Cellular level of reactive oxygen species (ROS) was evaluated with fluorescence-activated cell sorting. Tetramethylrhodamine ethyl ester was used to analyze mitochondrial membrane potential. Activation of caspase-3 was analyzed by western blotting. Chromatin immunoprecipitation was performed to investigate the binding affinity of specificity protein 1 (SP1) on the promoters of target genes. mRNA expression was analyzed by quantitative real-time polymerase chain reaction. As a result, we found that MGCD infusion ameliorated STZ-induced hyperglycemia, islet deformation, decreased insulin level, and macrophage infiltration. STZ injection promoted the production of ROS, which induced caspase activity and β-cell death. 4-Hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL), a mimetic of superoxide dismutase (SOD), reduced STZ-induced caspase activity and β-cell death. MGCD treatment increased SOD expression and histone acetylation level on promoters. Infusion of MGCD promoted acetylation of SP1 and its enrichment on SOD promoters. Thus, MGCD protects pancreatic β-cells from STZ-induced oxidative stress and cell death through the induction of antioxidant enzymes such as SODs.

Patterns of failure were studied in two consecutive randomized trials of intensified induction therapy carried out by the Australian Leukaemia Study Group (ALSG) between 1984 and 1991 to determine the impact of dose intensification. Patients received standard dose cytarabine and daunorubicin (7-3), 7-3 plus etoposide (7-3-7) or 7-3 plus high-dose cytarabine (HIDAC-3-7) chemotherapy. Patients with FAB M3 morphology were excluded. Time to failure (TTF) was defined as the time from randomization to induction death or removal from study for non-responders, or to relapse or death in complete response (CR) for complete responders. An estimated 86% of 470 de novo patients with acute myeloid leukaemia failed within 10 years of randomization, as a result of death in induction in 17% of the randomized patients, failure to achieve CR in a further 17%, relapse in 44% and death in CR in 8% of patients. An estimated 66% of patients failed as a result of refractory disease or relapse within that period (disease-related failures). Multifactor analysis identified age and peripheral blast count as the most significant pretreatment factors associated with overall TTF. These factors, together with cytogenetics, were significantly associated with disease-related failures. High-dose cytarabine in induction significantly decreased the disease-related failure rate as did allogeneic transplantation in first CR. The impact of high-dose cytarabine did not depend on the cytogenetic risk group.

D-allulose, which has 70% of the sweet taste of sucrose but nearly no calories, has been reported to inhibit the absorption of lipids and suppress body weight gain in obese mice. Fats in non-dairy creamer consist of highly saturated fatty acids, which can cause various lipid disorders when consumed over a long period. We investigated whether D-allulose supplementation alleviates the effects of a non-dairy creamer-enriched high-fat diet on lipid metabolism. High-fat diets enriched with non-dairy creamer were administered to C57BL/6J mice with or without D-allulose supplementation for eight weeks by the pair-feeding design. Lipid metabolic markers were compared between the non-dairy creamer control group (NDC) and non-dairy creamer allulose group (NDCA). Body, adipose tissue, and liver weights, and fasting blood glucose levels, were significantly lower in the NDCA group than in the NDC group. Fecal fatty acid and triglyceride levels were significantly higher in the NDCA group than in the NDC group. Supplementing a non-dairy creamer-enriched high-fat diet with D-allulose improved overall lipid metabolism, including the plasma and hepatic lipid profiles, hepatic and adipose tissue morphology, and plasma inflammatory adipokine levels in mice. These results suggest that D-allulose can be used as a functional food component for preventing body fat accumulation from a high-fat diet that includes hydrogenated plant fats.