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Inhibitory effect of kaempferol about mouse cancer malignancy cell line B16 in vivo and in vitro.
Pancreatitis is a disease for which there are numerous etiologies but no effective treatments. Although the expression of the pancreatitis-associated protein-1 (PAP-1) serves as a marker for the disease, its biological function is unknown. The present study was carried out to determine if PAP-1 performs a protective role against oxidative stress-induced pancreatic cell death. For this purpose, we used cerulein-stimulated pancreatic acinar AR42J cells as an experimental model of acute pancreatitis. First, we demonstrated that PAP-1 gene expression is increased by cerulein in a dose- and time-dependent manner. In parallel, the level of active nuclear factor kappaB (NF-κB) was found to be increased in cells treated with cerulein. To test whether activation of the oxidant-sensitive transcription factor NF-κB is mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the primary source of reactive oxygen species, cerulein-stimulated NADPH oxidase activity was suppressed by using the NADPH oxidase inhibitor diphenyleneiodonium and, separately, by anti-sense oligonucleotides directed against NADPH oxidase subunits p22phox and p47phox. We observed that a decrease in NADPH oxidase activity resulted in decreased NF-κB activation and decreased PAP-1 gene expression. To determine whether the cerulein-induced NF-κB activation involves PAP-1 expression, cells were transfected to overexpress the MAD3 double-point IκBα mutant. In response, NF-κB activation and PAP-1 gene expression were decreased. Lastly, we observed that the cerulein-induced reduction in cell viability and increase in apoptosis are reversed by overexpression of PAP-1 in PAP-1-transfected cells. Taken together, these results support the postulate that PAP-1 inhibits cerulein-induced apoptosis in response to NADPH oxidase-mediated NF-κB activation in pancreatic acinar cells.Nesfatin-1, a recently discovered peptide, was shown to have anti-inflammatory effects. Acute pancreatitis (AP) is a life-threatening condition caused by various reasons. Although the etiology of AP is well-known, its pathogenesis is not clear. The aim of this study is to investigate the possible anti-inflammatory role of nesfatin-1 and its probable protective underlying mechanisms in an acute pancreatitis model. Caerulein was applied intraperitoneally to induce acute pancreatitis in Sprague-Dawley female rats. Nesfatin-1 was administered 5 minutes before the application of caerulein to determine its potential anti-inflammatory role on AP. Five minutes before nesfatin-1 injection, in order to investigate the underlying mechanism, oxytocin receptor antagonist (atosiban), melanocortin receptor antagonist (HS024), or ghrelin receptor antagonist (cortistatin) were administered. Five minutes after nesfatin-1 administration, two doses of caerulein were applied one hour apart. The rats were sacrified 12 hours after nesfatin-1 had an anti-inflammatory effect on acute pancreatitis via mainly effecting melanocortin receptors.Resveratrol is a naturally occurring polyphenolic compound present in many plant species and wine. It possesses a wide range of beneficial biological properties including anticancer activity. Resveratrol has been demonstrated to induce both autophagy and apoptosis in several human cancer cell lines. The aim of this study was to investigate whether resveratrol modulates autophagy and apoptosis in MOLT-4 human lymphoblastic leukemia and HL-60 human promyelocytic leukemia cells. Cell viability was evaluated by the neutral red uptake assay. Cell cycle distribution, phosphatidylserine externalization, caspase-3 activation, changes of the mitochondrial membrane potential, intracellular production of reactive oxygen species were evaluated by flow cytometry. LC3-I to LC3-II conversion was examined based on Western blotting and immunofluorescence analyses. The level of p62/SQSTM1 protein and PARP1 cleavage were analyzed by Western blotting. The DNA degradation was assessed by gel electrophoresis. We found that resveratrol is able to modulate autophagy in MOLT-4 and HL-60 cells, as evidenced by the detection of an increased level of LC3-II and p62/SQSTM1 proteins. Moreover, resveratrol induced apoptosis in both cell lines which was associated with phosphatidylserine externalization, disruption of the mitochondrial membrane potential, caspase-3 activation, internucleosomal DNA fragmentation, PARP1 cleavage, chromatin condensation, and fragmentation of cell nuclei. The present study provides evidence that resveratrol can act as an autophagy modulator as well as an apoptosis inducer in MOLT-4 and HL-60 human leukemia cells. Our findings imply that resveratrol can be a promising chemotherapeutic agent in the treatment of leukemia.Prediabetes is a state of elevated plasma glucose in which the threshold for diabetes has not yet been reached and can predispose to the development of type 2 diabetes and cardiovascular diseases. AICAR concentration Insulin resistance and impaired beta-cell function are often already present in prediabetes. Hyperglycemia can upregulate markers of chronic inflammation and contribute to increased reactive oxygen species (ROS) generation, which ultimately cause vascular dysfunction. Conversely, increased oxidative stress and inflammation can lead to insulin resistance and impaired insulin secretion. Proper treatment of hyperglycemia and inhibition of ROS overproduction is crucial for delaying onset of diabetes and for prevention of cardiovascular complications. Thus, it is imperative to determine the mechanisms involved in the progression from prediabetes to diabetes including a clarification of how old and new medications affect oxidative and immune mechanisms of diabetes. In this review, we discuss the relationship between oxidative stress and hyperglycemia along with links between inflammation and prediabetes. Additionally, the effects of hyperglycemic memory, microvesicles, micro-RNA, and epigenetic regulation on inflammation, oxidative state, and glycemic control are highlighted. Adipose tissue and their influence on chronic inflammation are also briefly reviewed. Finally, the role of immune-targeted therapies and anti-diabetic medication on glycemic control and oxidative stress are discussed.
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