Krebslynge1962
Copyright © 2020 JCBN.Decreases in plasma vitamin D concentrations have been reported in diabetes, although the mechanism involved in this decrease is unclear. Here, we investigated the association between Cyp24a1, a vitamin D catabolic enzyme, and abnormalities in vitamin D metabolism in streptozotocin-induced diabetes rats, an animal model of type 1 diabetes. Plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were significantly lower in streptozotocin-induced diabetes rats and renal Cyp24a1 mRNA expression levels were increased. Western blotting analysis of streptozotocin-induced diabetes rats kidney tissues with anti-CYP24A1 antibody showed a strong signal around 40 kDa, which differs from the predicted 50-55 kDa molecular weight for full-length Cyp24a1 and could represent the Cyp24a1-splicing variant that lacks exons 1 and 2. We observed high levels of renal Cyp24a1-splicing variant mRNA expression in streptozotocin-induced diabetes rats. We also confirmed transcriptional up-regulation of endogenous Cyp24a1 mRNA expression through glucocorticoid receptors by glucocorticoid in opossum kidney proximal cells. Taken together, our results indicated that high Cyp24a1 expression levels may play a role in the decrease of plasma 1,25(OH)2D levels in streptozotocin-induced diabetes rats. High plasma corticosterone levels in diabetes may affect transcriptional regulation to promote increases in Cyp24a1 expression. Copyright © 2020 JCBN.This study tested the effect of isoflavone supplementation in addition to combined exercise training in salivary oxidative stress markers in non-obese postmenopausal women. Thirty-two postmenopausal women without hormone therapy were randomly assigned to exercise + placebo (n = 15) or exercise + isoflavone supplementation (n = 17) groups. They performed 30 sessions of combined exercises (aerobic plus resistance) over ten weeks and consumed 100 mg of isoflavone supplementation or placebo. Saliva samples were collected after an overnight fast. Superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, catalase, total protein and nitrite were determined before and after ten weeks of the intervention. The ANOVA two-way analysis of variance was applied with α of 5%. Both groups increase (p less then 0.05) superoxide dismutase activity and decrease catalase levels. There was interaction (time × group) in both nitrite and thiobarbituric acid reactive substances results, with increase (p less then 0.05) in placebo group and decrease (p less then 0.05) in isoflavone group. No difference was found for total antioxidant capacity or total protein. The combination of isoflavone supplementation and exercise training can promote an antioxidant effect through reduction of lipid peroxidation and concentrations of salivary nitrite. Copyright © 2020 JCBN.This study was conducted to evaluate the regulation mechanism of influenza virus replication following treatment of Madin-Darby canine kidney cells with the soy isoflavone daidzein. We performed comparative qualitative and quantitative analyses of lipid peroxide between mock-infected and virus-infected cells treated with or without daidzein, as it had been reported that daidzein was an antioxidant and lipid peroxide levels increased upon virus infection. Contrary to our belief, lipid peroxides were not elevated in virus-infected cells and no decrease in lipid peroxides was observed in daidzein-treated cells. In daidzein-treated cells, 5-hydroxyeicosatetraenoic acid, the 5-lipoxygenase product derived from arachidonate, was significantly elevated compared to other lipid peroxides. Zileuton (5-lipoxygenase inhibitor) and 5-lipoxygenase knockdown reduced the daidzein-induced antiviral effect. Moreover, virus replication was regulated by treatment with 5-hydroperoxyeicosatetraenoic acid, a precursor of 5-hydroxyeicosatetraenoic acid and 5-lipoxygenase primary product. These results suggest that daidzein regulates virus replication via signal transduction through 5-lipoxygenase products. Copyright © 2020 JCBN.To gain a better understanding of how nitrate may affect carbohydrate and lipid metabolism, female wild-type mice were fed a high-fat, high-fructose diet supplemented with either 0, 400, or 800 mg nitrate/kg diet for 28 days. Additionally, obese female db/db mice were fed a 5% fat diet supplemented with the same levels and source of nitrate. Nitrate decreased the sodium-dependent uptake of glucose by ileal mucosa in wild-type mice. Moreover, nitrate significantly decreased triglyceride content and mRNA expression levels of Pparγ in liver and Glut4 in skeletal muscle. Oral glucose tolerance as well as plasma cholesterol, triglyceride, insulin, leptin, glucose and the activity of ALT did not significantly differ between experimental groups but was higher in db/db mice than in wild-type mice. Nitrate changed liver fatty acid composition and mRNA levels of Fads only slightly. Further hepatic genes encoding proteins involved in lipid and carbohydrate metabolism were not significantly different between the three groups. Biomarkers of inflammation and autophagy in the liver were not affected by the different dietary treatments. Overall, the present data suggest that short-term dietary supplementation with inorganic nitrate has only modest effects on carbohydrate and lipid metabolism in genetic and dietary-induced mouse models of obesity. Copyright © 2020 JCBN.Neutrophil extracellular trap (NET) formation plays an important role in inflammatory diseases. Although it is known that NET formation occurs via NADPH oxidase (NOX)-dependent and NOX-independent pathways, the detailed mechanism remains unknown. Therefore, in this study, we aimed to elucidate the role of mitochondria in NOX-dependent and NOX-independent NET formation. We generated mitochondrial DNA-deficient cells (ρ0 cells) by treating HL-60 cells with dideoxycytidine and differentiated them to neutrophil-like cells. These neutrophil-like ρ0 cells showed markedly reduced NOX-independent NET formation but not NOX-dependent NET formation. However, NET-associated intracellular histone citrullination was not inhibited in ρ0 cells. Furthermore, cells membrane disruption in NOX-dependent NET formation occurred in a Myeloperoxidase (MPO) and mixed lineage kinase domain like pseudokinase (MLKL)-dependent manner; however, cell membrane disruption in NOX-independent NET formation partially occurred in an MLKL-dependent manner. These results highlight the importance of mitochondria in NOX-independent NET formation. Copyright © 2020 JCBN.Trapa bispinosa Roxb. is an annual aquatic grass of the citrus family. Although its hot water extract displays antioxidative activity in vitro, little is known about its biological effectiveness. In the present study, we evaluated the extract's inhibitory effect on diabetic cataractogenesis and formation of advanced glycation end-product. Lutein, which is beneficial for eye diseases, was administered concurrently. For short-term administration, Trapa bispinosa Roxb. hot water extract and/or lutein were administered to type 1 diabetic rats. N ɛ-(carboxymethyl)lysine and N ɛ-(carboxyethyl)lysine were quantified in serum using mass spectrometry. The long-term administration study was similar to the short-term, except that the dosages were lower. In the short-term study, co-administration of the extract and lutein inhibited N ɛ-(carboxymethyl)lysine and N ɛ-(carboxyethyl)lysine in serum. However, in the long-term study, only lutein inhibited N ɛ-(carboxymethyl)lysine and N ɛ-(carboxyethyl)lysine in serum. These results suggest that lutein exerts its long-term effect regardless of the concentration administered, while the extract exerts its effect when its concentration is increased. Relative to the consumption of the control diet, oral intake of the combination of the extract and lutein significantly inhibited the progression of cataractogenesis in the lens of diabetic rats, even at low doses, and the combination was more effective than individual treatments. Copyright © 2020 JCBN.Selenoprotein P (encoded by SELENOP) contains the essential trace element selenium in the form of selenocysteine, which is an analog of cysteine that contains selenium instead of sulfur. Selenoprotein P is a major selenium-containing protein in human plasma and is mainly synthesized in the liver. It functions as a selenium-transporter to maintain antioxidative selenoenzymes in several tissues, such as the brain and testis, and plays a pivotal role in selenium-metabolism and antioxidative defense. A decrease of selenoprotein P and selenoproteins causes various dysfunctions related to oxidative stress. On the other hand, recent studies indicate that excess selenoprotein P exacerbates glucose metabolism and promotes type 2 diabetes. This review focuses on the biological functions of selenoprotein P, particularly its role in selenium-metabolism and antioxidative defense. Furthermore, the effects of excess selenoprotein P on glucose metabolism, and resulting diseases are described. The development of a therapeutic agent that targets excess selenoprotein P is discussed. Copyright © 2020 JCBN.Investigating the performance that can be achieved with different hydrological models across catchments with varying characteristics is a requirement for identifying an adequate model for any catchment, gauged or ungauged, just based on information about its climate and catchment properties. As parameter uncertainty increases with the number of model parameters, it is important not only to identify a model achieving good results but also to aim at the simplest model still able to provide acceptable results. The main objective of this study is to identify the climate and catchment properties determining the minimal required complexity of a hydrological model. As previous studies indicate that the required model complexity varies with the temporal scale, the study considers the performance at the daily, monthly, and annual timescales. In agreement with previous studies, the results show that catchments located in arid areas tend to be more difficult to model. They therefore require more complex models for achieal Processes published by John Wiley & Sons Ltd.Dacomitinib, a second-generation tyrosine kinase inhibitor, was irreversible inhibitor forming covalent bonds with the kinase domains of EGFR and other ErbB family receptors. Dacomitinib has been approved for the treatment of locally advanced or metastatic non-small cell lung cancer. In this study, we aimed to develop an immunohistochemistry to detect dacomitinib-ErbB family receptor conjugates. Immunostaining was performed in rat intestine and skin tissues after oral administration of dacomitinib. Following a single oral dose of dacomitinib, strong staining was observed after 24 hr in the ileum and colon, with only slight staining in the duodenum and jejunum. In the skin, strong staining was observed in the epidermis, hair follicles, and sebaceous glands. Moreover, significant amounts of dacomitinib remained for up to 72 hr post-administration in the ileum, colon, and skin. This report is the first to elucidate the localization and accumulation of dacomitinib in the rat intestine and skin and should be valuable during efforts to clarify the mechanism dacomitinib-induced diarrhea or skin toxicities.