Cytochrome P450 is the most important enzyme in the body and involved in the biotransformation of endogenous substances and exogenous chemicals (Dey et al., 1999). In particular, cytochrome P450 1A2 (CYP1A2) is
Under the stressed condition, a complex feedback mechanism of the hypothalamo-pituitary-adrenal (HPA) axis is activated to regulate interactions to stress to maintain homeostasis of the body (Iwasa et al., 2018;Kim, 2019). In particular, the hormones in HPA axis with respect to corticotrophin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and glucocorticoid reduce the pulsatile secretions of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH)
In previous studies, the increasing clinical importance of nonalcoholic fatty liver disease (NAFLD) has been recognized. However, the specific therapeutic strategies or drugs have not been discovered. Vitamin C is a water-soluble antioxidant and is a cofactor in many important biosynthesis pathways. Recently, many researchers have reported that the mega-dose vitamin C treatment had positive effects on various diseases. However, the precise relationship between mega-dose vitamin C and NAFLD has not been completely elucidated. This study has been designed to discover the effects of mega-dose vitamin C on the progression of NAFLD. Twelve-week-old wild-type C57BL6 mice were fed chow diets and high-fat and high-fructose diet (fast-food diet) ad libitum for 11 weeks with or without of vitamin C treatment. Vitamin C was administered in the drinking water (1.5 g/L). In this study, 11 weeks of the mega-dose vitamin C treatment significantly suppressed the development of nonalcoholic steatohepatitis (NASH) independently of the catabolic process. Vitamin C supplements in fast-food diet fed mice significantly decreased diet ingestion and increased water intake. Histopathological analysis revealed that the mice fed a fast-food diet with vitamin C water had a mild renal injury suggesting osmotic nephrosis due to fructose-mediated purine derivatives. These data suggest that the mega-dose vitamin C treatment suppresses high-fructose-diet-mediated NAFLD progression by decreasing diet ingestion and increasing water intake.
Chaga mushroom (Inonotus obliquus) comprises polyphenolic compounds, triterpenoids, polysaccharides, and sterols. Among the triterpenoid components, inotodiol has been broadly examined because of its various biological activities. The purpose of this study is to examine inotodiol from a safety point of view and to present the potential possibilities of inotodiol for medical usage. From chaga mushroom extract, crude inotodiol (INO20) and pure inotodiol (INO95) were produced. Mice were treated with either INO20 or INO95 once daily using oral administration for repeated dose toxicity evaluation. Serum biochemistry parameters were analyzed, and the level of pro-inflammatory cytokines in the serum was quantified. In parallel, the effect of inotodiol on food allergic symptoms was investigated. Repeated administration of inotodiol did not show any mortality or abnormalities in organs. In food allergy studies, the symptoms of diarrhea were ameliorated by administration with INO95 and INO20. Furthermore, the level of MCPT-1 decreased by treatment with inotodiol. In this study, we demonstrated for the first time that inotodiol does not cause any detrimental effect by showing anti-allergic activities in vivo by inhibiting mast cell function. Our data highlight the potential to use inotodiol as an immune modulator for diseases related to inflammation.
BackgroundThis study was performed to investigate the predictors of 1-year mortality at discharge in sepsis survivors.
MethodsThis study was a retrospective analysis of patients with sepsis and septic shock at a single centre. Patients who survived hospitalization for sepsis or septic shock from January 2016 to December 2017 were included. Age; sex; body mass index (BMI); laboratory results such as blood cell count, C-reactive protein (CRP) and albumin; and the Sequential Organ Failure Assessment (SOFA) score at the time of discharge were compared between survivors and nonsurvivors at 1 year postdischarge. Multivariate logistic regression was performed to identify the predictors of 1-year mortality.
ResultsDuring the study period, 725 survivors were included in the analysis, of whom 64 (8.8%) died within the rst year. Nonsurvivors were older and had a lower BMI and higher SOFA score at discharge than survivors (P < 0.05). Among the laboratory results at discharge, haemoglobin, platelet counts and albumin concentrations were lower in the nonsurvivors than in the survivors, whereas CRP was higher in the nonsurvivors than in the survivors. In the multivariate logistic regression analysis, serum albumin < 2.5 mg/dl and a SOFA score ≥ 2 at discharge were identi ed as independent prognostic factors for 1-year mortality (odds ratio 2.698, 95% con dential interval 1.488-4.883 for albumin < 2.5 mg/dl and 2.114, 1.204-3.814 for SOFA score ≥ 2, respectively).
ConclusionsA low serum albumin concentration of < 2.5 mg/dL and high SOFA score of ≥ 2 at the time of discharge were prognostic factors for 1-year mortality in sepsis survivors.
The cellular distribution of silica nanoparticles (NPs) in the liver is not well understood. Targeting specific cells is one of the most important issues in NP-based drug delivery to improve delivery efficacy. In this context, the present study analyzed the relative cellular distribution pattern of silica NPs in the liver, and the effect of surface energy modification on NPs. Hydrophobic NP surface modification enhanced NP delivery to the liver and liver sinusoid fFendothelial cells (LSECs). Conversely, hydrophilic NP surface modification was commensurate with targeting hepatic stellate cells (HSCs) rather than other cell types. There was no notable difference in NP delivery to Kupffer cells or hepatocytes, regardless of hydrophilic or hydrophobic NP surface modification, suggesting that both the targeting of hepatocytes and evasion of phagocytosis by Kupffer cells are not associated with surface energy modification of silica NPs. This study provides useful information to target specific cell types using silica NPs, as well as to understand the relationship between NP surface energy and the NP distribution pattern in the liver, thereby helping to establish strategies for cell targeting using various NPs.
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