The correlation between polymorphisms at the tumor necrosis factor (TNF) gene and generalized pustular psoriasis (GPP) has rarely been reported. The goal of this study is to investigate whether TNF polymorphisms (?238 A/G, ?308 A/G, ?857C/T) are associated with susceptibility to GPP in a Han population from Eastern China and to perform subgroup analysis to explore the influence of age onset. Polymorphisms were assessed by polymerase chain reaction amplification and resequencing in 91 GPP patients and 102 healthy controls. The frequencies of the TNF ?238A allele and GA+AA genotypes were significantly higher in GPP patients than in those of healthy controls. The subgroup analysis revealed that these significant associations were still present between ?238A variants and pediatric‐onset GPP patients who developed GPP at less than 18 years old (PGPP), but not for patients with adult‐onset GPP who developed GPP at 18 years old or more. There were no significant differences in genotype or allele frequencies of TNF ?308 A/G and ?857C/T polymorphisms between GPP and controls. In conclusion, individuals carrying TNF ?238A may be more susceptible to PGPP. 相似文献
Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100?nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H2O2. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability. 相似文献
Alpinetin is a natural flavonoid showing a variety of pharmacological effects such as anti-inflammatory, anti-tumor and hypolipidemic activities. Here, we aim to determine the roles of UDP-glucuronosyltransferases (UGTs) and breast cancer resistance protein (BCRP) in disposition of alpinetin.
Glucuronidation potential of alpinetin was evaluated using pooled human liver microsomes (pHLM), pooled human intestine microsomes (pHIM) and expressed UGT enzymes supplemented with the cofactor UDPGA. Activity correlation analyses with a bank of individual HLMs were performed to identify the main contributing UGT isozymes in hepatic glucuronidation of alpinetin. The effect of BCRP on alpinetin disposition was assessed using HeLa cells overexpressing UGT1A1 (HeLa1A1) cells.
Alpinetin underwent extensive glucuronidation in pHLM and pHIM, generating one glucuronide metabolite. Of 12 test UGT enzymes, UGT1A3 was the most active one toward alpinetin with an intrinsic clearance (CLint?=?Vmax/Km) value of 66.5?μl/min/nmol, followed by UGT1A1 (CLint?=?48.6?μl/min/nmol), UGT1A9 (CLint?=?21.0?μl/min/nmol), UGT2B15 (CLint?=?16.7?μl/min/nmol) and UGT1A10 (CLint?=?1.60?μl/min/nmol). Glucuronidation of alpinetin was significantly correlated with glucuronidation of estradiol (an activity marker of UGT1A1), chenodeoxycholic acid (an activity marker of UGT1A3), propofol (an activity marker of UGT1A9) and 5-hydroxyrofecoxib (an activity marker of UGT2B15), confirming the important roles of UGT1A1, UGT1A3, UGT1A9 and UGT2B15 in alpinetin glucuronidation. Inhibition of BCRP by its specific inhibitor Ko143 significantly reduced excretion of alpinetin glucuronide, leading to a significant decrease in cellular glucuronidation of alpinetin.
Our data suggest UGTs and BCRP as two important determinants of alpinetin pharmacokinetics.
Tim‐3 is expressed on monocytes/macrophages and is involved in the regulation of inflammatory responses. The aim of this study was to determine the effect of Tim‐3 on inflammatory response triggered by peripheral monocytes from patients with chronic hepatitis B (CHB). Tim‐3 expression on peripheral monocytes and frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) derived from CHB patients were detected. Followed by lipopolysaccharides (LPS) activation of circulating monocytes from CHB patients, expression of inflammatory cytokines including TNF‐α,IL‐1β and IL‐6 were examined in the presence and absence of Galectin‐9 which is the ligand for Tim‐3. Subsequently, after purified CD4+T cells were cocultured with LPS‐activated monocytes from CHB patients in the presence of anti‐Tim‐3 antibody, percentage of Th17 cells and production of IL‐17 were measured. Tim‐3 expression was significantly upregulated and closely correlated to the frequency of Th17 cells in patients with CHB. Expression of TNF‐α,IL‐1β and IL‐6 increased significantly in monocytes stimulated with LPS and Galectin‐9, compared to LPS stimulation alone. LPS‐activated monocytes from CHB patients could drive differentiation of memory CD4+T cells to Th17 cells. However, under the blockade of Tim‐3 signalling by anti‐Tim‐3 antibody, percentage of Th17 cells and production of IL‐17 decreased significantly. Our results demonstrate that upregulated expression of Tim‐3 on circulating monocytes accelerates inflammatory response by promoting production of inflammatory cytokines and Th17 responses in CHB. 相似文献
Objective: The assessment of prognostic nutritional index (PNI) before and during radiotherapy is an important parameter for the prognosis in patients with cancer. In this study, enteral tube feeding (ETF) was used during radiotherapy in patients with EC. Dynamic changes of various nutritional indicators (including PNI) were monitored.
Methods: Patients with EC who underwent radiotherapy between June 2016 and July 2017 were enrolled. ETF was performing with the energy of 25?kcal?×?kg/d. Nutritional status were evaluated. Least significant difference (LSD) was used for multiple comparisons between groups.
Results: A total of 148 patients were admitted, including 51 patients fed via ETF. For patients who were not scheduled to nutritional support, significant difference were observed in albumin (ALB) (P?<?0.001), prealbimnin (PA) (P?=?0.05) and PNI (P?<?0.001) compared to levels before radiotherapy. In the patients fed via enteral tube, no significant difference were found in weight, BMI, ALB, retinol binding protein (RBP) and PA before and after radiotherapy, while PNI significantly decreased (P?<?0.001).
Conclusion: After preforming ETF with the energy of 25?kcal?×?kg/d in patients with EC during radiotherapy, PNI, the key nutritional index reflecting prognosis, significantly decreased. 相似文献