ABSTRACT
BACKGROUND: UGT2B7 was recently acknowledged as a new critical enzyme involved in biotransformation of a variety of carcinogens, whose function was reported to be significantly associated with its encoding gene (UGT2B7) polymorphisms. However, results regarding the associations between single nucleotide polymorphisms (SNPs) of UGT2B7 and cancer risk still remained controversial. Therefore, a meta-analysis was conducted to further elucidate the role of UGT2B7 SNPs on cancer susceptibilities. METHODS: PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP) and Wan Fang Database were searched for eligible studies until March 2019. All analysis was carried out using the Review Manager 5.3 software. Subgroup analyses were performed by cancer types, ethnicity or source of controls. RESULTS: 13 studies with a total of 7688 cancer cases and 11,281 controls were included in this meta-analysis. The results showed that UGT2B7 rs7439366 increased the colorectal cancer risk in dominant model (ORâ¯=â¯0.76, 95% CIâ¯=â¯0.61-0.95, Pâ¯=â¯0.02). However, as for the rs7435335 and rs12233719, we did not find their associations with cancer risk in all genetic models. In addition, the rs7441774 was found to be associated with breast cancer risk and significantly reduced papillary thyroid cancer risk in rs3924194 was also observed. Nevertheless, these findings remained to be further proven in future studies since these 2 SNPs were only respectively involved in 1 study. CONCLUSION: This meta-analysis confirmed the association of UGT2B7 rs7439366 with colorectal cancer risk, which may be a potential promising biomarker for prediction of colorectal cancer risk.
Subject(s)
Colorectal Neoplasms/genetics , Glucuronosyltransferase/genetics , Neoplasms/genetics , Case-Control Studies , Female , Genetic Predisposition to Disease/genetics , Genotype , Glucuronosyltransferase/metabolism , Glucuronosyltransferase/physiology , Humans , Male , Polymorphism, Single Nucleotide/genetics , Risk FactorsABSTRACT
The present study was aimed to investigate the underlying mechanisms of the protective effect of proanthocyanidin (Pro) against hypoxia/reoxygenation (H/R) injury in H9C2 cells with a focus on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. H9C2 cells were randomly assigned to 5 groups, including the control group (Con), the H/R-injured group (H/R), the Pro-treated group (H/R+Pro), the JAK2 siRNA-treated group (H/R+Pro+JAK2 siRNA) and the JAK2 siRNA control group (H/R+JAK2 siRNA). The cells were pretreated with Pro (40 µmol/L) for 8 h before 2 h of hypoxia and 4 h of reoxygenation. Cellular viability and apoptosis rate were detected by MTT and TUNEL methods, and superoxide generation was measured. JAK2/STAT3 signaling, oxidative stress markers and endoplasmic reticulum stress markers were also detected by Western blot. We found that Pro treatment significantly improved cellular viability and reduced apoptosis rate in H/R-treated H9C2 cells. In addition, Pro treatment significantly up-regulated the phosphorylation levels of JAK2 and STAT3, down-regulated the superoxide generation, gp91phox, glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and caspase-12 expression. However, these protective effects of Pro were all attenuated by JAK2 siRNA administration. Taken together, we demonstrated that Pro protects H9C2 cells against H/R-induced oxidative stress and endoplasmic reticulum stress injury via JAK2/STAT3 signaling pathway.
Subject(s)
Signal Transduction , Animals , Apoptosis , Cell Hypoxia , Cell Line , Cell Survival , Endoplasmic Reticulum Stress , In Situ Nick-End Labeling , Janus Kinase 3 , Oxidation-Reduction , Phosphorylation , Proanthocyanidins , Protective Agents , RNA, Small Interfering , Rats , STAT3 Transcription Factor , Up-RegulationABSTRACT
BACKGROUND: Hypernatremia is an uncommon but important electrolyte abnormality in intensive care unit patients. Sepsis is one of the most common causes of intensive care unit admission, but few studies about the role of hypernatremia in sepsis has been published yet. In this study, we aimed to explore the risk factors for developing hypernatremia in patients with sepsis, and the prognosis of patients with sepsis with or without hypernatremia was also assessed. MATERIALS AND METHODS: In this retrospective cohort study of 51 septic intensive care unit patients at a single center, we examined the risk factors for the development of hypernatremia and the association of hypernatremia with clinical outcomes using univariate and multivariable analyses. Clinical outcomes such as mortality and hospital duration of patients with or without hypernatremia were also compared. RESULTS: Acute Physiology and Chronic Health Evaluation II score (odds ratio = 1.15; 95% CI: 1.022-1.294) was found to be the only independent risk factor for hypernatremia in patients with sepsis. Moreover, patients developing hypernatremia during hospitalization showed significantly higher morbidity and mortality. CONCLUSIONS: Acute Physiology and Chronic Health Evaluation II score may be an independent risk factor for hypernatremia in patients with sepsis. Moreover, hypernatremia is strongly associated with worse outcome in sepsis.
