The principle factors underlying gastric cancer (GC) development and outcomes are not well characterized resulting in a paucity of validated therapeutic targets. To identify potential molecular targets, we analyze gene expression data from GC patients and identify the nuclear receptor ESRRG as a candidate tumor suppressor. ESRRG expression is decreased in GC and is a predictor of a poor clinical outcome. Importantly, ESRRG suppresses GC cell growth and tumorigenesis. Gene expression profiling suggests that ESRRG antagonizes Wnt signaling via the suppression of TCF4/LEF1 binding to the CCND1 promoter. Indeed, ESRRG levels are found to be inversely correlated with Wnt signaling-associated genes in GC patients. Strikingly, the ESRRG agonist DY131 suppresses cancer growth and represses the expression of Wnt signaling genes. Our present findings thus demonstrate that ESRRG functions as a negative regulator of the Wnt signaling pathway in GC and is a potential therapeutic target for this cancer.
Objectives Although smoking is known to have a negative impact in patients with metabolic syndrome (MetS), only a few studies have examined the association between electronic cigarette (ecig) use and MetS. Methods Among 22,948 participants in the 6th Korea National Health and Nutrition Examination Survey, 14,738 (13,459 [91.3%] never, 954 [6.5%] ever, and 325 [2.2%] current e-cig users) were selected. The relationship between e-cig exposure and MetS (based on the National Cholesterol Education Program Adult Treatment Panel [NCEP-ATP] III criteria) was evaluated using a multivariable logistic regression analysis. An unweighted analysis was performed to evaluate this association without a sampling weight. A subgroup analysis was performed among active smokers to compare dual users with never e-cig users. Results Among current e-cig users, 85.0% were dual users, 12.7% were former cigarette users, and 2.2% were only e-cig users. After adjustment for covariates, abdominal obesity and hypertriglyceridemia were significantly associated with current e-cig exposure (odds ratio [OR]: 1.88, 95% confidence interval [CI]: 1.41-2.50 and OR: 1.32, 95% CI: 1.00-1.74 respectively [compared with the never e-cig users group]). Compared with never e-cig users, current ecig users showed an OR of 1.27 (95% CI: 0.96-1.70, P trend = 0.01) for MetS. In the unweighted analysis, the OR for MetS in current e-cig users was 1.40 (95% CI: 1.08-1.81, P trend <0.01). Compared with never e-cig users, dual users showed a higher OR for abdominal obesity (OR: 1.71, 95% CI: 1.25-2.34, P trend <0.001).
The anti-inflammatory effects of oridonin (Ordn) have been well established in previous studies. However, the apoptotic effects of Ordn on oral cancer cells have not yet been evaluated, at least to the best of our knowledge. The aim of this study was to examine the apoptotic activity of Ordn in oral squamous cell carcinoma cells and to eluciudate the underlying mechanisms. For this purpose, we employed experimental techniques, such as MTT assay, DAPI staining, soft agar assay, flow cytometry and western blot analysis. Our results revealed that Ordn suppressed oral cancer cell proliferation and soft agar colony formation, while it induced reactive oxygen species (ROS)-dependent apoptosis in a dose or time-dependent manner. The generation of ROS was detected in HN22 and HSC4 cells treated with Ordn and the use of the free radical scavenger, N-acetyl-L-cysteine, almost blocked Ordn-induced apoptosis. The phosphorylation of JNK and p38 mitogen-activated protein kinase (MAPK) was manifested in the Ordn-treated cells. Furthermore, Ordn induced the apoptosis of oral cancer cells through the mitochondrial-dependent pathway, involving the loss of mitochondrial membrane potential, the release of cytochrome c, the induction of poly(ADP-Ribose) polymerase (PARP) cleavage, alterations in the ratios of apoptotic proteins and the activation of the caspase cascade. Taken together, these findings indicate that Ordn induces the apoptosis of oral cancer cells probably via ROS-mediated JNK/p38 MAPK and mitochondrial pathways; thus, Ordn may have potential for use in the treatment of oral cancer.
(1) Background: To evaluate the association between obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) in the general population using a nationally representative sample from South Korea; (2) Methods: This study included 4275 adults aged ≥40 years who completed the snoring, tiredness, observed apnea, high blood pressure, body mass index (BMI), age, neck circumference, and gender (STOP-Bang) questionnaire. The risk of OSA was stratified into low, intermediate, and high grades according to the STOP-Bang score. The prevalence of NAFLD according to the STOP-Bang score was calculated, and the increasing trend was measured. A complex sample multivariable regression analysis with adjustments for possible confounding variables was used to calculate the odds ratio of NAFLD and advanced fibrosis. Subgroup analysis was conducted with stratification based on sex and obesity status; (3) Results: We identified 1021 adults with NAFLD and 3254 adults without NAFLD. The prevalence of NAFLD increased significantly with higher STOP-Bang scores in both men and women. Participants of both sexes with high STOP-Bang scores were more likely to have NAFLD. Compared to non-obese individuals, the risk of NAFLD according to the STOP-Bang score was more intense in obese individuals. With respect to hepatic steatosis, there was no significant association between advanced fibrosis and STOP-Bang score; (4) Conclusions: OSA, the risk of which was measured using the STOP-Bang model, was closely associated with NAFLD in both Korean men and women. Clinicians should consider screening for NAFLD in individuals with a high STOP-Bang score.
The immune-acquired responses after vaccination vary depending on the type of vaccine and the individual. The purpose of this study was to investigate the relationship between the acquisition of immunity and the side effects, health status, and lifestyle after completion of the second dose of AZD1222. Blood samples were collected after a second dose of AZD1222. The Euroimmun Anti-SARS-CoV-2 ELISA (IgG) for anti-S1 antibody, the cPASS SARS-CoV-2 neutralizing antibody detection kit for the surrogate virus neutralization test, and the T-spot Discovery SARS-CoV-2 kit were used to identify cellular immunogenicity. Patient experience of adverse effects was investigated using questionnaires. Information on health status and lifestyle were collected from the most recent health checkup data. Generally, females experience more reactogenicity in both intensity and duration. The rash of the first shot and chills of the second shot were associated with humoral immunity. However, comprehensive adverse effects had no correlation with humoral and cellular immunity. The T-spot-positive group had a higher creatinine level, which reflects muscle mass, than the T-spot-negative group. Males presented a higher level of T-spot assays. Body mass index and age were negatively correlated with the T-spot assay and anti-S1 antibody, respectively. Immune acquisition after the second AZD1222 shot was not associated with reactogenicity. However, individuals’ sex, age, and BMI were found to be associated with immunogenicity after vaccination.
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