ABSTRACT
BACKGROUND: Immune imbalance of regulatory T cells (Treg)/T helper 17 cells (Th17) contributes to the development of immune thrombocytopenic purpura (ITP). The dysregulation of miRNAs is important in the development of ITP. However, the role of miR-106b-5p in Treg/Th17 imbalance remains unknown in ITP. MATERIALS AND METHODS: Peripheral blood was collected from patients with ITP and healthy controls, and CD4 + T cells were further isolated. miR-106b-5p, nuclear receptor subfamily 4 group A member 3 (NR4A3), forkhead box protein 3 (Foxp3), IL-17A, and TGF-ß expressions were detected by qRT-PCR, western blot, or ELISA. The effect of miR-106b-5p on NR4A3 was detected by dual-luciferase reporter gene assay. RESULTS: Compared with healthy controls, miR-106b-5p was elevated in peripheral blood of patients with ITP, and NR4A3 expression was decreased. sh-NR4A3 significantly decreased Foxp3 and TGF-ß expressions, indicating that NR4A3 may regulate Treg differentiation via Foxp3. Additionally, NR4A3 was identified to be a target of miR-106b-5p, and miR-106b-5p was able to negatively modulate NR4A3 expression. Moreover, we found miR-106b-5p induced immune imbalance of Treg/Th17 through NR4A3. In vivo experiments revealed that silencing miR-106b-5p promoted Treg differentiation and increased the number of platelets, suggesting the relief of ITP. CONCLUSION: miR-106b-5p regulated immune imbalance of Treg/Th17 in ITP through the NR4A3/Foxp3 pathway.
Subject(s)
DNA-Binding Proteins/metabolism , Forkhead Transcription Factors/metabolism , MicroRNAs/metabolism , Purpura, Thrombocytopenic, Idiopathic/genetics , Purpura, Thrombocytopenic, Idiopathic/immunology , Receptors, Steroid/metabolism , Receptors, Thyroid Hormone/metabolism , Signal Transduction , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Animals , Base Sequence , Cell Differentiation , Child , Child, Preschool , Female , Gene Silencing , Humans , Male , Mice, Inbred BALB C , MicroRNAs/blood , MicroRNAs/genetics , Platelet Count , Purpura, Thrombocytopenic, Idiopathic/bloodABSTRACT
OBJECTIVE: To investigate the effects of Notch signal on hypoxic induction factor (HIF-1α) and autophagy-associated genes Beclin1, LC3I, LC3II in oxygen-glucose deprivation (OGD) induced myocardial cell injury. METHODS: The OGD model was established using hypoxic culture box and hypoglycemic DMEM medium. The cells were divided into normal control group, OGD group, OGD + NC siRNA group, OGD + Notch1 siRNA group and OGD + HIF-1α siRNA group. Western blot was used to detect the interference effects of HIF-1α siRNA and Notch1 siRNA. The effects of Notch1 siRNA and HIF-1α siRNA on the activity of myocardial cells in OGD model were detected by the CCK-8 assay. The effects of Notch1 siRNA and HIF-1α siRNA on autophage-associated genes Beclin1, LC3I and LC3II expression were detected by Western blot. RESULTS: The results of Western blot showed that HIF-1α siRNA could effectively knock down the expression of HIF-1α in myocardial cells in OGD model, and Notch1 siRNA could effectively knock down the expression of Notch1 and HIF-1α in myocardial cells in OGD model. The result of CCK-8 assay showed that Notch1 siRNA and HIF-1α siRNA reduced the activity of myocardial cells in OGD model, and there was no statistical difference between the two groups. Western blot results showed that Notch1 siRNA and HIF-1α siRNA could reduce the expressions of the autophagy-associated genes Beclin1, LC3I and LC3II, and reduce the ratio of LC3II to LC3I at mRNA level. CONCLUSION: Notch1 plays a role in myocardial protection by regulating the expression of HIF-1α to regulate the autophagy in OGD model cells.
Subject(s)
Autophagy , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Myocytes, Cardiac/cytology , Receptors, Notch/metabolism , Signal Transduction , Beclin-1/metabolism , Cell Hypoxia , Cells, Cultured , Glucose , Humans , Microtubule-Associated Proteins/metabolism , Myocytes, Cardiac/pathology , OxygenABSTRACT
Based on the grey correlation analysis method, the chilling damage inducing factors and yield structure traits of rice in different growth stages, and the yield structure traits and final yield of rice were regarded as two grey systems. By seeking the grey relations of the grey systems and using the multi level grey correlation analysis method, the comprehensive assessment model of rice chil-ling damage was constructed, and the comprehensive assessment indices of chilling damages in sepa rate stages were established. The rice chilling damages at 27 stations in Northeast China from 1961 to 2015 were assessed separately. The results showed that there was a good corresponding relationship between the chilling damage and the rice yield. The low temperature during the vegetative growth stage, the vegetative growth and reproductive stage, the pollination stage or the grain filling stage significantly decreased the panicle number per plant, the average panicle grain number or the thousand kernel mass, and increased the empty grain rate. A good correspondence existed between temperature and rice yield in the typical chilling damage years.
Subject(s)
Oryza , China , Cold Temperature , Edible Grain , TemperatureABSTRACT
The relationships between the NAD(P)H quinone oxidoreductase 1 (NQO1) C609T polymorphism and the risk of digestive tract (DT) cancer are controversial. Therefore, we performed a meta-analysis to assess the relationships. The databases of Medline, Embase, and WanFang (updated to 15 May 2011) were reviewed. Odds ratios and 95% confidence intervals were calculated to assess the strength of the associations. Overall, 21 individual case-control studies in 20 papers with 5340 cases and 5911 controls were included in this meta-analysis. The results of combined analyses indicated that the T allele of NQO1 C609T was significantly associated with increased risk of DT cancer [odds ratio (95% CI): 1.58 (1.22-2.07) for TT vs. CC and 1.13 (1.06-1.22) for T carriers vs. C carriers]. Subgroup analyses for different types of cancers indicated that the T allele was significantly associated with an increased risk of gastric cancer [1.19 (1.13-1.47) for T carriers vs. C carriers], but not with esophageal cancer [1.05 (0.86-1.27) for T carriers vs. C carriers] and colorectal cancer [1.09 (0.98-1.21) for T carriers vs. CC]. Subgroup analyses for ethnicities and countries indicated that the T allele was associated with risk of DT cancer among Europeans [1.52 (1.05-2.19) for TT vs. CC] and Asians [1.52 (1.05-2.19) for TT vs. CC], and German, Indian, and Chinese populations but not among English and Japanese populations. In addition, subgroup analyses also indicated that the T allele was significantly associated with risk of DT cancer in studies with large and small sample sizes and in population-based studies, but not in hospital-based studies. This meta-analysis suggests that NQO1 C609T is significantly associated with risk of DT cancer among both Europeans and Asians, especially gastric cancer. Because of the limited number of cases and controls in the subgroup analyses, more well-designed studies with a large sample of participants are needed to verify our findings.
Subject(s)
Gastrointestinal Neoplasms/genetics , Genetic Predisposition to Disease , NAD(P)H Dehydrogenase (Quinone)/genetics , Polymorphism, Genetic , Asian People/genetics , Case-Control Studies , Gastrointestinal Neoplasms/ethnology , Genetic Predisposition to Disease/ethnology , Humans , White People/geneticsABSTRACT
The relationships between some metabolic (including EPHX1, GSTs and NQO1) gene polymorphisms and colorectal adenoma (CRA) risk have been commonly studied, and no conclusions are available up to now. Therefore, we quantitatively studied the relationships by a metaanalysis. The databases of Medline and Embase were retrieved updated to June 15th, 2011. Crude or adjusted odds ratio (crude OR or adjusted OR) and 95% confidence interval (95%CI) were calculated to present the strength of the associations. Overall, nine case-control studies for EPHX1 Tyr113His and His139Arg, five case-control studies for GSTM1, four studies for GSTP1 Ile105Val, two studies for GSTP1 Ala114Val, six studies for GSTT1 and four studies for NQO1 Pro187Ser were included in this metaanalysis. The results of combined analyses indicated that EPHX1 Tyr113His and His139Arg, GSTT1, GSTM1, GSTP1 Ile105Val and Ala114Val were not associated with CRA risk [crude OR (95%CI): 0.98 (0.90-1.07) and P ( z-test) = 0.65 for EPHX1 His carriers vs. Tyr/Tyr; 1.05 (0.97-1.15) and P ( z-test) = 0.21 for EPHX1 Arg carriers vs. His/His; 1.05 (0.92-1.20) and P ( z-test) = 0.47 for GSTT1 Null vs. Present; 1.01 (0.90-1.13) and P ( z-test) = 0.90 for GSTM1 Null vs. Present; 1.04 (0.92-1.17) and P ( z-test) = 0.56 for G carriers vs. AA for GSTP1 Ile105Val; 0.88 (0.70-1.11) and P ( z-test) = 0.28 for T carriers vs. CC for GSTP1 Ala114Val]. In contrast, Ser allele of NQO1 Ser187Pro might be a modest risk factor for CRA development [1.19 (1.06-1.33) and P ( z-test) = 0.003 for Ser carriers vs. Pro/Pro]. To get more precise evidences, adjusted ORs (95%CI) for EPHX1 Tyr113His, His139Arg, GSTP1 Ile105Val and NQO1 Ser187Pro were also calculated based on adjusted ORs (95%CIs) reported in primary studies. The results still indicated that EPHX1 Tyr113His, His139Arg and GSTP1 Ile105Val were not associated with CRA risk except for NQO1 Ser187Pro. When subgroup analyses were performed for population-based case-control studies or studies in HWE for EPHX1 Tyr113His and His139Arg, and NQO1 Ser187Pro polymorphisms, the results were persistent. Although with modest limitations and biases, this metaanalysis suggests that EPHX1 Tyr113His and His139Arg, GSTT1, GSTM1, GSTP1 Ile105Val and Ala114Val polymorphisms may be not risk factors for CRA development, while Ser allele of NQO1 Ser187 Pro may be a modest risk factor for CRA development, and may be used with other genetic markers for screening CRA in the future.
