Effect of RORC inhibitor on HIF-1α and VEGF in nasal mucosa of allergic rhinitis of mice / 中华耳鼻咽喉头颈外科杂志

Objective@#To investigate the effects of the retinoic acid receptor related orphan C (RORC) inhibitor (SR1001) on the expression changes of proteins of hypoxia induced factor (HIF-1α) and vascular endothelial growth factor (VEGF) in the nasal mucosa of mice with allergic rhinitis (AR) model.@*Methods@#Thirty BALB/c were randomly divided into normal group, AR model group and RORC inhibitor group, 10 mice each group. AR model of mice was established by ovalbumin (OVA) sensitization method. RORC inhibitor group was given intraperitoneal injection of SR1001 (25 mg/kg), while AR model group intraperitoneal injection of the same volume of 0.9% normal saline. The symptom score of the mice was determined every weekend after administration. The pathological morphological changes in the nasal mucosa tissue obtained from anesthetized mice were observed by light microscope. The expression of HIF-1α and VEGF protein were detected by immunohistochemistry. IFN-γ, IL-17, and sIgE in the serum were detected by ELISA and the expression of HIF-1α and VEGF in the nasal mucosal tissue of the mice were measured by Western blot. One-way ANOVA was used for inter-group comparison. LSD method was used for inter-group comparison with equal variance, and Dunnett T3 method for inter-group comparison with unequal variance. P<0.05 was considered statistically significant.@*Results@#The AR model was successfully established. Compared with the model group, the RORC inhibitor group significantly reduced the symptom score of AR mice (4.02±0.97 vs 8.50±1.76, t=7.050, P<0.01). The damaged mucosal epithelium appeared to be improved, the glands and dilated ducts tended to be normal, the mast goblet cells significantly reduced, and the infiltration of inflammatory cells in the inherent mucosa reduced. Meanwhile, the content of IL-17 and sIgE in serum decreased [(25.10±4.11) ng/ml vs (42.56±5.98) ng/ml, (0.875±0.244) ng/ml vs (1.982±0.365) ng/ml, t value was 14.141, 10.275, respectively, all P<0.01] and the content of IFN-γ increased [(61.32±8.83) pg/ml vs (38.94±5.97) pg/ml, t=8.133, P<0.01]. The expression of HIF-1α and VEGF protein in the nasal mucosal tissues of AR mice significantly reduced (0.92±0.08 vs 1.67±0.31, 1.12±0.21 vs 2.54±0.46, t value was 7.408, 8.880, respectively, all P<0.01).@*Conclusion@#The RORC inhibitor has the therapeutic effect on AR by changing the content of inflammatory factors in AR mice and reducing the expression level of HIF-1α and VEGF in the nasal mucosa.

Circadian Polymorphisms in Night Owls, in Bipolars, and in Non-24-Hour Sleep Cycles

People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness-eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and "eveningness" were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression.

Effect of CD40 siRNA on T helper lymphocyte-17 cells and interleukin-17, interleukin-23 in rats with experimental autoimmune myocarditis / 中华实用儿科临床杂志

Objective To investigate the effect of CD40siRNA on the pathologic changes and T helper lymphocyte (Th)-17 cells of myocardium and IL-17,IL-23 of serum in rats with experimental autoimmune myocarditis (EAM).Methods Forty 6-8 week old healthy male Lewis rats with body weight of 185-210 g were divided into EAM group,CD40siRNA group,siRNA group,and normal control group randomly,with 10 rats in each group.The rats in EAM group,CD40siRNA group and siRNA group were induced by immunization with cardiac C protein and completed Freund adjuvant in double foot pads.The rats in normal control group were injected with PBS buffer in double foot pads.On the 8th day after immunization,the rats in CD40siRNA group were injected with CD40 siRNA expression vector,and the rats in siRNA group were injected with siRNA expression vector.The rats were sacrificed on day 21 after inoculation.The histopathologic changes were observed by light microscope and the myocardial histopathology scores were calculated.The expression of RORC mRNA of myocardium was detected by real-time quantitative polymerase chain reaction (RTPCR).Enzyme linked immunoabsorption assay was used to determine the serum level of IL-17 and IL-23.Results Compared with EAM group,the myocardial histopathology score(2.34 ±0.60 vs 3.40 ±0.35,P ＜0.05),the expression ofRORC mRNA(2.13 ±0.28 vs 2.93 ±0.36,P ＜0.05) and the serum level of IL-17 (114.38 ± 8.29 vs 148.70 ± 5.04,P ＜ 0.05) and IL-23 (107.00 ± 7.69 vs 136.98 ± 23.16,P ＜ 0.05) were significantly lower in CD40 siRNA group.Conclusions It is suggested that CD40 siRNA expression vector might reduce myocardial injury by inhibiting Th-17 activation and down-regulating the expression of IL-17 and IL-23.

Expression of orphan nuclear receptor RORC in rat alveolar macrophages during sepsis and regulation mechanism / 临床儿科杂志

Objective To detect the expression of orphan nuclear receptor RORC gene and the level of serum interleukin-17 in acute lung injury (ALI) rats, and to explore the effects and possible regulation mechanisms of helper T lymphocyte 17 (Th17) in the ALI.Methods Twenty four SD male rats were randomly assigned to three groups, control group, model group, and pyrrolidine dithiocarbamates (PDTC) prevention group.The rats in model group and PDTC prevention group were intravenously injected LPS (6 mg/kg) for inducing ALI.The PDTC prevention group had been intraperitoneally injected PDTC (120 mg/kg) thirty minutes before LPS injection.All rats were killed twelve hours after LPS injecttion.The lung wet/dry weight ratio was measured.Lung pathologic tissue scored after hematoxylin-eosin (HE) stain.The expression of alveolar macrophages (AM) nuclear factor-KBP65 (NF-κBP65) was detected by immunohistochemistry.The level of serum IL-17 was detected by ELISA method.The expression of AM orphan nuclear receptor RORC gene was determined by SYBR Green Ⅰ real-time polymerase chain reaction.Results Compared with control group.the lung wet/dry weight ratio.lung pathologic tissue score, the expression of AM NF-κBP65.the level of serum IL-17 and the expression of AM orphan nuclear receptor RORC gene were significantly increased (P < 0.05).However, compared with model group, these changes were prevented in PDTC prevention group.Conclusions Th17 might participate in the pathological process of ALI.Activation of NF-кB might influence RORC gene expression, induce Th17 differentiation, and elevate the level of serum IL-17.