CTLA-4 CT60 (rs3087243) polymorphism and autoimmune thyroid diseases susceptibility: a comprehensive meta-analysis.

OBJECTIVE: To determine whether the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) CT60 polymorphism (rs3087243) confers susceptibility to autoimmune thyroid disease (AITDs). METHODS: A meta-analysis was performed using: (1) allelic contrast, (2) recessive model and (3) dominant model. Electronic search of PubMed, Medline and Chinese National Knowledge Infrastructure (CNKI) was conducted to select studies. RESULTS: Finally, a total of 20 separate studies were available for the current meta-analysis: Graves' disease (GD): 18 studies including 1 Iranian, 6 Caucasian and 11 Asian populations; Hashimoto's thyroiditis (HT): seven studies including one Iranian, three Caucasian and three Asian populations. A significant association was found between the CTLA-4 CT60 polymorphism (rs3087243) and GD, with regard to comparisons between allele and genotype frequencies (all p < 0.001). After stratification by ethnicity, significant relationships were consistently identified both in Caucasian and Asian populations. Furthermore, the association between this allelic variant and HT risk was also found in overall and Asian populations (OR: 1.26, 95% CI: 1.10-1.44; OR: 1.45, 95% CI: 1.19-1.76, respectively). CONCLUSION: Taken together, our study suggested that the CT60 polymorphism (rs3087243) in CTLA-4 gene might confer susceptibility to the AITDs (GD/HT).

Effects of electroacupuncture on rats with cognitive impairment: An iTRAQ-based proteomics analysis.

OBJECTIVE: The study explores the effects of electroacupuncture (EA) at the governing vessel (GV) on proteomic changes in the hippocampus of rats with cognitive impairment. METHODS: Healthy male rats were randomly divided into 3 groups: sham, model and EA. Cognitive impairment was induced by left middle cerebral artery occlusion in the model and EA groups. Rats in the EA group were treated with EA at Shenting (GV24) and Baihui (GV20) for 7 d. Neurological deficit was scored using the Longa scale, the learning and memory ability was detected using the Morris water maze (MWM) test, and the proteomic profiling in the hippocampus was analyzed using protein-labeling technology based on the isobaric tag for relative and absolute quantitation (iTRAQ). The Western blot (WB) analysis was used to detect the proteins and validate the results of iTRAQ. RESULTS: Compared with the model group, the neurological deficit score was significantly reduced, and the escape latency in the MWM test was significantly shortened, while the number of platform crossings increased in the EA group. A total of 2872 proteins were identified by iTRAQ. Differentially expressed proteins (DEPs) were identified between different groups: 92 proteins were upregulated and 103 were downregulated in the model group compared with the sham group, while 142 proteins were upregulated and 126 were downregulated in the EA group compared with the model group. Most of the DEPs were involved in oxidative phosphorylation, glycolipid metabolism and synaptic transmission. Furthermore, we also verified 4 DEPs using WB technology. Although the WB results were not exactly the same as the iTRAQ results, the expression trends of the DEPs were consistent. The upregulation of heat-shock protein ß1 (Hspb1) was the highest in the EA group compared to the model group. CONCLUSION: EA can effect proteomic changes in the hippocampus of rats with cognitive impairment. Hspb1 may be involved in the molecular mechanism by which acupuncture improves cognitive impairment.

Wide Pulse Width Electroacupuncture Ameliorates Denervation-Induced Skeletal Muscle Atrophy in Rats via IGF-1/PI3K/Akt Pathway.

OBJECTIVE: To evaluate the effect of the pulse width of electroacupuncture (EA) in the treatment of denervation-induced skeletal muscle atrophy in rats and examine the role of insulin-like growth factor 1 (IGF-1)/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway during EA. METHODS: Sciatic nerve functional index (SFI), muscle wet weight and the cross-sectional area (CSA) of the gastrocnemius muscle were analyzed after treatment in model rats with EA of various pulse widths (0.5, 50, 100 and 200 ms). The apoptosis index (AI) and paired box (PAX)3 and PAX7 protein expression were also determined. Further, the mRNA and protein expressions of components of IGF-1/PI3K/Akt pathway and their downstream targets were determined, along with the inhibiting effect of the pathway with a PI3-specific inhibitor. RESULTS: EA with a pulse width of 200 ms was found to have the best effect with regard to increasing SFI, CSA and muscle weight, decreasing AI, and increasing the expression of PAX3 and PAX7. The IGF-1/PI3K/Akt pathway was found to be activated by denervation, although the downstream forkhead box O (FoxO) pathway was not suppressed by its activation. The PI3K/Akt pathway and its downstream molecule mammalian target of rapamycin (mTOR) were up-regulated further by EA to promote muscle protein synthesis. Meanwhile, the expressions of downstream FoxO and F-box protein 32 (ATROGIN-1) were down-regulated to reduce protein degradation. CONCLUSIONS: EA with 200-ms pulse width was found to have a more significant effect than 0.5-ms EA. The positive effects of EA disappeared after inhibition of the PI3K/Akt pathway.