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Objective To study the preventive effect of microinsulin on cognitive dysfunction induced by sevoflurane inhalation anesthesia in rats and its possible mechanism. Methods Sixty newborn rats were randomly divided into control group (CON), insulin prevention low dose group (LIP), insulin prevention hihg dose group (HIP), and sevoflurane model group (MOD). The prevention group and the model group were induced by sevoflurane to construct rat cognitive dysfunction model. Morris water maze directional sailing test and space exploration test were used to evaluate the learning and memory function of rats; HE staining was used to observe the pathological morphological changes of hippocampus in rats; Flow cytometry was used to detect the hippocampus of rats cell apoptosis; Detection of rapamycin target protein (mTOR) and eukaryotic peptide chain elongation factor 2 (eEF-2) mRNA levels in hippocampus by RT-PCR; The expression levels of brain-derived neurotrophic factor (BDNF), post-synaptic dense protein-95 (PSD-95), synapsin- I, and calmodulin kinase II α (CaMK II α), mTOR and eEF-2 protein were detected by Western blotting. Results The result of the Morris water maze experiment showed that insulin significantly reduced the escape latency and swimming distance of rats, and increased the number of crossing platforms; Flow cytometry result showed that the insulin prevention group significantly inhibited the apoptosis of rat brain neurons, and the inhibition effect of high-dose insulin prevention group was more obvious; RT-PCR and Western blotting analysis found that the expression levels of mTOR and eEF-2 mRNA and proteins in the hippocampus of the model group increased significantly, while the expression levels of BDNF, PSD-95, synapsin- I, and CaMK II α proteins reduced significantly. The expression levels of mTOR and eEF-2 mRNA and proteins in the hippocampus of rats in the insulin prevention group decreased significantly, while the expression levels of BDNF, PSD-95, synapsin- I, and CaMK II α protein increased significantly. The difference was statistically significant (P < 0.05). Conclusion Trace insulin can increase the expression of synapse-related proteins in the hippocampus of cognitive dysfunction rats, reduce their mTOR and eEF-2 mRNA expression levels, and prevent sevoflurane-induced cognitive impairment in rats. The mechanism may be related to the regulation of mTOR-eEF-2 approach.
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Objective@#Schizophrenia is one of the most devastating neuropsychiatric disorders. Genetic epidemiological studies have confirmed that schizophrenia is a genetic disease. Genes promoting neurodevelopment may be potential candidates for schizophrenia. As an adaptor linking a number of tyrosine kinase receptors in multiple intracellular signaling cascades, Src homology 2 domain containing transforming protein 3 (SHC3) is a member of the Shc-like adaptor protein family, and expressed predominantly in the mature neurons of the central nervous system (CNS). In the present study, we aimed to investigate the association of SHC3 and schizophrenia. @*Methods@#An independent case-control association study was performed in a sample including 710 schizophrenia patients and 1314 healthy controls from a Northeast Chinese Han population. @*Results@#The allelic and genotypic association analyses showed that four SNPs in SHC3 significantly associated with schizophrenia (rs2316280, rs4877041, rs944485 and rs7021743). The haplotype composing of these four SNPs also showed significantly individual and global association with schizophrenia. @*Conclusion@#Our present results suggest SHC3 as a susceptibility gene for schizophrenia.
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OBJECTIVE@#To study the mechanism of naoxintong capsule (NXT) -inhibiting peripheral ischemic inflammation.@*METHODS@#Mice were randomly double-blindly divided into 3 groups: sham-operation group, model group and NXT group. Both model and NXT groups underwent the hind limb ischemia (HLI) surgery followed by oral gavage with saline or NXT, respectively, one hour after operation. Three days after operation, the percentages of neutrophils and macrophages in the gastrocnemius muscle were examined by flow cytomety and immunohistochemical method. The changes in gene and protein expressions induced by NXT were examined by real-time PCR and protein chip, respectively. The changes of signaling pathways were analyzed.@*RESULTS@#Compared with sham oparation and model groups, NXT could decrease the ratios of neutrophils and macrophages in gastrocnemius inflammation site (P＜0.01), and downregulate the mRNA expression of gene EMR1 (P＜0.01). NXT reduced the expression of TNF-α and IL-1β at both mRNA (P＜0.001) and protein levels (P＜0.05). The proteomic analysis showed that the use of NXT resulted in the expression changes of 13 proteins. The expression of 6 cytokines was increased, and the secretion of 7 proteins was upregulated. Besides, most of identified 13 proteins were involved in the function regulation of other immune cells.@*CONCLUSION@#NXT can significantly alleviate ischemia-induced peripheral inflammation by reducing the ratio of immune cells and altering the expression patterns of mRNA and protein. The expression changes provide theoretical guidance and the potential targets for the clinical use of NXT in the treatment of ischemia-induced peripheral inflammatory diseases.