Sepsis-associated encephalopathy (Sae) is characterized by neuronal apoptosis and changes in mental status. accumulating evidence has. indicated that dexmedetomidine is capable of protecting the brain against external stimuli and improving cognitive dysfunctions. The aim of the present study was to investigate the possible neuroprotective effects of dexmedetomidine on Sae and the role of heat-shock protein (Hsp)90/aKT signaling in an experimental model of sepsis. The Sae model was established by cecal ligation and perforation (clP) in vivo and lipopolysaccharide (lPS) treated hippocampal neuronal cultures in vitro. it was found that dexmedetomidine inhibited caspase-3, but increased the expression level ofBcl-2 in clP rats. clP rats also exhibited a decreased level of phosphorylated aKT Thr 308 and Hsp90, and their expression could be reversed by treatment with dexmedetomidine. additionally, application of dexmedetomidine increased cell survival and decreased neuronal apoptosis in vitro. Furthermore, the neuroprotective effects of dexmedetomidine could be reversed by 17-aaG (a Hsp90 inhibitor), or wortmannin (a Pi3K inhibitor). analysis of Tunel staining indicated that dexmedetomidine improved lPS-induced neuronal apoptosis, which could be eradicated by aKT short hairpin rna transfection, prazosin or yohimbine. Finally, dexmedetomidine ameliorated both the emotional and spatial cognitive disorders without alteration in locomotor activity. The present findings suggested that dexmedetomidine may protect the brain against Sae, and that the Hsp90/aKT pathway may be involved in this process.

This study investigated expression of serum miR-27b and miR-451 in patients with congenital heart disease associated pulmonary arterial hypertension (CHD-PAH), and analyzed the risk factors of CHD-PAH. A total of 114 patients with CHD admitted to the First Affiliated Hospital of the University of South China were recruited and allocated into a study group (61 patients with PAH) and a control group (53 patients without PAH). Reverse transcription-polymerase chain reaction (RT-PCR) was employed for the qualification of serum miR-27b and miR-451, and an automatic biochemical analyzer was used for the measurement of biochemical indexes in peripheral blood, and enzyme-linked immunosorbent assay (ELISA) for the detection of serum brain natriuretic peptide (BNP) and asymmetric dimethylarginine (ADMA). The patients with CHD-PAH showed higher serum miR-27b, BNP and ADMA but lower miR-451 than the controls. Serum miR-27b was positively correlated with mean pulmonary artery pressure (mPAP), BNP and ADMA, whereas serum miR-451 was negatively correlated with them. The combined detection of miR-27b and miR-451 was more valuable than a single detection in the diagnosis of CHD-PAH. Logistic regression analysis showed that ADMA, miR-27b, miR-451 and ventricular septal defect (VSD) were independent risk factors for CHD-PAH. In conclusion, miR-27b is highly expressed and miR-451 and the expression is low in patients with CHD-PAH. miR-27b and miR-451 are significantly correlated with BNP, ADMA, and the severity of the disease. The combination of miR-27b and miR-451 has high diagnostic value and can be used as a biomarker for the diagnosis and assessment of CHD-PAH. CHD-PAH is common in children with CHD, which poses a serious threat to the life and safety. At present, there are no effective methods for its early diagnosis and treatment. MicroRNAs (miRNAs, miRs) have been found to be closely related to the pathogenesis of CHD-PAH. In this study, miR-27b and miR-451 with differential expression in CHD-PAH were evaluated, and it was found that they were of great significance in the diagnosis and assessment of CHD-PAH.

Background: To investigate the effect and mechanisms of exogenous hydrogen sulfide in surgery-induced neuroinflammatory cognitive dysfunction. Methods: C57BL/6 J male mice (n = 140) were used and randomly divided into seven groups: the sham group, surgery group, GYY4137 group, L-NAME group, surgery+GYY4137 group, surgery +L-NAME group, and surgery+GYY4137 + L-NAME group. After the interventions, open field tests (OFT) and the Morris water maze (MWM) test were conducted to evaluate learning and memory abilities in the mice. ELISAs, nitrate reductase assays, and Western blots (WB) were conducted to evaluate interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and antioxidant enzyme superoxide dismutase (SOD) levels. Furthermore, the expression level of microglial marker ionized calcium binding adaptor molecule 1 (IBA) in the hippocampal CA1 and CA3 areas was detected by an immunohistochemical (IHC) assay and apoptotic cells were observed using terminal deoxynucleotidyl transferase dUTP end-labeling (TUNEL) staining kits. Results: We found that surgery induced neuroinflammatory cognitive dysfunction, oxidative stress, microglial activation, and cell apoptosis in the hippocampus. Moreover, following surgery, NO and iNOS levels were elevated in the hippocampus. Notably, all the effects caused by surgery were reversed by the H 2 S donor GYY4137 or the iNOS inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME). However, the combined application of GYY4137 and L-NAME was not superior to treatment with either agent alone and the effect of GYY4137 was similar to that of L-NAME. Conclusion: The long-acting hydrogen sulfide donor GYY4137 had an ability to reversed the cognitive deficits and inflammation caused by carotid artery exposure surgery. This implies that NO signaling pathways might participate in this process. These results indicate that exogenous H 2 S may be a promising therapy for POCD.