Overexpressed HspB6 Underlines a Novel Inhibitory Role in Kainic Acid-Induced Epileptic Seizure in Rats by Activating the cAMP-PKA Pathway.

Epilepsy is a commonly occurring neurological disease that has a large impact on the patient's daily life. Phosphorylation of heat shock protein B6 (HspB6) has been reported to protect the central nervous system. In this investigation, we explored whether HspB6 played a positive effect on epilepsy with the involvement of the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway. The epileptic seizure was induced in rats by intraperitoneal injection of kainic acid (KA). The extent of HspB6 phosphorylation and expressions of HspB6, PKA, and inflammatory factors TNF-α, IL-1ß, and IL-6 were quantified along with neuronal apoptosis. To further understand the regulatory mechanism of the HspB6 in the hippocampus, we altered the expression and the extent of HspB6 phosphorylation to see whether the cAMP-PKA pathway was inactivated or not in hippocampal neurons of rats post KA. Results showed that HspB6 was poorly expressed, resulting in the inactivation of the cAMP-PKA pathway in rats post KA, as well as an aggravated inflammatory response and hippocampal neuronal apoptosis. HspB6 overexpression and the cAMP-PKA pathway activation decreased the expression of inflammatory factors and inhibited hippocampal neuronal apoptosis. Additionally, HspB6 phosphorylation further augments the inhibitory effects of HspB6 on the inflammatory response and hippocampal neuronal apoptosis. The cAMP-PKA pathway activation was found to result in increased HspB6 phosphorylation. HspB6 decreased apoptosis signal-regulating kinase 1 (ASK1) expression to inhibit inflammatory response and hippocampal neuronal apoptosis. Collectively, our findings demonstrate that activation of the cAMP-PKA pathway induces overexpression and partial phosphorylation of HspB6 lead to the inhibition of ASK1 expression. This in turn protects rats against epilepsy and provides a potential approach to prevent the onset of epileptic seizure in a clinical setting.

Changes in Levels of Homocysteine and C-Reactive Protein in Patients with Alzheimer's Disease and Their Correlation with Cognitive and UPDRS Functions.

Objective: To investigate the changes in the levels of homocysteine (Hcy) and C-reactive protein (CRP) in patients with Alzheimer's disease (AD) and analyze their correlation with cognitive and UPDRS functions. Methods: A total of 50 patients with AD admitted to our hospital from January 2020 to March 2022 were selected into the research group, and 50 healthy subjects were selected as the control group. The levels of Hcy and CRP of the two groups were analyzed, and the patients' cognitive functions were evaluated with the Mini-Mental State Examination (MMSE) score and UPDRS function scoring. The correlation between the changes in levels of Hcy and CRP, and cognitive and UPDRS functions in the two groups was compared and analyzed. Results: The levels of Hcy and CRP of the research group were higher than those of the control group, with statistical significance (P < 0.05). The following were evaluated for the scoring of patients' cognitive functions in the research group: orientation, attentional computation, short-term memory, language ability, visuospatial ability, instant memory, and MMSE total score, all of which were lower than those in the control group, with statistical significance (P < 0.05). UPDRS I, UPDRS, UPDRS, and total UPDRS score in the research group were higher than those in the control group, with statistical significance (P < 0.05). In the research group, the higher the Hcy level, the lower the MMSE score, with a negative correlation (P < 0.05), and the higher the Hcy level, the higher the UPDRS score, with a positive correlation (P < 0.05). And, the higher the CRP level, the lower the MMSE score, with a negative correlation (P < 0.05); the higher the CRP level, the higher the UPDRS score, with a positive correlation (P < 0.05). Conclusion: Compared with the health subject group, the levels of Hcy and CRP were higher in patients with AD, and their changes had a negative correlation with cognitive functions in patients with AD, and a positive correlation with UPDRS in patients with AD, with high clinical values in evaluating cognitive and UPDRS functions.

miR-3175 and miR-134 affect proliferation, invasion and apoptosis of glioma cells through PI3K/AKT signaling pathway.

PURPOSE: This study aimed to investigate the expressions of microRNA (miR)-3175 and miR-134 in gliomas and their effects on the proliferation and invasion of U251 glioma cells. METHODS: Tumor tissues of 42 patients with glioma and non-tumor tissues of 10 patients with severe craniocerebral injury were collected. These patients were diagnosed in Jinan City People's Hospital from March 2010 to April 2012. qRT-PCR was used to detect differences of miR-3175 and miR-134 expressions. Kaplan-Meier method was used to generate survival curves and Log-rank test to evaluate differences between miR-3175, miR-134 and 5-year survival of the patients. Western blot was used to detect levels of p-PI3K in PI3K signaling pathway. RESULTS: Proliferative activity of the cells in miR-3175 mimic group and miR-control group at different time points was significantly better than that of the cells in miR-3175 inhibitor group (p<0.05). The proliferative activity of the cells in miR-134 mimic group and miR-control group at different time points was significantly worse than that of the cells in miR-134 inhibitor group (p<0.05). Apoptosis rate of the cells in miR-3175 mimic group and miR control group was significantly lower than that of the cells in miR-3175 inhibitor group (p<0.05). Apoptosis rates of the cells in miR-134 mimic group and miR-control group were significantly higher than that of the cells in miR-134 inhibitor group (p<0.05). CONCLUSION: Downregulating expression of miR-3175 or facilitating expression of miR-134 could inhibit the proliferative and invasive activity of glioma cells and facilitate their apoptosis by inhibiting the activation of PI3K signaling pathway.

Thioredoxin is a novel diagnostic and prognostic marker in patients with ischemic stroke.

Serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity, was recognized as an oxidative-stress marker. The purpose of this study was to investigate the potential diagnostic and prognostic role of TRX in Chinese patients with acute ischemic stroke (AIS). From January 1, 2012, to December 31, 2013, all patients with first-ever acute ischemic stroke were recruited to participate in the study. Serum levels of TRX were assayed with solid-phase sandwich ELISA, and severity of stroke was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score on admission. Short-term functional outcome was measured by a modified Rankin scale (mRS) 3 months after admission. Multivariate analyses were performed using logistic regression models. We found the serum TRX reflected the disease severity of AIS. There was a significant positive association between serum TRX levels and NIHSS scores (r= 0.476, P<0.0001). Based on the ROC curve, the optimal cutoff value of serum TRX levels as an indicator for auxiliary diagnosis of AIS was projected to be 11.0 ng/ml, which yielded a sensitivity of 80.3% and a specificity of 73.7%, with the area under the curve at 0.807 (95% CI, 0.766-0.847). Elevated TRX (≥ 20.0 ng/ml) was an independent prognostic marker of short-term functional outcome [odds ratio (OR) 9.482 (95% CI, 3.11-8.15) P<0.0001; adjusted for NIHSS, other predictors and vascular risk factors] in patients with AIS. TRX improved the area under the receiver operating characteristic curve of the NHISS score for functional outcome from 0.722 (95% CI, 0.662-0.782) to 0.905 (95% CI, 0.828-0.962; P<0.0001). Our study demonstrated that elevated serum TRX level at admission was a novel diagnostic and prognostic marker in patients with acute ischemic stroke.