Ki20227 aggravates apoptosis, inflammatory response, and oxidative stress after focal cerebral ischemia injury.

The survival of microglia depends on the colony-stimulating factor-1 receptor (CSF1R) signaling pathway under physiological conditions. Ki20227 is a highly selective CSF1R inhibitor that has been shown to change the morphology of microglia. However, the effects of Ki20227 on the progression of ischemic stroke are unclear. In this study, male C57BL/6 mouse models of focal cerebral ischemic injury were established through the occlusion of the middle cerebral artery and then administered 3 mg/g Ki20227 for 3 successive days. The results revealed that the number of ionized calcium-binding adaptor molecule 1/bromodeoxyuridine double positive cells in the infarct tissue was reduced, the degree of edema was increased, neurological deficits were aggravated, infarct volume was increased, and the number of peri-infarct Nissl bodies was reduced. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in the peri-infarct tissue was increased. The expression levels of Bax and Cleaved caspase-3 were up-regulated. Bcl-2 expression was downregulated. The expression levels of inflammatory factors and oxidative stress-associated factors were increased. These findings suggested that Ki20227 blocked microglial proliferation and aggravated the pathological progression of ischemia/reperfusion injury in a transient middle cerebral artery occlusion model. This study was approved by the Animal Ethics Committee of Lanzhou University Second Hospital (approval No. D2020-68) on March 6, 2020.

Adequacy of health literacy and its effect on diabetes self-management: a meta-analysis.

This study evaluated the role of health literacy (HL) in the self-management of diabetes. A literature search was conducted in electronic databases and studies were selected using precise eligibility criteria. A meta-analysis was conducted to estimate the HL adequacy rate, factors affecting the adequacy of HL and correlations between HL and diabetes self-management variables. Thirty-three studies were included in the analysis. The HL adequacy rate was 67% (95% confidence interval (CI) 57, 76). Compared with patients with inadequate HL, patients with adequate HL were younger (mean difference -5.2 years; 95% CI -7.2, -3.2; P<0.00001), more likely to have a high school or higher level of education (odds ratio (OR) 8.39; 95% CI 5.03, 13.99]; P<0.00001) and were less likely to belong to a low-income group (OR 0.36; 95% CI 0.23, 0.56; P<0.00001). HL was positively correlated with self-monitoring (r=0.19; 95% CI 0.11, 0.27; P<0.00001), dietary and physical care (r=0.12; 95% CI 0.07, 0.18; P=0.009), diabetes knowledge (r=0.29; 95% CI 0.09, 0.45; P<0.001), self-efficacy (r=0.28; 95% CI 0.15, 0.41; P<0.00001), self-care (0.24; 95% CI 0.16, 0.31; P<0.00001), formal education (r=0.35; 95% CI 0.18, 0.53; P<0.00001) and social support (r=0.2; 95% CI 0.07, 0.33; P<0.00001). Patient age (r=-0.28; 95% CI -0.39, -0.17; P<0.00001) was inversely correlated with HL. In conclusion, 67% of diabetes patients had adequate HL, with a higher rate among better educated and higher income groups. HL had a statistically significant but weak positive correlation with diabetes self-management variables.

HDAC4 gene silencing alleviates epilepsy by inhibition of GABA in a rat model.

OBJECTIVES: Despite the availability of effective antiepileptic drugs, epileptic patients still suffer from intractable seizures and adverse events. Better control of both seizures and fewer side effects is needed in order to enhance the patient's quality of life. We performed the present study with an attempt to explore the effect that HDAC4 gene silencing would have on epilepsy simulated by model rats. Furthermore, the study made additional analysis on the relativity of the HDAC4 gene in regard to its relationship with the gamma-aminobutyric acid (GABA) signaling pathway. MATERIALS AND METHODS: Tremor rats were prepared in order to establish the epilepsy model. The rats would go on to be treated with si-HDAC4 in order to identify roles of the HDAC4 in levels of GABAARα1, GABAARα4, GAD65, GAT-1, and GAT-3. Finally, both electroencephalogram behavior and cognitive function of the rats following the treatment of si-HDAC4 were observed. RESULTS: Levels of the GABAARα1 and GABAARα4 showed an evident increase, while GAD65, GAT-1, and GAT-3 displayed a decline in the epilepsy rats treated with the aforementioned si-HDAC4 when compared with the epilepsy rats. After injection of si-HDAC4, the epilepsy rats presented with a reduction in seizure degree, latency and duration of seizure, amount of scattered epileptic waves, and occurrence of epilepsy, with an improvement in their cognitive function. CONCLUSION: The study highlighted the role that HDAC4 gene silencing played in easing the cases of epilepsy found in the model rats. This was shown to have occurred through the upregulation of both GABAARα1 and GABAARα4 levels, as well as in the downregulation of GAD65, GAT-1, and GAT-3 levels. The evidence provided shows that the HDAC4 gene is likely to present as a new objective in further experimentation in the treatment of epilepsy.