The efficacy and underlying mechanism of phosphodiesterase- 5 inhibitors in preventing cognitive impairment and Alzheimer pathology: A systematic review of animal studies.

BACKGROUND: Alzheimer disease (AD) initially presents with cognitive decline that affects the affected individual's daily activities. Cognitive decline reversal represents an important medical need, where Phosphodiesterase-5 inhibitors (PDE-5Is) might play a role. AIM: This systematic review was performed to verify the efficacy of PDE-5Is in preventing cognitive impairment and to elucidate the underlying mechanism. METHODS: Preclinical animal studies assessing the efficacy of PDE-5Is in preventing cognitive impairment and pathological changes by measuring Aß-42 ß42 and p-Tau were included in the analysis. CAMARADES Checklist was used to assess study quality. Further, various signaling pathways in different studies were examined. RESULTS AND OUTCOMES: Data of behavioral tests were extracted and a meta-analysis was conducted. Fifteen animal trials met the inclusion criteria, and all reported the prevention of cognitive deficits by PDE-5Is in Alzheimer's disease. A significant effect of PDE-5Is in increasing the time spent in the target quadrant was reported in four of seven studies using the water maze. Four studies showed significant improvement in contextual fear memory freezing time, and three studies showed improvement in the 14 unit maze number of errors. CONCLUSIONS: Cognitive decline in preclinical AD finds tauopathy has a more impact than Aß-42. This systematic review showed that PDE-5 inhibitors might help prevent cognitive impairment in AD, and while its mechanism of action is non-related to Aß-42, it might include decrease p-Tau, increase CREB and BDNF or suppressing apoptosis and inflammation. However, the efficacy of PDE-5 inhibitors in preventing cognitive impairment remains unclear due to various limitations, such as the small number of included studies, the high risk of bias, the lack of an integrated study design, and low reporting quality.

Clinical significance of miRNA-autophagy transcript expression in patients with hepatocellular carcinoma.

AIM: This study integrates autophagy transcripts miRNAs expression based on bioinformatic analysis followed by clinical validation. METHODOLOGY: Cellular jun proto-oncogene mRNA, LAMP2 mRNA, miR-16 and miR-146a level were investigated in the serum and tissue of patients with hepatocellular carcinoma (HCC), chronic hepatitis C and healthy volunteers by quantitative real-time PCR. The prognostic power of this serum RNA panel was explored. RESULTS: The expression of serum cellular jun proto-oncogene mRNA, LAMP2 mRNA, miR-16 and miR-146a were positive in 85.1, 94, 97.1 and 84.2% HCC patients, respectively and they were correlated with tissue levels. Our results suggested that the chosen panel is an independent prognostic factor for survival in patients with HCC. CONCLUSION: The current work provides four RNA-based biomarker panel for HCC diagnosis and prognosis.