Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK-3ß/TTBK1 pathway and decreasing Tau hyperphosphorylation in high-fat diet- streptozocin rat model.

The American Diabetes Association guidelines (2021) confirmed the importance of raising public awareness of diabetes-induced cognitive impairment, highlighting the links between poor glycemic control and cognitive impairment. The characteristic brain lesions of cognitive dysfunction are neurofibrillary tangles (NFT) and senile plaques formed of amyloid-ß deposition, glycogen synthase kinase 3 beta (GSK3ß), and highly homologous kinase tau tubulin kinase 1 (TTBK1) can phosphorylate Tau proteins at different sites, overexpression of these enzymes produces extensive phosphorylation of Tau proteins making them insoluble and enhance NFT formation, which impairs cognitive functions. The current study aimed to investigate the potential contribution of liraglutide and pramlintide in the prevention of diabetes-induced cognitive dysfunction and their effect on the PI3K/AKT/GSK-3ß/TTBK1 pathway in type 2 diabetic (T2D) rat model. T2D was induced by administration of a high-fat diet for 10 weeks, then injection of a single dose of streptozotocin (STZ); treatment was started with either pramlintide (200 µg/kg/day sc) or liraglutide (0.6 mg/kg/day sc) for 6 weeks in addition to the HFD. At the end of the study, cognitive functions were assessed by novel object recognition and T-maze tests. Then, rats were sacrificed for biochemical and histological assessment of the hippocampal tissue. Both pramlintide and liraglutide treatment revealed equally adequate control of diabetes, prevented the decline in memory function, and increased PI3K/AKT expression while decreasing GSK-3ß/TTBK1 expression; however, liraglutide significantly decreased the number of Tau positive cells better than pramlintide did. This study confirmed that pramlintide and liraglutide are promising antidiabetic medications that could prevent associated cognitive disorders in different mechanisms.

Interleukin-10 and Interferon Gamma Gene Polymorphisms and Hepatitis C Virus-Related Liver Cirrhosis Risk.

The aim of the study was to evaluate the association between the gene polymorphisms in interleukin-10 (IL-10) and interferon gamma (IFN-γ) genes with susceptibility and severity of hepatitis C virus (HCV) infection among Egyptian patients. Interleukin-10 -592 A/C, -1082 G/A and IFN-γ +874 T/A genotypes were determined in 100 chronic HCV patients and 50 healthy controls using restriction fragment length polymorphism (RFLP) and the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) respectively. IL-10 -592 A/C polymorphism genotyping revealed that the frequency of CC genotype was significantly higher in chronic HCV patients than in controls (58% versus 30%, P < 0.05). Regarding IL-10 -1082 G/A polymorphism genotyping, a higher frequency of GG genotype was found in chronic HCV patients compared to controls (31% versus 10%, P < 0.05). IFN-γ +874 T/A genotyping showed that TT genotype was significantly higher in chronic HCV participants than controls (31% versus 18%, P < 0.05), while a higher frequency of T allele was found in cirrhotic patients compared to noncirrhotic patients (P < 0.05). Our observations suggested that IL-10 -592 A/C, -1082 G/A, and IFN-γ +874 T/A polymorphisms had a strong association with susceptibility to HCV infection. However, no significant association was observed between the cytokines (IL-10 and IFN-γ) genotypes profile and HCV-liver cirrhosis risk in the studied population, except for the high frequency of IFN-γ +874 T allele in cirrhotic patients.