Aim: To investigate the effect of ursodeoxycholic acid (UDCA) on the degree of steatosis, indicators of carbohydrate, lipid metabolism, body weight in patients with type 2 diabetes mellitus (DM) in combination with non-alcoholic fatty liver disease (NAFLD).
Materials and methods: A prospective cohort comparative study included 36 patients with DM and NAFLD. Patients received UDCA at a dose of 15 mg/kg/day for 6 months, and also followed the recommendations for lifestyle changes through diet and exercise. To compare the results obtained during the study, a control group of patients was recruited that met the criteria for inclusion in the study. The statistical analysis included an assessment of the normality of the distribution of quantitative indicators, followed by the determination of the mean values and standard deviation or medians and quartiles, depending on the nature of the distribution, the reliability coefficient was determined by the Student, by Wilcoxon. Statistical processing was carried out in the Statistica 10 program.
Results: According to the results of the study, a positive trend was noted in the change in the severity of fatty hepatosis. During the study, a statistically significant decrease in the level of ALT, AST was achieved in the group receiving UDCA (Ursofalk). The results of our study showed that the inclusion of UDCA (Ursofalk) in complex hypoglycemic therapy provides an additional improvement in carbohydrate metabolism. The obtained indicators in the course of the study demonstrate the positive effect of UDCA on weight loss. The greatest result was achieved in reducing waist, which is a positive prognostic factor in reducing the development and progression of NAFLD, diabetes and cardiovascular diseases. Positive changes were observed in relation to the lipid profile.
Conclusion: The study demonstrated the positive effect of the drug UDCA (Ursofalk) on reducing the degree of liver steatosis, on carbohydrate, lipid metabolism, body weight in patients with DM in combination with NAFLD.
Hepatitis E virus (HEV) is the main cause of acute hepatitis worldwide. HEV accounts for up to 30% mortality rate in pregnant women, with highest incidences reported for genotype 1 (G1) HEV. The contributing factors in adverse cases during pregnancy in women due to HEV infection is still debated. The mechanism underlying the pathogenesis of viral infection is attributed to different genomic component of HEV, i.e., open reading frames (ORFs): ORF1, ORF2, ORF3 and ORF4. Recently, ORF4 has been discovered in enhancing the replication of GI isolates of HEV through regulation of an IRES-like RNA element. However, its characterization through computational methodologies remains unexplored. In this novel study, we provide comprehensive overview of ORF4 protein's genetic and molecular characteristics through analyzing its sequence and different structural levels. A total of three different datasets (Human, Rat and Ferret) of ORF4 genomes were built and comparatively analyzed. Several non-synonymous mutations in conjunction with higher entropy values were observed in rat and ferret datasets, however, limited variation was observed in human ORF4 genomes. Higher transition to tranversion ratio was observed in the ORF4 genomes. Studies have reported the association of intrinsic disordered proteins (IDP) with drug discovery due to its role in several signaling and regulatory processes through protein-protein interactions (PPIs). As PPIs are potent drug target sources, thus the ORF4 protein was explored by analyzing its polypeptide structure in order to shed light on its intrinsic disorder. Pressures that lead towards preponderance of disordered-promoting amino acid residues shaped the evolution of ORF4. The intrinsic disorder propensity analysis revealed ORF4 protein (Human) as a highly disordered protein (IDP). Predominance of coils and lack of secondary structure further substantiated our findings suggesting its involvement in binding to ligand molecules. Thus, ORF4 contributes to cellular signaling processes through protein-protein interactions, as IDPs are targets for regulation to accelerate the process of drug designing strategies against HEV infections.