Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common disease and has been increasing in recent years. To date, no FDA-approved drug specifically targets NAFLD. Methods: The terms "Non-alcoholic Fatty Liver Disease" and "NAFLD" were used in a search of ClinicalTrials.gov on August 24, 2023. Two evaluators independently examined the trials using predetermined eligibility criteria. Studies had to be interventional, NAFLD focused, in Phase IV, and completed to be eligible for this review. Results: The ClinicalTrials.gov database was searched for trials examining pharmacotherapeutics in NAFLD. The search revealed 1364 trials, with 31 meeting the inclusion criteria. Out of these, 19 were finalized for evaluation. The dominant intervention model was Parallel. The most prevalent studies were in Korea (26.3%) and China (21.1%). The most common intervention was metformin (12.1%), with others like Exenatide and Pioglitazone accounting for 9.1%. Conclusion: Therapeutics used to manage NAFLD are limited. However, various medications offer potential benefits. Further investigations are definitely warranted.

Molecular characterization and phylogenetic relationships among Rhynchophorus sp. haplotypes in Makkah Al-Mukarramah Region-KSA.

The study aims at detecting and characterizing haplotypes of red palm weevil (RPW) Rhynchophorus sp. in the Western region of Saudi Arabia based on the cytochrome oxidase subunit I (COI) gene sequence. The results indicated the occurrence of 17 nucleotide substitutions, of which three were nonsynonymous (NS). These three NS substitutions resulted in the variation in amino acid sequence in three positions, out of 133. These amino acids are isoleucine/valine, glycine/serine, and arginine/histidine. Based on the chemical properties of the cytochrome C oxidase (COX) enzyme, it is likely that the change at the first position has no effect, while changes at the other two positions can affect the chemical properties of the enzyme. At the three-dimensional (3D) level, the first two positions exist at the border or inside loop 3-4 of the enzyme, while the third position exists inside loop 4-5. These two loops influence the folding pattern of the enzyme, thus, likely affecting the function of the enzyme. However, it is unlikely that variations in the three positions will affect the binding ability of the heme group, which promotes the action of the COX enzyme in the electron transport chain. Variations in chemical properties and 3D structure of COX enzyme might be an evolutionary process (positive selection) that promotes in-time and in-site adaptation to the insect. In conclusion, this study can be helpful in pest management programs and in tracing RPW geographic spread and migration in Saudi Arabia.

Effect of neat and binary vehicle systems on the solubility and cutaneous delivery of piperine.

Vitiligo is a skin disease characterized by depigmentation disorders due to lack of melanin production. Piperine, an alkaloid extracted from black piper, is active in melanocytes proliferation. To achieve this, the drug has to reach the melanocytes which exist in the deep layer of the epidermis. Higher drug concentration can be obtained after application of optimized formulation to skin. Accordingly, the aim of this work is to investigate the effect of vehicles on skin penetration of piperine as the first step in development of optimized formulation. The tested vehicles include ethanol (Eth), propylene glycol (PG), polyethylene glycol 400 (PEG), and oleic acid (OA) and their combinations. Water was used as the control and skin permeation was monitored using rabbit ear model skin. The highest piperine solubility (48.6 mg/ml) and flux (40.8 µg/cm2 h) was achieved by Eth and the lowest piperine flux (1.17 µg/cm2 h) was reported for PEG. PG and OA showed piperine flux values comparable to that of the control. Among different combination systems, Eth-OA (75:25) binary system had the highest piperine flux (59.3 µg/cm2 h) followed by Eth-OA (50:50) (32.3 µg/cm2 h) and PG-OA (90:10) (22.7 µg/cm2 h). The study thus introduced a vehicle system as the first step in the development of topical formulation of piperine.