Apolipoprotein A-V gene therapy for disease prevention/treatment:a critical analysis

Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.

Comparative Analyses of the Efficacy of Dry and Fresh <i>Mangifera indica</i>Ethanolic Extracts on <i>E. coli</i>and <i>S. aureus</i>

Background: The need to identify and characterize new antimicrobial agents is important due to the increasing development of resistance by microorganisms to the existing antimicrobial agents. Aim: This study examined the efficacies of Mangifera indica on Escherichia coli and Staphylococcus aureus. Method: Three parts (leaf [L], root [R], and bark [B]) of the plant were analyzed. The extraction of the samples was performed by aseptically grinding the samples, dissolving in absolute ethanol, and filtering through whatman filter paper. The efficacy of the extracts bothsingle and combined was determined using agar well diffusion assay with gentamycin [10 μl] (E. coli) and vancomycin [30 μl] (S. aureus) as control antibiotics. Results: The higher concentration (C2 = 3.0 g/ml) showed more antibacterial effectiveness than the lower concentration (C1 = 1.5 g/ml) against both bacterial isolates with significant differences (P < 0.05) in all extracts except for single extracts (E. coli dry leaf extract;fresh bark extract), double extracts (S. aureus: dry and fresh leaf extracts) and triple extract (E. coli and S. aureus dry extracts). For the single extracts the bacteria has the following significant results: E. coli L (dry 6.3 ± 2.5 mm, fresh 14.7 ± 0.6 mm, P = 0.0050), R (dry 11.3 ± 1.5 mm, fresh 7.3 ± 1.5 mm, P = 0.0327);for S. aureus L (dry 7.0 ± 1.7 mm, fresh 11.0 ± 1.0 mm, P = 0.0257), R (dry 7.0 ± 2.0 mm, fresh 11.7 ± 1.5 mm, P = 0.0325), and B (dry 5.0 ± 1.0 mm, fresh 16.0 ± 1.0 mm, P = 0.0002). For the double extracts the bacteria has the following significant results: E. coli L + R (dry 15.7 ± 2.3 mm, fresh 1.7 ± 1.5 mm, P = 0.0070), R + B (dry 18.7 ± 1.5 mm, fresh 9.7 ± 1.5 mm, P = 0.0020), and L + B (dry 9.7 ± 1.5 mm, fresh 6.3 ± 0.6 mm, P = 0.0241);S. aureus L + R (dry 14.7 ± 1.5 mm, fresh 7.0 ± 1.0 mm, P = 0.0019), R + B (dry 15.3 ± 1.5 mm, fresh 11.7 ± 1.5 mm, P = 0.0424). For the triple extracts, the fresh leaves showed significantly higher levels of efficacy than the dry for both E. coli L + R + B (P = 0.0101) and S. aureus (P = 0.0307). The fresh extracts showed higher levels of efficacy than dry extracts against both bacteria for all the single and three combined conditions. Conclusions: Fresh extracts show better efficacies against E. coli while dry extracts show greater efficacies against S. aureus for both single and triple combined extracts. The reverse is true for double combined extracts.