UDP glucuronosyltransferase (UGT) 1A6 is a major isoform in human liver that glucuronidates numerous drugs, toxins, and endogenous substrates with high interindividual variability. The molecular basis for this variability remains unknown, although it likely involves genetic and environmental factors. Phenotypegenotype studies were conducted using a well characterized human liver bank (n ϭ 54) and serotonin glucuronidation as a UGT1A6-specific phenotype marker. A positive moderate-toheavy alcohol use history (Ͼ14 drinks per week) was the only demographic factor examined that correlated with phenotype and was associated with 2-fold higher serotonin glucuronidation (p Ͻ 0.001), UGT1A6 protein content (p ϭ 0.004), and UGT1A6 mRNA content (p ϭ 0.025). UGT1A6 gene resequencing identified three nonsynonymous polymorphisms (S7A, T181A, and R184S) in exon 1 and eight novel polymorphisms in the 5Ј-regulatory region (to Ϫ2052 base pairs). S7A was in complete linkage disequilibrium with three 5Ј-regulatory region polymorphisms (Ϫ1710c3g, Ϫ1310del5, and Ϫ652g3a). Initial univariate analyses did not identify any significant phenotype-genotype associations. However, in livers without substantial alcohol exposure, 50% lower UGT1A6 mRNA levels (p ϭ 0.026) were found in carriers of the linked S7A-enhancer polymorphisms compared with noncarriers but without significant effect on UGT1A6 protein content or glucuronidation activities.
Since the beginning of the 21st century, several viral outbreaks have threatened humankind and posed a new challenge to the modern healthcare system. The recent outbreak in Wuhan (December 2019), China, represents a beta coronavirus classified as novel Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) which belongs to the Coronaviridae family. Novel SARS-CoV-2 represents a significant similarity with previous coronaviruses such as SARS-CoV in 2002, China and MERS-CoV in 2015, Middle East. However, preliminary research investigations have shown the novel SARS-CoV-2 evolved with several mutations and developed the capacity to cross the species, i.e., animal to human. The initial findings have shown that spike proteins are vital molecules target hACE2 receptor for its attachment and entry into cells. After successful entry virus primarily focuses on respiratory airway cell lines and triggers a massive immune response leading to mucus generation. In severe conditions, the virus is capable of forcing viral pneumonia leading to the collapse of the respiratory system, i.e., COVID19. So far, there is a lack of immunity against the virus in humans. At the same in the absence of therapeutic interventions, many countries experienced high mortality, such as the United States, European countries, i.e., Italy, Spain, France, and the United Kingdom. The vaccine development is underway and experiencing challenges, as many reports demonstrated genetic variations in viral genome and proteins as well. The present study provides a complete comprehensive overview of the novel SARS-CoV-2 outbreak, human transmission, and global spread.
Context. Poly(beta-amino ester) (PBAE) with its pH sensitiveness and Poly(lactic-co-glycolic acid) (PLGA) with huge DNA cargo capacity in combination prove to be highly efficient as DNA delivery system. Objective. To study the effectiveness of novel synthesized PBAE polymer with PLGA blend at different ratios in DNA vaccine delivery. Methods. In the present study, multifunctional polymer blend microparticles using a combination of PLGA and novel PBAE polymers A1 (bis(3-(propionyloxy)propyl)3,3′-(propane-1,3-diyl-bis(methylazanediyl))dipropanoate) and A2 (bis(4-(propionyloxy)butyl)3,3′-(ethane-1,2-diyl-bis(isopropylazanediyl))dipropanoate) at different ratios (85 : 15, 75 : 25, and 50 : 50) were prepared by double emulsion solvent removal method. The microparticles were characterized for cytotoxicity, transfection efficiency, and DNA encapsulation efficiency. Result. It was evident from results that among the microparticles prepared with PLGA/PBAE blend the PLGA : PBAE at 85 : 15 ratio was found to be more effective combination than the microparticles prepared with PLGA alone in terms of transfection efficiency and better DNA integrity. Microparticles made of PLGA and PBAE A1 at 85 : 15 ratio, respectively, were found to be less toxic when compared with microparticles prepared with A2 polymer. Conclusion. The results encourage the use of the synthesized PBAE polymer in combination with PLGA as an effective gene delivery system.
The seed kernels of Sesamum indicum L. (family: Pedaliaceae) were extracted with ethanol and yield of components determined by Gas Chromatography/Mass Spectrometry (GC/MS). The free radical scavenging activities of ethanolic extract against1, 1-Diphenyl-2-picrylhydrazyl (DPPH) were determined by UV spectrophotometer at 517 nm. Phytochemical screening revealed the presence of numerous bioactive compounds including steroids, phenolic, terpenoids, fatty acids and different types of ester compounds. The ethanolic extract was purified and analyzed by GC MS.The prevailing compounds found in ethanolic extract were Carvacrol (0.04%),Sesamol (0.11%), 4-Allyl-2-methoxy-phenol(0.04%),Palmitic acid (1.08%), cis-9-Hexadecenal (85.40%), Lineoleoyl chloride (0.52%), Palmitic acid β-monoglyceride (0.40%), Dihydro-aplotaxene (0.61%), Oleoyl chloride (1.11%), (+)-Sesamin (4.73%), 1,3-Benzodioxole, 5-[4-(1,3-benzodioxol-5-yloxy)tetrahydro-1 H,3 H-furo [3,4-c]furan-1-yl], [1 S-(1,3,4,6α.), (2.01%)], 6-Nitrocholest-5-en-3-yl acetate (0.22%), Ergost-5-en-3β-ol (2.35%) and 24-Propylidenecholesterol (0.16%). The presence ofsaturated and unsaturated fatty acids in ethanolicextract justifies the use of this plant to treat many ailments in folk and traditional medicine. Ethanolic extract have shown significant antioxidant activity(IC120.38±2.8 µg/ml). The presence of phenolic (Sesamol), lignin (Sesamin) compounds and unsaturated fatty acids are reported as possible contributor for antioxidantactivity of seed extract.
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