Influenza A viruses: why focusing on M2e-based universal vaccines

The threat of highly virulent avian influenza, such as H5N1 and swine-origin H1N1 influenza viruses, bring out an urgent need to develop a universal influenza vaccine, which may provide cross-protection against different strain of influenza A viruses. The extra-domain of influenza M2 protein (M2e), which is almost completely conserved among all subtypes of influenza A viruses, is considered as a promising candidate target for the development of a broad-spectrum recombinant influenza A vaccine. The results of several preclinical studies with M2e protein, with or without carriers, have already proved the successful protection of M2e-based vaccinated animal model against lethal challenge of heterologous and homologous influenza A viruses. Recently, the results of Phase I/II clinical trail studies with M2e-based vaccines have raised hopes for considering these vaccines against seasonal and pandemic influenza A strains. Hence, it is expected that more and more effective and safe universal influenza vaccines based on M2e will be developed for prevention of seasonal and pandemic influenza in the near future.     

Sequence analysis of cox1 and nad1 genes in Echinococcus granulosus G3 genotype in camels (Camelus dromedarius) from central Iran

Nineteen hydatid cyst isolates collected from camels in central Iran were subjected to sequences analysis of mitochondrial cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1) genes. A consensus sequence obtained containing 366 nucleotides for cox1 and 471 nucleotides for nad1 genes. Overall, the camel isolates indicated five different sequences in cox1 and nine in nad1 genes. The sequences analysis indicated that 26.3%, 42.1%, and 31.6% of isolates belonging to G1, G3, and G6 genotypes of Echinococcus granulosus, respectively. The isolates with G3 genotype indicated one cox1 sequence having 100% homology with reference G3 sequence (AN: M84663) and two different nad1 sequences, one having100% homology with reference G3 sequence (AN: AJ237634) and the other with a silent mutation (G to A) in position 279. The presence of G3 genotype (buffalo strain) of E. granulosus as dominant genotype in camels is emphasized. As G3 genotype has formerly been reported in human, the epidemiological role of camels is warranted in future surveys.     

A functional polymorphism in the miR-146a gene is associated with the risk of childhood acute lymphoblastic leukemia: a preliminary report

Growing evidence showed that microRNAs (miRs) are involved in normal hematopoiesis and the pathogenesis of several hematological malignancies. Genetic variations or mutations occurring in the miR gene region may affect the property of miRs through altering miR expression and/or maturation. The aim of the present study was to evaluate the possible relationship between two miRs polymorphisms, hsa-miR-146a (rs2910164 G>C) and hsa-miR-499 (rs3746444 T>C), and the susceptibility to childhood acute lymphoblastic leukemia (ALL) in a sample of Iranian population. This case–control study was performed on 75 children diagnosed with ALL and 115 age- and sex-matched children with no history of cancer of any type (as the control group). Tetra-primer amplification refractory mutation system-polymerase chain reaction was applied for genotyping the variants. We found that the rs2910164 G>C variant of hsa-miR-146a significantly increased the risk of ALL (CC vs. GG, OR?=?4.24, 95 %CI?=?1.52–11.87, P?=?0.006; GC vs. GG, OR?=?3.55, 95 % CI?=?1.41–8.93, P?=?0.007; C vs. T, OR?=?1.73, 95 % CI?=?1.13–2.67, P?=?0.012). With respect to hsa-miR-499 rs3746444 T/C, no significant difference in allele and genotype frequencies of the rs3746444 variant between ALL patients and controls was observed. Our results for the first time demonstrated that the miR-146a rs2910164, but not miR-499 rs3746444 variant, was associated with increased risk for developing pediatrics ALL in an Iranian population.     

Association of functional polymorphism at the miR-502-binding site in the 3′ untranslated region of the SETD8 gene with risk of childhood acute lymphoblastic leukemia,a preliminary report

MicroRNAs (miRNAs), a class of non-coding RNAs, bind to the 3′ untranslated regions (UTRs) of mRNAs, where they interfere with translation of genes and are implicated in the pathogenesis of diverse diseases. In the present study, we evaluate the impact of rs16917496 polymorphism within the miR-502 miRNA seed region at the 3′UTR of SEDT8 on childhood acute lymphoblastic leukemia (ALL). This case-control study was done on 75 ALL and 115 healthy children. Genotyping of rs16917496 C/T polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that CT as well as CT?+?TT decreased the risk of ALL in comparison with CC genotype (odds ratio (OR)?=?0.29, 95 % confidence intervals (95 % CI)?=?0.11–0.78, P?=?0.014 and OR?=?0.31, 95 % CI?=?0.12–0.82, P?=?0.016, respectively). Our results demonstrated that SETD8 rs16917496 C/T polymorphism was associated with decreased risk of developing pediatric ALL in Zahedan, southeast Iran. Larger studies with different ethnicities are desired to validate our findings.     

Solid dispersions of α-mangostin improve its aqueous solubility through self-assembly of nanomicelles

α-Mangostin is an oxygenated heterocyclic xanthone with remarkable pharmacological properties, but poor aqueous solubility and low oral bioavailability hinder its therapeutic application. This study sought to improve the compound's solubility and study the mechanism underlying solubility enhancement. Solid dispersions of α-mangostin were prepared in polyvinylpyrrolidone (PVP) by solvent evaporation method and showed substantial enhancement of α-mangostin's solubility from 0.2 ± 0.2 μg/mL to 2743 ± 11 μg/mL. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated interaction between α-mangostin and PVP. Transmission electron microscopy and dynamic light scattering showed self-assembly of round anionic nanomicelles with particle size in the range 99-127 nm. Powder X-ray diffraction indicated conversion of α-mangostin from crystalline into amorphous state, and scanning electron microscopy showed the presence of highly porous powder. Studies using the fluorescent probe pyrene showed that the critical micellar concentration is about 77.4 ± 4 μg/mL. Cellular uptake of nanomicelles was found to be mediated via endocytosis and indicated intracellular delivery of α-mangostin associated with potent cytotoxicity (median inhibitory concentration of 8.9 ± 0.2 μg/mL). Improved solubility, self-assembly of nanomicelles, and intracellular delivery through endocytosis may enhance the pharmacological properties of α-mangostin, particularly antitumor efficacy.     

Effect of Ageing on the Passive and Active Tension and Pharmacodynamic Characteristics of Rat Coronary Arteries: Age-Dependent Increase in Sensitivity to 5-HT and K

The influence of ageing on the passive and active tension and pharmacodynamic characteristics of intramural coronary arteries from 3-month-old and 2-year-old male Wistar rats was investigated using an isometric myograph. The passive vessel wall tension measured in Ca(2+)-free physiological salt solution at L(0) was significantly greater in arteries from old rats (1.46 ± 0.10 Nm(-1), n = 7) than in young rats (1.13 ± 0.13 Nm(-1), n = 6). However, the maximal active tension at L(0) was similar. The spontaneous myogenic tone was increased by age and the vasorelaxation induced by extracellular K(+) was significantly higher in coronary arteries of old rats. The sensitivity (pD(2)) to 5-HT was significantly higher in arteries from old (6.43 ± 0.11, n = 22) than from young rats (6.16 ± 0.08, n = 29). Ketanserin induced a concentration-dependent rightward shift of the 5-HT concentration-response curve in arteries from both young and old rats. The slopes of the regression lines of the Schild plots were not significantly different from unity and the estimated pK(B) values for ketanserin were similar. In conclusion, ageing is associated with changes in passive mechanical characteristics as well as changes in pharmacological properties in rat coronary small arteries.