Different applications of virus‐like particles in biology and medicine: Vaccination and delivery systems

Virus‐like particles (VLPs) mimic the whole construct of virus particles devoid of viral genome as used in subunit vaccine design. VLPs can elicit efficient protective immunity as direct immunogens compared to soluble antigens co‐administered with adjuvants in several booster injections. Up to now, several prokaryotic and eukaryotic systems such as insect, yeast, plant, and E. coli were used to express recombinant proteins, especially for VLP production. Recent studies are also generating VLPs in plants using different transient expression vectors for edible vaccines. VLPs and viral particles have been applied for different functions such as gene therapy, vaccination, nanotechnology, and diagnostics. Herein, we describe VLP production in different systems as well as its applications in biology and medicine. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 113–132, 2016.     

A causal network analysis in an observational study identifies metabolomics pathways influencing plasma triglyceride levels

Introduction

Plasma triglyceride levels are a risk factor for coronary heart disease. Triglyceride metabolism is well characterized, but challenges remain to identify novel paths to lower levels. A metabolomics analysis may help identify such novel pathways and, therefore, provide hints about new drug targets.

Objectives

In an observational study, causal relationships in the metabolomics level of granularity are taken into account to distinguish metabolites and pathways having a direct effect on plasma triglyceride levels from those which are only associated with or have indirect effect on triglyceride.

Method

The analysis began by leveraging near-complete information from the genome level of granularity using the GDAG algorithm to identify a robust causal network over 122 metabolites in an upper level of granularity. Knowing the metabolomics causal relationships, we enter the triglyceride variable in the model to identify metabolites with direct effect on plasma triglyceride levels. We carried out the same analysis on triglycerides measured over five different visits spanning 24 years.

Result

Nine metabolites out of 122 metabolites under consideration influenced directly plasma triglyceride levels. Given these nine metabolites, the rest of metabolites in the study do not have a significant effect on triglyceride levels at significance level alpha = 0.001. Therefore, for the further analysis and interpretations about triglyceride levels, the focus should be on these nine metabolites out of 122 metabolites in the study. The metabolites with the strongest effects at the baseline visit were arachidonate and carnitine, followed by 9-hydroxy-octadecadenoic acid and palmitoylglycerophosphoinositol. The influence of arachidonate on triglyceride levels remained significant even at the fourth visit, which was 10 years after the baseline visit.

Conclusion

These results demonstrate the utility of integrating multi-omics data in a granularity framework to identify novel candidate pathways to lower risk factor levels.

     

Up Regulation of cystathione γ lyase and Hydrogen Sulphide in the Myocardium Inhibits the Progression of Isoproterenol–Caffeine Induced Left Ventricular Hypertrophy in Wistar Kyoto Rats

Hydrogen sulphide (H₂S) is an emerging molecule in many cardiovascular complications but its role in left ventricular hypertrophy (LVH) is unknown. The present study explored the effect of exogenous H₂S administration in the regression of LVH by modulating oxidative stress, arterial stiffness and expression of cystathione γ lyase (CSE) in the myocardium. Animals were divided into four groups: Control, LVH, Control-H₂S and LVH-H₂S. LVH was induced by administering isoprenaline (5mg/kg, every 72 hours, S/C) and caffeine in drinking water (62mg/L) for 2 weeks. Intraperitoneal NaHS, 56μM/kg/day for 5 weeks, was given as an H₂S donor. Myocardial expression of Cystathione γ lyase (CSE) mRNA was quantified using real time polymerase chain reaction (qPCR).There was a 3 fold reduction in the expression of myocardial CSE mRNA in LVH but it was up regulated by 7 and 4 fold in the Control-H₂S and LVH-H₂S myocardium, respectively. Systolic blood pressure, mean arterial pressure, pulse wave velocity were reduced (all P<0.05) in LVH-H₂S when compared to the LVH group. Heart, LV weight, myocardial thickness were reduced while LV internal diameter was increased (all P<0.05) in the LVH-H₂S when compared to the LVH group. Exogenous administration of H₂S in LVH increased superoxide dismutase, glutathione and total antioxidant capacity but significantly reduced (all P<0.05) plasma malanodialdehyde in the LVH-H₂S compared to the LVH group. The renal cortical blood perfusion increased by 40% in LVH-H₂S as compared to the LVH group. Exogenous administration of H₂S suppressed the progression of LVH which was associated with an up regulation of myocardial CSE mRNA/ H₂S and a reduction in pulse wave velocity with a blunting of systemic hemodynamic. This CSE/H₂S pathway exhibits an antihypertrophic role by antagonizing the hypertrophic actions of angiotensin II(Ang II) and noradrenaline (NA) but attenuates oxidative stress and improves pulse wave velocity which helps to suppress LVH. Exogenous administration of H₂S augmented the reduced renal cortical blood perfusion in the LVH state.     

The association between low-carbohydrate diet score and sleep duration among Iranian adults

Sleep and Biological Rhythms - Sleep disorders are linked to obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). The evidence suggests that dietary carbohydrate content may...     

Microbial structuring of marine ecosystems

Despite the impressive advances that have been made in assessing the diversity of marine microorganisms, the mechanisms that underlie the participation of microorganisms in marine food webs and biogeochemical cycles are poorly understood. Here, we stress the need to examine the biochemical interactions of microorganisms with ocean systems at the nanometre to millimetre scale--a scale that is relevant to microbial activities. The local impact of microorganisms on biogeochemical cycles must then be scaled up to make useful predictions of how marine ecosystems in the whole ocean might respond to global change. This approach to microbial oceanography is not only helpful, but is in fact indispensable.     

Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized,double blind,crossover study

Data on the effect of combined genetic polymorphisms, involved in folate metabolism, on the concentration of serum folate after folic acid supplementation are scarce. Therefore, we investigated the impact of seven gene polymorphisms on the concentration of serum folate and p-tHcy in healthy subjects after short-term folic acid supplementation. In a randomized, double blind, crossover study, apparently healthy subjects were given either 0.8 mg folic acid per day (n = 46) or placebo (n = 45) for 14 days. The washout period was 14 days. Fasting blood samples were collected on day 1, 15, 30 and 45. Data on subjects on folic acid supplementation (n = 91) and on placebo (n = 45) were used for the statistical analysis. The concentration of serum folate increased higher in subjects with higher age (53.5 ± 7.0 years) than in subjects with lower age (24.3 ± 3.2 years) after folic acid supplementation (p = 0.006). The baseline concentration of serum folate in subjects with polymorphism combination, reduced folate carrier protein, RFC1-80 GA and methylenetetrahydrofolate reductase, MTHFR677 CT+TT, was lower than RFC1-80 AA and MTHFR677 CT+TT (p = 0.002). After folic acid supplementation, a higher increase in the concentration of serum folate was detected in subjects with polymorphism combination RFC1-80 GA and MTHFR677 CC than RFC1-80 GG and MTHFR CT+TT combination (p < 0.0001). The baseline concentration of plasma total homocysteine (p-tHcy) was altered by combined polymorphisms in genes associated with folate metabolism. After folic acid supplementation, in subjects with combined polymorphisms in methylenetetrahydrofolate dehydrogenase, MTHFD1-1958 and MTHFR-677 genes, the concentration of p-tHcy was changed (p = 0.002). The combination of RFC1-80 and MTHFR-677 polymorphisms had a profound affect on the concentration of serum folate in healthy subjects before and after folic acid supplementation.     

Application of a Multi-Criteria Decision-Making Approach for Ranking Environmental Risks Caused by Petrochemical Industries: A Case Study of a Sodium Carbonate Production Unit

The occurrence of accidents in petrochemical industries that cause environmental catastrophes has persuaded experts to use risk-oriented approaches. The approach is to rank the key elements of risk assessment by which the priority of each risk is specified compared to the other ones. The present study was performed to test the applicability of a multi-criteria decision-making approach for prioritizing environmental risks of a petrochemical complex in southwestern Iran. Accordingly, all risky activities of the Sodium Carbonate Production Unit (SCPU) were identified initially. Afterward, the relevant environmental components affected by the risky activities were specified. According to the specification, the most significant risks were shortlisted using experts’ judgment based on three criteria: “impact intensity,” “occurrence probability,” and the “extent of contamination dispersion in the environment.” The shortlisted environmental risks were then prioritized by the Method “Elimination et Choice Translating Reality (Elimination and Choice Expressing Reality)” abbreviated as ELECTRE. Based on the obtained results, “decreased air quality” and “manpower health threatening” are the top-priority risks while “poor quality of groundwater” was identified as the least priority risk. In a general conclusion, a multi-criteria decision-making approach is quite useful for assessing environmental risks of petrochemical industries.