Role of NAD(P)H:quinone oxidoreductase polymorphism at codon 187 in susceptibility to lung,laryngeal and oral/pharyngeal cancers

NAD(P)H:quinone oxidoreductase (NQO1) has been proposed to play a protective role against the toxic effects of benzo[a]pyrene quinones. The C⁶⁰⁹T base change in the NQO1 gene, resulting in a Pro¹⁸⁷Ser amino acid change in the protein, has been associated with deficient enzyme activity. We examined whether this polymorphism modified the risks of smoking-related cancers in a case-control study involving patients with lung cancer (n = 150), laryngeal cancer (n = 129), oral/pharyngeal cancer (n = 121) and control individuals (n = 172), all Caucasian smokers. No statistically significant associations were observed between the NQO1 genotypes and smoking-related cancers, although the Ser/Ser genotype was associated with a tendency towards increased risk for lung cancer (odds ratio [OR] = 2.2, 95% confidence interval [CI] 0.7-6.7) and for oral/pharyngeal cancer (OR = 2.3, 95% CI 0.6-8.2). No significant interaction between the NQO1 genotype and either smoking exposure or GSTM1 genotype was found. Our results are consistent with the hypothesis that lack of NQO1 activity may be involved in some smoking-related cancers. However, they were based on small numbers of individuals with the putative atrisk genotype, and the associations did not reach statistical significance. Moreover, these results contrast with those observed in some other ethnic populations, where a protective effect of the NQO1 Ser allele was found. Further studies are therefore clearly needed for a better understanding of the potential role of NQO1 activity in tobacco-related cancers.     

A profound computational study to prioritize the natural compound inhibitors against the P. falciparum orotidine-5-monophosphate decarboxylase enzyme

Abstract

In the current contribution, a multicomplex-based pharmacophore modeling approach was employed on the structural proteome of Plasmodium falciparum orotidine-5-monophosphate decarboxylase enzyme (PfOMPDC). Among the constructed pharmacophore models, the representative hypotheses were selected as the primary filter to screen the molecules with the complementary features responsible for showing inhibition. Thereafter, auxiliary evaluations were performed on the screened candidates via drug-likeness and molecular docking studies. Subsequently, the stability of the docked protein-ligand complexes was scrutinized by employing molecular dynamics simulations and molecular mechanics-Poisson Boltzmann surface area based free binding energy calculations. The stability the docked candidates was compared with the highly active crystallized inhibitor (3S9Y-FNU) to seek more potential candidates. All the docked molecules displayed stable dynamic behavior and high binding free energy in comparison to 3S9Y-FNU. The employed workflow resulted in the retrieval of five drug-like candidates with diverse scaffolds that may show inhibitory activity against PfOMPDC and could be further used as the novel scaffold to develop novel antimalarials.

Communicated by Ramaswamy H. Sarma     

Growth performance and feed conversion of Ruspolia differens on plant-based by-product diets

The use of food industry by-products in insect feeds has gained increasing attention recently. However, the understanding of how well the economically valuable edible insect Ruspolia differens (Serville) (Orthoptera: Tettigoniidae) can grow and develop with plant-based by-product feeds is currently lacking. It is important to determine the nutritional requirements, especially protein demand, of this species before developing artificial feeds for mass-rearing. We reared R. differens with four control diets and 12 plant-based by-product diets in which the major protein source came from food industry by-products, including potato-protein, barley mash, barley feed, turnip rape, a mix of broad bean and pea, and a mix of potato, carrot, and apple. We asked whether the performance (development time, survival, and weight), feed conversion, and fatty acid composition and content differed among diet treatments. Furthermore, the 12 experimental by-product diets were designed to reach six protein levels. We found that R. differens can be reared with various by-product diets, but development time, survival, and weight differed among diets. Barley feed, barley mash, and potato protein diets seem to be good options for rearing, and potato glycoalkaloids do not affect the performance of R. differens. Individuals fed on the various by-product diets also differed in their fatty acid composition and content. Increasing protein levels in diet up to 17% enhanced growth, development time, and survival, but no further enhancements were seen when fed diets with protein levels higher than this. The high protein levels decreased feed conversion rate. Our results can be valuable for designing feeds for insect mass-rearing technology. The use of food industry by-products in the diets for R. differens could increase the re-use of local resources and enhance circular economy.     

p42/p44-MAPK and PI3K are sufficient for IL-6 family cytokines/gp130 to signal to hypertrophy and survival in cardiomyocytes in the absence of JAK/STAT activation

The effect of differential signalling by IL-6 and leukaemia inhibitory factor (LIF) which signal by gp130 homodimerisation or LIFRβ/gp130 heterodimerisation on survival and hypertrophy was studied in neonatal rat cardiomyocytes. Both LIF and IL-6 [in the absence of soluble IL-6 receptor (sIL-6Rα)] activated Erk1/2, JNK1/2, p38-MAPK and PI3K signalling peaking at 20 min and induced cytoprotection against simulated ischemia-reperfusion injury which was blocked by the MEK1/2 inhibitor PD98059 but not the p38-MAPK inhibitor SB203580. In the absence of sIL-6R, IL-6 did not induce STAT1/3 phosphorylation, whereas IL-6/sIL-6R and LIF induced STAT1 and STAT3 phosphorylation. Furthermore, IL-6/sIL-6R induced phosphorylation of STAT1 Tyr⁷⁰¹ and STAT3 Tyr⁷⁰⁵ were enhanced by SB203580. IL-6 and pheneylephrine (PE), but not LIF, induced cardiomyocyte iNOS expression and nitric oxide (NO) production. IL-6, LIF and PE induced cardiomyocyte hypertrophy, but with phenotypic differences in ANF and SERCA2 expression and myofilament organisation with IL-6 more resembling PE than LIF. Transfection of cardiomyocytes with full length or truncated chimaeric gp130 cytoplasmic domain/Erythropoietin receptor (EpoR) extracellular domain fusion constructs showed that the membrane proximal Box 1 and Box 2 containing region of gp130 was necessary and sufficient for MAPK and PI3K activation; hypertrophy; SERCA2 expression and iNOS/NO induction in the absence of JAK/STAT activation. In conclusion, IL-6 can signal in cardiomyocytes independent of sIL-6R and STAT1/3 and furthermore, that Erk1/2 and PI3K activation by IL-6 are both necessary and sufficient for induced cardioprotection. In addition, p38-MAPK may act as a negative feedback regulator of JAK/STAT activation in cardiomyocytes.     

Proteomics: A Paradigm Shift

ABSTRACT

Proteome—the protein complement of a genome—has become the protein renaissance and a key research tool in the post-genomic era. The basic technology involves the routine usage of gel electrophoresis and spectrometry procedures for deciphering the primary protein sequence/structure as well as knowing certain unique post-translational modifications that a particular protein has undergone to perform a specific function in the cell. However, the recent advancements in protein analysis have ushered this science to provide deeper, bigger and more valuable perspectives regarding performance of subtle protein-protein interactions. Applications of this branch of molecular biology are as vast as the subject is and include clinical diagnostics, pharmaceutical and biotechnological industries. The 21st century hails the use of products, procedures and advancements of this science as finer touches required for the grooming of fast-paced technology.     

Combination treatment of elevated UVB radiation,CO2 and temperature has little effect on silver birch (Betula pendula) growth and phytochemistry

Elevations of carbon dioxide, temperature and ultraviolet‐B (UBV) radiation in the growth environment may have a high impact on the accumulation of carbon in plants, and the different factors may work in opposite directions or induce additive effects. To detect the changes in the growth and phytochemistry of silver birch (Betula pendula) seedlings, six genotypes were exposed to combinations of ambient or elevated levels of CO₂, temperature and UVB radiation in top‐closed chambers for 7 weeks. The genotypes were relatively similar in their responses, and no significant interactive effects of three‐level climate factors on the measured parameters were observed. Elevated UVB had no effect on growth, nor did it alter plant responses to CO₂ and/or temperature in combined treatments. Growth in all plant parts increased under elevated CO₂, and height and stem biomass increased under elevated temperature. Increased carbon distribution to biomass did not reduce its allocation to phytochemicals: condensed tannins, most flavonols and phenolic acids accumulated under elevated CO₂ and elevated UVB, but this effect disappeared under elevated temperature. Leaf nitrogen content decreased under elevated CO₂. We conclude that, as a result of high genetic variability in phytochemicals, B. pendula seedlings have potential to adapt to the tested environmental changes. The induction in protective flavonoids under UVB radiation together with the positive impact of elevated CO₂ and temperature mitigates possible UVB stress effects, and thus atmospheric CO₂ concentration and temperature are the climate change factors that will dictate the establishment and success of birch at higher altitudes in the future.     

Fermentation of glycerol and production of valuable chemical and biofuel molecules

Glycerol has attracted the attention of scientific and industrial communities due to its generation in bulk quantities as a byproduct of biofuel industries. With the rapid growth of these industries in recent years, glycerol is frequently treated as a very low-value byproduct or even a waste product with a disposal cost associated to it. Glycerol is not only abundant and inexpensive but also can generate more reducing equivalents than glucose or xylose. This unique characteristic of glycerol offers a tremendous opportunity for its biological conversion to valuable products at higher yield. This review focuses on research efforts to utilize glycerol as a carbon source for the production of a variety of fuels and chemicals by both native and metabolically engineered microorganisms.