Membrane—vanadium interaction: A toxicokinetic evaluation

Vanadium is an important trace metal widely distributed in environment. Interaction of vanadate with skeletal muscle sarcolemma and basement membrane has been focussed. Scatchard analysis indicated the presence of more than one binding site for vanadate. Vanadate inhibits sarcolemmal and intestinal brush border membrane enzymes in a non-competitive manner. Membrane-vanadium interaction may lead to several structural and functional changes. The binding of vanadium to basement membrane may have some protective role.     

Effect of Lower Doses of Vanadate in Combination with Azadirachta indica Leaf Extract on Hepatic and Renal Antioxidant Enzymes in Streptozotocin-Induced Diabetic Rats

The present study was undertaken to investigate short-term (21 days) effects of oral administration of Azadirachta indica leaf extract and vanadate, separately and in combination, on the activities of antioxidant enzymes in streptozotocin-induced diabetic rats. Vanadate is a remarkable antidiabetic agent and shows insulin mimetic effect. However, severe toxicity is associated with vanadate when used in high concentration while at lower concentration the hypoglycemic property of vanadate is reduced. So, we used a low dose of vanadate in combination with A. indica leaf extract and evaluated their effect on the antioxidant defense system. Streptozotocin-diabetic rats were treated separately with insulin, vanadate (0.6 mg/ml), A. indica, and with combined dose of vanadate (0.2 mg/ml) and A. indica. At the end of the experiment, rats were sacrificed and serum glucose levels and activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were determined in cytosolic fraction of liver and kidney. Diabetic rats showed hyperglycemic condition and alteration in antioxidant enzyme activities. Treatment with antidiabetic compounds resulted in the reduction of glucose levels and restoration of enzyme activities to normal. Results showed that combined treatment of vanadate and A. indica leaf extract was the most effective in normalizing altered antioxidant enzyme system.     

Urinary Triclosan is Associated with Elevated Body Mass Index in NHANES

Background

Triclosan—a ubiquitous chemical in toothpastes, soaps, and household cleaning supplies—has the potential to alter both gut microbiota and endocrine function and thereby affect body weight.

Methods

We investigated the relationship between triclosan and body mass index (BMI) using National Health and Nutrition Examination Surveys (NHANES) from 2003–2008. BMI and spot urinary triclosan levels were obtained from adults. Using two different exposure measures—either presence vs. absence or quartiles of triclosan—we assessed the association between triclosan and BMI. We also screened all NHANES serum and urine biomarkers to identify correlated factors that might confound observed associations.

Results

Compared with undetectable triclosan, a detectable level was associated with a 0.9-point increase in BMI (p<0.001). In analysis by quartile, compared to the lowest quartile, the 2nd, 3rd and 4th quartiles of urinary triclosan were associated with BMI increases of 1.5 (p<0.001), 1.0 (p = 0.002), and 0.3 (p = 0.33) respectively. The one strong correlate of triclosan identified in NHANES was its metabolite, 2,4-dichlorophenol (ρ = 0.4); its association with BMI, however, was weaker than that of triclosan. No other likely confounder was identified.

Conclusions

Triclosan exposure is associated with increased BMI. Stronger effect at moderate than high levels suggests a complex mechanism of action.     

Cardiotonic steroids as potential Na+/K+-ATPase inhibitors – a computational study

Abstract

Cardiotonic steroids (CTS) are steroidal drugs, processed from the seeds and dried leaves of the genus Digitalis as well as from the skin and parotid gland of amphibians. The most commonly known CTS are ouabain, digoxin, digoxigenin and bufalin. CTS can be used for safer medication of congestive heart failure and other related conditions due to promising pharmacological and medicinal properties. Ouabain isolated from plants is widely utilized in in vitro studies to specifically block the sodium potassium (Na⁺/K⁺-ATPase) pump. For checking, whether ouabain derivatives are robust inhibitors of Na⁺/K⁺-ATPase pump, molecular docking simulation was performed between ouabain and its derivatives using YASARA software. The docking energy falls within the range of 8.470?kcal/mol to 7.234?kcal/mol, in which digoxigenin was found to be the potential ligand with the best docking energy of 8.470?kcal/mol. Furthermore, pharmacophore modeling was applied to decipher the electronic features of CTS. Molecular dynamics simulation was also employed to determine the conformational properties of Na⁺/K⁺-ATPase-ouabain and Na⁺/K⁺-ATPase-digoxigenin complexes with the plausible structural integrity through conformational ensembles for 100?ns which promoted digoxigenin as the most promising CTS for treating conditions of congestive heart failure patients.     

Energy Homeostasis and Obesity: The Therapeutic Role of Anorexigenic and Orexigenic Peptide

International Journal of Peptide Research and Therapeutics - The brain detects changes in energy depots and actuates metabolic and behavioral responses planned to hold energy balance. Hunger,...     

Seed Priming with Iron Oxide Nanoparticles Triggers Iron Acquisition and Biofortification in Wheat (Triticum aestivum L.) Grains

Iron deficiency anaemia is a major challenge among consumers in developing countries. Given the deficiency of iron in the diet, there is an urgent need to devise a strategy for providing the required iron in the daily diet to counter the iron deficiency anaemia. We propose that iron biofortification of wheat (Triticum aestivum L.) through seed priming would be an innovative strategy to address this issue. This investigation attempts to find the interaction of iron oxide nanoparticles on germination, growth parameters and accumulation of grain iron in two contrasting wheat genotypes WL711 (low-iron genotype) and IITR26 (high-iron genotype). Wheat seeds were primed with different concentrations of iron oxide nanoparticles in the range of 25–600 ppm, resulting in differential accumulation of grain iron contents. We observed a pronounced increase in germination percentage and shoot length at 400 and 200 ppm treatment concentrations in IITR26 and WL711 genotypes, respectively. Intriguingly, the treatment concentration of 25 ppm demonstrated higher accumulation with a significant increase in grain iron contents to 45.7% in IITR26 and 26.8% in WL711 genotypes, respectively. Seed priming represents an innovative and user-friendly approach for wheat biofortification which triggers iron acquisition and accumulation in grains.

     

Pleistocene rapid uplift of the Himalayan frontal ranges recorded in the Kathmandu and Siwalik basins

Core-drilling project carried out in the southern margin of the Kathmandu Basin revealed that muddy debris flow deposits dammed up the Proto-Bagmati river to form the Paleo-Kathmandu Lake during the Jaramillo subchron from 1.07 to 0.97 Ma. Subsequent deposition of the alluvial fanglomerate, derived from the uplifting Mahabharat Range to the south, raised the dam deepening the lake-water. After 1 Ma, in the southern part of the basin, palaeo-current directions changed from southward to northward and deposition of gneissose and granitic detritus are replaced by meta-sediments derived from the Mahabharat Range.During the same time, at about 1 Ma, the boulder conglomerates were deposited on top of the Siwalik Group as piggy-back basins in front of an intra-basinal high, along the Main Dung Thrust in Nepal and NW India. Onset of movement of the Main Dung Thrust is dated back to 3 to 2.4 Ma [Mugnier, J.L., Huyge, P., Leturmy, P., Jouanne, F., 2003, Episodicity and rates of thrust-sheet motion in the Himalayas, Western Nepal. Am. Assoc. Petrol. Geol., Mem. 82, 1-24]. The Main Frontal Thrust is most active at present suggesting that imbricated structure of the Siwalik Group was formed by convergence of the Indian plate during the last 3 myr. The accretionary wedge of the Siwalik Group, stacked beneath the Main Boundary Thrust, might have started to jack up the frontal range of the Lesser Himalaya since 1 Ma.Coeval uplift and erosion of the frontal range of the Lesser Himalaya and the intra-basinal high in the Siwalik since 1 Ma are possible causes of an abrupt increase in both sedimentation rate and grain size of detrital quartz, and changes in composition of clay minerals, recorded in the sediments of the Bengal Deep Sea Fan at 0.9 Ma.     

Cellular Size as a Means of Tracking mTOR Activity and Cell Fate of CD4+ T Cells upon Antigen Recognition

mTOR is a central integrator of metabolic and immunological stimuli, dictating immune cell activation, proliferation and differentiation. In this study, we demonstrate that within a clonal population of activated T cells, there exist both mTOR^hi and mTOR^lo cells exhibiting highly divergent metabolic and immunologic functions. By taking advantage of the role of mTOR activation in controlling cellular size, we demonstrate that upon antigen recognition, mTOR^hi CD4+ T cells are destined to become highly glycolytic effector cells. Conversely, mTOR^lo T cells preferentially develop into long-lived cells that express high levels of Bcl-2, CD25, and CD62L. Furthermore, mTOR^lo T cells have a greater propensity to differentiate into suppressive Foxp3+ T regulatory cells, and this paradigm was also observed in human CD4+ T cells. Overall, these studies provide the opportunity to track the development of effector and memory T cells from naïve precursors, as well as facilitate the interrogation of immunologic and metabolic programs that inform these fates.     

Direct Delivery of Inoculum to Shoot Tissue Interferes with Genotypic Resistance to Ralstonia solanacearum in Tomato Seedlings

Employing known susceptible and resistant genotypes and pure bacterial inoculum (0.1 OD; 10⁸ CFU/ml^?1), five different inoculation methods were tried to assess the response of tomato genotypes to Ralstonia solanacearum. This included seed‐soaking inoculation, seed‐sowing followed by inoculum drenching, or at 2‐week stage through petiole‐excision inoculation, soaking of planting medium with inoculum either directly or after imparting seedling root‐injury. Seed‐based inoculations or mere inoculum drenching at 2 weeks did not induce much disease in seedlings. Petiole inoculation induced 90–100% mortality in susceptible checks but also 50–60% mortality in normally resistant genotypes within 7–10 days. Root‐injury inoculation at 2‐week seedling stage appeared the best for early and clearer distinction between resistant and susceptible lines. The observations suggest a role played by the root system in governing genotypic resistance to the pathogen. Direct shoot inoculation is to be adopted only for selecting highly resistant lines or to thin down segregating populations during resistance breeding.