Effectiveness of Lactoferrin in the Treatment of Anemia in Chronic Kidney Disease: A Single-Center Pilot Study.

Background: Anemia occurs in majority of patients with chronic kidney disease despite adequate dialysis and iron replete status. This study was done to evaluate the effects of lactoferrin with or without iron supplementation for the treatment of anemia in patients with chronic kidney disease (CKD). Materials and Methods: In this prospective, observational, single-center, single-arm pilot study, adult patients aged >18 years, having stage 5 CKD (estimated glomerular filtration rate [eGFR] <15 ml/min/1.73 m2), and who had anemia (hemoglobin [Hb] <10 g/dl; transferrin saturation [Tsat] >20%) were included. Patients were treated with 100 mg of oral lactoferrin twice a day for one month with or without iron supplementation. Patients had been on stable erythropoietin doses for ≥1 month prior to inclusion in the study. We report on the improvement in Hb levels and effect on inflammatory markers from baseline at four weeks. Results: A total of 46 CKD patients having anemia were included. Patients had a mean age of 39.3 years, and a majority were men (69.6%). Improvement in the mean (SD) Hb level (g/dl) was observed from baseline (8.18 [1.19]) to Week 2 (8.54 [1.57]), which attained significance at Week 4 (8.96 [1.93]; P < 0.001; mean difference: -0.76; 95% confidence interval [CI]: -1.291 to - 0.2383). The improvement in Hb was higher in women than in men (P = 0.48) and in patients receiving lactoferrin with iron supplementation than in those receiving lactoferrin alone (P = 0.14). There was a non-significant decrease in the erythrocyte sedimentation rate (P = 0.14) and a non-significant increase in C-reactive protein (P = 0.54) level. Conclusion: Oral lactoferrin therapy was effective in improving hemoglobin levels in patients with advanced CKD and anemia. The effects of lactoferrin therapy on inflammatory markers remain uncertain.

Challenges and technological interventions in rice-wheat system for resilient food-water-energy-environment nexus in North-western Indo-Gangetic Plains: A review.

Rice (Oryza sativa L.)-wheat (Triticum aestivum L.) cropping system in north-western Indo-Gangetic Plains performed a crucial role in the national food security. However, the widespread and intensive cultivation of this system has led to serious problems such as declining groundwater table (~1 meter year-1) with sharp increase in number of districts under over-exploitation category, residue burning, higher greenhouse gases emission and herbicide resistance in weeds, causing stagnant crop productivity and lesser profitability. In this review article, an attempt has been made to discuss the major issues pertaining to intensive rice-wheat cultivation amidst climate vagaries and futuristic approach to address these challenges. Different tillage- and crop-specific recommendations such as adoption of direct seeded rice, diversification with lesser resource guzzling crops such as maize (Zea mays L.) at least on the periodic manner especially in light-medium soils, inclusion of summer legumes and alternative tillage systems (permanent beds and zero tillage with residue retention) have been suggested to address these issues. However, crop performance under these techniques has been found to be location, soil and cultivar specific. The absence of aerobic tailored genotypes and weeds have been identified as the major constraints in adoption of direct seeded rice. The integrated strategies of conservation tillage, crop breeding program and resource conserving region- and soil-specific agronomic measures with crop diversification would be helpful in tackling the sustainability issues. It requires future efforts on developing crop genotypes suited to conservation tillage, effective weed control strategies and trainings and demonstrations to farmers to switch from conventional rice-wheat system to alternative cropping systems.

Unusual Robustness of Neurotransmitter Vesicle Membranes against Serotonin-Induced Perturbations.

Nature confines hundreds of millimolar of amphiphilic neurotransmitters, such as serotonin, in synaptic vesicles. This appears to be a puzzle, as the mechanical properties of lipid bilayer membranes of individual major polar lipid constituents of synaptic vesicles [phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS)] are significantly affected by serotonin, sometimes even at few millimolar concentrations. These properties are measured by atomic force microscopy, and their results are corroborated by molecular dynamics simulations. Complementary 2H solid-state NMR measurements also show that the lipid acyl chain order parameters are strongly affected by serotonin. The resolution of the puzzle lies in the remarkably different properties displayed by the mixture of these lipids, at molar ratios mimicking those of natural vesicles (PC:PE:PS:Cholesterol = 3:5:2:5). Bilayers constituting of these lipids are minimally perturbed by serotonin, and show only a graded response at physiological concentrations (>100 mM). Significantly, the cholesterol (up to 33% molar ratio) plays only a minor role in dictating these mechanical perturbations, with PC:PE:PS:Cholesterol = 3:5:2:5 and 3:5:2:0 showing similar perturbations. We infer that nature uses an emergent mechanical property of a specific mixture of lipids, all individually vulnerable to serotonin, to appropriately respond to physiological serotonin levels.

Understanding curcumin-induced modulation of protein aggregation.

Curcumin, a diarylheptanoid compound, found in spice turmeric is known to alter the aggregation of proteins and reduce the toxicity of the aggregates. This review looks at the molecular basis of modulating protein aggregation and toxicity of the aggregates. Foremost, we identify the interaction of curcumin and its derivatives with proteins/peptides and the effect of their interaction on the conformational stability and unfolding/folding pathway(s). The unfolding/folding processes generate partially folded/unfolded intermediate, which serve as aggregation precursor state. Secondly, we discuss the effect of curcumin binding on the kinetics parameters of the aggregation process, which give information about the mechanism of the aggregation inhibition. We describe, in addition, that curcumin can accelerate/promote fibril formation by binding to oligomeric intermediate(s) accumulated in the aggregation pathway. Finally, we discuss the correlation of curcumin-induced monomeric and/or oligomeric precursor states with aggregate structure and toxicity. On the basis of these discussions, we propose a model describing curcumin-induced inhibition/promotion of formation of amyloid-like fibrils.

A comparative study of fibrillation kinetics of two homologous proteins under identical solution condition.

Human lysozyme is homologous in the three-dimensional structure to hen lysozyme and the latter is commonly used to understand folding and amyloid aggregation pathway of the former. The fibrillation of the two proteins is known to occur via partial unfolding. A work dedicated to comparing the aggregation-prone conformations and their subsequent conversion into amyloid-like fibrils in an identical condition is not available. This has provided an opportunity to compare the fibrillation behaviors of the two homologous proteins under identical solution condition. In this work, we have shown that the temperature-induced unfolding of the two proteins at pH 1.5 occurred via a three states process. We found that temperature-unfolded states of the two proteins differ in contents of residual secondary and tertiary structures. The temperature-unfolded states of both proteins rapidly converted into well-defined amyloid-like fibrils on stirring at 230 RPM. We further observed that the kinetic parameters, lag time (tlag) and apparent rate constant (kapp) of aggregation of hen lysozyme were markedly enhanced than human lysozyme. Amyloid fibrils formed by the two proteins only slightly differ in their morphology and Tinctorial properties. Therefore, on the basis of our in vitro aggregation and in silico aggregation and α-helical propensities prediction studies, we concluded that the major determinant of acceleration of aggregation of hen lysozyme is the stabilization of amyloidogenic native α-helices in highly dynamics partially-folded state. Comparison of aggregation-prone conformations and their aggregation kinetics parameters also with other protein systems can serve as a useful model to understand the factors promoting amyloid aggregation.