In silico design of small peptides antagonist against leptin receptor for the treatment of obesity and its associated immune-mediated diseases.

Excess adiposity in obese inhibits negatively impacts immune function and host defence. Obesity is characterized by a state of low-grade, chronic inflammation in addition to disturbed levels of circulating nutrients and metabolic hormones. The impact of metabolic abnormalities on obesity-related co-morbidities has undergone intense scrutiny over the past decades. Thus, treatment of obesity and its associated immune-mediated diseases is challenging due to impaired function of leptin system. These disorders are managed through antibiotics and by cytokines replacement. However, the effectiveness of cytokines coupled to the complexity of the cytokine network leads to severe side-effects, which can still occur after careful preclinical evaluation. In addition, synthetic immunotherapeutics carry a degree of risk, time-consuming and expensive. Hence, the complexity of existing therapy and adverse effects emphasizes the need for an alternative approach for the management of immune dysfunction associated with obesity. Computer-aided small molecule antibody technology has been successful in the design of novel biologicals for the diagnosis of diseases and therapeutic interventions. In this study, the crystal structure of leptin receptor (LEPR) complex with monoclonal antibody (9F8 Fab) was explored to predict Ag-Ab interactions using bioinformatics tools. The LEPR of complementarity-determining region (CDR) loops were mutated with published positive control residues of Ser, Thr, Tyr, Trp, and Phe to design a set of 678 peptides which were evaluated through Ag-peptide docking, binding free-energies, and interaction energies. Thus, hypothesized novel peptides can be explored as clinically applicable antagonists for the treatment of obesity and associated immune-mediated diseases.

Adolescent life-event stress in boys is associated with elevated IL-6 and hepcidin but not hypoferremia.

OBJECTIVE: The link between stress-related increases in inflammatory markers, hepcidin, and iron status are poorly understood, especially in developing countries like India. The aim of the study was to examine the relationship between adolescent life-event stress (ALES), inflammatory markers, and its association with hepcidin and biomarkers of iron status among adolescent boys. METHODS: Data pertaining to a subsample of 145 participants from a cross-sectional, school-based study recruiting 370 adolescent boys aged 15-19 years, from 5 schools in Hyderabad, India, were analyzed. Stress was assessed using the ALES scale, psychological distress by the General Health Questionnaire-2 (GHQ-12), and approach and avoidance coping using the Coping Strategies Scale. Biomarkers of iron and concentrations of other micronutrients, hepcidin, IL-6 and C-reactive protein (CRP) in plasma were analyzed. Data were subjected to regression, path analyses, and analysis of covariance (ANCOVA). RESULTS: ALES was a significant predictor of interleukin (IL)-6 (ß = 0.196, p = 0.012), CRP (ß = 0.217, p = 0.010), and log hepcidin (ß = 0.228, p = 0.006). Hepcidin correlated significantly (p < 0.001) with IL-6 (r = 0.344) and CRP (r = 0.370) but not with the biomarkers of iron status. Path analysis showed that the model had an acceptable fit, with a root mean square error of approximation of 0.019, 90% confidence interval (CI) of 0.00-0.074, comparative fit index of 0.988, chi-square p = 0.393, and chi-square/df of 1.053. CONCLUSIONS: Adolescent life-event stress is associated with elevated IL-6 and hepcidin concentration but not hypoferremia. These findings may help in iron supplementation programs for tackling anemia.

Micronized ferric pyrophosphate supplied through extruded rice kernels improves body iron stores in children: a double-blind, randomized, placebo-controlled midday meal feeding trial in Indian schoolchildren.

BACKGROUND: Micronized ferric pyrophosphate (MFPP) in extruded rice kernels mixed in a rice-based meal could be an effective strategy for improving iron status of children in India. OBJECTIVE: The objective was to determine the impact of MFPP supplied through extruded rice kernels in a rice-based meal on iron status of children participating in the midday meal (MDM) scheme in India. DESIGN: The sensory characteristics of cooked rice containing MFPP in extruded rice kernels, in vitro availability, and loss of iron during cooking from a typical MDM consisting of 125 g rice (dry weight) containing 19 mg Fe [fortified rice (FR); normal rice mixed with Ultra Rice (extruded kernels containing MFPP of ∼3.14-µm mean particle size)] in comparison with unfortified rice (UFR) were tested. A double-blind, 8-mo, placebo-controlled trial was conducted in 5-11-y-old schoolchildren (n = 140) who were randomly assigned to receive either an FR-MDM or a UFR-MDM. Average consumption amounts of the MDM, height, weight, hemoglobin, ferritin, and C-reactive protein were measured at baseline and at 8 mo. RESULTS: The sensory qualities of cooked FR and UFR were similar. The in vitro iron availability from FR-MDM (1.3%) was significantly (P < 0.05) lower than that from UFR-MDM (3.3%). Providing FR-MDM to the schoolchildren for 8 mo improved ferritin significantly (P < 0.001), by 8.2 ± 2.10 µg/L. However, the increase in hemoglobin was similar between groups (FR: 0.99 ± 0.10 g/dL; UFR: 1.15 ± 0.10 g/dL), which suggests that other factors beyond additional iron intake had a large influence on hemoglobin concentration. The prevalence of iron deficiency decreased significantly (P < 0.05) in the FR group (33-14%) and increased marginally in the UFR group (31-37%). The prevalence of anemia and iron deficiency anemia was similar between groups at baseline and at 8 mo. CONCLUSION: Regular intake of 19 mg Fe/d in MFPP supplied through extruded rice kernels improves iron stores and reduces iron deficiency among schoolchildren in India.

Association of hypertension with risk factors & hypertension related behaviour among the aboriginal Nicobarese tribe living in Car Nicobar Island, India.

BACKGROUND & OBJECTIVES: There are no composite estimates on prevalence of hypertension among indigenous tribes in India. The present study was carried out to estimate the prevalence of hypertension, its association with determinants, and to assess the hypertension related behaviour of the Nicobarese aborigines. METHODS: This cross-sectional survey was carried during 2007 and 2009. Subjects were chosen by two stage design. Total 975 subjects of 1270 (response rate of 76.8%) were investigated (M: 43.5%; F: 56.5%). The data were collected by history, clinical examination (blood pressure), and examination (weight and height). The association of hypertension with age, education, tobacco, alcohol consumption and their dependency status (KF score, QF value, and AUDIT score) and nutritional status was estimated by bivariate regression analysis; the increasing trend in the prevalence of hypertension with increasing age and decreasing educational status was analysed by χ2 for linear trend. Significant variables in bivariate regression analysis (age, education, alcohol consumption status, and nutritional status) were subjected to multiple logistic regression analysis (MLR). RESULTS: The prevalence of hypertension was 50.5 per cent [95% CI 46.1-54.9 (M: 50.7%; F: 50.3%)]. The prevalence of tobacco, alcohol consumption, and overweight/obesity was 88, 54, and 37 per cent respectively. The bivariate analysis has shown association between hypertension and age, education subcategories, alcohol consumption, and overweight/obesity (P<0.05). The increasing trend in the prevalence of hypertension with increasing age (χ2 for linear trend=95.88, P< 0.001) and decreasing educational status (χ2 for linear trend=25.55, P< 0.001) was statistically significant. MLR analysis revealed a significant association between hypertension and various age categories and overweight/obesity. INTERPRETATION & CONCLUSIONS: The findings of the present study highlight high prevalence of hypertension among Nicobarese aborigenes.