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.

A systematic review and meta-analysis of the circulatory, erythrocellular and CSF selenium levels in Alzheimer's disease: A metal meta-analysis (AMMA study-I).

BACKGROUND: Available studies in the literature on the selenium levels in Alzheimer's disease (AD) are inconsistent with some studies reporting its decrease in the circulation, while others reported an increase or no change as compared to controls. AIM: The objective of this study was to perform a meta-analysis of circulatory (plasma/serum and blood), erythrocyte and cerebrospinal fluid (CSF) selenium levels in AD compared controls. We also performed a meta-analysis of the correlation coefficients (r) to demonstrate the associations between selenium and glutathione peroxidase (GPx) in AD patients. METHODS: All major databases were searched for eligible studies. We included 12 case-control/observational studies reporting selenium concentrations in AD and controls. Pooled-overall effect size as standardized mean difference (SMD) and pooled r-values were generated using Review Manager 5.3 and MedCalc 15.8 software. RESULTS: Random-effects meta-analysis indicated a decrease in circulatory (SMD=-0.44), erythrocellular (SMD=-0.52) and CSF (SMD=-0.14) selenium levels in AD patients compared to controls. Stratified meta-analysis demonstrated that the selenium levels were decreased in both the subgroups with (SMD=-0.55) and without (SMD=-0.37) age matching between AD and controls. Our results also demonstrated a direct association between decreased selenium levels and GPx in AD. CONCLUSION: This meta-analysis suggests that circulatory selenium concentration is significantly lower in AD patients compared to controls and this decrease in selenium is directly correlated with an important antioxidant enzyme, the GPx, in AD.

A meta-analysis of the association of serum ischaemia-modified albumin levels with human hypothyroidism and hyperthyroidism.

Serum levels of ischaemia-modified albumin (IMA) have been studied as a novel and simple measure of oxidative stress (OXS) in different thyroid pathologies. However, results of available studies in the literature were not consistent. This meta-analysis was attempted to quantify the overall effect size for serum IMA levels in human hypothyroidism (HT) and hyperthyroidism (HYT) and to study its associations with the thyroid profile. Databases of PubMed/Medline, EMBASE, Google Scholar, Web of Science and Science Direct were searched for articles. Data on serum IMA levels in HT, HYT patients and euthyroid controls were extracted to compute standardized mean differences (SMD) by the random-effects model. The associations between IMA and thyroid profile were computed by the meta-analysis of correlation coefficients. IMA levels in HT patients (SMD=1.12; Z=2.76; P=0.006) and HYT patients (SMD=1.64; Z=2.57; P=0.01) were significantly higher than in euthyroid controls and the thyroid treatment showed a favourble effect on serum IMA levels. There were strong and significant correlations between IMA and hormonal status in HT and HYT groups. This meta-analysis showing increased IMA level in both HT and HYT patients and its association with thyroid profile suggests that serum IMA could be used as a simple measure of increased OXS in thyroid dysfunction.

Ischemia modified albumin (IMA) and albumin adjusted-IMA (AAIMA) as biomarkers for diabetic retinopathy.

INTRODUCTION: Oxidative stress has important role in the pathophysiology of diabetic retinopathy (DR). Ischemia modified albumin (IMA) has been recently considered as a marker of oxidative damage in diabetes. However, there is scarcity of published information about both IMA and albumin adjusted-IMA (AAIMA) in DR patients. OBJECTIVES: To evaluate the serum levels of IMA and AAIMA in patients with DR and in healthy controls. MATERIAL AND METHODS: This was a cross sectional study. Serum was obtained to measure lipids, albumin and IMA from the the patients with DR and non-diabetic subjects. The IMA level was measured by a colorimetric albumin cobalt binding (ACB) assay and the values were presented as absorbance units (ABSU). The IMA levels were adjusted for albumin interference and the AAIMA by using a formula [Individual serum albumin/median albumin concentration of the population X IMA]. RESULTS: This study was done on 18 DR and 20 non- diabetic patients. The mean Serum IMA values in DR group and controls were 0.50±0.17 and 0.32±0.17, respectively (P=0.002). The mean serum AAIMA values in DR group and controls were 0.48±0.20 and 0.32±0.17, respectively (P=0.01). The albumin and HDL- Cholesterol levels were significantly lower in DR patients compared to controls (p=0.004 and p=0.01, respectively). CONCLUSIONS: The level of IMA and AAIMA were higher in cases of DR compared to that of non-diabetic subjects. The levels of albumin and HDL-Cholesterol were lower in DR patients compared to controls.

Urban-rural differences in atherogenic dyslipidaemia (URDAD Study): a retrospective report on diabetic and non-diabetic subjects of Northern India.

Diabetes and urbanization are major contributors to increased risk factors of cardiovascular diseases. Studying whether atherogenic dyslipidaemia increases with urbanization in type 2 diabetes mellitus is, therefore, important. The sample of the present study consisted of 400 subjects. They were categorized according to residential area and diabetes into four groups: urban diabetic group, urban non-diabetic control group (from a metropolitan city Delhi), rural non-diabetic diabetic group, and rural control group (from villages of Khanpur Kalan, Sonepat, Haryana). Differences in lipid levels and risk factors of emerging cardiovascular diseases between groups were evaluated with analysis of variance. Diabetic patients of both urban and rural areas had significantly higher total cholesterol (TC), triglycerides (TG), very low-density lipoproteins (VLDL), TC to high-density lipoprotein cholesterol (TC/HDL) ratio, TG to high-density lipoprotein cholesterol (TG/HDL) ratio, and atherogenic index (AI) compared to respective controls (p<0.05). The HDL concentrations in urban diabetics were significantly lower (p<0.05) than in urban non-diabetic group and rural diabetic group. Comparison between urban and rural diabetic groups showed significantly higher atherogenic dyslipidaemia (AD) in the urban patient-group (p<0.05). We evaluated significant relationships of diabetes and urbanization with AD by multiple regression analysis. Receiver operating curve (ROC) analysis showed high area under curve (AUC) for TG/HDL in urban diabetic group (0.776, p<0.0001) and in rural diabetic group (0.692, p<0.0001). It is concluded that diabetes was associated with higher AD parameters. Urbanization in diabetes is also associated with elevated levels of AD, indicating higher risk in urban population. This study suggests that TG/HDL may be particularly useful as atherogenic risk predictor in newly-diagnosed type 2 diabetic patients.