Skewed X-chromosome inactivation in scleroderma.

Scleroderma is a female-prevalent autoimmune disease of unclear etiology. Two fundamental gender differences, skewed X-chromosome inactivation (XCI) and pregnancy-related microchimerism, have been implicated in scleroderma. We investigated the XCI patterns of female scleroderma patients and the parental origin of the inactive X chromosome in those patients having skewed XCI patterns (>80%). In addition, we investigated whether a correlation exists between XCI patterns and microchimerism in a well-characterized cohort. About 195 female scleroderma patients and 160 female controls were analyzed for the androgen receptor locus to assess XCI patterns in the DNA extracted from peripheral blood cells. Skewed XCI was observed in 67 (44.9%) of 149 informative patients and in 10 of 124 healthy controls (8.0%) [odds ratio (OR) = 9.3 (95% confidence interval (CI) 4.3-20.6, P 90%) was present in 44 of 149 patients (29.5%) but only in 3 of 124 controls (2.4%; OR = 16.9; 95% CI 4.8-70.4, P < 0.0001). Parental origin of the inactive X chromosome was investigated for ten patients for whom maternal DNA was informative, and the inactive X chromosome was of maternal origin in eight patients and of paternal origin in two patients. Skewed XCI mosaicism could be considered as an important risk factor in scleroderma

Case-Control Study of Fetal Microchimerism and Breast Cancer

Prior pregnancy is known to protect against development of breast cancer. Recent studies have demonstrated that pregnancy has the capacity to establish small numbers of immunologically active fetal-derived cells in the mother, a phenomenon known as fetal microchimerism (FMc). We asked whether presence of FMc, routinely acquired during pregnancy, is a protective factor for breast cancer.DNA extracts from peripheral blood specimens were obtained from a population-based case-control study of risk factors for breast cancer in women 21 to 45 years old. Specimens were tested with quantitative PCR for presence and concentrations of male DNA presumed to derive from prior pregnancies with a male fetus. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with consideration of multiple established reproductive and environmental risk factors for breast cancer. FMc results were generated on 99 parous women, 54 with primary invasive breast cancer and 45 general population controls. FMc prevalence was 56% (25/45) and 26% (14/54) in controls and cases, respectively. Women harboring FMc were less likely to have had breast cancer (OR = 0.29, 95% CI 0.11-0.83; p = 0.02, adjusting for age, number of children, birth of a son, history of miscarriage, and total DNA tested). In addition, FMc concentrations were higher in controls versus cases (p = 0.01). Median concentrations were 2 (0-78) and 0 (0-374) fetal genomes/10(6) maternal genomes in controls and cases, respectively.Results suggest that the enigma of why some parous women are not afforded protection from breast cancer by pregnancy might in part be explained by differences in FMc. Mechanistic studies of FMc-derived protection against breast cancer are warranted

EFFECT OF SUPPLEMENTATION OF VITAMIN C ON BLOOD GLUCOSE AND GLYCOSYLATED HEMOGLOBIN LEVELS IN EXPERIMENTALLY-INDUCED DIABETIC RABBITS: EFFECT OF SUPPLEMENTATION OF VITAMIN C ON BLOOD GLUCOSE AND HbA1c LEVELS IN EXPERIMENTALLY INDUCED DIABETIC RABBITS.

Objectives: Diabetes mellitus (DM) is a spectrum of common metabolic disorders, arising from a variety of pathogenic mechanisms resulting in hyperglycemia that causes chronic micro- and macro-vascular complications. Vitamin C is structurally similar to glucose and can replace it in many chemical reactions and thus is effective in the prevention of non-enzymatic glycosylation of proteins. Hence, the present study taken up to see the effect of supplementation of Vitamin C on blood glucose and glycosylated hemoglobin (HbA1c) along with metformin in experimentally-induced diabetic rabbits. Methods: Twenty-four adult New Zealand white rabbits (1.5–2.5 kg) were divided into four groups, each containing six rabbits. Group 1: Normal control (distilled water); Group 2: Metformin (23.33 mg/kg) is given orally; Group 3: Metformin (23.33 mg/kg) plus Vitamin C 250 mg are given orally; and Group 4: Metformin (23.33 mg/kg) plus Vitamin C 500 mg are given orally. Animals were treated for 30 days. The blood samples were collected on days 0 and 30 from the marginal ear vein of rabbits for the estimation of blood glucose and HbA1c levels. Results: Statistically analyzed by ANOVA test followed by post hoc Tukey’s test using GraphPad Prism software. Results shown that Vitamin C 500 mg oral supplementation with metformin had very highly significantly reduced HbA1c levels by 40.12% (p = 0.0001***) and blood glucose levels by 49.12% (p = 0.0003***), whereas Vitamin C 250 mg oral supplementation with metformin also significantly reduced HbA1c levels by 25.49% (p = 0.0001***) and blood glucose levels by 42.95% (p = 0.0026**) when compared to metformin alone, which reduced HbA1c levels by 22% (p = 0.0001***) and blood glucose levels by 39.58% (p = 0.0001***). Conclusion: Oral supplementation of Vitamin C 500 mg/250 mg to the metformin was superior in reducing HbA1c levels and blood glucose levels compared to metformin alone in rabbits. Hence, Vitamin C oral supplementation may be helpful in lowering blood glucose levels and HbA1c levels and improving glycemic control in Type 2 DM

Appraisal of 1-Butylimidazole-Derived Ionic Liquids as Anthelmintic Agents: An Experimental and In Silico Approach

We have synthesized and characterized 1-butyl-3-alkylimidazolium derived ionic liquids (ILs) functionalized with various alkyl groups (-C2H5, -C4H9, -C6H13, -C8H17, and -C10H21) and counter anions ((Formula presented.)). Further, these ILs were tested for the vermicidal activity and cell-viability study against the Pheretima posthuma (Indian earthworm) and MC3T3-L1 cells, respectively. IL-OH with higher alkyl chains (-C10H21) displayed promising vermicidal activity as compared to other counterparts (IL−Br and IL-BF4). Further, quantitative-structure-activity-relationships (QSAR) modelling was carried out using density functional theory (DFT) derived quantum mechanical descriptors to assess the factors responsible for the biological activities. Based on the QSAR study it was found that LUMO of the anion and polar surface area of the cation possess significant correlation (r2, 0.85; RMSE, 0.06). Also, receptor-binding based molecular docking was carried out to study the binding patterns of the tested IL. Introduction. In past few decades, ionic liquids (ILs) have generated paramount interest in several field of chemistry, i.e., catalysis, electrochemistry,, biotechnology, biomass energy and pharmaceutical applications–, and many others. This wide range of applications are due to their characteristic tunable nature of ILs which facilitate desired biochemical properties via varying their counter anions and alkyl chain length., Subsequent tailoring of biologically active cations or anions can add substantial potential to their therapeutic implication and administration as active pharmaceutical ingredients (APIs)., Efforts are made to probe the effects of various anions, alkyl chains and charge on the quaternary nitrogen atom. It has been articulated that medicinal aspect of ILs is greatly impeded by their toxicity; however, attempts are in the progress to afford a balance between toxicity and biochemical/ biopharmaceutical properties. In particular, the maxim “poison is in the dose”, encouraged to develop ILs as useful therapeutics. Earlier, we have screened the imidazolium derived ILs for their vermicidal activity with varying alkyl chains (R= -C2H5, -C4H9, -C6H13, -C8H17) and Br−/OH− as counter anions

Single Ion Conducting Polymer Electrolytes Based On Versatile Polyurethanes

Single-ion polymer electrolytes are expected to play an important role in the development of next-generation lithium metal batteries. In this paper, the synthesis and characterization of single-ion conducting polyurethanes (SIPUs) based on PEG and a specifically designed ionic liquid monomer (bis-MPTFSI) is presented. Exploiting the flexible chemistry of polyurethanes, it was possible to tailor the composition and chemical structure of SIPE, obtaining both segmented and crosslinked lithium ion-conductive (σ = 10−8−10−4 S cm−1) and free-standing films with the lithium transference number close to unity. Finally, the performances of gel polymer electrolytes based on SIPUs for lithium metal batteries operating at room temperature were investigated (80 cycles at C/10 with nearly 100% efficiency). To the best of our knowledge, these SIPUs represent one of the first examples of polyurethane-based poly(ionic liquid)s for application in the field of battery science

Anthropometry and physical fitness in individuals with family history of type-2 diabetes mellitus: A comparative study

Context: The risk of becoming a diabetic for an individual with a positive family history of diabetes increases by two- to fourfold. Aim: To record the anthropometric indices and the physical fitness in individuals with family history of type-2 diabetes mellitus and compare these results with those of controls. Settings and Design: This is a comparative study done in the department of physiology. Materials and Methods: Thirty-two apparently healthy medical students with family history of type-2 Diabetes Mellitus were chosen for the study and matched with equal number of controls. Anthropometric measurements (height, weight, waist circumference, hip circumference, thigh circumference, upper segment and lower segment) were recorded. Body mass index (BMI), waist-hip ratio (WHR), waist-thigh ratio (WTR), and upper to lower segment ratio (US/LS ratio) were calculated. Blood pressure and heart rate were measured. Physical fitness was evaluated using Queen′s College step test protocol. Rate Pressure Product (RPP) and Physical Fitness Index (PFI) were calculated before and after exercise. Statistical Analysis: Statistical analysis was done using SPSS software. Results: BMI, WHR, US/LS ratio, and RPP at rest were significantly higher (P < 0.05), whereas WTR, PFI, and RPP after exercise lower (P > 0.05) in cases as compared to controls. Conclusions: It can be concluded that apparently healthy individuals with family history of type-2 diabetes mellitus have higher anthropometric values and lower physical fitness than the controls