DNA methylation and type 2 diabetes: a systematic review.

Objective: DNA methylation influences gene expression and function in the pathophysiology of type 2 diabetes mellitus (T2DM). Mapping of T2DM-associated DNA methylation could aid early detection and/or therapeutic treatment options for diabetics.

Design: A systematic literature search for associations between T2DM and DNA methylation was performed.

Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population.

Introduction: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants.

Untargeted Maternal Plasma Metabolomics in Hirschsprung Disease: A Pilot Study.

Background And Aims: Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology affecting the enteric nervous system (ENS). Since the early gestational development of the ENS is dependent on the prenatal maternal metabolic environment, the objective of this pilot study was to explore the role of specific maternal plasma metabolites in the etiology of HSCR.

Methods: In this cross-sectional study, postnatal (as a surrogate for prenatal) plasma samples were obtained from mothers of children diagnosed with HSCR ( = 7) and age-matched mothers of normal children ( = 6).

Evaluation of the expression of genes associated with iron metabolism in peripheral blood mononuclear cells from Type 2 diabetes mellitus patients.

Aims: Type 2 Diabetes (T2DM) has been linked to ferroptosis. This study aimed to assess expression levels of genes linked with iron metabolism in peripheral blood mononuclear cells (PBMCs) from T2DM patients and to investigate the association of these expression levels with anthropometric and clinical parameters.

Methods: Gene expression of iron metabolism genes (Ferritin Light Chain, FTL; Ferritin Heavy Chain, FTH1; Transferrin Receptor, TFRC; Divalent Metal Transporter 1, SLC11A2; Ferroportin, SLC40A1) in archival PBMCs was assessed using quantitative real-time PCR assays.

Bioavailability and daily requirement of vitamin B in adult humans: an observational study of its colonic absorption and daily excretion as measured by [C]-cyanocobalamin kinetics.

Background: Clinical and biochemical vitamin B (B) deficiency is lower than anticipated in vegetarians. Extraileal absorption, such as from the colon, as well as reduced daily excretion, may be adaptive mechanisms to maintain B homeostasis with marginal intakes.

Objective: To measure the absorption of B from the small and large intestine, and its daily rate of excretion from the body, using a [C]-cyanocobalamin tracer.

The Effect of Zinc Biofortified Wheat Produced via Foliar Application on Zinc Status: A Randomized, Controlled Trial in Indian Children.

Background: Agronomic zinc biofortification of wheat by foliar application increases wheat zinc content and total zinc absorption in humans.

Objectives: To assess the effect of agronomically biofortified whole wheat flour (BFW) on plasma zinc (PZC) compared with a postharvest fortified wheat (PHFW) and unfortified control wheat (CW) when integrated in a midday school meal scheme.

Methods: We conducted a 20-wk double-blind intervention trial in children (4-12 y, n = 273) individually randomly assigned to 3 groups to receive a daily school lunch consisting of 3 chapattis prepared with the 3 different wheat flour types.

Maternal Vitamin A Status as a Risk Factor of Hirschsprung Disease in the Child.

Introduction: The gene-environment interaction of the REarranged during Transfection ( RET ) gene with vitamin A in the etiopathogenesis of Hirschsprung disease (HSCR) has been suggested in rodents. The aim of this study was to evaluate vitamin A status in mothers of children with HSCR and to assess its association with pathogenic variants of the RET gene in affected children.

Methods: This was a case-control study of stable isotope-based vitamin A measurement stores of mothers of children diagnosed with HSCR (within 8 months from birth, n = 7) and age-matched mothers of normal children (n = 6).

Identification of stable reference genes in peripheral blood mononuclear cells from type 2 diabetes mellitus patients.

Reference genes are obligatory for accurate normalization of mRNA transcript levels across samples and experimental conditions in Real Time-polymerase chain reaction (qRT-PCR) based quantitative gene expression assays. Selection of stably expressed reference genes is therefore crucial for ensuring reproducibility of such assays. However, there is a complete dearth of data on stability of commonly used reference genes in Peripheral Blood Mononuclear Cells (PBMCs) from Type 2 diabetes mellitus (T2DM) patients.

Unique attributes of obesity in India: A narrative review.

Obesity has become a burgeoning epidemic in India, even though the country is still dealing with undernutrition. As a significant determinant of the Metabolic Syndrome (MetS) and non-communicable diseases (NCDs) such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), understanding the Indian context of the problem and learning how to deal with the obesity epidemic in this country has gained paramount importance. This narrative review points to the unique features of the obesity epidemic in India and its associated contributing factors, including the evolving nature of the Indian diet, the peculiarity of the increased adiposity at lower BMIs, unique obesity-associated genetic variants in Indians, the contribution of the gut microbiome, the impact of chronic inflammation and the role of ambient air pollution, and the contribution of decreased physical activity levels concerning the rapid urbanisation and the built environment.

Intraindividual double burden of malnutrition: The contribution of the infant gut microbiome.

The prevalence of the double burden of malnutrition in society is well known with the coexistence of undernutrition with an increase in overweight/obesity; this has been increasing globally with nutritional imbalances and infectious diseases being the major etiological factors. However, there is also the coexistence of inappropriate adiposity or metabolic dysfunction in an individual who appears currently undernourished by anthropometric standards (stunted or underweight); this is the intraindividual double burden of malnutrition. It could also occur in temporal sequence, as anthropometric overweight in an individual who has previously endured childhood under-nutrition.

Placental expression of miR-517-5p and miR-518f-5p: Fetal sex-specific relations with human fetoplacental growth.

Objective: We aimed to assess association of chromosome 19 miRNA cluster microRNAs (miR-517-5p and miR-518f-5p) expression with maternal, placental and newborn parameters and with their potential angiogenesis-associated target genes ENG, VEGF and FLT in a set of 68 small- (SGA, n = 30) and appropriate- (AGA, n = 38) for gestational age full-term singleton pregnancies, in relation to fetal sex.

Study Design: In this retrospective case-control study, placental transcript abundances of miR-517-5p and miR-518f-5p were assessed by real-time quantitative PCR after normalization to reference miRNA, mir-16-5p. Placental transcript abundances of VEGF, FLT and ENG were assessed after normalizing to a set of reference genes.

Variability of human fasted venous plasma metabolomic profiles with tourniquet induced hemostasis.

Venous plasma metabolomics is a potent and highly sensitive tool for identifying and measuring metabolites of interest in human health and disease. Accurate and reproducible insights from such metabolomic studies require extreme care in removing preanalytical confounders; one of these is the duration of tourniquet application when drawing the venous blood sample. Using an untargeted plasma metabolomics approach, we evaluated the effect of varying durations of tourniquet application on the variability in plasma metabolite concentrations in five healthy female subjects.

Gut microbiota profiles of young South Indian children: Child sex-specific relations with growth.

Gut microbiota has been implicated as a modifier of childhood growth. Here, 16S rRNA sequencing-based fecal microbiota profiles of 18-24 month old Indian children were evaluated (n = 41), in relation to their anthropometric parameters, intestinal permeability, body composition and total energy expenditure. Pathway analyses were conducted to assess microbial functions related to stunting, underweight and wasting.

Protocol for a prospective, observational, deep phenotyping study on adipose epigenetic and lipidomic determinants of metabolic homoeostasis in South Asian Indians: the Indian Diabetes and Metabolic Health (InDiMeT) study.

Introduction: We describe the rationale and broad study design of the Indian Diabetes and Metabolic Health (InDiMeT) study, a new prospective, observational study incorporating extensive epigenetic (DNA methylation) and lipidomic signatures to examine their association with the dysregulation of adipose de novo lipogenesis (DNL) in South Asian Indians. The InDiMeT study aims to use a case-control design to identify genetic and modifiable-environmental-lifestyle associated determinants of (1) epigenomic (DNA methylome) dysregulation of adipose DNL in type 2 diabetes mellitus (T2DM) adipose tissue, (2) identify correlates of epigenomic (DNA methylome) dysregulation of adipose DNL in peripheral blood mononuclear cells (PBMCs) from T2DM subjects and (3) elucidate plasma lipidomic correlates of adipose DNL in T2DM that can be used as biomarkers of adipose tissue dysfunction.

Methods And Analysis: The InDiMeT study will involve recruitment of 176 normoglycaemic and T2DM individuals who will be undergoing laparoscopic surgery for clinical conditions.

Metabolome and microbiome alterations related to short-term feeding of a micronutrient-fortified, high-quality legume protein-based food product to stunted school age children: A randomized controlled pilot trial.

Background & Aims: Stunting in children is a comorbid condition in undernutrition that may be ameliorated by the provision of high-quality foods that provide protein and micronutrients. Addressing this problem in lower social economic environments requires, in part, affordable and scalable food-based solutions with efficacious food products. Towards this end, biochemical/metabolic indicators for fast-throughput screening of foods and their components are desired.

Acyl ethanolamides in Diabetes and Diabetic Nephropathy: Novel targets from untargeted plasma metabolomic profiles of South Asian Indian men.

The pathophysiology of diabetic nephropathy (DN) in type 2 diabetes (T2D) patients is minimally understood. We compared untargeted high-resolution accurate mass (HRAM) orbitrap-based plasma metabolomic profiles of 31 T2D-DN (with estimated glomerular filtration rate ≤80 mL/min/1.73 m), 29 T2D and 30 normal glucose tolerance (NGT) Indian men.

Introducing a molecular basis to physiology in undergraduate medical education.

Background: Medical professionals in India need to understand the concepts of molecular genetics to stay up-to-date with clinical care as well as to strengthen basic research in the biomedical sciences.

Methods: We introduced a modular course on 'Fundamentals in molecular and cellular biology' for first-year medical undergraduate students in the second semester of the first MBBS year in 2015, as part of 'Innovations in teaching physiology' at St John's Medical College. This was a voluntary, add-on course with didactic lectures, hands-on practical classes and a research paper presentation.

Placental expression of angiogenesis-related genes and their receptors in IUGR pregnancies: correlation with fetoplacental and maternal parameters.

Aberrations in placental vascular development compromising fetal supply of oxygen and essential nutrients can be a significant contributor to intrauterine growth restriction (IUGR). The development of placental vascular tree is under the influence of two families of growth factors, namely the vascular endothelial growth factor (VEGF) family and angiopoietin/TEK family. In this study, we have examined the expression of angiogenesis-related growth factors, mainly VEGF family and angiopoietin-TEK (endothelial-specific receptor tyrosine kinase) family genes in placentae from IUGR pregnancies uncomplicated by preeclampsia (PE) compared to normal pregnancies.

Combined Vitamin B-12 and Balanced Protein-Energy Supplementation Affect Homocysteine Remethylation in the Methionine Cycle in Pregnant South Indian Women of Low Vitamin B-12 Status.

Low-quality dietary protein intake and vitamin B-12 deficiency could interact to decrease methionine transmethylation and remethylation rates during pregnancy and may affect epigenetic modifications of the fetal genome. The objective of this randomized, partially open-labeled intervention trial was to examine the effect of supplemental high-quality protein and vitamin B-12 on third-trimester methionine kinetics in pregnant Indian women with a low vitamin B-12 status. Pregnant women with low serum vitamin B-12 concentrations (<200 pmol/L) were randomly assigned to 1 of 3 groups: the first group received balanced protein-energy supplementation of 500 mL milk/d plus a 10-μg vitamin B-12 tablet/d (M+B-12 group; = 30), the second group received milk (500 mL/d) plus a placebo tablet (M+P group; = 30), and the third group received a placebo tablet alone (P group; = 33).

Dehydro-alpha-lapachone, a plant product with antivascular activity.

Antivascular agents have become a standard of treatment for many malignancies. However, most of them target the VEGF pathway and lead to refractoriness. To improve the diversity of options for antivascular therapy, we applied a high-throughput screen for small molecules targeting cell adhesion.

ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish.

Arterial morphogenesis is an important and poorly understood process. In particular, the signaling events controlling arterial formation have not been established. We evaluated whether alterations in the balance between ERK1/2 and PI3K signaling pathways could stimulate arterial formation in the setting of defective arterial morphogenesis in mice and zebrafish.

Deciphering arterial identity through gene expression, genetics, and chemical biology.

Purpose Of Review: The present review presents a current view of vascular development, with a focus on the factors contributing to the establishment of arterial-venous identity and the potential of chemical biology for providing new insights into this field.

Recent Findings: Genetics and gene expression studies have begun to define the complex network of molecular pathways that govern the formation of the embryonic vasculature, but these approaches have limited ability to spatially and temporally manipulate gene expression and function. Recently, the power of chemical biology, combined with model systems like zebrafish, has enabled discovery of additional contributors to vascular development and has provided a means of manipulating gene function with enhanced spatial and temporal control.

Fishing for new antimicrobials.

The discovery of antibiotics and other antimicrobial agents in the 1930s is arguably the most significant therapeutic advance in medical history. Penicillin and the sulfa drugs touched off the search for and discovery of countless derivative compounds and several new antibiotic classes. However, the pace of discovery has slowed down, and there is growing appreciation that much of the low-lying fruit accessible to traditional methods of antimicrobial discovery has been harvested.

Embryonic stem cell and tissue-specific expression of a novel conserved gene, asrij.

We have identified a novel gene expressed in murine embryonic stem (ES) cells and in a restricted, tissue-specific pattern during mouse development. The gene is also expressed in blood vessels; hence, we have named it asrij (Sanskrit; asRîj= blood). The gene encodes a novel conserved, predicted transmembrane protein of 247 amino acids, which is localized to lysosomes and endosomes.