
Raghunath ManchalaICMR National Institute of Nutrition · Endocrinology and Metabolism
Raghunath Manchala
M.Sc.,Ph.D.
About
133
Publications
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January 1979 - May 2017
January 2007 - present
January 2004 - December 2012
Publications
Publications (133)
Background
Traditionally associated with recreational and spiritual uses, psychedelics have gained attention in psychotherapy for their therapeutic potential. Functioning as potent 5‐hydroxytryptamine (5HT) agonists, these compounds have demonstrated the ability to enhance neural plasticity by activating serotoninergic and glutamatergic systems. De...
Background
Obesity and ageing individually pose significant challenges to global public health, leading to preventable deaths. With an increasing geriatric population due to improved medical interventions, the intersection of these health issues becomes a critical concern worldwide. Both developed and developing countries grapple with the consequen...
The weaknesses of healthcare systems have been sharply revealed amid the instability of the COVID-19 pandemic and the ongoing conflicts across the borders of different countries. One thing unites these two crises that appear to be separate: the incapacity of healthcare systems to provide for the most basic human requirements in emergency situations...
Fenugreek seeds are rich in various essential compounds and these components play a significant role in healing and treating diseases by regulating several biological activities. The purpose of this study was to evaluate the metabolic effects of fenugreek seed (FS) and its bioactive compounds such as Fenu pulse (FP), Fenu fiber (FF), Diosgenin (Dsg...
Abstract: Major Depressive Disorder (MDD), colloquially known as depression, is a debilitating condition affecting an estimated 3.8% of the population globally, of which 5.0% are adults and 5.7% are above the age of 60. MDD is differentiated from common mood changes and short-lived emotional responses due to subtle alterations in gray and white mat...
AML remains incurable four decades after its discovery. AML (t-AML) treatment remained unchanged without any improvements in outcomes. AML is characterized by cytogenetic abnormalities along with genetic and epigenetic changes. Molecular aberrated mutations, like FLT3-ITD and NPM1mut, are associated with high relapse rates. However, the persistence...
Background
One of the most common neurodegenerative diseases is Alzheimer’s disease where complex etiological alterations have been observed along with the typical pathology. Specifically, it has been proposed that epigenetic activation of specific genes due to other physiological conditions may also contribute to its pathology.
Method
Ageing bein...
Introduction. Maternal micronutrient deficiencies are predominant in developing countries. Vitamin B12 deficiency is common in women, especially during child-bearing age. Maternal vitamin B12 deficiency is known to have a profound impact on the developing fetus and programs it to a number of complex adult-onset disorders like cardiovascular disease...
Obesity has become a worldwide health problem. It triggers additional co-morbidities like cardiovascular diseases, cancer, depression, sleep disorders, gastrointestinal problems and many more. Excess accumulation of fat in obesity could be caused by many factors like sedentary lifestyle, consumption of high fat diet, genetic predisposition, etc. Im...
Background: Osteoporosis is a skeletal disorder characterized by low bone mass with consequent increase in bone fragility and fracture. The interplay between genetics and environment has a crucial role in determining the bone mineral density. Many studies showed that the genetic polymorphisms of MTHFR gene and its impact in the development of numer...
Vitamin B12 deficiency is a critical problem worldwide and peri-conceptional deficiency of this vitamin is associated with the risk of complex cardio-metabolic diseases. Nutritional perturbations during these stages of development may lead to changes in the fetal epigenome. Using Wistar rat model system, we have earlier shown that low maternal B12...
Alzheimer’s disease (AD) is a chronic neurodegenerative disease affecting the elderly. AD is associated with a progressive decline in memory and cognitive abilities, drastic changes in behavioural patterns and other psychiatric manifestations. It leads to a significant decline in the quality of life at personal, household as well as national level....
Obesity and noncommunicable diseases (NCDs) like diabetes are epidemic in India. Developmental origins of health and disease hypothesis, based on epidemiological evidence, associates maternal undernutrition and low birth weight (LBW) of the offspring with increased obesity and diabetes in their later life. Considering widespread maternal micronutri...
Background
In severe acute pancreatitis (AP), intravenous glutamine has been shown to reduce the rate of complications, hospital stay, and mortality. In the present randomized trial, we aimed to evaluate the effect of enteral glutamine supplementation on clinical outcomes, gut permeability, systemic inflammation, oxidative stress, and plasma glutam...
The death of 154 undernourished children from acute encephalitis syndrome in a short period of 3 weeks is deeply concerning. The World Report by Patralekha Chatterjee is a timely update on a situation that recurs almost every year in Bihar, India. Chatterjee rightly pinpoints undernutrition, inadequate health facilities, and poor awareness among th...
Obesity is one of the leading causes of preventable mortalities in many parts of the globe. The rise in geriatric population due to better treatment opportunities has also emerged as a major public health challenge. Both of these health challenges have impacted developed as well as developing countries. Obesity is attributed as a powerful risk fact...
A sub-optimal nutritional environment from early life can be envisaged as a stressor that translates into mental health problems in adulthood. Considering the widespread prevalence of vitamin B12 deficiency especially amongst women in developing countries and the importance of vitamin B12 in normal brain function, in this study we have elucidated t...
Acceleration of natural ageing occurs due to multiple reasons such as stress, obesity and Type 2 diabetes working in a vicious cycle. In the present study, we tested if superimposing type 2 diabetes in a rat model of obesity accelerates ageing or not. We aggravated insulin resistance/ induced type 2 diabetes by feeding high sucrose diet (HSD) to 9-...
Magnesium plays a major role in many vital functions in the body. We reported earlier that maternal magnesium restriction altered body composition, fat metabolism, and insulin resistance in WNIN rat offspring and was associated with increased glucocorticoid stress in the offspring in their later life. We hypothesize that increased glucocorticoid st...
Tumour mass increases when tumour initiating cells (CSC) proliferate They need to activate mitochondrial respiratory and energy metabolism for proliferation Metabolic reprogramming in proliferative cells is active only in G1 phase of cell cycle We hypothesize that five transcription factors (TFs), p53, c-Myc, HIF1 and HIF 2, and FoxO, modulat...
We tried to the Cross talk between the transcription factors coupled by modulating the epigenetic modifications of regulatory genes in cancer cells. Its an insilico analysis approach to see the Spatio-Temporal interactions.
Background: Obesity and Type 2 Diabetes (T2D) are chronic nutrient-related disorders that occur together and pose a grave burden to society. They are among the most common causes of ageing and death. Obesity and T2D per se accelerate ageing albeit the underlying mechanisms are unclear yet. Also, it is not clear whether or not superimposing T2D on o...
We have demonstrated previously that severe but not moderate vitamin B12 deficiency altered body composition and induced adiposity in female C57BL/6 mice. This study aims to elucidate the effects of chronic transgenerational dietary vitamin B12 restriction on body composition and various biochemical parameters in the F1 generation offspring of our...
Ageing is a universal biological phenomenon. The incidence of age related disorders like cancer, obesity, diabetes, neurodegenerative diseases increase rapidly with ageing. Diabetes and obesity are most common chronic disorders on old age. The objective of the current study is to assess homeostasis of neurometabolites and the cerebral metabolic rat...
DNA damage caused by various sources remains one of the most researched topics in the area of aging and neurodegeneration. Increased DNA damage causes premature aging. Aging is plastic and is characterised by the decline in the ability of a cell/organism to manitain genomic stability. Lifespan can be modulated by various interventions like calorie...
Vitamin B12 deficiency is widely prevalent in women of childbearing age, especially in developing countries. In the present study, through dietary restriction, we have established mouse models of severe and moderate vitamin B12 deficiencies to elucidate the impact on body composition, biochemical parameters, and reproductive performance. Female wea...
Introduction: Deficiency of vitamin B12 (which regulates
one carbon metabolism including DNAmethylation) is
common in Indian population especially in pregnant mothers.
In-utero deficiency of vitamin B12 may be an important cause
for the fetal programming for complex diseases including
cardiovascular disease in the offspring. We are interested in
un...
This study was carried out to assess the anti-hyperglycaemic effects if any of novel synthetic binary chromium (III)-amino acid complexes in a high sucrose (HS) induced insulin resistance (IR) and or impaired glucose tolerant male Sprague Dawley (SD) rat model. Aqueous solutions of chromium chloride hexahydrate (CrCl 3 .6H 2 O) and D/L amino acids...
Maternal under-nutrition increases the risk of developing metabolic diseases. We studied the effects of chronic maternal dietary vitamin B12 restriction on lean body mass (LBM), fat free mass (FFM), muscle function, glucose tolerance and metabolism in Wistar rat offspring. Prevention/reversibility of changes by rehabilitating restricted mothers fro...
Progeria is characterized by clinical features that mimic premature ageing. Although the mutation responsible for this syndrome has been deciphered, the mechanism of its action remains elusive. Progeria research has gained momentum particularly in the last two decades because of the possibility of revealing evidences about the ageing process in nor...
Wistar of National Institute of Nutrition obese (WNIN/Ob) is a unique rat strain isolated and established at NIN, Hyderabad, India, in 1996, from its existing stock of Wistar rat colony (WNIN). This animal model exhibits all the traits of metabolic syndrome and has a remarkably reduced lifespan (1.5 years as compared to 3 years in parental WNIN rat...
Obesity has become an epidemic in worldwide population. Leptin gene defect could be one of the causes for obesity. Two mutant obese rats WNIN/Ob and WNIN/GROb, isolated at National Centre for Laboratory Animal Sciences (NCLAS), Hyderabad, India, were found to be leptin resistant. The present study aims to understand the regulatory mechanisms underl...
Unlabelled:
Maternal nutritional deficiency in-utero is known to predict risk of complex disorders like cardiovascular disease, diabetes and many neurological disorders in the offspring and vitamin B12 is one such critical micronutrient. Here we performed 2D-DIGE followed by MALDI TOF/TOF analysis to identify proteins that are differentially expre...
Background
Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, po...
Phytochemicals protect against oxidative stress which in turn helps in maintaining the balance between oxidants and antioxidants. In recent times natural antioxidants are gaining considerable interest among nutritionists, food manufacturers, and consumers because of their perceived safety, potential therapeutic value, and long shelf life. Plant foo...
Fetal growth is a complex process which depends both on the genetic makeup and intrauterine environment. Maternal nutrition during pregnancy is an important determinant of fetal growth. Adequate nutrient supply is required during pregnancy and lactation for the support of fetal/infant growth and development. Macro- and micronutrients are both impor...
In press
http://dx.doi.org/10.1016/j.ijdevneu.2012.03.253
DNA methylation is crucial for gene regulation and maintenance of genomic stability. Rat has been a key model system in understanding mammalian systemic physiology, however detailed rat methylome remains uncharacterized till date. Here, we present the first high resolution methylome of rat liver generated using Methylated DNA immunoprecipitation an...
Saturation curve. The curve shows saturation at the end on plotting the percentage of peak covered by sampling (y-axis) against the percentage of raw reads take during data reduction approach (x-axis).
(TIF)
Concordance between replicates. Read coverage at each base pair was calculated separately for both the replicates and then Pearson's correlation was calculated using R programming and statistical language.
(TIF)
Methylation density in different bins. Methylation density within genomic features along with all the repeat class (DNA, RNA, LTR, LC, LINE, SINE, SATELLITE, SIMPLE REPEAT, OTHER REPEATS, and UNKNOWN REPEATS) and rRNA (a component of RNA class) was calculated. Genomic features include RefSeq exons, introns, identified liver expressed gene exons and...
Methylated and Unmethylated CGI distribution around TSS. Methylation pattern in methylated/unmethylated CpG Island around their start site. Distribution of peak summit count in 100 bp sliding window, 5 kb upstream and downstream from the start site was calculated for methylated and unmethylated CpG Islands.
(TIF)
Distribution of CGI based on size. Distribution of mCGI and uCGI based on their size and genomic location.
(DOCX)
MACS model for MeDIP-Seq data. The reads generated from the MeDIP sequencing was processed through MACS (Model-based Analysis for ChIP-Seq) software version 1.4.0 beta for the generation of MACS model. The fragment size was 200 bp and the distance d between the forward and the reverse tags is 38.
(TIF)
CpG methylation distribution around TSS in Human, mice and rats. Average methylation density around Transcription Start Site (TSS) of 3 different species. Distribution of peak summit count in 100 bp sliding window, 5 kb upstream and downstream from the start site was calculated for all RefSeq genes of A – Human and B - Mouse. Smoothing of peaks was...
Methylation density at the start site of non coding 2nd exons. Distribution of peak summit count in 10 bp sliding window, 200 bp upstream and downstream from the start site was calculated for all 2nd exons which were non coding. Smoothing of peaks was done by taking moving average of 5.
(TIF)
PCR amplification products of alternate splice events. PCR amplification of introns of IR category showing methylation in our MeDIP-Seq data (A; IRM1 to IRM7) and their constitutive counterparts (B; IRC1 to IRC7).
(TIF)
Primer list. List of primers used in the study: The list contains primers used for calculating MeDIP-Seq enrichment efficiency, for bisulfite PCR and those used for the reverse transcriptase PCR of the rat liver cDNA.
(DOCX)
Methylation peak summit file. Details of each methylation peak generated by MACS.
(XLSX)
Bisulfite validation of MeDIP Seq data. Two regions (SSG06 and SSG08) showing high methylation and one region showing no methylation (SSG04) but with a number of CpGs were sequenced after bisulfite conversion and PCR amplification.
(TIF)
CpG methylation distribution at exon boundaries in Human, mice and rats. Methylation density around Exon/Intron junction of 3 different species. Distribution of peak summit count in 10 bp sliding window, 200 bp upstream and downstream from the start site was calculated for all exons of A- Human and B– Mouse. Smoothing of peaks was done by taking mo...
Chromosomal distribution of methylation. The methylation tracks visualized in UCSC genome browser with CGI tracks and RefSeq genes for all chromosomes.
(DOCX)
Methylation distribution in alternate splice events. CpG methylation distribution in two different alternate splice events. A: Distribution of peak summit count in 10 bp sliding window, 200 bp upstream and downstream from the start site of all RefSeq exons and cassette exons. Smoothing of peaks was done by taking moving average of 5. B: Distributio...
Real Time PCR validation of the MeDIP process. The methylated regions were selected as imprinted regions either in rat (H19) or in Human and mice (Gnas). Negative regions were randomly taken from the genome where there were no CpGs. The enrichment is shown as E.
(DOCX)
Table showing percentage of reads versus percentage of peaks called by MACS. Table showing the data generated by MACS employing data reduction approach after the model generation.
(DOCX)
List of proteins found in proteomics study. Proteins with their accession Ids and related information.
(XLSX)
Chemotherapeutic agents induce small intestinal mucositis that is characterized structurally by crypt loss and villus atrophy and functionally by absorptive and barrier impairments. We studied the effect of selected individual vitamins and multiple-vitamin mixture supplementation in modulating cisplatin-induced intestinal damage and apoptosis.
Thir...
Adult Wistar NIN (WNIN) rats (6 months old) of both sexes were orally fed Amalakirasayana at a dose of 4.5 g per kg body weight, five days in a week. The Amalakirasayana was prepared by Arya Vaidya Sala, Kottakkal, Kerala, India, which is considered as gold standard. After 3, 9 and 15 months of such therapeutic regime, rats were sacrificed and vari...
Robust evidence suggests that nutritional insult during fetal development could program the offspring to glucose intolerance, impaired insulin response and insulin resistance (IR). Considering the importance of chromium (Cr) in maintaining carbohydrate metabolism, this study determined the effect of maternal Cr restriction (CrR) on glucose metaboli...
Non-alcoholic fatty liver disease (NAFLD) is considered an integral part of metabolic syndrome (MS). We aimed to explore the inter-relations of MS and dietary composition in subjects with and without hepatic steatosis and to identify the nutritional risk factors contributing to NAFLD.
In all 98 subjects with steatosis and 102 controls were selected...
Food provides not only essential nutrients required for life, but also bioactive compounds usefull to maintan good health and disease prevention. Abundant epidemiological evidences suggest that consumption of food rich in antioxi-dants (non-nutritional components) can prevent degenerative diseases. A total of 26 commonly consumed nuts, oil seeds, e...
The purpose of this study was to (a) determine the dosage of cisplatin required to induce intestinal epithelial cell apoptosis, without causing lethality or necrosis and (b) to assess the biochemical changes in intestinal mucosa with different doses of cisplatin administration. A total of 9 WNIN weanling male rats were divided into three groups (n=...
Growth in utero is largely a reflection of nutrient and oxygen supply to the foetus. We studied the effects of Mn restriction per se, maternal Mn restriction, and postnatal high-fat feeding in modulating body composition, lipid metabolism and adipocyte function in Wistar/NIN (WNIN) rat offspring. Female weanling, WNIN rats received ad libitum for 4...
Epidemiological evidence suggests that consumption of vegetables can prevent degenerative diseases caused by oxidative stress. Considering scanty data available on antioxidant activity (AOA) of roots, tubers and vegetables commonly consumed in India, the objective of the present study was to assess their AOA and relate it to their total phenolic co...
We thank Vincent and Rasco (1) for showing interest in our work. In this present study (2), diets were prepared as per AIN 93G formulations, which use chromium (Cr) at a level of 1 mg/kg diet as recommended earlier for rodents (3). Despite this, the finding that the control diet had 1.56 mg Cr/kg diet suggests that this could be due to contribution...