Singapore Institute of Clinical Science

Singapore, Singapore

Singapore Institute of Clinical Science

Singapore, Singapore
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Gao J.,National University of Singapore | Ong J.J.-X.,McGill University | Henry J.,Singapore Institute of Clinical Science | Zhou W.,National University of Singapore
Food Quality and Preference | Year: 2017

This study aimed to understand the impact of bread structure and its dynamic transformation on people's chewing behaviour and texture perception. Results from 20 trained panellists showed that bread crust/skin was the dominating factor in oral processing. This ‘outer layer’ introduced a mechanical contrast which increased chewing effort, lowered swallowing thresholds but did not elicit more a complex texture sensation. Furthermore, a single-panellist study was conducted as a proof-of-concept to demonstrate a new temporal correlation method. Progressive fragmentation and hydration diminished the differences between heterogeneous and homogeneous samples, leading to converged bolus properties and chewing effort. However, the differences in texture perception and chewing frequency due to the presence of the crust/skin were not diminished and even became larger throughout oral processing. Hence, chewing force and chewing rhythm might have different modulation mechanisms. Overall, bolus hydrated sensation was largely used by the panellist to gauge the swallowing point while bolus texture was used in a feedback control to regulate the mastication behaviour. © 2017

Gao J.,National University of Singapore | Wong J.X.,National University of Singapore | Lim J.C.-S.,National University of Singapore | Henry J.,Singapore Institute of Clinical Science | Zhou W.,National University of Singapore
Journal of Food Engineering | Year: 2015

The strong interconnection between food structure and its resistance to breakdown is the rationale behind designing bread structure to control its digestion, starting from the oral phase. Three types of bread, i.e. baguette, baked bread and steamed bread, with distinct cellular structures and textures were prepared by only varying the processing conditions. Baguette with thick and dry curst required a larger chewing force and a longer chewing time than steamed bread which has a moist and soft skin. Greater chewing effort resulted in more saliva impregnated and smaller particle size in baguette bolus which might elevate starch digestion and glycaemic response. The impact of crumb structure on oral processing was more complicated which involved both the mechanical strength of the crumb and the textural perception it elicited. Strong correlation was found among bread structure, texture, and oral processing behavior. Our study demonstrated that two important factors, grain feature of bread crumb and the relative portion of bread crust, should be considered when designing bread structure. © 2015 Elsevier Ltd. All rights reserved.

Tai E.S.,National University of Singapore | Tan M.L.S.,Singapore Health Services | Stevens R.D.,Sarah edman Nutrition And Metabolism Center | Low Y.L.,Singapore Institute of Clinical science | And 10 more authors.
Diabetologia | Year: 2010

Aims/hypothesis: Insulin resistance (IR) is associated with obesity, but can also develop in individuals with normal body weight. We employed comprehensive profiling methods to identify metabolic events associated with IR, while controlling for obesity. Methods: We selected 263 non-obese (BMI approximately 24 kg/m2) Asian-Indian and Chinese men from a large cross-sectional study carried out in Singapore. Individuals taking medication for diabetes or hyperlipidaemia were excluded. Participants were separated into lower and upper tertiles of IR based on HOMA indices of ≥1.06 or ≤1.93, respectively. MS-based metabolic profiling of acylcarnitines, amino acids and organic acids was combined with hormonal and cytokine profiling in all participants. Results: After controlling for BMI, commonly accepted risk factors for IR, including circulating fatty acids and inflammatory cytokines, did not discriminate the upper and lower quartiles of insulin sensitivity in either Asian-Indian or Chinese men. Instead, IR was correlated with increased levels of alanine, proline, valine, leucine/isoleucine, phenylalanine, tyrosine, glutamate/glutamine and ornithine, and a cluster of branched-chain and related amino acids identified by principal components analysis. These changes were not due to increased protein intake by individuals in the upper quartile of IR. Increased abdominal adiposity and leptin, and decreased adiponectin and IGF-binding protein 1 were also correlated with IR. Conclusions/interpretation: These findings demonstrate that perturbations in amino acid homeostasis, but not inflammatory markers or NEFAs, are associated with IR in individuals of relatively low body mass. © 2009 Springer-Verlag.

Sriram S.,Nanyang Technological University | Subramanian S.,Nanyang Technological University | Sathiakumar D.,Nanyang Technological University | Venkatesh R.,Nanyang Technological University | And 5 more authors.
Aging Cell | Year: 2011

Abnormal levels of reactive oxygen species (ROS) and inflammatory cytokines have been observed in the skeletal muscle during muscle wasting including sarcopenia. However, the mechanisms that signal ROS production and prolonged maintenance of ROS levels during muscle wasting are not fully understood. Here, we show that myostatin (Mstn) is a pro-oxidant and signals the generation of ROS in muscle cells. Myostatin, a transforming growth factor-β (TGF-β) family member, has been shown to play an important role in skeletal muscle wasting by increasing protein degradation. Our results here show that Mstn induces oxidative stress by producing ROS in skeletal muscle cells through tumor necrosis factor-α (TNF-α) signaling via NF-κB and NADPH oxidase. Aged Mstn null (Mstn -/-) muscles, which display reduced sarcopenia, also show an increased basal antioxidant enzyme (AOE) levels and lower NF-κB levels indicating efficient scavenging of excess ROS. Additionally, our results indicate that both TNF-α and hydrogen peroxide (H 2O 2) are potent inducers of Mstn and require NF-κB signaling for Mstn induction. These results demonstrate that Mstn and TNF-α are components of a feed forward loop in which Mstn triggers the generation of second messenger ROS, mediated by TNF-α and NADPH oxidase, and the elevated TNF-α in turn stimulates Mstn expression. Higher levels of Mstn in turn induce muscle wasting by activating proteasomal-mediated catabolism of intracellular proteins. Thus, we propose that inhibition of ROS induced by Mstn could lead to reduced muscle wasting during sarcopenia. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Sriram S.,Nanyang Technological University | Subramanian S.,Nanyang Technological University | Juvvuna P.K.,National University of Singapore | Ge X.,Singapore Institute of Clinical science | And 6 more authors.
Molecular Endocrinology | Year: 2014

Smad (Sma and Mad-related protein) 2/3 are downstream signaling molecules for TGF-β and myostatin (Mstn). Recently, Mstn was shown to induce reactive oxygen species (ROS) in skeletal muscle via canonical Smad3, nuclear factor-κB, and TNF-α pathway. However, mice lacking Smad3 display skeletal muscle atrophy due to increased Mstn levels. Hence, our aims were first to investigate whether Mstn induced muscle atrophy in Smad3-/- mice by increasing ROS and second to delineate Smad3-independent signaling mechanism for Mstn-induced ROS. Herein we show that Smad3-/- mice have increased ROS levels in skeletal muscle, and inactivation of Mstn in these mice partially ablates the oxidative stress. Furthermore, ROS induction by Mstn in Smad3-/- muscle was not via nuclear factor-κB (p65) signaling but due to activated p38, ERK MAPK signaling and enhanced IL-6 levels. Consequently, TNF-α, nicotinamide adenine dinucleotide phosphate oxidase, and xanthine oxidase levels were up-regulated, which led to an increase in ROS production in Smad3-/- skeletal muscle. The exaggerated ROS in the Smad3-/- muscle potentiated binding of C/EBP homology protein transcription factor to MuRF1 promoter, resulting in enhanced MuRF1 levels leading to muscle atrophy. © 2014 by the Endocrine Society.

PubMed | National University of Singapore and Singapore Institute of Clinical science
Type: Journal Article | Journal: Journal of cellular biochemistry | Year: 2016

The infants of mothers with gestational diabetes mellitus (GDM) have an increased risk of metabolic and cardiovascular disease. It has been difficult to study the direct effects of maternal hyperglycemia on the fetus because of inaccessibility of fetal tissues. The development of tissues that simulate the function of fetal organs using stem cell technology provides an unprecedented opportunity to study this disorder. Stem cells in the Whartons jelly of the umbilical cord (hWJSCs), possess unique properties that are different from other stem cells. They are primitive, present in large numbers, non-tumorigenic, hypoimmunogenic, tumoricidal, and carry a genetic signature that represents the fetus. They are multipotent but their differentiation into functional pancreatic and cardiovascular tissues has been challenging. We have been able to reprogram hWJSCs from normal and GDM cords into induced pluripotent stem cells (iPSCs) from which a variety of functional fetal tissues including insulin-producing and cardiovascular tissues could be derived. Such tissues from reprogrammed hWJSCs of normal and GDM cords that physiologically and genetically mimic the fetus of the diabetic or non-diabetic mother are an ideal platform to study the effects of glucose, the Zika virus, and other harmful agents on the fetus. The immature stemness phenotype of hWJSCs, easy accessibility, availability in large numbers without the need for propagation, and lower risk of accumulation of epigenetic mutations make them the most attractive candidate over other umbilical cord cell types for reprogramming. Additionally, some of their beneficial genes may be retained in memory in the iPSCs derived from them. J. Cell. Biochem. 118: 437-441, 2017. 2016 Wiley Periodicals, Inc.

Godfrey K.M.,University of Southampton | Sheppard A.,University of Auckland | Sheppard A.,Agresearch Ltd. | Gluckman P.D.,University of Auckland | And 14 more authors.
Diabetes | Year: 2011

OBJECTIVE - Fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans. RESEARCH DESIGN AND METHODS - Using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5′ from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ≥5% and a 5-95% range ≥10%, we related methylation status to maternal pregnancy diet and to child's adiposity at age 9 years. Replication was sought in a second independent cohort. RESULTS - In cohort 1, retinoid X receptor-a (RXRA) chr9: 136355885+ and endothelial nitric oxide synthase (eNOS) chr7: 150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [β] 17% per SD change in methylation [95% CI 4-31], P = 0.009, n = 64, and β = 20% [9-32], P < 0.001, n = 66, respectively) and %fat mass (β = 10% [1-19], P = 0.023, n = 64 and β =12% [4-20], P = 0.002, n = 66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9: 136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (β = 6% [2-10] and β = 4% [1-7], respectively, both P = 0.002, n = 239). CONCLUSIONS - Our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later obesity and metabolic disease. © 2011 by the American Diabetes Association.

Hanson M.A.,University of Southampton | Gluckman P.D.,University of Auckland | Gluckman P.D.,Singapore Institute of Clinical science | Ma R.C.W.,Chinese University of Hong Kong | And 3 more authors.
BMC Public Health | Year: 2012

Background: The global burden of diabetes and other non-communicable diseases is rising dramatically worldwide and is causing a double poor health burden in low- and middle-income countries. Early life influences play an important part in this scenario because maternal lifestyle and conditions such as gestational diabetes and obesity affect the risk of diabetes in the next generation. This indicates important periods during the lifecourse when interventions could have powerful affects in reducing incidence of non-communicable diseases. However, interventions to promote diet and lifestyle in prospective parents before conception have not received sufficient attention, especially in low- and middle-income countries undergoing socio-economic transition. Discussion. Interventions to produce weight loss in adults or to reduce weight gain in pregnancy have had limited success and might be too late to produce the largest effects on the health of the child and his/her later risk of non-communicable diseases. A very important factor in the prevention of the developmental component of diabetes risk is the physiological state in which the parents enter pregnancy. We argue that the most promising strategy to improve prospective parents' body composition and lifestyle is the promotion of health literacy in adolescents. Multiple but integrated forms of community-based interventions that focus on nutrition, physical activity, family planning, breastfeeding and infant feeding practices are needed. They need to address the wider social economic context in which adolescents live and to be linked with existing public health programmes in sexual and reproductive health and maternal and child health initiatives. Summary. Interventions aimed at ensuring a healthy body composition, diet and lifestyle before pregnancy offer a most effective solution in many settings, especially in low- and middle-income countries undergoing socio-economic transition. Preparing a mother, her partner and her future child for "the 1000 days", whether from planned or unplanned conception would break the cycle of risk and demonstrate benefit in the shortest possible time. Such interventions will be particularly important in adolescents and young women in disadvantaged groups and can improve the physiological status of the fetus as well as reduce the prevalence of pregnancy conditions such as gestational diabetes mellitus which both predispose to non-communicables diseases in both the mother and her child. Pre-conception interventions require equipping prospective parents with the necessary knowledge and skills to make healthy lifestyle choices for themselves and their children. Addressing the promotion of such health literacy in parents-to-be in low- and middle-income countries requires a wider social perspective. It requires a range of multisectoral agencies to work together and could be linked to the issues of women's empowerment, to reproductive health, to communicable disease prevention and to the Millennium Development Goals 4 and 5. © 2012 Hanson et al.; licensee BioMed Central Ltd.

Ma R.C.W.,Chinese University of Hong Kong | Chan J.C.N.,Chinese University of Hong Kong | Tam W.H.,Chinese University of Hong Kong | Hanson M.A.,University of Southampton | And 2 more authors.
Clinical Obstetrics and Gynecology | Year: 2013

A greater proportion of women of reproductive age are now overweight or obese. Gestational diabetes mellitus and maternal obesity are associated with long-term adverse consequences in the offspring and subsequent generations, and are important drivers of the escalating global burden of diabetes and cardiovascular disease. We review the evidence linking gestational diabetes mellitus and maternal obesity with a greater risk of metabolic compromise in the offspring. We use an evolutionary perspective to elucidate the origins of gestational diabetes. Focusing efforts on maternal health is an important approach to combating the growing burden of diabetes and other noncommunicable diseases. © 2013, Lippincott Williams & Wilkins.

Lagger S.,Medical University of Vienna | Meunier D.,Medical University of Vienna | Mikula M.,Medical University of Vienna | Brunmeir R.,Medical University of Vienna | And 12 more authors.
EMBO Journal | Year: 2010

Histone deacetylase (HDAC) inhibitors induce cell cycle arrest, differentiation or apoptosis in tumour cells and are, therefore, promising anti-cancer reagents. However, the specific HDAC isoforms that mediate these effects are not yet identified. To explore the role of HDAC1 in tumourigenesis and tumour proliferation, we established an experimental teratoma model using wild-type and HDAC1-deficient embryonic stem cells. HDAC1-deficient teratomas showed no significant difference in size compared with wild-type teratomas. Surprisingly, loss of HDAC1 was not only linked to increased apoptosis, but also to significantly enhanced proliferation. Epithelial structures showed reduced differentiation as monitored by Oct3/4 expression and changed E-cadherin localization and displayed up-regulated expression of SNAIL1, a regulator of epithelial cell plasticity. Increased levels of the transcriptional regulator SNAIL1 are crucial for enhanced proliferation and reduced differentiation of HDAC1-deficient teratoma. Importantly, the analysis of human teratomas revealed a similar link between loss of HDAC1 and enhanced tumour malignancy. These findings reveal a novel role for HDAC1 in the control of tumour proliferation and identify HDAC1 as potential marker for benign teratomas. © 2010 European Molecular Biology Organization.

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