Heredity of type 2 diabetes confers increased susceptibility to oxidative stress and inflammation.

INTRODUCTION AND OBJECTIVE: Heredity of type 2 diabetes mellitus (T2DM) is associated with greater risk for developing T2DM. Thus, individuals who have a first-degree relative with T2DM (FDRT) provide a natural model to study factors of susceptibility towards development of T2DM, which are poorly understood. Emerging key players in T2DM pathophysiology such as adverse oxidative stress and inflammatory responses could be among possible mechanisms that predispose FDRTs to develop T2DM. Here, we aimed to examine the role of oxidative stress and inflammatory responses as mediators of this excess risk by studying dynamic postprandial responses in FDRTs. RESEARCH DESIGN AND METHODS: In this open-label case-control study, we recruited normoglycemic men with (n=9) or without (n=9) a family history of T2DM. We assessed plasma glucose, insulin, lipid profile, cytokines and F2-isoprostanes, expression levels of oxidative and inflammatory genes/proteins in circulating mononuclear cells (MNC), myotubes and adipocytes at baseline (fasting state), and after consumption of a carbohydrate-rich liquid meal or insulin stimulation. RESULTS: Postprandial glucose and insulin responses were not different between groups. Expression of oxidant transcription factor NRF2 protein (p<0.05 for myotubes) and gene (pgroup=0.002, ptime×group=0.016), along with its target genes TXNRD1 (pgroup=0.004, ptime×group=0.007), GPX3 (pgroup=0.011, ptime×group=0.019) and SOD-1 (pgroup=0.046 and ptime×group=0.191) was upregulated in FDRT-derived MNC after meal ingestion or insulin stimulation. Synergistically, expression of target genes of inflammatory transcription factor nuclear factor kappa B such as tumor necrosis factor alpha (pgroup=0.001, ptime×group=0.007) was greater in FDRT-derived MNC than in non-FDRT-derived MNC after meal ingestion or insulin stimulation. CONCLUSIONS: Our findings shed light on how heredity of T2DM confers increased susceptibility to oxidative stress and inflammation. This could provide early insights into the underlying mechanisms and future risk of FDRTs for developing T2DM and its associated complications

Associations Between Eczema and Attention Deficit Hyperactivity Disorder Symptoms in Children

Background: Epidemiological studies suggest a link between eczema and attention deficit hyperactivity disorder (ADHD), but underlying mechanisms have not been examined.Objective: We aim to investigate the association between eczema and subsequent ADHD symptoms in the Growing Up in Singapore Towards healthy Outcomes cohort and explore the role of pro-inflammatory cytokines and gut microbiome.Methods: The modified International Study of Asthma and Allergies in Childhood questionnaire and Computerized Diagnostic Interview Schedule for Children Version IV were administered to assess reported eczema within the first 18 months and presence of ADHD symptoms at 54 months, respectively. Skin prick testing at 18 months, cytokines in maternal blood during pregnancy and cord blood and the mediating role of the gut microbiome at 24 months were assessed.Results: After adjusting for confounders, eczema with or without a positive skin prick test was associated with doubling the risk of ADHD symptoms. No differences in maternal and cord blood cytokines were observed in children with and without eczema, or children with and without ADHD. Gut microbiome dysbiosis was observed in children with eczema and children with ADHD. Children with eczema also had lower gut bacterial Shannon diversity. However, the relationship between eczema and ADHD was not mediated by gut microbiome.Conclusion: Early life eczema diagnosis is associated with a higher risk of subsequent ADHD symptoms in children. We found no evidence for underlying inflammatory mechanism or mediation by gut microbiome dysbiosis. Further research should evaluate other mechanisms underlying the link between eczema and ADHD.Peer reviewe

Novel melanocortin-3 and -4 receptor functional variants in Asian children with severe obesity

Pendingdoi:10.25540/0JXP-5FP

Engineering the Gut Microbiome for Treatment of Obesity: A Review of Current Understanding and Progress

10.1002/biot.202000013BIOTECHNOLOGY JOURNAL151

Androgen-dependent tissue factor pathway inhibitor regulating protein: a review of its peripheral actions and association with cardiometabolic diseases

10.1007/s00109-021-02160-5JOURNAL OF MOLECULAR MEDICINE-JMM1002185-196complete

Differences in <i>AMY1</i> Gene Copy Numbers Derived from Blood, Buccal Cells and Saliva Using Quantitative and Droplet Digital PCR Methods: Flagging the Pitfall

<div><p>Introduction</p><p>The human salivary (<i>AMY1</i>) gene, encoding salivary α-amylase, has variable copy number variants (CNVs) in the human genome. We aimed to determine if real-time quantitative polymerase chain reaction (qPCR) and the more recently available Droplet Digital PCR (ddPCR) can provide a precise quantification of the <i>AMY1</i> gene copy number in blood, buccal cells and saliva samples derived from the same individual.</p><p>Methods</p><p>Seven participants were recruited and DNA was extracted from the blood, buccal cells and saliva samples provided by each participant. Taqman assay real-time qPCR and ddPCR were conducted to quantify <i>AMY1</i> gene copy numbers. Statistical analysis was carried out to determine the difference in AMY1 gene copy number between the different biological specimens and different assay methods.</p><p>Results</p><p>We found significant within-individual difference (p<0.01) in <i>AMY1</i> gene copy number between different biological samples as determined by qPCR. However, there was no significant within-individual difference in <i>AMY1</i> gene copy number between different biological samples as determined by ddPCR. We also found that <i>AMY1</i> gene copy number of blood samples were comparable between qPCR and ddPCR, while there is a significant difference (p<0.01) between <i>AMY1</i> gene copy numbers measured by qPCR and ddPCR for both buccal swab and saliva samples.</p><p>Conclusions</p><p>Despite buccal cells and saliva samples being possible sources of DNA, it is pertinent that ddPCR or a single biological sample, preferably blood sample, be used for determining highly polymorphic gene copy numbers like <i>AMY1</i>, due to the large within-individual variability between different biological samples if real time qPCR is employed.</p></div

Detection of ADTRP in circulation and its role as a novel biomarker for coronary artery disease

10.1371/journal.pone.0237074PLOS ONE15

Determination of <i>AMY1</i> gene copy number by qPCR.

<p>1–7 represents each of the 7 subjects recruited for this study, 8 represents the positive control known to have 14 diploid copies of <i>AMY1</i> gene. The bars represent the different DNA samples extracted from blood, buccal swab and saliva of each individual. * denotes significant difference of p<0.01 (after bonferroni adjustment) between the different biological samples in each subject using ANOVA analysis.</p