Consumption of plant sterols-enriched soy milk with a healthy dietary pattern diet lowers blood pressure in adults with metabolic syndrome: A randomized controlled trial.

Background & Aims: Plant sterols (PS) have been shown to lower blood lipid-lipoproteins concentrations and may serve as a potential functional ingredient for cardiovascular disease (CVD) risk management. However, there are limited studies examining this effect in individuals with metabolic syndrome (MetS). The aim of this study was to evaluate the effects of PS-enriched food consumption as part of a healthy dietary pattern (HDP) on blood pressure and endothelial function in Singaporean adults with MetS.

A genomic enhancer signature associates with hepatocellular carcinoma prognosis.

Background & Aims: Lifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 surgically resected tumours and the matched adjacent normal tissues to understand the aberrant epigenetic events associated with HCC.

Methods: We identified tumour differential enhancers and the associated genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) and Hi-C/HiChIP data from the resected tumour samples of 30 patients with early-stage HCC.

Comprehensive molecular phenotyping of -deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities.

Objective: Gastric cancer (GC) is a leading cause of cancer mortality, with being the second most frequently mutated driver gene in GC. We sought to decipher -specific GC regulatory networks and examine therapeutic vulnerabilities arising from loss.

Design: Genomic profiling of GC patients including a Singapore cohort (>200 patients) was performed to derive mutational signatures of inactivation across molecular subtypes.

Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma.

Background: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC).

Methods: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples.

Trans-interaction of risk loci 6p24.1 and 10q11.21 is associated with endothelial damage in coronary artery disease.

Background And Aims: Single nucleotide polymorphism rs6903956 has been identified as one of the genetic risk factors for coronary artery disease (CAD). However, rs6903956 lies in a non-coding locus on chromosome 6p24.1.

BNIP-2 Activation of Cellular Contractility Inactivates YAP for H9c2 Cardiomyoblast Differentiation.

Rho GTPases and Hippo kinases are key regulators of cardiomyoblast differentiation. However, how these signaling axes are coordinated spatiotemporally remains unclear. Here, the central and multifaceted roles of the BCH domain containing protein, BNIP-2, in orchestrating the expression of two key cardiac genes (cardiac troponin T [cTnT] and cardiac myosin light chain [Myl2]) in H9c2 and human embryonic stem cell-derived cardiomyocytes are delineated.

Regulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities.

Objective: Gastric cancer (GC) comprises multiple molecular subtypes. Recent studies have highlighted mesenchymal-subtype GC (Mes-GC) as a clinically aggressive subtype with few treatment options. Combining multiple studies, we derived and applied a consensus Mes-GC classifier to define the Mes-GC enhancer landscape revealing disease vulnerabilities.

11C-Metomidate PET-CT versus adrenal vein sampling to subtype primary aldosteronism: a prospective clinical trial.

Objective: Adrenal vein sampling (AVS) is recommended to subtype primary aldosteronism, but it is technically challenging. We compared 11C-Metomidate-PET-computed tomography (PET-CT) and AVS for subtyping of primary aldosteronism.

Methods: Patients with confirmed primary aldosteronism underwent both AVS and 11C-Metomidate PET-CT (post-dexamethasone).

Time-restricted feeding modulates the DNA methylation landscape, attenuates hallmark neuropathology and cognitive impairment in a mouse model of vascular dementia.

Vascular dementia (VaD) is the second most common cause of dementia worldwide. The increasing contribution of lifestyle-associated risk factors to VaD has pointed towards gene-environment interactions (i.e.

8-Oxoguanine DNA Glycosylase (OGG1) Deficiency Exacerbates Doxorubicin-Induced Cardiac Dysfunction.

Doxorubicin is an anthracycline widely used for the treatment of various cancers; however, the drug has a common deleterious side effect, namely a dose-dependent cardiotoxicity. Doxorubicin treatment increases the generation of reactive oxygen species, which leads to oxidative stress in the cardiac cells and ultimately DNA damage and cell death. The most common DNA lesion produced by oxidative stress is 7,8-dihydro-8-oxoguanine (8-oxoguanine), and the enzyme responsible for its repair is the 8-oxoguanine DNA glycosylase (OGG1), a base excision repair enzyme.

Integrative epigenomic and transcriptomic analyses reveal metabolic switching by intermittent fasting in brain.

Intermittent fasting (IF) remains the most effective intervention to achieve robust anti-aging effects and attenuation of age-related diseases in various species. Epigenetic modifications mediate the biological effects of several environmental factors on gene expression; however, no information is available on the effects of IF on the epigenome. Here, we first found that IF for 3 months caused modulation of H3K9 trimethylation (H3K9me) in the cerebellum, which in turn orchestrated a plethora of transcriptomic changes involved in robust metabolic switching processes commonly observed during IF.

Integrative epigenomic and high-throughput functional enhancer profiling reveals determinants of enhancer heterogeneity in gastric cancer.

Background: Enhancers are distal cis-regulatory elements required for cell-specific gene expression and cell fate determination. In cancer, enhancer variation has been proposed as a major cause of inter-patient heterogeneity-however, most predicted enhancer regions remain to be functionally tested.

Methods: We analyzed 132 epigenomic histone modification profiles of 18 primary gastric cancer (GC) samples, 18 normal gastric tissues, and 28 GC cell lines using Nano-ChIP-seq technology.

Germline genome modification through novel political, ethical, and social lenses.

Much has been written about gene modifying technologies (GMTs), with a particularly strong focus on human germline genome editing (HGGE) sparked by its unprecedented clinical research application in 2018, shocking the scientific community. This paper applies political, ethical, and social lenses to aspects of HGGE to uncover previously underexplored considerations that are important to reflect on in global discussions. By exploring 4 areas-(1) just distribution of HGGE benefits through a realist lens; (2) HGGE through a national interest lens; (3) "broad societal consensus" through a structural injustice lens; and (4) HGGE through a scientific trustworthiness lens-a broader perspective is offered, which ultimately aims to enrich further debates and inform well-considered solutions for developments in this field.

Disrupting the LINC complex by AAV mediated gene transduction prevents progression of Lamin induced cardiomyopathy.

Mutations in the LaminA gene are a common cause of monogenic dilated cardiomyopathy. Here we show that mice with a cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3-4 weeks after inducing the mutation. When the same Lmna mutations are induced in mice genetically deficient in the LINC complex protein SUN1, life is extended to more than one year.

Dimethyl sulfoxide (DMSO) enhances direct cardiac reprogramming by inhibiting the bromodomain of coactivators CBP/p300.

Aims: Direct cardiac reprogramming represents an attractive way to reversing heart damage caused by myocardial infarction because it removes fibroblasts, while also generating new functional cardiomyocytes. Yet, the main hurdle for bringing this technique to the clinic is the lack of efficacy with current reprogramming protocols. Here, we describe our unexpected discovery that DMSO is capable of significantly augmenting direct cardiac reprogramming in vitro.

Enhancing the cardiovascular protective effects of a healthy dietary pattern with wolfberry (Lycium barbarum): A randomized controlled trial.

Background: The consumption of wolfberry (Lycium barbarum), a rich source of carotenoids and bioactive polysaccharides, may serve as a potential dietary strategy for cardiovascular disease (CVD) risk management although limited studies examined its effects as whole fruits.

Objectives: To investigate the impact of wolfberry consumption as part of a healthy dietary pattern on vascular health-related outcomes and classical CVD risk factors in middle-aged and older adults in Singapore.

Methods: This is a 16-week, parallel design, randomized controlled trial.

Cohort profile: the Diet and Healthy Aging (DaHA) study in Singapore.

How diet is related with cognition and health has not been systematically examined in Asians whose eating habits are very different from their counterparts in the West and the biological mechanisms underlying such links are not well known yet. The diet and healthy aging (DaHA) study is a community-based longitudinal study conducted to examine the role of diet and nutrition in promoting cognitive, emotional, and physical health among community-living elderly Singaporeans. The first wave of DaHA, conducted from 2011 to 2017, provided detailed information on diet and baseline cognitive function and health from 1010 community-living elderly in Singapore.

International Reporting Mechanism for Unethical Germline Gene Editing Experiments Is Needed.

Recent reporting found that a number of scientists internationally knew about the experiment resulting in the birth of the first gene-edited babies well before the news broke. Because scientists have a responsibility to reveal such activities, an international governance mechanism for reporting unethical gene editing experiments should be established.