MicroRNA Biogenesis, Gene Regulation Mechanisms, and Availability in Foods.

MicroRNAs (miRNAs) are small, non-coding RNAs that control gene expression by degrading or repressing mRNA translation into proteins. Research recently suggested that food-derived miRNAs are bioavailable and may be absorbed in the gastrointestinal tract (GIT). Since these small RNAs may reach the circulation and organs, possible interactions with host genes will lead to epigenetic effects that alter metabolism.

Influence of previous plane of nutrition on molecular mechanisms regulating the expression of urea and water metabolism related genes in the rumen and kidney of finishing crossbred Angus steers.

This study aimed to understand how molecular mechanisms controlling water and urea metabolism at the finishing phase can be affected by previous plane of nutrition of crossbred Angus beef steers. Twenty-four ( = 24) animals were randomly distributed into either a moderate (MP) or high plane of nutrition during the background phase for 85 d. Animals were then blocked by their previous plane and were moved onto a 105-d finishing phase in a 2 × 2 factorial arrangement.

Emodin Inhibited Pathological Cardiac Hypertrophy in Response to Angiotensin-Induced Hypertension and Altered the Gut Microbiome.

Objective: Evidence suggests that food bioactives affect the epigenome to prevent pathological cardiac hypertrophy. Recently, we showed that emodin, an anthraquinone, attenuated pathological cardiac hypertrophy and histone deacetylase (HDAC) activity. However, we only examined the cardioprotective effects of emodin's parent compound and not those of emodin metabolites or of emodin-gut microbiome interactions.

Class I HDAC inhibitors attenuate dexamethasone-induced muscle atrophy via increased protein kinase C (PKC) delta phosphorylation.

Skeletal muscle atrophy is defined by wasting or decrease in muscle mass owing to injury, aging, malnutrition, chronic disuse, or physical consequences of chronic illness. Under normal physiological conditions, a network of signal transduction pathways serves to balance muscle protein synthesis and proteolysis; however, metabolic shifts occur from protein synthesis to protein degradation that leads to a reduction in cross-sectional myofibers and can result in loss of skeletal muscle mass (atrophy) over time. Recent evidence highlights posttranslational modifications (PTMs) such as acetylation and phosphorylation in contractile dysfunction and muscle wasting.

HDAC8 regulates protein kinase D phosphorylation in skeletal myoblasts in response to stress signaling.

Skeletal muscle differentiation involves activation of quiescent satellite cells to proliferate, differentiate and fuse to form new myofibers; this requires coordination of myogenic transcription factors. Myogenic transcription is tightly regulated by various intracellular signaling pathways, which include members of the protein kinase D (PKD) family. PKD is a family of serine-threonine kinases that regulate gene expression, protein secretion, cell proliferation, differentiation and inflammation.

DUSP5-mediated inhibition of smooth muscle cell proliferation suppresses pulmonary hypertension and right ventricular hypertrophy.

Pulmonary hypertension (PH) is associated with structural remodeling of pulmonary arteries (PAs) because of excessive proliferation of fibroblasts, endothelial cells, and smooth muscle cells (SMCs). The peptide hormone angiotensin II (ANG II) contributes to pulmonary vascular remodeling, in part, through its ability to trigger extracellular signal-regulated kinase (ERK1/2) activation. Here, we demonstrate that the ERK1/2 phosphatase, dual-specificity phosphatase 5 (DUSP5), functions as a negative regulator of ANG II-mediated SMC proliferation and PH.

Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy.

Plant-based foods, like fruits, vegetables, whole grains, legumes, nuts, seeds and other foodstuffs, have been deemed as heart healthy. The chemicals within these plant-based foods, i.e.

The Role of Histone Acetylation and the Microbiome in Phytochemical Efficacy for Cardiovascular Diseases.

Cardiovascular diseases (CVD) are the main cause of death worldwide and create a substantial financial burden. Emerging studies have begun to focus on epigenetic targets and re-establishing healthy gut microbes as therapeutic options for the treatment and prevention of CVD. Phytochemicals, commonly found in fruits and vegetables, have been shown to exert a protective effect against CVD, though their mechanisms of action remain incompletely understood.

Emodin and emodin-rich rhubarb inhibits histone deacetylase (HDAC) activity and cardiac myocyte hypertrophy.

Pathological cardiac hypertrophy is a classical hallmark of heart failure. At the molecular level, inhibition of histone deacetylase (HDAC) enzymes attenuate pathological cardiac hypertrophy in vitro and in vivo. Emodin is an anthraquinone that has been implicated in cardiac protection.

Dietary natural products as epigenetic modifiers in aging-associated inflammation and disease.

Covering: up to 2020Chronic, low-grade inflammation is linked to aging and has been termed "inflammaging". Inflammaging is considered a key contributor to the development of metabolic dysfunction and a broad spectrum of diseases or disorders including declines in brain and heart function. Genome-wide association studies (GWAS) coupled with epigenome-wide association studies (EWAS) have shown the importance of diet in the development of chronic and age-related diseases.

YY1 is a cis-regulator in the organoid models of high mammographic density.

Motivation: Our previous study has shown that ERBB2 is overexpressed in the organoid model of MCF10A when the stiffness of the microenvironment is increased to that of high mammographic density (MD). We now aim to identify key transcription factors (TFs) and functional enhancers that regulate processes associated with increased stiffness of the microenvironment in the organoid models of premalignant human mammary cell lines.

Results: 3D colony organizations and the cis-regulatory networks of two human mammary epithelial cell lines (184A1 and MCF10A) are investigated as a function of the increased stiffness of the microenvironment within the range of MD.

The nonepigenetic role for small molecule histone deacetylase inhibitors in the regulation of cardiac function.

Eight million US adults are projected to suffer from heart failure (HF) by 2030. Of concern, 5-year mortality rates following HF diagnosis approximate 40%. Small molecule histone deacetylase (HDAC) inhibitors have demonstrated efficacy for the treatment and reversal of HF.

The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart.

Approximately five million United States (U.S.) adults are diagnosed with heart failure (HF), with eight million U.

Dual-specificity phosphatases regulate mitogen-activated protein kinase signaling in adipocytes in response to inflammatory stress.

Obesity is a strong predictor of heart disease, insulin resistance, and type II diabetes. Chronic, low-grade inflammation links obesity and insulin resistance through mitogen-activated protein kinase (MAPK) signaling pathways. Upstream kinases activate MAPK signaling, while MAPK-specific dual-specificity phosphatases (DUSPs) act as key modulators and controllers of MAPK deactivation (i.

Sodium propionate and sodium butyrate effects on histone deacetylase (HDAC) activity, histone acetylation, and inflammatory gene expression in bovine mammary epithelial cells.

Histone deacetylase (HDAC) inhibition attenuates inflammation in rodents and short-chain fatty acids (SCFAs) are effective HDAC inhibitors. Therefore, the objective of this study was to evaluate the role of the SCFAs sodium propionate (SP) and sodium butyrate (SB) as HDAC-dependent regulators of inflammatory gene expression in bovine mammary epithelial cells (MAC-Ts). We postulated that SP and SB would decrease inflammation in MAC-Ts by inhibiting HDAC activity and increasing histone H3 acetylation and consequently decreasing inflammatory gene expression.

HDAC1/2-mediated regulation of JNK and ERK phosphorylation in bovine mammary epithelial cells in response to TNF-α.

Bovine mammary epithelial cells (MAC-Ts) are a common cell line for the study of mammary epithelial inflammation; these cells are used to mechanistically elucidate molecular underpinnings that contribute to bovine mastitis. Bovine mastitis is the most prevalent form of disease in dairy cattle that culminates in annual losses of two billion dollars for the US dairy industry. Thus, there is an urgent need for improved therapeutic strategies.

Food Bioactive HDAC Inhibitors in the Epigenetic Regulation of Heart Failure.

Approximately 5.7 million U.S.

HDAC11 suppresses the thermogenic program of adipose tissue via BRD2.

Little is known about the biological function of histone deacetylase 11 (HDAC11), which is the lone class IV HDAC. Here, we demonstrate that deletion of HDAC11 in mice stimulates brown adipose tissue (BAT) formation and beiging of white adipose tissue (WAT). Consequently, HDAC11-deficient mice exhibit enhanced thermogenic potential and, in response to high-fat feeding, attenuated obesity, improved insulin sensitivity, and reduced hepatic steatosis.

Polyphenols: Novel Signaling Pathways.

Background: Cardiovascular disease (CVD) is currently the leading cause of death globally. The metabolic syndrome (MetS), a clustering of risk factors including hypertension, hyperglycemia, elevated low-density lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol and increased visceral adiposity, is a significant risk factor for the development of CVD. Non-alcoholic fatty liver disease (NAFLD), often referred to as the hepatic manifestation of MetS, is a constellation of progressive liver disorders closely linked to obesity, diabetes, and insulin resistance.

DUSP5 functions as a feedback regulator of TNFα-induced ERK1/2 dephosphorylation and inflammatory gene expression in adipocytes.

Adipose tissue inflammation is a central pathological element that regulates obesity-mediated insulin resistance and type II diabetes. Evidence demonstrates that extracellular signal-regulated kinase (ERK 1/2) activation (i.e.

Class I HDACs control a JIP1-dependent pathway for kinesin-microtubule binding in cardiomyocytes.

Class I histone deacetylase (HDAC) inhibitors block hypertrophy and fibrosis of the heart by suppressing pathological signaling and gene expression programs in cardiac myocytes and fibroblasts. The impact of HDAC inhibition in unstressed cardiac cells remains poorly understood. Here, we demonstrate that treatment of cultured cardiomyocytes with small molecule HDAC inhibitors leads to dramatic induction of c-Jun amino-terminal kinase (JNK)-interacting protein-1 (JIP1) mRNA and protein expression.

A grape seed procyanidin extract inhibits HDAC activity leading to increased Pparα phosphorylation and target-gene expression.

Scope: Histone deacetylases (HDACs) have emerged as epigenetic regulators of risk factors associated with the metabolic syndrome (MetS), and certain botanical extracts have proven to be potent HDAC inhibitors. Understanding the role of dietary procyanidins in HDAC inhibition is important in exploring the therapeutic potential of natural products.

Methods: C57BL/6 mice were gavaged with vehicle (water) or grape seed procyanidin extract (GSPE, 250 mg/kg) and terminated 14 h later.