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Dietary methyl-consuming compounds and metabolic syndrome

Posted on December 11, 2019 at 11:20 AM Comments comments (0)

Shi-Sheng Zhou1,2, Yi-Ming Zhou3, Da Li1 and Yong-Zhi Lun2

The metabolic syndrome, a major risk factor for type 2 diabetes and cardiovascular disease, is a cluster of metabolic

abnormalities including obesity, insulin resistance, hypertension and dyslipidemia. Although systemic oxidative stress and

aberrant methylation status are known to have important roles in the development of metabolic syndrome, how they occur

remains unclear. The metabolism of methyl-consuming compounds generates reactive oxygen species and consumes labile methyl

groups; therefore, a chronic increase in the levels of methyl-consuming compounds in the body can induce not only oxidative

stress and subsequent tissue injury, but also methyl-group pool depletion and subsequent aberrant methylation status. In the past

few decades, the intake amount of methyl-consuming compounds has substantially increased primarily due to pollution, food

additives, niacin fortification and high meat consumption. Thus, increased methyl consumers might have a causal role in the

development and prevalence of metabolic syndrome and its related diseases. Moreover, factors that decrease the elimination/

metabolism of methyl-consuming compounds and other xenobiotics (for example, sweat gland inactivity and decreased liver

function) or increase the generation of endogenous methyl-consuming compounds (for example, mental stress-induced increase in

catecholamine release) may accelerate the progression of metabolic syndrome. Based on current nutrition knowledge and the

available evidence from epidemiological, ecological, clinical and laboratory studies on metabolic syndrome and its related

diseases, this review outlines the relationship between methyl supply-consumption imbalance and metabolic syndrome, and

proposes a novel mechanism for the pathogenesis and prevalence of metabolic syndrome and its related diseases.

Hypertension Research (2011) 34, 1239–1245; doi:10.1038/hr.2011.133; published online 4 August 2011

Keywords: cardiovascular disease; diet; metabolic syndrome; methyl-consuming compounds; niacin


The metabolic syndrome, a major risk factor for type 2 diabetes (T2D)

and cardiovascular disease (CVD), is a cluster of metabolic abnorm-

alities including obesity, insulin resistance, hypertension and dyslipi-

demia.1,2 In the past few decades, there has been an exponential

increase in the prevalence of metabolic syndrome worldwide not only

in adults but also in children and adolescents. For example, in the

United States, the prevalence of obesity, a major component of

metabolic syndrome, has doubled in the adult population3 and tripled

in the adolescent population only in two decades (1980s and 1990s),4

while the prevalence of diabetes, the primary clinical outcome of

metabolic syndrome, has also doubled during the past two decades

(1988–2008) and still shows an increasing trend.5 To date, although

the exact cause of metabolic syndrome remains unknown, it is known

that diet may have a major role in the pathogenesis and prevalence of

metabolic syndrome.6

Increasing evidence indicates that the pathogenic mechanism

underlying metabolic syndrome and its clinical outcomes may involve

oxidative stress, characterized by an increased production of reactive

oxygen species (ROS),1 and aberrant methylation status, character-

ized by changes in the levels of plasma methyl donors7 and homo-

cysteine8–12 and altered DNA methylation (an epigenetic mechanism

that alters gene expression).2 Recently, emerging evidence suggests that

DNA methylation may be involved in the regulation of insulin gene

expression in T2D and the pathogenesis of insulin resistance.13–15

Therefore, understanding the origin of oxidative stress and aberrant

methylation status is of both fundamental and practical importance in

identifying the cause of metabolic syndrome.

Methyl consumers include a variety of compounds that are meta-

bolized by methylation and are known to be involved in both the

generation of ROS and aberrant methylation status of the body.

Methyl consumers from dietary sources are usually toxic xenobiotics,

such as pesticides, heavy metals, food additives and even clinical drugs.

In the past few decades, there has been a significant increase in methyl

consumers in dietary sources that is primarily due to pollution, food

additives and food fortification. Therefore, the focus of this review was

on the possible role of methyl consumers in the development of

metabolic syndrome.

Received 13 February 2011; revised 17 May 2011; accepted 9 June 2011; published online 4 August 2011..........

Bright Star Apothecary Harm Reduction Initiative Research: Methyl Donors & Methyl Consumers

Posted on December 11, 2019 at 11:15 AM Comments comments (0)

Methyl consumers from dietary sources are usually toxic xenobiotics, such as pesticides, heavy metals, food additives and even clinical drugs....

The Implications of DNA Methylation for Toxicology: Toward Toxicomethylomics, the Toxicology of DNA Methylation

Posted on December 11, 2019 at 11:05 AM Comments comments (0)

The realization that long-range damage could be caused without changing the DNA sequence has important implications on the way we assess the safety of chemicals, drugs, and food and broadens the scope of definition of toxic agents. ....

Maternal intake of methyl-group donors affects DNA methylation of metabolic genes in infants

Posted on December 11, 2019 at 11:05 AM Comments comments (0)

This study suggests that maternal dietary and supplemental intake of methyl-group donors, especially in the periconception period, can influence infant’s buccal DNA methylation in genes related to metabolism, growth, appetite regulation, and maintenance of DNA methylation reactions. ...

Methyl Donor Supplementation Blocks the Adverse Effects of Maternal High Fat Diet on Offspring Physiology

Posted on December 11, 2019 at 11:00 AM Comments comments (0)

Maternal consumption of a high fat diet during pregnancy increases the offspring risk for obesity. Using a mouse model, we have previously shown that maternal consumption of a high fat (60%) diet leads to global and gene specific decreases in DNA methylation in the brain of the offspring. The present experiments were designed to attempt to reverse this DNA hypomethylation through supplementation of the maternal diet with methyl donors, and to determine whether methyl donor supplementation could block or attenuate phenotypes associated with maternal consumption of a HF diet. Metabolic and behavioral (fat preference) outcomes were assessed in male and female adult offspring. Expression of the mu-opioid receptor and dopamine transporter mRNA, as well as global DNA methylation were measured in the brain. Supplementation of the maternal diet with methyl donors attenuated the development of some of the adverse effects seen in offspring from dams fed a high fat diet; including weight gain, increased fat preference (males), changes in CNS gene expression and global hypomethylation in the prefrontal cortex. Notable sex differences were observed. These findings identify the importance of balanced methylation status during pregnancy, particularly in the context of a maternal high fat diet, for optimal offspring outcome.....

The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway

Posted on December 11, 2019 at 11:00 AM Comments comments (0)

Methyl groups are important for numerous cellular functions such as DNA methylation, phosphatidylcholine synthesis, and protein synthesis. The methyl group can directly be delivered by dietary methyl donors, including methionine, folate, betaine, and choline. The liver and the muscles appear to be the major organs for methyl group metabolism. Choline can be synthesized from phosphatidylcholine via the cytidine-diphosphate (CDP) pathway. Low dietary choline loweres methionine formation and causes a marked increase in S-adenosylmethionine utilization in the liver. The link between choline, betaine, and energy metabolism in humans indicates novel functions for these nutrients. This function appears to goes beyond the role of the nutrients in gene methylation and epigenetic control. Studies that simulated methyl-deficient diets reported disturbances in energy metabolism and protein synthesis in the liver, fatty liver, or muscle disorders. Changes in plasma concentrations of total homocysteine (tHcy) reflect one aspect of the metabolic consequences of methyl group deficiency or nutrient supplementations. Folic acid supplementation spares betaine as a methyl donor. Betaine is a significant determinant of plasma tHcy, particularly in case of folate deficiency, methionine load, or alcohol consumption. Betaine supplementation has a lowering effect on post-methionine load tHcy. Hypomethylation and tHcy elevation can be attenuated when choline or betaine is available.....

Bright Star Apothecary Harm Reduction Initiative Research: Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome

Posted on December 11, 2019 at 10:40 AM Comments comments (0)

DNA methylation is an epigenetic mechanism that is essential for regulating gene transcription. However, aberrant DNA methylation, which is a nearly universal finding in cancer, can result in disturbed gene expression. DNA methylation is modified by environmental factors such as diet that may modify cancer risk and tumor behavior. Abnormal DNA methylation has been observed in several cancers such as colon, stomach, cervical, prostate, and breast cancers. These alterations in DNA methylation may play a critical role in cancer development and progression. Dietary nutrient intake and bioactive food components are essential environmental factors that may influence DNA methylation either by directly inhibiting enzymes that catalyze DNA methylation or by changing the availability of substrates required for those enzymatic reactions such as the availability and utilization of methyl groups. In this review, we focused on nutrients that act as methyl donors or methylation co-factors and presented intriguing evidence for the role of these bioactive food components in altering DNA methylation patterns in cancer. Such a role is likely to have a mechanistic impact on the process of carcinogenesis and offer possible therapeutic potentials.


Keywords: methyl donors, nutrients, DNA methylation, cancer, folate, Vitamin B, choline, betaine, methyltransferase, dietary

1. Introduction

Cancer is an outcome of aberrant genetic and epigenetic events. Epigenetic mechanisms are responsible for regulating gene expression without changing the DNA sequence. These mechanisms mainly include chromatin remodeling, histone modification, and DNA methylation, the latter being the most investigated mechanism and the focus of the current review [1]. The process of DNA methylation includes the addition of methyl groups to the cytosine residues; a biological process that depends on the availability of methyl groups and accordingly the function of methyl donors and acceptors [2]. Micronutrients such as folate, choline, betaine, vitamin B12, and other B vitamins contribute to DNA methylation as methyl donors and co-factors [3]. Therefore, the status of these nutrients might correlate with DNA methylation and offer potential preventive and therapeutic targets in pathological conditions such as cancer where aberrant DNA methylation is frequently observed. ....

Bright Star Apothecary Harm Reduction Initiative Research: Diet, Methyl Donors and DNA Methylation: Interactions between Dietary Folate, Methionine and Choline

Posted on December 11, 2019 at 10:35 AM Comments comments (0)

In summary, as we consider dietary requirements and possible effects on DNA methylation, it is important to realize that methionine, methyl-THF and choline can be fungible sources of methyl groups, and the design of our studies should reflect this. ....

Antibacterial Free Fatty Acids and Monoglycerides: Biological Activities, Experimental Testing, and Therapeutic Applications

Posted on December 11, 2019 at 9:10 AM Comments comments (0)

Antimicrobial lipids such as fatty acids and monoglycerides are promising antibacterial agents that destabilize bacterial cell membranes, causing a wide range of direct and indirect inhibitory effects. The goal of this review is to introduce the latest experimental approaches for characterizing how antimicrobial lipids destabilize phospholipid membranes within the broader scope of introducing current knowledge about the biological activities of antimicrobial lipids, testing strategies, and applications for treating bacterial infections. To this end, a general background on antimicrobial lipids, including structural classification, is provided along with a detailed description of their targeting spectrum and currently understood antibacterial mechanisms. Building on this knowledge, different experimental approaches to characterize antimicrobial lipids are presented, including cell-based biological and model membrane-based biophysical measurement techniques. Particular emphasis is placed on drawing out how biological and biophysical approaches complement one another and can yield mechanistic insights into how the physicochemical properties of antimicrobial lipids influence molecular self-assembly and concentration-dependent interactions with model phospholipid and bacterial cell membranes. Examples of possible therapeutic applications are briefly introduced to highlight the potential significance of antimicrobial lipids for human health and medicine, and to motivate the importance of employing orthogonal measurement strategies to characterize the activity profile of antimicrobial lipids.


Keywords: antimicrobial lipid, fatty acid, monoglyceride, antibacterial, therapy, phospholipid membrane

1. Introduction

Molecular design principles underpin the structure and function of biological assemblies such as cells, and amphiphilic molecules drive the spontaneous self-assembly of key architectural elements like phospholipid membranes [1,2,3]. Understanding the role of molecular self-assembly in directing the formation of biological macromolecular structures, including lipid bilayers, proteins, and assemblies thereof, is part of the nanoarchitectonics field [4,5], and such insights can help solve outstanding biomedical problems. Within this scope, one of the greatest public health problems in the world today is the growing rise of antibiotic-resistant bacteria and the associated challenges to treat and prevent bacterial infections [6]. Less than a century ago, the world’s first antibiotic, penicillin, was discovered, and the specificity of antibiotics to inhibit bacterial enzymes and other proteins necessary for bacterial cell function proved highly effective and a remarkable example of molecular pharmaceutics, as evidenced by marked improvements in healthcare capabilities to treat bacterial infections. As a result, many formerly fatal or debilitating diseases caused by bacterial pathogens were suddenly curable with antibiotic treatment [7].


With high potency and working against a broad spectrum of bacterial targets, antibiotics became the standard drug option to treat bacterial infections, and are also widely used as precautionary measures to treat suspected infections, even when the microbial origin is unknown and could be bacterial, fungal, or viral among other possibilities. Antibiotics are also administered prophylactically in cases where bacterial infections might arise, such as after surgical operations. In addition, antibiotics are commonly used in the agricultural sector to not only treat and prevent bacterial infections among livestock, but also serve as growth promoters to accelerate the time to reach maturity as well as increase the body mass of animals. For all these reasons, antibiotics have become ubiquitous in society and have played an outsized role in shaping modern life.


However, despite numerous benefits, the drawbacks of antibiotics being so widely prevalent are now becoming apparent as well. With increasing exposure to antibiotics and corresponding selective pressure, bacteria have evolved to become resistant to many antibiotics, and antibiotic-resistant bacteria are widespread. As a result, existing antibiotics are losing their effectiveness to treat bacterial infections, and the problem is further compounded by the dearth of new antibiotics that have been discovered in recent years. In part, the problem is economic because pharmaceutical companies have had weak interest in developing new antibiotics due to low price points, however, the more pressing scientific issue is that the chemical space available for identifying and refining antibiotics is limited. There is growing recognition that society faces an impending post-antibiotic era [8], and hence, there is an urgent need to develop new classes of antibacterial agents that work against novel molecular targets. ..,

Bright Star Apothecary Harm Reduction Initiative Research: Tanzawaic Acids, a Chemically Novel Set of Bacterial Conjugation Inhibitors

Posted on December 11, 2019 at 8:55 AM Comments comments (0)

Tanzawaic acids showed reduced toxicity in bacterial, fungal or human cells, when compared to synthetic conjugation inhibitors, opening the possibility of their deployment in complex environments, including natural settings relevant for antibiotic resistance dissemination. ....

Bright Star Apothecary Harm Reduction Initiative Research: Epigenetics of drug abuse: predisposition or response

Posted on December 11, 2019 at 8:45 AM Comments comments (0)

Drug addiction continues to be a serious medical and social problem. Vulnerability to develop an addiction to drugs is dependent on genetic, environmental, social and biological factors. In particular, the interactions of environmental and genetic factors indicate the significance of epigenetic mechanisms, which have been found to occur in response to illicit drug use or as underlying factors in chronic substance abuse and relapse. Epigenetics is defined as the heritable and possibly reversible modifications in gene expression that do not involve alterations in the DNA sequence. This review discusses the various types of epigenetic modifications and their relevance to drug addiction to elucidate whether epigenetics is a predisposing factor, or a response to, developing an addiction to drugs of abuse.


Keywords: alcohol, azacitidine, cocaine, Depakote, dependence, epigenetic, gene, histone, methylation, opioid, SAHA, sodium butyrate, suberoylanilide, hydroxamic acid, trichostatin A, valproic acid

Drug addiction, a chronic relapsing brain disease, is a major medical and social problem. Approximately 22.1 million people in the USA are classified as demonstrating substance dependence or abuse [101]. Over 1 million people are addicted to cocaine and over 350,000 to heroin. From 2002 to 2010 the number of people addicted to cocaine decreased from 1.5 to 1.0 million, while those addicted to heroin increased from 214,000 to 359,000, and the number of prescription opiate abusers rose to over 1 million. Currently, 17.9 million people are alcoholics, in comparison with 18.1 million in 2002 [102].


Addiction develops in several stages: initiation of drug use, intermittent to regular use, and finally, addiction and relapse. Features of addiction are the development of dependence on the drug, such that there is a physiological need for the drug for the individual to function properly; the development of tolerance, whereby larger doses of the drug are required to achieve the same effect; and the development of withdrawal, symptoms that occur once a drug is discontinued. Drugs of abuse alter physiological systems, contribute to the maintenance of the addictive state and influence withdrawal and relapse [1,2].


Vulnerability to addiction and chronic addiction are influenced by convergent biological, social, environmental and genetic factors [3]. Twin studies have revealed that there are common heritable genetic components that predispose an individual to drug addiction, and that these genetic factors contribute approximately 20–50% to the variance of developing a drug addiction, with the remaining contribution due to nongenetic factors [4–6]. Recent studies have elucidated the inter-related nature of these determinants, clarifying the idea that individual biological factors and broader biosocial influences interact.


Recent studies have revealed the role of gene–environment interactions, which occur when genetic factors interact with the environment to influence behavioral phenotype. For example, several studies have focused on the 5-HTTLPR variation in the promoter of the serotonin transporter SLC6A4 gene, which codes for the serotonin transporter, a target for cocaine and 3,4-methylenedioxy-N-methylamphetamine (ecstasy) [7]. The short 5-HTTLPR allele decreases both serotonin transporter expression and serotonin uptake [8]. For example, in a study of adolescents, the rate of substance abuse initiation in subjects with one or two copies of the short allele was moderated by exposure to supportive parenting or membership in community-building initiatives [9]. Studies such as this demonstrate that environmental conditions can regulate, or fully attenuate, genetic predispositions to psychiatric conditions such as addiction vulnerability.


Although the effects of gene–environment interactions remain unclear, there may be more of a genetic influence on exhibited phenotypes than traditional nature–nurture dichotomy studies would indicate. In the context of drug addiction, the interactions between genotype and environmental factors point toward an important role for epigenetic mechanisms in the acute response to drugs and the development of addiction. This epigenetic perspective is consistent with the longevity of psychiatric conditions and the difficulty in developing pharmacotherapeutic interventions to effectively treat chronic behavioral disorders.


Epigenetics is the regulation of the heritable and potentially reversible changes in gene expression that occur without alterations in the DNA sequence [10]. The primary mechanisms controlling epigenetic inheritance are DNA methylation and chromatin remodeling. Epigenetic modifications can be immediate or accumulate slowly, and may be passed on to daughter cells or to successive generations through mitotic or meiotic inheritance. These epigenetic alterations may be due to inheritance through genomic imprinting, prior life events, chronic drug use or pharmacotherapies for the addictions. .....

Bright Star Apothecary Harm Reduction Initiative Research: Epigenetic Changes in Response to Tai Chi Practice: A Pilot Investigation of DNA Methylation Marks

Posted on December 11, 2019 at 8:40 AM Comments comments (0)

In the tai chi cohort all six marks demonstrate significant slowing (by 5-70%) of the age-related methylation losses or gains observed in the controls, suggesting that tai chi practice may be associated with measurable beneficial epigenetic changes. Conclusions. The results implicate the potential use of DNA methylation as an epigenetic biomarker to better understand the biological mechanisms and the health and therapeutic efficacies of tai chi.......

Bright Star Apothecary Harm Reduction Initiative Research: Yoga, Meditation and Mind-Body Health

Posted on December 11, 2019 at 8:35 AM Comments comments (0)

Yoga, Meditation and Mind-Body Health: Increased BDNF, Cortisol Awakening Response, and Altered Inflammatory Marker Expression after a 3-Month Yoga and Meditation Retreat


We hypothesize that the patterns of change observed here reflect mind-body integration and well-being. The increased BDNF levels observed is a potential mediator between meditative practices and brain health, the increased CAR is likely a reflection of increased dynamic physiological arousal, and the relationship of the dual enhancement of pro- and anti-inflammatory cytokine changes to healthy immunologic functioning is discussed. ....

Bright Star Apothecary Harm Reduction Initiative: DHEA Enhances Emotion Regulation Neurocircuits and Modulates Memory for Emotional Stimuli

Posted on December 11, 2019 at 8:30 AM Comments comments (0)

Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant, and antiglucocorticoid properties. It is endogenously released in response to stress, and may reduce negative affect when administered exogenously. Although there have been multiple reports of DHEA's antidepressant and anxiolytic effects, no research to date has examined the neural pathways involved. In particular, brain imaging has not been used to link neurosteroid effects to emotion neurocircuitry. To investigate the brain basis of DHEA's impact on emotion modulation, patients were administered 400 mg of DHEA (N=14) or placebo (N=15) and underwent 3T fMRI while performing the shifted-attention emotion appraisal task (SEAT), a test of emotional processing and regulation. Compared with placebo, DHEA reduced activity in the amygdala and hippocampus, enhanced connectivity between the amygdala and hippocampus, and enhanced activity in the rACC. These activation changes were associated with reduced negative affect. DHEA reduced memory accuracy for emotional stimuli, and also reduced activity in regions associated with conjunctive memory encoding. These results demonstrate that DHEA reduces activity in regions associated with generation of negative emotion and enhances activity in regions linked to regulatory processes. Considering that activity in these regions is altered in mood and anxiety disorders, our results provide initial neuroimaging evidence that DHEA may be useful as a pharmacological intervention for these conditions......

Bright Star Apothecary Harm Reduction Initiative Research: Genome-wide methylation in alcohol use disorder subjects

Posted on December 11, 2019 at 8:20 AM Comments comments (0)

These data suggest that alcohol-dependent aberrant DNA methylation of NR3C1 and consequent changes in other stress-related genes might be fundamental in the pathophysiology of AUD and lay the groundwork for treatments targeting the epigenetic mechanisms regulating NR3C1 in AUD. ....

Bright Star Apothecary Harm Reduction Initiative Research: A DNA Methylation Signature of Addiction in T Cells and Its Reversal With DHEA Intervention

Posted on December 11, 2019 at 8:20 AM Comments comments (0)

Previous studies in animal models of cocaine craving have delineated broad changes in DNA methylation profiles in the nucleus accumbens. A crucial factor for progress in behavioral and mental health epigenetics is the discovery of epigenetic markers in peripheral tissues. Several studies in primates and humans have associated differences in behavioral phenotypes with changes in DNA methylation in T cells and brain. Herein, we present a pilot study (n = 27) showing that the T cell DNA methylation profile differentiates persons with a substance use disorder from controls. Intervention with dehydroepiandrosterone (DHEA), previously shown to have a long-term therapeutic effect on human addicts herein resulted in reversal of DNA methylation changes in genes related to pathways associated with the addictive state. .....

Regulation of gene transcription in bipolar disorders: Role of DNA methylation in the relationship between prodynorphin and brain derived neurotrophic factor.

Posted on December 11, 2019 at 8:15 AM Comments comments (0)

Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Italy; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. Electronic address:


Centro Sant'Ambrogio Ordine Ospedaliero San Giovanni di Dio Fatebenefratelli, Milano, Italy.


Department of Psychiatry, Università degli Studi di Milano, Fondazione IRRCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.


Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Italy.


Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.


Department of Neurology, Università degli Studi di Milano, Fondazione IRRCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.


Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy; European Center for Brain Research, IRCCS Santa Lucia Foundation, Rome, Italy.


Department of Psychiatry, Università degli Studi di Milano, Fondazione IRRCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy; Department of Psychiatry and Behavioral Sciences, Bipolar Disorders Clinic, Stanford University, CA, USA. Electronic address:


Bipolar Disorder (BD) is a prevalent and disabling condition, determined by gene-environment interactions, possibly mediated by epigenetic mechanisms. The present study aimed at investigating the transcriptional regulation of BD selected target genes by DNA methylation in peripheral blood mononuclear cells of patients with a DSM-5 diagnosis of type I (BD-I) and type II (BD-II) Bipolar Disorders (n=99), as well as of healthy controls (CT, n=42). The analysis of gene expression revealed prodynorphin (PDYN) mRNA levels significantly reduced in subjects with BD-II but not in those with BD-I, when compared to CT. Other target genes (i.e. catechol-O-methyltransferase (COMT), glutamate decarboxylase (GAD67), serotonin transporter (SERT) mRNA levels remained unaltered. Consistently, an increase in DNA methylation at PDYN gene promoter was observed in BD-II patients vs CT. After stratifying data on the basis of pharmacotherapy, patients on mood-stabilizers (i.e., lithium and anticonvulsants) were found to have lower DNA methylation at PDYN gene promoter. A significantly positive correlation in promoter DNA methylation was observed in all subjects between PDYN and brain derived neurotrophic factor (BDNF), whose methylation status had been previously found altered in BD. Moreover, among key genes relevant for DNA methylation establishment here analysed, an up-regulation of DNA Methyl Transferases 3b (DNMT3b) and of the methyl binding protein MeCP2 (methyl CpG binding protein 2) mRNA levels was also observed again just in BD-II subjects. A clear selective role of DNA methylation involvement in BD-II is shown here, further supporting a role for BDNF and its possible interaction with PDYN. These data might be relevant in the pathophysiology of BD, both in relation to BDNF and for the improvement of available treatments and development of novel ones that modulate epigenetic signatures.

Zinc/copper imbalance reflects immune dysfunction in human leishmaniasis: an ex vivo and in vitro study

Posted on December 11, 2019 at 8:10 AM Comments comments (0)

1. Zn deficiency in VL and ML indicate possible therapeutic administration of Zn in these severe forms of leishmaniasis. 2. Plasma Cu positively correlates to humoral immune response across patient groups. 3. Environmentally or genetically determined increases in Cu levels might augment susceptibility to infection with intracellular pathogens, by causing a decrease in IFN-γ production.......

BDNF DNA methylation changes as a biomarker of psychiatric disorders: literature review and open access database analysis

Posted on December 11, 2019 at 8:00 AM Comments comments (0)

Brain-derived neurotrophic factor (BDNF) plays an important role in nervous system development and function and it is well established that BDNF is involved in the pathogenesis of a wide range of psychiatric disorders. Recently, numerous studies have associated the DNA methylation level of BDNF promoters with certain psychiatric phenotypes. In this review, we summarize data from current literature as well as from our own analysis with respect to the correlation of BDNF methylation changes with psychiatric disorders and address questions about whether DNA methylation related to the BDNF can be useful as biomarker for specific neuropsychiatric disorders. ....

Roles of Zinc Signaling in the Immune System

Posted on December 11, 2019 at 7:55 AM Comments comments (0)

Zinc (Zn) is an essential micronutrient for basic cell activities such as cell growth, differentiation, and survival. Zn deficiency depresses both innate and adaptive immune responses. However, the precise physiological mechanisms of the Zn-mediated regulation of the immune system have been largely unclear. Zn homeostasis is tightly controlled by the coordinated activity of Zn transporters and metallothioneins, which regulate the transport, distribution, and storage of Zn. There is growing evidence that Zn behaves like a signaling molecule, facilitating the transduction of a variety of signaling cascades in response to extracellular stimuli. In this review, we highlight the emerging functional roles of Zn and Zn transporters in immunity, focusing on how crosstalk between Zn and immune-related signaling guides the normal development and function of immune cells. .....