Lifestyle-Driven Variations in Nutrimiromic MicroRNA Expression Patterns across and beyond Genders.

The importance of diet and lifestyle in maintaining overall health has long been recognised. MicroRNAs (miRNAs) have emerged as key players in the intricate interplay between health and disease. This study, including 305 participants, examined the role of miRNAs from capillary blood as indicators of individual physiological characteristics, diet, and lifestyle influences. Key findings include specific miRNAs associated with inflammatory processes and dietary patterns. Notably, miR-155 was associated with subjects with metabolic diseases and upregulated in age. Additionally, the study revealed diet-related miRNA expressions: high consumption of vegetables, fruits, and whole grains correlated with increased levels of miR-let-7a and miR-328, both implicated in anti-inflammatory pathways, and decreased expression of pro-inflammatory miR-21. In the context of smoking, we found a significant decrease in miRNA-142, known for its downregulation in lung cancer. We observed a sex-biased expression of various miRNAs with significant upregulation of miR-151a in females and a higher expression of miR-155 in ageing females, representing a possible mechanism for the increased susceptibility to autoimmune diseases. In conclusion, the study underscores the significant influence of lifestyle, nutrition, and sex on miRNA profiles. Circulating miRNAs demonstrate significant potential as biomarkers in personalized medicine, highlighting their utility in tailoring healthcare to individual needs.

Epigenetic Aspects of a New Probiotic Concept-A Pilot Study.

Several studies report the important role of an altered gut microbiota in the development of obesity, highlighting the potential use of probiotics in the treatment of obesity. The aim of this study is to investigate the effect of a novel probiotic approach on the expression of specific miRNAs and mRNAs associated with obesity in combination with the hypocholesterolemic octacosanol. Twenty overweight/obese women participated in a randomized, placebo-controlled, double-blind study and were randomly divided into two groups: the intervention group (daily one capsule containing Lactobacillus plantarum 299v (DSM9843), Saccharomyces cerevisiae var. boulardii, and 40 mg octacosanol; N = 12) and the placebo group (N = 8). Changes in lipid parameters and expression of miRNAs and mRNAs were assessed before (T0) and after the 12-week intervention (T1). After the intervention, the expression of miR-155-5p (9.38 ± 0.85 vs. 8.38 ± 1.06, p = 0.05) and miR-24-3p (3.42 ± 0.38 vs. 2.71 ± 0.97, p = 0.031) showed significant decreases in the intervention group when compared to the control group. At T1, the expression of miR-155-5p (8.69 ± 1.31 vs. 9.3 ± 0.85, p = 0.04), miR-125b-5p (5.41 ± 1.18 vs. 5.99 ± 1.36, p = 0.049), and TNF-α (10.24 ± 1.66 vs. 11.36 ± 1.12, p = 0.009) were significantly decreased in the intervention group. No changes in lipids and anthropometric parameters were observed. The novel probiotic approach had a positive effect on regulating the expression of certain miRNAs and mRNAs important for regulating inflammation and adipogenesis, which are essential for obesity onset and control.

MiR-10a, miR-15a, let-7a, and let-7g expression as stress-relevant biomarkers to assess acute or chronic psychological stress and mental health in human capillary blood.

BACKGROUND: Psychological stress, as an important cofactor in the development of many acute and chronic diseases, is crucial for general health or well-being, and improved markers are needed to distinguish situations of progressive pathological development, such as depression, anxiety, or burnout, to be recognized at an early stage. Epigenetic biomarkers play an important role in the early detection and treatment of complex diseases such as cancer, and metabolic or mental disorders. Therefore, this study aimed to identify so-called miRNAs, which would be suitable as stress-related biomarkers. METHODS AND RESULTS: In this study, 173 participants (36.4% males, and 63.6% females) were interviewed about stress, stress-related diseases, lifestyle, and diet to assess their acute and chronic psychological stress status. Using qPCR analysis, 13 different miRNAs (miR-10a-5p, miR-15a-5p, miR-16-5p, miR-19b-3p, miR-26b-5p, miR-29c-3p, miR-106b-5p, miR-126-3p, miR-142-3p, let-7a-5p, let-7g-5p, miR-21-5p, and miR-877-5p) were analyzed in dried capillary blood samples. Four miRNAs were identified, miR-10a-5p, miR-15a-5p, let-7a-5p, and let-7g-5p (p < 0.05), which could be used as possible candidates for measuring pathological forms of acute or chronic stress. Let-7a-5p, let-7g-5p, and miR-15a-5p (p < 0.05) were also significantly higher in subjects with at least one stress-related disease. Further, correlations were identified between let-7a-5p and meat consumption (p < 0.05) and between miR-15a-5p and coffee consumption (p < 0.05). CONCLUSION: The examination of these four miRNAs as biomarkers using a minimally invasive method offers the possibility of detecting health problems at an early stage and counteracting them to maintain general and mental health.

Sex-Specific miRNA Differences in Liquid Biopsies from Subjects with Solid Tumors and Healthy Controls.

Dysregulation of epigenetic mechanisms has been recognized to play a crucial role in cancer development, but these mechanisms vary between sexes. Therefore, we focused on sex-specific differences in the context of cancer-based data from a recent study. A total of 12 cell-free DNA methylation targets in CpG-rich promoter regions and 48 miRNAs were analyzed by qPCR in plasma samples from 8 female and 7 male healthy controls as well as 48 female and 80 male subjects with solid tumors of the bladder, brain, colorectal region (CRC), lung, stomach, pancreas, and liver. Due to the small sample size in some groups and/or the non-balanced distribution of men and women, sex-specific differences were evaluated statistically only in healthy subjects, CRC, stomach or pancreas cancer patients, and all cancer subjects combined (n female/male-8/7, 14/14, 8/15, 6/6, 48/80, respectively). Several miRNAs with opposing expressions between the sexes were observed for healthy subjects (miR-17-5p, miR-26b-5p); CRC patients (miR-186-5p, miR-22-3p, miR-22-5p, miR-25-3p, miR-92a-3p, miR-16-5p); stomach cancer patients (miR-133a-3p, miR-22-5p); and all cancer patients combined (miR-126-3p, miR-21-5p, miR-92a-3p, miR-183-5p). Moreover, sex-specific correlations that were dependent on cancer stage were observed in women (miR-27a-3p) and men (miR-17-5p, miR-20a-5p). Our results indicate the complex and distinct role of epigenetic regulation, particularly miRNAs, depending not only on the health status but also on the sex of the patient. The same miRNAs could have diverse effects in different tissues and opposing effects between the biological sexes, which should be considered in biomarker research.

MiRNA-based "fitness score" to assess the individual response to diet, metabolism, and exercise.

Background: Regular, especially sustained exercise plays an important role in the prevention and treatment of multiple chronic diseases. Some of the underlying molecular and cellular mechanisms behind the adaptive response to physical activity are still unclear, but recent findings suggest a possible role of epigenetic mechanisms, especially miRNAs, in the progression and management of exercise-related changes. Due to the combination of the analysis of epigenetic biomarkers (miRNAs), the intake of food and supplements, and genetic dispositions, a "fitness score" was evaluated to assess the individual response to nutrition, exercise, and metabolic influence. Methods: In response to a 12-week sports intervention, we analyzed genetic and epigenetic biomarkers in capillary blood from 61 sedentary, healthy participants (66.1% females, 33.9% males, mean age 33 years), including Line-1 methylation, three SNPs, and ten miRNAs using HRM and qPCR analysis. These biomarkers were also analyzed in a healthy, age- and sex-matched control group (n, 20) without intervention. Food frequency intake, including dietary supplement intake, and general health questionnaires were surveyed under the supervision of trained staff. Results: Exercise training decreased the expression of miR-20a-5p, -22-5p, and -505-3p (p < 0.02) and improved the "fitness score," which estimates eight different lifestyle factors to assess, nutrition, inflammation, cardiovascular fitness, injury risk, regeneration, muscle and hydration status, as well as stress level. In addition, we were able to determine correlations between individual miRNAs, miR-20a-5p, -22-5p, and -101-3p (p < 0.04), and the genetic predisposition for endurance and/or strength and obesity risk (ACE, ACTN3, and FTO), as well as between miRNAs and the body composition (p < 0.05). MiR-19b-3p and -101-3p correlated with the intake of B vitamins. Further, miR-19b-3p correlated with magnesium and miR-378a-3p with iron intake (p < 0.05). Conclusions: In summary, our results indicate that a combined analysis of several biomarkers (miRNAs) can provide information about an individual's training adaptions/fitness, body composition, nutritional needs, and possible recovery. In contrast to most studies using muscle biopsies, we were able to show that these biomarkers can also be measured using a minimally invasive method.

PGC-1α Methylation, miR-23a, and miR-30e Expression as Biomarkers for Exercise- and Diet-Induced Mitochondrial Biogenesis in Capillary Blood from Healthy Individuals: A Single-Arm Intervention.

Healthy mitochondria and their epigenetic control are essential to maintaining health, extending life expectancy, and improving cardiovascular performance. Strategies to maintain functional mitochondria during aging include training; cardiovascular exercise has been suggested as the best method, but strength training has also been identified as essential to health and healthy aging. We therefore investigated the effects of concurrent exercise training and dietary habits on epigenetic mechanisms involved in mitochondrial (mt) functions and biogenesis. We analyzed epigenetic biomarkers that directly target the key regulator of mitochondrial biogenesis, PGC-1α, and mtDNA content. Thirty-six healthy, sedentary participants completed a 12-week concurrent training program. Before and after the intervention, dried blood spot samples and data on eating habits, lifestyle, and body composition were collected. MiR-23a, miR-30e expression, and mtDNA content were analyzed using real-time quantitative polymerase chain reaction (qPCR) analysis. PGC-1α methylation was analyzed using bisulfite pyrosequencing. MiR-23a, miR-30e expression, and PGC-1α methylation decreased after the intervention (p < 0.05). PGC-1α methylation increased with the consumption of red and processed meat, and mtDNA content increased with the ingestion of cruciferous vegetables (p < 0.05). Our results indicate that concurrent training could improve mitochondrial biogenesis and functions by altering the epigenetic regulation. These alterations can also be detected outside of the skeletal muscle and could potentially affect athletic performance.

Comprehensive Approach to Distinguish Patients with Solid Tumors from Healthy Controls by Combining Androgen Receptor Mutation p.H875Y with Cell-Free DNA Methylation and Circulating miRNAs.

Liquid biopsy-based tests emerge progressively as an important tool for cancer diagnostics and management. Currently, researchers focus on a single biomarker type and one tumor entity. This study aimed to create a multi-analyte liquid biopsy test for the simultaneous detection of several solid cancers. For this purpose, we analyzed cell-free DNA (cfDNA) mutations and methylation, as well as circulating miRNAs (miRNAs) in plasma samples from 97 patients with cancer (20 bladder, 9 brain, 30 breast, 28 colorectal, 29 lung, 19 ovarian, 12 pancreas, 27 prostate, 23 stomach) and 15 healthy controls via real-time qPCR. Androgen receptor p.H875Y mutation (AR) was detected for the first time in bladder, lung, stomach, ovarian, brain, and pancreas cancer, all together in 51.3% of all cancer samples and in none of the healthy controls. A discriminant function model, comprising cfDNA mutations (COSM10758, COSM18561), cfDNA methylation markers (MLH1, MDR1, GATA5, SFN) and miRNAs (miR-17-5p, miR-20a-5p, miR-21-5p, miR-26a-5p, miR-27a-3p, miR-29c-3p, miR-92a-3p, miR-101-3p, miR-133a-3p, miR-148b-3p, miR-155-5p, miR-195-5p) could further classify healthy and tumor samples with 95.4% accuracy, 97.9% sensitivity, 80% specificity. This multi-analyte liquid biopsy-based test may help improve the simultaneous detection of several cancer types and underlines the importance of combining genetic and epigenetic biomarkers.

Different bisphenols induce non-monotonous changes in miRNA expression and LINE-1 methylation in two cell lines.

4,4'-Isopropylidenediphenol (bisphenol A, BPA), a chemical substance that is widely used mainly as a monomer in the production of polycarbonates, in epoxy resins, and in thermal papers, is suspected to cause epigenetic modifications with potentially toxic consequences. Due to its negative health effects, BPA is banned in several products and is replaced by other bisphenols such as bisphenol S and bisphenol F. The present study examined the effects of BPA, bisphenol S, bisphenol F, p,p'-oxybisphenol, and the BPA metabolite BPA ß-d-glucuronide on the expression of a set of microRNAs (miRNAs) as well as long interspersed nuclear element-1 methylation in human lung fibroblast and Caco-2 cells. The results demonstrated a significant modulation of the expression of different miRNAs in both cell lines including miR-24, miR-155, miR-21, and miR-146a, known for their regulatory functions of cell cycle, metabolism, and inflammation. At concentrations between 0.001 and 10 µg/ml, especially the data of miR-155 and miR-24 displayed non-monotonous and often significant dose-response curves that were U- or bell-shaped for different substances. Additionally, BPA ß-d-glucuronide also exerted significant changes in the miRNA expression. miRNA prediction analysis indicated effects on multiple molecular pathways with relevance for toxicity. Besides, long interspersed nuclear element-1 methylation, a marker for the global DNA methylation status, was significantly modulated by two concentrations of BPA and p,p'-oxybisphenol. This pilot study suggests that various bisphenols, including BPA ß-d-glucuronide, affect epigenetic mechanisms, especially miRNAs. These results should stimulate extended toxicological studies of multiple bisphenols and a potential use of miRNAs as markers.

Five Days Periodic Fasting Elevates Levels of Longevity Related Christensenella and Sirtuin Expression in Humans.

Periodic fasting (PF) is an increasingly popular approach that assists in the management of metabolic and inflammatory diseases as well as in preventing mechanisms involved in aging. However, little is known about the effects of fasting on gut microbiota and its impact on the epigenetic regulation of metabolically relevant enzymes, especially sirtuins (SIRTs). We analyzed the effect of periodic fasting on the human gut microbiota, SIRTs expression, and mitochondrial content in 51 males and females. The participants fasted under supervision for five consecutive days following the Buchinger fasting guidelines. Ketogenesis, selected mRNAs, miRNAs, mitochondrial (mt) DNA, and gut composition were analyzed before and after PF. PF triggered a significant switch in metabolism, as indicated by the increase in ß-hydroxybutyrate (BHB) and pyruvate dehydrogenase kinase isoform 4 (PDK4) expression in the capillary blood. MtDNA, SIRT1, SIRT3, and miRlet7b-5p expression in blood cells were elevated, whereas SIRT6 and miR125b-5p were not affected. Following fasting, gut microbiota diversity increased, and a statistically significant correlation between SIRT1 gene expression and the abundance of Prevotella and Lactobacillus was detected. The abundance of longevity related Christensenella species increased after fasting and inversely correlated with age as well as body mass index (BMI). Thus, this represents the first study that showing that fasting not only changes the composition of the gut microbiota, making it more diverse, but also affects SIRT expression in humans.

Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer's Disease: A Systematic Review.

Aging and the emergence of age-associated illnesses are one of the major challenges of our present society. Alzheimer's disease (AD) is closely associated with aging and is defined by increasing memory loss and severe dementia. Currently, there are no therapy options available that halt AD progression. This work investigates three hallmarks of the disease (autophagy, neuroinflammation, and senescence) and systematically analyzes if there is a beneficial effect from three substances derived from food sources, the so called "nutraceuticals" epigallocatechin gallate, fisetin, and spermidine, on these hallmarks. The results imply a positive outlook for the reviewed substances to qualify as a novel treatment option for AD. A combination of nutraceutical substances and other preventive measures could have significant clinical impact in a multi-layered therapy approach to counter AD.

Epigallocatechin Gallate Effectively Affects Senescence and Anti-SASP via SIRT3 in 3T3-L1 Preadipocytes in Comparison with Other Bioactive Substances.

AIM: We investigated different bioactive compounds including epigallocatechin gallate (EGCG), anthocyanidin, resveratrol, phloretin, spermidine, butyrate, and ß-hydroxybutyrate with regard to their effect on SIRT3 via NRF2 and modulation of the proinflammatory senescence-associated secretory phenotype (SASP) in senescence induced 3T3-L1 preadipocytes. METHODS: For induction of senescence, 3T3-L1 preadipocytes were incubated with bromodeoxyuridine (BrdU) for 8 days. Cell cycle inhibition was observed, and ß-galactosidase activity was measured. After BrdU treatment, cells were treated with different bioactive compounds in various concentrations for 96 h. ELISA was used for determining proinflammatory cytokine IL6 in SASP cells. RESULTS: CDKN1a increased significantly after BrdU incubation compared to untreated control (p < 0.01). All secondary plant ingredients used for treatment, but not anthocyanidin 50 µM, decrease CDKN1a expression (p < 0.05), whereas most endogenous substances did not attenuate CDKN1a. IL6 secretion positively correlated with CDKN1a (p < 0.01), whereas EGCG could diminish both, IL6 and CDKN1a with the strongest effect (p < 0.01). Although NRF2 positively correlated with SIRT3 activation (p < 0.05), only resveratrol (p < 0.01) and anthocyanidin (p < 0.05) could activate NRF2 significantly. Solely anthocyanidin 50 µM (p < 0.05) and 100 µM (p < 0.01) and EGCG 50 µM (p < 0.01) could increase SIRT3 expression. Activation of SIRT3 with EGCG correlated with lowered IL6 secretion significantly (p < 0.05) but not with anthocyanidin. CONCLUSION: Accumulation of senescent cells in adipose tissue plays an important role in obesity and age-related diseases. SIRT3, located in the mitochondria, can regulate ROS via different pathways. Thus, targeting SIRT3 activating compounds such as EGCG may delay senescence of cells and senescence induced inflammatory processes.

Vaginal Microbiome Signature Is Associated With Spontaneous Preterm Delivery.

Background: Preterm delivery (PTD) represents an important public health and therapeutic challenge. Despite the reported link between the composition of vaginal microbiome and PTD, previous studies were inconsistent in their conclusions and utilized non-uniform designs. We performed an independent case-control study carried out on the Slovenian population, where we re-evaluated the role of the vaginal microbiome in PTD. Methods: Vaginal microbiomes of pregnant women who delivered preterm were compared to those delivered at term to examine differences in the microbial richness, diversity, and differential abundance of specific taxa. We obtained vaginal swab samples from 155 Caucasian women who were classified as either term (≥380/7 weeks, n = 107) or preterm (≤366/7 weeks, n = 48) in exclusion of any other medical or obstetric conditions. The vaginal microbiomes of these women were characterized by 16S ribosomal RNA (rRNA) gene sequencing of the V3-V4 region on the MiSeq platform. Results: Women who experienced PTD had a higher microbial richness (Chao1, P = 0.011) and alpha diversity (Shannon, P = 0.00059) than women with term deliveries. We report that overall vaginal microbial community composition (beta-diversity) was significantly different by delivery gestational age category (P WeightedUnifrac < 0.001). Women who delivered preterm had decreased Lactobacilli spp. abundance as well as increased abundance of Gardnerella and other bacterial vaginosis (BV) and aerobic vaginitis (AV) associated genera including Atopobium, Sneathia, Gemella, Megasphaera, Dorea, Streptococcus, and Escherichia/Shigella. Conclusions: In the present study, we provide further evidence that vaginal microbiome composition is associated with PTD.

Impact of Weight Loss Strategies on Obesity-Induced DNA Damage.

SCOPE: Obesity causes DNA damage, which is causally related to several disorders including cancer, infertility, and cognitive dysfunctions. The aim of this study is to investigate whether weight loss improves the integrity of the genetic material. METHODS AND RESULTS: Overweight mice are fed ad libitum either with a Western diet (WD), with a 40% caloric restricted WD, or with a high carbohydrate low protein (HCLP) diet. Caloric restriction and also the HCLP diet lead to ca. 30% weight loss, which is paralleled by decreased DNA damage ("comet" formation) and oxidative damage of purines in inner organs, additionally the activity of nucleotide excision repair increased. The effects are more pronounced in animals that have received the HCLP chow. Results of biochemical analyses indicate that the reduction of DNA damage is associated with a decrease of pro-inflammatory cytokines and lower insulin levels. CONCLUSION: The study indicates that weight loss may prevent obesity-associated adverse health effects due to reduction of overall DNA damage.

Gallic acid, a common dietary phenolic protects against high fat diet induced DNA damage.

PURPOSE: Aim of the study was to find out if gallic acid (GA), a common phenolic in plant foods, prevents obesity induced DNA damage which plays a key role in the induction of overweight associated cancer. METHODS: Male and female C57BL6/J mice were fed with a low fat or a high fat diet (HFD). The HFD group received different doses GA (0, 2.6-20 mg/kg b.w./day) in the drinking water for 1 week. Subsequently, alterations of the genetic stability in blood and inner organs were monitored in single cell gel electrophoresis assays. To elucidate the underlying molecular mechanisms: oxidized DNA bases, alterations of the redox status, lipid and glucose metabolism, cytokine levels and hepatic NF-κB activity were monitored. RESULTS: HFD fed animals had higher body weights; increased DNA damage and oxidation of DNA bases damage were detected in colon, liver and brain but not in blood and white adipose tissue. Furthermore, elevated concentrations of insulin, glucose, triglycerides, MCP-1, TNF-α and NF-κB activity were observed in this group. Small amounts of GA, in the range of human consumption, caused DNA protection and reduced oxidation of DNA bases, as well as biochemical and inflammatory parameters. CONCLUSIONS: Obese animals have increased DNA damage due to oxidation of DNA bases. This effect is probably caused by increased levels of glucose and insulin. The effects of GA can be explained by its hypoglycaemic properties and indicate that the consumption of GA-rich foods prevents adverse health effects in obese individuals.

Identification of Clostridium spp. derived from a sheep and cattle slaughterhouse by matrix-assisted laser desorption and ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rDNA sequencing.

Clostridia are widespread and some of them are serious human pathogens. Identification of Clostridium spp. is important for managing microbiological risks in the food industry. Samples derived from sheep and cattle carcasses from a slaughterhouse in Iran were analyzed by MALDI-TOF MS using direct transfer and extended direct transfer sample preparation methods and 16S rDNA sequencing. MALDI-TOF MS could identify ten species in 224 out of 240 Clostridium isolates. In comparison to the 16S rDNA sequencing, correct identification rate of the Clostridium spp. at the species level by MALDI-TOF MS technique was 93.3%. 16 isolates were not identified by MALDI-TOF MS but 16s rDNA sequencing identified them as C. estertheticum, C. frigidicarnis, and C. gasigenes species. The most frequently identified Clostridium species were: C. sporogenes (13%), C. cadaveris (12.5%), C. cochlearium (12%) and C. perfringens (10%). Extended direct transfer method [2.26 ± 0.18 log (score)] in comparison to direct transfer method [2.15 ± 0.23 log (score)] improved Clostridium spp. IDENTIFICATION: Using a cut-off score of 1.7 was sufficient for accurate identification of Clostridium species. MALDI-TOF MS identification scores for Clostridium spp. decreased with longer incubation time. Clostridium species predominantly were isolated from carcasses after skinning and evisceration steps in the slaughterhouse. MALDI-TOF MS could be an accurate way to identify Clostridium species. Moreover, continuous improvement of the database and MALDI-TOF MS instrument enhance its performance in food control laboratories.

Impact of obesity and overweight on DNA stability: Few facts and many hypotheses.

Health authorities are alarmed worldwide about the increase of obesity and overweight in the last decades which lead to adverse health effects including inflammation, cancer, accelerated aging and infertility. We evaluated the state of knowledge concerning the impact of elevated body mass on genomic instability. Results of investigations with humans (39 studies) in which DNA damage was monitored in lymphocytes and sperm cells, are conflicting and probably as a consequence of heterogeneous study designs and confounding factors (e.g. uncontrolled intake of vitamins and minerals and consumption of different food types). Results of animal studies with defined diets (23 studies) are more consistent and show that excess body fat causes DNA damage in multiple organs including brain, liver, colon and testes. Different molecular mechanisms may cause genetic instability in overweight/obese individuals. ROS formation and lipid peroxidation were found in several investigations and may be caused by increased insulin, fatty acid and glucose levels or indirectly via inflammation. Also reduced DNA repair and formation of advanced glycation end products may play a role but more data are required to draw firm conclusions. Reduction of telomere lengths and hormonal imbalances are characteristic for overweight/obesity but the former effects are delayed and moderate and hormonal effects were not investigated in regard to genomic instability in obese individuals. Increased BMI values affect also the activities of drug metabolizing enzymes which activate/detoxify genotoxic carcinogens, but no studies concerning the impact of these alterations of DNA damage in obese individuals are available. Overall, the knowledge concerning the impact of increased body weight and DNA damage is poor and further research is warranted to shed light on this important issue.

Counteraction of Oxidative Stress by Vitamin E Affects Epigenetic Regulation by Increasing Global Methylation and Gene Expression of MLH1 and DNMT1 Dose Dependently in Caco-2 Cells.

Obesity- or diabetes-induced oxidative stress is discussed as a major risk factor for DNA damage. Vitamin E and many polyphenols exhibit antioxidative activities with consequences on epigenetic regulation of inflammation and DNA repair. The present study investigated the counteraction of oxidative stress by vitamin E in the colorectal cancer cell line Caco-2 under normal (1 g/l) and high (4.5 g/l) glucose cell culture condition. Malondialdehyde (MDA) as a surrogate marker of lipid peroxidation and reactive oxygen species (ROS) was analyzed. Gene expression and promoter methylation of the DNA repair gene MutL homolog 1 (MLH1) and the DNA methyltransferase 1 (DNMT1) as well as global methylation by LINE-1 were investigated. Results revealed a dose-dependent counteracting effect of vitamin E on H2O2-induced oxidative stress. Thereby, 10 µM vitamin E proved to be more efficient than did 50 µM in reducing MDA. Further, an induction of MLH1 and DNMT1 gene expression was noticed, accompanied by an increase in global methylation. Whether LINE-1 hypomethylation is a cause or effect of oxidative stress is still unclear. In conclusion, supplementation of exogenous antioxidants like vitamin E in vitro exhibits beneficial effects concerning oxidative stress as well as epigenetic regulation involved in DNA repair.

The Role of Microbiota in Depression - a brief review.

The microbiota-gut-brain axis is a bidirectional homeostatic route of communication between both of the organs direct via receptors of the CNS or via epigenetic mechanisms of divers metabolites e.g. SCFA, GABA, ß-hydroxybutyrate. Thus, a modulation of gut microbiota via nutrition, lifestyle etc. might be effective for emotional status and depressive disorders. The dietary composition has an influence on gut microbiota composition, microbial metabolite profile and the according consequences on emotional status and depression within a system biologic approach. There are changes in gut microbiota composition and gut microbial profile (butyrate, GABA, ß-hydroxybutyrate) effecting epigenetic regulation (histone acetylation, DNA methylation) and gene expression of receptors and mediators (SLC6A4, BDNF, GABA, GPRs) involved in depressive disorders.

Bacterial Diversity in Traditional Doogh in Comparison to Industrial Doogh.

Forty-four samples of traditional Doogh and yoghurt were collected from 13 regions of 4 provinces in west of Iran (13 area) and analyzed using molecular methods including PCR, denaturing gradient gel electrophoresis (DGGE) of 16S rDNA, and sequencing. Moreover, collected samples as well as samples from industrially Doogh were analyzed with quantitative real-time PCR (RT-PCR). Analyzed 16S rRNA gene sequences of Doogh samples could be allocated to the presence of Lactobacillus spp. The typical yoghurt starter culture bacteria included four different Lactobacillus species with possible probiotic properties, L. acidophilus, L. helveticus, L. kefiranofaciens, and L. amylovorus. DGGE of traditional Doogh and yoghurt and RT-PCR of traditional Doogh and yoghurt and also industrial Doogh samples demonstrated that traditional Doogh and yoghurt show a higher abundance of total bacteria and lactobacilli and a higher bacterial diversity, respectively. Considering diversity and higher probiotic bacteria content in traditional Doogh, consumers' healthiness in tribes and villages could be promoted with these indigenous products.