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The Importance of Nutrigenetics and Microbiota in Personalized Medicine: From Phenotype to Genotype.Cureus May 2024Background After the completion of the Human Genome Project in 2003, the impact of genetic variations among people on human health was better understood. Precision...
Background After the completion of the Human Genome Project in 2003, the impact of genetic variations among people on human health was better understood. Precision medicine, also called 4P (Predictive, Preventive, Personalized, Participatory) medicine, is used to determine personal health risks, prevent, diagnose, and treat chronic diseases, and aims to identify the phenotypic, genotypic, and environmental factors that affect individual health risks instead of applying the same approach to everyone. Methods The study was conducted with 24 patients aged between 7 and 57. The patient group was selected from individuals who had undergone genetic and microbiota testing at Epigenetic Coaching Company. The patients' age, gender, and health status were documented. Genomic analysis of buccal samples was subsequently conducted using a custom Infinium HTS iSelect microarray on an Illumina iScan instrument, and microbiota metagenome analysis was performed using an Illumina NextSeq 500 platform. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Biruni University Molecular Biology and Genetics Ethics Committee, with the decision number 2023/78-03. Results The genotypes of 19 cases carrying genetic variants involved in the metabolism of Vitamin D, Folate, B12, and Choline were analyzed. Eight of the cases were included in our study as autism patients, eight as allergy patients, and three as autoimmune thyroiditis patients. The Vitamin D receptor (VDR) genetic variants and microbiota diversity (using the Firmicutes/Bacteroides ratio, an indicator of dysbiosis) of 11 cases (9 allergy and two autism patients) participating in the study were evaluated together. Conclusions Translating nutrigenetic and nutrigenomic research into multidisciplinary clinical practice is the most challenging aspect. It is now evident that integrating data regarding phenotype and genotype, and using nutrition, lifestyle, and supplements tailored to an individual's genetics can increase clinical success. Importantly, if we wish to adopt an epigenomic approach, we must incorporate analyses of nutrigenetics, microbiota, and personalized risk based on test results.
PubMed: 38807972
DOI: 10.7759/cureus.61256 -
Cellular and Molecular Neurobiology May 2024Considering the variability in individual responses to opioids and the growing concerns about opioid addiction, prescribing opioids for postoperative pain management...
Considering the variability in individual responses to opioids and the growing concerns about opioid addiction, prescribing opioids for postoperative pain management after spine surgery presents significant challenges. Therefore, this study undertook a novel pharmacogenomics-based in silico investigation of FDA-approved opioid medications. The DrugBank database was employed to identify all FDA-approved opioids. Subsequently, the PharmGKB database was utilized to filter through all variant annotations associated with the relevant genes. In addition, the dpSNP ( https://www.ncbi.nlm.nih.gov/snp/ ), a publicly accessible repository, was used. Additional analyses were conducted using STRING-MODEL (version 12), Cytoscape (version 3.10.1), miRTargetLink.2, and NetworkAnalyst (version 3). The study identified 125 target genes of FDA-approved opioids, encompassing 7019 variant annotations. Of these, 3088 annotations were significant and pertained to 78 genes. During variant annotation assessments (VAA), 672 variants remained after filtration. Further in-depth filtration based on variant functions yielded 302 final filtered variants across 56 genes. The Monoamine GPCRs pathway emerged as the most significant signaling pathway. Protein-protein interaction (PPI) analysis revealed a fully connected network comprising 55 genes. Gene-miRNA Interaction (GMI) analysis of these 55 candidate genes identified miR-16-5p as a pivotal miRNA in this network. Protein-Drug Interaction (PDI) assessment showed that multiple drugs, including Ibuprofen, Nicotine, Tramadol, Haloperidol, Ketamine, L-Glutamic Acid, Caffeine, Citalopram, and Naloxone, had more than one interaction. Furthermore, Protein-Chemical Interaction (PCI) analysis highlighted that ABCB1, BCL2, CYP1A2, KCNH2, PTGS2, and DRD2 were key targets of the proposed chemicals. Notably, 10 chemicals, including carbamylhydrazine, tetrahydropalmatine, Terazosin, beta-methylcholine, rubimaillin, and quinelorane, demonstrated dual interactions with the aforementioned target genes. This comprehensive review offers multiple strong, evidence-based in silico findings regarding opioid prescribing in spine pain management, introducing 55 potential genes. The insights from this report can be applied in exome analysis as a pharmacogenomics (PGx) panel for pain susceptibility, facilitating individualized opioid prescribing through genotyping of related variants. The article also points out that African Americans represent an important group that displays a high catabolism of opioids and suggest the need for a personalized therapeutic approach based on genetic information.
Topics: Humans; Pain, Postoperative; Precision Medicine; Analgesics, Opioid; Pharmacogenetics; Pain Management; Computer Simulation; Spine
PubMed: 38801645
DOI: 10.1007/s10571-024-01466-5 -
FEBS Open Bio May 2024The cellular response to oxidants or xenobiotics comprises two key pathways, resulting in modulation of NRF2 and FOXO transcription factors, respectively. Both mount a...
The cellular response to oxidants or xenobiotics comprises two key pathways, resulting in modulation of NRF2 and FOXO transcription factors, respectively. Both mount a cytoprotective response, and their activation relies on crucial protein thiol moieties. Using fumaric acid esters (FAEs), known thiol-reactive compounds, we tested for activation of NRF2 and FOXO pathways in cultured human hepatoma cells by dimethyl/diethyl as well as monomethyl/monoethyl fumarate. Whereas only the diesters caused acute glutathione depletion and activation of the stress kinase p38, all four FAEs stimulated NRF2 stabilization and upregulation of NRF2 target genes. However, no significant FAE-induced activation of FOXO-dependent target gene expression was observed. Therefore, while both NRF2 and FOXO pathways are responsive to oxidants and xenobiotics, FAEs selectively activate NRF2 signaling.
PubMed: 38794848
DOI: 10.1002/2211-5463.13833 -
Scientific Reports May 2024This study investigated the effects of supplemental nucleotides, autolyzed yeast (Saccharomyces cerevisiae), and sodium butyrate in diets for nursery pigs on growth...
This study investigated the effects of supplemental nucleotides, autolyzed yeast (Saccharomyces cerevisiae), and sodium butyrate in diets for nursery pigs on growth performance, diarrhea incidence, blood profile, intestinal morphology, mRNA expression of nutrient transporters, inflammatory markers, antioxidant profile, and tight junction proteins in the small intestine. One hundred eighty 21-day-old pigs (5.17 ± 0.57 kg) were assigned in a randomized block design to 1 of 4 dietary treatments: (1) CON: control, basal diet, (2) NUC: CON + nucleotides, (3) YSC: CON + lysed yeast S. cerevisiae, (4) ASB: CON + acidifier sodium butyrate. Pigs were fed for 24 days, phase 1 (21-32 days) and 2 (32-45 days). During phase 1, YSC and ASB improved average daily gain (ADG) and feed conversion (FC) compared with CON. At the overall period, ASB improved ADG and YSC improved FC compared with CON. The NUC diet did not affect growth performance. The ASB increased ileal villus height compared to CON. The YSC and ASB reduced the number of Peyer's patches in the ileum compared with CON. The YSC increased mRNA expression of nutrient transporters (SMCT2, MCT1, and PepT1), tight junction proteins (OCL and ZO-1), antioxidants (GPX), and IL1-β in the jejunum compared with CON. The ASB increased mRNA expression of nutrient transporters (SGLT1 and MCT1), tight junction proteins (OCL and ZO-1), and antioxidants (GPX and SOD) compared with CON. In conclusion, autolyzed yeast and sodium butyrate promoted growth performance by improving the integrity of the intestinal barrier, the mRNA expression of nutrient transporters, and antioxidant enzymes in the jejunum of nursery pigs whereas supplementation of nucleotides did not show such effects.
Topics: Animals; Swine; Butyric Acid; Dietary Supplements; Saccharomyces cerevisiae; Weaning; Animal Feed; Tight Junction Proteins; Intestinal Mucosa; Antioxidants; Intestines
PubMed: 38789563
DOI: 10.1038/s41598-024-62551-9 -
Gels (Basel, Switzerland) May 2024The wound-healing effect of St. John's Wort (SJW) is mainly attributed to hyperforin (HP), but its low stability restricts its topical administration. This study...
The wound-healing effect of St. John's Wort (SJW) is mainly attributed to hyperforin (HP), but its low stability restricts its topical administration. This study investigates how "free" HP-rich SJW extract (incorporated into a bigel; B/SJW) and extract "protected" by nanostructured lipid carriers (also included in a biphasic semisolid; B/NLC-SJW) affect tissue regeneration in a rat skin excision wound model. Wound diameter, histological changes, and tissue gene expression levels of fibronectin (Fn), matrix metalloproteinase 8 (MMP8), and tumor necrosis factor-alpha (TNF-α) were employed to quantify the healing progress. A significant wound size reduction was achieved after applying both extract-containing semisolids, but after a 21-day application period, the smallest wound size was observed in the B/NLC-SJW-treated animals. However, the inflammatory response was affected more favorably by the bigel containing the "free" SJW extract, as evidenced by histological studies. Moreover, after the application of B/SJW, the expression of Fn, MMP8, and TNF-α was significantly higher than in the positive control. In conclusion, both bigel formulations exhibited beneficial effects on wound healing in rat skin, but B/SJW affected skin restoration processes in a comprehensive and more efficient way.
PubMed: 38786258
DOI: 10.3390/gels10050341 -
Cells May 2024The early stages of life, especially the period from conception to two years, are crucial for shaping metabolic health and the risk of obesity in adulthood. Adipose... (Review)
Review
The early stages of life, especially the period from conception to two years, are crucial for shaping metabolic health and the risk of obesity in adulthood. Adipose tissue (AT) plays a crucial role in regulating energy homeostasis and metabolism, and brown AT (BAT) and the browning of white AT (WAT) are promising targets for combating weight gain. Nutritional factors during prenatal and early postnatal stages can influence the development of AT, affecting the likelihood of obesity later on. This narrative review focuses on the nutritional programming of AT features. Research conducted across various animal models with diverse interventions has provided insights into the effects of specific compounds on AT development and function, influencing the development of crucial structures and neuroendocrine circuits responsible for energy balance. The hormone leptin has been identified as an essential nutrient during lactation for healthy metabolic programming against obesity development in adults. Studies have also highlighted that maternal supplementation with polyunsaturated fatty acids (PUFAs), vitamin A, nicotinamide riboside, and polyphenols during pregnancy and lactation, as well as offspring supplementation with myo-inositol, vitamin A, nicotinamide riboside, and resveratrol during the suckling period, can impact AT features and long-term health outcomes and help understand predisposition to obesity later in life.
Topics: Humans; Animals; Obesity; Micronutrients; Adipose Tissue, Brown; Female; Pregnancy; Adipose Tissue; Anti-Obesity Agents
PubMed: 38786092
DOI: 10.3390/cells13100870 -
Biomolecules Apr 2024Ginseng, a popular herbal supplement among athletes, is believed to enhance exercise capacity and performance. This study investigated the short-term effects of Panax... (Randomized Controlled Trial)
Randomized Controlled Trial
Short-Term Panax Ginseng Extract Supplementation Reduces Fasting Blood Triacylglycerides and Oxygen Consumption during Sub-Maximal Aerobic Exercise in Male Recreational Athletes.
Ginseng, a popular herbal supplement among athletes, is believed to enhance exercise capacity and performance. This study investigated the short-term effects of Panax ginseng extract (PG) on aerobic capacity, lipid profile, and cytokines. In a 14-day randomized, double-blind trial, male participants took 500 mg of PG daily. Two experiments were conducted: one in 10 km races ( = 31) and another in a laboratory-controlled aerobic capacity test ( = 20). Blood lipid and cytokine profile, ventilation, oxygen consumption, hemodynamic and fatigue parameters, and race time were evaluated. PG supplementation led to reduced total blood lipid levels, particularly in triacylglycerides (10 km races -7.5 mg/dL (95% CI -42 to 28); sub-maximal aerobic test -14.2 mg/dL (95% CI -52 to 23)), while post-exercise blood IL-10 levels were increased (10 km 34.0 pg/mL (95% CI -2.1 to 70.1); sub-maximal aerobic test 4.1 pg/mL (95% CI -2.8 to 11.0)), and oxygen consumption decreased during the sub-maximal aerobic test (VO: -1.4 mL/min/kg (95% CI -5.8 to -0.6)). No significant differences were noted in race time, hemodynamic, or fatigue parameters. Overall, PG supplementation for 2 weeks showed benefits in blood lipid profile and energy consumption during exercise among recreational athletes. This suggests a potential role for PG in enhancing exercise performance and metabolic health in this population.
Topics: Humans; Male; Panax; Plant Extracts; Dietary Supplements; Adult; Exercise; Oxygen Consumption; Triglycerides; Athletes; Double-Blind Method; Young Adult; Fasting
PubMed: 38785940
DOI: 10.3390/biom14050533 -
Gene & Protein in Disease Mar 2024The D2 dopamine receptor () gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its...
The D2 dopamine receptor () gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its initial association with severe alcoholism in 1990, particularly through the identification of the allele, numerous international investigations have been conducted to elucidate its role in different conditions. As of February 22, 2024, there are 5485 articles focusing on the gene listed in PUBMED. There have been 120 meta-analyses with mixed results. In our opinion, the primary cause of negative reports regarding the association of various gene polymorphisms is the inadequate screening of controls, not adequately eliminating many hidden reward deficiency syndrome behaviors. Moreover, pleiotropic effects of variants have been identified in neuropsychologic, neurophysiologic, stress response, social stress defeat, maternal deprivation, and gambling disorder, with epigenetic DNA methylation and histone post-translational negative methylation identified as discussed in this article. There are 70 articles listed in PUBMED for DNA methylation and 20 articles listed for histone methylation as of October 19, 2022. For this commentary, we did not denote DNA and/or histone methylation; instead, we provided a brief summary based on behavioral effects. Based on the fact that Blum and Noble characterized the allele as a generalized reward gene and not necessarily specific alcoholism, it now behooves the field to find ways to either use effector moieties to edit the neuroepigenetic insults or possibly harness the idea of potentially removing negative mRNA-reduced expression by inducing "dopamine homeostasis."
PubMed: 38766604
DOI: 10.36922/gpd.1966 -
Scientific Reports May 2024Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas...
Maternal choline supplementation mitigates premature foetal weight gain induced by an obesogenic diet, potentially linked to increased amniotic fluid leptin levels in rats.
Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11-17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects.
Topics: Animals; Female; Leptin; Pregnancy; Choline; Dietary Supplements; Amniotic Fluid; Rats; Male; Placenta; Fetal Development; Obesity; Fetal Weight; Rats, Sprague-Dawley; Diet, Western
PubMed: 38762543
DOI: 10.1038/s41598-024-62229-2 -
Nutrients Apr 2024Flavonoids exert vasculoprotective effects in humans, but interindividual variability in their action has also been reported. This study aims to identify genes that are...
Integrated Analysis of Genomic and Genome-Wide Association Studies Identified Candidate Genes for Nutrigenetic Studies in Flavonoids and Vascular Health: Path to Precision Nutrition for (Poly)phenols.
Flavonoids exert vasculoprotective effects in humans, but interindividual variability in their action has also been reported. This study aims to identify genes that are associated with vascular health effects of flavonoids and whose polymorphisms could explain interindividual variability in response to their intake. Applying the predetermined literature search criteria, we identified five human intervention studies reporting positive effects of flavonoids on vascular function together with global genomic changes analyzed using microarray methods. Genes involved in vascular dysfunction were identified from genome-wide association studies (GWAS). By extracting data from the eligible human intervention studies, we obtained 5807 differentially expressed genes (DEGs). The number of identified upstream regulators (URs) varied across the studies, from 227 to 1407. The search of the GWAS Catalog revealed 493 genes associated with vascular dysfunction. An integrative analysis of transcriptomic data with GWAS genes identified 106 and 42 , while subsequent functional analyses and a search of the literature identified 20 top priority candidate genes: , , , , , , , , , , , , , , , , , , , and . In conclusion, this integrated analysis identifies important genes to design future nutrigenetic studies for development of precision nutrition for polyphenols.
Topics: Humans; Genome-Wide Association Study; Nutrigenomics; Flavonoids; Polyphenols; Precision Medicine; Genomics
PubMed: 38732608
DOI: 10.3390/nu16091362