Genes and Nutrition

Impact of single nucleotide polymorphisms (SNPs) in antioxidant-enzyme genes on the concentrations of folate, homocysteine and glutathione in plasma from healthy subjects after folic acid supplementation - a randomized controlled crossover trial
Mansoor MA, Stea TH, Slettan A, Perera E, Maddumage R, Kottahachchi D, Ali DS, Cabo R and Blomhoff R
One-carbon metabolism links folate and methionine metabolism and this is essential for nucleotide synthesis in the cells. Alterations in one-carbon metabolism are associated with cardiovascular disease (CVD), type 2 diabetes and cancer. Our aim was to investigate whether SNPs in antioxidant-enzyme genes impact the concentrations of folate in serum (s-folate), plasma total homocysteine (p-tHcy) and total glutathione in plasma (p-tGSH) in healthy subjects after supplementation with folic acid.
A double knockout for zinc transporter 8 and somatostatin in mice reveals their distinct roles in regulation of insulin secretion and obesity
Yang Z, Kirschke CP, Cai Y and Huang L
Both zinc transporter 8 (ZnT8) and somatostatin (Sst) play crucial roles in the regulation of insulin and glucagon secretion. However, the interaction between them in controlling glucose metabolism was not well understood. The aim of this study was to explore the interactive effects of a double knockout of Znt8 and Sst on insulin and glucose metabolism in mice.
Visnagin alleviates rheumatoid arthritis via its potential inhibitory impact on malate dehydrogenase enzyme: in silico, in vitro, and in vivo studies
Khamis AA, Sharshar AH, Mohamed TM, Abdelrasoul EA and Salem MM
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. The present study aimed to evaluate the in silico, in vitro, and in vivo inhibitory effect of visnagin on malate dehydrogenase activity and elucidate its inflammatory efficacy when combined with methotrexate in the RA rat model. The molecular docking, ADMET simulations, MDH activity, expression, and X-ray imaging were detected. Moreover, CRP, RF, (anti-CCP) antibody, (TNF-α), (IL-6), (IL-17), and (IL-10) were evaluated. The expression levels of MMP3 and FOXP3 genes and CD4, CD25, and CD127 protein levels were assessed. Histological assessment of ankle joints was evaluated. The results revealed that visnagin showed reversible competitive inhibition on MDH with inhibitory constant (Ki) equal to 141 mM with theoretical IC50 equal to 1202.7 mM, LD50 equal to 155.39 mg/kg, and LD25 equal to 77.69 mg/kg. In vivo studies indicated that visnagin exhibited anti-inflammatory effects through decreasing MDH1 activity and expression and induced proliferation of anti-inflammatory CD4CD25FOXP3 regulatory T cells with increasing the anti-inflammatory cytokine IL-10 levels. Moreover, visnagin reduced the levels of inflammatory cytokines and the immuno-markers. Our findings elucidate that visnagin exhibits an anti-inflammatory impact against RA through its ability to inhibit the MDH1 enzyme, improve methotrexate efficacy, and reduce oxidative stress.
Hypothetical proteins of chicken-isolated Limosilactobacillus reuteri subjected to in silico analyses induce IL-2 and IL-10
Adejumo IO
Lactic acid bacteria (LAB) probiotics are health-promoting but their characteristics, safety profile and functional mechanisms are not fully understood. Hence, this study aimed to characterize some hypothetical proteins of the chicken-isolated Limosilactobacillus reuteri genome and unravel their IL-2 and IL-10-inducing potential to understand mechanisms of their immunological functionality for sustainable applications. The selected proteins were subjected to in silico analyses for transmembrane topology, sub-cellular localization, IL-2 and IL-10-inducing ability and IL-2 and IL-10 gene expression across various conditions. IL-2 and IL-10-inducing mutants were statistically analyzed using a one-way analysis of variance of a general linear model of SAS and statistical significance was set at p < 0.05. The analyzed proteins are stable under a wide temperature range. All the hypothetical proteins are IL-2 and IL-10-inducing but QHPv.2.12, QHPv.2.13 and QHPv.2.15 are non-immunogenic. The evaluated mutants are IL-2 and IL-10-inducers but QHPv.2.13 and QHPv.2.15 are not immunogenic. This study sheds light on understanding the functional mechanisms of chicken-isolated L. reuteri and suggests it or its proteins as potent candidates for feed additive and therapeutic purposes.
Quercetin supplementation in metabolic syndrome: nutrigenetic interactions with the Zbtb16 gene variant in rodent models
Kábelová A, Malínská H, Marková I, Hüttl M, Liška F, Chylíková B and Šeda O
Quercetin is a promising phytochemical in treating abnormalities associated with metabolic syndrome (MetS). This study aimed to explore the morphometric, metabolic, transcriptomic, and nutrigenetic responses to quercetin supplementation using two genetically distinct MetS models that only differ in the variant of the MetS-related Zbtb16 gene (Zinc Finger And BTB Domain Containing 16).
Genistein inhibited endocytosis and fibrogenesis in keloid via CTGF signaling pathways
Lu CT, Ko JL, Ou CC, Hsu CT, Hsiao YP and Tang SC
This study aimed to evaluate soy isoflavones' effect and potential use-specifically genistein-in treating human keloid fibroblast cells (KFs) and in a keloid tissue culture model.
Effects of the oral administration of glycosaminoglycans with or without native type II collagen on the articular cartilage transcriptome in an osteoarthritic-induced rabbit model
Mariné-Casadó R, Domenech-Coca C, Fernández S, Costa A, Segarra S, López-Andreo MJ, Puiggròs F, Cerón JJ, Martínez-Puig D, Soler C, Sifre V, Serra CI and Caimari A
In a previous study, the 84-day administration of glycosaminoglycans (GAGs), with or without native collagen type II (NC), in an osteoarthritis (OA)-induced rabbit model slowed down OA progression, improved several micro- and macroscopic parameters and magnetic resonance imaging (MRI) biomarkers in cartilage, and increased hyaluronic acid levels in synovial fluid. To elucidate the potential underlying mechanisms, a transcriptomics approach was conducted using medial femoral condyle and trochlea samples.
miR-450a-2-3p targets ERK(1/2) to ameliorate ISO-induced cardiac fibrosis in mice
Liu L and Luo F
Cardiac fibrosis is an important contributor to atrial fibrillation (AF). Our aim was to identify biomarkers for AF using bioinformatics methods and explore the regulatory mechanism of miR-450a-2-3p in cardiac fibrosis in mice.
Protective effects of Nogo-B deficiency in NAFLD mice and its multiomics analysis of gut microbiology and metabolism
Dong X, Xiong YT, He T, Zheng C, Li J, Zhuang Y, Xu Y, Xiu Y, Wu Z, Zhao X, Xiao X, Bai Z and Gao L
Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver ailment that can lead to serious conditions such as cirrhosis and hepatocellular carcinoma. Hepatic Nogo-B regulates glucose and lipid metabolism, and its inhibition has been shown to be protective against metabolic syndrome. Increasing evidence suggests that imbalances in the gut microbiota (GM) and lipid metabolism disorders are significant contributors to NAFLD progression. Nevertheless, it is not yet known whether Nogo-B can affect NAFLD by influencing the gut microbiota and metabolites. Hence, the aim of the present study was to characterize this process and explore its possible underlying mechanisms.
Dry blood spots as a sampling strategy to identify insulin resistance markers during a dietary challenge
Duarte SG, Donado-Pestana CM, More TH, Rodrigues L, Hiller K and Fiamoncini J
This study aimed to identify markers of postprandial dysglycemia in the blood of self-described healthy individuals using dry blood spots (DBS) as a sampling strategy. A total of 54 volunteers, including 31 women, participated in a dietary challenge. They consumed a high-fat, high-sugar mixed meal and underwent multiple blood sampling over the course of 150 min to track their postprandial responses. Blood glucose levels were monitored with a portable glucometer and individuals were classified into two groups based on the glucose area under the curve (AUC): High-AUC (H-AUC) and Low-AUC (L-AUC). DBS sampling was performed at the same time points as the assessment of glycemia using Whatman 903 Protein Saver filter paper. A gas chromatography-mass spectrometry-based metabolite profiling was conducted in the DBS samples to assess postprandial changes in blood metabolome. Higher concentrations of metabolites associated with insulin resistance were observed in individuals from the H-AUC group, including sugars and sugar-derived products such as fructose and threonic acid, as well as organic acids and fatty acids such as succinate and stearic acid. Several metabolites detected in the GC-MS analysis remained unidentified, indicating that other markers of hyperglycemia remain to be discovered in DBS. Based on these observations, we demonstrated that the use of DBS as a non-invasive and inexpensive sampling tool allows the identification of metabolites markers of dysglycemia in the postprandial period.
Homocysteine, blood pressure and gene-diet interactions in relation to vascular function measures of black South Africans
du Plessis JP, Lammertyn L, Schutte AE and Nienaber-Rousseau C
We investigated circulating homocysteine (Hcy), a cardiovascular disease (CVD) risk factor, examining its dietary associations to provide personalized nutrition advice. This study addressed the inadequacy of current dietary interventions to ultimately address the disproportionately high incidence of CVD in Black populations.
The role of diet in cancer: the potential of shaping public policy and clinical outcomes in the UK
Britten O and Tosi S
Cancer universally represents one of the largest public health concerns, substantially contributing to global disease burden and mortality. The multifaceted interplay of environmental and genetic factors in the disease aetiology and progression has required comprehensive research to elucidate modifiable elements which can reduce the risk of incidence and improve prognosis. Among these factors, diet and nutrition have emerged as the most fundamental with a significant potential for influence and effect. Nutrition is not only an essential part of human survival, but also a vital determinant of overall health. Certain dietary requirements are necessary to support normal physiology. This includes individualised levels of macronutrients (proteins, carbohydrates and fats) and specific micronutrients (vitamins and minerals). Extensive research has demonstrated that diet plays a role in cancer pathogenesis at the genetic, epigenetic and cellular level. Therefore, its potential as a modifiable determinant of cancer pathogenesis for the purpose of prevention and improving management of disease must be further explored and implemented. The ability to influence cancer incidence and outcomes through dietary changes is underutilised in clinical practice and insufficiently recognised among the general public, healthcare professionals and policy-makers. Dietary changes offer the opportunity for autonomy and control over individuals health outcomes. Research has revealed that particular dietary components, as well as cultural behaviours and epidemiological patterns may act as causative or protective factors in cancer development. This review aims to comprehensively synthesise this research to further explore how to best utilise this knowledge within the community and clinical environment for more effective cancer prevention and therapeutic strategies. The identified key areas for improvement include the development of more specific, widely accepted guidelines, promoting increased involvement of dieticians within cancer multidisciplinary teams, enhancing nutritional education for healthcare professionals and exploring the potential implementation of personalised nutrition tools. A greater understanding of the complex interactions between diet and cancer will facilitate informed clinical interventions and public health policies to reduce global cancer burden and improve care for cancer patients and survivors.
Exploring the therapeutic potential of garlic in alcoholic liver disease: a network pharmacology and experimental validation study
Gao S, Gao T, Li L, Wang S, Hu J, Zhang R, Zhou Y and Dong H
Employing network pharmacology and molecular docking, the study predicts the active compounds in garlic and elucidates their mechanism in inhibiting the development of alcoholic liver disease (ALD). ALD is a global chronic liver disease with potential for hepatocellular carcinoma progression.
Genetic association between FADS and ELOVL polymorphisms and the circulating levels of EPA/DHA in humans: a scoping review
Loukil I, Mutch DM and Plourde M
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are two omega-3 fatty acids that can be synthesized out of their precursor alpha-linolenic acid (ALA). FADS and ELOVL genes encode the desaturase and elongase enzymes required for EPA and DHA synthesis from ALA; however, single nucleotide polymorphisms (SNPs) in FADS and ELOVL genes could modify the levels of EPA and DHA synthesized from ALA although there is no consensus in this area. This review aims to investigate EPA and DHA circulating levels in human blood and their association with FADS or ELOVL.
Correction: Tracing vitamins on the long non-coding lane of the transcriptome: vitamin regulation of LncRNAs
Yazarlou F, Alizadeh F, Lipovich L, Giordo R and Ghafouri-Fard S
Effects of N-acetylcysteine on the expressions of UCP1 and factors related to thyroid function in visceral adipose tissue of obese adults: a randomized, double-blind clinical trial
Sohouli MH, Eslamian G, Ardehali SH, Raeissadat SA, Shimi G, Pourvali K and Zand H
Evidences have shown that obesity is influenced by various factors, including various hormones such as thyroid hormones and the body's metabolism rate. It seems that practical solutions such as weight loss diets and common drugs can affect these potential disorders. In this study, we investigate one of these common drugs, N-Acetylcysteine (NAC), on expressions of UCP1 and factors related to thyroid function in adults with obesity.
The potential impact of dietary choices on melanoma risk: an anti-inflammatory diet
Fortes C, Mastroeni S, Levati L, Alotto M, Ricci F and D'Atri S
The role of inflammation in the aetiology of cancer is recognized. However, no study yet examined the association between an anti-inflammatory diet and cutaneous melanoma and explored whether it could be modified by genetic variations in cyclooxygenase-2 (COX-2), a key enzyme in inflammation. A case-control study was conducted in the IDI-IRCCS hospital in Rome, Italy with 273 cases of primary cutaneous melanoma and 269 controls frequency matched to cases. Information on socio-demographic and pigmentary characteristics, medical history, sun exposure and dietary habits were collected for all subjects. The - 765G > C polymorphism was identified in DNA extracted from blood samples. An anti-inflammatory diet score was created. Logistic regression models were fitted to obtain odds ratios (ORs) and 95% confidence intervals (CIs). A high anti-inflammatory diet score (≥ 8 anti-inflammatory dietary items) was associated with a decreased risk of cutaneous melanoma (OR: 0.29; 95%CI: 0.17-0.49, P < 0.0001) after adjusting for sex, age, education, number of common nevi, skin photo-type, solar lentigines and sunburns in childhood. COX-2 -765 G > C polymorphism was not an independent risk factor for cutaneous melanoma. Although interaction between - 765G > C genotypes and anti-inflammatory diet score was not statistically significant (p = 0.25), when stratified by -765 G > C genotypes the effect of the anti-inflammatory diet was slightly more pronounced for participants carrying - 765GG (OR: 0.17; 95%CI: 0.06-0.47, P < 0.001). Our study findings suggest that adherence to an anti-inflammatory diet is associated with a decreased risk of developing cutaneous melanoma. These results suggest the potential impact of dietary choices on melanoma risk.
Comprehensive overview of how to fade into succinate dehydrogenase dysregulation in cancer cells by naringenin-loaded chitosan nanoparticles
Ragab EM, Khamis AA, Gamal DME and Mohamed TM
Mitochondrial respiration complexes play a crucial function. As a result, dysfunction or change is intimately associated with many different diseases, among them cancer. The epigenetic, evolutionary, and metabolic effects of mitochondrial complex IΙ are the primary concerns of our review. Provides novel insight into the vital role of naringenin (NAR) as an intriguing flavonoid phytochemical in cancer treatment. NAR is a significant phytochemical that is a member of the flavanone group of polyphenols and is mostly present in citrus fruits, such as grapefruits, as well as other fruits and vegetables, like tomatoes and cherries, as well as foods produced from medicinal herbs. The evidence that is now available indicates that NAR, an herbal remedy, has significant pharmacological qualities and anti-cancer effects. Through a variety of mechanisms, including the induction of apoptosis, cell cycle arrest, restriction of angiogenesis, and modulation of several signaling pathways, NAR prevents the growth of cancer. However, the hydrophobic and crystalline structure of NAR is primarily responsible for its instability, limited oral bioavailability, and water solubility. Furthermore, there is no targeting and a high rate of breakdown in an acidic environment. These shortcomings are barriers to its efficient medical application. Improvement targeting NAR to mitochondrial complex ΙΙ by loading it on chitosan nanoparticles is a promising strategy.
Tracing vitamins on the long non-coding lane of the transcriptome: vitamin regulation of LncRNAs
Yazarlou F, Alizadeh F, Lipovich L, Giordo R and Ghafouri-Fard S
A major revelation of genome-scale biological studies in the post-genomic era has been that two-thirds of human genes do not encode proteins. The majority of non-coding RNA transcripts in humans are long non-coding RNA (lncRNA) molecules, non-protein-coding regulatory transcripts with sizes greater than 500 nucleotides. LncRNAs are involved in nearly every aspect of cellular physiology, playing fundamental regulatory roles both in normal cells and in disease. As result, they are functionally linked to multiple human diseases, from cancer to autoimmune, inflammatory, and neurological disorders. Numerous human conditions and diseases stem from gene-environment interactions; in this regard, a wealth of reports demonstrate that the intake of specific and essential nutrients, including vitamins, shapes our transcriptome, with corresponding impacts on health. Vitamins command a vast array of biological activities, acting as coenzymes, antioxidants, hormones, and regulating cellular proliferation and coagulation. Emerging evidence suggests that vitamins and lncRNAs are interconnected through several regulatory axes. This type of interaction is expected, since lncRNA has been implicated in sensing the environment in eukaryotes, conceptually similar to riboswitches and other RNAs that act as molecular sensors in prokaryotes. In this review, we summarize the peer-reviewed literature to date that has reported specific functional linkages between vitamins and lncRNAs, with an emphasis on mammalian models and humans, while providing a brief overview of the source, metabolism, and function of the vitamins most frequently investigated within the context of lncRNA molecular mechanisms, and discussing the published research findings that document specific connections between vitamins and lncRNAs.
Causal relationship between dietary salt intake and dementia risk: Mendelian randomization study
Shi K, Yu Y, Li Z, Hou M and Li X
Observational research has indicated a potential link between dietary salt intake and susceptibility to dementia. However, it is important to note that these types of studies are prone to the issues of reverse causation and residual confounding. Therefore, we conducted a two-sample Mendelian randomization (MR) study to explore the causality.
Probiotics ameliorate endocrine disorders via modulating inflammatory pathways: a systematic review
Nemati M, Ebrahimi B and Montazeri-Najafabady N
Probiotics has offered a new prospect to treat and manage a variety of endocrine disorders such as obesity, diabetes, non- alcoholic fatty liver disease and metabolic syndrome. The precise mechanisms by which probiotics exert their beneficial effects on endocrine disorders and its associated problems are still indecisive. It seems that regulating the immune system and suppressing pro-inflammatory pathways like tumor necrosis factor-α and interleukin-6 or triggering anti-inflammatory pathways like interleukin-4 and 10 may be one of the potential mechanisms in the managing of endocrine disorders. In this systematic review, we hypothesized that various probiotic strains (Lactobacillus, Biofidiobacteria, Streptococcus, Entrococcus, Clostridium, and Bacillus) alone or in combination with each other could manage endocrine disorders via modulating inflammatory pathways such as suppressing pro-inflammatory cytokines (IL-6, IL-12, TNF-α, TNF-β, NFκB, and MCP-1), stimulating anti-inflammatory cytokines (IL-4,IL-6, IL-22, IL-23, IL-33, and TGF-β) and maintaining other factors like C-reactive protein, Toll like receptors, LPS, and NK cells. Data source this search was performed in PubMed and Scopus. Both human and animal studies were included. Among more than 15,000 papers, 25 studies were identified as eligible for more assessments. Quality assessment of the studies was cheeked by two researchers independently by title and abstract screening, then article which have inclusion criteria were included, and data retrieved from the included full text studies as the authors had originally reported. Results specified that Lactobacillus has been the most widely used probiotic as well as which one exhibiting the extend of the therapeutic effects on endocrine disorders, especially obesity by modulating immune responses. Also, most studies have revealed that probiotics through suppressing pro-inflammatory pathways specially via reducing levels TNF-α cytokine exhibited protective or beneficial effects on endocrine diseases particularly obesity as well as through decreasing level of IL-6 induced therapeutic effects in diabetes. This systematic review suggests that probiotics could ameliorate endocrine disorders via their immunomodulatory effects.