Genes and Nutrition最新文献

Background: 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.

Results: The administration of chondroitin sulfate (CS), glucosamine hydrochloride (GlHCl), and hyaluronic acid (HA), with (CGH-NC) or without (CGH) NC, strongly modulated several genes involved in chondrocyte extracellular matrix (ECM) remodeling and homeostasis when compared to non-treated rabbits (CTR group). Notably, both treatments shared the main mechanism of action, which was related to ECM modulation through the down-regulation of genes encoding proteolytic enzymes, such as ADAM metallopeptidase with thrombospondin type 1 motif, 9 (Adamts9), and the overexpression of genes with a relevant role in the synthesis of ECM components, such as aggrecan (Acan) in both CGH-NC and CGH groups, and fibronectin 1 (Fn1) and collagen type II, alpha 1 (Col2A1) in the CGH group. Furthermore, there was a significant modulation at the gene expression level of the mTOR signaling pathway, which is associated with the regulation of the synthesis of ECM proteolytic enzymes, only in CGH-NC-supplemented rabbits. This modulation could account for the better outcomes concerning the microscopic and macroscopic evaluations reported in these animals.

Conclusions: In conclusion, the expression of key genes involved in chondrocyte ECM remodeling and homeostasis was significantly modulated in rabbits in response to both CGH and CGH-NC treatments, which would partly explain the mechanisms by which these therapies exert beneficial effects against OA.

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.

Background: 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.

Methods: A NAFLD model was constructed by administering a high-fat diet (HFD) to Nogo-B^-/- and WT mice from the same litter, and body weight was measured weekly in each group. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to assess blood glucose levels. At the end of the 12-week period, samples of serum, liver, and intestinal contents were collected and used for serum biochemical marker and inflammatory factor detection; pathology evaluation; and gut microbiome and metabolomics analysis. Spearman's correlation analysis was performed to determine possible correlations between differential gut microbiota and differential serum metabolites between groups.

Results: Nogo-B deficiency attenuated the effects of the HFD, including weight gain, liver weight gain, impaired glucose tolerance, hepatic steatosis, elevated serum lipid biochemicals levels, and liver function. Nogo-B deficiency suppressed M1 polarization and promoted M2 polarization, thus inhibiting inflammatory responses. Furthermore, Nogo-B^-/--HFD-fed mice presented increased gut microbiota richness and diversity, decreased Firmicutes/Bacteroidota (F/B) ratios, and altered serum metabolites compared with those of WT-HFD-fed mice. During analysis, several differential gut microbiota, including Lachnoclostridium, Harryflintia, Odoribacter, UCG-009, and unclassified_f_Butyricoccaceae, were screened between groups. These microbiota were found to be positively correlated with upregulated purine metabolism and bile acid metabolites in Nogo-B deficiency, while they were negatively correlated with downregulated corticosterone and tricarboxylic acid cyclic metabolites in Nogo-B deficiency.

Conclusion: Nogo-B deficiency delayed NAFLD progression, as demonstrated by reduced hepatocellular lipid accumulation, attenuated inflammation and liver injury, and ameliorated gut microbiota dysbiosis and metabolic disorders. Importantly, Odoribacter was strongly positively correlated with ALB and taurodeoxycholic acid, suggesting that it played a considerable role in the influence of Nogo-B on the progression of NAFLD, a specific feature of NAFLD in Nogo-B^-/- mice. The regulatio

Objective: 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.

Methods: Two datasets, GSE115574 and GSE79768, were obtained from the Gene Expression Omnibus (GEO) database and subsequently merged for further analysis. Differential gene expression analysis was performed to identify differentially expressed genes (DEGs) and miR-450a-2-3p-related differentially expressed genes (MRDEGs). To investigate the underlying mechanism of cardiac fibrosis, a mouse model was established by treating mice with isoproterenol (ISO) and the miR-450a-2-3p agomir.

Results: A total of 127 DEGs and 31 MRDEGs were identified and subjected to Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the functions and pathways involved in AF. In the animal model, histological analysis using HE and Masson staining, as well as quantification of the collagen volume fraction (CVF), was performed. The increased expression of α-smooth muscle actin (α-SMA), collagen type I (COL1), collagen type III (COL3), and extracellular signal-regulated kinase 1/2 (ERK(1/2)) at both the transcriptional and translational levels indicated the significant development of myocardial fibrosis in mice induced with isoproterenol (ISO). In addition, the cross-sectional area of cardiomyocytes and the expression of atrial natriuretic peptide (NPPA) and brain natriuretic peptide (NPPB) were increased in the ISO group compared with the control group. However, after overexpression of the miR-450a-2-3p agomir through caudal vein injection, there was a notable improvement in cardiac morphology in the treated group. The expression levels of α-SMA, COL1, COL3, ERK(1/2), NPPA, and NPPB were also significantly decreased.

Conclusion: Our study reveals the mechanistic connection between ISO-induced myocardial fibrosis and the miR-450a-2-3p/ERK(1/2) signaling pathway, highlighting its role in the development of cardiac fibrosis. Modulating miR-450a-2-3p expression and inhibiting ERK(1/2) activation are promising approaches for therapeutic intervention in patients with AF.

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.

Background and aims: 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.

Methods and results: Cross-sectional analyses of 1,867 Black individuals of the PURE-SA study allowed the identification of dietary intake and cardiovascular measure interactions on three sub-categories: (1) normal blood pressure (BP), hypertension or Hcy-related hypertension (H-type), (2) low, normal or high Hcy concentrations, and (3) Hcy-related genetic combinations. Favorable body composition, but adverse dietary intake and cardiovascular determinants, were observed in higher Hcy categories. H-types, compared to regular hypertensives, had higher alcohol and lower macronutrient and micronutrient consumption. Inverse associations with carotid-radial pulse wave velocity were evident between monounsaturated fatty acid (FA) consumption and H-type hypertension as well as polyunsaturated FA and CBS883/ins68 TT carriers. Energy intake was positively associated with vascular cell adhesion molecule-1 (VCAM-1) in variant CBST883C/ins68 and CBS9276 GG carriers. VCAM-1 was also positively associated with plant protein intake in CBS9276 GG and MTR2756 AA carriers and negatively with total protein intake and CBS9276 GG carriers. Alcohol intake was positively associated with intercellular adhesion molecule-1 in MTR2756 minor allele carriers.

Conclusion: Because Hcy gene-diet interactions are evident, personalized nutrition, by adjusting diets based on genetic profiles (e.g., CBS and MTR variations) and dietary interactions (e.g., FAs and proteins), can enhance cardiovascular outcomes by managing Hcy and related hypertension in genetically susceptible individuals.

Objective: 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.

Methods: The main active ingredients and targets of garlic were identified through screening the TCMSP, TCM-ID, and ETCM databases. ALD disease targets were sourced from DisGeNET, GeneCards, and DiGSeE databases, and intervention targets for garlic were determined through intersections. Protein interaction networks were constructed using the STRING platform, and GO and KEGG pathway enrichment analyses were performed with R software. The garlic component-disease-target network was established using Cytoscape software. Validation of active ingredients against core targets was conducted through molecular docking simulations using AutoDock Vina software. Expression validation of core targets was carried out using human sequencing data of ALD obtained from the GEO database.

Results: Integration of garlic drug targets with ALD disease targets identified 83 target genes. Validation through an alcohol-induced ALD mouse model supported certain network pharmacology findings, suggesting that garlic may impede disease progression by mitigating the inflammatory response and promoting ethanol metabolism.

Conclusion: This study provides insights into the potential therapeutic mechanisms of garlic in inhibiting ALD development. The identified active ingredients offer promising avenues for further investigation and development of treatments for ALD, emphasizing the importance of botanical remedies in liver disease management.

Background: 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.

Methods: PubMed, Cochrane, and Scopus databases were used to identify research articles. They were subsequently reviewed by two independent investigators.

Results: Initially, 353 papers were identified. After removing duplicates and articles not meeting inclusion criteria, 98 full text papers were screened. Finally, this review included 40 studies investigating FADS and/or ELOVL polymorphisms. A total of 47 different SNPs in FADS genes were reported. FADS1 rs174537, rs174547, rs174556 and rs174561 were the most studied SNPs, with minor allele carriers having lower levels of EPA and DHA. SNPs in the FADS genes were in high linkage disequilibrium. SNPs in FADS were correlated with levels of EPA and DHA. No conclusion could be drawn with the ELOVL polymorphisms since the number of studies was too low.

Conclusion: Specific SNPs in FADS gene, such as rs174537, have strong associations with circulating levels of EPA and DHA. Continued investigation regarding the impact of genetic variants related to EPA and DHA synthesis is warranted.

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.