Genes and Nutrition最新文献

{"title":"Changes in triglyceride-rich lipoprotein particle profiles in response to one-week on a low fat or Mediterranean diet by TCF7L2 rs7903146 genotype: a randomized crossover dietary intervention trial.","authors":"Chao-Qiang Lai, Julie E Gervis, Laurence D Parnell, Alice H Lichtenstein, Jose M Ordovas","doi":"10.1186/s12263-025-00763-y","DOIUrl":"10.1186/s12263-025-00763-y","url":null,"abstract":"<p><strong>Background: </strong>The TCF7L2 gene is a significant genetic factor contributing to the risk of metabolic and cardiovascular diseases (CVD). We previously found that subjects with the TT genotype of TCF7L2 rs7903146 variant, who consume a low-fat diet (LF) had a higher incidence of stroke than subjects with the CC genotype. Yet this association was abolished in subjects with the TT genotype who consumed a Mediterranean-type diet (MetD). However, the mechanism by which MetD diet modulates the association between TCF7L2 and CVD risk is unclear. This study aims to validate these findings under real-world conditions and clinical practice to elucidate the biological mechanisms involved in this correlation.</p><p><strong>Methods: </strong>Thirty-five participants with BMI ranging from 27 to 34 kg/m² were recruited based on rs7903146 genotype. Of those consented to participate, 21 had the CC and 14 had the TT genotype. Participants were randomly assigned to two dietary intervention groups, ensuring an equal distribution of CC and TT carriers. Each participant followed one of two diets (LF or MetD) for one week, followed by a 10-day washout period before switching to the other diet for one week. Blood samples were collected before and after each diet for metabolomic analysis using nuclear magnetic resonance (NMR) spectroscopy. The differential effect of the diets on triglyceride-rich lipoproteins was determined based on TCF7L2 genotype.</p><p><strong>Results: </strong>The MetD significantly reduced triglyceride-rich lipoprotein concentrations compared to the LF diet. After consuming the LF diet, TT carriers exhibited more small VLDL particles, potentially contributing to CVD risk compared to CC carriers. However, this difference in risk was not observed with the MetD. Furthermore, the order in which the two diets were crossed affected the triglyceride-rich lipoprotein profile, with LF-MetD regimen showing a stronger effect on triglyceride-rich lipoproteins (TRL) levels than the MetD-LF regimen.</p><p><strong>Conclusions: </strong>Our findings suggest that rs7903146 TT carriers benefit more from a MetD than a LF diet in terms of their triglyceride-rich lipoprotein profile, which may reduce their risk of CVD. These results support the notion that genotype is a factor in determining the extent to which the MetD affects cardiovascular health.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"4"},"PeriodicalIF":3.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decomposed interaction testing improves detection of genetic modifiers of the relationship of dietary omega-3 fatty acid intake and its plasma biomarkers with hsCRP in the UK Biobank.","authors":"Kenneth E Westerman, Chirag J Patel, James B Meigs, Daniel I Chasman, Alisa K Manning","doi":"10.1186/s12263-025-00765-w","DOIUrl":"10.1186/s12263-025-00765-w","url":null,"abstract":"<p><p>Discovery and translation of gene-environment interactions (GxEs) influencing clinical outcomes is limited by low statistical power and poor mechanistic understanding. Molecular omics data may help address these limitations, but their incorporation into GxE testing requires principled analytic approaches. We focused on genetic modification of the established mechanistic link between dietary long-chain omega-3 fatty acid (dN3FA) intake, plasma N3FA (pN3FA), and chronic inflammation as measured by high sensitivity CRP (hsCRP). We considered an approach that decomposes the overall genetic effect modification into components upstream and downstream of a molecular mediator to increase the potential to discover gene-N3FA interactions. Simulations demonstrated improved power of the upstream and downstream tests compared to the standard approach when the molecular mediator for many biologically plausible scenarios. The approach was applied in the UK Biobank (N = 188,700) with regression models that used measures of dN3FA (based on fish and fish oil intake), pN3FA (% of total fatty acids measured by nuclear magnetic resonance), and hsCRP. Mediation analysis showed that pN3FA fully mediated the dN3FA-hsCRP main effect relationship. Next, we separately tested modification of the dN3FA-hsCRP (\"standard\"), dN3FA-pN3FA (\"upstream\"), and pN3FA-hsCRP (\"downstream\") associations. The known FADS1-3 locus variant rs174535 reached p = 1.6 × 10^-12 in the upstream discovery analysis, with no signal in the downstream analysis (p = 0.94). It would not have been prioritized based on a naïve analysis with dN3FA exposure and hsCRP outcome (p = 0.097), indicating the value of the decomposition approach. Gene-level enrichment testing of the genome-wide results further prioritized two genes from the downstream analysis, CBLL1 and MICA, with links to immune cell counts and function. In summary, a molecular mediator-focused interaction testing approach enhanced statistical power to identify GxEs while homing in on relevant sub-components of the dN3FA-hsCRP pathway.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"3"},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary polyunsaturated fatty acids affect PPARγ promoter methylation status and regulate the PPARγ/COX2 pathway in some colorectal cancer cell lines.","authors":"Esmaeel Babaeenezhad, Peyman Khosravi, Mostafa Moradi Sarabi","doi":"10.1186/s12263-025-00764-x","DOIUrl":"10.1186/s12263-025-00764-x","url":null,"abstract":"<p><strong>Background: </strong>Promoter methylation silencing of peroxisome proliferator-activated receptor gamma (PPARγ) and dysregulation of the PPARγ/COX2 axis contribute to colorectal cancer (CRC) pathogenesis. This study investigated for the first time the effects of dietary polyunsaturated fatty acids (PUFAs) on promoter methylation of PPARγ and the PPARγ/COX2 axis in five CRC cell lines.</p><p><strong>Methods: </strong>Five CRC cell lines (SW742, HCT116, Caco2, LS180, and HT29/219) were treated with 100 µM of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) or linoleic acid (LA). The methylation patterns of the four regions within the PPARγ promoter were determined using methylation-specific PCR (MSP). Additionally, the mRNA expression levels of PPARγ and COX2 were examined using RT-qPCR.</p><p><strong>Results: </strong>Our results showed that M3 segment within the PPARγ promoter was hemimethylated in SW742 cells, whereas other cell lines remained unmethylated in this region. The M4 region was hemimethylated in all the CRC cell lines. Of all PUFAs, DHA demethylated the M3 region of the PPARγ promoter in SW742 cells and the M4 region in Caco2 cells. Functionally, these changes were accompanied by significant upregulation of PPARγ in SW742 (9.22-fold; p = 0.01) and Caco2 cells (8.87-fold; p = 0.04). Additionally, COX2 expression was significantly downregulated in all CRC cell lines after exposure to PUFAs (p < 0.05).</p><p><strong>Conclusions: </strong>This study demonstrated that PUFAs, particularly DHA, altered PPARγ promoter methylation and expression, as well as modulated the PPARγ/COX2 axis in CRC cells in a cell type-dependent manner. DHA was more effective than the other PUFAs in regulating PPARγ promoter methylation. Our results highlight the potential clinical use of PUFAs in CRC treatment.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"2"},"PeriodicalIF":3.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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.","authors":"Mohammad Azam Mansoor, Tonje Holte Stea, Audun Slettan, Erandie Perera, Ridmi Maddumage, Darshana Kottahachchi, Dhikra Saleem Ali, Rona Cabo, Rune Blomhoff","doi":"10.1186/s12263-024-00761-6","DOIUrl":"10.1186/s12263-024-00761-6","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>In a randomized, double blind, crossover study, healthy subjects received 0.8 mg folic acid per day or a placebo for two weeks. Twenty-four male, and sixty-seven female subjects participated in this study. Participants were aged 36.4 ± 14.8 years (mean ± SD). We studied SNPs in six genes by PCR methods. The concentrations of s-folate, p-tHcy and p-tGSH were measured in fasting samples with Cobas and an HPLC-fluorescence method. Student T-tests and ANOVA were used for the statistical calculations.</p><p><strong>Main findings: </strong>The subjects with SNP (rs4880) in superoxide dismutase (SOD2) gene (CC) allele had higher concentrations of s-folate and lower concentrations of p-tHcy than subjects with (CT + TT) alleles, (p = 0.014 and p = 0.012). Contrary to SOD2 (CC) allele, the subjects with SNP (rs1001179) catalase (CAT) CC allele had lower concentrations of s-folate (p = 0.029), higher concentrations of p-tGSH (0.017) and higher concentrations of p-tHcy before and after folic acid supplementations (p = 0.015, p = 0.017) than the subjects with (CT + TT) allele. Glutathione transferase (theta)1 (GST-T1) genotype was associated with higher concentrations of s-folate than GST-T0 before (p = 0.025) and after folic acid supplementation (p = 0.047). SNP (rs1050450) in glutathione peroxidase (GPX1) had also impact on the concentrations of p-tGSH (p = 0.011) in healthy subjects.</p><p><strong>Conclusion: </strong>SNPs in SOD2 (rs4880), CAT (rs1001179), and GST1 impact the concentrations of s-folate, and p-tHcy in healthy subjects before and after folic acid supplementation. Our findings suggest that SNPs in antioxidant-genes have a role in health and disease by impacting the concentrations of s-folate, p-tHcy and p-tGSH.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"1"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A double knockout for zinc transporter 8 and somatostatin in mice reveals their distinct roles in regulation of insulin secretion and obesity.","authors":"Zhongyue Yang, Catherine P Kirschke, Yimeng Cai, Liping Huang","doi":"10.1186/s12263-024-00759-0","DOIUrl":"10.1186/s12263-024-00759-0","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Co-expression of ZnT8 with hormones secreted from gastrointestinal endocrine cells of mice was determined using immunofluorescence. Male Znt8 knockout (Znt8KO), Sst knockout (SstKO), double knockout for Sst and Znt8 (DKO), and the wild-type (WT) mice were fed a regular chow diet (CD) or a high-fat diet (HFD) at 3 weeks old for 15 weeks. Weights and fasting or fed glucose levels were determined. Glucose and insulin tolerance tests were performed; metabolic-relevant hormone levels including insulin, glucagon, glucagon-like peptide 1, Pyy, and leptin were determined.</p><p><strong>Results: </strong>ZnT8 is co-expressed with Sst in a subpopulation of endocrine D cells in the gastrointestinal tract. The absence of ZnT8 expression resulted in an increased density of the dense cores in the secretory granules of the D cell. DKO mice had reduced weight compared to WT when maintained on the CD. Compared to Znt8KO and SstKO, DKO mice did not show significant differences in fed or fasting blood glucose level regardless of dietary conditions. However, the CD-fed DKO mice had impaired insulin secretion without alterations in islet morphology or numbers. Moreover, DKO mice displayed diet-induced insulin resistance and disrupted secretion of metabolic-related hormones.</p><p><strong>Conclusions: </strong>Somatostatin as well as a normal insulin sensitivity are required for normalizing glucose metabolism in Znt8KO mice. ZnT8 may play a role in regulating fat mass and leptin secretion. These findings shed light on the multifaceted nature of Znt8 and Sst interactions, opening new avenues to understand their roles in controlling glucose metabolism and fat mass.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"19 1","pages":"24"},"PeriodicalIF":3.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genistein inhibited endocytosis and fibrogenesis in keloid via CTGF signaling pathways.","authors":"Chun-Te Lu, Jiunn-Liang Ko, Chu-Chyn Ou, Chih-Ting Hsu, Yu-Ping Hsiao, Sheau-Chung Tang","doi":"10.1186/s12263-024-00758-1","DOIUrl":"10.1186/s12263-024-00758-1","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>To investigate the effects of genistein on keloid, a wound-healing assay was performed to detect cell migration. Flow cytometry was used to measure apoptosis. Western blotting and immunofluorescence staining were performed to detect the expression of target proteins. KF tissues were isolated, cultured, and divided into the control, silenced connective tissue growth factor (CTGF) proteins, and shNC (negative control) groups.</p><p><strong>Results: </strong>Genistein suppressed cell proliferation and migration, triggering the cell cycle at the G2/M phase and increasing the expression of p53 dose-dependent in keloids. Genistein inhibited the expression of COL1A1, FN, and CTGF mRNA and protein. Knockdown CTGF reduced the migrated ability in KFs. Genistein also abated TGF-β1-induced keloid fibrosis through the endocytosis model. Separated and cultured the keloid patient's tissues decreased the cell migration ability by genistein treatment and was time-dose dependent.</p><p><strong>Conclusions: </strong>This study indicated that genistein-induced p53 undergoes cell cycle arrest via the CTGF pathway-inhibited keloid cultured cells, and genistein suppressed the primary keloid cell migration, suggesting that our research provides a new strategy for developing drugs for treating keloids.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"19 1","pages":"23"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin supplementation in metabolic syndrome: nutrigenetic interactions with the Zbtb16 gene variant in rodent models.","authors":"Adéla Kábelová, Hana Malínská, Irena Marková, Martina Hüttl, František Liška, Blanka Chylíková, Ondřej Šeda","doi":"10.1186/s12263-024-00757-2","DOIUrl":"10.1186/s12263-024-00757-2","url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Results: </strong>Quercetin supplementation led to a significant reduction in the relative weight of retroperitoneal adipose tissue in both investigated strains. A decrease in visceral (epididymal) fat mass, accompanied by an increase in brown fat mass after quercetin treatment, was observed exclusively in the SHR strain. While the levels of serum triglycerides decreased within both strains, the free fatty acids levels decreased in SHR-Zbtb16-Q rats only. The total serum cholesterol levels were not affected by quercetin in either of the two tested strains. While there were no significant changes in brown adipose tissue transcriptome, quercetin supplementation led to a pronounced gene expression shift in white retroperitoneal adipose tissue, particularly in SHR-Zbtb16-Q.</p><p><strong>Conclusion: </strong>Quercetin administration ameliorates certain MetS-related features; however, the efficacy of the treatment exhibits subtle variations depending on the specific variant of the Zbtb16 gene.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"19 1","pages":"22"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothetical proteins of chicken-isolated Limosilactobacillus reuteri subjected to in silico analyses induce IL-2 and IL-10.","authors":"Isaac Oluseun Adejumo","doi":"10.1186/s12263-024-00755-4","DOIUrl":"https://doi.org/10.1186/s12263-024-00755-4","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"19 1","pages":"21"},"PeriodicalIF":3.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visnagin alleviates rheumatoid arthritis via its potential inhibitory impact on malate dehydrogenase enzyme: in silico, in vitro, and in vivo studies.","authors":"Abeer A Khamis, Amira H Sharshar, Tarek M Mohamed, Elsayed A Abdelrasoul, Maha M Salem","doi":"10.1186/s12263-024-00756-3","DOIUrl":"10.1186/s12263-024-00756-3","url":null,"abstract":"<p><p>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 CD4⁺CD25⁺FOXP3 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.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"19 1","pages":"20"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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.","authors":"Roger Mariné-Casadó, Cristina Domenech-Coca, Salvador Fernández, Andrea Costa, Sergi Segarra, Maria José López-Andreo, Francesc Puiggròs, José Joaquín Cerón, Daniel Martínez-Puig, Carme Soler, Vicente Sifre, Claudio Iván Serra, Antoni Caimari","doi":"10.1186/s12263-024-00749-2","DOIUrl":"10.1186/s12263-024-00749-2","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"19 1","pages":"19"},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}