Abstract: Background Genetic instability leads to genome mutations, changes in nucleotide sequences, rearrangements, and gains or losses of part of the chromosomes. This instability can initiate and develop cancer. This study evaluated genomic stability in methotrexate and anthocyanin-treated mammary adenocarcinoma model. Seventy albino mice were divided into seven groups: negative control, anthocyanin, methotrexate, Ehrlich’s solid tumor; Ehrlich’s solid tumor and methotrexate; Ehrlich’s solid tumor and anthocyanin; and Ehrlich’s solid tumor, methotrexate, and anthocyanin groups. Results Tumor weight and size were evaluated. Serum arylesterase activity was low in all the induced tumors and those treated with anthocyanin, methotrexate, or both. Poly[adenosine diphosphate (ADP)-ribose] polymerase activity was high, and glutathione S-transferase activity was low in the tumors treated with anthocyanin, methotrexate, or both, compared with that of the untreated tumor. There was an increase in DNA damage in the mice with solid tumors and those injected with methotrexate or methotrexate and anthocyanin, compared with that in the untreated mice. Conclusions There was a decrease in genetic instability and DNA damage in the tumor-bearing mice treated with anthocyanin, with a concomitant increase in nuclear poly[adenosine diphosphate (ADP)-ribose] polymerase activity, compared with those of the untreated group. Anthocyanin exerted positive effects in the treatment of mammary adenocarcinoma. PubDate: 2022-05-05
Abstract: Background Metabolic syndrome (MetS) is characterized by the coexistence of disorders such as diabetes, hypertension, hyperlipidemia, and obesity and is affected by genetic factors. Previous genome-wide association studies (GWAS) suggested that APOA5 gene variants were significantly associated with MetS and its components. Dietary factors such as red and processed meat consumption can cause chronic diseases, including hypertension, diabetes, and vascular depression. The aim of this study was to investigate the modulation of the incidence of MetS by the interaction between APOA5 rs662799 polymorphism and red and processed meat consumption. Methods In this prospective cohort study, 3266 participants were collected from the Korea Association REsource (KARE) cohort of the Korean Genome and Epidemiology Study (KoGES) from 2001 to 2016. APOA5 rs662799 polymorphism was extracted by GWAS using the Korean Chip. Red and processed meat consumption data were assessed using a semi-quantitative food frequency questionnaire. Results The incidence of MetS in carriers of the minor G allele of rs662799 (AG + GG) and the third tertile of red and processed meat consumption (serving/day) was higher than those with the major allele of rs662799 (AA) and the first tertile of red and processed meat consumption (HR 1.70, 95% CI 1.30–2.22, p interaction = 0.002). Conclusions An association between the presence of the minor alleles of rs662799 and high red and processed meat consumption and the incidence of MetS was observed in Korean adults. PubDate: 2022-04-25
Abstract: Background Chronic exposure to ultraviolet (UV) rays causes severe skin damage by inducing oxidative stress and inflammation. Identifying a safe and natural substance for skin protection is a crucial research goal. Objective The aim of this study was to clarify the effects of genistein on skin inflammation and photoaging by using 3 models (humans: skin parameters; animals: wrinkle formation; and cells: anti-inflammatory effects). Methods Food frequency questionnaire data and serum and skin parameter data from 120 volunteers (a group with a genistein-rich diet [RG group] and a control group). Human keratinocytes were pretreated with genistein before ultraviolet B (UVB) irradiation. Genistein was topically applied to the dorsal skin of rats. Results The blood samples of the RG group had lower serum uric acid levels and blood urea nitrogen levels. The dynamic elasticity level in the RG group was higher than that in the controls. Genistein pretreatment suppressed the expression of proinflammatory cytokines (CXCL1, IL-1, MIF, and PLANH1) and the proteins released by UVB-treated keratinocytes. Topical application of genistein to the dorsal skin of rats reduced the severity of UVB-induced wrinkling. Both intake and topical application of genistein combated UVB-induced inflammation and aging. Conclusions Genistein could be used as a safe and natural compound for use in novel anti-inflammatory agents for topical application. Graphical abstract The experimental design procedure, including the skin parameter and blood serum measurements of 137 participants. Genistein-rich compounds provide protection against UVB-induced inflammation, as determined using in vitro and in vivo animal model experiments. PubDate: 2022-02-24 DOI: 10.1186/s12263-022-00706-x
Abstract: Background Cancer therapy targeting programmed death receptor-1 (PD-1 or CD279) or programmed death-ligand 1 (PD-L1 or CD274) gives hope to Tongue Squamous Cell Carcinoma (TSCC) treatment. However, the tumor-intrinsic mechanism of PD-L1 is not fully elucidated in TSCC. On the other hand, lycopene showed antitumor effects and chemotherapy/radiotherapy-enhancing effects by mechanisms closely correlated with PD-L1. Purpose We aimed to explore whether the mechanisms of PD-L1 signaling and regulation are reversible by lycopene treatment in TSCC. Methods We collected TSCC tissues and normal tissues for assessment of PD-L1 expression by immunohistochemical technique and western blotting. We measured the expression of PD-L1 in three TSCC cell lines and constructed cell lines with knockdown and overexpression of PD-L1. Then, we measured the proliferation by CCK-8 assay, migration and invasion by Transwell assay, and apoptosis by TUNEL assay in five groups with treatment of blank control, negative control with vector transfection, PD-L1 knockdown/overexpression, 4 μM lycopene, and combined 4 μM lycopene and PD-L1 knockdown/overexpression. We also systematically analyzed the PD-L1 constitutive signaling pathways and their effect EMT pathways. In order to bring out the mechanism underlying PI3K/AKT depressing Raf/MEK/ERK, we used PI3K inhibitor LY294002. Results We detected significant PD-L1 upregulation in biopsies by western blot and immunohistochemistry. Our study demonstrated that PD-L1 upregulation elevated IGF-1R to activate the PI3K/AKT pathway but inactivated the Raf/MEK/ERK pathway in TSCC cell line CAL27, while PD-L1 knockdown decreased IGF-1R to inactivate both PI3K/AKT and Raf/MEK/ERK pathways in cell line SCC9, to increase/decrease p-FOXOs and decrease/increase p-GSK-3β, producing further changes in EMT, proliferation, migration, invasion, and apoptosis. Lycopene reversed PD-L1 signaling and expression by mechanisms opposite to PD-L1 upregulation but similar to PD-L1 knockdown. Conclusion Taken together, this study firstly confirmed PD-L1 expression and signaling are reversible by lycopene via PI3K/AKT and Raf/MEK/ERK pathways in TSCC. Our study provides a sounder basis for comprehending PD-L1 signaling and expression and prevention and treatment of TSCC. PubDate: 2022-02-14 DOI: 10.1186/s12263-022-00705-y
Abstract: Background Previous observational studies have demonstrated inconsistent and inconclusive results of changes in the intestinal microbiota in patients with obesity and metabolic disorders. We performed a systematic review to explore evidence for this association across different geography and populations. Methods We performed a systematic search of MEDLINE (OvidSP) and Embase (OvidSP) of articles published from Sept 1, 2010, to July 10, 2021, for case–control studies comparing intestinal microbiome of individuals with obesity and metabolic disorders with the microbiome of non-obese, metabolically healthy individuals (controls). The primary outcome was bacterial taxonomic changes in patients with obesity and metabolic disorders as compared to controls. Taxa were defined as “lean-associated” if they were depleted in patients with obesity and metabolic disorders or negatively associated with abnormal metabolic parameters. Taxa were defined as “obesity-associated” if they were enriched in patients with obesity and metabolic disorders or positively associated with abnormal metabolic parameters. Results Among 2390 reports screened, we identified 110 full-text articles and 60 studies were included. Proteobacteria was the most consistently reported obesity-associated phylum. Thirteen, nine, and ten studies, respectively, reported Faecalibacterium, Akkermansia, and Alistipes as lean-associated genera. Prevotella and Ruminococcus were obesity-associated genera in studies from the West but lean-associated in the East. Roseburia and Bifidobacterium were lean-associated genera only in the East, whereas Lactobacillus was an obesity-associated genus in the West. Conclusions We identified specific bacteria associated with obesity and metabolic disorders in western and eastern populations. Mechanistic studies are required to determine whether these microbes are a cause or product of obesity and metabolic disorders. PubDate: 2022-01-29 DOI: 10.1186/s12263-021-00703-6
Abstract: Background Vitamin D (Vit-D) promotes vascular repair and its deficiency is closely linked to the development of type 2 diabetes mellitus (T2DM) and hypertension. Whether genetially predicted vitamin D status (serological 25-hydroxyvitamin D [25(OH)D]) confers secondary protection against cardiovascular diseases (CVD) among high-risk hypertensive-diabetic subjects was unknown. Methods This is a prospective, individual-data, two-sample Mendelian randomization study. We interrogated 12 prior GWAS-detected SNPs of comprehensive Vit-D mechanistic pathways using high-throughput exome chip analyses in a derivation subcohort (n = 1460) and constructed a genetic risk score (GRS) (rs2060793, rs4588, rs7041; F-statistic = 32, P < 0.001) for causal inference of comprehensive CVD hard clinical endpoints in an independent sample of hypertensive subjects (n = 3746) with prevailing co-morbid T2DM (79%) and serological 25(OH)D deficiency [< 20 ng/mL] 45%. Results After 55.6 ± 28.9 months, 561 (15%) combined CVD events including myocardial infarction, unstable angina, ischemic stroke, congestive heart failure, peripheral vascular disease, and cardiovascular death had occurred. Kaplan-Meier analysis showed that genetically predicted reduced vitamin D status was associated with reduced event-free survival from combined CVD events (log-rank = 13.5, P = 0.001). Multivariate-adjusted per-allele increase in GRS predicted reduced combined CVD events (HR = 0.90 [0.84 to 0.96], P = 0.002). Mendelian randomization indicates that increased Vit-D exposure, leveraged through each 1 ng/mL genetically instrumented rise of serum Vit-D, protects against combined CVD events (Wald’s estimate: OR = 0.86 [95%CI 0.75 to 0.95]), and myocardial infarction (OR = 0.76 [95%CI 0.60 to 0.90]). Furthermore, genetically predicted increase in Vit-D status ameliorates risk of deviation from achieving guideline-directed hypertension control (JNC-8: systolic target < 150 mmHg) (OR = 0.89 [95%CI 0.80 to 0.96]). Conclusions Genetically predicted increase in Vit-D status [25(OH)D] may confer secondary protection against incident combined CVD events and myocardial infarction in a hypertensive-diabetic population where serological 25(OH)D deficiency is common, through facilitating blood pressure control. PubDate: 2022-01-29 DOI: 10.1186/s12263-022-00704-z
Abstract: Background Worldwide, the prevalence of obesity and insulin resistance has grown dramatically. Gene expression profiling in blood represents a powerful means to explore disease pathogenesis, but the potential impact of inter-individual differences in a cell-type profile is not always taken into account. The objective of this project was to investigate the whole blood transcriptome profile of insulin-resistant as compared to insulin-sensitive individuals independent of inter-individual differences in white blood cell profile. Results We report a 3% higher relative amount of monocytes in the insulin-resistant individuals. Furthermore, independent of their white blood cell profile, insulin-resistant participants had (i) higher expression of interferon-stimulated genes and (ii) lower expression of genes involved in cellular differentiation and remodeling of the actin cytoskeleton. Conclusions We present an approach to investigate the whole blood transcriptome of insulin-resistant individuals, independent of their DNA methylation-derived white blood cell profile. An interferon-related signature characterizes the whole blood transcriptome profile of the insulin-resistant individuals, independent of their white blood cell profile. The observed signature indicates increased systemic inflammation possibly due to an innate immune response and whole-body insulin resistance, which can be a cause or a consequence of insulin resistance. Altered gene expression in specific organs may be reflected in whole blood; hence, our results may reflect obesity and/or insulin resistance-related organ dysfunction in the insulin-resistant individuals. PubDate: 2021-12-09 DOI: 10.1186/s12263-021-00702-7
Abstract: Background Copy number (CN) variation (CNV) of the salivary amylase gene (AMY1) influences the ability to digest starch and may influence glucose homeostasis, obesity and gut microbiota composition. Hence, the aim was to examine the association of AMY1 CNV with fasting glucose, BMI, and gut microbiota composition considering habitual starch intake and to investigate the effect of AMY1 CNV on the postprandial response after two different starch doses. Methods The Malmö Offspring Study (n = 1764, 18–71 years) was used to assess interaction effects between AMY1 CNV (genotyped by digital droplet polymerase chain reaction) and starch intake (assessed by 4-day food records) on fasting glucose, BMI, and 64 gut bacteria (16S rRNA sequencing). Participants with low (≤ 4 copies, n = 9) and high (≥ 10 copies, n = 10) AMY1 CN were recruited for a crossover meal study to compare postprandial glycemic and insulinemic responses to 40 g and 80 g starch from white wheat bread. Results In the observational study, no overall associations were found between AMY1 CNV and fasting glucose, BMI, or gut microbiota composition. However, interaction effects between AMY1 CNV and habitual starch intake on fasting glucose (P = 0.03) and BMI (P = 0.05) were observed, suggesting inverse associations between AMY1 CNV and fasting glucose and BMI at high starch intake levels and positive association at low starch intake levels. No associations with the gut microbiota were observed. In the meal study, increased postprandial glucose (P = 0.02) and insulin (P = 0.05) were observed in those with high AMY1 CN after consuming 40 g starch. This difference was smaller and nonsignificant after consuming 80 g starch. Conclusions Starch intake modified the observed association between AMY1 CNV and fasting glucose and BMI. Furthermore, depending on the starch dose, a higher postprandial glucose and insulin response was observed in individuals with high AMY1 CN than in those with low AMY1 CN. Trial registration ClinicalTrials.gov, NCT03974126. Registered 4 June 2019—retrospectively registered. PubDate: 2021-11-17 DOI: 10.1186/s12263-021-00701-8
Abstract: Background and objectives Circulating branched chain amino acids (BCAAs) increase the risk of type 2 diabetes (T2D). The genetic variants in the BCAA metabolic pathway influence the individual metabolic ability of BCAAs and may affect circulating BCAA levels together with dietary intakes. So, we investigated whether genetic predisposition to impaired BCAA metabolism interacts with dietary BCAA intakes on the risk of type 2 diabetes and related parameters. Methods We estimated dietary BCAA intakes among 434 incident T2D cases and 434 age-matched controls from The Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases. The genetic risk score (GRS) was calculated on the basis of 5 variants having been identified in the BCAA metabolic pathway. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and HbA1c. Results Dietary BCAAs significantly interact with metabolism related GRS on T2D risk and HbA1c (p for interaction = 0.038 and 0.015, respectively). A high intake of dietary BCAAs was positively associated with diabetes incidence only among high GRS (OR 2.40, 95% CI 1.39, 4.12, P for trend = 0.002). Dietary BCAAs were associated with 0.14% elevated HbA1c (p = 0.003) and this effect increased to 0.21% in high GRS (p = 0.003). Furthermore, GRS were associated with 9.19 μmol/L higher plasma BCAA levels (p = 0.006, P for interaction = 0.015) only among the highest BCAA intake individuals. Conclusions Our study suggests that genetic predisposition to BCAA metabolism disorder modifies the effect of dietary BCAA intakes on T2D risk as well as HbA1c and that higher BCAA intakes exert an unfavorable effect on type 2 diabetes risk and HbA1c only among those with high genetic susceptibility. PubDate: 2021-11-02 DOI: 10.1186/s12263-021-00695-3
Abstract: Objective Until now, observational studies have explored the impact of vitamin C intake on Alzheimer’s disease (AD) risk, however, reported ambiguous findings. To develop effective therapies or prevention, the causal link between vitamin C levels and AD should be established. Methods Here, we selected 11 plasma vitamin C genetic variants from a large-scale plasma vitamin C GWAS dataset (N = 52,018) as the potential instrumental variables. We extracted their corresponding summary statistics from large-scale IGAP clinically diagnosed AD GWAS dataset (N = 63,926) and UK Biobank AD proxy phenotype GWAS dataset (N = 314,278), as well as two UK Biobank subgroups including the maternal AD group (27,696 cases of maternal AD and 260,980 controls) and paternal AD group (14,338 cases of paternal AD and 245,941 controls). We then performed a Mendelian randomization (MR) study to evaluate the causal association between plasma vitamin C levels and the risk of AD and AD proxy phenotype. Meanwhile, we further verified these findings using a large-scale cognitive performance GWAS dataset (N = 257,841). Results In IGAP, we found no significant causal association between plasma vitamin C levels and the risk of AD. In UK Biobank, we found that per 1 SD increase in plasma vitamin C levels (about 20.2 μmol/l) was significantly associated with the reduced risk of AD proxy phenotype (OR = 0.93, 95% CI 0.88–0.98, P = 7.00E−03). A subgroup MR analysis in UK Biobank indicated that per 1 SD increase in plasma vitamin C levels could significantly reduce the risk of AD proxy phenotype in the maternal AD group (OR = 0.89, 95% CI 0.84–0.94, P = 7.29E−05), but not in the paternal AD group (OR = 1.02, 95% CI 0.92–1.12, P = 7.59E−01). The leave-one-out permutation further showed that the SLC23A1 rs33972313 variant largely changed the precision of the overall MR estimates in all these four GWAS datasets. Meanwhile, we did not observe any significant causal effect of plasma vitamin C levels on the cognitive performance. Conclusion We demonstrated that there may be no causal association between plasma vitamin C levels and the risk of AD in people of European descent. The insistent findings in clinically diagnosed AD and AD proxy phenotype may be caused by the phenotypic heterogeneity. PubDate: 2021-10-29 DOI: 10.1186/s12263-021-00700-9
Abstract: Background Nutrient composition of vegetarian diets is greatly different from that of omnivore diets, which may fundamentally influence the gut microbiota and fecal metabolites. The interactions between diet pattern and gut environment need further illustration. This study aims to compare the difference in the gut microbiota and fecal metabolites between vegetarian and omnivore female adults and explore associations between dietary choices/duration and gut environment changes. Methods In this study, investigations on the fecal metabolome together with the gut microbiome were performed to describe potential interactions with quantitative functional annotation. In order to eliminate the differences brought by factors of gender and living environment, 80 female adults aged 20 to 48 were recruited in the universities in Beijing, China. Quantitative Insights Into Microbial Ecology (QIIME) analysis and Ingenuity Pathway Analysis (IPA) were applied to screen differential data between groups from gut microbiota and fecal metabolites. Furthermore, weighted gene correlation network analysis (WGCNA) was employed as the bioinformatics analysis tool for describing the correlations between gut microbiota and fecal metabolites. Moreover, participants were further subdivided by the vegetarian diet duration for analysis. Results GPCR-mediated integration of enteroendocrine signaling was predicted to be one of the regulatory mechanisms of the vegetarian diet. Intriguingly, changes in the gut environment which occurred along with the vegetarian diet showed attenuated trend as the duration increased. A similar trend of returning to “baseline” after a 10-year vegetarian diet was detected in both gut microbiota and fecal metabolome. Conclusions The vegetarian diet is beneficial more than harmful to women. Gut microbiota play roles in the ability of the human body to adapt to external changes. PubDate: 2021-10-02 DOI: 10.1186/s12263-021-00697-1
Abstract: Background Quantitative real-time polymerase chain reaction (qPCR) is a reliable and efficient method for quantitation of gene expression. Due to the increased use of qPCR in examining nutrient-gene interactions, it is important to examine, develop, and utilize standardized approaches for data analyses and interpretation. A common method used to normalize expression data involves the use of reference genes (RG) to determine relative mRNA abundance. When calculating the relative abundance, the selection of RG can influence experimental results and has the potential to skew data interpretation. Although common RG may be used for normalization, often little consideration is given to the suitability of RG selection for an experimental condition or between various tissue or cell types. In the current study, we examined the stability of gene expression using BestKeeper, comparative delta quantitation cycle, NormFinder, and RefFinder in a variety of tissues obtained from iron-deficient and pair-fed iron-replete rats to determine the optimal selection among ten candidate RG. Results Our results suggest that several commonly used RG (e.g., Actb and Gapdh) exhibit less stability compared to other candidate RG (e.g., Rpl19 and Rps29) in both iron-deficient and iron-replete pair-fed conditions. For all evaluated RG, Tfrc expression significantly increased in iron-deficient animal livers compared to the iron-replete pair-fed controls; however, the relative induction varied nearly 4-fold between the most suitable (Rpl19) and least suitable (Gapdh) RG. Conclusion These results indicate the selection and use of RG should be empirically determined and RG selection may vary across experimental conditions and biological tissues. PubDate: 2021-10-02 DOI: 10.1186/s12263-021-00698-0
Abstract: Background Vitamin D status has been associated with the presence and severity of several premenstrual symptoms (PMSx) in some, but not all studies. Inconsistencies among findings may be explained by unaccounted genetic variation in the vitamin D receptor (VDR). Objective To determine whether associations between vitamin D status and individual PMSx are influenced by VDR genotype. Methods Seven hundred sixteen women aged 20-29 years old from the Toronto Nutrigenomics and Health study provided plasma samples and completed a questionnaire on the presence and severity of 15 common PMSx. Plasma 25-hydroxyvitamin D (25(OH)D) concentration was measured and participants were categorized into sufficient (≥ 50 nmol/L) and insufficient (< 50 nmol/L) vitamin D status groups. DNA was obtained from blood samples to genotype for a common VDR single nucleotide variant, rs796858. Using logistic regression, odds of experiencing PMSx were compared between vitamin D-sufficient and insufficient women, stratified by genotype. Results Among CC homozygotes, insufficient vitamin D status was associated with higher odds of experiencing premenstrual fatigue (OR, 2.53; 95% CI, 1.40, 4.56) and nausea (OR, 2.44; 95% CI, 1.00, 5.95). Among TT homozygotes, insufficient vitamin D status was associated with lower odds of experiencing fatigue (OR, 0.44; 95% CI, 0.20, 0.97) and increased appetite (OR, 0.48; 95% CI, 0.22, 1.04). Insufficient vitamin D status was associated with higher odds of increased appetite in women with the CT genotype (OR, 1.78; 95% CI, 1.03, 3.07). VDR genotype modified the association between vitamin D status and the following PMSx: increased appetite (interaction p = 0.027), fatigue (interaction p = 0.016), and nausea (interaction p = 0.039). Conclusion We found evidence that VDR genotype may modify the association between 25(OH)D and some PMSx. Insufficient 25(OH)D was associated with a higher risk of premenstrual fatigue in those with the CC genotype, but lower risk in those with the TT genotype. PubDate: 2021-09-22 DOI: 10.1186/s12263-021-00696-2
Abstract: Background Given the key role of methionine (Met) in biological processes like protein translation, methylation, and antioxidant defense, inadequate Met supply can limit performance. This study investigated the effect of different dietary Met sources on the expression profile of various Met transporters along the gastrointestinal tract (GIT) of pigs. Methods A total of 27 pigs received a diet supplemented with 0.21% DL-Met, 0.21% L-Met, or 0.31% DL-2-hydroxy-4-(methylthio)butanoic acid (DL-HMTBA). Changes in mRNA expression of B0AT1, ATB0,+, rBAT, ASCT2, IMINO, LAT4, y+LAT1, LAT2, and SNAT2 were evaluated in the oral mucosa, cardia, fundus, pylorus, duodenum, proximal jejunum, middle jejunum, ileum, cecum, proximal colon, and distal colon, complemented by protein expression analysis of B0AT1, ASCT2, LAT2, and LAT4. Results Expression of all investigated transcripts differed significantly along the GIT. B0AT1, rBAT, y+LAT1, LAT2, and LAT4 showed strongest mRNA expression in small intestinal segments. ASCT2, IMINO, and SNAT2 were similarly expressed along the small and large intestines but expression differed in the oral mucosa and stomach. ATB0,+ showed highest mRNA expression in large intestinal tissues, cardia, and pylorus. In pigs fed DL-Met, mRNA expression of ASCT2 was higher than in pigs fed DL-HMTBA in small intestinal tissues and mRNA expression of IMINO was lower than in pigs fed L-Met in large intestinal tissues. Dietary DL-HMTBA induced a stronger mRNA expression of basolateral uptake systems either in the small (LAT2) or large (y+LAT1) intestine. Protein expression of B0AT1 was higher in the middle jejunum and ileum in pigs fed DL-Met when compared with the other Met supplements. LAT4 expression was higher in pigs fed DL-HMTBA when compared with DL-Met (small intestine) and L-Met (small intestine, oral mucosa, and stomach). Conclusion A high expression of several Met transporters in small intestinal segments underlines the primary role of these segments in amino acid absorption; however, some Met transporters show high transcript and protein levels also in large intestine, oral mucosa, and stomach. A diet containing DL-Met has potential to increase apical Met transport in the small intestine, whereas a diet containing DL-HMTBA has potential to increase basolateral Met transport in the small intestine and, partly, other gastrointestinal tissues. PubDate: 2021-09-06 DOI: 10.1186/s12263-021-00694-4
Abstract: Background It is reported that circular RNAs (circRNAs) play a key role in atherosclerosis (AS). Foam cell formation, which is the main feature of AS, can be significantly inhibited by cholesterol efflux. Methods We established a model of astaxanthin (AST) promoting cholesterol efflux from macrophages through oil red O staining, real-time quantitative PCR (qRT-PCR), and western blot and used RNA sequencing to detect the expression of circRNAs in AST-treated and untreated THP-1 cells. Finally, siRNA transfection screened out circRNAs that were significantly differentially expressed. The data analysis was performed by Student’s t test and P < 0.05 was considered statistically significant. Results In the model of AST promoting cholesterol efflux from THP-1 cells, there were a total of 7276 circRNAs differentially expressed, among which the top 25 upregulated and the top 25 downregulated circRNAs were selected based on the log2 (fold change). GO analysis showed that differential expression of circRNAs in biological process (2066/3098; 66.69%), molecular function (543/3098; 17.53%), and cellular component (489/3098; 15.78%). Based on KEGG analysis, RNA transport was the most enriched pathway. Finally, we obtained 3 significantly upregulated circRNAs by siRNA transfection and qRT-PCR. Conclusions The 3 differentially expressed circRNAs may play an important role in the process of AST promoting cholesterol efflux and may be used as biomarkers to prevent AS. PubDate: 2021-08-28 DOI: 10.1186/s12263-021-00693-5
Abstract: Background and objectives Peripheral blood mononuclear cells (PBMCs) have shown promise as a tissue sensitive to subtle and possibly systemic transcriptomic changes, and as such may be useful in identifying responses to weight loss interventions. The primary aim was to comprehensively evaluate the transcriptomic changes that may occur during weight loss and to determine if there is a consistent response across intervention types in human populations of all ages. Methods Included studies were randomised control trials or cohort studies that administered an intervention primarily designed to decrease weight in any overweight or obese human population. A systematic search of the literature was conducted to obtain studies and gene expression databases were interrogated to locate corresponding transcriptomic datasets. Datasets were normalised using the ArrayAnalysis online tool and differential gene expression was determined using the limma package in R. Over-represented pathways were explored using the PathVisio software. Heatmaps and hierarchical clustering were utilised to visualise gene expression. Results Seven papers met the inclusion criteria, five of which had raw gene expression data available. Of these, three could be grouped into high responders (HR, ≥ 5% body weight loss) and low responders (LR). No genes were consistently differentially expressed between high and low responders across studies. Adolescents had the largest transcriptomic response to weight loss followed by adults who underwent bariatric surgery. Seven pathways were altered in two out of four studies following the intervention and the pathway ‘cytoplasmic ribosomal proteins’ (WikiPathways: WP477) was altered between HR and LR at baseline in the two datasets with both groups. Pathways related to ‘toll-like receptor signalling’ were altered in HR response to the weight loss intervention in two out of three datasets. Conclusions Transcriptomic changes in PBMCs do occur in response to weight change. Transparent and standardised data reporting is needed to realise the potential of transcriptomics for investigating phenotypic features. Registration number PROSPERO: CRD42019106582 PubDate: 2021-07-19 DOI: 10.1186/s12263-021-00692-6
Abstract: Background In recent years, the exciting emergence of circulating miRNAs as stable, reproducible, and consistent among individuals has opened a promising research opportunity for the detection of non-invasive biomarkers. A firm connection has been established between circulating miRNAs and glycaemic as well as metabolic homeostasis, showing that levels of specific miRNAs vary under different physio-pathological conditions. Objective In this pilot study, we investigated the expression of candidate miRNAs, hsa-miR-191-3p and hsa-miR-375, in relation to biomarkers associated with insulin sensitivity in a subgroup (n=58) of subjects participating to the European I.Family Study, a project aimed to assess the determinants of eating behaviour in children and adolescents and related health outcomes. The sample included overweight/obese children/adolescents since overweight/obesity is a known risk factor for impaired glucose homeostasis and metabolic disorders. Biological targets of candidate miRNAs were also explored in silico. Results We observed a significant association of the two miRNAs and early changes in glycaemic homeostasis, independent of covariates including country of origin, age, BMI z-score, puberty status, highest educational level of parents, total energy intake, energy from fats, energy from carbohydrates, and energy from proteins. Conclusion Identification of circulating miRNAs associated with insulin impairment may offer novel approaches of assessing early variations in insulin sensitivity and provide evidence about the molecular mechanisms connected to early changes in glycaemic homeostasis. Trial registration ISRCTN, ISRCTN62310987. Retrospectively registered, http://isrctn.com/ISRCTN62310987 PubDate: 2021-07-09 DOI: 10.1186/s12263-021-00689-1
Abstract: Background Previous observational studies have provided conflicting results on the association between serum iron status and the risk of breast cancer. Considering the relevance of this relationship to breast cancer prevention, its elucidation is warranted. Object We used a two-sample Mendelian randomisation (MR) study to explore the causal relationship between serum iron status and the risk of breast cancer. Method To select single nucleotide polymorphisms (SNPs) that could be used as instrumental variables for iron status, we used the Genetics of Iron Status consortium, which includes 11 discovery and 8 replication cohorts, encompassing 48,972 individuals of European descent. Moreover, we used the OncoArray network to select SNPs that could be considered instrumental variables for the outcome of interest (breast cancer); this dataset included 122,977 individuals of European descent with breast cancer and 105,974 peers without breast cancer. Both conservative (SNPs associated with overall iron status markers) and liberal (SNPs associated with the levels of at least one iron status marker) approaches were used as part of the MR analysis. For the former, we used an inverse-variance weighted (IVW) method, whereas for the latter, we used the IVW, MR-Egger regression, weighted median and simple mode methods. Results When the conservative approach was used, iron status showed no significant association with the risk of breast cancer or any of its subtypes. However, when the liberal approach was used, transferrin levels were found to be positively associated with the risk of ER-negative breast cancer based on the simple mode method (OR for MR, 1.225; 95% CI, 1.064, 1.410; P = 0.030). Nevertheless, the levels of the other iron status markers showed no association with the risk of breast cancer or its subtypes (P > 0.05). Conclusion In our MR study, the liberal approach suggested that changes in the concentration of transferrin could increase the risk of ER-negative breast cancer, although the levels of other iron status markers had no effect on the risk of breast cancer or its subtypes. This should be verified in future studies. PubDate: 2021-07-06 DOI: 10.1186/s12263-021-00691-7
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