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1.
Food Chem ; 366: 130618, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34330028

RESUMO

The objective of this study was to compare the effects of the micronization (MT), steam explosion (SE), and gamma irradiation (GI) treatment on the chemical composition, structure, physicochemical properties, and in vitro digestibility of dietary fiber from soybean hulls. GI (1200 kGy) treatment exerted the optimum effects on improving soluble dietary fiber content, in vitro gross energy digestibility (IVGED), and reducing sugar yield (RS) in the three modification methods, increased by 342.88%, 55.24%, and 117.02%, respectively. Compared with GI treatment, MT-GI combined treatment could further enhance the degradation effect of irradiation and improve the physicochemical properties (p<0.05) in soybean fibers. From the results of correlation analysis, RS was a significant positive correlation (p<0.05) with IVGED, and RS = -112.24 + 4.90 × IVGED (r2 = 0.82, p<0.01). In summary, MT-GI combined treatment could be considered the ideal modification method to improve the quality of soybean fiber.


Assuntos
Soja , Vapor , Ração Animal/análise , Fibras na Dieta/análise , Digestão
2.
Food Chem ; 367: 130781, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34391997

RESUMO

The aim of this study was to investigate effects of dietary grape seed proanthocyanidin extract (GSPE) supplementation on meat quality, muscle fiber characteristics and antioxidant capacity of finishing pigs. The data showed GSPE increased pH24 h, redness, crude protein content and decreased shear force, drip loss48 h, lactate content and glycolytic potential in longissimus dorsi (LD) muscle, accompanied by increased contents of total polyunsaturated fatty acid (PUFA), n-3 PUFA, and the ratio of PUFA to saturated fatty acid. GSPE promoted MyHC I mRNA and slow MyHC protein expression, and increased slow-twitch fiber percentage. The activities of total antioxidant capacity, total superoxide dismutase, catalase and glutathione peroxidase in LD muscle were increased by GSPE while malondialdehyde content was decreased. Together, this study demonstrated that dietary GSPE supplementation can effectively improve the color, water-holding capacity, tenderness and nutritional value of pork, and increase slow-twitch fiber percentage and antioxidant capacity of finishing pigs.


Assuntos
Antioxidantes , Extrato de Sementes de Uva , Ração Animal/análise , Suplementos Nutricionais , Carne/análise , Fibras Musculares Esqueléticas , Proantocianidinas , Suínos
3.
Circ Genom Precis Med ; : CIRCGEN121003460, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34732054

RESUMO

BACKGROUND: Elevated cardiac troponin levels in blood are associated with increased risk of cardiovascular diseases and mortality. Cardiac troponin levels are heritable, but their genetic architecture remains elusive. METHODS: We conducted a transethnic genome-wide association analysis on high-sensitivity cTnT (cardiac troponin T; hs-cTnT) and high-sensitivity cTnI (cardiac troponin I; hs-cTnI) levels in 24 617 and 14 336 participants free of coronary heart disease and heart failure from 6 population-based cohorts, followed by a series of bioinformatic analyses to decipher the genetic architecture of hs-cTnT and hs-cTnI. RESULTS: We identified 4 genome-wide significant loci for hs-cTnT including a novel locus rs3737882 in PPFIA4 and 3 previously reported loci at NCOA2, TRAM1, and BCL2. One known locus at VCL was replicated for hs-cTnI. One copy of C allele for rs3737882 was associated with a 6% increase in hs-cTnT levels (minor allele frequency, 0.18; P=2.80×10-9). We observed pleiotropic loci located at BAG3 and ANO5. The proportions of variances explained by single-nucleotide polymorphisms were 10.15% and 7.74% for hs-cTnT and hs-cTnI, respectively. Single-nucleotide polymorphisms were colocalized with BCL2 expression in heart tissues and hs-cTnT and with ANO5 expression in artery, heart tissues, and whole blood and both troponins. Mendelian randomization analyses showed that genetically increased hs-cTnT and hs-cTnI levels were associated with higher odds of atrial fibrillation (odds ratio, 1.38 [95% CI, 1.25-1.54] for hs-cTnT and 1.21 [95% CI, 1.06-1.37] for hs-cTnI). CONCLUSIONS: We identified a novel genetic locus associated with hs-cTnT in a multiethnic population and found that genetically regulated troponin levels were associated with atrial fibrillation.

4.
Diabetes Care ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732526

RESUMO

OBJECTIVE: To assess the relationship between body fat distribution and incident lower-extremity arterial disease (LEAD). RESEARCH DESIGN AND METHODS: We included 155,925 postmenopausal women with anthropometric measures from the Women's Health Initiative who had no known LEAD at recruitment. A subset of 10,894 participants had body composition data quantified by DXA. Incident cases of symptomatic LEAD were ascertained and adjudicated through medical record review. RESULTS: We identified 1,152 incident cases of LEAD during a median 18.8 years follow-up. After multivariable adjustment and mutual adjustment, waist and hip circumferences were positively and inversely associated with risk of LEAD, respectively (both P-trend < 0.0001). In a subset (n = 22,561) where various cardiometabolic biomarkers were quantified, a similar positive association of waist circumference with risk of LEAD was eliminated after adjustment for diabetes and HOMA of insulin resistance (P-trend = 0.89), whereas hip circumference remained inversely associated with the risk after adjustment for major cardiometabolic traits (P-trend = 0.0031). In the DXA subset, higher trunk fat (P-trend = 0.0081) and higher leg fat (P-trend < 0.0001) were associated with higher and lower risk of LEAD, respectively. Further adjustment for diabetes, dyslipidemia, and blood pressure diminished the association for trunk fat (P-trend = 0.49), yet the inverse association for leg fat persisted (P-trend = 0.0082). CONCLUSIONS: Among U.S. postmenopausal women, a positive association of upper-body fat with risk of LEAD appeared to be attributable to traditional risk factors, especially insulin resistance. Lower-body fat was inversely associated with risk of LEAD beyond known risk factors.

5.
Anim Nutr ; 7(4): 1052-1060, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34738035

RESUMO

Certain hormones play important roles in modulating mammalian reproductive behaviour. Daidzein is a well-known isoflavonic phytoestrogen that possesses oestrogenic activity. This study was conducted to probe the effects of daidzein supplementation in gestation diets on the reproductive performance in sows. A total of 120 multiparous sows (Landrace × Yorkshire) were randomly assigned to 2 groups (n = 60) and fed either a base diet (control) or one containing 200 mg/kg daidzein during gestation. We discovered that daidzein supplementation significantly increased the total number of piglets born per litter and number of piglets born alive per litter (P < 0.05), decreased the farrowing time (P < 0.05) and increased the serum oestrogen and progesterone concentrations (P < 0.05) at 35 d of gestation. Moreover, serum immunoglobulin G (IgG) concentration and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were higher in the daidzein-treated group than in the control group at 35 d of gestation (P < 0.05). Daidzein increased the serum SOD activity and total anti-oxidative capacity (T-AOC) at 85 d of gestation (P < 0.05). Interestingly, daidzein elevated the expression levels of the sodium-coupled neutral amino acid transporter 1 (SLC38A1) and insulin-like growth factor 1 (IGF-1) genes in the placenta (P < 0.05). These results suggest that daidzein ingestion could improve sow reproductive performance by changing serum hormones, elevating anti-oxidative capacity and up-regulating critical functional genes in the placenta.

6.
Anim Nutr ; 7(4): 1078-1086, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34738038

RESUMO

This experiment was conducted to evaluate the effects of different levels of tannic acid (TA) on growth performance, diarrhea rate, nutrient digestibility and intestinal health in weaned piglets. A total of 180 weaned piglets (Duroc × Landrace × Yorkshire, 24 d of age, initial average BW = 7.77 ± 0.17 kg) were allotted to 5 groups (6 pigs/pen and 6 replicates/group) in a randomized complete block design according to their gender and body weight. Piglets were fed a basal diet, or the basal diet supplemented with 0.05%, 0.1%, 0.2% or 0.4% TA for 28 d. The supplementary levels of TA in the diets were obtained by adding tannalbin containing 51% TA and 40.17% protein. The results showed that, compared with the CON group, dietary TA did not affect ADFI, ADG or F:G, and linearly reduced (P < 0.01) the diarrhea rate and diarrhea index of piglets. There were no significant effects on apparent total tract digestibility (ATTD) in the 0.05%, 0.1% and 0.2% TA groups, while negative effects (P < 0.05) on apparent digestibility of crude protein and gross energy were observed in the 0.4% TA group. In addition, the nutrient digestibility of dry matter, crude protein and gross energy linearly decreased (P < 0.01) with the increase of TA dosage. Supplementation of TA increased (P < 0.05) the villus height of the duodenum and jejunum, as well as increased (P < 0.05) catalase (CAT) activity in serum. Dietary TA improved (P < 0.05) the Bacillus counts in cecal digesta. Further, TA significantly improved (P < 0.05) Bacillus counts and reduced (P < 0.05) the Escherichia coli counts in colonic digesta. The concentration of acetic acid, propionic acid, butyric acid and isovaleric acid in cecal digesta were significantly increased (P < 0.05). The mRNA expression level of zonula occludens-1 (ZO-1), zonula occludens-2 (ZO-2), and claudin-2 (CLDN-2) in the jejunum were greater (P < 0.05) in TA supplemented groups. The study showed that, compared to the control, TA prevented post-weaning diarrhea and improved intestinal health of weaned piglets, and the appropriate level of TA supplementation would be from 0.1% to 0.2%.

7.
Diabetes ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753797

RESUMO

Fructosamine is a measure of short-term glycemic control, which has been suggested as a useful complement to glycated hemoglobin (HbA1c) for the diagnosis and monitoring of diabetes. To date, a single genome-wide association study (GWAS) including 8,951 US White and 2,712 US Black individuals without a diabetes diagnosis has been published. Results in Whites and Blacks yielded different association loci, near RCN3 and CNTN5, respectively. Here we performed a GWAS on 20,734 European ancestry blood donors, and meta-analysed our results with previous data from US White participants from The Atherosclerosis Risk in Communities (ARIC) study (Nmeta=29,685). We identified a novel association near GCK (rs3757840, betameta=0.0062, MAF=0.49, pmeta=3.66x10-08) and confirmed the association near RCN3 (rs113886122, betameta=0.0134, MAF=0.17, pmeta= 5.71x10-18). Co-localization analysis with whole blood eQTL data suggested FCGRT as the effector transcript at the RCN3 locus. We further showed that fructosamine has low heritability (h2=7.7%), has no significant genetic correlation with HbA1c and other glycemic traits in individuals without a diabetes diagnosis (p>0.05), but has evidence of shared genetic etiology with some anthropometric traits (Bonferroni corrected p<0.0012). Our results broaden knowledge of the genetic architecture of fructosamine and prioritize FCGRT for downstream functional studies atthe established RCN3 locus.

8.
Br J Nutr ; : 1-27, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34763738

RESUMO

Diarrhea caused by pathogens such as enterotoxigenic E. coli (ETEC) is a serious threat to the health of young animals and human infants. Here, we investigated the protective effect of fructooligosaccharides (FOS) on the intestinal epithelium with ETEC-challenge in a weaned piglet model. Twenty-four weaned piglets were randomly divided into three groups: (1) non-ETEC-challenged control (CON), (2) ETEC-challenged control (ECON), and (3) ETEC challenge + 2.5 g/kg FOS (EFOS). On day 19, the CON pigs were orally infused with sterile culture, while the ECON and EFOS pigs were orally infused with active ETEC (2.5 × 109 colony-forming units). On day 21, pigs were slaughtered to collect venous blood and small intestine. Result showed that the pre-treatment of FOS improved the antioxidant capacity and the integrity of intestinal barrier in the ETEC-challenged pigs without affecting their growth performance. Specifically, comparing with ECON pigs, the level of GSH-Px (glutathione peroxidase) and CAT (catalase) in the plasma and intestinal mucosa of EFOS pigs was increased (P<0.05), and the intestinal barrier marked by ZO-1 and plasmatic DAO was also improved in EFOS pigs. A lower level (P<0.05) of inflammatory cytokines in the intestinal mucosa of EFOS pigs might be involved in the inhibition of TLR4/MYD88/NF-κB pathway. The apoptosis of jejunal cells in EFOS pigs was also lower than that in ECON pigs (P<0.05). Our findings provide convincing evidence of possible prebiotic and protective effect of FOS on the maintenance of intestinal epithelial function under the attack of pathogens.

9.
Int Immunopharmacol ; 101(Pt A): 108339, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34758440

RESUMO

Inulae Flos was widely distributed throughout Europe, Africa, and Asia, and was commonly used as a folk medicine in clinic for treating various respiratory diseases, including cough, asthma, bronchitis, pulmonary fibrosis, and pneumonia. However, the ingredients responsible for the pharmacology effects of I. Flos and the underlying mechanisms remain unclear. In this study, the effects of 16 known sesquiterpene lactones and flavonoids from I. Flos on TGF-ß1-induced fibroblast activation were assessed by phenotypic high-content screening. Among those sixteen compounds, 1ß-hydroxy alantolactone (HAL), the main characteristic sesquiterpene lactone from I. Flos, exhibited remarkable inhibitory activity. The further studies showed that HAL significantly inhibited the proliferation and induced the apoptosis of human fibroblast cell lines HELF and MRC-5 in a concentration-dependent manner. It also reduced intracellular ROS production, suppressed the mRNA expressions of E-cad, TGF-ß1, Smad3, Col I, α-SMA and TNF-α, and downregulated protein expressions of α-SMA and F-actin. Furthermore, HAL significantly reduced the levels of HA, LN, PC-III and IV-C in serum, TNF-α and IL-6 in BALF, and TGF-ß1, HYP and Col I in lung tissues of bleomycin (BLM)-treated rats. HAL significantly downregulated the expressions of p-JNK, FOXO1, p-p65, α-SMA, p-smad3 and Col I but upregulated p-FOXO1, which could be reversed by JNK agonist anisomycin. These results demonstrated that HAL induced the apoptosis of lung fibroblast cells activated by TGF-ß1 and improved BLM-induced lung fibrosis in rats via inhibiting JNK/FOXO1/NF-κB pathway.

10.
J Hazard Mater ; 424(Pt C): 127602, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34749230

RESUMO

Emerging infectious diseases caused by the spread of bacteria and viruses are a major burden on global economic development and public health. At present, most personal protective equipment has weak antibacterial and anti-viral properties. The PAN/PTHP nanofibers reported in this article provide a new method for the development of personal protective equipment. In this study, a mixture of PTHP and PAN was prepared into PAN/PTHP nanofibers with high-efficiency and long-lasting antibacterial effects (>99.999%) through the electrospinning process. Live/dead staining and cell proliferation experiments showed that the preparation of PAN/PTHP nanofibers has good cell compatibility. In addition, PAN/PTHP nanofibers show obvious destructive effects on lentiviruses. Based on these characteristics, PAN/PTHP nanofibers were applied to facial masks, which can be used as the inflatable biocidal layer of facial masks and have an excellent interception effect on particles in the air. The successful synthesis of these fascinating materials may provide new insights for the development of new protective materials.

11.
Anim Biotechnol ; : 1-6, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34802366

RESUMO

This study was conducted to explore the effects of dietary ferulic acid (FA) supplementation on intestinal antioxidant capacity and intestinal barrier function in weaned piglets. Eighteen 21-day-old castrated male DLY (Duroc × Landrace × Yorkshire) weaned piglets were randomly divided into control, 0.05% FA, and 0.45% FA groups, respectively. The experiment lasted for 5 weeks. The results showed that dietary 0.05 and 0.45% FA supplementation significantly increased catalase activity (p < 0.001), the protein levels of nuclear factor E2-related factor 2 (Nrf2) and NAD(P)H quinone dehydrogenase 1 (p < 0.05), and the mRNA levels of superoxide dismutase 1, glutathione reductase and Nrf2 (p < 0.05) in jejunum when compared with the control group. Dietary 0.05% FA supplementation also increased the mRNA level of glutathione S-transferase (p < 0.05) in jejunum. Meanwhile, Dietary 0.05 and 0.45% FA supplementation significantly increased the protein expression of zonula occludens 1 (ZO-1) (p < 0.05), and dietary supplementation of 0.05% FA increased the mRNA levels of ZO-1, zonula occludens 2, mucin 1, mucin 2, occluding, and claudin-1 (p < 0.05) in jejunum. Together, our data suggest that dietary 0.05% FA supplementation improves the intestinal antioxidant capacity and intestinal barrier function of weaned piglets.

12.
Kidney Int ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774559

RESUMO

Circulating metabolites are by-products of endogenous metabolism or exogenous sources and may inform disease states. Our study aimed to identify the source of variability in the association of metabolites with estimated glomerular filtration rate (eGFR) in Hispanics/Latinos with low chronic kidney disease prevalence and tested the association of 640 metabolites in 3,906 participants of the Hispanic Community Health Study/Study of Latinos. Metabolites were quantified in fasting serum through non-targeted mass spectrometry analysis. eGFR was regressed on inverse normally transformed metabolites in models accounting for study design and covariates. To identify the source of variation on eGFR associations, we tested the interaction of metabolites with lifestyle and clinical risk factors with results integrated with genotypes to identify metabolite genetic regulation. The mean age was 46 years, 43% were men, 22% were current smokers, 47% had a Caribbean Hispanic background, 19% had diabetes and the mean cohort eGFR was 96.4 ml/min/1.73 m2. We identified 404 eGFR-metabolite associations (False Discovery Rate under 0.05). Of these, 69 were previously reported, and 79 were novel associations with eGFR replicated in one or more published studies. There were significant interactions with lifestyle and clinical risk factors, with larger differences in eGFR-metabolite associations within strata of age, urine albumin to creatinine ratio, diabetes and Hispanic/Latino background. Several newly identified metabolites were genetically regulated, and variants were located at genomic regions previously associated with eGFR. Thus, our results suggest complex mechanisms contribute to the association of eGFR with metabolites and provide new insights into these associations.

13.
Clin J Am Soc Nephrol ; 16(11): 1620-1629, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34737201

RESUMO

BACKGROUND AND OBJECTIVES: Moderate coffee consumption has been associated with lower risk of CKD; however, the exact biologic mechanisms underlying this association are unknown. Metabolomic profiling may identify metabolic pathways that explain the association between coffee and CKD. The goal of this study was to identify serum metabolites associated with coffee consumption and examine the association between these coffee-associated metabolites and incident CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using multivariable linear regression, we identified coffee-associated metabolites among 372 serum metabolites available in two subsamples of the Atherosclerosis Risk in Communities study (ARIC; n=3811). Fixed effects meta-analysis was used to pool the results from the two ARIC study subsamples. Associations between coffee and metabolites were replicated in the Bogalusa Heart Study (n=1043). Metabolites with significant associations with coffee in both cohorts were then evaluated for their prospective associations with incident CKD in the ARIC study using Cox proportional hazards regression. RESULTS: In the ARIC study, mean (SD) age was 54 (6) years, 56% were daily coffee drinkers, and 32% drank >2 cups per day. In the Bogalusa Heart Study, mean (SD) age was 48 (5) years, 57% were daily coffee drinkers, and 38% drank >2 cups per day. In a meta-analysis of two subsamples of the ARIC study, 41 metabolites were associated with coffee consumption, of which 20 metabolites replicated in the Bogalusa Heart Study. Three of these 20 coffee-associated metabolites were associated with incident CKD in the ARIC study. CONCLUSIONS: We detected 20 unique serum metabolites associated with coffee consumption in both the ARIC study and the Bogalusa Heart Study, and three of these 20 candidate biomarkers of coffee consumption were associated with incident CKD. One metabolite (glycochenodeoxycholate), a lipid involved in primary bile acid metabolism, may contribute to the favorable kidney health outcomes associated with coffee consumption. Two metabolites (O-methylcatechol sulfate and 3-methyl catechol sulfate), both of which are xenobiotics involved in benzoate metabolism, may represent potential harmful aspects of coffee on kidney health.

14.
BMC Infect Dis ; 21(1): 1183, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819019

RESUMO

BACKGROUND: We investigate the long-term effects of SARS-CoV on patients' lung and immune systems 15 years post-infection. SARS-CoV-2 pandemic is ongoing however, another genetically related beta-coronavirus SARS-CoV caused an epidemic in 2003-2004. METHODS: We enrolled 58 healthcare workers from Peking University People's Hospital who were infected with SARS-CoV in 2003. We evaluated lung damage by mMRC score, pulmonary function tests, and chest CT. Immune function was assessed by their serum levels of globin, complete components, and peripheral T cell subsets. ELISA was used to detect SARS-CoV-specific IgG antibodies in sera. RESULTS: After 15 years of disease onset, 19 (36.5%), 8 (34.6%), and 19 (36.5%) subjects had impaired DL (CO), RV, and FEF25-75, respectively. 17 (30.4%) subjects had an mMRC score ≥ 2. Fourteen (25.5%) cases had residual CT abnormalities. T regulatory cells were a bit higher in the SARS survivors. IgG antibodies against SARS S-RBD protein and N protein were detected in 11 (18.97%) and 12 (20.69%) subjects, respectively. Subgroup analysis revealed that small airway dysfunction and CT abnormalities were more common in the severe group than in the non-severe group (57.1% vs 22.6%, 54.5% vs 6.1%, respectively, p < 0.05). CONCLUSIONS: SARS-CoV could cause permanent damage to the lung, which requires early pulmonary rehabilitation. The long-lived immune memory response against coronavirus requires further studies to assess the potential benefit. Trial registration ClinicalTrials.gov, NCT03443102. Registered prospectively on 25 January 2018.


Assuntos
Anticorpos Antivirais , COVID-19 , Humanos , Pulmão , Pandemias , SARS-CoV-2
15.
Artigo em Inglês | MEDLINE | ID: mdl-34774311

RESUMO

Technologies that can effectively address the environmental issues arisen from the use of agrochemicals and P fertilizers are needed for the development of green agriculture. Here, we reporta new core-shell P-laden biochar/ZnO/g-C3N4 composite (Pbi-ZnO-g-C3N4) used both as an efficient photocatalyst for degrading atrazine and a promising slow-release fertilizer for improving the P utilization efficiency. In comparison with P-laden biochar/ZnO (Pbi-ZnO), Pbi-ZnO-g-C3N4 exhibits enhanced photocatalytic activity with the maximum atrazine degradation efficiency of 85.3% after 260 min. Pbi-ZnO-g-C3N4 also shows superior P slow-release performance with the cumulative P release concentration of 216.40 g/L in 260 min. Besides, it is found that the coating of g-C3N4 on the surface of Pbi-ZnO improves the utilization of visible light and separation of photoinduced electron-hole pairs, producing more radicals (•OH and •O2-) under visible light irradiation. The mechanistic study reveals that Z-shaped heterojunction is formed between ZnO and g-C3N4 in Pbi-ZnO-g-C3N4, and biochar serves as an electron-transfer bridge that promotes the separation of electron-hole pairs. Finally, pot experiments reveal that the P utilization efficiency for pepper seedlings fertilized by Pbi-ZnO-g-C3N4 is higher than that by Pbi-ZnO. The application of Pbi-ZnO-g-C3N4 is beneficial for the growth of native soil microorganism.

16.
Genet Epidemiol ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779012

RESUMO

Hematological measures are important intermediate clinical phenotypes for many acute and chronic diseases and are highly heritable. Although genome-wide association studies (GWAS) have identified thousands of loci containing trait-associated variants, the causal genes underlying these associations are often uncertain. To better understand the underlying genetic regulatory mechanisms, we performed a transcriptome-wide association study (TWAS) to systematically investigate the association between genetically predicted gene expression and hematological measures in 54,542 Europeans from the Genetic Epidemiology Research on Aging cohort. We found 239 significant gene-trait associations with hematological measures; we replicated 71 associations at p < 0.05 in a TWAS meta-analysis consisting of up to 35,900 Europeans from the Women's Health Initiative, Atherosclerosis Risk in Communities Study, and BioMe Biobank. Additionally, we attempted to refine this list of candidate genes by performing conditional analyses, adjusting for individual variants previously associated with hematological measures, and performed further fine-mapping of TWAS loci. To facilitate interpretation of our findings, we designed an R Shiny application to interactively visualize our TWAS results by integrating them with additional genetic data sources (GWAS, TWAS from multiple reference panels, conditional analyses, known GWAS variants, etc.). Our results and application highlight frequently overlooked TWAS challenges and illustrate the complexity of TWAS fine-mapping.

17.
J Am Heart Assoc ; 10(22): e022635, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34726069

RESUMO

Background We evaluated whether immigration status modified the association between sex and the quality of primary cardiovascular disease prevention in Ontario, Canada. Methods and Results We used a population-based administrative database-derived cohort of community-dwelling adults (aged ≥40 years) without prior cardiovascular disease residing in Ontario on January 1, 2011. In the preceding 3 years, we evaluated screening for hyperlipidemia and diabetes in those not previously diagnosed; diabetes control (HbA1c <7%); and medication use to control hypertension, hyperlipidemia, or diabetes in those with previous diagnosis. We calculated the absolute prevalence difference (APD) between women and men for each metric stratified by immigration status and then determined the difference-in-differences for immigrants compared with long-term residents. Our sample included 5.3 million adults (19% immigrants), with receipt of each metric ranging from 55% to 90%. Among immigrants, women were more likely than men to be screened for hyperlipidemia (APD, 10.8%; 95% CI, 10.5-11.2) and diabetes (APD, 11.5%; 95% CI, 11.1-11.8) and to be treated with medications for hypertension (APD, 3.5%; 95% CI, 2.4-4.5), diabetes (APD, 2.1%; 95% CI, 0.7-3.6) and hyperlipidemia (APD, 1.8%; 95% CI, 0.5-3.1). Among long-term residents, findings were similar except poorer medication use for diabetes (APD, -2.8%; 95% CI, -3.4 to -2.2) and hyperlipidemia (APD, -3.5%; 95% CI, -4.0 to -3.0]) in women compared with men. Conclusions The overall quality of primary preventive care can be improved for all adults, and future research should evaluate the impact of observed equal or better care in women than men, irrespective of immigration status, on cardiovascular disease incidence.

18.
Stroke ; : STROKEAHA121037388, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34743536

RESUMO

BACKGROUND AND PURPOSE: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke. METHODS: We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association of CHIP and commonly mutated individual CHIP driver genes (DNMT3A, TET2, and ASXL1) with any stroke, ischemic stroke, and hemorrhagic stroke. RESULTS: CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14 [95% CI, 1.03-1.27]; P=0.01) after adjustment for age, sex, and race. We observed associations with CHIP with risk of hemorrhagic stroke (hazard ratio, 1.24 [95% CI, 1.01-1.51]; P=0.04) and with small vessel ischemic stroke subtypes. In gene-specific association results, TET2 showed the strongest association with total stroke and ischemic stroke, whereas DMNT3A and TET2 were each associated with increased risk of hemorrhagic stroke. CONCLUSIONS: CHIP is associated with an increased risk of stroke, particularly with hemorrhagic and small vessel ischemic stroke. Future studies clarifying the relationship between CHIP and subtypes of stroke are needed.

20.
Int J Biol Macromol ; 192: 241-249, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34619281

RESUMO

Intestinal epithelial cells (IECs) offer a primary physical barrier against commensal and pathogenic microorganisms in the gastrointestine. However, the influence of IECs on the development and regulation of mucosal immunity to infection is unknown. Here, we show that the porcine ß-defensin 114 (PBD114) is an endotoxin-responsive gene expressed in IECs. Analysis on expression profiling of PBD114 gene using an infected porcine model and IPEC-J2 cells unveiled a pattern of induction in response to stimulation of various toll-like receptors (TLRs). By means of promoter analysis, PBD114 was found to be a NF-κB-dependent gene. Importantly, PBD114 suppresses endotoxin-induced inflammation and apoptosis in IECs through downregulation of two critical inflammation-associated signaling proteins, NF-kappa-B inhibitor alpha (IkB-α) and extracellular signal-regulated kinase1/2 (ERK1/2). PBD114 also suppresses inflammation and IEC apoptosis in mice exposed to bacterial endotoxins. Thus, we propose that TLR-activated NF-kB rapidly increases the expression of PBD114 that operates a feedback control of the NF-kB-dependent inflammation. The NF-kB-dependent induction of PBD114 may be a key event through which the mammalian host maintains intestinal epithelium homeostasis in response to various infections or diseases.

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