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1.
Food Res Int ; 184: 114241, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609221

RESUMO

This review aimed to critically and comparatively analyze the physicochemical, proximate, nutritional, phytochemical composition, and bioactivities of araticum (Annona crassiflora Mart.) (AAc), a fruit from the Brazilian Cerrado. Additionally, the potential applications of this fruit in the food industry were reviewed. Data and information were collected from the Scopus, Web of Science, and Google Scholar databases. AAc, a fruit mainly studied in the Brazilian regions of Minas Gerais and Goiás, has well-documented physicochemical, proximate, and nutritional characteristics. It is rich in fiber, sugars, vitamins A and C, minerals, and oil, making it attractive to the food industry. However, there are research gaps, such as the impact of climatic conditions on the AAc chemical composition. Additional studies are needed, especially for the peel and seeds, and investigations of pre-treatments effect on the chemical composition are recommended. The application of AAc in food products is mainly limited to pulp, but there is potential for using peels and seeds. AAc is a rich source of phytochemical compounds with various biological properties, such as antioxidants, hepatoprotective, and antimicrobial activities. Future studies should explore other phytochemicals present in the fruit beyond phenolic compounds. The consumption of AAc can contribute to combating food insecurity malnutrition, and promoting the conservation of the Brazilian Cerrado.


Assuntos
Annona , Indústria Alimentícia , Frutas , Sementes , Compostos Fitoquímicos
2.
Microbiol Spectr ; : e0421823, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651879

RESUMO

SARS-CoV-2 virus emerged as a new threat to humans and spread around the world, leaving a large death toll. As of January 2023, Brazil is among the countries with the highest number of registered deaths. Nonpharmacological and pharmacological interventions have been heterogeneously implemented in the country, which, associated with large socioeconomic differences between the country regions, has led to distinct virus spread dynamics. Here, we investigate the spatiotemporal dispersion of SARS-CoV-2 lineages in the Pernambuco state (Northeast Brazil) throughout the distinct epidemiological scenarios that unfolded in the first 2 years of the pandemic. We generated a total of 1,389 new SARS-CoV-2 genomes from June 2020 to August 2021. This sampling captured the arrival, communitary transmission, and the circulation of the B1.1, B.1.1.28, and B.1.1.33 lineages; the emergence of the former variant of interest P.2; and the emergence and fast replacement of all previous variants by the more transmissible variant of concern P.1 (Gamma). Based on the incidence and lineage spread pattern, we observed an East-to-West to inner state pattern of transmission, which is in agreement with the transmission of more populous metropolitan areas to medium- and small-size country-side cities in the state. Such transmission patterns may be partially explained by the main routes of traffic across municipalities in the state. Our results highlight that the fine-grained intrastate analysis of lineages and incidence spread can provide actionable insights for planning future nonpharmacological intervention for air-borne transmissible human pathogens.IMPORTANCEDuring the COVID-19 pandemic, Brazil was one of the most affected countries, mainly due its continental-size, socioeconomic differences among regions, and heterogeneous implementation of intervention methods. In order to investigate SARS-CoV-2 dynamics in the state of Pernambuco, we conducted a spatiotemporal dispersion study, covering the period from June 2020 to August 2021, to comprehend the dynamics of viral transmission during the first 2 years of the pandemic. Throughout this study, we were able to track three significant epidemiological waves of transmission caused by B1.1, B.1.1.28, B.1.1.33, P.2, and P.1 lineages. These analyses provided valuable insights into the evolution of the epidemiological landscape, contributing to a deeper understanding of the dynamics of virus transmission during the early years of the pandemic in the state of Pernambuco.

3.
Metabolites ; 14(3)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38535334

RESUMO

The role of gut microbe-derived metabolites in the development of metabolic syndrome (MetS) remains unclear. This study aimed to evaluate the associations of gut microbe-derived metabolites and MetS traits in the cross-sectional Metabolic Syndrome In Men (METSIM) study. The sample included 10,194 randomly related men (age 57.65 ± 7.12 years) from Eastern Finland. Levels of 35 metabolites were tested for associations with 13 MetS traits using lasso and stepwise regression. Significant associations were observed between multiple MetS traits and 32 metabolites, three of which exhibited particularly robust associations. N-acetyltryptophan was positively associated with Homeostatic Model Assessment for Insulin Resistant (HOMA-IR) (ß = 0.02, p = 0.033), body mass index (BMI) (ß = 0.025, p = 1.3 × 10-16), low-density lipoprotein cholesterol (LDL-C) (ß = 0.034, p = 5.8 × 10-10), triglyceride (0.087, p = 1.3 × 10-16), systolic (ß = 0.012, p = 2.5 × 10-6) and diastolic blood pressure (ß = 0.011, p = 3.4 × 10-6). In addition, 3-(4-hydroxyphenyl) lactate yielded the strongest positive associations among all metabolites, for example, with HOMA-IR (ß = 0.23, p = 4.4 × 10-33), and BMI (ß = 0.097, p = 5.1 × 10-52). By comparison, 3-aminoisobutyrate was inversely associated with HOMA-IR (ß = -0.19, p = 3.8 × 10-51) and triglycerides (ß = -0.12, p = 5.9 × 10-36). Mendelian randomization analyses did not provide evidence that the observed associations with these three metabolites represented causal relationships. We identified significant associations between several gut microbiota-derived metabolites and MetS traits, consistent with the notion that gut microbes influence metabolic homeostasis, beyond traditional risk factors.

4.
Sci Rep ; 14(1): 6374, 2024 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493259

RESUMO

We evaluated the association of cardiovascular autonomic neuropathy (CAN), blood pressure (BP) and Vitamin D (VD) levels before and after high-dose cholecalciferol supplementation (4000/10,000) UI/day) for 12 weeks in patients (N = 67) with type 1 diabetes mellitus (T1DM). Based on this prospective controlled pilot study, patients were divided into group 1 (N = 23 with CAN) and group 2 (N = 44 without CAN). At baseline, group 1 had higher systolic BP (SBP) during sleep (115 ± 14 vs. 107 ± 12 mmHg, p = 0.04) and lower nocturnal dipping (3 ± 5 vs. 8 ± 6%, p = 0.009). Among those with loss of nocturnal dipping, 45.4% (20/44) had CAN, while in normal nocturnal dipping group it occurred only in 13% (3/23) (p = 0.007). Non-dipper group had worse CAN parameters when compared to dipper group [Very low frequency (VLF) (2.5 ± 0.5vs.2.8 ± 0.4 s, p = 0.01), total power (TP) (2.9 ± 0.6 vs. 3.3 ± 0.4 s, p = 0.01), Valsalva coefficient (1.5 ± 0.4 vs. 1.8 ± 0.6, p = 0.06)]. After VD, only group 1 improved CAN parameters [TP (2.5 ± 0.4 vs. 2.8 ± 0.6, p = 0.01) and VLF (2.2 ± 0.4 vs. 2.4 ± 0.5, p = 0.03). Group 1 presented a reduction in morning SBP (120 ± 20 vs. 114 ± 17 mmHg, p = 0.038) and in morning SBP surge (13 ± 13 vs. 5 ± 14, p = 0.04). High-dose VD was associated with improved CAN parameters and reduced awake SBP and morning SBP surge. These findings suggest that VD may benefit patients with cardiovascular autonomic neuropathy. ISRCTN32601947, registration date: 31/07/2017.


Assuntos
Diabetes Mellitus Tipo 1 , Hipertensão , Hipotensão , Humanos , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Colecalciferol/uso terapêutico , Ritmo Circadiano/fisiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Suplementos Nutricionais , Estudos Prospectivos
5.
Nature ; 628(8006): 130-138, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38448586

RESUMO

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1-7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8-11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.


Assuntos
Biomarcadores , Estudo de Associação Genômica Ampla , Metabolômica , Feminino , Humanos , Gravidez , Acetona/sangue , Acetona/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/metabolismo , Estudos de Coortes , Estudo de Associação Genômica Ampla/métodos , Hipertensão/sangue , Hipertensão/genética , Hipertensão/metabolismo , Lipoproteínas/genética , Lipoproteínas/metabolismo , Espectroscopia de Ressonância Magnética , Análise da Randomização Mendeliana , Redes e Vias Metabólicas/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Complicações na Gravidez/sangue , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo
6.
Glob Heart ; 19(1): 20, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38404615

RESUMO

Background: Although there is evidence of peer support in high-income countries, the use of peer support as an intervention for cardiometabolic disease management, including type 2 diabetes (T2DM), in low- and middle-income countries (LMICs), is unclear. Methods: A scoping review methodology was used to search the databases MEDLINE, Embase, Emcare, PsycINFO, LILACS, CDSR, and CENTRAL. Results: Twenty-eight studies were included in this scoping review. Of these, 67% were developed in Asia, 22% in Africa, and 11% in the Americas. The definition of peer support varied; however, peer support offered a social and emotional dimension to help individuals cope with negative emotions and barriers while promoting disease management. Conclusions: Findings from this scopingreview highlight a lack of consistency in defining peer support as a component of CMD management in LMICs. A clear definition of peer support and ongoing program evaluation is recommended for future research.


Assuntos
Países em Desenvolvimento , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Renda , Avaliação de Programas e Projetos de Saúde , Ásia
7.
Biomed Res Int ; 2024: 8322844, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327803

RESUMO

Neuroimaging data in humans and neurobiological studies in rodents have suggested an involvement of the insular cortex (IC) in anxiety manifestations. However, the local neurochemical mechanisms involved are still poorly understood. Corticotropin-releasing factor (CRF) neurotransmission has been described as a prominent neurochemical mechanism involved in the expression of anxiety-like behaviors, but the brain sites related are poorly understood. Additionally, several findings indicate that control of physiological and behavioral responses by the IC occurs in a site-specific manner along its rostrocaudal axis. Thus, this study is aimed at evaluating the effect of CRF receptor agonism and antagonism within the anterior and posterior subregions of the IC in controlling anxiety-related behaviors in the elevated plus maze (EPM). For this, independent groups (six groups) of animals received bilateral microinjections of vehicle, the selective CRF1 receptor antagonist CP376395, or CRF into either the anterior or posterior subregions of the IC. Ten minutes later, the behavior in the EPM was evaluated for five minutes. Treatment of the anterior IC with CP376395, but not with CRF, increased the time and number of entries into the open arms of the EPM. CRF, but not the CRF1 receptor antagonist, microinjected into the posterior IC also increased exploration of the EPM open arms. Taken together, these data indicate that CRFergic neurotransmission in the anterior IC is involved in the expression of anxiety-related behaviors in the EPM. This neurochemical mechanism does not seem to be activated within the posterior IC during exposure to the EPM, but the effects caused by CRF microinjection indicate that activation of CRF receptors in this IC subregion might evoke anxiolytic-like effects.


Assuntos
Aminopiridinas , Ansiolíticos , Receptores de Hormônio Liberador da Corticotropina , Humanos , Ratos , Animais , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Hormônio Liberador da Corticotropina/farmacologia , Hormônio Liberador da Corticotropina/metabolismo , Teste de Labirinto em Cruz Elevado , Córtex Insular , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Ansiolíticos/farmacologia
8.
Pflugers Arch ; 476(3): 351-364, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38228895

RESUMO

Despite the importance of physiological responses to stress in a short-term, chronically these adjustments may be harmful and lead to diseases, including cardiovascular diseases. The lateral hypothalamus (LH) has been reported to be involved in expression of physiological and behavioral responses to stress, but the local neurochemical mechanisms involved are not completely described. The corticotropin-releasing factor (CRF) neurotransmission is a prominent brain neurochemical system implicated in the physiological and behavioral changes induced by aversive threats. Furthermore, chronic exposure to aversive situations affects the CRF neurotransmission in brain regions involved in stress responses. Therefore, in this study, we evaluated the influence of CRF neurotransmission in the LH on changes in cardiovascular function and baroreflex activity induced by chronic variable stress (CVS). We identified that CVS enhanced baseline arterial pressure and impaired baroreflex function, which were followed by increased expression of CRF2, but not CRF1, receptor expression within the LH. Local microinjection of either CRF1 or CRF2 receptor antagonist within the LH inhibited the baroreflex impairment caused by CVS, but without affecting the mild hypertension. Taken together, the findings documented in this study suggest that LH CRF neurotransmission participates in the baroreflex impairment related to chronic stress exposure.


Assuntos
Hormônio Liberador da Corticotropina , Região Hipotalâmica Lateral , Ratos , Animais , Hormônio Liberador da Corticotropina/metabolismo , Hormônio Liberador da Corticotropina/farmacologia , Região Hipotalâmica Lateral/metabolismo , Barorreflexo , Encéfalo/metabolismo , Transmissão Sináptica
9.
bioRxiv ; 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37961277

RESUMO

Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. Here, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34K conditionally distinct expression quantitative trait locus (eQTL) signals in 18K genes. Over half of eQTL genes exhibited at least two eQTL signals. Compared to primary signals, non-primary signals had lower effect sizes, lower minor allele frequencies, and less promoter enrichment; they corresponded to genes with higher heritability and higher tolerance for loss of function. Colocalization of eQTL with conditionally distinct genome-wide association study signals for 28 cardiometabolic traits identified 3,605 eQTL signals for 1,861 genes. Inclusion of non-primary eQTL signals increased colocalized signals by 46%. Among 30 genes with ≥2 pairs of colocalized signals, 21 showed a mediating gene dosage effect on the trait. Thus, expanded eQTL identification reveals more mechanisms underlying complex traits and improves understanding of the complexity of gene expression regulation.

10.
Front Endocrinol (Lausanne) ; 14: 1239335, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795366

RESUMO

Statins are widely used to prevent cardiovascular disease events. Cardiovascular diseases and type 2 diabetes are tightly connected since type 2 diabetes is a major risk factor for cardiovascular diseases. Additionally, cardiovascular diseases often precede the development of type 2 diabetes. These two diseases have common genetic and environmental antecedents. Statins are effective in the lowering of cardiovascular disease events. However, they have also important side effects, including an increased risk of type 2 diabetes. The first study reporting an association of statin treatment with the risk of type 2 diabetes was the WOSCOPS trial (West of Scotland Coronary Prevention Study) in 2001. Other primary and secondary cardiovascular disease prevention studies as well as population-based studies have confirmed original findings. The purpose of our review is to examine and summarize the most important findings of these studies as well as to describe the mechanisms how statins increase the risk of type 2 diabetes.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco
11.
Diabetes ; 72(11): 1707-1718, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37647564

RESUMO

Understanding differences in adipose gene expression between individuals with different levels of clinical traits may reveal the genes and mechanisms leading to cardiometabolic diseases. However, adipose is a heterogeneous tissue. To account for cell-type heterogeneity, we estimated cell-type proportions in 859 subcutaneous adipose tissue samples with bulk RNA sequencing (RNA-seq) using a reference single-nuclear RNA-seq data set. Cell-type proportions were associated with cardiometabolic traits; for example, higher macrophage and adipocyte proportions were associated with higher and lower BMI, respectively. We evaluated cell-type proportions and BMI as covariates in tests of association between >25,000 gene expression levels and 22 cardiometabolic traits. For >95% of genes, the optimal, or best-fit, models included BMI as a covariate, and for 79% of associations, the optimal models also included cell type. After adjusting for the optimal covariates, we identified 2,664 significant associations (P ≤ 2e-6) for 1,252 genes and 14 traits. Among genes proposed to affect cardiometabolic traits based on colocalized genome-wide association study and adipose expression quantitative trait locus signals, 25 showed a corresponding association between trait and gene expression levels. Overall, these results suggest the importance of modeling cell-type proportion when identifying gene expression associations with cardiometabolic traits.


Assuntos
Doenças Cardiovasculares , Estudo de Associação Genômica Ampla , Humanos , Índice de Massa Corporal , Obesidade/genética , Expressão Gênica , Doenças Cardiovasculares/genética
12.
J Clin Endocrinol Metab ; 109(1): 100-106, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37560996

RESUMO

CONTEXT: Diabetic retinopathy (DR) is a specific microvascular complication in patients with diabetes and the leading cause of blindness. Recent advances in omics, especially metabolomics, offer the possibility identifying novel potential biomarkers for DR. OBJECTIVE: The aim was to identify metabolites associated with DR. METHODS: We performed a 12-year follow-up study including 1349 participants with type 2 diabetes (1021 without DR, 328 with DR) selected from the METSIM cohort. Individuals who had retinopathy before the baseline study were excluded (n = 63). The diagnosis of retinopathy was based on fundus photography examination. We performed nontargeted metabolomics profiling to identify metabolites. RESULTS: We found 17 metabolites significantly associated with incident DR after adjustment for confounding factors. Among amino acids, N-lactoyl isoleucine, N-lactoyl valine, N-lactoyl tyrosine, N-lactoyl phenylalanine, N-(2-furoyl) glycine, and 5-hydroxylysine were associated with an increased risk of DR, and citrulline with a decreased risk of DR. Among the fatty acids N,N,N-trimethyl-5-aminovalerate was associated with an increased risk of DR, and myristoleate (14:1n5), palmitoleate (16:1n7), and 5-dodecenoate (12:1n7) with a decreased risk of DR. Sphingomyelin (d18:2/24:2), a sphingolipid, was significantly associated with a decreased risk of DR. Carboxylic acid maleate and organic compounds 3-hydroxypyridine sulfate, 4-vinylphenol sulfate, 4-ethylcatechol sulfate, and dimethyl sulfone were significantly associated with an increased risk of DR. CONCLUSION: Our study is the first large population-based longitudinal study to identify metabolites for DR. We found multiple metabolites associated with an increased and decreased risk for DR from several different metabolic pathways.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Seguimentos , Estudos Longitudinais , Fatores de Risco , Sulfatos
13.
medRxiv ; 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37425837

RESUMO

Metabolites are small molecules that are useful for estimating disease risk and elucidating disease biology. Nevertheless, their causal effects on human diseases have not been evaluated comprehensively. We performed two-sample Mendelian randomization to systematically infer the causal effects of 1,099 plasma metabolites measured in 6,136 Finnish men from the METSIM study on risk of 2,099 binary disease endpoints measured in 309,154 Finnish individuals from FinnGen. We identified evidence for 282 causal effects of 70 metabolites on 183 disease endpoints (FDR<1%). We found 25 metabolites with potential causal effects across multiple disease domains, including ascorbic acid 2-sulfate affecting 26 disease endpoints in 12 disease domains. Our study suggests that N-acetyl-2-aminooctanoate and glycocholenate sulfate affect risk of atrial fibrillation through two distinct metabolic pathways and that N-methylpipecolate may mediate the causal effect of N6, N6-dimethyllysine on anxious personality disorder. This study highlights the broad causal impact of plasma metabolites and widespread metabolic connections across diseases.

14.
Front Vet Sci ; 10: 1198678, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37520006

RESUMO

The good productive and reproductive performance of the animals depends on multiple factors, including favorable climatic conditions, which are responsible for causing changes in the physiological and behavioral responses. Thus, the objective of this study was to evaluate the temperature and humidity index (THI) to support the implementation of a rearing system in ruminants in the Western Amazon, Brazil. Monthly temperature and relative humidity data were obtained from the Database for Teaching and Research (BDMEP) for the capitals Manaus (Amazonas), Boa Vista (Roraima), and Rio Branco (Acre), considering a historical series of 27 years (1993 to 2020), referring from January to December. In the capital Boa Vista, the months of January, February, May, June, and July showed an indication of mild stress and the months of March, April, August, September, October, November, and December had moderate stress. In Rio Branco, all months of the year presented the average THI in mild stress with variations of lower THI (73) and higher THI (77). In the capital Manaus, the months from January to July signaled mild stress, but from August to November, there was moderate stress, and in December, there was mild stress. It is possible to observe significant climatic variations during the months as well as the years of study, with the animals under thermal stress with THI > 72 or in a warning signal, with a gradual increase in temperature and humidity indices over the last 10 years. The importance of the breeding system and the consideration of environmental factors, such as the THI, are fundamental for the wellbeing and performance of cattle raised in the field. Our results support the adoption of heat stress mitigation strategies for ruminants in Western Amazon.

15.
PLoS One ; 18(7): e0288257, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37437036

RESUMO

The goal of this study was to verify the effect of heterogeneity of variance (HV) on milk production in up to 305 days of lactation (L305) of daughters of Girolando, Gir and Holstein sires, as well as in the genetic evaluation of these sires and their progenies. in Brazil. The model included contemporary groups (consisting of herd, year and calving season) as a fixed effect, cow age at calving (linear and quadratic effects) and heterozygosity (linear effect) as covariates, in addition to the random effects of direct additive genetic and environmental, permanent and residual. The first analysis consisted of the single-trait animal model, with L305 records (disregarding HV). The second considered classes of standard deviations (SD): two-trait model including low and high classes (considering HV), according to the standardized means of L305 for herd-year of calving. The low SD class was composed of herds with SD equal to or less than zero and the high class with positive SD values. Estimates of (co)variance components and breeding values were obtained separately for each scenario using Bayesian inference via Gibbs sampling. Different heritability was estimated. Higher for the high DP class in the Gir (0.20) and Holstein (0.15) breeds, not occurring the same in the Girolando breed, with a lower value among the classes for the high DP (0.10). High values of genetic correlations were also found between low and high SD classes (0.88; 0.85 and 0.79) for the Girolando, Gir and Holstein breeds, respectively. Like the order correlations (Spearman) which were also high for the three breeds analyzed (equal to or above 0.92). Thus, the presence of HV had a smaller impact for L305 and did not affect the genetic evaluation of sires.


Assuntos
Cobalto , Leite , Feminino , Animais , Bovinos/genética , Teorema de Bayes , Brasil , Heterozigoto
16.
Diabetologia ; 66(8): 1472-1480, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37280435

RESUMO

AIMS/HYPOTHESIS: Determining how high BMI at different time points influences the risk of developing type 2 diabetes and affects insulin secretion and insulin sensitivity is critical. METHODS: By estimating childhood BMI in 441,761 individuals in the UK Biobank, we identified which genetic variants had larger effects on adulthood BMI than on childhood BMI, and vice versa. All genome-wide significant genetic variants were then used to separate the independent genetic effects of high childhood BMI from those of high adulthood BMI on the risk of type 2 diabetes and insulin-related phenotypes using Mendelian randomisation. We performed two-sample MR using external studies of type 2 diabetes, and oral and intravenous measures of insulin secretion and sensitivity. RESULTS: We found that a childhood BMI that was one standard deviation (1.97 kg/m2) higher than the mean, corrected for the independent genetic liability to adulthood BMI, was associated with a protective effect for seven measures of insulin sensitivity and secretion, including increased insulin sensitivity index (ß=0.15; 95% CI 0.067, 0.225; p=2.79×10-4) and reduced fasting glucose levels (ß=-0.053; 95% CI -0.089, -0.017; p=4.31×10-3). However, there was little to no evidence of a direct protective effect on type 2 diabetes (OR 0.94; 95% CI 0.85, 1.04; p=0.228) independently of genetic liability to adulthood BMI. CONCLUSIONS/INTERPRETATION: Our results provide evidence of the protective effect of higher childhood BMI on insulin secretion and sensitivity, which are crucial intermediate diabetes traits. However, we stress that our results should not currently lead to any change in public health or clinical practice, given the uncertainty regarding the biological pathway of these effects and the limitations of this type of study.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina/genética , Índice de Massa Corporal , Fenótipo , Insulina/genética , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único
17.
Nat Genet ; 55(6): 973-983, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37291194

RESUMO

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Insulina/genética , Estudo de Associação Genômica Ampla , Resistência à Insulina/genética , Diabetes Mellitus Tipo 2/genética , Glucose/metabolismo , Glicemia/genética
18.
Front Vet Sci ; 10: 1150763, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37138916

RESUMO

In Brazil, the study on equine thermoregulation has not shown considerable advances, moreover, in the Amazon, this is a little explored aspect. This study aims to evaluate the thermoregulation of horses submitted to two methods of post-exercise cooling, in the climatic conditions of the Eastern Amazon. The experiment was conducted at Centro Hipico, Ananindeua, Para, for 15 days. Ten male horses, castrated of the Brazilian breed, aged 13 years and with an average weight of 482.3 kg were used. Equestrianism, which was exercised with pre-established protocol in the arena and track, for 30 min. After the exercise, the animals were divided into two groups for application of the treatments, which were two cooling methods, such as a bath with water at room temperature (about 25°C) and a hiper cooling method (6-9°C). During the experimental period, air temperature (AT) and relative humidity (RH) data were recorded and the Temperature and Humidity Index (THI) was calculated. Data from the rectal temperature (RT), heart rate (HR), respiratory rate (RR) and Body surface temperature (BST) of the animals were also measured at three moments: before exercise, after exercise and after applying the cooling methods. The adaptability index used was the Benezra Thermal Comfort Index (BTCI). The BST was performed with the help of infrared thermograph, which were the left side of the neck, thorax, rump, and right side to the armpi, before the exercise, after the exercise and after applying the cooling methods. The statistical design was completely randomized. Analysis of variance was performed using the GLM Procedure of SAS 9.1.3. After the application of the cooling techniques in the animals, the AT and THI were higher and the highest RH values were found before the exercise (87.21%). The highest RT, RR, HR, BST, and BTCI values were observed after exercise. There was no significant dierence (P > 0.05) between cooling methods. There was a highly significant and positive correlation (P < 0.01) between all physiological variables (RT, RR, HR, and BST) and the Iberian Index with AT and THI and negative with RH (P < 0.01), thus demonstrating the influence of the environment on the thermoregulation of animals. It is concluded the evaluation of stress, welfare and thermoregulation of horses submitted to two methods of post-exercise cooling, in the climatic conditions of the Eastern Amazon, demonstrated that the studied cooling methods showed to reduce the rectal temperature, the respiratory rate, the heart rate and the body surface temperature with equal efficiency. However, in terms of practical ease of use, the room temperature water cooling method has proven to be more practical.

19.
Int J Mol Sci ; 24(8)2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37108138

RESUMO

Diabetes mellitus (DM) and hypothyroidism (HT) are prevalent diseases associated with dry eye (DE). Their impact on the lacrimal functional unit (LFU) is poorly known. This work evaluates the changes in the LFU in DM and HT. Adult male Wistar rats had the disease induced as follows: (a) DM: streptozotocin and (b) HT: methimazole. The tear film (TF) and blood osmolarity were measured. Cytokine mRNA was compared in the lacrimal gland (LG), trigeminal ganglion (TG), and cornea (CO). Oxidative enzymes were evaluated in the LG. The DM group showed lower tear secretion (p = 0.02) and higher blood osmolarity (p < 0.001). The DM group presented lower mRNA expression of TRPV1 in the cornea (p = 0.03), higher Il1b mRNA expression (p = 0.03), and higher catalase activity in the LG (p < 0.001). The DM group presented higher Il6 mRNA expression in the TG (p = 0.02). The HT group showed higher TF osmolarity (p < 0.001), lower expression of Mmp9 mRNA in the CO (p < 0.001), higher catalase activity in the LG (p = 0.002), and higher expression of Il1b mRNA in the TG (p = 0.004). The findings revealed that DM and HT induce distinct compromises to the LG and the entire LFU.


Assuntos
Diabetes Mellitus , Hipotireoidismo , Aparelho Lacrimal , Ratos , Animais , Masculino , Aparelho Lacrimal/metabolismo , Catalase/metabolismo , Ratos Wistar , Lágrimas/metabolismo , Interleucina-1/metabolismo , Diabetes Mellitus/metabolismo , Hipotireoidismo/metabolismo , Estresse Oxidativo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
PeerJ ; 11: e14768, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37065705

RESUMO

Background: The production of animal-based foods from native breeds have a synergistic relationship with the regional culture, the local climate, and mainly the maintenance of alternative genetic resources for a system with a lower environmental impact. Thus the efficiency of conservation and production depends on assessing the variability of these local breeds. In the case of Curraleiro Pé-duro cattle, the most adapted individuals have undergone natural selection over five hundred years in the Brazilian savannas, mating with little or no human interference. The peculiarities of these biomes, where the regional flora is the food base and cattle is raised in extensive areas, likely influenced the genetic composition of the different groups that make up the first cattle breed of Brazil. Methods: To evaluate the composition, diversity, variation, differentiation, and genetic structure of the populations studied, samples of hair follicles from 474 individuals of different animal categories (calves, yearlings, heifers, cows, and bulls) from three farms, defined as subpopulations "A", "B", and "C", were collected. The animals were genotyped for 17 microsatellite markers using a DNA sequencer. After verification of monomorphic alleles, alleles outside the expected size range, and for the presence of stutter bands, the results were subjected to statistical analysis. Results: The markers used were suitable for the proposed application with a mean Polymorphism Information Content (PIC) of 0.62. On average, the effective alleles were 4.25 per marker, with mean heterozygosities of 0.74 (observed and expected), which was lower in herd A (0.70) in comparison to herds B (0.77) and C (0.74). The analysis of molecular variance (AMOVA) revealed a higher rate of variation within herds (98.5%) and lower among herds (1.5%) (FSTranging from 0.00723 and 0.03198; p-values < 0.05). However no significant differences among herds where found with the Mantel test based on geographic distances. The formation of genetic clusters of all animals sampled with the software Structure resulted in minimum cluster values, with two main genetic groups (K = 2) observed among the evaluated animals. Therefore, based on PIC and heterozygosity values, a wide genetic diversity was observed, despite little differences in population structure (AMOVA, FST, and Structure results) among sampling sites.


Assuntos
Variação Genética , Polimorfismo Genético , Animais , Bovinos/genética , Feminino , Masculino , Brasil , Heterozigoto , Genótipo
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