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1.
Molecules ; 26(14)2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34299488

RESUMO

Nitrogen-containing heterocyclic rings are common structural components of marketed drugs. Among these heterocycles, imidazole/fused imidazole rings are present in a wide range of bioactive compounds. The unique properties of such structures, including high polarity and the ability to participate in hydrogen bonding and coordination chemistry, allow them to interact with a wide range of biomolecules, and imidazole-/fused imidazole-containing compounds are reported to have a broad spectrum of biological activities. This review summarizes recent reports of imidazole/fused imidazole derivatives as anticancer agents appearing in the peer-reviewed literature from 2018 through 2020. Such molecules have been shown to modulate various targets, including microtubules, tyrosine and serine-threonine kinases, histone deacetylases, p53-Murine Double Minute 2 (MDM2) protein, poly (ADP-ribose) polymerase (PARP), G-quadraplexes, and other targets. Imidazole-containing compounds that display anticancer activity by unknown/undefined mechanisms are also described, as well as key features of structure-activity relationships. This review is intended to provide an overview of recent advances in imidazole-based anticancer drug discovery and development, as well as inspire the design and synthesis of new anticancer molecules.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Imidazóis/química , Imidazóis/farmacologia , Animais , Descoberta de Drogas/métodos , Humanos , Relação Estrutura-Atividade
2.
J Biol Chem ; 291(45): 23569-23577, 2016 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-27645997

RESUMO

HIV-1 integrase (IN) is essential for virus replication and represents an important multifunctional therapeutic target. Recently discovered quinoline-based allosteric IN inhibitors (ALLINIs) potently impair HIV-1 replication and are currently in clinical trials. ALLINIs exhibit a multimodal mechanism of action by inducing aberrant IN multimerization during virion morphogenesis and by competing with IN for binding to its cognate cellular cofactor LEDGF/p75 during early steps of HIV-1 infection. However, quinoline-based ALLINIs impose a low genetic barrier for the evolution of resistant phenotypes, which highlights a need for discovery of second-generation inhibitors. Using crystallographic screening of a library of 971 fragments against the HIV-1 IN catalytic core domain (CCD) followed by a fragment expansion approach, we have identified thiophenecarboxylic acid derivatives that bind at the CCD-CCD dimer interface at the principal lens epithelium-derived growth factor (LEDGF)/p75 binding pocket. The most active derivative (5) inhibited LEDGF/p75-dependent HIV-1 IN activity in vitro with an IC50 of 72 µm and impaired HIV-1 infection of T cells at an EC50 of 36 µm The identified lead compound, with a relatively small molecular weight (221 Da), provides an optimal building block for developing a new class of inhibitors. Furthermore, although structurally distinct thiophenecarboxylic acid derivatives target a similar pocket at the IN dimer interface as the quinoline-based ALLINIs, the lead compound, 5, inhibited IN mutants that confer resistance to quinoline-based compounds. Collectively, our findings provide a plausible path for structure-based development of second-generation ALLINIs.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/química , Inibidores de Integrase de HIV/farmacologia , Integrase de HIV/metabolismo , HIV-1/efeitos dos fármacos , Tiofenos/química , Tiofenos/farmacologia , Regulação Alostérica/efeitos dos fármacos , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Domínio Catalítico/efeitos dos fármacos , Cristalografia por Raios X , Descoberta de Drogas , Células HEK293 , Infecções por HIV/virologia , Integrase de HIV/química , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular
3.
Bioorg Med Chem Lett ; 26(19): 4748-4752, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27568085

RESUMO

Employing a scaffold hopping approach, a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) have been synthesized based on an indole scaffold. These compounds incorporate the key elements utilized in quinoline-based ALLINIs for binding to the IN dimer interface at the principal LEDGF/p75 binding pocket. The most potent of these compounds displayed good activity in the LEDGF/p75 dependent integration assay (IC50=4.5µM) and, as predicted based on the geometry of the five- versus six-membered ring, retained activity against the A128T IN mutant that confers resistance to many quinoline-based ALLINIs.


Assuntos
Inibidores de Integrase de HIV/farmacologia , Integrase de HIV/efeitos dos fármacos , Indóis/farmacologia , Regulação Alostérica , Cristalografia por Raios X , Inibidores de Integrase de HIV/química , Ligação de Hidrogênio , Relação Estrutura-Atividade
4.
Front Microbiol ; 15: 1342573, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694802

RESUMO

Introduction: Control of Campylobacter from farm to fork is challenging due to the frequent emergence of antimicrobial-resistant isolates. Furthermore, poultry production systems are known reservoirs of Campylobacter. The twin-arginine translocation (Tat) pathway is a crucial bacterial secretion system that allows Campylobacter to colonize the host intestinal tract by using formate as the main source of energy. However, Tat pathway is also a major contributing factor for resistance to copper sulfate (CuSO4). Methods: Since mammals and chickens do not have proteins or receptors that are homologous to bacterial Tat proteins, identification of small molecule (SM) inhibitors targeting the Tat system would allow the development of safe and effective control methods to mitigate Campylobacter in infected or colonized hosts in both pre-harvest and post-harvest. In this study, we screened 11 commercial libraries (n = 50,917 SM) for increased susceptibility to CuSO4 (1 mM) in C. jejuni 81-176, a human isolate which is widely studied. Results: Furthermore, we evaluated 177 SM hits (2.5 µg/mL and above) that increased the susceptibility to CuSO4 for the inhibition of formate dehydrogenase (Fdh) activity, a Tat-dependent substrate. Eight Tat-dependent inhibitors (T1-T8) were selected for further studies. These selected eight Tat inhibitors cleared all tested Campylobacter strains (n = 12) at >10 ng/mL in the presence of 0.5 mM CuSO4in vitro. These selected SMs were non-toxic to colon epithelial (Caco-2) cells when treated with 50 µg/mL for 24 h and completely cleared intracellular C. jejuni cells when treated with 0.63 µg/mL of SM for 24 h in the presence of 0.5 mM of CuSO4. Furthermore, 3 and 5-week-old chicks treated with SM candidates for 5 days had significantly decreased cecal colonization (up to 1.2 log; p < 0.01) with minimal disruption of microbiota. In silico analyses predicted that T7 has better drug-like properties than T2 inhibitor and might target a key amino acid residue (glutamine 165), which is located in the hydrophobic core of TatC protein. Discussion: Thus, we have identified novel SM inhibitors of the Tat pathway, which represent a potential strategy to control C. jejuni spread on farms.

5.
Curr Nutr Rep ; 12(4): 679-694, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37610590

RESUMO

PURPOSE OF REVIEW: Existing dietary and lifestyle interventions and recommendations, to improve the risk factors of obesity and type 2 diabetes with the target to mitigate this double global epidemic, have produced inconsistent results due to interpersonal variabilities in response to these conventional approaches, and inaccuracies in dietary assessment methods. Precision nutrition, an emerging strategy, tailors an individual's key characteristics such as diet, phenotype, genotype, metabolic biomarkers, and gut microbiome for personalized dietary recommendations to optimize dietary response and health. Precision nutrition is suggested to be an alternative and potentially more effective strategy to improve dietary intake and prevention of obesity and chronic diseases. The purpose of this narrative review is to synthesize the current research and examine the state of the science regarding the effect of precision nutrition in improving the risk factors of obesity and type 2 diabetes. RECENT FINDINGS: The results of the research review indicate to a large extent significant evidence supporting the effectiveness of precision nutrition in improving the risk factors of obesity and type 2 diabetes. Deeper insights and further rigorous research into the diet-phenotype-genotype and interactions of other components of precision nutrition may enable this innovative approach to be adapted in health care and public health to the special needs of individuals. Precision nutrition provides the strategy to make individualized dietary recommendations by integrating genetic, phenotypic, nutritional, lifestyle, medical, social, and other pertinent characteristics about individuals, as a means to address the challenges of generalized dietary recommendations. The evidence presented in this review shows that precision nutrition markedly improves risk factors of obesity and type 2 diabetes, particularly behavior change.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Obesidade/epidemiologia , Obesidade/prevenção & controle , Estado Nutricional , Fatores de Risco , Dieta
6.
PLoS One ; 18(11): e0294361, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38019731

RESUMO

OBJECTIVE: As a new type of consumer subject in the market that was formerly dominated by multiple person families, single households are driving the change in the buying structure. Food purchase activities have undergone significant changes since the outbreak of the COVID-19. The objective of this study was to assess and compare variations in food consumption, purchase and handling during the COVID-19 pandemic between single person households (SPH) and multiple person households. METHOD: A cross-sectional study conducted among 211 individuals in communities in Harris and Waller Counties, Texas. Sociodemographic, food purchase, food consumption and food handling activities during the COVID-19 pandemic were assessed with a validated COVID-19 Nutrition questionnaire. RESULTS: Non-Hispanic Black participants constituted 42.6%, and 28.4% were Hispanics. Participants were made up of mostly aged 18-24 years (39.3%), 47.9% single household composition, 30.4% in full time employment, and 29.1% partook in food assistance programs. A large proportion of them had never used grocery pickup services, online grocery shopping and a farmers' market. During the COVID-19 pandemic, majority of the participants used more of large supermarkets, restaurant/fast food, and online grocery but food consumption seemed to remain the same for the majority of participants. For beverages, majority of participants consumed more water, less soda, and no alcohol. There was a significant association between single person household and higher restaurant/fast foods purchase. Many of the participants reported weight gain and less physical activity during the pandemic. CONCLUSION: Restaurant meal purchases was more prevalent in single-person families. The results from the study have the potential to contribute to how public policy officials, food service, and health authorities forecast how different categories of consumers will react in pandemics and may be used to inform area-specific alleviation strategies to minimize the impact of the COVID-19 pandemic and future events.


Assuntos
COVID-19 , Assistência Alimentar , Humanos , Pandemias , Estudos Transversais , Pessoa Solteira , COVID-19/epidemiologia , Comportamento do Consumidor , Fast Foods , Abastecimento de Alimentos
7.
Food Nutr Res ; 662022.
Artigo em Inglês | MEDLINE | ID: mdl-35140560

RESUMO

BACKGROUND: Dietary diversity is generally considered as a good indicator of nutrient adequacy and is influenced by various factors at the national, household, and individual levels. OBJECTIVE: The present study sought to determine the relationships between household food insecurity, primary caregivers' nutrition knowledge, and dietary diversity of school-aged children in Ghana. METHODS: This forms part of a longitudinal study conducted in the Ayawaso West Municipal district in Accra (urban setting) and the Upper Manya Krobo district (rural setting) in Ghana. Data were collected from a total of 116 caregiver-child dyads using 24-h dietary recall and a short version of the US 12-month Household Food Security Survey Module. Nutrition knowledge and sociodemographic data were obtained using a structured questionnaire. Multivariable logistic regression was used to check for factors associated with children's dietary diversity. RESULTS: Majority of households reported food insecurity, with a higher percentage of insecure households located in the rural area (88.9% vs. 46.5%, P ≤ 0.0001), compared to the urban setting. Diet diversity among the study children was low, with a mean (standard deviation [SD]) of 5.8 (2.1) out of 14 food groups. Children living in food insecure households were three times more likely to have received low diverse diet compared to those from food secure households (adjusted odds ratio [OR] =3.3, 95% confidence interval [CI]: 1.4-8.0). Caregivers' nutrition knowledge was, however, not related to children's dietary diversity. DISCUSSION AND CONCLUSION: Household food insecurity was a main predictor of dietary diversity among school-age children in this study. Thus, caregiver knowledge in nutrition may not be enough, particularly in the presence of food insecurity to guarantee adequate nutrition for school-aged children.

8.
PLoS One ; 17(1): e0262359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34990476

RESUMO

INTRODUCTION: Nutrition literacy has been cited as a crucial life skill. Nutrition education as a primary school subject has been treated inconsequentially when compared to other subjects. We investigated an aspect of the current state of nutrition education in Ghana by engaging stakeholders about their sources of nutrition information and the perceived barriers in implementing nutrition education in mainstream primary schools. METHODS: Three hundred and fifty one (351) primary school children, 121 homebased caregivers, six schoolteachers, two headteachers, two Ghana Education Service (GES) officials, and six school cooks were involved in the study. Surveys were used to collect data on nutrition information acquisition behaviors and to record perceived barriers. Key Informant Interviews were conducted among GES officials, headteachers, schoolteachers and school cooks, while Focus Group Discussions were used among homebased caregivers and children to gather qualitative information. RESULTS: Only 36.3% of the primary school children had heard about nutrition, and 71% of those got nutrition information from their family members. About 70% of homebased caregivers had heard or seen nutrition messages, and their source of nutrition information was predominantly traditional media. Schoolteachers mostly received their nutrition information from non-governmental organizations and the Internet, while most of the school cooks stated their main source of nutrition information was hospital visits. Perceived barriers included schoolteachers' knowledge insufficiency, and lack of resources to adequately deliver nutrition education. Lack of a clear policy appeared to be an additional barrier. CONCLUSION: The barriers to the implementation of nutrition education in the mainstream curriculum at the primary school level that were identified in this study can be resolved by: providing schoolteachers with learning opportunities and adequate nutrition education resources for practical delivery, having specific national policy framework, and including family members and school cooks in the nutrition education knowledge and information dissemination process.


Assuntos
Currículo/normas , Educação em Saúde/normas , Inclusão Escolar/normas , Instituições Acadêmicas/normas , Adulto , Criança , Aconselhamento/educação , Feminino , Grupos Focais/métodos , Gana , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Terapia Nutricional/métodos , Estado Nutricional/fisiologia , Pesquisa Qualitativa
9.
ACS Omega ; 7(5): 4482-4491, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35155940

RESUMO

Human immunodeficiency virus-1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome (AIDS). HIV-1, like all retroviruses, stably integrates its vDNA copy into host chromatin, a process allowing for permanent infection. This essential step for HIV-1 replication is catalyzed by viral integrase (IN) and aided by cellular protein LEDGF/p75. In addition, IN is also crucial for proper virion maturation as it interacts with the viral RNA genome to ensure encapsulation of ribonucleoprotein complexes within the protective capsid core. These key functions make IN an attractive target for the development of inhibitors with various mechanisms of action. We conducted a high-throughput screen (HTS) of ∼370,000 compounds using a homogeneous time-resolved fluorescence-based assay capable of capturing diverse inhibitors targeting multifunctional IN. Our approach revealed chemical scaffolds containing diketo acid moieties similar to IN strand transfer inhibitors (INSTIs) as well as novel compounds distinct from all current IN inhibitors including INSTIs and allosteric integrase inhibitors (ALLINIs). Specifically, our HTS resulted in the discovery of compound 12, with a novel IN inhibitor scaffold amenable for chemical modification. Its more potent derivative 14e similarly inhibited catalytic activities of WT and mutant INs containing archetypical INSTI- and ALLINI-derived resistant substitutions. Further SAR-based optimization resulted in compound 22 with an antiviral EC50 of ∼58 µM and a selectivity index of >8500. Thus, our studies identified a novel small-molecule scaffold for inhibiting HIV-1 IN, which provides a promising platform for future development of potent antiviral agents to complement current HIV-1 therapies.

10.
Curr Nutr Rep ; 10(4): 364-374, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34837637

RESUMO

PURPOSE OF REVIEW: Nutritional status is affected by the COVID-19 pandemic, directly or indirectly. Even with the recent rollout of the coronavirus disease 2019 (COVID-19) vaccines and availability of medicines such as remdesivir, and monoclonal antibodies, host nutritional status is pivotal in the fight against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and outcomes. The purpose of this review is to discuss the effects of COVID-19-related lockdown on lifestyle behaviors, and the nutritional consequences, and the direct sequelae of the infection on nutrition including potential nutritional interventions. RECENT FINDINGS: The COVID-19-related lockdown imposed radical changes in lifestyle behaviors with considerable short-term and long-term health and nutritional consequences including weight gain and obesity and increased cardiometabolic risk, consistently linked to worsened prognosis. The extent of the impact was dependent on food insecurity, overall stress and disordered eating, physical inactivity, and exposure to COVID-19-related nutrition information sources. COVID-19 could directly induce inflammatory responses and poor nutrient intake and absorption leading to undernutrition with micronutrient deficiencies, which impairs immune system function with subsequent amplified risk of infection and disease severity. Nutrition interventions through nutrition support, dietary supplementation, and home remedies such as use of zinc, selenium, vitamin D, and omega-3 fatty acids showed the most significant promise to mitigate the course of COVID-19 infection and improve survival rates. The nutrition-COVID-19 relationship and related dietary changes mimic a vicious cycle of the double burden of malnutrition, both obesity and undernutrition with micronutrient deficiencies, which promote infection, disease progression, and potential death.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis , Humanos , Estado Nutricional , Pandemias , SARS-CoV-2
11.
Diabetol Metab Syndr ; 12: 25, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256715

RESUMO

BACKGROUND: Detecting early type 2 diabetes (T2D) risk factors may reduce or prevent the development of the disease. We conducted a pilot study to generate preliminary data on the perception of T2D and further determined the prevalence of T2D risk factors among college students at an upstate New York campus. METHODS: Metabolic profiles were available for 44 college students for cross-sectional analysis. The American Diabetes Association screening guidelines were used to determine risk factors, and perceived susceptibility, perceived seriousness, and self-efficacy were determined with the Health Belief Model's constructs. Sociodemographic and anthropometric data, nutrition knowledge, and metabolic profiles were obtained. RESULTS: The most common T2D risk factors were lack of physical activity (61.4%), decreased high-density lipoprotein cholesterol (HDL-c, 56.8%), high fasting blood glucose (FBG, 45.5%), family history of T2D (43.2%), increased body mass index (BMI, 36.4%), and high blood pressure (15.9%). A high proportion (70%) of participants with detected impaired FBG perceived they were at low risk of developing T2D. Participants with a family history of T2D (mean rank = 24.2) perceived the seriousness of T2D at a similar level as those without family history (mean rank = 21.2), with no significant difference (U = 205, P = 0.430). Nearly 30% of students did not feel confident they could prevent the development of T2D. Pearson's correlations revealed direct relationships between perceived risk of T2D and BMI (r = 0.49, P = 0.001), fat mass percent (r = 0.51, P < 0.001), and waist circumference (r = 0.42, P = 0.005), and an inverse relationship was found with HDL-c (r = - 0.41, P = 0.005). The association of perceived risk of T2D with a family history of T2D revealed a trend toward significance (Chi-squared = 5.746, P = 0.057), and the association of perceived risk of T2D with physical activity was not significant (Chi-squared = 1.520, P = 0.468). The nutrition knowledge score was 74.32 ± 15.97 (recommended is > 75). However, knowledge scores regarding recommended intake of fruits, vegetables, high sodium foods, and whole grains to prevent T2D were only 36.36%, 34.09%, 47.73%, and 63.6%, respectively. CONCLUSIONS: The discordance between college students' perceived risk and prevalence of T2D risk factors warrants strategies to address misperceptions of T2D risk and improve lifestyle behaviors among this study sample.

12.
Glob Health Promot ; 27(4): 114-122, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32783498

RESUMO

This study was performed to evaluate the effect of a six-week nutrition education intervention on the nutrition knowledge, attitude, practices, and nutrition status of school-age children (aged 6-12 years) in basic schools in Ghana. Short-term effects of nutrition education training sessions on teachers and caregivers were also assessed. Pre-post controlled design was used to evaluate the program. Intervention groups had significantly higher nutrition knowledge scores (8.8 ± 2.0 vs. 5.9 ± 2.1, P < 0.0001) compared to controls in the lower primary level. A higher proportion of children in the intervention group strongly agreed they enjoyed learning about food and nutrition issues compared to the control group (88% vs. 77%, P = 0.031). There was no significant difference in dietary diversity scores (4.8 ± 2.0 vs. 5.1 ± 1.4, P = 0.184) or in measured anthropometric indices (3.6% vs. 8.2%, P = 0.08). A marginally lower proportion of stunted schoolchildren was observed among the intervention group compared to the control group (3.6% vs. 8.2%, P = 0.080). Nutrition knowledge of teachers and caregivers significantly improved (12.5 ± 1.87 vs. 9.2 ± 2.1; P = 0.031) and (5.86 ± 0.73 to 6.24 ± 1.02, P = 0.009), respectively. Nutrition education intervention could have positive impacts on knowledge and attitudes of school children, and may be crucial in the development of healthy behaviors for improved nutrition status.


Assuntos
Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Criança , Gana , Humanos , Estado Nutricional , Instituições Acadêmicas
13.
J Antibiot (Tokyo) ; 72(7): 555-565, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30918323

RESUMO

Campylobacter is a leading cause of bacterial foodborne gastroenteritis worldwide, and poultry are a major source of human campylobacteriosis. The control of Campylobacter from farm to fork is challenging due to emergence of microbial resistance and lack of effective control methods. We identified a benzyl thiophene sulfonamide based small molecule (compound 1) with a minimal inhibitory concentration (MIC) of 100 µM against Campylobacter jejuni 81-176 and Campylobacter coli ATCC33559, good drug-like properties, and low toxicity on eukaryotic cells. Compound 1 was used as a lead for the preparation of 13 analogues. Two analogues, compounds 4 and 8 (TH-4 and TH-8), were identified with better antimicrobial properties than compound 1. TH-4 and TH-8 had a MIC of 12.5 µM and 25 µM for C. coli and 50 µM and 100 µM for C. jejuni, respectively. Cytological studies revealed that both compounds affected C. jejuni envelope integrity. Further, both compounds had no effect on other foodborne pathogens. TH-4 and TH-8 had a minimal impact on the chicken cecal microbiota and were not toxic to colon epithelial cells and chicken macrophages, and red blood cells at 200 µM. Further, TH-4 and TH-8 reduced the Campylobacter load in chicken ceca (up to 2-log reduction) when infected chickens were orally treated for 5 days with 0.254 mg kg-1; as well as against internalized Campylobacter in Caco-2 cells at 12.5 µM and higher. Our study identified two novel specific and safe benzyl thiophene sulfonamide derivatives having potential for control of Campylobacter in chickens and humans.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Campylobacter/efeitos dos fármacos , Sulfonamidas/síntese química , Sulfonamidas/farmacologia , Tiofenos/síntese química , Tiofenos/farmacologia , Animais , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Infecções por Campylobacter/tratamento farmacológico , Infecções por Campylobacter/microbiologia , Campylobacter coli/efeitos dos fármacos , Campylobacter jejuni/efeitos dos fármacos , Ceco/efeitos dos fármacos , Ceco/microbiologia , Linhagem Celular , Galinhas , Colo/efeitos dos fármacos , Colo/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Sulfonamidas/uso terapêutico , Tiofenos/uso terapêutico
14.
BMC Nutr ; 4: 50, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-32153911

RESUMO

BACKGROUND: To report the association of serum 25-hydroxyvitamin D [25(OH)D] and its association with adipokines and cardiometabolic risk factors in Haitian Americans (HA) and African Americans (AA) by ethnicity and type 2 diabetes (T2D) status. METHODS: A cross-sectional study in 197 HA (92 with T2D and 102 without T2D) and 200 AA (97 with T2D and 103 without T2D) recruited in South Florida. Serum 25(OH)D concentrations and adipokines were analyzed by ELISA and cardiometabolic risk factors were indexed by obesity, glycemic control, insulin sensitivity, lipid profile, and blood pressure. RESULTS: Controlling for age, BMI, energy intake, smoking status and HOMA2-IR in multivariate linear regression analyses, serum 25(OH)D concentrations were significantly associated with WC (R2 = 0.760, B = - 0.092, P = 0.027), HbA1C (R2 = 0.142, B = - 0.012, P = 0.010), and TG (R2 = 0.159, B = - 1.192, P = 0.003) in only HA without T2D. While serum 25(OH)D concentrations were significantly associated with TC (R2 = 0.168, B = - 0.329, P = 0.040), log leptin (R2 = 0.544, B = - 0.007, P = 0.021), and adiponectin (R2 = 0.144, B = 0.111, P = 0.033), but slightly associated with LDL-c (R2 = 0.133, B = - 0.278, P = 0.064) in only AA without T2D. Among individuals with T2D, serum 25(OH)D concentrations were marginally associated with IL-6 (R2 = 0.109, B = 0.076, P = 0.085) in HA with T2D, and there was a trend toward significance with log leptin (R2 = 0.393, B = - 0.006, P = 0.075) in AA with T2D in regression analysis. CONCLUSIONS: The findings that the associations of serum 25(OH)D concentrations with adipokines and cardiometabolic factors differ between HA and AA has clinical and public implications to guide design of T2D preventive strategies that are culturally specific even within the same ethnicity.

16.
J Immigr Minor Health ; 18(1): 228-33, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25628028

RESUMO

To validate a sun exposure questionnaire against objective measures of change in skin color and to assess its validity in predicting 25(OH)D in a sample of African Americans and Hispanics with type 2 diabetes. Ninety subjects were enrolled. The sun exposure score was calculated by multiplying the time spent outdoors times the skin exposed score. Skin color was determined by reflectance colorimetry. The relationship between serum 25(OH)D, skin exposure score and stomach skin color was evaluated by a multi-linear regression model. The unadjusted model showed that skin exposure score (P = 0.037), and stomach skin color (P = 0.021) were associated with serum 25(OH)D. This relationship remained significant only for stomach skin color (P = 0.020) after controlling for covariates. It may be possible that the color of the skin is a better predictor of 25(OH)D in this particular population than sun exposure behaviors.


Assuntos
Negro ou Afro-Americano , Diabetes Mellitus Tipo 2/sangue , Hispânico ou Latino , Pigmentação da Pele , Inquéritos e Questionários/normas , Vitamina D/sangue , Adulto , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Florida/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Estômago , Banho de Sol
17.
Front Microbiol ; 7: 405, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27092106

RESUMO

Campylobacter is a leading cause of foodborne bacterial gastroenteritis worldwide and infections can be fatal. The emergence of antibiotic-resistant Campylobacter spp. necessitates the development of new antimicrobials. We identified novel anti-Campylobacter small molecule inhibitors using a high throughput growth inhibition assay. To expedite screening, we made use of a "bioactive" library of 4182 compounds that we have previously shown to be active against diverse microbes. Screening for growth inhibition of Campylobacter jejuni, identified 781 compounds that were either bactericidal or bacteriostatic at a concentration of 200 µM. Seventy nine of the bactericidal compounds were prioritized for secondary screening based on their physico-chemical properties. Based on the minimum inhibitory concentration against a diverse range of C. jejuni and a lack of effect on gut microbes, we selected 12 compounds. No resistance was observed to any of these 12 lead compounds when C. jejuni was cultured with lethal or sub-lethal concentrations suggesting that C. jejuni is less likely to develop resistance to these compounds. Top 12 compounds also possessed low cytotoxicity to human intestinal epithelial cells (Caco-2 cells) and no hemolytic activity against sheep red blood cells. Next, these 12 compounds were evaluated for ability to clear C. jejuni in vitro. A total of 10 compounds had an anti-C. jejuni effect in Caco-2 cells with some effective even at 25 µM concentrations. These novel 12 compounds belong to five established antimicrobial chemical classes; piperazines, aryl amines, piperidines, sulfonamide, and pyridazinone. Exploitation of analogs of these chemical classes may provide Campylobacter specific drugs that can be applied in both human and animal medicine.

18.
J Environ Public Health ; 2014: 315042, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25530764

RESUMO

BACKGROUND: Lack of adherence to dietary and physical activity guidelines has been linked to an increase in chronic diseases in the United States (US). The aim of this study was to assess the association of lifestyle behaviors with self-rated health (SRH). METHODS: This cross-sectional study used self-reported data from Living for Health Program (N = 1,701) which was conducted from 2008 to 2012 in 190 health fair events in South Florida, US. RESULTS: Significantly higher percent of females as compared to males were classified as obese (35.4% versus 27.0%), reported poor/fair SRH (23.4% versus 15.0%), and were less physically active (33.9% versus 25.4%). Adjusted logistic regression models indicated that both females and males were more likely to report poor/fair SRH if they consumed ≤2 servings of fruits and vegetables per day (OR = 2.14, 95% CI 1.30-3.54; OR = 2.86, 95% CI 1.12-7.35, resp.) and consumed mostly high fat foods (OR = 1.58, 95% CI 1.03-2.43; OR = 3.37, 95% CI 1.67-2.43, resp.). The association of SRH with less physical activity was only significant in females (OR = 1.66, 95% CI 1.17-2.35). CONCLUSION: Gender differences in health behaviors should be considered in designing and monitoring lifestyle interventions to prevent cardiovascular diseases.


Assuntos
Dieta , Nível de Saúde , Estilo de Vida , Atividade Motora , Adolescente , Adulto , Estudos Transversais , Feminino , Florida , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
19.
Br J Med Med Res ; 4(26): 4455-4469, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31667161

RESUMO

BACKGROUND: Metabolic outcomes of obesity and its associated disorders may not be equivalent across ethnicity and diabetes status. AIM: In this paper, we examined the association of abdominal obesity, by ethnicity and diabetes status, for indicators of glucose metabolism in Blacks. METHODS: A cross sectional study was conducted in Haitian Americans (n= 186) and African Americans (n= 148) with and without type 2 diabetes mellitus (T2DM). Student's t-test and Chi-squared test were used to assess differences in mean and proportion values between ethnicities with and without type 2 diabetes mellitus. Relationship between insulin resistance, ethnicity, diabetes status, abdominal obesity, and adiponectin levels were analyzed by analysis of covariance while controlling for confounding variables. RESULTS: Haitian American participants were older (P = .032), had higher fasting plasma glucose (P = .036), and A1C (P = .016), but had lower levels of Hs-CRP (P < .001), insulin and HOMA2-IR and lower abdominal obesity (P = .030), than African Americans. Haitian Americans had significantly lower HOMA2-IR (P = .008) than African Americans when comparing both ethnicities with T2DM, high abdominal obesity, and adiponectin levels lower than the median (<14.75 ng/mL). CONCLUSION: The clinical significance of observed differences in insulin resistance, abdominal obesity, and adiponectin levels between Haitian Americans and African Americans could assist in forming public health policies that are ethnic specific.

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