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1.
Nutrients ; 15(18)2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37764837

RESUMO

Moderate red wine intake has been associated with lower cardiovascular mortality, due in part to the intake of polyphenols and anthocyanins, whose content can vary from varietal and year of harvest. This study assessed the vascular effects in response to a single intake of 2015 and 2018 Zweigelt red wines from Hokkaido, Japan. Healthy men were randomly assigned to consume 240 mL each of a red wine, or a sparkling white grape juice as a control in a randomized three-arm cross-over design with a 7 day washout between arms. The augmentation index (AI; a measure of arterial stiffness) and AI at 75 beats/min (AI75), reactive hyperemia index, systolic and diastolic blood pressure (SBP and DBP, respectively), and platelet reactivity were assessed at baseline and two and four hours after each beverage intake. Changes from the baseline were analyzed using a linear mixed model. Significant treatment effects (p = 0.02) were observed, with AI 13% lower after the intake of the 2015 or 2018 vintages compared to the control. Intake of the 2018 vintage reduced SBP and DBP (-4.1 mmHg and -5.6 mmHg, respectively; p = 0.02) compared to the 2015 wine and the control drink. The amount of hydroxytyrosol in the 2018 wine was almost twice the amount as in the 2015 wine, which may help explain the variable blood pressure results. Future studies exploring the vascular effects of the same red wine from different vintage years and different phenolic profiles are warranted.

2.
Adv Nutr ; 14(5): 1005-1028, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37536565

RESUMO

Consumption of nuts and berries are considered part of a healthy eating pattern. Nuts and berries contain a complex nutrient profile consisting of essential vitamins and minerals, fiber, polyunsaturated fatty acids, and phenolics in quantities that improve physiological outcomes. The spectrum of health outcomes that may be impacted by the consumptions of nuts and berries includes cardiovascular, gut microbiome, and cognitive, among others. Recently, new insights regarding the bioactive compounds found in both nuts and berries have reinforced their role for use in precision nutrition efforts. However, challenges exist that can affect the generalizability of outcomes from clinical studies, including inconsistency in study designs, homogeneity of test populations, variability in test products and control foods, and assessing realistic portion sizes. Future research centered on precision nutrition and multi-omics technologies will yield new insights. These and other topics such as funding streams and perceived risk-of-bias were explored at an international nutrition conference focused on the role of nuts and berries in clinical nutrition. Successes, challenges, and future directions with these foods are presented here.


Assuntos
Frutas , Nozes , Humanos , Ácidos Graxos Insaturados , Comportamento Alimentar
3.
Antimicrob Agents Chemother ; 67(4): e0142522, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-36920244

RESUMO

Recent advances on the development of bumped kinase inhibitors for treatment of cryptosporidiosis have focused on the 5-aminopyrazole-4-carboxamide scaffold, due to analogs that have less hERG inhibition, superior efficacy, and strong in vitro safety profiles. Three compounds, BKI-1770, -1841, and -1708, showed strong efficacy in C. parvum infected mice. Both BKI-1770 and BKI-1841 had efficacy in the C. parvum newborn calf model, reducing diarrhea and oocyst excretion. However, both compounds caused hyperflexion of the limbs seen as dropped pasterns. Toxicity experiments in rats and calves dosed with BKI-1770 showed enlargement of the epiphyseal growth plate at doses only slightly higher than the efficacious dose. Mice were used as a screen to check for bone toxicity, by changes to the tibia epiphyseal growth plate, or neurological causes, by use of a locomotor activity box. These results showed neurological effects from both BKI-1770 and BKI-1841 and bone toxicity in mice from BKI-1770, indicating one or both effects may be contributing to toxicity. However, BKI-1708 remains a viable treatment candidate for further evaluation as it showed no signs of bone toxicity or neurological effects in mice.


Assuntos
Antineoplásicos , Antiprotozoários , Criptosporidiose , Cryptosporidium parvum , Animais , Bovinos , Camundongos , Ratos , Criptosporidiose/tratamento farmacológico , Antiprotozoários/farmacologia , Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Oocistos
4.
Nutr Rev ; 81(6): 670-683, 2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-36094616

RESUMO

Lutein, zeaxanthin, and meso-zeaxanthin are three xanthophyll carotenoid pigments that selectively concentrate in the center of the retina. Humans cannot synthesize lutein and zeaxanthin, so these compounds must be obtained from the diet or supplements, with meso-zeaxanthin being converted from lutein in the macula. Xanthophylls are major components of macular pigments that protect the retina through the provision of oxidant defense and filtering of blue light. The accumulation of these three xanthophylls in the central macula can be quantified with non-invasive methods, such as macular pigment optical density (MPOD). MPOD serves as a useful tool for assessing risk for, and progression of, age-related macular degeneration, the third leading cause of blindness worldwide. Dietary surveys suggest that the dietary intakes of lutein and zeaxanthin are decreasing. In addition to low dietary intake, pregnancy and lactation may compromise the lutein and zeaxanthin status of both the mother and infant. Lutein is found in modest amounts in some orange- and yellow-colored vegetables, yellow corn products, and in egg yolks, but rich sources of zeaxanthin are not commonly consumed. Goji berries contain the highest known levels of zeaxanthin of any food, and regular intake of these bright red berries may help protect against the development of age-related macular degeneration through an increase in MPOD. The purpose of this review is to summarize the protective function of macular xanthophylls in the eye, speculate on the compounds' role in maternal and infant health, suggest the establishment of recommended dietary values for lutein and zeaxanthin, and introduce goji berries as a rich food source of zeaxanthin.


Assuntos
Luteína , Degeneração Macular , Feminino , Humanos , Zeaxantinas , Xantofilas , Dieta , Degeneração Macular/prevenção & controle , Suplementos Nutricionais
5.
J Acad Nutr Diet ; 122(3): 614-629, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34728412

RESUMO

The potential role of plant-based foods in the promotion of skin health is an emerging area of nutrition research. Plant-based foods are rich in bioactive compounds, including vitamin C, vitamin E, beta carotene, polyphenols, and phenolic acids, which can contribute to oxidant defense, lower inflammation, and promote structural support of the skin. Epidemiological studies have associated higher intakes of select fruits and vegetables with positive skin health. Beneficial effects of certain fruits, vegetables, nuts, legumes, and polyphenolic-rich beverages on the skin have been reported, with each of these providing a unique phytochemical composition. Although most studies use extracts, this review will focus on data from whole foods and minimally processed products. Collectively, the evidence to date suggests a promising future for plant-based dietary interventions that promote skin barrier health and function. However, additional research is required to address issues such as the optimal quality and duration of intake as well as potential mechanisms. Studies in the above areas will help formulate specific targeted dietary recommendations.


Assuntos
Dieta Vegetariana , Plantas Comestíveis , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Fabaceae , Frutas , Humanos , Nozes , Polifenóis , Verduras
6.
Nutrients ; 13(12)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34959963

RESUMO

Age-related macular degeneration (AMD) is the third leading cause of blindness worldwide. Macular pigment optical density (MPOD), a biomarker for AMD, is a non-invasive measure to assess risk. The macula xanthophyll pigments lutein (L) and zeaxanthin (Z) protect against blue light and provide oxidant defense, which can be indexed by MPOD. This study examined the effects of Z-rich goji berry intake on MPOD and skin carotenoids in healthy individuals. A randomized, unmasked, parallel-arm study was conducted with 27 participants, aged 45-65, who consumed either 28 g of goji berries or a supplement containing 6 mg L and 4 mg Z (LZ), five times weekly for 90 days. After 90 days, MPOD was significantly increased in the goji berry group at 0.25 and 1.75 retinal eccentricities (p = 0.029 and p = 0.044, respectively), while no changes were noted in the LZ group. Skin carotenoids were significantly increased in the goji berry group at day 45 (p = 0.025) and day 90 (p = 0.006), but not in the LZ group. Regular intake of goji berries in a healthy middle-aged population increases MPOD may help prevent or delay the development of AMD.


Assuntos
Suplementos Nutricionais , Ingestão de Alimentos/fisiologia , Luteína/metabolismo , Lycium , Macula Lutea/metabolismo , Degeneração Macular/prevenção & controle , Pigmento Macular/metabolismo , Zeaxantinas/metabolismo , Idoso , Carotenoides/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Degeneração Macular/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pele/metabolismo
7.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925062

RESUMO

Cardiovascular disease is a leading cause of death globally, presenting an immense public and economic burden. Studies on cardioprotective foods and their bioactive components are needed to address both personal and public health needs. Date fruit is rich in polyphenols, particularly flavonoids, certain micronutrients, and dietary fiber, which can impact vascular health, and have the potential to attenuate vascular disease in humans. Data from in vitro and animal studies report that consumption of date fruit or extracts can modulate select markers of vascular health, particularly plasma lipid levels including triglycerides and cholesterol, indices of oxidative stress and inflammation, but human data is scant. More investigation is needed to better characterize date polyphenols and unique bioactive compounds or fractions, establish safe and effective levels of intake, and delineate underlying mechanisms of action. Implementing scientific rigor in clinical trials and assessment of functional markers of vascular disease, such as flow-mediated dilation and peripheral arterial tonometry, along with gut microbiome profiles would provide useful information with respect to human health. Emerging data supports the notion that intake of date fruit and extracts can be a useful component of a healthy lifestyle for those seeking beneficial effects on vascular health.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Saudável , Frutas , Phoeniceae , Animais , Cardiotônicos/administração & dosagem , Cardiotônicos/química , Doenças Cardiovasculares/sangue , Feminino , Frutas/química , Humanos , Lipídeos/sangue , Masculino , Phoeniceae/química , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem
8.
Nutrients ; 12(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158079

RESUMO

Mangos are rich in ß-carotene and other carotenoids, along with several phenolic acids that may provide oxidant defense and photoprotection to the skin. The objectives of this study are to investigate the effects of Ataulfo mango intake on the development of facial wrinkles and erythema. A randomized two-group parallel-arm study was conducted to assess 16 weeks of either 85 g or 250 g of mango intake in healthy postmenopausal women with Fitzpatrick skin type II or III. Facial photographs were captured at weeks 0, 8, and 16, and wrinkles at the lateral canthi and erythema at the cheeks were quantified. Skin carotenoid values were measured with reflection spectroscopy. Deep wrinkle severity decreased significantly in the 85 g group after 8 (p = 0.007) and 16 (p = 0.03) weeks compared to baseline measures. In contrast, those in the 250 g group showed an increase after 16 weeks in average wrinkle severity (p = 0.049), average wrinkle length (p = 0.007), fine wrinkle severity (p = 0.02), and emerging wrinkle severity (p = 0.02). Erythema in the cheeks increased with 85 g of mango intake (p = 0.04). The intake of 85 g of mangos reduced wrinkles in fair-skinned postmenopausal women, while an intake of 250 g showed the opposite effect. Further studies feeding 85 g of mangos are warranted.


Assuntos
Eritema/fisiopatologia , Comportamento Alimentar , Frutas/química , Mangifera/química , Pós-Menopausa/fisiologia , Envelhecimento da Pele/fisiologia , Idoso , Pressão Sanguínea , Carotenoides/metabolismo , Ingestão de Alimentos , Eritema/sangue , Feminino , Humanos , Lipídeos/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Pele/metabolismo
9.
Int J Parasitol ; 50(5): 413-422, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32224121

RESUMO

Bumped Kinase Inhibitors, targeting Calcium-dependent Protein Kinase 1 in apicomplexan parasites with a glycine gatekeeper, are promising new therapeutics for apicomplexan diseases. Here we will review advances, as well as challenges and lessons learned regarding efficacy, safety, and pharmacology that have shaped our selection of pre-clinical candidates.


Assuntos
Apicomplexa/efeitos dos fármacos , Coccidiose/tratamento farmacológico , Inibidores de Proteínas Quinases , Animais , Apicomplexa/metabolismo , Criptosporidiose/tratamento farmacológico , Cryptosporidium/efeitos dos fármacos , Cryptosporidium/metabolismo , Humanos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/efeitos dos fármacos , Proteínas Quinases/metabolismo , Toxoplasma/efeitos dos fármacos , Toxoplasma/metabolismo , Toxoplasmose/tratamento farmacológico
10.
Food Funct ; 11(1): 32-44, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31942892

RESUMO

Cardiovascular disease is a leading cause of death in the United States and much of the developed world, costing billions of dollars in lost work time, lower productivity and high health care expenditures. Research on foods and bioactive food components that have cardioprotective benefits may provide new insights as to how modest changes in one's diet may result in a reduced risk of vascular disease. In intervention trials, the consumption of strawberries, either fresh or freeze-dried, has been reported to improve select markers of cardiovascular health, including improved lipid profiles, microvascular function, and platelet reactivity. Consistent with the above, epidemiological studies suggest beneficial effects of strawberries on vascular function. Preliminary studies on the effects of freeze-dried strawberry powder on vascular health are reviewed in the current paper.


Assuntos
Cardiotônicos/administração & dosagem , Sistema Cardiovascular , Frutas , Lipídeos/sangue , Adolescente , Biomarcadores , Doenças Cardiovasculares/prevenção & controle , Dieta , Fragaria , Liofilização , Humanos , Masculino , Pós , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Cancers (Basel) ; 11(10)2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31590367

RESUMO

Pancreatic cancer is a complex disease, in need of new therapeutic approaches. In this study, we explored the effect and mechanism of action of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, alone and in combination with current chemotherapeutics on pancreatic cancer cell growth, focusing on glycolysis metabolism. Moreover, we investigated whether EGCG's effect is dependent on its ability to induce reactive oxygen species (ROS). EGCG reduced pancreatic cancer cell growth in a concentration-dependent manner and the growth inhibition effect was further enhanced under glucose deprivation conditions. Mechanistically, EGCG induced ROS levels concentration-dependently. EGCG affected glycolysis by suppressing the extracellular acidification rate through the reduction of the activity and levels of the glycolytic enzymes phosphofructokinase and pyruvate kinase. Cotreatment with catalase abrogated EGCG's effect on phosphofructokinase and pyruvate kinase. Furthermore, EGCG sensitized gemcitabine to inhibit pancreatic cancer cell growth in vitro and in vivo. EGCG and gemcitabine, given alone, reduced pancreatic tumor xenograft growth by 40% and 52%, respectively, whereas the EGCG/gemcitabine combination reduced tumor growth by 67%. EGCG enhanced gemcitabine's effect on apoptosis, cell proliferation, cell cycle and further suppressed phosphofructokinase and pyruvate kinase levels. In conclusion, EGCG is a strong combination partner of gemcitabine reducing pancreatic cancer cell growth by suppressing glycolysis.

12.
Nutrients ; 11(8)2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31405071

RESUMO

Most pancreatic cancers are usually diagnosed at an advanced stage when they have already metastasized. Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, has been shown to reduce pancreatic cancer growth, but its effect on metastasis remains elusive. This study evaluated the capacity of EGCG to inhibit pancreatic cancer cell migration and invasion and the underlying mechanisms. EGCG reduced pancreatic cancer cell growth, migration, and invasion in vitro and in vivo. EGCG prevented "Cadherin switch" and decreased the expression level of TCF8/ZEB1, ß-Catenin, and Vimentin. Mechanistically, EGCG inhibited the Akt pathway in a time-dependent manner, by suppressing IGFR phosphorylation and inducing Akt degradation. Co-treatment with catalase or N-Acetyl-L-cysteine did not abrogate EGCG's effect on the Akt pathway or cell growth. Moreover, EGCG synergized with gemcitabine to suppress pancreatic cancer cell growth, migration, and invasion, through modulating epithelial-mesenchymal transition markers and inhibiting Akt pathway. In summary, EGCG may prove beneficial to improve gemcitabine sensitivity in inhibiting pancreatic cancer cell migration and invasion, to some extent through the inhibition of Akt pathway and epithelial-mesenchymal transition.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Catequina/análogos & derivados , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Catequina/farmacologia , Linhagem Celular Tumoral , Desoxicitidina/farmacologia , Estabilidade Enzimática , Humanos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteólise , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Carga Tumoral , Gencitabina
13.
J Med Food ; 22(10): 982-992, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31194598

RESUMO

Osteoporosis and cardiovascular disease are global health burdens, with postmenopausal women being at great risk. Dried plums/prunes (DPs) have been reported to provide bone health benefits in animal models, which is consistent with in vitro models. Data from human studies suggest that DP intake can enhance lipid metabolism, anti-inflammatory, and oxidant defense systems, which can impact cardiovascular health. We tested the hypothesis that short-term consumption of low and reasonable levels of DPs augments bone resorption and vascular function. Twenty-seven healthy, postmenopausal women were randomly assigned to consume six DPs (∼42 g) or two DPs (∼14 g) per day for 2 weeks, then a 2-week washout period and then crossed over. Serum C-telopeptide, beta-crosslinked (CTX) was used as a measure of bone resorption. Peripheral artery tonometry (PAT) was used to assess microvascular function. The pattern of changes in CTX in the second 2-week period (no change or decline) differed significantly from the pattern in the first 2 weeks (increases in both groups; F = 9.26, P = .006), suggesting a trend in CTX reduction (i.e., a decrease in bone resorption) in those consuming six DPs per day in the second phase. No effects on vascular function were noted. A significant interaction was observed for the augmentation index, a measure of arterial stiffness, between treatment and years after menopause (P = .045). The results suggest a potentially favorable impact of DPs on bone health when assessed with a short-term, crossover study design in postmenopausal women. Given the novel assessments used in this study, follow-up studies are warranted.


Assuntos
Reabsorção Óssea , Colágeno Tipo I/sangue , Frutas , Peptídeos/sangue , Prunus domestica , Rigidez Vascular , Idoso , Glicemia/análise , Pressão Sanguínea , Estudos Cross-Over , Feminino , Humanos , Lipídeos/sangue , Manometria , Pessoa de Meia-Idade , Pós-Menopausa
14.
J Nutr Biochem ; 68: 51-58, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31030167

RESUMO

Walnut consumption can provide both vascular and metabolic health benefits, and walnut-induced changes in lipoprotein particle chemical payloads may be responsible for these health benefits. To explore this possibility with a focus on metabolic health, this study investigated the impact of walnut consumption on lipoprotein lipid composition and changes in LDL anti-inflammatory properties, as reported by inflamed adipocyte. Hypercholesterolemic, postmenopausal females were treated with 40 g/day (i.e., 1.6 servings/day; n=15) of walnuts for 4 weeks. Fatty acids and their oxygenated metabolites, i.e., oxylipins, were quantified in isolated lipoproteins. Human primary adipocytes were exposed to LDL and TNFα-stimulated adipokine production was measured. Walnut treatment elevated α-linolenic acid and its epoxides in all lipoproteins and depleted mid-chain alcohols in VLDL and LDL, but not HDL. Walnuts also reduced TNFα-induced diabetic adipocyte production of IL-6 (-48%, P=.0006) and IL-8 (-30%, P=.01), changes inversely correlated with levels of α-linolenic acid-derived epoxides but not α-linolenic acid itself. In conclusion, modest walnut consumption can alter lipoprotein lipid profiles and enhance their ability to inhibit TNFα-dependent pro-inflammatory responses in human diabetic primary adipocytes. Moreover, this study suggests the oxylipins, rather than the parent fatty acids, mediate LDL action of adipocytes.


Assuntos
Adipócitos/metabolismo , Citocinas/metabolismo , Hipercolesterolemia/dietoterapia , Juglans , Lipoproteínas/sangue , Nozes , Adipócitos/efeitos dos fármacos , Adipócitos/patologia , Adipocinas/metabolismo , Células Cultivadas , Diabetes Mellitus/patologia , Ácidos Graxos/análise , Ácidos Graxos/sangue , Feminino , Humanos , Lipoproteínas/química , Pessoa de Meia-Idade , Oxilipinas/sangue , Oxilipinas/química , Fator de Necrose Tumoral alfa/farmacologia
15.
J Med Chem ; 62(6): 3135-3146, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30830766

RESUMO

Cryptosporidium is a leading cause of pediatric diarrhea worldwide. Currently, there is neither a vaccine nor a consistently effective drug available for this disease. Selective 5-aminopyrazole-4-carboxamide-based bumped-kinase inhibitors (BKIs) are effective in both in vitro and in vivo models of Cryptosporidium parvum. Potential cardiotoxicity in some BKIs led to the continued exploration of the 5-aminopyrazole-4-carboxamide scaffold to find safe and effective drug candidates for Cryptosporidium. A series of newly designed BKIs were tested for efficacy against C. parvum using in vitro and in vivo (mouse infection model) assays and safety issues. Compound 6 (BKI 1708) was found to be efficacious at 8 mg/kg dosed once daily (QD) for 5 days with no observable signs of toxicity up to 200 mg/kg dosed QD for 7 days. Compound 15 (BKI 1770) was found to be efficacious at 30 mg/kg dosed twice daily (BID) for 5 days with no observable signs of toxicity up to 300 mg/kg dosed QD for 7 days. Compounds 6 and 15 are promising preclinical leads for cryptosporidiosis therapy with acceptable safety parameters and efficacy in the mouse model of cryptosporidiosis.


Assuntos
Antiprotozoários/uso terapêutico , Ácidos Carboxílicos/química , Criptosporidiose/tratamento farmacológico , Pirazóis/farmacologia , Animais , Antiprotozoários/farmacocinética , Linhagem Celular , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Desenvolvimento de Medicamentos , Humanos , Interferon gama/genética , Camundongos , Camundongos Knockout , Pirazóis/química , Pirazóis/farmacocinética
16.
Food Funct ; 9(11): 5682-5696, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30310905

RESUMO

Numerous studies propose that epigallocatechin-3-gallate (EGCG), an abundant polyphenol in green tea, has anti-cancer properties. However, its mechanism of action in breast cancer remains unclear. This study investigated the capacity of EGCG to suppress breast cancer cell growth in vitro and in vivo, characterizing the underlying mechanisms, focusing on the effect of EGCG on glucose metabolism. EGCG reduced breast cancer 4T1 cell growth in a concentration- (10-320 µM) and time- (12-48 h) dependent manner. EGCG induced breast cancer apoptotic cell death at 24 h, as evidenced by annexin V/PI, caspase 3, caspase 8 and caspase 9 activation. Furthermore, EGCG affected the expression of 16 apoptosis-related genes, and promoted mitochondrial depolarization. EGCG induced autophagy concentration-dependently in 4T1 cells by modulating the levels of the autophagy-related proteins Beclin1, ATG5 and LC3B. Moreover, EGCG affected glucose, lactate and ATP levels. Mechanistically, EGCG significantly inhibited the activities and mRNA levels of the glycolytic enzymes hexokinase (HK), phosphofructokinase (PFK), and lactic dehydrogenase (LDH), and to a lesser extent the activity of pyruvate kinase (PK). In addition, EGCG decreased the expression of hypoxia-inducible factor 1α (HIF1α) and glucose transporter 1 (GLUT1), critical players in regulating glycolysis. In vivo, EGCG reduced breast tumor weight in a dose-dependent manner, reduced glucose and lactic acid levels and reduced the expression of the vascular endothelial growth factor (VEGF). In conclusion, EGCG exerts an anti-tumor effect through the inhibition of key enzymes that participate in the glycolytic pathway and the suppression of glucose metabolism.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Catequina/análogos & derivados , Proliferação de Células/efeitos dos fármacos , Glucose/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Catequina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Polifenóis/farmacologia , Chá/química , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Am Coll Nutr ; 37(7): 553-567, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29718795

RESUMO

An individual's diet affects numerous physiological functions and can play an important role in reducing the risk of cardiovascular disease. Epidemiological and clinical studies suggest that dietary flavanols can be an important modulator of vascular risk. Diets and plant extracts rich in flavanols have been reported to lower blood pressure, especially in prehypertensive and hypertensive individuals. Flavanols may act in part through signaling pathways that affect vascular function, nitric oxide availability, and the release of endothelial-derived relaxing and constricting factors. During exercise, flavanols have been reported to modulate metabolism and respiration (e.g., maximal oxygen uptake, O2 cost of exercise, and energy expenditure), and reduce oxidative stress and inflammation, resulting in increased skeletal muscle efficiency and endurance capacity. Flavanol-induced reductions in blood pressure during exercise may decrease the work of the heart. Collectively, these effects suggest that flavanols can act as an ergogenic aid to help delay the onset of fatigue. More research is needed to better clarify the effects of flavanols on vascular function, blood pressure regulation, and exercise performance and establish safe and effective levels of intake. Flavanol-rich foods and food products can be useful components of a healthy diet and lifestyle program for those seeking to better control their blood pressure or to enhance their physical activity. Key teaching points • Epidemiological and clinical studies indicate that dietary flavanols can reduce the risk of vascular disease. • Diets and plant extracts rich in flavanols have been reported to lower blood pressure and improve exercise performance in humans. • Mechanisms by which flavanols may reduce blood pressure function include alterations in signaling pathways that affect vascular function, nitric oxide availability, and the release of endothelial-derived relaxation and constriction factors. • Mechanisms by which flavanols may enhance exercise performance include modulation of metabolism and respiration (e.g., maximal oxygen uptake, O2 cost of exercise, and energy expenditure) and reduction of oxidative stress and inflammation. These effects can result in increased skeletal muscle efficiency and endurance capacity. • Further research is needed to clarify the amount, timing, and frequency of flavanol intake for blood pressure regulation and exercise performance.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Dieta , Exercício Físico/fisiologia , Flavonóis/farmacologia , Flavonóis/administração & dosagem , Humanos
18.
Int J Parasitol ; 47(12): 753-763, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28899690

RESUMO

Improvements have been made to the safety and efficacy of bumped kinase inhibitors, and they are advancing toward human and animal use for treatment of cryptosporidiosis. As the understanding of bumped kinase inhibitor pharmacodynamics for cryptosporidiosis therapy has increased, it has become clear that better compounds for efficacy do not necessarily require substantial systemic exposure. We now have a bumped kinase inhibitor with reduced systemic exposure, acceptable safety parameters, and efficacy in both the mouse and newborn calf models of cryptosporidiosis. Potential cardiotoxicity is the limiting safety parameter to monitor for this bumped kinase inhibitor. This compound is a promising pre-clinical lead for cryptosporidiosis therapy in animals and humans.


Assuntos
Criptosporidiose/tratamento farmacológico , Cryptosporidium parvum/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Administração Oral , Animais , Animais Recém-Nascidos , Bovinos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Coração/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Interferon gama/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Testes de Mutagenicidade , Gravidez , Ligação Proteica , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/sangue , Inibidores de Proteínas Quinases/toxicidade , Segurança
19.
Food Chem ; 232: 777-787, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28490140

RESUMO

Antioxidant properties and flavor characteristic profile of pomegranate wine during winemaking were investigated. The total phenol content and radical scavenging activity exhibited a slightly decrease in the end edge. Punicalagins and gallic acid were revealed to be the most abundant phenolic compounds, followed by ellagic acid and vanillic acid. These constituents were mainly responsible for the effective antioxidant capacity of pomegranate wine. The major changes of flavor qualities occurred in the initial stage, particularly 0-4day of fermentation. Fermentation significantly reduced the relative content of aldehydes, ketones, heterocyclic and aromatic compounds, but promoted the generation of esters and alcohols. This is the first time of using E-nose and E-tongue to monitor odour and taste changes in the brewing process of pomegranate wine. The study may provide a promising instruction for improving functional features and quality control of the pomegranate wine.


Assuntos
Antioxidantes , Vinho , Fermentação , Frutas , Lythraceae
20.
J Dairy Sci ; 100(5): 3413-3423, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28284699

RESUMO

Glucosamine (GlcN) and microbial transglutaminase (Tgase) are used separately or together to improve the emulsifying properties of whey protein isolate (WPI). However, little is known about how the emulsifying properties change when GlcN residues are incorporated into WPI cross-linked by Tgase. We used Tgase as a biocatalyst to cross-link WPI in the presence of GlcN in a liquid system for 12 h at a moderate temperature (25°C). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analyses indicated that protein polymerization and GlcN conjugation occurred simultaneously, phenomena also supported by the loss of free amines (9.4-20.5%). Addition of 5 U Tgase/g protein improved the emulsifying properties of moderately cross-linked WPI polymers. The Tgase-treated WPI polymers had a larger particle size (∼2.6-fold) than native WPI, which may have reduced coalescence and flocculation in an oil-in-water emulsion system. However, the incorporation of GlcN residues into WPI, predominantly via enzymatic glycation, partly inhibited the cross-links between the WPI molecules catalyzed by Tgase, reducing the size of the WPI polymers 0.81- to 0.86-fold). Consequently, WPI+GlcN conjugates provided less stability to the emulsion. Moreover, high NaCl concentration (0.2 M) decreased the emulsifying properties of the WPI+GlcN conjugates by neutralizing negative electric charges in the glycoconjugates. However, the improved emulsifying properties of WPI cross-linked by Tgase may be useful in food processing at higher NaCl concentrations due to the formation of the thicker steric barrier at the oil-water interface.


Assuntos
Proteínas do Leite/metabolismo , Proteínas do Soro do Leite , Animais , Emulsões/química , Glucosamina , Transglutaminases/metabolismo
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