Beetroot, A Remarkable Vegetable: Its Nitrate and Phytochemical Contents Can be Adjusted in Novel Formulations to Benefit Health and Support Cardiovascular Disease Therapies

The cardioprotective effects of dietary nitrate from beetroot in healthy and hypertensive individuals are undeniable and irrefutable. Nitrate and nitrate-derived nitrite are precursors for nitric oxide synthesis exhibiting an effect on cardiomyocytes and myocardial ischemia/reperfusion, improving endothelial function, reducing arterial stiffness and stimulating smooth muscle relaxation, decreasing systolic and diastolic blood pressures. Beetroot phytochemicals like betanin, saponins, polyphenols, and organic acids can resist simulated gastrointestinal digestion, raising the hypothesis that the cardioprotective effects of beetroots result from the combination of nitrate/nitrite and bioactive compounds that limit the generation of reactive oxygen species and modulate gene expression. Nitrate and phytochemical concentrations can be adjusted in beet formulations to fulfill requirements for acute or long-term supplementations, enhancing patient adherence to beet intervention. Based on in vitro, in vivo, and clinical trials, beet nitrate and its bioactive phytochemicals are promising as a novel supportive therapy to ameliorate cardiovascular diseases

Identification of Novel Protein Kinase Receptor Type 2 Inhibitors Using Pharmacophore and Structure-Based Virtual Screening

The Protein Kinase Receptor type 2 (RIPK2) plays an important role in the pathogenesis of inflammatory diseases; it signals downstream of the NOD1 and NOD2 intracellular sensors and promotes a productive inflammatory response. However, excessive NOD2 signaling has been associated with various diseases, including sarcoidosis and inflammatory arthritis; the pharmacological inhibition of RIPK2 is an affinity strategy that demonstrates an increased expression of pro-inflammatory secretion activity. In this study, a pharmacophoric model based on the crystallographic pose of ponatinib, a potent RIPK2 inhibitor, and 30 other ones selected from the BindingDB repository database, was built. Compounds were selected based on the available ZINC compounds database and in silico predictions of their pharmacokinetic, toxicity and potential biological activity. Molecular docking was performed to identify the probable interactions of the compounds as well as their binding affinity with RIPK2. The compounds were analyzed to ponatinib and WEHI-345, which also used as a control. At least one of the compounds exhibited suitable pharmacokinetic properties, low toxicity and an interesting binding affinity and high fitness compared with the crystallographic pose of WEHI-345 in complex with RIPK2. This compound also possessed suitable synthetic accessibility, rendering it a potential and very promising RIPK2 inhibitor to be further investigated in regards to different diseases, particularly inflammatory ones

Efficient synthesis and antitumor evaluation of 4-aminomethyl-N-arylpyrazoles: discovery of potent and selective agents for ovarian cancer

A new one-pot two-step sequential methodology for synthesis of novel 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives is reported. One-pot transformation of β-enamino diketones and arylhydrazines generated 4-iminium-N-arylpyrazole salt intermediates in situ, which were easily transformed into 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives by NaBH3CN. The products could be isolated in the free or hydrochloride salt forms. Also, it was possible to obtain the products in the zwitterionic form by ester group hydrolysis. Furthermore, all synthesised compounds were evaluated in vitro against a panel of eight human tumor cell lines. The 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives were much more powerful than the hydrochloride and zwitterionic forms. Moreover, the results suggest that the N-aryl group at the pyrazole ring is vital for modulating antiproliferative activity. The 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-phenylpyrazoles 3a–g exhibited higher inhibitory activities against OVCAR-3, with GI50 values of 0.013–8.78 μM, and lower inhibitory activities against normal human cell lines. Molecular docking was performed to evaluate the probable binding mode of 3a into active site of CDK229COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESSem informaçã

Equilíbrio nutricional e distúrbios fisiológicos em manga 'Tommy Atkins' Nutritional balance and physiological disorders in mango 'Tommy Atkins'

Com o objetivo de avaliar o efeito do equilíbrio nutricional sobre a incidência de distúrbios fisiológicos em manga 'Tommy Atkins' cultivada no Vale do São Francisco, realizou-se um ensaio com frutos coletados no estádio de maturação fisiológica, classificados em frutos sem sintomas e com sintomas de distúrbio fisiológico. Os frutos das duas classes foram separados em casca, polpa e caroço, e levados para secagem em estufa a 65 &deg;C. Este material foi submetido a mineralização para a determinação das concentrações de N, K, Ca, Mg e B. Antes da desidratação, uma parte da polpa foi separada para as determinações do teor de sólidos solúveis totais (SST) e da acidez total titulável (ATT). Os resultados permitem concluir que, tanto as concentrações elevadas de Ca e Mg, como as baixas relações N/Ca e K/Ca, tanto na polpa quanto na casca, foram eficientes na prevenção de distúrbios fisiológicos nos frutos de mangueira; a concentração de nutrientes obtida na casca pode refletir melhor a condição da fisiopatia do que a concentração dos nutrientes na polpa dos frutos; os valores de SST e a relação SST/ATT determinada nos frutos com sintomas foram muito mais elevados do que nos frutos sem sintomas, devido a uma sobrematuração desordenada dos tecidos da polpa.<br>With the objective of evaluating the effect of the nutritional balance on the incidence of physiological disorders in mango cv. Tommy Atkins, grown in São Francisco River Valley, a trial was carried out with fruits harvested at physiological ripening stage, classified as fruits without and with physiological disorder symptoms. From all of them, skin, flesh and pit were separated and dried in a stove at 65ºC. This material was mineralized in order to determine N, K, Ca, Mg and B contents. Before dehydration, part of the flesh was taken for estimation of the total soluble solids (TSS) and total titrable acidity (TTA). The results allow to conclude that: high concentrations of Ca and Mg , as well as low ratios N/Ca and K/Ca, both in the flesh and in the skin, were efficient to prevent physiological disorders in mango fruits; the nutrient concentration in the skin may show better the condition of physiological disorders than the nutrient concentration in fruit flesh; and the TSS values and TSS/TTA ratio in fruits with symptoms were much higher than in fruits without symptoms, due to over ripening of flesh tissues