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1.
Nutr Cancer ; 75(9): 1687-1709, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37553896

RESUMO

Melanoma is a skin cancer with a high mortality rate due to its invasive characteristics. Currently, immunotherapy and targeted therapy increase patient survival but are ineffective in the advanced stages of the tumor. Quercetin (Que) is a natural compound that has demonstrated chemopreventive effects against different types of tumors. This review provides evidence for the therapeutic potential of Que in melanoma and identifies its main targets. The Scopus, Web of Science, and PubMed databases were searched, and studies that used free or encapsulated Que in melanoma models were included, excluding associations, analogs, and extracts. As a result, 73 articles were retrieved and their data extracted. Que has multiple cellular targets in melanoma models, and the main regulated pathways are cell death, redox metabolism, metastasis, and melanization. Que was also able to regulate important targets of signaling pathways, such as PKC, RIG-I, STAT, and P53. In murine models, treatment with Que reduced tumor growth and weight, and decreased metastatic nodules and angiogenic vasculature. Several studies have incorporated Que into carriers, demonstrating improved efficacy and delivery to tumors. Thus, Que is a promising therapeutic agent for the treatment of melanoma; however, further studies are needed to evaluate its effectiveness in clinical trials.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Animais , Camundongos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Quercetina/farmacologia , Quercetina/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Melanoma Maligno Cutâneo
2.
Molecules ; 28(16)2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37630321

RESUMO

Millions of people in the world live in food insecurity, so identifying a tuber with characteristics capable of meeting the demand for food and also identifying active compounds that can be used to minimize harm to human health is of great value. The aim was to carry out a review based on systematic review tools and the main objective was to seek information on botanical, food, pharmacological, and phytochemical aspects of Casimirella sp. and propose possible applications. This review showed papers that addressed botanical, food, pharmacological, and phytochemical aspects of the Mairá-potato and presented suggestions for using this tuber allied to the information described in the works found in the Google Academic, Scielo, Science Direct, Scopus, PubMed, and Web of Science databases. This review synthesized knowledge about the Mairá-potato that can contribute to the direction of further research on the suggested technological applications, both on the use of this tuber as a polymeric material and its use as biomaterial, encapsulation, bioactive use, and 3D printing, because this work collected information about this non-conventional food plant (PANC) that shows great potential for use in various areas of study.


Assuntos
Magnoliopsida , Solanum tuberosum , Humanos , Alimentos , Materiais Biocompatíveis , Bases de Dados Factuais , Compostos Fitoquímicos/farmacologia
3.
Molecules ; 28(18)2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37764435

RESUMO

Açai seeds have been discarded improperly around the Amazonia region, but they can be seen as promising low-cost substrates for fermentation processes. The structural carbohydrates and physicochemical characterization of açai seeds from the Amazonia were assessed followed by the determination of the optimal hydrolysis conditions using H3PO4 (phosphoric acid) and H2SO4 (sulfuric acid) to obtain a liquor with high contents of simple carbohydrates and low levels of potential microbial inhibitors usually generated during acid hydrolysis of carbohydrates. A central composite rotational design was carried out varying the concentrations of diluted acid (0-5%, w/v), solids (0.1-25%, w/v), and hydrolysis time (9.5-110 min). Acid hydrolysis with H2SO4 was more effective in producing reducing sugars (15.9-103.1 g/L) than H3PO4 (2.9-33.9 g/L) during optimization. The optimal hydrolysis conditions with H2SO4 were 3.5% of acid (w/v), 25% of solids during 70 min at 121 °C, which provided a liquor with 55 g/L of reducing sugars and low levels of microbial inhibitors: acetic acid (1.8 g/L), hydroxymethyl furfural (338 mg/L), and furfural (10 mg/L). Thus, açai seeds were characterized as promising agroindustrial waste with high potential to be used as a low-cost substrate in biotechnological processes, comprising relevant environmental and bioeconomic aspects for the development of the Amazonia.


Assuntos
Euterpe , Euterpe/química , Hidrólise , Furaldeído/análise , Carboidratos/química , Sementes/química , Açúcares/análise
4.
Prostaglandins Other Lipid Mediat ; 155: 106553, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33975019

RESUMO

This study aimed to characterize the relationship between the COX2 and ALOX5 genes, as well as their link with the multidrug resistance (MDR) phenotype in sensitive (K562) and MDR (K562-Lucena and FEPS) erythroleukemia cells. For this, the inhibitors of 5-LOX (zileuton) and COX-2 (acetylsalicylic acid-ASA) and cells with the silenced ABCB1 gene were used. The treatment with ASA caused an increase in the gene expression of COX2 and ABCB1 in both MDR cell lines, and a decrease in the expression of ALOX5 in the FEPS cells. Silencing the ABCB1 gene induced a decrease in COX2 expression and an increase in the ALOX5 gene. Treatment with zileuton did not alter the expression of COX2 and ABCB1. Cytometry data showed that there was an increase in ABCB1 protein expression after exposure to ASA. In addition, the increased activity of ABCB1 in the K562-Lucena cell line indicates that ASA may be a substrate for this efflux pump, corroborating the molecular docking that showed that ASA can bind to ABCB1. Regardless of the genetic alteration in COX2 and ABCB1, the direct relationship between these genes and the inverse relationship with ALOX5 remained in the MDR cell lines. We assume that ABCB1 can play a regulatory role in COX2 and ALOX5 during the transformation of the parental cell line K562, explaining the increased gene expression of COX2 and decreased ALOX5 in the MDR cell lines.


Assuntos
Ciclo-Oxigenase 2
5.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445525

RESUMO

Carotenoids are natural lipophilic pigments mainly found in plants, but also found in some animals and can be synthesized by fungi, some bacteria, algae, and aphids. These pigments are used in food industries as natural replacements for artificial colors. Carotenoids are also known for their benefits to human health as antioxidants and some compounds have provitamin A activity. The production of carotenoids by biotechnological approaches might exceed yields obtained by extraction from plants or chemical synthesis. Many microorganisms are carotenoid producers; however, not all are industrially feasible. Therefore, in this review, we provide an overview regarding fungi that are potentially interesting to industry because of their capacity to produce carotenoids in response to stresses on the cultivation medium, focusing on low-cost substrates.


Assuntos
Antioxidantes/metabolismo , Biotecnologia/métodos , Carotenoides/metabolismo , Engenharia Genética , Animais , Humanos , Especificidade por Substrato
6.
Molecules ; 26(2)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440885

RESUMO

This study aimed to identify the volatile compounds in the fermented and dried cocoa beans conducted with three distinct inoculants of yeast species due to their high fermentative capacity: Saccharomyces cerevisiae, Pichia kudriavzevii, the mixture in equal proportions 1:1 of both species, and a control fermentation (with no inoculum application). Three starter cultures of yeasts, previously isolated and identified in cocoa fermentation in the municipality of Tomé-Açu, Pará state, Brazil. The seeds with pulp were removed manually and placed in wooden boxes for the fermentation process that lasted from 6 to 7 days. On the last day of fermentation, the almonds were packaged properly and placed to dry (36 °C), followed by preparation for the analysis of volatile compounds by GC-MS technique. In addition to the control fermentation, a high capacity for the formation of desirable compounds in chocolate by the inoculants with P. kudriavzevii was observed, which was confirmed through multivariate analyses, classifying these almonds with the highest content of aldehydes, esters, ketones and alcohols and low concentration of off-flavours. We conclude that the addition of mixed culture starter can be an excellent alternative for cocoa producers, suggesting obtaining cocoa beans with desirable characteristics for chocolate production, as well as creating a product identity for the producing region.


Assuntos
Cacau/metabolismo , Chocolate/análise , Fermentação , Pichia/metabolismo , Saccharomyces cerevisiae/metabolismo , Compostos Orgânicos Voláteis/análise , Indústria Alimentícia , Sementes/metabolismo
7.
Molecules ; 26(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206169

RESUMO

In addition to the vast diversity of fauna and flora, the Brazilian Amazon has different climatic periods characterized by periods with greater and lesser rainfall. The main objective of this research was to verify the influence of climatic seasons in the Brazilian Amazon (northeast of Pará state) concerning the aromatic and bioactive profiles of fermented and dried cocoa seeds. About 200 kg of seeds was fermented using specific protocols of local producers. Physicochemical analyzes (total titratable acidity, pH, total phenolic compounds, quantification of monomeric phenolics and methylxanthines) and volatile compounds by GC-MS were carried out. We observed that: in the summer, the highest levels of aldehydes were identified, such as benzaldehyde (6.34%) and phenylacetaldehyde (36.73%), related to the fermented cocoa and honey aromas, respectively; and a total of 27.89% of this same class was identified during winter. There were significant differences (p ≤ 0.05, Tukey test) in the profile of bioactive compounds (catechin, epicatechin, caffeine, and theobromine), being higher in fermented almonds in winter. This study indicates that the climatic seasons in the Amazon affect the aromatic and bioactive profiles and could produce a new identity standard (summer and winter Amazon) for the cocoa almonds and their products.


Assuntos
Cacau , Ecossistema , Flavonoides , Fenóis , Estações do Ano , Sementes , Cacau/química , Cacau/metabolismo , Flavonoides/química , Flavonoides/metabolismo , Odorantes , Fenóis/química , Fenóis/metabolismo , Sementes/química , Sementes/metabolismo
8.
An Acad Bras Cienc ; 91(1): e20180262, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30916156

RESUMO

The crimson speckled moth, Utetheisa pulchella (Linnaeus, 1758), is recorded in Brazilian Amazon for the first time. A moth (male) was collected with light trap in a multiple cropping area, in Mojuí dos Campos municipality, Pará State, Brazil. This record expands the area of occurrence and distribution of this rare species in the Neotropical Region. In addition, the occurrence of U. pulchella in the Amazon was unexpected, since this species is generally associated with open ecosystems and drier climates.


Assuntos
Ecossistema , Lepidópteros/fisiologia , Distribuição Animal , Animais , Brasil , Masculino , Mariposas/fisiologia
9.
Nanomedicine ; 11(8): 1975-84, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26238081

RESUMO

Growth factor therapies to induce angiogenesis and thereby enhance the blood perfusion, hold tremendous potential to address the shortcomings of current impaired wound care modalities. Vascular endothelial growth factor stimulates (VEGF) wound healing via multiple mechanisms. Poly(lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. Hence, we hypothesized that the administration of VEGF encapsulated in PLGA nanoparticles (PLGA-VEGF NP) would promote fast healing due to the sustained and combined effects of VEGF and lactate. In a splinted mouse full thickness excision model, compared with untreated, VEGF and PLGA NP, PLGA-VEGF NP treated wounds showed significant granulation tissue formation with higher collagen content, re-epithelialization and angiogenesis. The cellular and molecular studies revealed that PLGA-VEGF NP enhanced the proliferation and migration of keratinocytes and upregulated the expression of VEGFR2 at mRNA level. We demonstrated the combined effects of lactate and VEGF for active healing of non-diabetic and diabetic wounds. FROM THE CLINICAL EDITOR: The study of wound healing has been under a tremendous amount of research over recent years. In diabetic wounds, vasculopathy leading to localized ischemia would often result in delayed wound healing. In this article, the authors encapsulated vascular endothelial growth factor stimulates (VEGF) in PLGA nanoparticles and studies the potential pro-healing effects. It was found that the combination of these two components provided synergistic actions for healing. The encouraging results should provide a basis for combination therapy in the future.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Ácido Láctico/uso terapêutico , Nanopartículas/uso terapêutico , Ácido Poliglicólico/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno/metabolismo , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Ácido Láctico/administração & dosagem , Camundongos , Nanopartículas/administração & dosagem , Neovascularização Fisiológica/efeitos dos fármacos , Peroxidase/metabolismo , Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Fator A de Crescimento do Endotélio Vascular/administração & dosagem
10.
J Food Sci Technol ; 52(6): 3919-24, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26028777

RESUMO

The physical and chemical characteristics of unripe genipap fruits and the proximate and amino acid compositions of the endocarp and mesocarp of the unripe fruits were determined, placing special emphasis on the possible role of the protein-amino acid fraction on the formation of the typical blue pigment of the matrix. The two parts of the fruit analyzed have low energy (49.88 kcal/100 g for mesocarp and 43.48 kcal/100 g for endocarp) and high fiber content (7.88 % for mesocarp and 16.76 % for endocarp). The endocarp showed protein content (3.19 %) five times higher than the mesocarp (0.62 %), which may explain in part the greater amounts of blue pigment formed in the endocarp when compared to the mesocarp. Furthermore, the pH found in mesocarp (4.49) and endocarp (5.21) is within the optimum range for the formation of the blue pigment. A significant color change (ΔE (*) = 26.45) was observed in endocarp during its exposure to the air for 2 h. Free aspartic and glutamic acids and cystine were the predominant amino acids in the mesocarp, while glutamic and aspartic acids and leucine were predominant in the endocarp. According to the results, the formation of blue pigment does not cause any change in the amino acid composition.

11.
Qual Life Res ; 23(3): 953-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24081875

RESUMO

PURPOSE: The aim of this study was to validate the Rhinoplasty Outcomes Evaluation (ROE) questionnaire adapted to the Brazilian Portuguese. METHOD: A prospective study was conducted with ROE administration to 56 patients submitted to rhinoplasty (preoperatively, and then 15-day and 90-day postoperatively) and 100 volunteers without the need or desire of cosmetic or functional nasal surgery. Reliability (internal consistency and test-retest reproducibility), validity, responsiveness and clinical interpretability were assessed. RESULTS: Rhinoplasty patients' mean preoperative score was 7.14, 15 days post-op 17.73 and 90 days post-op 20.50, while controls presented 17.94 points (p < 0.0001), showing the questionnaire's validity and responsiveness. Internal consistency was 0.86. Inter- and intra-examiner test-retest reproducibility was 0.90 and 0.94, respectively. The effect size caused by the surgery was considered large (15 days post-op compared to the preoperative score: effect size = 3.22; 90 days post-op compared to preoperative score: effect size = 4.06). The minimally important difference was 8.67 points, so changes smaller than 9 points in ROE might not be perceived by the patient as an improvement or worsening. CONCLUSION: The Brazilian Portuguese version of ROE is a valid instrument to assess results in rhinoplasty patients.


Assuntos
Avaliação de Resultados da Assistência ao Paciente , Qualidade de Vida , Rinoplastia/psicologia , Inquéritos e Questionários/normas , Adolescente , Adulto , Idoso , Brasil , Estudos de Casos e Controles , Comparação Transcultural , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal/etnologia , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Reprodutibilidade dos Testes , Rinoplastia/métodos , Traduções , Adulto Jovem
12.
Food Chem X ; 22: 101486, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38840720

RESUMO

The study investigated the behavior of seventeen amino acids during spontaneous (SF) and starter culture (SC) fermentation of Criollo cocoa beans from Copallín, Guadalupe and Tolopampa, Amazonas-Peru. For this purpose, liquid chromatography (UHPLC) was used to quantify amino acids. Multivariate analysis was used to differentiate the phases of the fermentation process. The percentage of essential amino acids during SC fermentation (63.4%) was higher than SF (61.8%); it was observed that the starter culture accelerated their presence and increased their concentration during the fermentation process. The multivariate analysis identified a first stage (day 0 to day 2), characterized by a low content of amino acids that increased due to protein hydrolysis. The study showed that adding the starter culture (Saccharomyces cerevisiae) to the fermentation mass increased the concentration of essential amino acids (63.0%) compared to the spontaneous process (61.8%). Moreover, this addition reduced the fermentation time (3-4 days less), demonstrating that the fermentation process with a starter culture allows obtaining a better profile of amino acids precursors of flavor and aroma.

13.
Water Sci Technol ; 67(2): 333-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23168632

RESUMO

Eucalyptus bleached kraft pulp production, an important sector of the Brazilian national economy, is responsible for generating large volume, high pollutant load effluents, containing a considerable fraction of recalcitrant organic matter. The objectives of this study were to quantify the biological activity of the effluent from a eucalyptus bleached kraft pulp mill, characterize the nature of compounds responsible for biological activity and assess the effect of ozone treatment on its removal. Primary and secondary effluents were collected bimonthly over the course of one year at a Brazilian bleached eucalypt kraft pulp mill and their pollutant loads (biochemical oxygen demand (BOD), chemical oxygen demand (COD), total organic carbon (TOC), adsorbable organic halogen (AOX), lignin, extractives) and biological activity (acute and chronic toxicity and estrogenic activity) quantified. The effluent studied did not present acute toxicity to Daphnia, but presented the chronic toxicity effects of algal growth inhibition and reduced survival and reproduction in Ceriodaphnia, as well as estrogenic activity. Chronic toxicity and estrogenic activity were reduced but not eliminated during activated sludge biological treatment. The toxicity identification evaluation revealed that lipophilic organic compounds (such as residual lignin, extractives and their byproducts) were responsible for the toxicity and estrogenic activity. Ozone treatment (50 mg/L O(3)) of the secondary effluent eliminated the chronic toxicity and significantly reduced estrogen activity.


Assuntos
Clareadores/química , Resíduos Industriais/análise , Ozônio/farmacologia , Papel , Esgotos/química , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/toxicidade , Animais , Biodegradação Ambiental/efeitos dos fármacos , Brasil , Clorófitas/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Estrogênios/farmacologia , Peso Molecular , Sifonápteros/efeitos dos fármacos , Testes de Toxicidade
14.
Foods ; 12(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37048267

RESUMO

The objective of this investigation was to develop a nutraceutical product, in bars, using defatted Brazil nut by-products. The methodological bases of analyses followed the guidelines of the Association of Official Analytical Chemists international and experimental tests of formulations. The bars presented with high protein content with high nutraceutical potential expressed as high levels of magnesium, sodium, calcium and potassium, with emphasis on selenium, supplying around 50% of the daily recommendations. The sulfur amino acids reach approximately the recommended chemical score (97%), the aromatic amino acids with a proportion close to 50% and those of the branched chain supplying the established recommendations for adults. In the sensory tests, the formulation that presented the best attributes and the greatest acceptance (91.78% for the flavor and 97.89% for the general impression) by the tasters was the bar formulation made with a 75:25 ratio of defatted Brazil nuts flour and isolated soy protein.

15.
Foods ; 12(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37048271

RESUMO

Jambu (Acmella oleracea) is a vegetable used in human food. Drying is an alternative to increase the shelf life of the product. High temperatures can induce the degradation of carotenoids and reduce the health benefits of these compounds. This study investigated the effect of the Jambu leaves' drying temperature on the carotenoid composition. It was performed previously by screening 16 plants from different localities based on the total carotenoid content. The process of drying by convection was carried out at temperatures of 35, 40, 50, and 60 °C in an air circulation oven, at an air velocity of 1.4 m/s-1 and a processing time of ~20 h. The drying data were fitted to six mathematical models and the quantification of the carotenoid retention was determined by HPLC-DAD. The study demonstrates that the carotenoid content among the samples collected from the 16 producers varied by 72% (lower-175 ± 16 µg/g, higher-618 ± 46 µg/g). Among the models, the Page model was found to be the most suitable model to explain the variation of the experimental data. The drying process at 40 °C reduces the Jambu leaves' carotenoid content significantly (p < 0.05) (All-trans-ß-carotene-86 ± 2 µg/g, All-trans-lutein-141 ± 0.2 µg/g) but does not alter the carotenoid profile. The occurrence of similar reduction behavior was observed for the different carotenoids at all the temperatures studied. The drying process at 35 °C was the condition that ensured the highest retention of carotenoids, and also a product classified as a very high source of carotenoids (total carotenoids-748 ± 27 µg/g, vitamin A-17 ± 1 µg RAE/g). Thus, this study concludes that a temperature of 35 °C for 14 h (air velocity-1.4 m/s-1) is the best drying condition for Jambu leaves using a low-cost dryer and as a possibility for the preservation and marketing of this Amazonian raw material.

16.
Foods ; 12(23)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38231841

RESUMO

Tucupi is a broth derived from cassava roots which is produced after the spontaneous fermentation of manipueira (the liquid portion obtained by pressing cassava roots), followed by cooking. This product is widely consumed along with traditional dishes in the Brazilian Amazonia and is already used in different places worldwide. In this study, tucupi obtained from the markets of Belém (Pará, Brazil) and produced using agroindustrial (11 samples) and non-agroindustrial (11 samples) units were investigated to determine their physicochemical characteristics, total and free HCN contents, and free bioactive amine profiles. Most of the samples showed significant variations (p ≤ 0.05) in pH (2.82-4.67), total acidity (0.14-1.36 g lactic acid/100 mL), reducing sugars (up to 2.33 g/100 mL), and total sugars (up to 4.35 g/100 mL). Regarding the amines, four biogenic amines (0.5-4.2 mg/L tyramine, 1.0-23.1 mg/L putrescine, 0.5-66.8 mg/L histamine, and 0.6-2.9 mg/L tryptamine) and one polyamine (0.4-1.7 mg/L spermidine) were identified in the tucupi samples. Even in the tucupi produced using the agroindustrial units, which had quality seals provided by the local regulatory agency, high levels of biogenic amines (4.4-78.2 mg/L) were observed, as well as high dosages of total (8.87-114.66 mg/L) and free (0.80-38.38 mg/L) HCN. These facts highlight the need for better knowledge regarding the product manufacturing process to establish standardization and high-quality conditions for tucupi processing since high contents of biogenic amines and HCN are commonly associated with adverse health effects.

17.
Antioxidants (Basel) ; 12(5)2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37237978

RESUMO

Eryngium foetidum L. is an edible plant widespread in Amazonian cuisine and its leaves have high levels of promising phenolic compounds for the production of extracts to be used as natural antioxidant additives. In this study, the in vitro scavenging capacity of three freeze-dried extracts of E. foetidum leaves, obtained by ultrasound-assisted extraction using green solvents [water (H2O), ethanol (EtOH), and ethanol/water (EtOH/H2O)], was investigated against the most common reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated in both physiological and food systems. Six phenolic compounds were identified, chlorogenic acid (2198, 1816 and 506 µg/g) being the major compound for EtOH/H2O, H2O, and EtOH extracts, respectively. All E. foetidum extracts were efficient in scavenging all the ROS and RNS (IC50 = 45-1000 µg/mL), especially ROS. The EtOH/H2O extract showed the highest contents of phenolic compounds (5781 µg/g) and showed the highest efficiency in scavenging all the reactive species, with high efficiency for O2•- (IC50 = 45 µg/mL), except for ROO•, for which EtOH extract was the most efficient. Therefore, E. foetidum leaf extracts, especially EtOH/H2O, showed high antioxidant potential to be used as natural antioxidants in food formulations and are promising for nutraceuticals products.

18.
Pharmaceutics ; 14(5)2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35631612

RESUMO

Combination immunotherapy has emerged as a promising strategy to increase the immune response in glioblastoma (GBM) and overcome the complex immunosuppression occurring in its microenvironment. In this study, we hypothesized that combining DNA vaccines-to stimulate a specific immune response-and dual immune checkpoint blockade (ICB)-to decrease the immunosuppression exerted on T cells-will improve the immune response and the survival in an orthotopic unresectable GL261 model. We first highlighted the influence of the insertion position of a GBM epitope sequence in a plasmid DNA vaccine encoding a vesicular stomatitis virus glycoprotein (VSV-G) (here referred to as pTOP) in the generation of a specific and significant IFN-γ response against the GBM antigen TRP2 by inserting a CD8 epitope sequence in specific permissive sites. Then, we combined the pTOP vaccine with anti-PD-1 and anti-CTLA-4 ICBs. Immune cell analysis revealed an increase in effector T cell to Treg ratios in the spleens and an increase in infiltrated IFN-γ-secreting CD8 T cell frequency in the brains following combination therapy. Even if the survival was not significantly different between dual ICB and combination therapy, we offer a new immunotherapeutic perspective by improving the immune landscape in an orthotopic unresectable GBM model.

19.
Plants (Basel) ; 12(1)2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36616256

RESUMO

This study evaluated the effect of convective drying on the degradation of color and phenolic compounds of purple basil (Ocimum basilicum L.) leaves, and the hygroscopic behavior of dried leaves. The fresh leaves underwent drying at 40 °C, 50 °C, 60 °C, and 70 °C. Degradation of chlorophyll, flavonoids, and phenolic compounds were evaluated during drying and the hygroscopicity was evaluated through the moisture sorption isotherms. The drying mathematical modeling and the moisture sorption data were performed. The effective diffusivity for the drying increased from 4.93 × 10−10 m2/s at 40 °C to 18.96 × 10−10 m2/s at 70 °C, and the activation energy value (39.30 kJ/mol) showed that the leaves present temperature sensibility. The leaves dried at 40 °C had less degradation of phenolic compounds and color variation, but the drying process was too slow for practical purposes. Modified Page, Diffusion Approximation, and Verna models had excellent accuracy in drying kinetics. The isotherms showed that, in environments with relative humidity above 50%, the purple basil leaves are more susceptible to water gain, and at 8.83 g H2O/100 g db moisture, it guarantees the microbiological stability of the dried leaves. The Oswin model was the most suitable for estimating the moisture sorption isotherms of the dried leaves.

20.
Eur J Pharm Biopharm ; 171: 39-49, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34998911

RESUMO

Bromodomain and extraterminal domain protein inhibitors (BETi) for cancer treatment did not convince during their first clinical trials. Their epigenetic mechanism of action is still not well understood, even if MYC is generally considered as its main downstream target. In this context, we intended to assess two new nanoformulations of the BETi JQ1 for the treatment of colorectal cancer (CRC). JQ1 was encapsulated at 10 mg/mL in lipid nanocapsules (LNC) or polymeric micelles (PM), both compatible for an intravenous administration. Their effect was compared with free JQ1 on several CRC cell lines in vitro and with daily intraperitoneal cyclodextrin (CD)-loaded JQ1 on the CT26 CRC tumor model in vivo. We showed that LNC preferentially accumulated in tumor, liver, and lymph nodes. LNC-JQ1 and CD-JQ1 similarly delayed tumor growth and increased median survival from 15 to 23 or 20.5 days. JQ1 altered MYC in only two among four CRC cell lines. This MYC-independence found in CT26 was confirmed in vivo by PCR and immunohistochemistry. The main explanation of the JQ1 anticancer effect was an increase in apoptosis. The investigation of its impact on the tumor microenvironment did not show significant effects. Finally, JQ1 association with irinotecan did not synergize in vivo with JQ1 nanoformulations. In conclusion, we demonstrated that the JQ1 anticancer effect was not improved by nanoencapsulation even if their tumor delivery was probably higher. MYC inhibition was not associated to JQ1 efficacy in the case of the CT26 CRC murine model.


Assuntos
Antineoplásicos/farmacologia , Azepinas/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Lipossomos , Nanopartículas , Proteínas/antagonistas & inibidores , Triazóis/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Azepinas/administração & dosagem , Azepinas/uso terapêutico , Linhagem Celular Tumoral/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Infusões Intravenosas , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-myc/metabolismo , Triazóis/administração & dosagem , Triazóis/uso terapêutico
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