The present investigation describes the synthesis of novel cinnamides and a bis cinnamate bearing 1,2,3-triazole functionalities and investigation of their antiproliferative and antimetastatic effects on melanoma cells. The necessity for the development of new chemotherapeutic agents for melanoma treatment motivated this work. Sixteen derivatives were obtained with yields ranging from 23-81% and fully characterized by spectroscopic (1H and 13C nuclear magnetic resonance, infrared) and spectrometric high resolution mass spectrometry (HRMS) techniques. The derivatives were in vitro evaluated against B16-F10 murine melanoma cell line. The most effective compound (a bis cinnamate) (6b) reduced the melanoma cell viability, generated cell cycle arrest, and influenced the metastatic behavior of melanoma cells by decreasing migration, invasion, and colony formation. Based on these findings, it is believed that compound 6b may represent an interesting scaffold to be explored toward the development of new antimelanoma agents.

O plasma rico em plaquetas (PRP) é um produto derivado da centrifugação do sangue total, sendo rico em fatores bioativos, como os de crescimento. Apesar da ampla utilização em processos cicatriciais, há controvérsia sobre a eficácia da terapia na cicatrização cutânea. O objetivo desse estudo foi quantificar e comparar a concentração dos fatores TGF-β1 e PDGF-BB no PRP, plasma sanguíneo e pele, durante diferentes fases do processo de cicatrização da pele tratada ou não com PRP. Foram utilizados sete equinos machos castrados, mestiços, hígidos, com idade entre 16 e 17 (16,14±0,63) anos. Três lesões em formato quadrangular (6,25cm²) foram produzidas cirurgicamente nas regiões glúteas direita e esquerda de todos os animais. Doze horas após indução das feridas, 0,5mL do PRP foi administrado em cada uma das quatro extremidades das feridas de uma das regiões glúteas (Grupo tratado = GT), escolhida aleatoriamente. A região contralateral foi utilizada como controle (GC). As feridas foram submetidas à limpeza diária com água Milli Q, e amostras foram obtidas mediante biópsias realizadas com Punch de 6mm. Foram obtidas seis biópsias de pele, sendo a primeira realizada logo após a produção da ferida (T0), e as demais com 1 (T1) 2 (T2) 7 (T3) e 14 (T4) dias após a indução da lesão. A sexta biópsia (T5) foi obtida após completo fechamento da pele, que ocorreu aproximadamente aos 37 dias (36,85±7,45, GC; 38,85±6,46, GT). Também foram obtidas amostras de sangue com EDTA em todos os tempos mencionados. A quantificação dos fatores de crescimento TGF-β1 e PDGF-BB na pele, PRP e plasma sanguíneo foi realizada pela técnica ELISA. Os dados foram analisados estatisticamente pelo teste t, correlação de Pearson e regressão, utilizando nível de significância de 5%. Não houve diferença entre os grupos, nos valores dos dois fatores de crescimento mensurados na pele, nos diferentes tempos. Também não houve correlação entre a quantidade dos fatores de crescimento presentes na pele e no plasma. Por outro lado, correlação positiva foi observada entre PRP e pele no grupo tratado, para os fatores de crescimento TGF-β1 (r=0,31) e PDGF-BB (r=0,38), bem como entre ambos os fatores de crescimento presentes no PRP (r=0,81). Considerando as concentrações dos fatores de crescimento no T0, os maiores valores cutâneos (p<0,05) do TGF-β1, em ambos os grupos, ocorreram nos tempos T3 e T5. Valores mais elevados (p<0,05) do PDGF-BB ocorreram no T4 (GT) e T5 (GC). No plasma não houve alteração nas concentrações desses fatores em relação ao T0, o que sugere que o PRP não acarreta efeito sistêmico, quando os procedimentos adotados na presente pesquisa são utilizados. A administração local de PRP no volume estudado, 12 h após indução cirúrgica de ferida cutânea na região glútea de equinos não ocasiona maiores concentrações dos fatores de crescimento TGF-β1 e PDGF-BB no plasma sanguíneo e pele, durante o processo de cicatrização.

Platelet-rich plasma (PRP) is a product derived from total blood centrifugation, rich in bioactive factors, such as growth factors. Despite largely used in healing processes, there is a controversy whether the therapy is effective in promoting skin healing. The objective of this study was to quantify and compare the concentrations of the factors TGF-β1 and PDGF-BB in PRP, blood plasma and skin, at different phases of the healing process of skin treated or not with PRP. Seven healthy crossbred 16 to 17-year-old geldings (16.14±0.63) were used. Three quadrangular-shaped lesions (6.25cm²) were surgically induced into the right and left gluteal regions of all animals. Twelve hours after induction of the wounds, 0.5mL of the PRP was administered in each of the four edges of the wound in one of the gluteal regions (Treated group = TG) randomly chosen. The contralateral region was used as control (CG). The wounds were submitted to daily cleaning with Milli-Q water, and samples were obtained with a 6mm diameter biopsy Punch. Six skin biopsies were obtained, the first carried out immediately after the production of the wound (T0), and the others 1 (T1), 2 (T2), 7 (T3), and 14 (T4) days after the lesion was induced. The sixth biopsy (T5) was obtained after complete healing of the skin, which occurred at about day 37 (36.85±7.45, CG; 38.85±6.46, TG). EDTA blood samples were also obtained, at all the times mentioned. Quantification of TGF-β1 and PDGF-BB growth factors on the skin, PRP, and blood plasma was carried out by the ELISA technique. Data were statistically analyzed by the t test, Pearson correlation and regression, at a significance level of 5%. No difference was found between the groups in the values of the two growth factors measured on the skin, at the different times. Also, no correlation was found between the amount of growth factors present in the skin and plasma. On the other hand, a positive correlation was observed between PRP and skin in the treated group, for the growth factors TGF-β1 (r=0.31) and PDGF-BB (r=0.38), as well as between both growth factors present in PRP (r=0.81). Considering the growth factor concentrations at T0, the highest skin values (p<0.05) of TGF-β1, in both groups, occurred at T3 and T5. Higher values (p<0.05) of PDGF-BB occurred at T4 (TG) and T5 (CG). No plasma changes occurred at the concentration of these factors in relation to T0, suggesting that PRP does not cause a systemic effect when the procedures adopted in this research are used. Local administration of PRP in the volume studied, 12 h after surgical induction of cutaneous wound gluteal equine does not cause higher concentrations of the growth factors TGF-β1 and PDGF-BB in the plasma and skin during the healing process.

Introduction: The effects of dietary glycemic load (GL) on cardiometabolic risk factors in physically active subjects are not completely known. Objective: This cross-sectional study assessed the association of habitual dietary GL with cardiometabolic risk factors in physically active Brazilian middle-aged men. Methods: One-hundred seventy-six subjects (Age: 50.6 ± 5.0 years, BMI: 25.5 ± 3.6 kg/m²) were evaluated. Anthropometry, lifestyle features, insulin resistance, oxidative stress biomarkers (8-iso-prostaglandin F2α; 8-iso-PGF2α and 8-hydroxydeoxyguanosine; 8-OHdG) and lipid profile were assessed. Dietary intake was estimated through a quantitative food frequency questionnaire. Results: The dietary GL was positively associated with free fatty acid concentrations (β = 0.311, r² = 0.13, P-value = 0.034) and triglycerides/HDL cholesterol ratio (β = 0.598, r² = 0.19, P-value = 0.028) regardless of confounding factors (central obesity, red meat consumption, age and energy intake). The oxidative stress biomarker, 8-OHdG, was associated with habitual dietary GL (β = 0.432, r² = 0.11, P-value = 0.004), regardless of previous confounding factors plus excessive alcohol consumption, iron intake and current smoking status. Conclusions: The dietary GL was positively associated with lipid profile (free fatty acid concentrations and triglycerides/HDL cholesterol ratio) and oxidative stress biomarker (8-OHdG). These results indicate potential harmfulness of diet with higher GL to cardiometabolic risk factors in middle-aged men, even in physically active individuals.

Introducción: Los efectos de la carga glucémica (CG) de la dieta sobre los factores de riesgo cardiometabólico en sujetos físicamente activos no están establecidos por completo. Objetivo: Este estudio transversal evaluó la asociación entre la CG de la dieta habitual y los factores de riesgo cardiometabólico en hombres brasileños de mediana edad físicamente activos. Métodos: Ciento setenta y seis sujetos (índice de masa corporal: 25,5 ± 3,6 kg/m²; edad: 50,6 ± 5,0 años) fueron evaluados. Antropometría, características del estilo de vida, la resistencia a la insulina, biomarcadores del estrés oxidativo (8-iso-prostaglandina F2α, 8-iso-PGF2α y 8 hidroxideoxiguanosina, 8-OHdG) y el perfil lipídico fueron evaluados. La ingesta dietética se estimó por medio de un cuestionario cuantitativo de frecuencia de consumo. Resultados: La CG de la dieta se asoció positivamente con las concentraciones de ácidos grasos libres (β = 0,311, r² = 0,13, P = 0,034) y la razón triglicéridos/colesterol HDL (β = 0,598, r² = 0,19, P = 0,028), independientemente de los factores de confusión (obesidad central, consumo de carne roja, edad e ingesta calórica). El biomarcador del estrés oxidativo, 8-OHdG, también se asoció con CG de la dieta habitual (β = 0,432, r² = 0,11, P = 0,004), independientemente de los factores de confusión anteriores más el consumo excesivo de alcohol, la ingesta de hierro y tabaquismo actual. Conclusiones: La CG de la dieta se asoció positivamente con el perfil lipídico (concentraciones de ácidos grasos libres y razón triglicéridos/HDL colesterol) y el biomarcador de estrés oxidativo 8-OHdG. Estos resultados indican el potencial de nocividad de una dieta con mayor CG respecto a los factores de riesgo cardiometabólico en hombres de mediana edad, incluso en aquellos físicamente activos.