ABSTRACT Purpose: Gene expressions of vascular Endothelial Growth Factor Alpha (VEGFa), Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B cells (NFkB) and cytokines could be useful for identifying potential therapeutic targets to alleviate ischemia-reperfusion injury after liver transplantation. Cytokine gene expressions, VEGFa and NFkB were investigated in a preclinical swine model of liver transplantation. Methods: A total of 12 pigs were used as donors and recipients in liver transplantation without venovenous bypass or aortic clamping. NFkB, IL-6, IL-10, VEGFa and Notch1 gene expression were assessed. These samples were collected in two specific times: group 1 (n= 6) - control, samples were collected before recipient’s total hepatectomy and group 2 - liver transplantation group (n=6), where the samples were collected one hour after graft reperfusion. Results: Liver transplantation was successfully performed in all recipients. Liver enzymes were elevated in the transplantation group. NFkB gene expression was significantly decreased in the transplantation group in comparison with the control group (0.62±0.19 versus 0.39±0.08; p= 0.016). No difference was observed between groups Interleucine 6 (IL-6), interleucine 10 (IL-10), VEGFa and Notch homolog 1 (Notch1). Conclusions: In this survey a decreased NFkB gene expression in a porcine model of liver transplantation was observed. Purpose VEGFa, , (VEGFa) KappaLightChainEnhancer Kappa Light Chain Enhancer (NFkB ischemiareperfusion ischemia reperfusion Methods clamping IL6, IL6 IL 6, IL-6 IL10, IL10 10, IL-10 assessed times n= n (n recipient s n=6, n6 n=6 (n=6) Results 0.62±0.19 062019 0 62 19 (0.62±0.1 0.39±0.08 039008 39 08 p 0.016. 0016 0.016 . 016 0.016) (IL-6) (IL-10) Notch1. (Notch1) Conclusions (VEGFa IL- IL1 IL-1 (n=6 0.62±0.1 06201 (0.62±0. 0.39±0.0 03900 3 001 0.01 01 (IL-6 (IL-10 (Notch1 0.62±0. 0620 (0.62±0 0.39±0. 0390 00 0.0 (IL- (IL-1 (Notch 0.62±0 062 (0.62± 0.39±0 039 0. (IL 0.62± 06 (0.62 0.39± 03 0.62 (0.6 0.39 0.6 (0. 0.3 (0 (

Abstract Background: Although phytase has been widely used in poultry nutrition, the effects of the enzyme on broilers fed low levels of phosphorus are poorly understood. Objective: To evaluate the effects of two commercial phytases on live performance and bone quality of broilers fed diets with normal and reduced levels of phosphorus. Methods: Two experiments were conducted with four treatments and six repetitions with 30 birds each, for a total of 24 groups. The first experiment (Exp. I) used a reference level of available phosphorus (AP) with four treatments, as follows: Positive control= 0.45% AP starter diet/0.40% AP grower diet without phytase; Phytase X= 0.35% AP starter diet/0.30% AP grower diet + Phytase X; Phytase Y= 0.35% AP starter diet/0.30% AP grower diet + Phytase Y; and Negative control= 0.35% AP starter diet/0.30% AP grower diet, without phytase. In experiment II (Exp. II) the same treatments were used, but AP levels were reduced by 0.10%. The variables analyzed were: performance from one to 35 days, and bone quality at 35 days of age. Both experiments were analyzed using a completely randomized design. Results: In Exp. I, the positive control resulted in greater body weight gain (2,558 g; p<0,05) compared to Phytase Y (2,470 g) and negative control (2,472 g), and better feed conversion ratio (1.48; p<0,05) than the negative control (1.51). However, when phosphorus was reduced in Exp. II, the positive control and treatments with Phytase X showed better results (p<0.01) for feed intake (3,608 g and 3,593 g, respectively) and weight gain (2,430 g and 2,400 g, respectively) compared to the negative control (2,889 g of feed intake and 1,915 g of weight gain; p<0.01), which also presented low bone ash (36.8%) and phosphorus in the tibia (5.48%; p<0.01). Conclusion: Reducing AP concentration in diets not added with phytase negatively affects weight gain and feed intake of broilers.

Resumen Antecedentes: Aunque la fitasa ha sido ampliamente utilizada en nutrición aviar, sus efectos en pollos de engorde alimentados con bajos niveles de fósforo son poco comprendidos. Objetivo: Evaluar el efecto de dos fitasas comerciales sobre el desempeño y la calidad ósea de pollos de engorde alimentados con dietas con niveles normales y reducidos de fósforo. Métodos: Se realizaron dos experimentos con cuatro tratamientos y seis repeticiones de 30 aves cada una, totalizando 24 grupos. En el primero (Exp. I) se utilizó el nivel de referencia de fósforo disponible (Pd) con cuatro tratamientos, así: Control positivo= 0,45% Pd dieta inicial/0,40% Pd dieta de engorde, sin fitasa; Fitasa X= 0,35% Pd dieta inicial/0,30% Pd dieta engorde + Fitasa X; Fitasa Y= 0,35% Pd dieta inicial/0,30% Pd dieta engorde + Fitasa Y; finalmente, Control negativo= 0,35% Pd dieta inicial/0,30% Pd dieta engorde, sin fitasa. En el segundo experimento (Exp. II) se utilizaron los mismos tratamientos, pero reduciendo en 0,10% el nivel de Pd. Las variables analizadas fueron: desempeño de uno a siete días y de uno a 35 días y calidad ósea a los 35 días de edad. Ambos experimentos se analizaron mediante un diseño completamente aleatorizado. Resultados: En el Exp. I, control positivo presentó una mayor ganancia de peso corporal (2.558 g; p<0,05) en comparación con la Fitasa Y (2.470 g) y el control negativo (2.472 g), y mejor índice de conversión alimenticia (1,48; p<0,05) que el control negativo (1,51). Sin embargo, cuando se redujo el nivel de fósforo en el Exp. II, el control positivo y los tratamientos con Fitasa X mostraron mejores resultados (p<0,01) para el consumo de alimento (3.608 g y 3.593 g, respectivamente) y la ganancia de peso (2.430 g y 2.400 g, respectivamente) en comparación con el control negativo (2.889 g de consumo de alimento y 1.915 g de ganancia de peso; p<0,01), el cual también presentó baja concentración de cenizas óseas (36,8%) y fósforo en tibia (5,48%; p<0,01). Conclusión: La reducción de la concentración de Pd en dietas no aditivadas con fitasa afecta negativamente la ganancia de peso y el consumo de alimento del pollo de engorde.

Resumo Antecedentes: A fitase é uma enzima amplamente utilizada na nutrição de frangos de corte. No entanto existem várias opções comerciais e seus efeitos com níveis reduzidos de fósforo, são pouco avaliados. Objetivo: Avaliar o efeito da suplementação de fitases comerciais no desempenho e na qualidade óssea de frangos de corte, alimentados com níveis normais e reduzidos de fósforo. Métodos: Dois experimentos foram conduzidos com quatro tratamentos e seis repetições, com 30 aves em cada, totalizando 24 grupos. No primeiro (I) utilizou o nível de referência de fósforo disponível (Pd), totalizando quatro tratamentos: controle positivo= 0,45% Pd dieta inicial/0,40% Pd dieta crescimento, sem fitase; tratamento fitase X= 0,35% Pd dieta inicial/0,30% Pd dieta crescimento + Fitase X; tratamento fitase Y= 0,35% Pd dieta inicial/0,30% Pd dieta de crescimento + Fitase Y; e controle negativo 0,35% Pd dieta inicial/0,30% Pd dieta crescimento, sem fitase. O segundo experimento utilizou os mesmos tratamentos, reduzindo 0,10% o nível de Pd. As variáveis analisadas foram: desempenho de um a sete dias e de sete a 35 dias e qualidade óssea aos 35 dias. Ambos os experimentos foram analisados usando um delineamento inteiramente casualizado. Resultados: No Experimento I, o tratamento controle positivo apresentou maior ganho de peso corporal (2.557,86 g; p<0,05) em relação a fitase Y (2.470,27 g) e o controle negativo (2.471,73 g) e melhor índice de conversão alimentar (1,48; p<0,05) do que o tratamento controle negativo (1,51). Porém, quando o nível de fósforo foi reduzido no Experimento II, o controle positivo e os tratamentos com fitase X apresentaram os melhores resultados (p<0,01) para consumo de ração (3.608,0 g e 3.593,1 g, respectivamente) e ganho de peso corporal (2.429,8 g e 2.399,9 g, respectivamente) em comparação ao tratamento controle negativo (2.889,0 g de ingestão de ração e 1.915,3 g de ganho de peso corporal; p<0,01) que também apresentou baixa concentração de cinzas ósseas (36,8%) e fósforo na tíbia (5,48%; p<0,01). Conclusões. A redução da concentração de AP sem o uso de fitase reduz o ganho de peso corporal e o consumo de ração de frangos de corte.

Abstract Introduction: The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA). Methods: This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases. Results: Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies’ results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA. Conclusion: There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.

Abstract Background: Qualea grandiflora (QG) (Vochysiaceae), also known as "pau-ferro", "pau-terra" or "pau-de-tucano", is a very common deciduous tree in the Brazilian Cerrado used in traditional medicine to treat inflammations, ulcers, diarrhea, and infections. There are reports in the scientific literature that demonstrate the medicinal effects of the bark and leaf of the QG. However, studies involving this plant are rather imited. Aim of the study: To perform the phytochemical analysis of the QG hydroalcoholic extract (HAE) of leaves, and to investigate it effects on fibroblast and preosteoblasts. Methods: Phytochemical analysis was done by HPLC-DAD. Murine NIH/3T3 fibroblasts and MC3T3-E1 preosteoblasts cell lines (ATCC) were used for the experiments. Cell viability was assessed by the MTT colorimetric assay and the expression of MMP-14 and HIF-1α by immunofluorescence. Results and conclusion: The following compounds were identified by HPLC-DAD, such as quinic acid, ethyl galate, ellagic acid derivatives as O-methylellagic acid O-galloyl, O-methylellagic acid O-deoxyhexoside, galloyl derivatives, flavonol glycoside as kaempferol-O-deoxyhexoside, quercetin-O-deoxyhexoside, myricetin-O-deoxyhexoside and the pentacyclic triterpene arjunglucoside. Cell viability results demonstrated no cytotoxic effects in the studied concentrations. We found in QG HAE some compounds with therapeutic properties that can increase the expression of MMP-14 and HIF-1α, in fibroblasts and preosteoblasts. These data suggest that QG HAE has an action on these two molecules widely involved in physiological conditions, such as collagen remodeling, bone development and growth and pathological processes as HIF signaling in cancer metastasis.

ABSTRACT The main objective of this study was to evaluate the effect of placement time on the performance of broiler chickens and the development of their gastrointestinal tract. Two methodologies for measuring broiler performance were compared, one considering day of pulling as the first day, the other considering day of placement as the first day. A total of 1,056 one-day old male Cobb® 500 broiler chicks were subjected to treatments of different placement times after pulling from the hatchery: 3, 24, 48, and 72 h. The studied traits were: feed intake, body weight, feed conversion, viability, and gastrointestinal tract development. When day of pulling was considered the first day, feed intake and body weight at 39 days decreased as placement time increased. However, when day of placement was considered the first day, fasting up to 72 h did not have any negative effect on broiler performance at 39 days post-placement. Placement time did not affect yolk sac utilization or liver weight. At nine days post-placement, weights of gizzard + proventriculus, pancreas, and small intestine increased with increasing placement time. At seven days of age, there was no effect of placement time on villus height or crypt depth. It is possible to place broiler chicks up to 72 h post-hatching with no negative effects when day of placement is considered the first day for evaluating broiler performance.

Abstract Objectives: The aim of this study was to assess the effect of Myracrodruon urundeuva All. and Qualea grandiflora Mart. leaves hydroalcoholic extracts on viability and metabolism of a microcosm biofilm and on enamel demineralization prevention. Methodology: Microcosm biofilm was produced on bovine enamel using inoculum from pooled human saliva mixed with McBain saliva, under 0.2% sucrose exposure, for 14 days. The biofilm was daily-treated with the extracts for 1 min. At the end, it was analyzed with respect to viability by fluorescence, CFU counting and extracellular polysaccharides (phenol-sulphuric acid colorimetric assay) and lactic acid (enzymatic assay) production. The demineralization was measured by TMR. The data were compared using ANOVA or Kruskal-Wallis (p<0.05). Results: M. urundeuva All. at 100, 10 and 0.1 μg/mL and Q. grandiflora Mart. at 100 and 0.1 μg/mL reduced biofilm viability similarly to positive control (chlorhexidine) and significantly more than the negative-vehicle control (35% ethanol). M. urundeuva at 1000, 100 and 0.1 μg/mL were able to reduce both lactobacilli and mutans streptococci CFU counting, while Q. grandiflora (1000 and 1.0 μg/mL) significantly reduced mutans streptococci CFU counting. On the other hand, the natural extracts were unable to significantly reduce extracellular polysaccharides and lactic acid productions neither the development of enamel carious lesions. Conclusions: The extracts showed antimicrobial properties on microcosm biofilm, however, they had no effect on biofilm metabolism and caries protection.

Abstract: Hymenaea courbaril has been used to treat different diseases, although its properties are yet to be scientifically validated. The objective of this study was to determine the cytotoxicity, genotoxicity, antigenotoxicity and antioxidant potentials of hydroethanolic extract from H. courbaril seeds. Therefore, for the cytotoxicity test an anti-melanoma assay was performed in B16F10 strain cells. The genotoxicity and antigenotoxicity was evaluated in bone marrow cells (Permit number: 002/2010) of mice, the antioxidant activity was determined by the DPPH test and the total flavonoid content was also determined. The hydroethanolic extract showed antigenotoxic effect and antioxidant activity. It was verified that total flavonoid content was 442.25±18.03 mg RE/g dry extract. HPLC-PAD chromatogram revealed presence of flavones as majority compound in evaluated extract. The results allowed us to also infer that the hydroethanolic extract from seeds shows cytotoxic activity against B16F10 melanoma cells line and it has dose-and-time-dependency.

ABSTRACT The deciduous plant Copaifera langsdorffii contains important medicinal compounds which may also be allelopathic and inhibitory to plant growth. The species is endemic to the Brazilian Cerrado where there is pronounced climatic seasonality. In this study we demonstrate the allelopathic capacity of extracts from the leaves of C. langsdorffii and pre-purified fractions of the extract. Analysis by HPLC-PAD-ESI-MS confirmed the presence of quercetin-3-O-α-rhamnoside and kaempferol-3-O-α-rhamnoside as major components, as well as phenolic acid derivatives of gallic acid. The extracts from samples collected during the wet season were rich in flavonoids and reduced the seed germination rate, root emergence time, and root growth of Sorghum bicolor seedlings. Leaves of C. langsdorffii collected in both the wet and the dry season did not differ in the overall phytotoxic potential of their extracts, but differences detected in tested subfractions seem to indicate subtle seasonal changes in chemical composition. These results indicate that changes in the seasonal water status of the Cerrado induces differential synthesis of compounds with higher allelopathic activity.