3-Hydroxykynurenic acid: Physicochemical properties and fluorescence labeling

Quinoline is one of the most important heterocyclic systems in life sciences. Some derivatives are normal metabolites, and others are used as antibacterial, antimalarial, and anticancer agents. In this work, we describe the synthesis, physicochemical properties, and fluorescence features of a new 4-quinolinone fluorophore, 3-hydroxykynurenic acid (3-HOKA). 3-HOKA was obtained by alkoxide-induced rearrangement of ethyl isatinacetate followed by acidification and then alkaline hydrolysis. The fluorescent compound was characterized by NMR, MS, IR, and UV–Vis spectra. 3-HOKA can exist under a keto-enol equilibrium, but the 4-quinolinone form is the predominant tautomer. In PBS (pH = 7.4), the anionic keto form of 3-HOKA showed a maximum absorption at 368 nm, a fluorescence peak at 474 nm, and a fluorescence quantum yield (ΦF): 0.73. 3-HOKA is photostable and is a moderately weak oxygen generator. Viability assays on HeLa cells indicated that 3-HOKA did not induce significative cytotoxic effects. Under UV excitation, a bright blue fluorescence was selectively found in a singular body within the cytoplasm, a labeling pattern that suggests the possible localization of the probe in the centriole or related structures. Therefore, this novel fluorophore represents a promising prototype compound owing to its biocompatibility and potential biological applications.Fil: Shmidt, María Sol. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Garcia Vior, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Ezquerra Riega, Sergio Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Lazaro Martinez, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Abasolo, María I.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Lazaro Carrillo, Ana. Universidad Autónoma de Madrid; EspañaFil: Tabero, Andrea. Universidad Autónoma de Madrid; EspañaFil: Villanueva, Angeles. Universidad Autónoma de Madrid; España. Instituto Madrileño de Estudios Avanzados en Nanociencia; EspañaFil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: del Blanco, María Mercedes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Stockert Cossu, Juan Carlos. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Instituto de Investigacion y Tecnología en Reproducción Animal; Argentin

Evaluación de la capacidad antioxidante y el índice glicémico de frutos promisorios amazónicos del Perú

Determinar la capacidad antioxidante y el Índice glicémico de frutos promisorios amazónicos del Perú. La Capacidad antioxidante de los jugos de frutos amazónicos diluidos al 1/100, se determinó mediante el método DPPH expresado como el porcentaje de inhibición, tomando como referencia el jugo de Limón diluido al 1/100. El índice glicémico expresado en porcentaje fue determinado por el área bajo la curva del alimento en prueba y de la glucosa, considerando el área de la curva de glucosa como el 100 % Se utilizaron 12 ratas albinas machos con peso aproximado de 250 g, a los cuales se determinó la glicemia (en ayunas) basal (tiempo cero) posteriormente se administró glucosa (estándar) por vía orogástrica a la dosis de 50 mg/70 g de peso, determinando la glicemia a diferentes tiempos (15, 30, 45, 60, 90, 120, 150 min). Días posteriores se administró el alimento de prueba por vía orogástrica a la dosis equivalente a la de la glucosa dependiendo del contenido de carbohidratos del alimento, determinando la glicemia a los diferentes tiempos. La capacidad antioxidante expresado como porcentaje de inhibición fueron: cajú 76%, cajá 201%, arazá 268%, caimito 302%, mango ciruela 353% y pitujaya 524% y los IG fueron: cajú 75,8 %, cajá 74%, caimito 71,6 %, mango ciruela 59,7%, pitujaya 51,8% y arazá 43,8%. Los frutos estudiados tienen alta capacida

Desired weight loss and its association with health, health behaviors and perceptions in an adult population with weight excess: One-year follow-up

Background: Metabolic syndrome (MetS) worsens quality of life and increases mortality. Dissatisfaction with weight in patients with MetS may modify the effect of lifestyle interventions to achieve changes in health-related behaviors. Objective: To assess 1-year changes in cardiovascular risk scores, self-perceived general health and health-related behaviors according to observed changes in desired weight loss during the first year of intervention in a large cardiovascular prevention trial. Design: Prospective analysis of the PREDIMED-PLUS trial, including 5,499 adults (55-75 years old) with overweight or obesity at baseline. Methods: The desired weight loss was the difference between ideal and measured weight. Tertiles of change in desired weight loss (1 year vs. baseline) were defined by the following cut-off points: >= 0.0 kg (T1, n = 1,638); 0.0 to -4.0 kg (T2, n = 1,903); <=-4.0 kg (T3, n = 1,958). A food frequency questionnaire assessed diet and the Minnesota-REGICOR questionnaire assessed physical activity. The Framingham equation assessed cardiovascular risks. The changes in the severity of MetS were also assessed. The Beck Depression Inventory assessed depressive symptoms and the SF-36 assessed health-related quality of life. Data were analyzed using general linear models. Results: BMI decreased at T2 and T3 (T1: 0.3, T2: -0.7, T3: -1.9). The most significant improvement in diet quality was observed at T3. Cardiovascular risk decreased at T2 and T3. Mean reductions in MetS severity score were: -0.02 at T1, -0.39 at T2 and -0.78 at T3. The perception of physical health increases in successive tertiles. Conclusions: In older adults with MetS, more ambitious desired weight loss goals were associated with improvements in diet, cardiovascular health and perceived physical health during the first year of a healthy lifestyle intervention programme. Weight dissatisfaction needs to be considered by health professionals

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.Peer reviewe

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Depression, Anxiety, and Social Environmental Adversity as Potential Modulators of the Immune Tumor Microenvironment in Breast Cancer Patients

Background: Mounting data suggest that exposure to chronic stress is associated with worse breast cancer outcomes. This study aimed to explore the impact of social environmental adversity (SEA, e.g., child abuse, crime, sexual, and physical violence), depressive symptomatology, and anxiety on immune cell infiltration into the breast tumor microenvironment. Methods: Participants (n = 33) completed a series of surveys assessing depression and anxiety symptoms, adverse childhood events (ACE), and trauma history. Tumor-associated macrophages (CD68+), B cells (CD19+), and T cells (CD3+) were identified by immunohistochemical analyses of formalin-fixed paraffin-embedded tumor samples and quantified. Spearman rank tests were used to explore the relationships between the variables studied. Results: Exposure to SEA was high (ACE = 72%, exposure to crime = 47%, and exposure to physical/sexual assault = 73%) among participants. Moreover, 30% reported a comorbid history of depression and ACE; 39% reported one or more traumatic events, and clinically significant depression symptomatology, while 21% reported trauma history and significant anxiety symptomatology. Increased tumor-infiltrating B cells were significantly correlated with exposure to crime, anxiety symptoms, and exposure to an ACE. The ACE plus anxiety group presented the highest infiltration of B cells, T cells, and macrophages. Conclusion: These findings support a role for SEA, anxiety symptoms, and depression as potential modulators of the immune tumor microenvironment in breast cancer

Evaluación de la capacidad antioxidante y el índice glicémico de frutos promisorios amazónicos del Perú

Determinar la capacidad antioxidante y el Índice glicémico de frutos promisorios amazónicos del Perú. La Capacidad antioxidante de los jugos de frutos amazónicos diluidos al 1/100, se determinó mediante el método DPPH expresado como el porcentaje de inhibición, tomando como referencia el jugo de Limón diluido al 1/100. El índice glicémico expresado en porcentaje fue determinado por el área bajo la curva del alimento en prueba y de la glucosa, considerando el área de la curva de glucosa como el 100 % Se utilizaron 12 ratas albinas machos con peso aproximado de 250 g, a los cuales se determinó la glicemia (en ayunas) basal (tiempo cero) posteriormente se administró glucosa (estándar) por vía orogástrica a la dosis de 50 mg/70 g de peso, determinando la glicemia a diferentes tiempos (15, 30, 45, 60, 90, 120, 150 min). Días posteriores se administró el alimento de prueba por vía orogástrica a la dosis equivalente a la de la glucosa dependiendo del contenido de carbohidratos del alimento, determinando la glicemia a los diferentes tiempos. La capacidad antioxidante expresado como porcentaje de inhibición fueron: cajú 76%, cajá 201%, arazá 268%, caimito 302%, mango ciruela 353% y pitujaya 524% y los IG fueron: cajú 75,8 %, cajá 74%, caimito 71,6 %, mango ciruela 59,7%, pitujaya 51,8% y arazá 43,8%. Los frutos estudiados tienen alta capacida