Acción antibacteriana de geopropolis de Melipona quadrifaciata en cultivo de secreción de otitis en perros

Objective. The objective of the present paper was to test the in vitro antibacterial activity of the Mandaçaia (Melipona quadrifaciata) bee’s geopropolis. Materials and methods. The experiment was carried out with secretion samples collected from animals with ear diseases evaluated at Unifeso’s Clinic School of Veterinary Medicine, where in vitro tests took place,  antibiograns with alcoholic extract of geopropolis were made 10 test tubes (two tubes for each concentration of 50%, 60%, 70%, 80%, 90%). Results. Were not identified microorganisms at concentrations of 70, 80 and 90%. Conclusions. The geopropolis of Melipona quadrifasciata showed antibacterial activity in vitro against microorganisms from ear secretion of dogs with otitis externa.Objetivo. El objetivo del presente trabajo fue probar la actividad antibacteriana in vitro de la geopropólea de la abeja Mandaçaia (Melipona quadrifasciata). Materiales y métodos. Se realizó el experimento con muestras de secreciones obtenidas de animales con enfermedades del oído evaluados en la Clínica Escuela de Medicina Veterinaria de Unifeso, donde tuvieron lugar las pruebas in vitro, antibiograns con extracto alcohólico de geopropolis fueron realizados 10 tubos de ensayo (dos tubos para cada concentración del 50%, 60%, 70%, 80%, 90%). Resultados. No se identificaron los microorganismos a concentraciones de 70, 80% y 90%. Conclusiones. La geopropolis de Melipona quadrifasciata mostró actividad antibacteriana, in vitro, frente a microorganismos de la secreción del oído de los perros con otitis externa

WNK2 inhibits autophagic flux in human glioblastoma cell line

The following are available online at http://www.mdpi.com/2073-4409/9/2/485/s1, Figure S1: Validation of WNK2 overexpression by RT-PCR.Autophagy is a cell-survival pathway with dual role in tumorigenesis, promoting either tumor survival or tumor death. WNK2 gene, a member of the WNK (with no lysine (K)) subfamily, acts as a tumor suppressor gene in gliomas, regulating cell migration and invasion; however, its role in autophagy process is poorly explored. The WNK2-methylated human glioblastoma cell line A172 WT (wild type) was compared to transfected clones A172 EV (empty vector), and A172 WNK2 (WNK2 overexpression) for the evaluation of autophagy using an inhibitor (bafilomycin A1—baf A1) and an inducer (everolimus) of autophagic flux. Western blot and immunofluorescence approaches were used to monitor autophagic markers, LC3A/B and SQSTM1/p62. A172 WNK2 cells presented a significant decrease in LC3B and p62 protein levels, and in LC3A/B ratio when compared with control cells, after treatment with baf A1 + everolimus, suggesting that WNK2 overexpression inhibits the autophagic flux in gliomas. The mTOR pathway was also evaluated under the same conditions, and the observed results suggest that the inhibition of autophagy mediated by WNK2 occurs through a mTOR-independent pathway. In conclusion, the evaluation of the autophagic process demonstrated that WNK2 inhibits the autophagic flux in glioblastoma cell line.This project was supported by the Barretos Cancer Hospital Internal Research Funds (PAIP) to Rui Manuel Reis and by the Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer Project), Campinas, Brazil. Ana Laura Vieira Alves is the recipient of a FAPESP master fellowship (2016/18907-0)

tackling malaria

Malaria is an infectious disease that affects over 216 million people worldwide, killing over 445,000 patients annually. Due to the constant emergence of parasitic resistance to the current antimalarial drugs, the discovery of new drug candidates is a major global health priority. Aiming to make the drug discovery processes faster and less expensive, we developed binary and continuous Quantitative Structure-Activity Relationships (QSAR) models implementing deep learning for predicting antiplasmodial activity and cytotoxicity of untested compounds. Then, we applied the best models for a virtual screening of a large database of chemical compounds. The top computational predictions were evaluated experimentally against asexual blood stages of both sensitive and multi-drug-resistant Plasmodium falciparum strains. Among them, two compounds, LabMol-149 and LabMol-152, showed potent antiplasmodial activity at low nanomolar concentrations (EC50 <500 nM) and low cytotoxicity in mammalian cells. Therefore, the computational approach employing deep learning developed here allowed us to discover two new families of potential next generation antimalarial agents, which are in compliance with the guidelines and criteria for antimalarial target candidates.publishersversionpublishe

A ingestão de bebidas energéticas antes do exercício afeta a dinâmica não linear da recuperação da variabilidade da frequência cardíaca? Um ensaio randomizado, crossover, duplo-cego e controlado por placebo

Introduction and Objectives: Energy drinks (ED) are recognized to influence the behavior of the sympathetic and parasympathetic components of the autonomic nervous system. We intended to study the influence of ED on non-linear heart rate variability (HRV) following exercise. Material and Methods: This randomized, crossover, double-blind, placebo-controlled clinical trial (Protocol number NCT02917889) was completed in a sample of 28 healthy males aged 24.11 ± 3.05 years (min-max 18-29). The first step involved the assessment of maximal oxygen consumption (VO2 max). In the second protocol, the subjects received a placebo (250ml of water) or ED (250ml of energy drink) 15 minutes before the 30-minute exercise on a treadmill. In the third protocol, participants received the alternative protocol to the previous step. The nonlinear HRV were calculated at different times during the protocols. Results: Fractal analysis via Detrended Fluctuation Analysis (DFA) revealed that in the placebo protocol there was an increase in its values compared to recovery (Rec1) vs. Rest (Cohen's d= 1.42) and continued increasing in the last recording intervals: vs. Rec6 (Cohen's d= 0.70) and vs. Rec7 (Cohen's d= 0.85). In the ED protocol, the increase in DFA was only demonstrated when comparing Rec1 vs. Rest (Cohen’s d=1.78). Conclusion: ED intake prior to modest aerobic exercise triggered a slight acceleration of recovery.Introducción y Objetivo: Se sabe que las bebidas energéticas (DE) influyen en el comportamiento de los componentes simpático y parasimpático del sistema nervioso autónomo. Pretendemos estudiar la influencia de la DE en la variabilidad no lineal de la frecuencia cardíaca (VFC) después del ejercicio. Material y métodos: este ensayo clínico aleatorizado, cruzado, doble ciego, controlado con placebo (número de protocolo NCT02917889) se completó en una muestra de 28 hombres sanos de 24,11 ± 3,05 años (mín-máx 18-29). El primer paso involucró la evaluación del consumo máximo de oxígeno (VO2 max). En el segundo protocolo, los sujetos recibieron placebo (250 ml de agua) o ED (250 ml de bebida energética) 15 minutos antes de los 30 minutos de ejercicio en cinta rodante. En el tercer protocolo, los participantes recibieron el protocolo alternativo al paso anterior. La HRV no lineal se calculó en diferentes momentos durante los protocolos. Resultados: El análisis fractal vía Detrended Fluctuation Analysis (DFA) reveló que en el protocolo placebo hubo un incremento en sus valores en relación a la recuperación (Rec1) vs. En reposo (d de Cohen= 1,42) y siguió aumentando en los últimos intervalos de registro: vs. Rec6 (d de Cohen = 0,70) y vs. Rec7 (d de Cohen = 0,85). En el protocolo ED, el aumento de DFA solo se demostró al comparar Rec1 vs. Reposo (d de Cohen=1,78). Conclusión: la ingesta de DE antes del ejercicio aeróbico moderado desencadenó una ligera aceleración de la recuperación.Introduzione e obiettivo: è noto che le bevande energetiche (DE) influenzano il comportamento delle componenti simpatiche e parasimpatiche del sistema nervoso autonomo. Intendiamo studiare l'influenza dell'ED sulla variabilità non lineare della frequenza cardiaca (HRV) dopo l'esercizio. Materiale e metodi: questo studio clinico randomizzato, incrociato, in doppio cieco, controllato con placebo (numero di protocollo NCT02917889) è stato completato su un campione di 28 uomini sani di età compresa tra 24,11 ± 3,05 anni (min-max 18-29). Il primo passo ha comportato la valutazione del consumo massimo di ossigeno (VO2 max). Nel secondo protocollo, i soggetti hanno ricevuto placebo (250 ml di acqua) o ED (250 ml di bevanda energetica) 15 minuti prima dell'esercizio di 30 minuti sul tapis roulant. Nel terzo protocollo, i partecipanti hanno ricevuto il protocollo alternativo al passaggio precedente. L'HRV non lineare è stato calcolato in momenti diversi durante i protocolli. Risultati: L'analisi frattale tramite Detrended Fluctuation Analysis (DFA) ha rivelato che nel protocollo placebo c'era un aumento dei suoi valori in relazione al recupero (Rec1) vs. A riposo (d di Cohen= 1.42) e ha continuato ad aumentare negli ultimi intervalli di registrazione: vs. Rec6 (d di Cohen = 0.70) e vs. Rec7 (d di Cohen = 0,85). Nel protocollo ED, l'aumento di DFA è stato dimostrato solo confrontando Rec1 vs. Riposo (Cohen d=1.78). Conclusione: l'ingestione di DE prima di un moderato esercizio aerobico ha innescato una leggera accelerazione del recupero.Introdução e Objetivo: As bebidas energéticas (DE) são reconhecidas por influenciar o comportamento dos componentes simpáticos e parassimpáticos do sistema nervoso autônomo. Pretendemos estudar a influência da DE na variabilidade não linear da frequência cardíaca (VFC) após o exercício. Material e Métodos: Este ensaio clínico randomizado, cruzado, duplo-cego, controlado por placebo (número do protocolo NCT02917889) foi concluído em uma amostra de 28 homens saudáveis com idade de 24,11 ± 3,05 anos (min-max 18-29). A primeira etapa envolveu a avaliação do consumo máximo de oxigênio (VO2 máx). No segundo protocolo, os sujeitos receberam placebo (250ml de água) ou ED (250ml de energético) 15 minutos antes do exercício de 30 minutos em esteira. No terceiro protocolo, os participantes receberam o protocolo alternativo à etapa anterior. A VFC não linear foi calculada em momentos diferentes durante os protocolos. Resultados: A análise fractal via Detrended Fluctuation Analysis (DFA) revelou que no protocolo placebo houve um aumento em seus valores em relação à recuperação (Rec1) vs. Repouso (Cohen's d= 1,42) e continuou aumentando nos últimos intervalos de registro: vs. Rec6 (d de Cohen = 0,70) e vs. Rec7 (d de Cohen = 0,85). No protocolo ED, o aumento do DFA só foi demonstrado ao comparar Rec1 vs. Rest (Cohen’s d=1,78). Conclusão: A ingestão de DE antes do exercício aeróbico moderado desencadeou uma ligeira aceleração da recuperação.Introdução e Objetivo: As bebidas energéticas (DE) são reconhecidas por influenciar o comportamento dos componentes simpáticos e parassimpáticos do sistema nervoso autônomo. Pretendemos estudar a influência da DE na variabilidade não linear da frequência cardíaca (VFC) após o exercício. Material e Métodos: Este ensaio clínico randomizado, cruzado, duplo-cego, controlado por placebo (número do protocolo NCT02917889) foi concluído em uma amostra de 28 homens saudáveis com idade de 24,11 ± 3,05 anos (min-max 18-29). A primeira etapa envolveu a avaliação do consumo máximo de oxigênio (VO2 máx). No segundo protocolo, os sujeitos receberam placebo (250ml de água) ou ED (250ml de energético) 15 minutos antes do exercício de 30 minutos em esteira. No terceiro protocolo, os participantes receberam o protocolo alternativo à etapa anterior. A VFC não linear foi calculada em momentos diferentes durante os protocolos. Resultados: A análise fractal via Detrended Fluctuation Analysis (DFA) revelou que no protocolo placebo houve um aumento em seus valores em relação à recuperação (Rec1) vs. Repouso (Cohen's d= 1,42) e continuou aumentando nos últimos intervalos de registro: vs. Rec6 (d de Cohen = 0,70) e vs. Rec7 (d de Cohen = 0,85). No protocolo ED, o aumento do DFA só foi demonstrado ao comparar Rec1 vs. Rest (Cohen’s d=1,78). Conclusão: A ingestão de DE antes do exercício aeróbico moderado desencadeou uma ligeira aceleração da recuperação

QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

An example of structural transformation of human skin sensitizers into various non-sensitizers based on interpretation of QSAR models

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using random forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers were 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the ScoreCard database of possible skin or sense organ toxicants as primary candidates for experimental validation

Liver biopsy may facilitate pancreatic graft evaluation: Positive association between liver steatosis and pancreatic graft adipose infiltration

OBJECTIVES: The number of pancreatic transplants has decreased in recent years. Pancreatic grafts have been underutilized compared to other solid grafts. One cause of discard is the macroscopic appearance of the pancreas, especially the presence of fatty infiltration. The current research is aimed at understanding any graft-related association between fatty tissue infiltration of the pancreas and liver steatosis. METHODS: From August 2013 to August 2014, a prospective cross-sectional clinical study using data from 54 multiple deceased donor organs was performed. RESULTS: Micro- and macroscopic liver steatosis were significantly correlated with the donor body mass index ([BMI]; p=0.029 and p=0.006, respectively). Positive gamma associations between pancreatic and liver macroscopic and microscopic findings (0.98; confidence interval [CI]: 0.95-1 and 0.52; CI 0.04-1, respectively) were observed. Furthermore, comparisons of liver microscopy findings showed significant differences between severe versus absent (

Linear and complex measures of heart rate variability during exposure to traffic noise in healthy women

Previous studies have described significant impact of different types of noise on the linear behavior of heart rate variability (HRV). However, there are few studies regarding the complexity of HRV during exposure to traffic noise. In this study, we evaluated the complexity of HRV during traffic noise exposure. We analyzed 31 healthy female students aged between 18 and 30 years. Volunteers remained at rest seated under spontaneous breathing during 10 minutes with an earphone turned off, and then they were exposed to traffic noise through an earphone for a period of 10 minutes. The traffic noise was recorded from a very busy city street and the sound was comprised of car, bus, and trucks engines and horn (71-104 dB). We observed no significant changes in the linear analysis of HRV. CFP3 (Cohen's d = 1.28, large effect size) and CFP6 (Cohen's d = 1.11, large effect size) parameters of chaotic global analysis and Shannon (Cohen's d = 1.13, large effect size), Renyi (Cohen's d = 1.06, large effect size), and Tsallis (Cohen's d = 1.14, large effect size) entropies significantly increased (p < 0.005) during traffic noise exposure. In conclusion, traffic noise under laboratory conditions increased the complexity of HRV through chaotic global analysis and some measures of entropy in healthy females

Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R2=0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q2ext = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential

Alarms about structural alerts

Integrative approach for safety assessment of new chemicals by combining structural alerts and QSAR models