Antiproliferative activity of thiazole and oxazole derivatives: A systematic review of in vitro and in vivo studies.

Thiazole and oxazole are compounds with a heterocyclic nucleus that have attracted the attention of medicinal chemistry due to the great variety of biological activities that they enable. In recent years, their study has increased, finding a wide range of biological activities, including antifungal, antiparasitic, anti-inflammatory, and anticancer activities. This systematic review provides evidence from the literature on the antiproliferative and antitumor activities of thiazole and oxazole and their derivatives from 2014 to April 2020. Three bibliographical databases were consulted (PubMed, Web of Science, and Scopus), and a total of 32 studies were included in this paper based on our eligibility criteria. The analysis of the activity-structure relationship allows us to conclude that most of the promising compounds identified contained thiazole nuclei or derivatives.

Phylodynamic analysis in the understanding of the current COVID-19 pandemic and its utility in vaccine and antiviral design and assessment.

Over the last decades, the use of phylogenetic methods in the study of emerging infectious diseases has gained considerable traction in public health. Particularly, the integration of phylogenetic analyses with the understanding of the pathogen dynamics at the population level has provided powerful tools for epidemiological surveillance systems. In the same way, the development of statistical methods and theory, as well as improvement of computational efficiency for evolutionary analysis, has expanded the use of these tools for vaccine and antiviral development. Today with the Coronavirus Disease 2019 (COVID-19), this seems to be critical. In this article, we discuss how the application of phylodynamic analysis can improve the understanding of current pandemic dynamics as well as the design, selection, and evaluation of vaccine candidates and antivirals.

Activation of the Keap1-Nrf2 pathway by specioside and the n-butanol extract from the inner bark of Tabebuia rosea (Bertol) DC.

Background: A large number of chemical compounds exert their antioxidant effects by activation of key transcriptional regulatory mechanisms, such as the transcription factor Nrf2. The aim of this study was to evaluate the activation of the Keap1-Nrf2 pathway by both the n-butanol extract obtained from the inner bark of Tabebuia rosea (Bertol) DC and specioside isolated from this extract. Methods: The antioxidant activity of the extract and specioside isolated from the inner bark of T. rosea were evaluated using the oxygen radical absorbance capacity (ORAC) and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH) techniques, whereas their effects on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The effects of the compound and the extract on activating the Keap1-Nrf2 pathway were evaluated using a Nrf2 Transcription Factor Assay kit. Induction of the Nrf2-mediated antioxidant response genes HMOX-1 and NQO1 was evaluated by real-time PCR. The protective effects against H 2O 2-induced oxidative stress in HepG2 cells was determined as the percent protection using the MTT method. Results: Both the n-butanol extract and specioside exhibited activity at low concentrations without affecting cellular viability, since the cell viability was greater than 80% after 24 hours of exposure at each tested concentration. In addition, Nrf2 dissociated from Keap1 after treatment with the n-butanol extract at a concentration of 0.25 µg/mL after 4 hours of exposure. An increase in the Nrf2 level in the cytoplasm after 4 hours of exposure to 2 µM specioside was observed. Nrf2 levels stabilized in the nucleus 12 hours after stimulation with both specioside and the extract. After 6 hours of stimulation, both the extract and specioside induced the expression of HMOX-1 and NQO1. Conclusion: The n-butanol extract from the inner bark of T. rosea and specioside produced protective effects against H 2O 2-induced oxidative stress in HepG2 cells.

Seroprevalencia de anticuerpos anti-Toxoplasma gondii en mujeres menores de 18 años de una localidad de Colombia / Seroprevalence of anti-Toxoplasma gondii antibodies in women under 18 years old from a locality of Colombia

Resumen OBJETIVO: Determinar la seroprevalencia de Toxoplasma gondii en mujeres menores de 18 años de dos instituciones educativas de un municipio de Colombia. MATERIALES Y MÉTODOS: Estudio de prevalencia, transversal, efectuado en 2016 en mujeres de dos colegios de Dosquebradas, Colombia, aprobado por los comités de ética de las instituciones participantes. Criterios de inclusión: ser menores de 18 años, firmar el consentimiento informado y responder las preguntas de una encuesta de datos demográficos. Criterios de exclusión: tener más de 18 años y haber tenido embarazos previos. Las muestras se analizaron contra anticuerpos IgM, IgG e IgG de avidez con antígenos recombinantes para Toxoplasma gondii altamente purificados con la prueba recomLine, con desarrollo de Western blot mikrogen Diagnostik. Para definir el momento infeccioso se determinó la avidez anti-IgG contra antígenos p30, MAG1, GRA1 y rSAG1 en muestras positivas para IgG total. La prueba se realizó e interpretó de acuerdo con las instrucciones del fabricante. RESULTADOS: Se estudiaron 80 pacientes con edad media de 15 años: 4 resultaron con IgM anti-Toxoplasma gondii, infección menor de 3 meses; 28 IgG anti-Toxoplasma gondii, con infección mayor a 3 meses y 17 IgG de avidez con infección superior a 6 meses. La prevalencia fue de 61.3%. CONCLUSIÓN: La seroprevalencia global de anticuerpos anti-toxoplasma encontrada fue de 61.3%, lo que pone de manifiesto que la toxoplasmosis es una enfermedad en la que debe pensarse para diagnosticarla y tratarla oportunamente.

Abstract OBJECTIVE: To determinate seroprevalence of Toxoplasma gondii in the female population of the municipality of Dosquebradas. MATERIALS AND METHODS: Cross-sectional prevalence study in reproductive age female of two school of the from a locality of Dosquebradas, Colombia, during 2016, was approved by the ethics committees of the participating institutions. The study volunteers signed the consent and completed the survey with demographic data, excluding women older than 18 years, and having had previous pregnancies. The samples were analyzed against IgM, IgG and avid IgG antibodies using highly purified recombinant antigens for Toxoplasma gondii using RecomLine test with development of Western blot mikrogen DIAGNOSTIK. To define the infectious moment, anti-IgG avidity against antigens p30, MAG1, GRA1 and rSAG1 were determined in samples positive for total IgG. The test was performed and interpreted according to the manufacturer's instructions. RESULTS: 80 patients were studied with average age of 15 years, 4 presented IgM anti-Toxoplasma gondii, infection less than 3 months; 28 IgG anti-Toxoplasma gondii, with infection greater than 3 months and 17 IgG of avidity with infection greater than 6 months, representing a prevalence of 61.3%. CONCLUSIONS: The global seroprevalence of anti-toxoplasma antibodies was 61.3%, which shows that toxoplasmosis is a disease in which it must be thought to diagnose and treat it in a timely manner.

Nrf2-Mediated Antioxidant Activity of the inner bark extracts obtained from Tabebuia rosea (Bertol) DC and Tabebuia chrysantha (JACQ) G. Nicholson.

Background: Several ethnobotanical and ethnopharmacological studies have shown the therapeutic potential of plants from the genus Tabebuia, which have long been used in traditional medicine in rural areas of South America, for the treatment of several human diseases. This study aimed to evaluate the Nrf2-mediated antioxidant activity of the inner bark extracts obtained from Tabebuia rosea and Tabebuia chrysantha. Methods: The antioxidant activity of extracts obtained from the inner bark of T. rosea and T. chrysantha was evaluated using the Oxygen radical absorbance capacity (ORAC) technique. The effect of extracts on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The translocation of Nrf2 to the nucleus after exposure of HepG2 cells to the extracts and controls (α-lipoic acid, curcumin and hydrogen peroxide) was evaluated using the Nrf2 transcription factor kit. Induction of the Nrf2-mediated antioxidant response gene ( NQO1) was evaluated by real-time PCR. Results: The ethyl acetate extract obtained from both species displayed the highest ORAC activity (12,523 and 6,325 µmoles Eq Trolox/g extract). In addition, the extracts had the ability to activate and to translocate Nrf2 to the nucleus, as well as to induce the expression of NQO1. Conclusion: These results indicate that the ethyl acetate extracts obtained from the inner bark of T. chrysantha and T. rosea have an important antioxidant effect mediated by Nrf2 activation, and could be used as a new source of natural antioxidants.

Association of Paraoxonase-1 Q192R (rs662) Single Nucleotide Variation with Cardiovascular Risk in Coffee Harvesters of Central Colombia.

Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, hydrolyzes several organophosphate pesticides and oxidized lipids. The PON1 Q192R polymorphism affects the catalytic efficiency and is considered a risk factor for pesticide intoxication and cardiovascular disease (CVD) but the association is not consistent between individuals or populations. We aimed to study the association of PON1 Q192R polymorphism with CVD risk in coffee harvesters of central Colombia. Demographics were collected from 205 subjects via standardized questionnaires. Lipid profiles and serum butyrylcholinesterase (BChE) were measured by standard procedures. The calculated 10-year atherosclerotic CVD (ASCVD) risk was used as the cardiovascular risk estimate. Q192R genotype was determined by real-time PCR. Prevalence of hypertension, hypercholesterolemia, and the 10-year ASCVD risk was 33%, 62%, and 22%, respectively. BChE levels were no indicative of recent pesticide exposure, although a positive correlation was observed with BChE and hypercholesterolemia. The Q192R genotype frequencies were 38% (QQ), 44% (QR), and 18% (RR). We found an association of the 192Q genotype with hypertension. The results of this study signal the importance to evaluate the influence and potential interactions of BChE and PON1 192Q allele with known genetic and environmental factors implicated in the pathogenesis of CVD.