Identification of autophagy receptors for the Crohn's disease-associated adherent-invasive Escherichia coli.

Introduction: Crohn's disease (CD) is a chronic inflammatory bowel disease, of which the etiology involves genetic, environmental and microbial factors. Adherent-invasive Escherichia coli (AIEC) and polymorphisms in autophagy-related genes have been implicated in CD etiology. Autophagy is a key process for the maintenance of cellular homeostasis, which allows the degradation of damaged cytoplasmic components and pathogens via lysosome. We have shown that a functional autophagy is necessary for AIEC clearance. Here, we aimed at identifying the autophagy receptor(s) responsible to target AIEC to autophagy for degradation. Methods: The levels of autophagy receptors p62, NDP52, NBR1, TAX1BP1 and Optineurin were knocked down in human intestinal epithelial cells T84 using siRNAs. The NDP52 knock-out (KO) and p62 KO HeLa cells, as well as NDP52 KO HeLa cells expressing the wild-type NDP52 or the mutated NDP52Val248Ala protein were used. Results and discussion: We showed that, among the tested autophagy receptors (p62, NDP52, NBR1, TAX1BP1 and Optineurin), diminished expression of p62 or NDP52 increased the number of the clinical AIEC LF82 strain inside epithelial cells. This was associated with increased pro-inflammatory cytokine production. Moreover, p62 or NDP52 directly colocalized with AIEC LF82 and LC3, an autophagy marker. As the NDP52Val248Ala polymorphism has been associated with increased CD susceptibility, we investigated its impact on AIEC control. However, in HeLa cell and under our experimental condition, no effect of this polymorphism neither on AIEC LF82 intracellular number nor on pro-inflammatory cytokine production was observed. Together, our results suggest that p62 and NDP52 act as autophagy receptors for AIEC recognition, controlling AIEC intracellular replication and inflammation.

The Contributions of Nina Fedorovna Talyzina to Research Developed in Brazilian Postgraduate Programs.

Background: Nina Fedorovna Talyzina was a Russian psychologist, whose theories have been applied in educational research in many countries around the world, including Brazil. Her name is mainly connected to the Activity Theory of Learning (ATL), which has been dubbed the Galperin-Talyzina system of developmental didactics. Objective: Investigate how N.F. Talyzina's ideas are applied in dissertations and theses developed in postgraduate programs in Brazil. Design: Our research was a bibliographic review which used the state of the question method to examine how Talyzina's ideas are applied in Brazilian academic publications. Data were gathered from three responsible databases - the Brazilian Digital Library, the CAPES Catalogue, and the Institutional Repositories (1987-2022). The method of content analysis was used for data analysis, according to pre-determined categories. Results: We found a prevalence of research based on the methodology of formative experiments carried out at different educational levels. Skills, scientific concept- formation, and problem-solving were the objects of investigation in most of the studies. The ideas proposed by L.S. Vygotsky, A.N. Leontiev, P.Ya. Galperin, and V.V. Davidov were expressed through references to Talyzina's work as the theoretical basis of many studies, thus evidencing a crucial dialogue with the Cultural-Historical School (CHS). Conclusion: Our study points out the growing interest in Talyzina's ideas, specifically her Activity Theory of Learning, which can be attributed to comprehensive dialogues with the ideas of L.S. Vygotsky and A.N. Leontiev which predominate in Brazilian research.

Photoluminous Response of Biocomposites Produced with Charcoal.

Due to the possible effects of global warming, new materials that do not have a negative impact on the environment are being studied. To serve a variety of industries and outdoor applications, it is necessary to consider the impact of photoluminosity on the performance of biocomposites in order to accurately assess their durability characteristics and prevent substantial damage. Exposure to photoluminosity can result in adverse effects such as discoloration, uneven surface, loss of mass, and manipulation of the intrinsic mechanical properties of biocomposites. This study aims to evaluate general charcoal from three pyrolysis temperatures to understand which charcoal is most suitable for photoluminosity and whether higher pyrolysis temperatures have any significant effect on photoluminosity. Porosity, morphology, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy of charcoal were analyzed. Charcoal obtained at a temperature of 800 °C demonstrates remarkable potential as a bioreinforcement in polymeric matrices, attributable to its significantly higher porosity (81.08%) and hydrophobic properties. The biocomposites were characterized for flexural strength, tensile strength, scanning electron microscopy (SEM), FTIR, and x-ray diffraction (XRD). The results showed an improvement in tensile strength after exposure to photoluminosity, with an increase of 69.24%, 68.98%, and 54.38% at temperatures of 400, 600, and 800 °C, respectively, in relation to the treatment control. It is notorious that the tensile strength and modulus of elasticity after photoluminosity initially had a negative impact on mechanical strength, the incorporation of charcoal from higher pyrolysis temperatures showed a substantial increase in mechanical strength after exposure to photoluminosity, especially at 800 °C with breaking strength of 53.40 MPa, and modulus of elasticity of 4364.30 MPA. Scanning electron microscopy revealed an improvement in morphology, with a decrease in roughness at 800 °C, which led to greater adhesion to the polyester matrix. These findings indicate promising prospects for a new type of biocomposite, particularly in comparison with other polymeric compounds, especially in engineering applications that are subject to direct interactions with the weather.

Indole Alkaloids of Rauvolfia ligustrina and Their Anxiolytic Effects in Adult Zebrafish.

Rauvolfia species are well known as producers of bioactive monoterpene indole alkaloids, which exhibit a broad spectrum of biological activities. A new vobasine-sarpagan-type bisindole alkaloid (1: ) along with six known monomeric indoles (2, 3/4, 5: , and 6/7: ) were isolated from the ethanol extract of the roots of Rauvolfia ligustrina. The structure of the new compound was elucidated by interpretation of their spectroscopic data (1D and 2D NMR and HRESIMS) and comparison with published data for analog compounds. The cytotoxicity of the isolated compounds was screened in a zebrafish (Danio rerio) model. The possible GABAergic (diazepam as the positive control) and serotoninergic (fluoxetine as the positive control) mechanisms of action in adult zebrafish were also evaluated. No compounds were cytotoxic. Compound 2: and the epimers 3: /4: and 6: /7: showed a mechanism action by GABAA, while compound 1: showed a mechanism action by a serotonin receptor (anxiolytic activity). Molecular docking studies showed that compounds 2: and 5: have a greater affinity by the GABAA receptor when compared with diazepam, whereas 1: showed the best affinity for the 5HT2AR channel when compared to risperidone.

Food nitrates and nitrites as possible causes of cancer: A review / Nitratos y nitratos alimentarios como posibles causas de cáncer: una revisión / Nitratos e nitratos dietéticos como possíveis causas de câncer: uma revisão

SUMMARY Introduction: Nitrates and nitrites can be found in meat and dairy products, vegetables, and fruits. The consumption of these preservatives has been associated with the emergence of gastric, colorectal cancer and non-Hodgkin's lymphoma, although studies are still inconclusive. Methodology: It is a review of literature of the narrative type, in which there was a recovery of articles published in English and Portuguese, in the databases SciELO, Lilacs, Science Direct and Capes journals. Articles related to nitrates and nitrites in foods were included, as well as articles that correlated the consumption of these preservatives with the appearance of cancers, regardless of the year of publication, although articles published between the years 2009 to 2019 were prioritized. Results: Nitrates and nitrites are generally associated with industrialized food products; therefore, it is possible to observe the presence of these salts in a wide variety of foods. The excessive consumption of nitrates and nitrites, whether through water or food, has been associated with a great diversity of diseases, stimulating the development of several studies investigating, including, the correlation between the consumption of these preservatives and the appearance of cancers. Conclusion: It is observed that nitrates and nitrites form compounds with a carcinogenic potential, making them interesting to avoid excessive consumption of these preservatives.

RESUMEN Introducción: Los nitratos y nitritos pueden ser encontrados en carnes y productos lácteos, verduras y frutas. El consumo de estos conservantes ha sido asociado con la aparición de cáncer gástrico, colorrectal y linfoma no Hodgkin, aunque los estudios aún no son concluyentes. Metodología: Se hizo una revisión de tipo narrativo de la literatura, en la que se recuperaron artículos publicados en inglés y portugués, en las bases de datos SciELO, Lilacs, Science Direct y revistas Capes. Se incluyeron artículos relacionados con nitratos y nitritos en alimentos, así como artículos que correlacionaban el consumo de estos conservantes con la aparición de cánceres, independientemente del año de publicación, aunque se priorizaron artículos publicados entre los años 2009 a 2019. Resultados: Los nitratos y nitritos se asocian generalmente con productos alimenticios industrializados; por tanto, es posible observar la presencia de estas sales en una amplia variedad de alimentos. El consumo excesivo de nitratos y nitritos, ya sea a través del agua o de los alimentos, se ha asociado a una gran diversidad de enfermedades, estimulando el desarrollo de varios estudios que investigan, entre ellos, la correlación entre el consumo de estos conservantes y la aparición de cánceres. Conclusión: Así, se observa que los nitratos y nitritos, forman compuestos con potencial carcinogénico, por lo que resulta interesante evitar el consumo excesivo de estos conservantes.

RESUMO Introdução: Nitratos e nitritos podem ser encontrados em carnes e laticínios, vegetais e frutas. O consumo desses conservantes tem sido associado ao desenvolvimento de câncer gástrico e colorretal e linfoma não Hodgkin, embora os estudos ainda não sejam conclusivos. Metodologia: Trata-se de uma revisão de literatura do tipo narrativa, na qual houve a recuperação de artigos publicados em inglês e português, nas bases de dados SciELO, Lilacs, Science Direct e Periódicos Capes. Foram incluídos artigos relacionados a nitratos e nitritos em alimentos, bem como artigos que correlacionassem o consumo desses conservantes com o aparecimento de cânceres, independentemente do ano de publicação, embora tenham sido priorizados os artigos publicados entre os anos de 2009 a 2019. Resultados: Nitratos e nitritos são geralmente associados a produtos alimentícios industrializados; portanto, é possível observar a presença desses sais em uma grande variedade de alimentos. O consumo excessivo de nitratos e nitritos, seja pela água ou pelos alimentos, tem sido associado a uma grande diversidade de doenças, estimulando o desenvolvimento de diversos estudos que investiguem, inclusive, a correlação entre o consumo desses conservantes e o aparecimento de cânceres. Conclusão: Assim, observa-se que nitratos e nitritos formam compostos com potencial carcinogê-nico, por isso é interessante evitar o consumo excessivo desses conservantes.

Survivin modulation in the antimelanoma activity of prodiginines.

Melanoma is a type of skin cancer with an elevated incidence of metastasis and chemoresistance. Such features hamper treatment success of these neoplasms, demanding the search for new therapeutic options. Using a two-step resin-based approach, we recently demonstrated that cytotoxic prodiginines bind to the inhibitor of apoptosis protein, survivin. Herein, we explore the role of survivin in melanoma and whether its modulation is related to the antimelanoma properties of three cytotoxic prodiginines (prodigiosin, cyclononylprodigiosin, and nonylprodigiosin) isolated from marine bacteria. In melanoma patients and cell lines, survivin is overexpressed, and higher levels negatively impact survival. All three prodiginines caused a decrease in cell growth with reduced cytotoxicity after 24 h compared to 72 h treatment, suggesting that low concentrations promote cytostatic effects in SK-Mel-19 (BRAF mutant) and SK-Mel-28 (BRAF mutant), but not in SK-Mel-147 (NRAS mutant). An increase in G1 population was observed after 24 h treatment with prodigiosin and cyclononylprodigiosin in SK-Mel-19. Further studies indicate that prodigiosin induced apoptosis and DNA damage, as detected by increased caspase-3 cleavage and histone H2AX phosphorylation, further arguing for the downregulation of survivin. Computer simulations suggest that prodigiosin and cyclononylprodigiosin bind to the BIR domain of survivin. Moreover, knockdown of survivin increased long-term toxicity of prodigiosin, as observed by reduced clonogenic capacity, but did not alter short-term cytotoxicity. In summary, prodiginine treatment provoked cytostatic rather than cytotoxic effects, cell cycle arrest at G0/G1 phase, induction of apoptosis and DNA damage, downregulation of survivin, and decreased clonogenic capacity in survivin knockdown cells.

Effect of indole alkaloids from roots of Rauvolfia ligustrina in the noradrenergic neurotransmission.

The new glucosyl sarpagan alkaloid designated as 21(R*)-(O-ß-glucosyl)-hydroxy-sarpagan-17-oic acid, along with eleven known alkaloids were isolated from a soluble alkaloidal fraction from the ethanol extract of Rauvolfia ligustrina. Their structures were elucidated by interpretation of spectroscopic data (1D and 2D NMR), HRESIMS experiment, GIAO 13C NMR calculations, and comparison with literature data. All the isolated alkaloids were screened by their neuroinhibitory effects using the electrically stimulated mice vas deferens bioassay. Compounds 1, 2 and 9 presented a potent inhibitory effect in the neurotransmission while 3 and 11 showed an acute neuroexcitatory effect. Compound 10 exhibited a very effective post-synaptic inhibitory activity.

4-Hydroxy-pyran-2-one and 3-hydroxy-N-methyl-2-oxindole derivatives of Salinispora arenicola from Brazilian marine sediments.

Three new 3-hydroxy-N-methyl-2-oxindole (1 and 2) and 4-hydroxy-pyran-2-one (3) derivatives, along with the known 3-hydroxy-N-methyl-2-oxindole (4) and 6-methoxy-N-methylisatin (5) were isolated from a marine Salinispora arenicola strain from sediments of the St. Peter and St. Paul Archipelago, Brazil. The structures of the new compounds were elucidated by a combination of spectroscopic (1D and 2D NMR and HR-ESIMS) data, including single-crystal X-ray diffraction analysis for 2 and 3. Compounds 1 to 5 were assayed for their antimicrobial properties, but only 4 and 5 were active against Enterococcus faecalis with MIC value of 15.6 µg/mL.

Antibacterial Salinaphthoquinones from a Strain of the Bacterium Salinispora arenicola Recovered from the Marine Sediments of St. Peter and St. Paul Archipelago, Brazil.

Salinaphthoquinones A-E (1-5) were isolated from a marine Salininispora arenicola strain, recovered from sediments of the St. Peter and St. Paul Archipelago, Brazil. The structures of the compounds were elucidated using a combination of spectroscopic (NMR, IR, HRESIMS) data, including single-crystal X-ray diffraction analysis. A plausible biosynthetic pathway for 1-5 is proposed. Compounds 1 to 4 displayed moderate activity against Staphylococcus aureus and Enterococcus faecalis with MIC values of 125 to 16 µg/mL.

The number of visits and blood pressure measurements influence the prevalence of high blood pressure in adolescents.

The aim of this study was to analyze the influence of the number of visits and the number of blood pressure (BP) measurements on the prevalence of high blood pressure (HBP) in adolescents. A cross-sectional epidemiologic study with 481 adolescents (14-19 years old) selected using a random cluster sampling strategy. We measured the BP three times in a first visit. Adolescents with HBP performed subsequent visits. The final calculation of BP followed four strategies: the 1st measure, mean of 1st and 2nd measurements, mean of all three measurements, and averaging the 2nd and 3rd measurements. The prevalence of HBP in the first and second visits was 6.4% and 1.9%, and the prevalence of hypertension (after three visits) was 1.7%. The prevalence of HBP varied from 8.6%-18.6% for boys and 4.6%-9.2% for girls, using the average 2nd and 3rd measurements and the 1st measurement, respectively. In all strategies, HBP and hypertension were more prevalent in boys and students attending the nocturnal shift. The number of visits and number of measurements affect the prevalence of HBP and hypertension in adolescents. Thus, clinicians and researchers should consider these aspects when assessing BP in adolescents aged 14-19 years old.

Prospecting Anticancer Compounds in Actinomycetes Recovered from the Sediments of Saint Peter and Saint Paul's Archipelago, Brazil.

Saint Peter and Saint Paul's Archipelago is a collection of 15 islets and rocks remotely located in the equatorial Atlantic Ocean. In this particular site, the present project intended to assess the biodiversity and biotechnological potential of bacteria from the actinomycete group. This study presents the first results of this assessment. From 21 sediment samples, 268 strains were isolated and codified as BRA followed by three numbers. Of those, 94 strains were grown in liquid media and submitted to chemical extractions with AcOEt (A), BuOH (B), and MeOH (M). A total of 224 extracts were screened for their cytotoxic activity and 41 were significantly active against HCT-116 cancer cells. The obtained IC50 values ranged from 0.04 to 31.55 µg/ml. The HR-LC/MS dereplication analysis of the active extracts showed the occurrence of several known anticancer compounds. Individual compounds, identified using HR-MS combined with analysis of the AntiMarin database, included saliniketals A and B, piericidins A and C and glucopiericidin A, staurosporine, N-methylstaurosporine, hydroxydimethyl-staurosporine and N-carbamoylstaurosporine, salinisporamycin A, and rifamycins S and B. BRA-199, identified as Streptomyces sp., was submitted to bioassay-guided fractionation, leading to isolation of the bioactive piericidins A and C, glucopiericidin, and three known diketopiperazines, cyclo(l-Phe-trans-4-OH-l-Pro), cyclo(l-Phe-l-Pro), and cyclo(l-Trp-l-Pro).

Al3+ environments in nanostructured ZnAl2O4 and their effects on the luminescence properties.

Single-phase zinc aluminate (ZnAl2O4) with the spinel structure was successfully obtained by the Pechini method at different calcining temperatures for 4 hours. The nanoparticles are highly crystalline with no impurities related to ZnO or Al2O3 residues. The microstructural environment of aluminium ions changes with heat treatment temperature, as observed by Fourier transform infrared spectroscopy. The spinel structure might present two different AlO6 sites as evidenced by 27Al solid-state magic-angle-spinning nuclear magnetic resonance spectra. Some AlO4 sites were also detected for samples calcined at a temperature lower than 900 degrees C. The photoluminescence spectra show that the emission can be tuned depending on the calcining temperature. This effect was discussed on the basis of symmetry and oxygen vacancies.