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At the beginning of the pandemic, the Brazilian Public Health System (SUS) did not to test all suspects cases of COVID-19, thus, hospitalized individuals, health professionals, and symptomatic contacts were prioritized. Contrary to the criteria adopted by the government, the municipality of Botucatu chose to test all people who manifested flu-like syndrome. We aimed to investigate whether positive cases for COVID-19 were more frequent in patients seeking diagnosis via SUS or in the group of people seeking diagnosis via Municipal Health Center and whether the viral load was expressed differently in hospitalized patients (HP) compared to mild symptoms (MHC). Results showed that there were no differences in the percentage between the groups. Regarding the viral load, significant differences were found between the samples from HP and MHC (3-10 days of symptoms), with HP presenting a lower viral load. The results provide significant information about the viral load at different time-lapses.

Introduction: Hepatitis C is a disease triggered due to an infection by the hepatitis C virus and presents challenges in its treatment, even with the development of multiple direct-acting antivirals agents. Patients with hepatic decompensation or hepatocellular carcinoma and who have experienced treatment failures due to viral variants depend on the development of new molecules, that can be effective as antivirals or with other alternative properties that collaborate to improve symptoms and to avoid or mitigate clinical consequences. Objective: The aim of this review was to verify which new molecules were discovered and can be promising in face of the still persistent challenges in the treatment of hepatitis C. Method: A narrative review was carried out, searching for the specific keywords in PubMed and Google Scholar and molecules with greater potential to meet the demand of difficult to treat patients were selected. Result: The literature search showed that researchers have been engaged in the identification and discovery of new active compounds using various tools for rational drug design, making possible structural modifications that lead to improved effectiveness and pharmacological properties. Conclusion: Several molecules are in the process of being tested to meet the demands of difficult-to-treat patients, including molecules from natural products, and have the potential to help these patients.

Ethanol (EtOH) alters many cellular processes in yeast. An integrated view of different EtOH-tolerant phenotypes and their long noncoding RNAs (lncRNAs) is not yet available. Here, large-scale data integration showed the core EtOH-responsive pathways, lncRNAs, and triggers of higher (HT) and lower (LT) EtOH-tolerant phenotypes. LncRNAs act in a strain-specific manner in the EtOH stress response. Network and omics analyses revealed that cells prepare for stress relief by favoring activation of life-essential systems. Therefore, longevity, peroxisomal, energy, lipid, and RNA/protein metabolisms are the core processes that drive EtOH tolerance. By integrating omics, network analysis, and several other experiments, we showed how the HT and LT phenotypes may arise: (1) the divergence occurs after cell signaling reaches the longevity and peroxisomal pathways, with CTA1 and ROS playing key roles; (2) signals reaching essential ribosomal and RNA pathways via SUI2 enhance the divergence; (3) specific lipid metabolism pathways also act on phenotype-specific profiles; (4) HTs take greater advantage of degradation and membraneless structures to cope with EtOH stress; and (5) our EtOH stress-buffering model suggests that diauxic shift drives EtOH buffering through an energy burst, mainly in HTs. Finally, critical genes, pathways, and the first models including lncRNAs to describe nuances of EtOH tolerance are reported here.

Made available in DSpace on 2020-12-12T01:54:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-28 Scheelea phalerata Mart. ex Spreng (Arecaceae) is a palm tree found in the Brazilian cerrado. There are no topics related to volatile oils from S. phalerata leaves in the literature. This work determines its chemical composition and evaluates the biological activity under two different seasonal conditions (dry and rainy seasons). The dry essential oil yield was 0.034 ± 0.001% and the rainy essential oil yield was 0.011 ± 0.003%. Both essential oils presented different qualitative and quantitative compositions (99.4 and 98.5%). The main constituents of the dry essential oil were phytol (36.7%), nonadecane (9.7%), linolenic acid (9.1%), (Z)-hex-3-en-1-ol (4.2%), and squalene (4.0%). The main constituents of the rainy essential oil were phytol (26.1%), palmitic acid (18.7%), hexan-1-ol (15.6%), (Z)-hex-3-en-1-ol (9.7%), and oleic acid (4.0%). The antileishmanial activity against promastigotes of Leishmania amazonensis was observed only for the rainy season essential oil (IC50 value of 165.05 ± 33.26 μg mL-1). A molecular docking study showed that alcohols exert a paramount efficacy and that the action of some essential oil compounds may be similar to that of amphotericin B. Still, only the essential oil from the dry season showed moderate antibacterial activity against S. sanguinis (MICs 200-400 μg mL-1). The cytotoxicity against Vero cells was identical (>512) for both essential oils. The novel data here for both chemical characterization and biological activity, in particular, evidence that the action of these compounds is similar to that of amphotericin B, provide valuable information to the drug-discovery field. Nucleus of Research in Natural Products (NuPPeN) Institute of Chemistry Federal University of Uberlândia Campus Santa Mônica, Av. João Naves de ávila, 2121 Institute of Biosciences of Botucatu Department of Microbiology and Immunology Unesp-São Paulo State University, 250 Distrito de Rubião Junior Institute of Biosciences of Botucatu Department of Physics and Biophysics Unesp-São Paulo State University, 250 Distrito de Rubião Junior Nucleus of Research in Sciences and Technology Laboratory of Research in Applied Microbiology (LaPeMA) University of Franca, 201 Parque Universitário Institute of Biomedical Sciences Laboratory of Trypanosomatids Federal University of Uberlândia Campus Umuarama, Av. Pará 1720 Bloco 2B Nucleus of Bioprospecting in Natural Products (NuBiProN) Chemistry Department Federal Institute of the Triângulo Mineiro, 4000 Distrito Industrial I Institute of Biosciences of Botucatu Department of Microbiology and Immunology Unesp-São Paulo State University, 250 Distrito de Rubião Junior Institute of Biosciences of Botucatu Department of Physics and Biophysics Unesp-São Paulo State University, 250 Distrito de Rubião Junior

Fundação de Amparo a Pesquisa do Estado de Minas Gerais Inga laurina (Sw.) Willd., popularly known as Angá or Ingá Branco, belongs to Leguminosae family, Inga genus, and some species of this genus are recognized due to their pharmacological and agronomic importance. The objective of this study was to provide information about I. laurina regarding to the chemical composition of the wood and stem bark and leaves essential oils. Additionally, biological activities of the extracts and oils were evaluated. Macromolecular analysis of the wood indicated higher amount of α-cellulose and hemicelluloses in the wood compared to bark. The amount of soluble and insoluble lignin in acid and the content of ash did not show quantitative variations. The seasonal chemical composition of essential oils from Inga laurina was determined by GC/MS. In the essential oil extracted from the bark during the dry season, the presence of terpenoids (30.05%) stood out, and phytol (9.76%) was the major compound identified. For the bark oil obtained during the rainy season, in addition to terpenoids (26.63%), were identified a large amount of fatty acids (46.84%), in particular palmitic acid (25.40%). Regarding the leaves\' essential oil obtained in the dry season, esters (42.35%) were the main components. The main ester present was (Z)-hex-3-enyl benzoate (10.15%) and the major compound of this oil was (Z)-hex-3-en-1-ol (14.23%). Terpenoids (33.84%), long-chain alkanes (27.04%) and fatty acids (21.72%) were the main components of the essential oil from leaves in the rainy season. Phytol (33.21%), nonacosane (21.95%) and palmitic acid (15.20%) were the major compounds identified. The antimicrobial activity against aerobic and anaerobic oral bacteria was evaluated by the microdilution method and cytotoxic activity was carried out with Vero cells. In general, all essential oils exhibited antimicrobial activity against the aerobic and anaerobic microorganisms evaluated. The better bacteriostatic effect was observed against P. gingivalis, S. mutans, S. sanguinis, S. salivarius and S. sobrinus when evaluated oils of the rainy season, with MIC values ranging from 25 to 50 mg mL-1. In contrast, ethanol crude extracts of the bark and leaves of I. laurina showed no significant antimicrobial activity (MIC < 100 μg mL-1) against the same bacteria evaluated. Analysis of selectivity index showed a higher selectivity by bacterias evaluated than toxicity to Vero cells. From the phytochemical screening and by the results obtained in the analysis of total phenols and proanthocyanidins for the ethanol extracts of bark and leaves from I. laurina, it is possible to purpose that phenolic compounds present in the samples tested are primarily responsible for efficient DPPH radical scavenging ability observed with EC50 values similar to the BHT. Thus, the promising results with respect to biological assays of oils and extracts from I. laurina encourage to additional investigations of this species. Inga laurina (Sw.) Willd., conhecida popularmente como Angá ou Ingá Branco, pertence a família Leguminosae e ao gênero Inga. Algumas espécies deste gênero tem importância farmacológica e agronômica. O objetivo deste trabalho foi fornecer informações sobre I. laurina com relação a constituição química da madeira, das cascas e dos óleos essenciais, bem como avaliar atividades biológicas dos extratos brutos e dos compostos voláteis. As análises da constituição macromolecular indicaram maior quantidade de hemicelulose e α-celulose na madeira quando comparada a casca. A quantidade de lignina solúvel e insolúvel em ácido e o teor de cinzas não apresentaram grandes variações quantitativas entre casca e madeira. A variação da composição química dos óleos essenciais obtidos em período chuvoso e de seca foi determinada por CG/EM. No óleo essencial das cascas, extraído durante a estação seca, destacou-se a presença de terpenoides (30,05%), sendo o fitol o composto majoritário (9,76%). Já para o óleo das cascas do período chuvoso, além dos terpenoides (26,63%), foram observados ácidos graxos em grande quantidade (46,84%), sendo o ácido palmítico o composto majoritário (25,40%). Com relação ao óleo essencial das folhas obtido durante a estação seca, os ésteres foram os principais componentes (42,35%). O principal éster presente foi o benzoato de (Z)-hex-3-enila (10,15%) e o composto majoritário deste óleo foi o (Z)-hex-3-en-1-ol (14,23%). Terpenoides (33,84%), alcanos de cadeia longa (27,04%) e ácidos graxos (21,72%) foram as principais classes de compostos do óleo essencial das folhas no período chuvoso. Fitol (33,21%), nonacosano (21,95%) e ácido palmítico (15,20%) foram os componentes majoritários identificados neste óleo. A atividade antimicrobiana contra patógenos orais aeróbicos e anaeróbicos foi avaliada pelo método de microdiluição em caldo e a atividade citotóxica realizada com células Vero. Em geral, todos os óleos essenciais exibiram atividade antimicrobiana contra os microrganismos aeróbicos e anaeróbicos avaliados. Os melhores resultados da ação bacteriostática foram observados contra P. gingivalis, S. mutans, S. sanguinis, S. salivarius e S. sobrinus quando avaliados os óleos do período chuvoso, que apresentaram valores de CIM variando entre 25 e 50 μg mL-1. Em contrapartida, extratos brutos etanólicos das cascas e folhas de I. laurina não apresentaram atividade antimicrobiana relevante (CIM < 100 μg mL-1) para as mesmas bactérias avaliadas. Pelo cálculo do índice de seletividade constatou-se maior seletividade pelas bactérias do que toxicidade para as células Vero. A partir da prospecção fitoquímica e dos resultados obtidos nas análises de fenóis totais e proantocianidinas, para os extratos etanólicos de cascas e folhas de I. laurina, foi possível propor que os compostos fenólicos presentes nas amostras avaliadas são os principais responsáveis pela eficiente capacidade sequestradora de radicais DPPH observada, com valores de CE50 equivalentes aos do BHT. Desta forma, os resultados promissores com relação aos ensaios biológicos de óleos e extratos de I. laurina incentivam investigações mais aprofundadas desta espécie. Mestre em Química

Ethanol (EtOH) is a substantial stressor for Saccharomyces cerevisiae. Data integration from strains with different phenotypes, including EtOH stress-responsive lncRNAs, are still not available. We covered these issues seeking systems modifications that drive the divergences between higher (HT) and lower (LT) EtOH tolerant strains under their highest stress conditions. We showed that these phenotypes are neither related to high viability nor faster population rebound after stress relief. LncRNAs work on many stress-responsive systems in a strain-specific manner promoting the EtOH tolerance. Cells use membraneless RNA/protein storage and degradation systems to endure the stress harming, and lncRNAs jointly promote EtOH tolerance. CTA1 and longevity are primer systems promoting phenotype-specific gene expression. The lower cell viability and growth under stress is a byproduct of sphingolipids and inositol phosphorylceramide dampening, acerbated in HTs by sphinganine, ERG9, and squalene overloads; LTs diminish this harm by accumulating inositol 1-phosphate. The diauxic shift drives an EtOH buffering by promoting an energy burst under stress, mainly in HTs. Analysis of mutants showed genes and lncRNAs in three strains critical for their EtOH tolerance. Finally, longevity, peroxisome, energy and lipid metabolisms, RNA/protein degradation and storage systems are the main pathways driving the EtOH tolerance phenotypes.

Aims The study was focused on the evaluation of antimicrobial activity in vitro of the essential oil (EO) of leaves from Schinus molle against bacteria and fungi of clinical importance in the search for the discovery of new active compounds. Methods and results The chemical composition of the S. molle EO was determined by gas chromatography/mass spectrometry and its antimicrobial effect was verified by broth microdilution method. The major compounds found were β-pinene (25·23%), epi-α-cadinol (21·29%), α-pinene (18·72%), myrcene (11·54%) and sabinene (5·02%). The EO showed significant antifungal activity against Paracoccidioides brasiliensis (39·06 μg ml-1 ), weak action against Cryptococcus neoformans (625 μg ml-1 ) and Trichophyton quinckeanum (625 μg ml-1 ) and was inactive against Candida sp. In the analysis of the antibacterial action, the micro-organisms tested did not show sensitivity. Conclusions This study showed a promising result of S. molle volatiles against the fungus P. brasiliensis, which causes paracoccidioidomycosis (PCM), a systemic mycosis of great clinical importance in Latin America. Significance and impact of the study The results found here are novel and encourage investigations of the compounds present in this EO, which represents a source of molecules with potential use in the treatment of PCM.

We aimed to investigate the antibacterial activities of carvacrol, thymol, eugenol, cinnamaldehyde, and lantibiotic nisin against standard bacterial strains of the milk pathogens Staphylococcus aureus ATCC 25923 and Listeria monocytogenes ATCC 15313 in cow milk. The minimum inhibitory concentrations (MIC) of these substances were recorded. The synergistic effects were also assessed in culture medium (time kill curve) and in a food model (cow milk) during the storage period (4 °C for 6 d) after inoculation with S. aureus and L. monocytogenes individually by combining nisin and the phenolic compounds at proportions of 1/4 + 1/4 the MIC (determined in a previous in vitro assay) in the culture medium and 1/4 + 1/4 of MIC in the food model. Inhibitory activities of nisin and the tested compounds, as well as synergism in the combinations, were found against both bacteria assayed. Bacteriostatic effects were found with all combinations and a significant difference in L. monocytogenes reduction was found compared with the control assays. Thus, the antibacterial activity of nisin combined with phenolic compounds was confirmed against these pathogenic bacteria that are important in the milk industry, or more broadly in food science, with potential applications for milk preservation.

Made available in DSpace on 2018-12-11T17:18:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-04 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Natural products represent a source of biologically active molecules that have an important role in drug discovery. The aromatic plant Blepharocalyx salicifolius has a diverse chemical constitution but the biological activities of its essential oils have not been thoroughly investigated. The aims of this paper were to evaluate in vitro cytotoxic, antifungal and antibacterial activities of an essential oil from leaves of B. salicifolius and to identify its main chemical constituents. The essential oil was extracted by steam distillation, chemical composition was determined by gas chromatography/mass spectrometry, and biological activities were performed by a microdilution broth method. The yield of essential oil was 0.86% (w/w), and the main constituents identified were bicyclogermacrene (17.50%), globulol (14.13%), viridiflorol (8.83%), γ-eudesmol (7.89%) and α-eudesmol (6.88%). The essential oil was cytotoxic against the MDA-MB-231 (46.60 µg·mL−1) breast cancer cell line, being more selective for this cell type compared to the normal breast cell line MCF-10A (314.44 µg·mL−1). Flow cytometry and cytotoxicity results showed that this oil does not act by inducing cell death, but rather by impairment of cellular metabolism specifically of the cancer cells. Furthermore, it presented antifungal activity against Paracoccidioides brasiliensis (156.25 µg·mL−1) but was inactive against other fungi and bacteria. Essential oil from B. salicifolius showed promising biological activities and is therefore a source of molecules to be exploited in medicine or by the pharmaceutical industry. Institute of Biosciences of Botucatu Laboratory of Bacteriology Unesp-São Paulo State University Institute of Biomedical Sciences Trypanosomatids Laboratory (LATRI) UFU-Federal University of Uberlândia Institute of Biosciences of Botucatu Laboratory of Fungi Biology Unesp-São Paulo State University Institute of Biosciences of Botucatu Laboratory of Phytomedicines Pharmacology and Biotechnology (PhytoPharmaTech) Unesp-São Paulo State University Institute of Biosciences of Botucatu Laboratory of Bacteriology Unesp-São Paulo State University Institute of Biosciences of Botucatu Laboratory of Fungi Biology Unesp-São Paulo State University Institute of Biosciences of Botucatu Laboratory of Phytomedicines Pharmacology and Biotechnology (PhytoPharmaTech) Unesp-São Paulo State University FAPESP: 2015/14278-6

The seasonal chemical composition of essential oils from Inga laurina was determined by GC/MS. In the stem bark’s essential oil extracted during the dry season, the presence of terpenoids (30.05%) stood out, and phytol (9.76%) was the major compound identified. For the stem bark oil obtained during the rainy season, in addition to terpenoids (26.63%), a large amount of fatty acids (46.84%) were identified, in particular palmitic acid (25.40%). Regarding the leaves’ essential oil obtained in the dry season, esters (42.35%) were the main components. The main ester present was (Z)-hex-3-enyl benzoate (10.15%) and the major compound of this oil was (Z)-hex-3-en-1-ol (14.23%). Terpenoids (33.84%), long-chain alkanes (27.04%) and fatty acids (21.72%) were the main components of the essential oil from leaves in the rainy season. Phytol (33.21%), nonacosane (21.95%) and palmitic acid (15.20%) were the major compounds identified. The antimicrobial activity against aerobic and anaerobic oral bacteria was evaluated by the microdilution broth method and cytotoxic activity was carried out with Vero cells. The essential oils from the rainy season showed a better inhibition of the bacterial growth with Minimal Inhibitory Concentrations (MIC) values of 25 or 50 µg·mL−1 for aerobic bacteria, and high selectivity against bacteria was observed. The large amount of fatty acids in rainy season oils may be related to the better inhibitory effects observed.

Diabetes mellitus is a chronic disease involving persistent hyperglycemia, which causes an imbalance between reactive oxygen species and antioxidant enzymes and results in damage to various tissues, including the brain. Many societies have traditionally employed medicinal plants to control the hyperglycemia. Pouteria ramiflora, a species occurring in the savanna biome of the Cerrado (Brazil) has been studied because of its possible ability to inhibit carbohydrate digestion. Rats with streptozotocin-induced diabetes treated with an alcoholic extract of Pouteria ramiflora show an improved glycemic level, increased glutathione peroxidase activity, decreased superoxide dismutase activity, and reduced lipid peroxidation and antioxidant status. The extract also restored myosin-Va expression and the nuclear diameters of pyramidal neurons of the CA3 subregion and that of the polymorphic cells of the hilus. We conclude that Pouteria ramiflora extract exerts a neuroprotective effect against oxidative damage and myosin-Va expression and is able to prevent hippocampal neuronal loss in the CA3 and hilus subfields of diabetic rats. However, future studies are needed to understand the mechanism of action of Pouteria ramiflora extract in acute and chronic diabetes.

We evaluated the polypeptide profiles, inhibition of human salivary α-amylase activity, and hemagglutination properties of a commercial phaseolamin sample. We also performed an in vivo assay to investigate the effects of a commercial phaseolamin treatment (100, 500, or 1500 mg/kg) over 20 days on the glycemia, body weight, and serum biochemical parameters (total cholesterol, triglycerides, alanine aminotransferase, and aspartate aminotransferase) of nondiabetic and streptozotocin-induced diabetic rats. The in vitro evaluation showed defined protein profiles, low hemagglutination activity, and high α-amylase inhibition. None of the experimental groups treated with phaseolamin or acarbose showed decreases in body weight. Our data demonstrate that phaseolamin inhibits amylase activity in vitro, reduces blood glucose levels, decreases or attenuates some of the renal and hepatic effects of diabetes in streptozotocin-induced rats, and could therefore have therapeutic potential in the treatment or prevention of the complications of diabetes.

The Ca 2+ /calmodulin complex interacts with and regulates various enzymes and target proteins known as calmodulin-binding proteins (CaMBPs). This group of proteins includes molecular motors such as myosins. In this study, we show that non-muscle myosin-IIB is overexpressed in the brains of diabetic rats. We isolated CaMBPs from the brains of non-diabetic rats and rats with streptozotocin-induced diabetes and purified them by immobilized-calmodulin affinity chromatography. The proteins were eluted with EGTA and urea, separated by SDS-PAGE, digested and submitted to peptide mass fingerprinting analysis. Thirteen intense bands were found in both types of brains, two were found exclusively in non-diabetic brains and four were found exclusively in diabetic brains. A large fraction of the eluted proteins contained putative IQ motifs or calmodulin-binding sites. The results of the myosin-IIB affinity chromatography elution, western blot and RT-PCR analyses suggest that myosin-IIB protein and mRNA are expressed at high levels in diabetic brains. This is the first study that has demonstrated differential expression of CaMBPs in diabetic and non-diabetic brain tissue through a comparative proteomic analysis, and it opens up a new approach to studying the relationship between the expression of myosins in the brain, hyperglycemia and intracellular calcium regulation.