Update on treatment of Hepatitis C: promising new molecules for difficult to treat patients: Atualizações no tratamento da Hepatite C: novas moléculas promissoras para pacientes de difícil tratamento

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

COVID-19 diagnosis and SARS-CoV-2 viral load in hospitalized patients versus people with Flu-Like Syndrome

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

Estudo químico, análise do óleo essencial e atividades biológicas de Inga laurina (Sw.) Willd

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.Fundação de Amparo a Pesquisa do Estado de Minas GeraisMestre em QuímicaInga 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

Chemical Composition and Bioactivity of Essential Oil from Blepharocalyx salicifolius

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

Integrative Analysis of the Ethanol Tolerance of Saccharomyces cerevisiae.

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

Brazilian Flora 2020: Leveraging the power of a collaborative scientific network

International audienceThe shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora