Prophylactic outcomes of casbane diterpene in Candida albicans and Candida glabrata biofilms

Biofilms are surface associated communities of microorganisms embedded within a self-produced extracellular matrix and adhered on inert and biotic surfaces. These biological consortia are considered the most prevalent growth form of microorganisms. Biofilm formation is a potent virulence factor for a number of Candida species, as it confers significant tolerance to antimicrobial therapy, primarily by limiting the penetration of substances through the biofilm matrix. Casbane Diterpenes (CD) belongs to the class of diterpenoids isolated from few species of plants from Euphorbiaceae family with important anticancer and antibacterial activities. So, the goal of this study was to assess the antibiofilm effect of a Casbane Diterpene isolated from the stalks of Croton nepetaefolius against Candida albicans and Candida glabrata. Biofilms were developed within the 96- well microtiterplates in the presence of the CD. After 24 hours of growth, 100 μL of cells suspensions (1 x 106 cells ml-1 in Nutrient Broth) and 100 μL of solution of CD (500 - 31.5 μg/mL) were pipetted into each well and incubated for 24 h at 37ºC in an orbital shaker at 120 rpm. Biofilms formation was characterized by total biomass, through crystal violet (CV), and number of viable cells, expressed as log CFU per cm2. CD showed to be able to reduce the biofilm formation of C. albicans and C. glabrata. CD reduced C. albicans biomass in 82, 64, 57 and 27 % at the concentrations of 500, 250, 125 and 62.5 μg/mL, respectively. C. glabrata biomass was reduced in 68 and 26 % at 500 and 250 μg/mL. Regarding the number of viable cells embedded in the yeast biofilms, CD at 500 and 250 μg/mL reduced 2 and 1 log of C. albicans biofilm CFUs, and 2.5 and 1 log for C. glabrata, respectively. Regarding the high resistance and recalcitrance of Candida biofilms to the traditional therapies, CD emerges as a good prophylactic alternative to be used alone or in combination with other traditional drugs

Antibacterial and antioxidant activities of Derriobtusone A isolated from Lonchocarpus obtusus

This study evaluated the effect of derriobtusone A, a flavonoid isolated from Lonchocarpus obtusus, on two important pathogenic bacteria, Staphylococcus aureus and Escherichia coli, as well as its antioxidant activity and toxicity. Planktonic growth assays were performed, and the inhibition of biofilm formation was evaluated. In addition, antioxidant activity was assessed by DPPH radical scavenging assay, ferrous ion chelating assay, ferric-reducing antioxidant power assay, and β-carotene bleaching assay. Toxicity was evaluated by the brine shrimp lethality test. Results showed that derriobtusone A completely inhibited the planktonic growth of S. aureus at 250 and 500 μg/mL; however, it did not have the same activity on E. coli. Derriobtusone A reduced the biomass and colony-forming unit (cfu) of S. aureus biofilm at concentrations of 250 and 500 μg/mL. In various concentrations, it reduced the biofilm biomass of E. coli, and, in all concentrations, it weakly reduced the cfu. Derriobtusone A showed highly efficient antioxidant ability in scavenging DPPH radical and inhibiting β-carotene oxidation. The compound showed no lethality to Artemia sp. nauplii. In conclusion, derriobtusone A may be an effective molecule against S. aureus and its biofilm, as well as a potential antioxidant compound with no toxicity.This study was supported by CAPES (Brazil) through the BEX NT 2052/11NT3 Project and by IBB-CEB and FCT (Portugal) and European Community Fund FEDER, through Program COMPETE, in the ambit of Project PTDC/SAU-ESA/646091/2006/FCOMP-01-0124-FEDER-007480. Otilia Deusdenia Loiola Pessoa, Benildo Sousa Cavada, and Edson Holanda Teixeira are Senior Fellows of CNPq. Mr. David Martin helped with the English editing of the paper

Casbane diterpene as a promising natural antimicrobial agent against biofilm-associated infections

Croton nepetaefolius is a native plant from northeastern Brazil that belongs to the Euphorbiaceae family. The biological action of this plant has been extensively explored, being the secondary metabolites responsible for its properties alkaloids, diterpenes, and triterpenes. This study aimed to evaluate the ability of casbane diterpene (CD), isolated from the ethanolic extract of C. nepetaefolius, to inhibit microbial growth and biofilm formation of several clinical relevant species (bacteria and yeasts). It was found that CD possessed biocidal and biostatic activity against the majority of the species screened, with minimal active concentrations ranging between 125 and 500 µg/mL. In addition, it was observed that biofilm formation was inhibited even when the planktonic growth was not significantly affected. In conclusion, CD showed potential to be a natural tool for the treatment of diseases caused by different infectious microorganismsThis study was supported by FUNCAP and CNPq (Brazil) and by FCT (Portugal) through the project PTDC/SAU-ESA/64609/2006

Chemical investigations of asterÃceas of CearÃ: Baccharis trinervis, Eupatorium ballotaefolium, Eupatorium betonicaeforme, Eupatorium pauciflorum, Pectis apodocephala, Pectis oligocephala, Verbesina diversifolia, Vernonia chalybaea e Vernonia scorpioides

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorEste trabalho descreve a investigaÃÃo quÃmica de plantas da famÃlia Asteraceae nativas da flora cearense, pertencentes aos gÃneros Baccharis, Eupatorium, Pectis, Verbesina e Vernonia. Eupatorium ballotaefolium H.B.K. e E. betonicaeforme Baker foram selecionados para o estudo da composiÃÃo quÃmica volÃtil e nÃo-volÃtil, enquanto Baccharis trinervis (Lam.) Pers., E. pauciflorum Kunth, Pectis apodocephala Baker, P. oligocephala Baker, Verbesina diversifolia D.C., Vernonia chalybaea Mart. e V. scorpioides (Lam.) Pers, tiveram exclusivamente a composiÃÃo quÃmica dos Ãleos essenciais determinados. O potencial antimicrobiano, larvicida e nematicida de alguns Ãleos foi avaliado. O Ãleo essencial de B. trinervis apresentou moderada atividade antimicrobiana, enquanto os Ãleos essenciais de P. apodocephala, P. oligocephala e E. betonicaeforme, incluindo dois de seus principais constituintes, 2,2-dimetil-6-vinilcroman-4-ona e 2-senecioil-4-vinilfenol, apresentaram significativa atividade larvicida contra larvas do Aedes aegypti. Os Ãleos essenciais das Pectis acima mencionadas, tambÃm apresentaram propriedades nematicida contra o fito-nematÃide Meloidogyne incognita. Neste trabalho investigou-se ainda, a composiÃÃo dos Ãcidos graxos contidos nas fraÃÃes apolares dos extratos hexÃnicos da parte aÃrea de E. ballotaefolium e E. betonicaeforme. Foram identificados um total de 13 Ãcidos graxos, sendo o Ãcido hexadecanÃico (C16:0) o constituinte majoritÃrio para ambas as espÃcies. A prospecÃÃo quÃmica relativa Ãs duas espÃcies de Eupatorium resultou no isolamento e identificaÃÃo de 11 substÃncias para E. ballotaefolium e 17 substÃncias para E. betonicaeforme. Do extrato hexÃnico da parte aÃrea de E. ballotaefolium isolou-se, em mistura, os fitoesterÃides β- sitosterol e estigmasterol e os triterpenos acetato de taraxasterila e taraxasterol, enquanto do extrato etanÃlico, foram isolados e caracterizados os flavonÃides nepetina e quercetina na forma glicosilada e as formas glicosÃdicas do sitostetol e estigmasterol. Do extrato hexÃnico das raÃzes foram isolados os triterpenos epifriedelanol e dammara-20,24-dien-3β-ol e do extrato etanÃlico foi obtida a cumarina 11-hidroxi-11,12-di-hidroobliquina. Do extrato hexÃnico das flores de E. betonicaeforme foram isolados uma lactona sesquiterpÃnica, 8β- angeloiloxi-9β,10β-di-hidroxi-1-oxo-germacra-4E,11(13)dien-12,6α-olido, uma lactona de cadeia longa, 3β-hidroxieicosan-1,5β-olido, os diterpenos Ãcido grandiflÃrico e Ãcido 15α- decanoiloxi-caur-16-en-19-Ãico, o esterÃide espinasterol e o Ãcido hexacosanÃico, enquanto do extrato etanÃlico, foram isolados o triterpeno acetato de taraxasterila e os flavonÃides, nepetina, canferol e ramnocitrina. Do extrato hexÃnico das raÃzes, isolou-se em mistura, os xxiv esterÃides β-sitosterol e estigmasterol, enquanto do extrato etanÃlico isolou-se a cromona 6,6- acetil-2,2-dimetilcroman-4-ona e o flavonÃide nepetina. Do extrato hexÃnico da parte aÃrea isolou-se a mistura binÃria dos triterpenos α- e β-amirina, alÃm do acetato de taraxasterila. De acordo com o levantamento bibliogrÃfico, o diterpeno denominado Ãcido 15α-decanoiloxicaur- 16-en-19-Ãico, ainda nÃo havia sido registrado na literatura e os constituintes 8β- angeloiloxi-9β,10β-di-hidroxi-1-oxo-germacra-4E,11(13)dien-12,6α-olido, 3β- hidroxieicosan-1,5β-olido, 2,2-dimetil-6-vinil-croman-4-ona, 6-acetil -2,2-dimetil-croman-4- ona, 2-senecioil-4-vinilfenol e damara-20,24-dien-3β-ol, estÃo sendo registrados pela primeira vez no gÃnero. A lactona 8β-angeloiloxi-9β,10β-di-hidroxi-1-oxo-germacra-4E,11(13)dien- 12,6α-olido e o flavonÃide nepetina apresentaram moderado potencial citotÃxico quando testados frente a um painel de cÃlulas tumorais, apresentando IC50 nas faixas de 1,27-7,16 e 5,48-15,12 μg/mL, respectivamente. A determinaÃÃo estrutural dos metabÃlitos secundÃrios isolados neste trabalho envolveu o uso de tÃcnicas espectromÃtricas como infravermelho (IV), espectrometria de massa (EM) e ressonÃncia magnÃtica nuclear de hidrogÃnio (RMN 1H) e carbono-13 (RMN 13C), incluindo tÃcnicas bidimensionais como COSY, HMQC, HMBC e NOESY, bem como comparaÃÃo com dados descritos na literatura.This work describes the chemical investigation of native plants of the Asteraceae family from Cearà State flora, belonging to the genera Baccharis, Eupatorium, Pectis, Verbesina and Vernonia. Eupatorium ballotaefolium H.B.K. and E. betonicaeforme Baker were selected to study their volatile and non-volatile chemical composition, while for Baccharis trinervis (Lam.) Pers., E. pauciflorum Kunth, Pectis apodocephala Baker, P. oligocephala Baker, Verbesina diversifolia D.C., Vernonia chalybaea Mart. and V. scorpioides (Lam.) Pers only the chemical composition of the essential oils, was determined. The antimicrobial, larvicidal and nematicidal potential of some of the oils were evaluated. The essential oil of B. trinervis showed moderate antimicrobial activity, while the essential oils of P. apodocephala, P. oligocephala and E. betonicaeforme, including two of their major constituents, 2,2-dimethyl-6-vinylchroman-4-one and 2-senecioyl-4-vinylphenol, showed significant larvicidal activity against the Aedes aegypti larvae. The essential oils from the above mentioned Pectis species also showed nematicidal properties against the nematode Meloidogyne incognita. The fatty acid composition of the apolar fractions from the hexane extracts of the aerial parts of E. ballotaefolium and E. betonicaeforme was also examined. A total of 13 fatty acids were identified, being hexadecanoic acid (C16:0) the major compound for both species. The chemical analysis of both Eupatorium species resulted in the isolation and characterization of 11 substances for E. ballotaefolium and 17 substances for E. betonicaeforme. From the hexane extract of the aerial parts of E. ballotaefolium was isolated a mixture of β-sitosterol and stigmasterol, the triterpenes taraxasteryl acetate and taraxasterol, while the flavonoids nepetin and quercetin-3-O-glucoside and a binary misture of sitosterol and stigmasterol glucosilated, were isolated from the ethanol extract. From the hexane extract of the roots were isolated the tritepenes epifriedelanol and dammara-20,24-dien-3β-ol and from the ethanol extract was obtained the coumarin 11-hydroxy-11,12-di-hydroobliquine. From the hexane extract of E. betonicaeforme flowers a sesquiterpene lactone, 8β- angeloyloxy-9β,10β-dihydroxy-1-oxo-germacra-4E,11(13)dien-12,6α-olide, a long chain lactone 3β-hydroxiicosan-1,5β-olide, the diterpenes grandifloric and 15α-decanoyloxy-kaur- 16-en-19-oic acids, the steroid spinasterol and hexacosanoic acid were isolated. From the ethanol extract were isolated taraxasteril acetate, nepetin, kaempferol and ramnocitrin. From the hexane extract of the roots were isolated the mixture of β-sitosterol and stigmasterol, while from the ethanol extract were isolated 6,6-acetyl-2,2-dimethylcroman-4-one and nepetin. The hexane extract of the aerial parts were obtained the binary mixture of α- and β- amyrin, and taraxasteryl acetate. To the best of our knowledge the diterpene characterized as 15α-decanoyloxy-kaur-16-en-19-oic acid is a new substance while the compounds 8β- angeloyloxy-9β,10β-dihydroxy-1-oxo-germacra-4E,11(13)dien-12,6α-olide, 3β- hydroxyeicosan-1,5β-olide, 2,2-dimethyl-6-vinyl-chroman-4-one, 6-acetyl-2,2-dimethylchroman- 4-one, 2-senecioyl-4-vinylphenol and dammara-20,24-dien-3β-ol are being reported for the first time to the genus. The lactone 8β-angeloyloxy-9β,10β-dihydroxy-1-oxogermacra- 4E,11(13)dien-12,6α-olide and the flavonoid nepetin showed moderated cytotoxic activity against a panel of five cell lines with IC50 in the range of 1,27-7,16 e 5,48-15,12 μg/mL, respectively. The structures of all secondary metabolites were established using spectrometric data such as IR, MS, 1H and 13C NMR, including bidimensional techniques (COSY, HMQC, HMBC and NOESY), and comparison with from the literature data

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use