Antioxidant activity, phenolic profile, cytotoxicity and genotoxicity of plant extracts

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Antioxidant activity, phenolic profile, cytotoxicity and genotoxicity of plant extracts

The outbreak of COVID-19 disease caused by SARS-CoV-2 forced the scientific world to search for new alternatives to help control the virus. Plant extracts have natural compounds that might provide a starting point for the research on the use of plants as an excellent source of new antiviral agents against viruses, including COVID-19 to be included in disinfectants, fabrics or other materials. In this study, the polyphenols content (Folin-Ciocalteu), antioxidant capacity (DPPH, ABTS and ORAC) and the phenolic profile (HPLC) of different hydroethanolic (ethanol:H2O 50:50 v/v) extracts of medicinal plants cultivated under controlled conditions in Portugal (echinacea, rosemary, laurel, thyme and rock rose) were determined, as well as the cytotoxicity effect against a keratinocyte cell line using cell viability assay by PrestoBlue and genotoxicity effect using the AMES test. According to the results, total phenolic content ranged from 204.54 ± 1.78 / 274.20 ± 3.14 (mg EAG/g extract) with the rock rose extract presenting the highest content (p < 0.05). The extracts showed a good antioxidant capacity demonstrated by the high values found for ORAC, which ranged 2855.03 ± 9.75 / 5285.35 ± 60.04 µMol Trolox/mg extract. HPLC analysis revealed the presence of different compounds in the extracts such as the kaempferol-O-glucuronide, catechin, protocatechuic acid and galloyl glucoside, representing a potential source of bioactive components with antioxidant capacity. No toxicity was observed towards the keratinocyte cells and none of them showed mutagenic effects. Based on the results of safety and high polyphenols content of the extracts they demonstrate a great potential as antimicrobial agents. This will allow the design of new experiments aimed at evaluating the antiviral activity of these extracts, especially against SARS-CoV-2.info:eu-repo/semantics/publishedVersio

Chemical characterization, cytotoxic evaluation and anti-SARS-CoV2 activity of plant extracts rich in hydrolysable tannins

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Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype

Copyright © 2021 Trombetta, Farias, Gomes, Godinho-Santos, Rosmaninho, Conceição, Laia, Santos, Almeida, Mota, Gomes, Serrano, Veldhoen, Sousa and Fernandes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.After more than one year since the COVID-19 outbreak, patients with severe disease still constitute the bottleneck of the pandemic management. Aberrant inflammatory responses, ranging from cytokine storm to immune-suppression, were described in COVID-19 and no treatment was demonstrated to change the prognosis significantly. Therefore, there is an urgent need for understanding the underlying pathogenic mechanisms to guide therapeutic interventions. This study was designed to assess myeloid cell activation and phenotype leading to recovery in patients surviving severe COVID-19. We evaluated longitudinally patients with COVID-19 related respiratory insufficiency, stratified according to the need of intensive care unit admission (ICU, n = 11, and No-ICU, n = 9), and age and sex matched healthy controls (HCs, n = 11), by flow cytometry and a wide array of serum inflammatory/immune-regulatory mediators. All patients featured systemic immune-regulatory myeloid cell phenotype as assessed by both unsupervised and supervised analysis of circulating monocyte and dendritic cell subsets. Specifically, we observed a reduction of CD14lowCD16+ monocytes, and reduced expression of CD80, CD86, and Slan. Moreover, mDCs, pDCs, and basophils were significantly reduced, in comparison to healthy subjects. Contemporaneously, both monocytes and DCs showed increased expression of CD163, CD204, CD206, and PD-L1 immune-regulatory markers. The expansion of M2-like monocytes was significantly higher at admission in patients featuring detectable SARS-CoV-2 plasma viral load and it was positively correlated with the levels of specific antibodies. In No-ICU patients, we observed a peak of the alterations at admission and a progressive regression to a phenotype similar to HCs at discharge. Interestingly, in ICU patients, the expression of immuno-suppressive markers progressively increased until discharge. Notably, an increase of M2-like HLA-DRhighPD-L1+ cells in CD14++CD16- monocytes and in dendritic cell subsets was observed at ICU discharge. Furthermore, IFN-γ and IL-12p40 showed a decline over time in ICU patients, while high values of IL1RA and IL-10 were maintained. In conclusion, these results support that timely acquisition of a myeloid cell immune-regulatory phenotype might contribute to recovery in severe systemic SARS-CoV-2 infection and suggest that therapeutic agents favoring an innate immune system regulatory shift may represent the best strategy to be implemented at this stage.The Research was funded by Fundação para a Ciência e Tecnologia (FCT), “APOIO ESPECIAL RESEARCH 4COVID-19” projects 803, 125, 231_596873172, and 729. AMCG and GF received fellowships funded by FCT (DOCTORATES4COVID-19, 2020.10202.BD), and JANSSEN- CILAG FARMACÊUTICA, respectively. The funder was not involved in the study design, collection, analysis, interpretation of data, writing of the article or decision to submit it for publication. MV was supported by the European Union H2020 ERA project (No 667824 – EXCELLtoINNOV). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 667824.info:eu-repo/semantics/publishedVersio

Red grape pomace extract: bioactive potential against bacteria, fungi and SARS-CoV-2

The outbreak of COVID-19 disease caused by SARS-CoV-2 forced the scientific world to search for new alternatives to help control the virus. Grape pomace, which is an industrial residue obtained from the winemaking process, has bioactive compounds derived from the grape [1], which can be a starting point for research on the use this residue as a source of new antiviral agents. Thus, the objective of this study was to obtain an extract from the by-product of red grapes discarded by the wine industry in Portugal to be used as an antiviral agent with possible application in disinfectants, fabrics or other materials. The red grape pomace extract was obtained by maceration in a hydroethanolic solution (ethanol:H2O 50:50 v/v) under optimized conditions and submitted to freeze drying. The extract was tested against pathogenic bacteria and a variety of fungi, and the antiviral activity was evaluated for SARS-CoV-2 in Vero cells. The extract showed antimicrobial activity against a large number of bacteria tested, e.g., B. cereus (1.56 mg/mL), L. monocytogenes and S. aureus (3.125 mg/mL), and E. coli and S. Typhimurium (50 mg/mL). Regarding its antifungal potential, this extract did not show inhibition against the environmental fungi tested, however, it inhibited two of the tested dermatophytes. T. mentagrophytes and the yeast M. furfur at a concentration of 6.25 mg/mL and 50 mg/mL, respectively. Regarding the antiviral activity, the results achieved for the viral titer was 6000 PFU/mL, the antiviral activity for SARS-CoV-2 was 1.36 ± 0.15 Mv and the percentage of reduction was of 95.38 ± 1.54%. The results showed that the obtained extract revealed consistent results of antiviral activity, presenting a potential for applications against SARS-CoV-2. In addition, it showed potential against some bacterial pathogens and fungal dermatophytes. Further studies are required for the validation and application of this extract.info:eu-repo/semantics/publishedVersio

Molecular profiling of a rare rosette-forming glioneuronal tumor arising in the spinal cord

Rosette-forming glioneuronal tumor (RGNT) of the IV ventricle is a rare and recently recognized brain tumor entity. It is histologically composed by two distinct features: a glial component, resembling pilocytic astrocytoma, and a component forming neurocytic rosettes and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in the spinal cord. Following an immunohistochemistry validation, we further performed an extensive genomic analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. We observed the loss of 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Local amplifications in 9q34.2 and 19p13.3 (encompassing the gene SBNO2) were identified. Moreover, we observed focal gains/losses in several chromosomes. Additionally, on chromosome 7, we identified the presence of the KIAA1549:BRAF gene fusion, which was further validated by RT-PCR and FISH. Across all mutational analyses, we detected and validated the somatic mutations of the genes MLL2, CNNM3, PCDHGC4 and SCN1A. Our comprehensive molecular profiling of this RGNT suggests that MAPK pathway and methylome changes, driven by KIAA1549:BRAF fusion and MLL2 mutation, respectively, could be associated with the development of this rare tumor entity.Conselho Nacional de Desenvolvimento Científico e Tecnológico [475358/2011-2] to RMR (www.cnpq.br); Fundação de Amparo a Pesquisa do Estado de São Paulo [2012/19590-0] to RMR and [2011/08523-7 and 2012/08287-4] to LTB (www.fapesp.br); the Foundation for Science and Technology (FCT) [PTDC/SAU-ONC/115513/2009] to RMR; and the National Cancer Institute [P30CA046934] to MG

Chromosome copy number changes carry prognostic information independent of KIT/PDGFRA point mutations in gastrointestinal stromal tumors

<p>Abstract</p> <p>Background</p> <p>Oncogenic point mutations in <it>KIT </it>or <it>PDGFRA </it>are recognized as the primary events responsible for the pathogenesis of most gastrointestinal stromal tumors (GIST), but additional genomic alterations are frequent and presumably required for tumor progression. The relative contribution of such alterations for the biology and clinical behavior of GIST, however, remains elusive.</p> <p>Methods</p> <p>In the present study, somatic mutations in <it>KIT </it>and <it>PDGFRA </it>were evaluated by direct sequencing analysis in a consecutive series of 80 GIST patients. For a subset of 29 tumors, comparative genomic hybridization was additionally used to screen for chromosome copy number aberrations. Genotype and genomic findings were cross-tabulated and compared with available clinical and follow-up data.</p> <p>Results</p> <p>We report an overall mutation frequency of 87.5%, with 76.25% of the tumors showing alterations in <it>KIT </it>and 11.25% in <it>PDGFRA</it>. Secondary <it>KIT </it>mutations were additionally found in two of four samples obtained after imatinib treatment. Chromosomal imbalances were detected in 25 out of 29 tumors (86%), namely losses at 14q (88% of abnormal cases), 22q (44%), 1p (44%), and 15q (36%), and gains at 1q (16%) and 12q (20%). In addition to clinico-pathological high-risk groups, patients with <it>KIT </it>mutations, genomic complexity, genomic gains and deletions at either 1p or 22q showed a significantly shorter disease-free survival. Furthermore, genomic complexity was the best predictor of disease progression in multivariate analysis.</p> <p>Conclusions</p> <p>In addition to <it>KIT/PDGFRA </it>mutational status, our findings indicate that secondary chromosomal changes contribute significantly to tumor development and progression of GIST and that genomic complexity carries independent prognostic value that complements clinico-pathological and genotype information.</p

Contrasting Geographical Distributions as a Result of Thermal Tolerance and Long-Distance Dispersal in Two Allegedly Widespread Tropical Brown Algae

BackgroundMany tropical marine macroalgae are reported from all three ocean basins, though these very wide distributions may simply be an artifact resulting from inadequate taxonomy that fails to take into account cryptic diversity. Alternatively, pantropical distributions challenge the belief of limited intrinsic dispersal capacity of marine seaweeds and the effectiveness of the north-south oriented continents as dispersal barriers. We aimed to re-assess the distribution of two allegedly circumtropical brown algae, Dictyota ciliolata and D. crenulata, and interpret the realized geographical range of the respective species in relation to their thermal tolerance and major tectonic and climatic events during the Cenozoic.Methodology/Principal FindingsSpecies delimitation was based on 184 chloroplast encoded psbA sequences, using a Generalized Mixed Yule Coalescent method. Phylogenetic relationships were inferred by analyzing a six-gene dataset. Divergence times were estimated using relaxed molecular clock methods and published calibration data. Distribution ranges of the species were inferred from DNA-confirmed records, complemented with credible literature data and herbarium vouchers. Temperature tolerances of the species were determined by correlating distribution records with local SST values. We found considerable conflict between traditional and DNA-based species definitions. Dictyota crenulata consists of several pseudocryptic species, which have restricted distributions in the Atlantic Ocean and Pacific Central America. In contrast, the pantropical distribution of D. ciliolata is confirmed and linked to its significantly wider temperature tolerance.Conclusions/SignificanceTectonically driven rearrangements of physical barriers left an unequivocal imprint on the current diversity patterns of marine macroalgae, as witnessed by the D. crenulata–complex. The nearly circumglobal tropical distribution of D. ciliolata, however, demonstrates that the north-south oriented continents do not present absolute dispersal barriers for species characterized by wide temperature tolerances