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1.
Braz J Biol ; 83: e266526, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37283371

RESUMO

Schistosomiasis is a neglected tropical disease caused by parasitic worms of several species of the genus Schistosoma. Transmission occurs by parasitic larvae that stay in freshwater snails of the genus Biomphalaria. Thus, the search for new products that are biodegradable has increased the interest in products of plant origin. The aim of this article is to review the isolated substances from natural products that showed molluscicidal activity against the species Biomphalaria glabrata in order to reevaluate the most promising prototypes and update the progress of research to obtain a new molluscicide. We perform searches using scientific databases, such as Scientific Electronic Library Online (SciELO), Google schoolar, PUBMED, Web of Science and Latin American and Caribbean Literature on Health Sciences (LILACS). From 2000 to 2022, using the keywords "isolated substances", "molluscicidal activity" and "Biomphalaria glabrata". In the present study, it was possible to observe 19 promising molluscicidal molecules with a lethal concentration below 20 µg/mL. Of these promising isolates, only 5 isolates had the CL90 calculated and within the value recommended by WHO: Benzoic acid, 2',4',6'-Trihydroxydihydrochalcone, Divaricatic acid, Piplartine and 2-hydroxy-1,4-naphthoquinone (Lapachol). We conclude that beyond a few results in the area, the researches don't follow the methodological pattern (exposure time and measure units, toxicity test), in this way, as they don't follow a pattern on the result's exposure (LC), not following, in sum, the recommended by WHO.


Assuntos
Produtos Biológicos , Biomphalaria , Moluscocidas , Animais , Biomphalaria/parasitologia , Produtos Biológicos/farmacologia , Caramujos , Moluscocidas/toxicidade
2.
Braz J Biol ; 83: e268859, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37132741

RESUMO

The use of medicinal plants as raw material for extracts production and pure substances isolation and subsequence development of new drugs represents a constantly growing area. However, some stages are indispensable before pharmacologically evaluating natural products such as medicines. Toxicity tests in mammalian cells are essential to initiate new drugs development or verify the substance's biocompatibility. Thus, we verified the toxicity of crude extracts and fractions with different polarities obtained from the leaves and stems of eight plant species. The toxic effect was evaluated on macrophages obtained from the bone marrow and peritoneal cavity of a Swiss webster mouse and J774 macrophages. G8 cell lineage. These macrophages were cultured in a 96-well plate, and the compounds were added at a concentration of 100 µg/mL for 24 hours. After this time, the supernatant was removed. The toxicity was evaluated for lactate dehydrogenase (LDH) release assay and the resazurin assay, which uses an indicator dye to measure oxidation-reduction reactions. The results showed a difference in the percentage of toxicity when comparing the same extract in different types of macrophages. This outcome indicates that these cells from different origins may exhibit different responses when exposed to the same natural compounds.


Assuntos
Extratos Vegetais , Plantas Medicinais , Camundongos , Animais , Extratos Vegetais/toxicidade , Macrófagos , Folhas de Planta , Mamíferos
3.
Braz J Biol ; 84: e260065, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35766654

RESUMO

Achatina fulica is a terrestrial mollusk known as the giant African snail that is related to environmental, economic, urban, and public health problems. As control measures for this mollusk, cooking salt (NaCl) and calcium oxide (CaO) are used, and baits are composed of metaldehyde. However, these measures have environmental toxicity and impact the soil. In this way, natural products have been tested on this mollusk to discover and develop a substance to combat this urban and agricultural pest. This article aims to evaluate studies involving natural products to control the population of Achatina fulica. Articles and works published in books were included in the present work. A total of 1,103 works were found during the search. Of these, 14 works met the objective of these review and were included in this article. The tests do not possess methodological standardization, do not have a maximum concentration to be considered active, or a maximum exposure time. A lack of standardization in the methodology of tests on A. fulica was observed. The performance of tests on other life stages of the mollusk, as well as tests that analyze other parameters, are essential. Only one article analyzed presented phytochemical analysis. No ecotoxicity tests were reported either. Some extracts showed promising results, highlighting the aqueous extract of Capsicum frutescens. More studies investigating the molluscicidal activity of natural products on A. fulica are needed. It is very relevant that the new studies present a phytochemical analysis of the tested extracts, as well as ecotoxicity studies.


Assuntos
Produtos Biológicos , Animais , Produtos Biológicos/farmacologia , Aves , Caramujos
4.
Biomed Pharmacother ; 142: 112006, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34392085

RESUMO

P2X7 receptor promotes inflammatory response and neuropathic pain. New drugs capable of impairing inflammation and pain-reducing adverse effects extracted from plant extracts have been studied. Physalis angulate L. possesses traditional uses and exhibits antiparasitic, anti-inflammatory, antimicrobial, antinociceptive, antimalarial, antileishmanial, immunosuppressive, antiasthmatic. diuretic, and antitumor activities. The most representative phytochemical constituents identified with medicinal importance are the physalins and withanolides. However, the mechanism of anti-inflammatory action is scarce. Although some physalins and withanolides subtypes have anti-inflammatory activity, only four physalins subtypes (B, D, F, and G) have further studies. Therefore, we evaluated the crude ethanolic extract enriched with physalins B, D, F, and G from P. angulata leaves, a pool containing the physalins B, D, F, G, and the physalins individually, as P2X7 receptor antagonists. For this purpose, we evaluated ATP-induced dye uptake, macroscopic currents, and interleukin 1-ß (IL-1ß) in vitro. The crude extract and pool dose-dependently inhibited P2X7 receptor function. Thus, physalin B, D, F, and G individually evaluated for 5'-triphosphate (ATP)-induced dye uptake assay, whole-cell patch-clamp, and cytokine release showed distinct antagonist levels. Physalin D displayed higher potency and efficacy than physalin B, F, and G for all these parameters. In vivo mice model as ATP-induced paw edema was potently inhibited for physalin D, in contrast to physalin B, F, and G. ATP and lipopolysaccharide (LPS)-induced pleurisy in mice were reversed for physalin D treatment. Molecular modeling and computational simulation predicted the intermolecular interactions between the P2X7 receptor and physalin derivatives. In silico results indicated physalin D and F as a potent allosteric P2X7 receptor antagonist. These data confirm physalin D as a promisor source for developing a new P2X7 receptor antagonist with anti-inflammatory action.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Physalis/química , Extratos Vegetais/farmacologia , Secoesteroides/farmacologia , Lesão Pulmonar Aguda/fisiopatologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Simulação por Computador , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Masculino , Camundongos , Modelos Moleculares , Extratos Vegetais/administração & dosagem , Folhas de Planta , Antagonistas do Receptor Purinérgico P2X/administração & dosagem , Antagonistas do Receptor Purinérgico P2X/isolamento & purificação , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/efeitos dos fármacos , Secoesteroides/isolamento & purificação
5.
J Mycol Med ; 31(4): 101199, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34418685

RESUMO

INTRODUCTION: Itraconazole is the first-choice option to treat human and animal sporotrichosis. However, the emergence of itraconazole-resistant strains has encouraged research on new active antifungals. Among them, the essential oil of rosemary (Rosmarinus officinalis Linn., Lamiaceae) has shown antifungal activity in vitro. OBJECTIVE: Assessing, for the first time, the effectiveness of rosemary essential oil in vivo in experimental cutaneous sporotrichosis, as well as its chemical composition and action mode. METHODS: Itraconazole-resistant Sporothrix brasiliensis was inoculated in the left foot pad of 30 Wistar rats, which were randomized (n=10) for treatment with saline solution (control, CONT), itraconazole (ITRA, 10 mg/kg) and rosemary oil (ROSM, 250 mg/kg) for 30 days at an oral dose of 1 mL, daily. Clinical evolution, histopathology and fungal burden were investigated. GC-MS was used for chemical analysis; sorbitol protection and ergosterol effect were used to evaluate the action mechanism of rosemary oil. RESULTS: ROSM was the only group evolving to skin lesion remission, lack of edema and exudate, and mild-to-absent yeast cells. Rosemary oil delayed fungal spreading and protected systemic organs, mainly liver and spleen. The ROSM group presented lower fungal load than that observed for the CONT and ITRA groups (p<0.05). Antifungal action took place at complexation level after ergosterol application. Most compounds were 1,8-cineole/eucalyptol (47.91%), camphor (17.92%), and α-pinene (11.52%). CONCLUSIONS: These findings have evidenced that rosemary oil is a promising antifungal to treat sporotrichosis, since it protects systemic organs from fungal spread.


Assuntos
Óleos Voláteis , Rosmarinus , Animais , Ratos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Itraconazol/farmacologia , Óleos Voláteis/farmacologia , Ratos Wistar , Sporothrix
6.
Colloids Surf B Biointerfaces ; 185: 110610, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31711736

RESUMO

Cancer gene therapy based on p53 tumor suppressor gene supplementation emerges as one of the most challenging and promising strategies. The development of a suitable gene delivery system is imperative to ensure the feasibility and viability of cancer gene therapy in a clinical setting. The conception of delivery systems based on cell- penetrating peptides may deeply contribute for the evolution of therapy efficacy. In this context, the present work explores the p53 encoding plasmid DNA (pDNA) condensation ability of RALA peptide to produce a suitable intracellular delivery platform. These carriers, formed at several nitrogen to phosphate groups (N/P) ratio, were characterized in terms of morphology, size, surface charges, loading and complexation capacity and the fine structure has been analyzed by Fourier-transformed infrared (FTIR) spectroscopy. Confocal microscopy studies confirmed intracellular localization of nanoparticles, resulting in enhanced sustained pDNA uptake. Moreover, in vitro transfection of HeLa cells mediated by RALA/pDNA vectors allows for gene release and p53 protein expression. From these progresses, apoptosis in cancer cells has been investigated. It was found that N/P ratio strongly tailors gene transfection efficiency and, thus, it can be fine-tuned for desired degree of both protein expression and apoptosis. The great asset of the proposed system relies precisely on the use of N/P ratio as a tailoring parameter that can not only modulate vector´s properties but also the extent of pDNA delivery, protein expression and, consequently, the efficacy of p53 mediated cancer therapy.


Assuntos
Apoptose , Terapia Genética , Vetores Genéticos/genética , Neoplasias/terapia , Nitrogênio/química , Peptídeos/genética , Fosfatos/química , Plasmídeos/genética , Sequência de Aminoácidos , Caspase 3/metabolismo , Caspase 9/metabolismo , Morte Celular , Sobrevivência Celular , DNA/genética , Fibroblastos/citologia , Células HeLa , Humanos , Nanopartículas/química , Neoplasias/genética , Tamanho da Partícula , Peptídeos/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transfecção , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
7.
Water Sci Technol ; 80(1): 173-183, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31461434

RESUMO

Wastewater treatment facilities collecting wastewater from longstanding sewer networks of five municipalities in the Ave River basin (located in NW Portugal) are especially vulnerable to water inflows since they have considerable extensions of sewers installed in stream and riverbeds. TRATAVE, the company responsible for operating the system, designed and implemented a monitoring network to measure discharges along the entire drainage network and treatment facilities in order to reduce those water inflows. Several flow measurement devices were installed at strategic locations within the sewer network and integrated with a SCADA system responsible for its operation. A decision support system (DSS) is being implemented using the Delft-FEWS platform, integrating monitoring data and models. Based on monitored data and model results, an estimation of infiltration volumes during wet periods is presented. Moreover, the capabilities of the DSS are illustrated in: (i) location of manholes losses along sewer networks during wet periods; (ii) identification and location of unknown connections to the sewer network using wastewater balances; and (iii) design of a PID controller for a pumping station using on-line tank water level measurement. Acquired knowledge resulting from the DSS greatly improved the utility performance both in terms of economic revenue and environmental protection.


Assuntos
Eliminação de Resíduos Líquidos/métodos , Águas Residuárias , Cidades , Portugal , Rios , Esgotos
8.
Arq. bras. med. vet. zootec. (Online) ; 71(3): 819-827, May-June 2019. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1011330

RESUMO

In this study, we described the antifungal activity of three Brazilian propolis extracts: brown, green and from jataí bees against Sporothrix brasiliensis. The extracts were obtained from ethanolic extraction and their chemical composition was determined by high-performance liquid chromatography coupled to mass spectrometry. The cellular toxicity was measured in MDBK (Madin-Darby Bovine Kidney) cells and quantified by the MTT assay (3- (4,5 dimethylthiazol-2yl -2,5-diphenyl-2H bromine tetrazolato). For antifungal activity, the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined by broth microdilution. The results showed that cell toxicity was not observed at lower concentrations (0.097 to 0.39μg/ml) for all extracts in comparison to cell control. Among the chemical compounds identified, caffeic acid, p-coumaric acid, chlorogenic acid, ferulic acid and rutin were quantified. In antifungal activity, green and jataí did not exhibit activity against the isolates (MIC and MFC greater than 0.78mg/ml). However, all isolates of S. brasiliensis were sensitive to brown propolis (MIC of 0.09 to 0.78mg/ml), including the standard strain (P<0.001). Among the Brazilian propolis studied, the brown propolis showed activity against the S. brasiliensis isolates and more studies should be undertaken in order to evaluate its promising use in the treatment of sporotrichosis.(AU)


Neste estudo, descreveu-se a atividade antifúngica de três extratos de própolis brasileiras: marrom, verde e de abelhas jataí (Tetragonisca angustula), contra Sporothrix brasiliensis. Os extratos foram obtidos de extração etanólica, e a sua composição química foi determinada por cromatografia líquida de alta eficiência, acoplada à espectrometria de massa. A toxicidade celular foi medida em células MDBK (Madin-Darby Bovine Kidney), avaliada por observação microscópica e quantificada pelo ensaio MTT (3- (4,5-dimetiltiazol-2-ilo -2,5-difenil-2H bromo tetrazolato). Para a atividade antifúngica, determinou-se a concentração inibitória mínima (CIM) e a concentração fungicida mínima (CFM) por meio de microdiluição em caldo. Os resultados mostraram que a toxicidade celular não foi observada em concentrações menores (0,097 a 0,39μg/ml). Entre os compostos químicos identificados, foram quantificados o ácido cafeico, ácido p-cumárico, ácido clorogênico, ácido ferúlico e a rutina. Na atividade antifúngica, as própolis verde e jataí não apresentaram atividade contra os isolados (CIM e CFM maior que 0,78mg/ml), porém todos os isolados de S. brasiliensis foram sensíveis à própolis marrom (CIM de 0,09 a 0,78mg/ml), incluindo a cepa padrão (P<0,001). Entre as própolis brasileiras estudadas, a marrom mostrou atividade contra S. brasiliensis, e mais estudos devem ser realizados para avaliar seu uso promissor no tratamento da esporotricose.(AU)


Assuntos
Humanos , Animais , Própole/análise , Própole/uso terapêutico , Sporothrix/isolamento & purificação , Itraconazol/uso terapêutico , Farmacorresistência Fúngica , Apiterapia/veterinária , Antifúngicos/análise
10.
Arq. bras. med. vet. zootec. (Online) ; 71(1): 204-210, jan.-fev. 2019. tab, graf
Artigo em Português | LILACS, VETINDEX | ID: biblio-989355

RESUMO

Aspergillus fumigatus, A. flavus e A. niger são os mais importantes agentes etiológicos da aspergilose, relevante micose aviária, com tratamento ineficaz e altas taxas de mortalidade. Em vista da importância da aspergilose, da necessidade de prospectar novos fármacos e do potencial terapêutico do óleo essencial de Origanum vulgare L. (OEO), o orégano, objetivou-se avaliar a sensibilidade in vitro de isolados clínicos de Aspergillus spp. em relação ao OEO. O óleo foi obtido por hidrodestilação em Clevenger, e a análise química realizada por cromatografia de massa (GC/MS). Observaram-se 15 diferentes compostos ativos, sendo 4-terpineol, hidrato de sabinene e timol os majoritários. Nos testes de microdiluição em caldo (Reference..., 2008), todos os isolados (n= 23) foram sensíveis ao OEO: A. fumigatus teve CIM entre 28,125mg/mL (0,1875%) e 450mg/mL (3,0%), A. flavus entre 112,5mg/mL (0,75%) e 450mg/mL, e A. niger 112,5mg/mL. CFM variou de 112,5mg/mL a 450mg/mL nos isolados de A. fumigatus, de 225mg/mL (1,5%) a 450mg/mL em A. flavus, e foi de 450mg/mL em A. niger. CIM e CFM foram idênticos em 6/14 isolados, o que demonstra que o óleo com a mesma concentração pode ter capacidade fungistática e fungicida. CIM 90 correspondeu à CIM máxima. Os resultados demonstram a atividade anti-Aspergillus do OEO, com CIM 90 de 450mg/mL (3%).(AU)


Aspergillus fumigatus, A. flavus and A. niger are the most important etiological agents of aspergillosis, a relevant avian mycosis, with innefective treatment and high mortality rates. Due the importance of aspergillosis, the necessity of prospection of new drugs and the therapeutic potential of the essential oil of Origanum vulgare L. (OEO), popularly known as oregano, aims to evaluate the in vitro sensitivity of Aspergillus spp. opposing to OEO. The oil was obtained by hydrodistillation in Clevenger, and the chemical analysis performed by mass chromatography (GC/MS). 15 different active compounds were observed, being 4-terpineol (18.4%), sabinene hydrate (15.6%) and thymol (13.6%), the majority components. In the in vitro susceptibility test, all strains showed sensitivity to OEO, MIC of Aspergillus fumigatus ranged from 28,125mg/mL (0,1875%) to 450mg/mL (3,0%), A. flavus 112,5mg/mL (0,75%) to 450mg/mL, and A. niger 112,5mg/mL. MFC ranged from 112,5mg/mL to 450mg/mL in the A. fumigatus isolates, 225mg/mL (1,5%) to 450mg/mL in A. flavus, and 450mg/mL for A. niger. The MIC and FMC values were identical in 6/14 of the isolated subjects, demonstrating that the oil with the same concentration can have fungistatic and fungicidal capacity. The results demonstrates anti-Aspergillus activities of OEO with CIM90 de 450mg/mL (3%).(AU)


Assuntos
Aspergillus/enzimologia , Óleos Voláteis/síntese química , Origanum/análise , Noxas
11.
Bioorg Med Chem ; 27(8): 1449-1455, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30528164

RESUMO

Extracellular adenosine 5'-triphosphate (ATP) triggers the P2X7 receptor (P2X7R) ionic channel to stimulate the release of the interleukin-IL-1ß cytokine into macrophages. The current study explored the reaction of six structurally diverse triazole derivatives on P2X7-mediated dye uptake into murine peritoneal macrophages. P2X7R activity determined by ATP-evoked fluorescent dye uptake. Triazole derivatives toxicity measured using dextran rhodamine exclusion based colorimetric assay. A740004 and BBG, both P2X7R antagonist, inhibited ATP-induced dye uptake. In contrast, the derivatives 5a, 5b, 5e, and 5f did not diminish P2X7R activity in concentrations until 100 µM. 5c and 5d analogs caused a potent inhibitory activity on P2X7-induced dye uptake. Dextran Rhodamine exclusion measurements after 24 h of continuous treatment with triazole derivatives indicated a moderated toxicity for all molecules. In conclusion, this study showed that a series of new hybrid 1,2,3-triazolic naphthoquinones reduces P2X7R-induced dye uptake into murine macrophages. In silico analysis indicates a good pharmacokinetic profile and molecular docking results of these analogs indicate the potential to bind into an allosteric site located into the P2X7R pore and juxtaposed with the ATP binding pocket. In this manner, the compounds 5c and 5d may be used as a scaffold for new P2X7R inhibitors with reduced toxicity, and good anti-inflammatory activity.


Assuntos
Naftoquinonas/química , Antagonistas do Receptor Purinérgico P2X/química , Receptores Purinérgicos P2X7/metabolismo , Triazóis/química , Sítio Alostérico , Animais , Sítios de Ligação , Células CACO-2 , Linhagem Celular , Corantes/metabolismo , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Microssomos Hepáticos/metabolismo , Simulação de Acoplamento Molecular , Permeabilidade/efeitos dos fármacos , Estrutura Terciária de Proteína , Antagonistas do Receptor Purinérgico P2X/metabolismo , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/química , Triazóis/metabolismo , Triazóis/farmacologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-30440254

RESUMO

The biological process of wound healing is one of the most complex occurrences during our lives turning a serious public health problem. The rate of healing chronic wounds in humans is relatively uniform, regardless of etiologies, and is estimated to be 0.63-0.65 mm/week for diabetics and non- diabetics [1], respectively, being visually unnoticeable throughout the daily care of a wound. A ruler designed for this purpose using a decal for setting the wound limits, however an area with a lot of irregularity requires a tool that carries out this measurement autonomously through image recognition, making the process feasible for the medical teams responsible for the treatment. The digitized images undergo morphological processes sing on the polygonal line that delimits the wound region. With the region delimited by the polygonal, the area and the perimeter are determined. A comparison with analytical methods demonstrates that this tool has the potential to become gold standard for estimating to estimate the area and the perimeter of wounds in the healing process.


Assuntos
Design de Software , Cicatrização , Humanos
13.
Eur J Med Chem ; 143: 1361-1372, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29133043

RESUMO

P2X7 receptor (P2X7R) is an ATP-gated ion-channel with potential therapeutic applications. In this study, we prepared and searched a series of 1,4-naphthoquinones derivatives to evaluate their antagonistic effect on both human and murine P2X7 receptors. We explored the structure-activity relationship and binding mode of the most active compounds using a molecular modeling approach. Biological analysis of this series (eight analogues and two compounds) revealed significant in vitro inhibition against both human and murine P2X7R. Further characterization revealed that AN-03 and AN-04 had greater potency than BBG and A740003 in inhibiting dye uptake, IL-1ß release, and carrageenan-induced paw edema in vivo. Moreover, we used electrophysiology and molecular docking analysis for characterizing AN-03 and AN-04 action mechanism. These results suggest 1,4-napthoquinones, mainly AN-04, as potential leads to design new P2X7R blockers and anti-inflammatory drugs.


Assuntos
Naftoquinonas/farmacologia , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/metabolismo , Animais , Desenho de Fármacos , Células HEK293 , Humanos , Camundongos , Simulação de Acoplamento Molecular , Naftoquinonas/química , Naftoquinonas/metabolismo , Conformação Proteica , Antagonistas do Receptor Purinérgico P2X/química , Antagonistas do Receptor Purinérgico P2X/metabolismo , Receptores Purinérgicos P2X7/química , Relação Estrutura-Atividade
14.
J Evol Biol ; 30(8): 1450-1477, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28786193

RESUMO

Speciation, the evolution of reproductive isolation among populations, is continuous, complex, and involves multiple, interacting barriers. Until it is complete, the effects of this process vary along the genome and can lead to a heterogeneous genomic landscape with peaks and troughs of differentiation and divergence. When gene flow occurs during speciation, barriers restricting gene flow locally in the genome lead to patterns of heterogeneity. However, genomic heterogeneity can also be produced or modified by variation in factors such as background selection and selective sweeps, recombination and mutation rate variation, and heterogeneous gene density. Extracting the effects of gene flow, divergent selection and reproductive isolation from such modifying factors presents a major challenge to speciation genomics. We argue one of the principal aims of the field is to identify the barrier loci involved in limiting gene flow. We first summarize the expected signatures of selection at barrier loci, at the genomic regions linked to them and across the entire genome. We then discuss the modifying factors that complicate the interpretation of the observed genomic landscape. Finally, we end with a road map for future speciation research: a proposal for how to account for these modifying factors and to progress towards understanding the nature of barrier loci. Despite the difficulties of interpreting empirical data, we argue that the availability of promising technical and analytical methods will shed further light on the important roles that gene flow and divergent selection have in shaping the genomic landscape of speciation.


Assuntos
Fluxo Gênico , Seleção Genética , Animais , Especiação Genética , Genoma , Genômica , Reprodução
15.
Aliment Pharmacol Ther ; 44(8): 866-76, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27562233

RESUMO

BACKGROUND: The new direct-acting anti-virals (DAAs) for hepatitis C virus (HCV) infection offer higher cure rates, but at a much higher cost than the standard interferon-based treatments. AIM: To identify the cost-effective treatment for patients with HCV infection with F3 liver fibrosis who are at high risk of progression to cirrhosis. METHODS: A decision-analytic Markov model compared the health benefits and costs of all currently licensed treatments as single treatments and in sequential therapy of up to three lines. Costs were expressed in pound sterling from the perspective of the UK National Health Service. Health benefits were expressed in quality-adjusted life years. RESULTS: Treatment before progression to cirrhosis always offers the most health benefits for the least costs. Sequential therapy with multiple treatment lines cures over 89% of patients across all HCV genotypes while ensuring a cost-effective use of resources. Cost-effective regimes for HCV genotype 1 patients include first-line oral therapy with sofosbuvir-ledipasvir while peginterferon continues to have a role in other genotypes. CONCLUSIONS: The cost-effective treatment for HCV can be established using decision analytic modelling comparing single and sequential therapies. Sequential therapy with DAAs is effective and cost-effective in HCV patients with F3 fibrosis. This information is of significant benefit to health care providers with budget limitations and provides a sound scientific basis for drug treatment choices.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Análise Custo-Benefício , Progressão da Doença , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Resultado do Tratamento
16.
Braz. j. biol ; 76(2): 367-373, Apr.-June 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-781379

RESUMO

Abstract The germination characteristics of the native cactus species are poorly known, being the temperature and the light the factors that the most interferes in that process. Thus, the objective of the present work was to characterize the fruits and evaluate the influence of the temperature and the light in the seed germination of Rhipsalis floccosa, Rhipsalis pilocarpa and Rhipsalis teres. The tested constant temperatures were 15, 20, 25, 30 and 35 °C and the alternate of 20-30 °C and 25-35 °C in a photoperiod of 10 hours, and with determination of the most appropriate temperature, the germination was tested in light absence. The germination percentage, the index of germination speed and medium time of germination were evaluated. For R. floccosa, the highest germination percentage was at 20 °C. For R. pilocarpa and R. teres, the highest germination percentages occurred in 15 °C and 20 °C. There was correlation to germination percentage between the three species, indicating that they had similar germination behavior. Total absence of germination was verified for the three species in condition of light absence. In conclusion, the temperature of 20 °C is the most suitable for the seed germination of R. floccosa. For the species R. pilocarpa and R. teres, the temperatures of 15 and 20 °C are the most suitable.


Resumo Existem poucos estudos sobre características germinativas de espécies de cactos nativos, sendo a temperatura e a luz, os fatores que mais interferem nesse processo. Assim, objetivou-se caracterizar os frutos e avaliar a influência da temperatura e luminosidade na germinação de sementes de Rhipsalis floccosa, Rhipsalis pilocarpa and Rhipsalis teres. Testou-se temperaturas constantes de 15, 20, 25, 30 e 35 °C e alternadas de 20-30 °C e 25-35 °C com fotoperíodo de 10 horas, e com a determinação da temperatura mais adequada, testou-se a germinação na ausência de luz. A porcentagem de germinação, o índice de velocidade de germinação e o tempo médio de germinação foram avaliados. Para R. floccosa, a maior porcentagem de germinação foi obtida a 20 °C. Para R. pilocarpa e R. teres, as maiores porcentagens de germinação ocorreram a 15 °C e 20 °C. Verificou-se correlação entre as três espécies para a porcentagem de germinação, indicando comportamento semelhante entre essas. Na ausência de luz não ocorreu a germinação das sementes das espécies estudas. Em conclusão, a temperatura de 20 °C é a mais indicada para a germinação de sementes de R. floccosa. Para as espécies R. pilocarpa e R. teres, as temperaturas de 15 e 20 °C são as mais indicadas.


Assuntos
Sementes/crescimento & desenvolvimento , Temperatura , Germinação/fisiologia , Cactaceae/crescimento & desenvolvimento , Cactaceae/fisiologia , Frutas/crescimento & desenvolvimento , Luz , Brasil , Fotoperíodo , Fenômenos Ecológicos e Ambientais
17.
Braz J Biol ; 76(2): 367-73, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26934150

RESUMO

The germination characteristics of the native cactus species are poorly known, being the temperature and the light the factors that the most interferes in that process. Thus, the objective of the present work was to characterize the fruits and evaluate the influence of the temperature and the light in the seed germination of Rhipsalis floccosa, Rhipsalis pilocarpa and Rhipsalis teres. The tested constant temperatures were 15, 20, 25, 30 and 35 °C and the alternate of 20-30 °C and 25-35 °C in a photoperiod of 10 hours, and with determination of the most appropriate temperature, the germination was tested in light absence. The germination percentage, the index of germination speed and medium time of germination were evaluated. For R. floccosa, the highest germination percentage was at 20 °C. For R. pilocarpa and R. teres, the highest germination percentages occurred in 15 °C and 20 °C. There was correlation to germination percentage between the three species, indicating that they had similar germination behavior. Total absence of germination was verified for the three species in condition of light absence. In conclusion, the temperature of 20 °C is the most suitable for the seed germination of R. floccosa. For the species R. pilocarpa and R. teres, the temperatures of 15 and 20 °C are the most suitable.


Assuntos
Cactaceae , Frutas/crescimento & desenvolvimento , Germinação/fisiologia , Luz , Sementes/crescimento & desenvolvimento , Temperatura , Brasil , Cactaceae/crescimento & desenvolvimento , Cactaceae/fisiologia , Fenômenos Ecológicos e Ambientais , Fotoperíodo
18.
J Bioenerg Biomembr ; 48(1): 1-12, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26728159

RESUMO

Ion channels allow for rapid ion diffusion through the plasma membrane. In some conditions, ion channels induce changes in the critical plasma membrane permeability that permit 900-Da solutes to enter cells. This process is known as the pore phenomenon. Some transient receptor potential (TRP) channel subtypes have been highlighted such as the P2X7 receptor, plasma membrane VDAC-1 channel, and pannexin hemichannels. The TRP ion channels are considered multimodal transducers that respond to several kinds of stimuli. In addition, many TRP channel subtypes are involved in physiological and pathophysiological processes such as inflammation, pain, and cancer. The TRPA1, TRPM8, and TRPV1-4 subtypes have been shown to promote large-molecular-weight solute uptake, including impermeable fluorescent dyes, QX-314 hydrophilic lidocaine derivative, gabapentin, and antineoplastic drugs. This review discusses the current knowledge of TRP-associated pores and encourages scientists to study their features and explore them as novel therapeutic tools.


Assuntos
Permeabilidade da Membrana Celular , Canais Iônicos de Abertura Ativada por Ligante/metabolismo , Potenciais da Membrana , Canais de Ânion Dependentes de Voltagem/metabolismo , Animais , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Transporte de Íons , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo
19.
Neuroscience ; 273: 1-11, 2014 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-24814727

RESUMO

Depression is a worldwide disability disease associated with high morbidity and has increased dramatically in the last few years. The differential diagnosis and the definition of an individualized therapy for depression are hampered by the absence of specific biomarkers. The aim of this study was to evaluate the phospholipidomic profile of the brain and myocardium in a mouse model of depression induced by chronic unpredictable stress (CUS). The lipidomic profile was evaluated by thin layer and liquid chromatography and mass spectrometry and lipid oxidation was estimated by FOX II assay. Antioxidant enzyme activity and the oxidized/reduced glutathione (GSH/GSSG) ratio were also evaluated. Results showed that chronic stress affects primarily the lipid profile of the brain, inducing an increase in lipid hydroperoxides, which was not detected in the myocardium. A significant decrease in phosphatidylinositol (PI) and in cardiolipin (CL) relative contents and also oxidation of CL and a significant increase of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were observed in the brain of mice after unpredictable chronic stress conditions. In the myocardium only an increase in PC content was observed. Nevertheless, both organs present a decreased GSH/GSSG ratio when compared to control groups, corroborating the occurrence of oxidative stress. The enzyme activities of catalase (CAT) and superoxide dismutase (SOD) were found to be decreased in the myocardium and increased in the brain, while glutathione reductase (GR) was decreased in the brain. Our results indicate that in a mouse model for studying depression induced by CUS, the modification of the expression of oxidative stress-related enzymes did not prevent lipid oxidation in organs, particularly in the brain. These observations suggest that depression has an impact on the brain lipidome and that further studies are needed to better understand lipids role in depression and to evaluate their potential as future biomarkers.


Assuntos
Encéfalo/metabolismo , Transtorno Depressivo/metabolismo , Miocárdio/metabolismo , Fosfolipídeos/metabolismo , Animais , Cardiolipinas/metabolismo , Catalase/metabolismo , Doença Crônica , Modelos Animais de Doenças , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Glutationa Redutase/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Oxirredução , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfatidilinositóis/metabolismo , Estresse Psicológico , Superóxido Dismutase/metabolismo , Incerteza
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