RESUMO
Leishmaniasis comprises a group of infectious diseases with worldwide distribution, of which both the visceral and cutaneous forms are caused by Leishmania parasites. In the absence of vaccines, efficacious chemotherapy remains the basis for leishmaniasis control. The available drugs are expensive and associated with several secondary adverse effects. Due to these limitations, the development of new antileishmanial compounds is imperative, and plants offer various perspectives in this regard. The present study evaluated the in vitro leishmanicidal activity of flavonoids isolated from Solanum paludosum Moric. and investigated the mechanisms of cell death induced by them. These compounds were evaluated in vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and they showed prominent leishmanicidal activity. The EtOAc fraction, gossypetin 3,7,8,4'-tetra-O-methyl ether (1), and kaempferol 3,7-di-O-methyl ether (3) were selected to be used in an in vitro assay against L. amazonensis amastigotes and cell death assays. The flavonoids (1) and (3) presented significant activity against L. amazonensis amastigotes, exhibiting the IC50 values of 23.3 ± 4.5 µM, 34.0 ± 9.6 µM, and 10.5 ± 2.5 µM for the EtOAc fraction, (1), and (3), respectively, without toxic effects to the host cells. Moreover, (1) and (3) induced blocked cell cycle progression at the G1/S transition, ultimately leading to G1/G0 arrest. Flavonoid (3) also induced autophagy. Using Raman spectroscopy in conjunction with principal component analysis, the biochemical changes in the cellular components induced by flavonoids (1) and (3) were presented. The obtained results indicated that the mechanisms of action of (1) and (3) occurred through different routes. The results support that the flavonoids derived from S. paludosum can become lead molecules for the design of antileishmanial prototypes.
Assuntos
Antiprotozoários/farmacologia , Morte Celular/efeitos dos fármacos , Flavonoides/farmacologia , Citometria de Fluxo/métodos , Leishmania/efeitos dos fármacos , Animais , Antiprotozoários/química , Autofagia/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Flavonoides/química , Quempferóis/química , Quempferóis/farmacologia , Leishmania/citologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Camundongos , Análise Espectral Raman , Estreptófitas/químicaRESUMO
Historically, medical imaging repositories have been supported by indoor infrastructures. However, the amount of diagnostic imaging procedures has continuously increased over the last decades, imposing several challenges associated with the storage volume, data redundancy and availability. Cloud platforms are focused on delivering hardware and software services over the Internet, becoming an appealing solution for repository outsourcing. Although this option may bring financial and technological benefits, it also presents new challenges. In medical imaging scenarios, communication latency is a critical issue that still hinders the adoption of this paradigm. This paper proposes an intelligent Cloud storage gateway that optimizes data access times. This is achieved through a new cache architecture that combines static rules and pattern recognition for eviction and prefetching. The evaluation results, obtained from experiments over a real-world dataset, show that cache hit ratios can reach around 80%, leading to reductions of image retrieval times by over 60%. The combined use of eviction and prefetching policies proposed can significantly reduce communication latency, even when using a small cache in comparison to the total size of the repository. Apart from the performance gains, the proposed system is capable of adjusting to specific workflows of different institutions.
Assuntos
Diagnóstico por Imagem , Computação em Nuvem , Armazenamento e Recuperação da Informação , Internet , Serviços TerceirizadosRESUMO
Electrocoagulation was investigated as a method for treating wastewater containing polyvinyl acetate (PVAc) from the furniture industry. The study evaluated the evolution of iron concentration and passivation during the treatment process. Laboratory-scale experiments were conducted to evaluate the effects of inter-electrode distance (d), current density, and mode on treatment performance. Three values of d (0.3, 0.6, and 0.9 cm) were studied and found to have no significant effect on performance. However, lower d values resulted in reduced energy consumption due to a decrease in applied voltage. Three values of current density (132, 158, and 197 A m-2) were studied under two current modes, Direct Current (DC) and Alternating Pulsed Current (APC). The best treatment performance for DC occurred under 158 A m-2 (the treated wastewater was characterized by pH = 4.59 ± 0.02, conductivity = 996 ± 21 µS cm-1, COD = 1940 ± 55 mgO2 L-1, TSS = 105 ± 14 mg L-1, and Fe = 50.39 ± 1.87 mgFe L-1). For APC, the best performance was achieved under 197 A m-2 (the treated wastewater was characterized by pH = 6.33 ± 0.06, conductivity = 988 ± 17 µS cm-1, COD = 1942 ± 312 mgO2 L-1, TSS = 199 ± 55 mg L-1, and Fe = 44.68 ± 4.60 mgFe L-1). Despite the promising results, treatment performance was insufficient to meet the legal requirements for water discharge. APC was found to be a more economically viable approach, as it reduced anode wear, electrode passivation, and energy consumption. The quantity of iron released increased with d, and the effect of current density on iron concentration was found to be non-linear. However, applying APC reduced the iron content for all tested current densities. The tests showed that EC was effective in removing chemical oxygen demand (COD) and total suspended solids (TSS), achieving removal efficiencies above 92% and 99%, respectively. However, the studied treatment procedures were insufficient to meet the EU legal requirements for water discharge. Therefore, the obtained wastewater should undergo a post-treatment process.
Assuntos
Águas Residuárias , Poluentes Químicos da Água , Eliminação de Resíduos Líquidos/métodos , Decoração de Interiores e Mobiliário , Óxido de Magnésio , Resíduos Industriais/análise , Concentração de Íons de Hidrogênio , Eletrocoagulação/métodos , Eletrodos , Ferro/química , Poluentes Químicos da Água/químicaRESUMO
This study presents the outcomes of the shared task competition BioCreative VII (Task 3) focusing on the extraction of medication names from a Twitter user's publicly available tweets (the user's 'timeline'). In general, detecting health-related tweets is notoriously challenging for natural language processing tools. The main challenge, aside from the informality of the language used, is that people tweet about any and all topics, and most of their tweets are not related to health. Thus, finding those tweets in a user's timeline that mention specific health-related concepts such as medications requires addressing extreme imbalance. Task 3 called for detecting tweets in a user's timeline that mentions a medication name and, for each detected mention, extracting its span. The organizers made available a corpus consisting of 182 049 tweets publicly posted by 212 Twitter users with all medication mentions manually annotated. The corpus exhibits the natural distribution of positive tweets, with only 442 tweets (0.2%) mentioning a medication. This task was an opportunity for participants to evaluate methods that are robust to class imbalance beyond the simple lexical match. A total of 65 teams registered, and 16 teams submitted a system run. This study summarizes the corpus created by the organizers and the approaches taken by the participating teams for this challenge. The corpus is freely available at https://biocreative.bioinformatics.udel.edu/tasks/biocreative-vii/track-3/. The methods and the results of the competing systems are analyzed with a focus on the approaches taken for learning from class-imbalanced data.
Assuntos
Mineração de Dados , Processamento de Linguagem Natural , Humanos , Mineração de Dados/métodosRESUMO
In this study, we perform mass transfer characterization (k(L) a) on a novel mechanically driven/stirred Process Scouting Device, PSD, (SuperSpinner D 1000®, SSD) and demonstrate that this novel device can be viewed as disposable bioreactor. Using patch-based optical sensors, we were able to monitor critical cell culture environmental conditions such as dissolved oxygen (DO) and pH in SSD for comparison to a 1 L standard spinner (SS) flask. We also coupled these mass transfer studies with mixing time studies where we observed relative high mixing times (5.2 min) that are typically observed in production scale bioreactors. Decreasing the mixing time 3.5-fold resulted in 30% increase in k(L) a (from 2.3 to 3.0 h(-1) ) and minimum DO level increased from 0% to 20% for our model hybridoma cell line. Finally, maximum viable cell density and protein titer stayed within ±20% of historical data, from our standard 5 L stirred bioreactor (Biostat®) operated under active DO control.
Assuntos
Reatores Biológicos , Biotecnologia/métodos , Meios de Cultura/química , Equipamentos Descartáveis , Animais , Técnicas de Cultura de Células/métodos , Linhagem Celular Tumoral , Sobrevivência Celular , Camundongos , Oxigênio/análise , Proteínas/análise , Fatores de TempoRESUMO
BACKGROUND: Onabotulinumtoxin A (OnabotA) injection has been investigated as a novel treatment for benign prostatic enlargement caused by benign prostatic hyperplasia. An OnabotA-induced volume reduction caused by sympathetic fibers impairment has been proposed as a potential mechanism of action. Our aim was to investigate the expression of apoptosis-regulating proteins in the rat prostate following OnabotA intraprostatic injection. METHODS: Adult Wistar rats were injected in the ventral lobes of the prostate with 10 U of OnabotA or saline. A set of OnabotA-injected animals was further treated with 0.5 mg/kg of phenylephrine (PHE) subcutaneously daily. All animals were sacrificed after 1 week and had their prostates harvested. Immunohistochemical staining was performed for Bax, Bcl-xL and caspase-3 proteins and visualized by the avidin-biotin method. The optical density of the glandular cells was also determined, with measurement of differences between average optical densities for each group. RESULTS: Saline-treated animals showed intense epithelial staining for Bcl-xL and a faint labelling for both Bax and Caspase-3. OnabotA-treated rats showed a reduced epithelial staining of Bcl-xL and a consistently increased Bax and Caspase-3 staining when compared with saline-treated animals. PHE-treated animals showed a stronger Bcl-xL staining and reduced staining of both Bax and Caspase-3 when compared to the OnabotA group. Mean signal intensity measurements for each immunoreaction confirmed a significant decrease of the signal intensity for Bcl-xL and a significant increase of the signal intensity for Bax and Caspase 3 in OnabotA-injected animals when compared with the control group. In OnabotA+PHE treated animals mean signal intensity for Bcl-xL, Bax and Caspase 3 immunoreactions was identical to that of the control animals. CONCLUSIONS: These results support the hypothesis that OnabotA activates apoptotic pathways in the rat prostate through a mechanism that involves sympathetic outflow impairment.
Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/genética , Toxinas Botulínicas Tipo A/administração & dosagem , Regulação da Expressão Gênica , Próstata/metabolismo , Animais , Proteínas Reguladoras de Apoptose/fisiologia , Caspase 3/biossíntese , Caspase 3/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Próstata/efeitos dos fármacos , Próstata/patologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/genética , Proteína bcl-X/biossíntese , Proteína bcl-X/genéticaRESUMO
Thioredoxin plays an essential role in bacterial antioxidant machinery and virulence; however, its regulatory actions in the host are less well understood. Reduced human Trx activates transient receptor potential canonical 5 (TRPC5) in inflammation, but there is no evidence of whether these receptors mediate bacterial thioredoxin effects in the host. Importantly, TRPC5 can form functional complexes with other subunits such as TRPC4. Herein, E. coli-derived thioredoxin induced mortality in lipopolysaccharide- (LPS-) injected mice, accompanied by reduction of leukocyte accumulation, regulation of cytokine release into the peritoneum, and impairment of peritoneal macrophage-mediated phagocytosis. Dual TRPC4/TRPC5 blockade by ML204 increased mortality and hypothermia in thioredoxin-treated LPS mice but preserved macrophage's ability to phagocytose. TRPC5 deletion did not alter body temperature but promoted additional accumulation of peritoneal leukocytes and inflammatory mediator release in thioredoxin-administered LPS mice. Thioredoxin diminished macrophage-mediated phagocytosis in wild-type but not TRPC5 knockout animals. TRPC5 ablation did not affect LPS-induced responses. However, ML204 caused mortality associated with exacerbated hypothermia and decreased peritoneal leukocyte numbers and cytokines in LPS-injected mice. These results suggest that bacterial thioredoxin effects under LPS stimuli are mediated by TRPC4 and TRPC5, shedding light on the additional mechanisms of bacterial virulence and on the pathophysiological roles of these receptors.
Assuntos
Escherichia coli/química , Lipopolissacarídeos/toxicidade , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Canais de Cátion TRPC/metabolismo , Tiorredoxinas/uso terapêutico , Animais , Peróxido de Hidrogênio/metabolismo , Indóis/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/metabolismo , Fagocitose/efeitos dos fármacos , Piperidinas/toxicidade , Síndrome de Resposta Inflamatória Sistêmica/induzido quimicamente , Canais de Cátion TRPC/antagonistas & inibidores , Virulência/efeitos dos fármacosRESUMO
INTRODUCTION: Investigations about the association between prostate cancer and environmental and/or occupational pesticide exposure have evidenced a possible role of these chemical substances on tumor etiology, related to their action as endocrine disruptors. OBJECTIVE: To assess the association between pesticide exposure and prostate cancer by conducting a systematic review of the scientific literature. MATERIALS AND METHODS: Articles published until August 18, 2015 were searched in the databases MEDLINE/Pubmed, Scielo, and Lilacs using the keywords "pesticides" and "prostate cancer". Only the analytical observational studies whose methodological quality met the criteria established by the New Castle-Ottawa scale were included in this review. RESULTS: The review included 49 studies published between 1993 and 2015. All studies were in English and analyzed exposure to pesticides and/or agricultural activities. Most studies (32 articles) found a positive association between prostate cancer and pesticides or agricultural occupations, with estimates ranging from 1.01 to 14.10. CONCLUSION: The evidence provided by the reviewed studies indicates a possible association between the development of prostate cancer and pesticide exposure and/or agricultural occupations.
Assuntos
Exposição Ambiental/efeitos adversos , Praguicidas/efeitos adversos , Neoplasias da Próstata/induzido quimicamente , Agricultura , Humanos , Masculino , Estudos Observacionais como Assunto , Exposição Ocupacional/efeitos adversos , Neoplasias da Próstata/epidemiologiaRESUMO
BACKGROUND: Clinically localized prostate cancer may be treated by different approaches of radiation therapy. The aim of this study was to report the results of disease control and toxicity in patients with clinically localized prostate cancer treated with high dose IMRT alone with 1 cm PTV posterior margin. METHODS: From September 2001 to April 2008, 140 patients with localized prostate cancer were treated with definitive IMRT (dose ≥ 74 Gy) without hormone therapy. Outcomes were measured from the conclusion of radiotherapy. Biochemical failure was defined as PSA nadir + 2.0 ng/dL. Toxicities were assessed using the NCI-CTCAE-version 3.0. Median follow-up was 58 months. RESULTS: Biochemical failure occurred in 13.6% of patients. Actuarial 5-year biochemical control rates were 91.7%, 82.5% and 85.9% for low-, intermediate-, and high-risk patients, respectively. Stage T2 patients presented a risk of biochemical failure almost three times higher than stage T1 (RR = 2.91; 95% CI: 1.04; 8.17). Distant metastases occurred in 3 (2%) patients. Five-year metastasis-free and overall survivals were 96% and 97.5%, respectively. Late grade 3 genitourinary and gastrointestinal toxicity rates were, respectively, 1.6% and 3%. CONCLUSION: High-dose IMRT alone with 1 cm posterior PTV margin was effective and safe for patients with localized prostate cancer.
Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X , Idoso , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Aceleradores de Partículas , Radioterapia/métodos , Radioterapia Guiada por Imagem/métodos , Estudos Retrospectivos , Risco , Resultado do TratamentoRESUMO
Previous studies from our group have indicated important biological properties of the ethanolic extract (EE) and isolated compounds from the bulbs of Cipura paludosa (Iridaceae), a native plant widely distributed in northern Brazil. In the present study, the effects of chronic treatment with the EE on the memory of adult rats exposed to methylmercury (MeHg) during early development were assessed. Pregnant rats were treated by gavage with a single dose of MeHg (8 mg/kg) on gestational day 15, the developmental stage critical for cortical neuron proliferation. Adult offspring were administered orally with the EE of C. paludosa (1, 10 or 100mg/kg) over 14 consecutive days. EE improved short-term social memory in a specific manner and facilitated the step-down inhibitory avoidance of short- and long-term memory. MeHg exposure induced pronounced long-lasting impairments in social recognition memory that were improved by EE. Moreover, EE significantly increased the step-down latencies specifically during the short-term session in prenatal MeHg-exposed rats. These results demonstrate that EE reduced the long-lasting short-term learning and memory deficits induced by MeHg exposure. These findings may encourage further studies evaluating the cognitive enhancing properties of C. paludosa and its components on neuropathological conditions associated with exposure to environmental contaminants.