RESUMO
BACKGROUND: The interaction of Cryptococcus neoformans with airway epithelial cells is crucial for the establishment of cryptococcosis. Aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways. METHOD: Here, we evaluated the effects of AT-RvD1 (1, 10 or 100 nM) on human bronchial epithelial cells (BEAS-2B) stimulated with C. neoformans (1, 10 or 100 multiplicities of infection; MOI). RESULTS: After 24 h, C. neoformans (all MOI) demonstrated no cytotoxic effects and increased IL-8 production on BEAS-2B cells when compared to controls. In addition, C. neoformans (MOI 100) increased the concentration of IL-6, but not of IL-10. AT-RvD1 (100 nM) significantly reduced the concentration of IL-8 and IL-6 and increased IL-10 production in C. neoformans-stimulated BEAS-2B cells. C. neoformans increased the phosphorylation of NF-κB and ERK1/2, and ALX/FPR2 expression. AT-RvD1 reduced the activation of NF-kB without altering the ERK1/2 and ALX/FPR2 expression. The anti-inflammatory effects of AT-RvD1 were dependent on the ALX/FPR2, once its antagonist (BOC2) reversed its anti-inflammatory effects. No alteration on the fungal burden as well as interactions with BEAS-2B cells was observed by AT-RvD1. CONCLUSION: AT-RvD1 demonstrated significant anti-inflammatory effects in bronchial epithelial cells infected with C. neoformans without affecting the development of C. neoformans infection in the airways. TRIAL REGISTRATION: Not applicable.
Assuntos
Anti-Inflamatórios/farmacologia , Criptococose/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/farmacologia , Inflamação/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Brônquios/citologia , Brônquios/microbiologia , Brônquios/patologia , Linhagem Celular , Criptococose/patologia , Cryptococcus neoformans/isolamento & purificação , Ácidos Docosa-Hexaenoicos/administração & dosagem , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Humanos , Inflamação/microbiologiaRESUMO
BACKGROUND: Fear of falling may be significantly associated with falls in Parkinson's disease (PD) and may have a negative impact on quality of life. Nevertheless, there are no valid and reliable tools to examine this condition in PD. The objective of this study was to design and determine the psychometric attributes of an instrument to assess fear of falling in PD. METHODS: A prospective 1-year, 2-phase study was conducted to validate the Fear of Falling Scale, a self-assessed instrument for assessing fear of falling in PD. During phase 1, we designed a scale to measure the severity of fear of falling and determine its baseline psychometric characteristics, whereas phase 2 was a 1-year follow-up study to assess the frequency of falls and other clinical factors linked to fear of falling. Convergent and discriminant validity were assessed against the Fear of Falling Measure and the Starkstein Apathy Scale, respectively. RESULTS: The Fear of Falling Scale showed high internal consistency, test-retest reliability, and strong convergent and discriminant validity. There was a significant association between fear of falling score and the presence of both generalized anxiety disorder and major depression, poor balance-related motor ability, increased nonmotor symptoms of PD, more severe impairments in activities of daily living, and increased motor fluctuations. Finally, generalized anxiety disorder was a significant predictor of number of falls during a 12-month follow-up period. CONCLUSIONS: The Fear of Falling Scale is a valid and reliable instrument to assess fear of falling in PD. Fear of falling in PD is associated with specific psychiatric and motor disorders and is significantly related to the performance of balance-related motor functions. © 2019 International Parkinson and Movement Disorder Society.
Assuntos
Acidentes por Quedas/prevenção & controle , Doença de Parkinson/fisiopatologia , Doença de Parkinson/reabilitação , Equilíbrio Postural/fisiologia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Qualidade de Vida/psicologia , Inquéritos e QuestionáriosRESUMO
Here, we present a closed genome sequence for Clostridium argentinense strain 89G, the first strain identified to produce botulinum neurotoxin type G (BoNT/G). Although discovered in 1970, to date, there have been no reference quality sequences publicly available for this species.
RESUMO
Bronchial epithelial cells represent the first line of defense against microorganisms and allergens in the airways and play an important role in chronic inflammatory processes such as asthma. In an experimental model, both RvD1 and AT-RvD1, lipid mediators of inflammation resolution, ameliorated some of the most important phenotypes of experimental asthma. Here, we extend these results and demonstrate the effect of AT-RvD1 on bronchial epithelial cells (BEAS-2B) stimulated with IL-4. AT-RvD1 (100 nM) decreased both CCL2 and CXCL-8 production, in part by decreasing STAT6 and NF-κB pathways. Furthermore, the effects of AT-RvD1 were ALX/FRP2 receptor dependent, as the antagonist of this receptor (BOC1) reversed the inhibition of these chemokines by AT-RvD1. In addition, AT-RvD1 decreased SOCS1 and increased SOCS3 expression, which play important roles in Th1 and Th17 modulation, respectively. In conclusion, AT-RvD1 demonstrated significant effects on the IL-4-induced activation of bronchial epithelial cells and consequently the potential to modulate neutrophilic and eosinophilic airway inflammation in asthma. Taken together, these findings identify AT-RvD1 as a potential proresolving therapeutic agent for allergic responses in the airways.
Assuntos
Brônquios/efeitos dos fármacos , Brônquios/imunologia , Ácidos Docosa-Hexaenoicos/farmacologia , Interleucina-4/imunologia , Asma/tratamento farmacológico , Asma/imunologia , Asma/metabolismo , Brônquios/metabolismo , Linhagem Celular , Quimiocina CCL2/biossíntese , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-8/biossíntese , NF-kappa B/metabolismo , Fator de Transcrição STAT6/metabolismo , Proteína 1 Supressora da Sinalização de Citocina , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genéticaRESUMO
Zymomonas mobilis ATCC 10988 is the type strain of the Z. mobilis subsp. mobilis taxon, members of which are some of the most rigorous ethanol-producing bacteria. Isolated from Agave cactus fermentations in Mexico, ATCC 10988 is one of the first Z. mobilis strains to be described and studied. Its robustness in sucrose-substrate fermentations, physiological characteristics, large number of plasmids, and overall genomic plasticity render this strain important to the study of the species. Here we report the finishing and annotation of the ATCC 10988 chromosomal and plasmid genome.
Assuntos
DNA Bacteriano/química , DNA Bacteriano/genética , Genoma Bacteriano , Análise de Sequência de DNA , Zymomonas/genética , Agave/microbiologia , Etanol/metabolismo , Fermentação , Microbiologia de Alimentos , México , Dados de Sequência Molecular , Plasmídeos , Sacarose/metabolismo , Zymomonas/isolamento & purificação , Zymomonas/metabolismo , Zymomonas/fisiologiaRESUMO
Although major depression is one of the most frequent psychiatric disorders among patients with Parkinson's disease, diagnostic criteria have yet to be validated. The main aim of our study was to validate depressive symptoms using latent class analysis for use as diagnostic criteria for major depression in Parkinson's disease. We examined a consecutive series of 259 patients with Parkinson's disease admitted to 2 movement disorders clinics for regular follow-ups. All patients were assessed with a comprehensive psychiatric interview that included structured assessments for depression, anxiety, and apathy. The main finding was that all 9 Diagnostic and Statistical Manual (4th edition) diagnostic criteria for major depression (ie, depressed mood, diminished interest or pleasure, weight or appetite changes, sleep changes, psychomotor changes, loss of energy, feelings of worthlessness or inappropriate guilt, poor concentration, and suicidal ideation) identified a patient class (severe depression group) with high statistical significance. Latent class analysis also demonstrated a patient class with minimal depressive symptoms (no-depression group), and a third patient class with intermediate depressive symptoms (moderate depression). Anxiety and apathy were both significant comorbid conditions of moderate and severe depression. Taken together, our findings support the use of the full Diagnostic and Statistical Manual (4th edition) criteria for major depression for use in clinical practice and research in Parkinson's disease and suggest that anxiety may be included as an additional diagnostic criterion.