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Challenging the basis of our chemical intuition, recent experimental evidence reveals the presence of a new type of intrinsic fluorescence in biomolecules that exists even in the absence of aromatic or electronically conjugated chemical compounds. The origin of this phenomenon has remained elusive so far. In the present study, we identify a mechanism underlying this new type of fluorescence in different biological aggregates. By employing non-adiabatic ab initio molecular dynamics simulations combined with a data-driven approach, we characterize the typical ultrafast non-radiative relaxation pathways active in non-fluorescent peptides. We show that the key vibrational mode for the non-radiative decay towards the ground state is the carbonyl elongation. Non-aromatic fluorescence appears to emerge from blocking this mode with strong local interactions such as hydrogen bonds. While we cannot rule out the existence of alternative non-aromatic fluorescence mechanisms in other systems, we demonstrate that this carbonyl-lock mechanism for trapping the excited state leads to the fluorescence yield increase observed experimentally, and set the stage for design principles to realize novel non-invasive biocompatible probes with applications in bioimaging, sensing, and biophotonics.
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Simulación de Dinámica Molecular , Péptidos , Fluorescencia , Espectrometría de FluorescenciaRESUMEN
Agathisflavone, purified from Cenostigma pyramidale (Tul.) has been shown to be neuroprotective in in vitro models of glutamate-induced excitotoxicity and inflammatory damage. However, the potential role of microglial regulation by agathisflavone in these neuroprotective effects is unclear. Here we investigated the effects of agathisflavone in microglia submitted to inflammatory stimulus in view of elucidating mechanisms of neuroprotection. Microglia isolated from cortices of newborn Wistar rats were exposed to Escherichia coli lipopolysaccharide (LPS, 1 µg/mL) and treated or not with agathisflavone (1 µM). Neuronal PC12 cells were exposed to a conditioned medium from microglia (MCM) treated or not with agathisflavone. We observed that LPS induced microglia to assume an activated inflammatory state (increased CD68, more rounded/amoeboid phenotype). However, most microglia exposed to LPS and agathisflavone, presented an anti-inflammatory profile (increased CD206 and branched-phenotype), associated with the reduction in NO, GSH mRNA for NRLP3 inflammasome, IL1-ß, IL-6, IL-18, TNF, CCL5, and CCL2. Molecular docking also showed that agathisflavone bound at the NLRP3 NACTH inhibitory domain. Moreover, in PC12 cell cultures exposed to the MCM previously treated with the flavonoid most cells preserved neurites and increased expression of ß-tubulin III. Thus, these data reinforce the anti-inflammatory activity and the neuroprotective effect of agathisflavone, effects associated with the control of NLRP3 inflammasome, standing out it as a promising molecule for the treatment or prevention of neurodegenerative diseases.
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CONTEXT: Saturated fats found in diets known as high-fat, cafeteria, or Western diets appear to have a negative effect on bone structure; however, few studies have focused on investigating this association, and the data available in the literature remain controversial. OBJECTIVE: The aim of the current review was to investigate the effects of a high-fat dietary intake on the bone structure of Wistar rats. DATA SOURCES: A search for articles was carried out in the Pubmed/MEDLINE, Web of Science, Embase, and Scopus databases. DATA EXTRACTION: In total, 447 articles were found in the initial search; 5 articles were included in the systematic review, after application of the exclusion criteria. DATA ANALYSIS: The review was guided by the PICOS strategy and based on the PRISMA protocol for animal reviews. CONCLUSION: High-fat diets appear to affect bone structure of Wistar rats. Diet composition and exposure time are the factors determining the strength of the effect.
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Dieta Alta en Grasa , Grasas de la Dieta , Ratas , Animales , Humanos , Dieta Alta en Grasa/efectos adversos , Ratas Wistar , Huesos , Ácidos GrasosRESUMEN
Exposure to a diet with a high saturated fat content can influence the characteristics of the gastrointestinal tract, causing losses in the absorption of nutrients and favoring the appearance of diseases. The objective was to assess the effects of a high-fat diet (HFD) in the perinatal (pregnancy and lactation) and post-weaning period on the histomorphometry, neuroplasticity, and histopathology of the ileum. Wistar rats were divided into four subgroups: Control/Control (CC, n = 10) rats fed a control diet (C) throughout the trial period; Control/HFD (CH, n = 9) rats fed diet C (perinatal) and HFD after weaning; HFD/Control (HC, n = 10) rats fed HFD (perinatal) and diet C (post-weaning); HFD/HFD (HH, n = 9) rats fed HFD throughout the experimental period. There was atrophy of the Ileum wall with a reduction in the muscular tunic, submucosa, and mucosa thickness in the HH group of 37%, 28%, and 46%, respectively (p < 0.0001). The depth of the crypts decreased by 29% (p < 0.0001) and height increased by 5% (p < 0.0013). Villus height decreased by 41% and 18% in HH and HC groups (p < 0.0001) and width decreased by 11% in the HH (p < 0.0001). The height of the enterocytes decreased by 18% in the HH (p < 0.0001). There was a decrease in the area of the myenteric and submucosal plexus ganglia in the HH and HC groups (p < 0.0001). The number, occupation, and granules of Paneth cells increased in the HH and HC groups (p < 0.0001). Intraepithelial lymphocytes (IELs) increased in all groups exposed to the HFD. Goblet cells decreased in groups CH and HH (p < 0.0001). The evidence from this study suggests that the HFD had altered the histomorphometry, neuroplasticity, and histopathology of the ileum of the rats.
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Dieta Alta en Grasa , Ácidos Grasos , Embarazo , Femenino , Ratas , Animales , Dieta Alta en Grasa/efectos adversos , Destete , Ratas Wistar , ÍleonRESUMEN
Antarctic harsh conditions favor the development of microbial adaptations. In this study, a molecular approach was applied to identify/refine the taxonomy of five yeasts isolated from different Antarctic samples, which were tested against ranges of temperature, UV radiations, salinity, and pH. Based on sequencing and phylogenetic analysis, strain CRM 1839 was confirmed as Naganishia sp., and strains CRM 1874, CRM 1565, CRM 2571, and CRM 2576 were identified as Goffeauzyma gilvescens, Goffeauzyma gastrica, Candida atlantica, and Camptobasidium sp., respectively, being this last one possibly a new species. Growth at different temperatures indicates that these yeasts are psychrotolerant, with the exception of Camptobasidium sp., which presents psychrophilic characteristics. G. gastrica recovered from marine sediment showed the best results of resistance to UV radiation, being able to grow even after the exposure to UVB dose of 9144 J/m² and UVC dose of 6102 J/m². C. atlantica isolated from glacier soil showed high cellular growth from 3 to 10% NaCl. The majority of the strains produced higher biomass at pH 7; nevertheless, G. gilvescens showed higher biomass production at pH 9. The studied Antarctic-derived yeasts have adaptations to extreme conditions, which makes them useful for biotechnological applications and studies of extremophiles.
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Sedimentos Geológicos , Levaduras , Regiones Antárticas , FilogeniaRESUMEN
CONTEXT: Hypothalamic inflammation and dysfunction may be induced by high-fat diets. However, the mechanisms involved in this process have not been fully elucidated. OBJECTIVE: To evidence, in animal models, of how a high-fat diet influence the mechanisms involved in hypothalamic inflammation. DATA SOURCES: Scopus, PubMed/Medline, Web of Science, Science Direct, and Embase databases were searched. DATA EXTRACTION: The exclusion criteria were human studies, studies with medicinal products or other substances not related to food, paper reviews, studies that used a surgical intervention or an intervention with food to reverse hypothalamic inflammation, and studies with genetically modified animals. The identified studies were evaluated according to the following inclusion criteria: animal studies, studies in which a control group was included in the experimental design, and studies in which markers of inflammation in the hypothalamus were evaluated. DATA ANALYSIS: A total of 322 studies were found, of which 9 met the inclusion criteria for a systematic review, conducted in accordance with the PRISMA guidelines, and were included in this review. CONCLUSION: The exposure of rodents to high-fat diets promoted an increase in levels of several pro-inflammatory cytokines and other proteins involved in the inflammatory process in the hypothalamus. This process was associated with increased glial cell activity.
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Dieta Alta en Grasa , Hipotálamo , Animales , Biomarcadores/metabolismo , Citocinas , Dieta Alta en Grasa/efectos adversos , Humanos , Hipotálamo/metabolismo , Inflamación/etiología , Inflamación/metabolismoRESUMEN
Este estudo avaliou o status do cálcio sérico em 39 vacas com deslocamento de abomaso (DA), provenientes de 30 propriedades leiteiras selecionadas, na região de Campos Gerais no Paraná. O diagnóstico do deslocamento de abomaso foi realizado por percussão auscultatória, além dos sinais clínicos e informações da anamnese. Previamente ao procedimento cirúrgico, amostras de sangue foram coletadas para a mensuração dos níveis sanguíneos de cálcio, albumina, proteína e glicose. Como grupo controle, amostras de sangue foram coletadas de vacas hígidas que se encontravam em semelhante período de lactação. Das 39 vacas com deslocamento de abomaso, 35 apresentaram hipocalcemia e no grupo controle, apenas um animal. Concentrações sanguíneas de glicose e proteína foram inferiores nos animais com DA, quando comparados com animais do grupo controle.(AU)
This study evaluated the status of serum calcium in 39 Holstein cows with displacement of the abomasum (DA), from 30 dairy farms selected in the region of Campos Gerais, Paraná state, Brazil.. The diagnosis of abomasal displacement was performed by auscultation and percussion, besides the clinical signs and history information. Before surgery, blood samples were collected to measure blood levels of calcium, albumin, protein and glucose. As a control group, blood samples were collected from healthy cows that were in similar period of lactation. Of the 39 cows with abomasal displacement, 35 had hypocalcemia and in the control group only one cow. Blood glucose and protein concentrations were lower in the animals with DA when compared with the control group.(AU)
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Animales , Bovinos , Abomaso/patología , Calcio/análisis , Calcio/sangre , Hipocalcemia/sangre , Hipocalcemia/veterinaria , Glucemia/análisis , Proteínas Sanguíneas/análisisRESUMEN
This study evaluated the status of serum calcium in 39 Holstein cows with displacement of the abomasum (DA), from 30 dairy farms selected in the region of Campos Gerais, Paraná state, Brazil.. The diagnosis of abomasal displacement was performed by auscultation and percussion, besides the clinical signs and history information. Before surgery, blood samples were collected to measure blood levels of calcium, albumin, protein and glucose. As a control group, blood samples were collected from healthy cows that were in similar period of lactation. Of the 39 cows with abomasal displacement, 35 had hypocalcemia and in the control group only one cow. Blood glucose and protein concentrations were lower in the animals with DA when compared with the control group.(AU)
Este estudo avaliou o status do cálcio sérico em 39 vacas com deslocamento de abomaso (DA), provenientes de 30 propriedades leiteiras selecionadas, na região de Campos Gerais no Paraná. O diagnóstico do deslocamento de abomaso foi realizado por percussão auscultatória, além dos sinais clínicos e informações da anamnese. Previamente ao procedimento cirúrgico, amostras de sangue foram coletadas para a mensuração dos níveis sanguíneos de cálcio, albumina, proteína e glicose. Como grupo controle, amostras de sangue foram coletadas de vacas hígidas que se encontravam em semelhante período de lactação. Das 39 vacas com deslocamento de abomaso, 35 apresentaram hipocalcemia e no grupo controle, apenas um animal. Concentrações sanguíneas de glicose e proteína foram inferiores nos animais com DA, quando comparados com animais do grupo controle.(AU)
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Animales , Bovinos , Hipocalcemia/sangre , Hipocalcemia/veterinaria , Abomaso/patología , Calcio/análisis , Calcio/sangre , Glucemia/análisis , Proteínas Sanguíneas/análisisRESUMEN
ABSTRACT: This study evaluated the status of serum calcium in 39 Holstein cows with displacement of the abomasum (DA), from 30 dairy farms selected in the region of Campos Gerais, Paraná state, Brazil.. The diagnosis of abomasal displacement was performed by auscultation and percussion, besides the clinical signs and history information. Before surgery, blood samples were collected to measure blood levels of calcium, albumin, protein and glucose. As a control group, blood samples were collected from healthy cows that were in similar period of lactation. Of the 39 cows with abomasal displacement, 35 had hypocalcemia and in the control group only one cow. Blood glucose and protein concentrations were lower in the animals with DA when compared with the control group.
RESUMO: Este estudo avaliou o status do cálcio sérico em 39 vacas com deslocamento de abomaso (DA), provenientes de 30 propriedades leiteiras selecionadas, na região de Campos Gerais no Paraná. O diagnóstico do deslocamento de abomaso foi realizado por percussão auscultatória, além dos sinais clínicos e informações da anamnese. Previamente ao procedimento cirúrgico, amostras de sangue foram coletadas para a mensuração dos níveis sanguíneos de cálcio, albumina, proteína e glicose. Como grupo controle, amostras de sangue foram coletadas de vacas hígidas que se encontravam em semelhante período de lactação. Das 39 vacas com deslocamento de abomaso, 35 apresentaram hipocalcemia e no grupo controle, apenas um animal. Concentrações sanguíneas de glicose e proteína foram inferiores nos animais com DA, quando comparados com animais do grupo controle.
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Portadores de fibromialgia queixam-se de dor generalizada, fadiga e distúrbios do sono. Os exames laboratoriais são caracteristicamente negativos nesta patologia. Devido à natureza pouco específica dos sintomas e a falta de provas palpáveis de um processo inflamatório, estes pacientes nem sempre têm as suas queixas devidamente valorizadas. No presente estudo procurou-se demonstrar o grande impacto desta patologia na qualidade de vida de seus portadores comparando-a com a de portadores de artrite reumatóide. Além disso procurou-se verificar se este prejuízo estava associado com o grau de dor percebido pelo paciente ou com o número de pontos sensíveis encontrados ao exame físico
Fibromyalgia patients complain of generalized pain, fatigue and sleep disturbance. Laboratory exams are typically negative in this pathology. Due to this lack of symptom's specificity and palpable proofs of inflammatory disease, these patients complaints are not taken seriously. In this study we try to demonstrate the high impact of fibromyalgia in the patient's life quality comparing them with rheumatoid arthritis patients. We also try to verify the relationship between poor life quality with generalized pain and number of tender points at physical examination
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Portadores de fibromialgia queixam-se de dor generalizada, fadiga e distúrbios do sono. Os exames laboratoriais são caracteristicamente negativos nesta patologia. Devido à natureza pouco específica dos sintomas e a falta de provas palpáveis de um processo inflamatório, estes pacientes nem sempre têm as suas queixas devidamente valorizadas. No presente estudo procurou-se demonstrar o grande impacto desta patologia na qualidade de vida de seus portadores comparando-a com a de portadores de artrite reumatóide. Além disso procurou-se verificar se este prejuízo estava associado com o grau de dor percebido pelo paciente ou com o número de pontos sensíveis encontrados ao exame físico.
Fibromyalgia patients complain of generalized pain, fatigue and sleep disturbance. Laboratory exams are typically negative in this pathology. Due to this lack of symptom's specificity and palpable proofs of inflammatory disease, these patients complaints are not taken seriously. In this study we try to demonstrate the high impact of fibromyalgia in the patient's life quality comparing them with rheumatoid arthritis patients. We also try to verify the relationship between poor life quality with generalized pain and number of tender points at physical examination.
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OBJECTIVE: We examined age of onset of bipolar disorder as a potential course-of-illness modifier with the hypothesis that early onset will engender more severe illness. STUDY DESIGN: A total of 480 carefully diagnosed adult outpatients with bipolar disorder (mean age, 42.5 +/- 11.6 years) were retrospectively rated for age of illness onset, time to first pharmacotherapy, and course of illness. Clinicians prospectively rated daily mood fluctuations over 1 year. RESULTS: Of the 480 patients, 14% experienced onset in childhood (12 years or younger); 36% in adolescence (13 to 18 years); 32% in early adulthood (19 to 29 years); and 19% in late adulthood (after 30 years). Childhood-onset bipolar illness was associated with long delays to first treatment, averaging more than 16 years. The patients with childhood or adolescent onset reported more episodes, more comorbidities, and rapid cycling retrospectively; prospectively, they demonstrated more severe mania, depression, and fewer days well. CONCLUSIONS: This study demonstrates that childhood onset of bipolar disorder is common and is associated with long delays to first treatment. Physicians and clinicians should be alert to a possible bipolar diagnosis in children in hopes of shortening the time to initiating treatment and perhaps ameliorating the otherwise adverse course of illness.
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Trastorno Bipolar/terapia , Adolescente , Adulto , Edad de Inicio , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/epidemiología , Niño , Femenino , Humanos , Masculino , Pronóstico , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Mitochondrial permeability transition (MPT) is a nonselective inner membrane permeabilization that contributes to neuronal cell death under circumstances such as brain trauma, ischemia, and hypoglycemia. Here we study the participation of MPT and the Bcl-2-sensitive apoptotic cell death pathway in glutamate receptor-mediated excitotoxicity. Intrastriatal infusions of the N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid caused massive striatal neurodegeneration in both rats and mice. Interestingly, transgenic mice overexpressing human Bcl-2 and rats systemically treated with cyclosporin A did not exhibit reduced sensitivity to quinolinic acid-induced striatal toxicity. Both Bcl-2 and cyclosporin A are inhibitors of MPT; in addition Bcl-2 also inhibits apoptotic stimuli-mediated release of mitochondrial apoptogenic factors. Isolated brain mitochondria from cyclosporin A-treated rats showed resistance to Ca(2+)-induced dissipation of the membrane potential, indicating protection against MPT. We conclude that quinolinic acid-mediated striatal excitotoxicity is not dependent on MPT and Bcl-2-sensitive apoptotic cell death pathways.