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INTRODUCTION: Cyanobacteria are microorganisms found in many parts of the world and several genera, such as Raphidiopsis raciborskii, are producers of cyanotoxins. Homeopathic potencies have been found to modulate toxicity in different biological models, and the present study endeavors to discover whether this might also be the case with cyanobacteria. OBJECTIVES: Our objective was to investigate the possible effects of homeopathic potencies on the resilience of Artemia franciscana (brine shrimp) embryos to saxitoxin (STX; cyanotoxin) and on controlling the growth of R. raciborskii in vitro. METHOD: A. franciscana cysts were cultivated in seawater in 96-well plates to evaluate the hatching rate and vitality, plus the gene expression of heat shock proteins (HSPs), after being challenged with R. raciborskii extract containing 2.5 µg/L of STX and treated with different homeopathic potencies. Untreated wells were used as controls ("base-line"). Potencies were chosen from a screening process based on seven selected homeopathic preparations according to the similitude of STX symptoms (Sulphur, Zincum metallicum, Nitric acidum, Plumbum metallicum, Mercurius solubilis, Phosphoric acidum, Isotherapic from R. raciborskii extract; all at 6cH, 30cH and 200cH). Cultures of R. raciborskii maintained in an artificial seawater medium were equally treated with screened homeopathic potencies selected from the same list but specifically for their growth control as a function of time. RESULTS: A 15% lower rate of hatching of A. franciscana cysts was observed after treatment with Nitric acidum 6cH in comparison with baseline (p = 0.05). A complete toxicity reversal was seen after treatment with Isotherapic 200cH, with a 23-fold increase of Hsp 26 gene expression (p = 0.023) and a 24-fold increase of p26 gene expression (p ≤ 0.001) in relation to baseline. Nitric acidum 200cH and Mercurius solubilis 30cH limited the exponential growth of cyanobacteria up to 95% and 85% respectively (p ≤ 0.003) in relation to baseline. Succussed water presented only a transitory 50% inhibition effect. CONCLUSION: Isotherapic 200cH improved A. franciscana bioresilience to STX; Nitric acidum 200cH and Mercurius solubilis 30cH showed the optimal performance on limiting R. raciborskii growth. The results point to the potential of homeopathic potencies to mitigate environmental problems related to water quality.
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INTRODUCTION: The control of cyanobacterial toxicity and growth by homeopathic potencies was described in Part 1 of this two-part report. Here, a parallel approach characterized the physico-chemical features of the potencies used and the liquid media treated with them, correlating these results with their respective biological effects. OBJECTIVES: Our objective was to establish if physico-chemical parameters can track homeopathic potencies in seawater or artificial seawater medium (ASM)-1 and to discover whether these parameters correlate with previously described biological effects. METHOD: Artemia franciscana (brine shrimp) cysts were cultivated in seawater challenged with Raphidiopsis raciborskii extract and treated with different homeopathic potencies chosen from a screening process. Cultures of R. raciborskii maintained in ASM-1 were also treated with previously screened homeopathic potencies, and their growth was monitored as a function of time. The physico-chemical properties of the treated media (seawater or ASM-1) were evaluated by their interaction with solvatochromic dyes and changes in pH, conductivity and temperature. RESULTS: Coumarin 7 was found to be a marker for Nitric acidum 6cH and Isotherapic (R. raciborskii extract) 200cH in seawater (analysis of variance [ANOVA], p = 0.0015). Nile red was found to be a marker for Nitric acidum 200cH and Mercurius solubilis 30cH in ASM-1 (ANOVA, p ≤ 0.001). An increase in pH of ASM-1 and endothermic effects were observed after these treatments (two-way ANOVA, p = 0.0001). Seawater and ASM-1 to which potencies had been added were also subjected to a constant unidirectional 2,400 Gauss static magnetic field and found to have enhanced effects on the solvatochromic dyes tested. CONCLUSION: Homeopathic potencies were specifically traceable in aqueous media using solvatochromic dyes, especially when the samples were subjected to a magnetic field. Results from monitoring other physical parameters, such as pH and temperature, were less specific in relation to potency tracking. However, potency-induced endothermic effects might provide valuable thermodynamic data relating to the nature of potencies.
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INTRODUCTION: Aspirin is one of the most commonly used drugs worldwide. It is known to present antipyretic, anti-inflammatory and anti-thrombotic actions, making it extremely useful in a wide range of clinical contexts. Interestingly, homeopathically prepared Aspirin 15cH has been found to have a pro-thrombotic effect in rats, raising the hypothesis that Aspirin 15cH could also modulate the activity of inflammatory cells in different pathological processes. OBJECTIVE: Our objective was to assess what effect Aspirin 15cH has on RAW 264.7 macrophages in vitro. METHODS: The effects of Aspirin 15cH on biochemical and morphological activities of lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were evaluated. These effects were compared with unchallenged macrophages (negative control), untreated LPS-stimulated macrophages, macrophages treated with succussed water (vehicle control), or aspirin 200 µg/mL (pharmacological inhibitor of LPS activity). Cell morphology (adhered cell area and cytoskeleton arrangements), cell viability, toll-like receptor-4 (TLR-4) expression, and the production of nitric oxide, cytokines and intracellular reactive oxygen species were assessed. RESULTS: Aspirin 15cH reduced the number of cells expressing TLR-4 on the surface (p = 0.03) and induced a "columnar" morphology of macrophage pseudopods, indicating changes in cytoskeleton arrangement. When cells were treated with both Aspirin 15cH and LPS, cell morphology became heterogeneous, suggesting that sub-populations of cells had differing sensitivities to LPS or Aspirin 15cH. Exposure of the cells to LPS alone, succussed water or aspirin 200 µg/mL produced effects consistent with the literature. CONCLUSION: Aspirin 15cH, aspirin 200 µg/mL, LPS and succussed water appear to act as independent stimuli able to induce different patterns of macrophage response. Aspirin 15cH induced changes suggestive of M2 polarization of the macrophages (i.e., toward a wound healing or tissue repair, rather than inflammatory, phenotype). These preliminary findings need to be confirmed in further specific studies.
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Homeopatía , Lipopolisacáridos , Ratas , Animales , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Aspirina/farmacología , Receptor Toll-Like 4/metabolismo , Macrófagos , Citocinas , AguaRESUMEN
The mutant bate-palmas ("claps"; symbol - bapa) mice induced by the mutagenic chemical ENU present motor incoordination and postural alterations. A previous study showed that bapa mice present increased motor/exploratory behaviors during the prepubertal period due to increased striatal tyrosine hydroxylase expression, suggesting striatal dopaminergic system hyperactivity. This study aimed to evaluate the involvement of striatal dopaminergic receptors in the hyperactivity of bapa mice. Male bapa mice and their wild strain (WT) were used. Spontaneous motor behavior was observed in the open-field test, and stereotypy was evaluated after apomorphine administration. The effects of DR1 and DR2 dopaminergic antagonists (SCH-23,390; sulpiride) and the striatal DR1 and D2 receptor gene expression were evaluated. Relative to WT, bapa mice showed: 1) increased general activity for four days; 2) increased rearing and sniffing behavior and decreased immobility after apomorphine; 3) blockage of rearing behavior after the DR2 antagonist but no effect after DR1 antagonist; 4) blockage of sniffing behavior after the DR1 antagonist in bapa and WT mice but no effect after the DR2 antagonist; 5) increased immobility after the DR1 antagonist but no effect after the DR2 antagonist; 6) increased expression of striatal DR1 receptor gene and reduced the DR2 expression gene after apomorphine administration. Bapa mice showed increased activity in open field behavior. The increased rearing behavior induced by apomorphine of bapa mice resulted from the increased gene expression of the DR1 receptor.
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Apomorfina , Benzazepinas , Animales , Masculino , Ratones , Apomorfina/farmacología , Benzazepinas/farmacología , Dopamina , Antagonistas de Dopamina/farmacología , Receptores de Dopamina D1 , Sulpirida/farmacologíaRESUMEN
Understanding the individual and global impact of pesticides on human physiology and the different stages of life is still a challenge in environmental health. We analyzed here whether administration of the organophosphate insecticide malathion before pregnancy could affect glucose homeostasis during pregnancy and, in addition, generate possible later consequences in mothers and offspring. For this, adult Wistar rats were allocated into two groups and were treated daily (intragastric) with malathion (14 or 140 mg/kg, body mass (bm)) for 21-25 days. Corn oil was used as vehicle in the Control group. Subgroups were defined based on the absence (nulliparous) or presence (pregnant) of a copulatory plug. Pregnant rats were followed by an additional period of 2 months after the term (post-term), without continuing malathion treatment. Fetuses and adult offspring of males and females were also evaluated. We ran an additional experimental design with rats exposed to malathion before pregnancy at a dose of 0.1 mg/kg bm. Malathion exposure resulted in glucose intolerance in the mothers during pregnancy and post-term period, regardless of the exposure dose. This was accompanied by increased visceral adipose tissue mass, dyslipidemia, unchanged pancreatic ß-cell mass, and varying insulin responses to glucose in vivo. The number of total newborns and birthweight was not affected by malathion exposure. Adult offspring from both sexes also became glucose-intolerant, regardless of the pesticide dose their dams were exposed to. This alteration could be associated with changes at the epigenomic level, as reduced hepatic mRNA content of DNA methylases and demethylases was found. We demonstrated that periconceptional exposure to malathion with doses aiming to mimic from work environment to indirect contamination predisposes progenitors and offspring rats to glucose intolerance. Thus, we conclude that subchronic exposure to malathion is a risk factor for gestational diabetes and prediabetes later in life.
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Intolerancia a la Glucosa , Efectos Tardíos de la Exposición Prenatal , Recién Nacido , Embarazo , Masculino , Femenino , Ratas , Animales , Humanos , Malatión/toxicidad , Glucemia , Ratas Wistar , Homeostasis , Glucosa , Efectos Tardíos de la Exposición Prenatal/inducido químicamenteRESUMEN
AIMS: This study investigated the possible relationships between the expression of the Kiss1 and Gpr54 gene expressions and the pituitary-gonadal hormones with the female onset of puberty and sexual behavior. The Kiss1 and Gpr54 gene expressions were examined because they are critical to controlling the hypothalamic activation of GnRH neurons and, in turn, the pituitary-gonadal hormones related to the early onset of puberty and sexual behavior. Further, it was evaluated that the pituitary and gonadal hormones involved in the vaginal opening and the expression of sexual behavior. METHODS: Pregnant rats exposed to PRS from gestation days 17 to 20 were evaluated for maternal and open-field behaviors. The maternal behavior was analyzed because it may alter brain sexual organization affecting the pups development. It was observed in female pups the physical and development and, in adult age, the open-field behavior, the anxiety-like behavior, the estrous cycle, the sexual behavior, the serum FSH, LH, estrogen, progesterone, and testosterone levels, and the gene expression of kisspeptin protein (Kiss1) and Gpr54 in the hypothalamus. RESULTS: the maternal and open-field behaviors were unaffected. In the F1 generation, PRS reduced weight at weaning, delayed the day of the vaginal opening and reduced the intensity of lordosis, the estrogen levels, and the Kiss1 and Gpr54 gene expression. These effects were attributed to hypothalamic kisspeptidergic system downregulation of transcripts genes and the reduced estrogen levels affected by the PRS.
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Kisspeptinas , Maduración Sexual , Embarazo , Ratas , Animales , Femenino , Kisspeptinas/genética , Maduración Sexual/fisiología , Hipotálamo/metabolismo , Estrógenos/farmacologíaRESUMEN
Resumo: O presente artigo tem por objetivo analisar as confluências entre a agenda neoliberal capitalista e o conservadorismo moralista religioso, sobretudo as alianças de ocasião travadas por ambos, observadas por Vaggione et al. (2020). Com ênfase nas opressões de gênero e sexualidade fomentadas pelo conservadorismo de matriz cristã, são traçadas perspectivas de resistência pelo Serviço Social brasileiro, em especial considerando a profunda relação entre este e os Movimentos Sociais.
Abstract: This article aims to analyze the confluences between the neoliberal capitalist agenda and religious moralist conservatism, especially the occasional alliances made by both, observed by Vaggione et al. (2020). Emphasizing the oppression of gender and sexuality fostered by conservatism of Christian origin, perspectives of resistance by the Brazilian Social Service are outlined, especially considering the deep relationship between it and the Social Movements.
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Erythroid-related nuclear factor 2 (NRF2) and the antioxidant-responsive-elements (ARE) signaling pathway are the master regulators of cell antioxidant defenses, playing a key role in maintaining cellular homeostasis, a scenario in which proper mitochondrial function is essential. Increasing evidence indicates that the regular practice of physical exercise increases cellular antioxidant defenses by activating NRF2 signaling. This manuscript reviewed classic and ongoing research on the beneficial effects of exercise on the antioxidant system in both the brain and skeletal muscle.
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The objective of this 9-month clinical study is to assess the impact of one-stage full-mouth disinfection (FMD) on salivary nitrite levels and systemic biomarkers and its correlation with total subgingival bacterial load in obese and non-obese patients with periodontitis. In total, 94 patients (55 obese and 39 non-obese) were initially evaluated, seven were lost during follow-up, resulting in 87 individuals at the end of the study. Outcomes were assessed at baseline, 3, 6, and 9 months post periodontal treatment by FMD. Salivary nitrite levels were determined using Griess reagent. Blood samples were collected to determine C-Reactive Protein (CRP), alkaline phosphatase and fasting blood glucose. Real-time PCR was used to determine the total subgingival bacterial load. FMD protocol resulted in increased salivary nitrite levels at 6- and 9-months post-treatment in the non-obese group (p<0.05). In obese individuals, FMD treatment led to an increase in salivary nitrite levels at 6 months (p<0.05); however, at 9 months, the nitrite levels returned to baseline levels. For both groups, the highest nitrite values were observed at 6 months. In addition, in both groups, FMD was associated with a decrease in biomarkers related to systemic inflammation and cardiovascular diseases, such as CRP (p<0.05) and alkaline phosphatase (p<0.05), and had no impact on the fasting blood glucose. This study demonstrates that obese patients with periodontitis present similar salivary nitrite levels when compared with non-obese individuals. FMD protocol resulted in increases in salivary nitrite levels and was associated with a positive impact on systemic biomarkers, regardless of obesity status.
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Nitritos , Periodontitis , Biomarcadores , Desinfección , Humanos , Obesidad/complicacionesRESUMEN
Abstract The objective of this 9-month clinical study is to assess the impact of one-stage full-mouth disinfection (FMD) on salivary nitrite levels and systemic biomarkers and its correlation with total subgingival bacterial load in obese and non-obese patients with periodontitis. In total, 94 patients (55 obese and 39 non-obese) were initially evaluated, seven were lost during follow-up, resulting in 87 individuals at the end of the study. Outcomes were assessed at baseline, 3, 6, and 9 months post periodontal treatment by FMD. Salivary nitrite levels were determined using Griess reagent. Blood samples were collected to determine C-Reactive Protein (CRP), alkaline phosphatase and fasting blood glucose. Real-time PCR was used to determine the total subgingival bacterial load. FMD protocol resulted in increased salivary nitrite levels at 6- and 9-months post-treatment in the non-obese group (p<0.05). In obese individuals, FMD treatment led to an increase in salivary nitrite levels at 6 months (p<0.05); however, at 9 months, the nitrite levels returned to baseline levels. For both groups, the highest nitrite values were observed at 6 months. In addition, in both groups, FMD was associated with a decrease in biomarkers related to systemic inflammation and cardiovascular diseases, such as CRP (p<0.05) and alkaline phosphatase (p<0.05), and had no impact on the fasting blood glucose. This study demonstrates that obese patients with periodontitis present similar salivary nitrite levels when compared with non-obese individuals. FMD protocol resulted in increases in salivary nitrite levels and was associated with a positive impact on systemic biomarkers, regardless of obesity status.
Resumo O objetivo deste estudo clínico, é avaliar o impacto da desinfecção bucal completa (DBC) nos níveis de nitrito salivar e biomarcadores sistêmicos e sua correlação com a carga bacteriana subgengival total em pacientes obesos e não obesos com periodontite. No total, 94 pacientes (55 obesos e 39 não obesos) foram avaliados inicialmente, sete foram perdidos durante o estudo, resultando em 87 indivíduos ao final. Os resultados foram avaliados no início do estudo, 3, 6 e 9 meses após o tratamento periodontal por DBC. Os níveis de nitrito salivar foram determinados usando o reagente de Griess. Amostras de sangue foram coletadas para determinação da Proteína C Reativa (PCR), fosfatase alcalina e glicemia de jejum. A PCR em tempo real foi usada para determinar a carga bacteriana subgengival total. O protocolo de DBC resultou em níveis aumentados de nitrito salivar em 6 e 9 meses após o tratamento no grupo de não obesos (p <0,05). Em indivíduos obesos, o tratamento da DBC levou a um aumento nos níveis de nitrito salivar em 6 meses (p <0,05); no entanto, aos 9 meses, os níveis de nitrito voltaram aos níveis basais. Para ambos os grupos, os maiores valores de nitrito foram observados aos 6 meses. Além disso, em ambos os grupos, a DBC foi associada à diminuição dos biomarcadores relacionados à inflamação sistêmica e doenças cardiovasculares, como PCR (p <0,05) e fosfatase alcalina (p <0,05), e não teve impacto na glicemia de jejum. Este estudo demonstra que pacientes obesos com periodontite apresentam níveis de nitrito salivar semelhantes quando comparados a indivíduos não obesos. O protocolo de DBC resultou em aumentos nos níveis de nitrito salivar e foi associado a um impacto positivo nos biomarcadores sistêmicos, independentemente do status de obesidade.
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Humanos , Periodontitis , Nitritos , Biomarcadores , Desinfección , Obesidad/complicacionesRESUMEN
Obesity and metabolic disorders are increasing worldwide and are associated with brain atrophy and dysfunction, which are risk factors for late-onset dementia and Alzheimer's disease. Epidemiological studies demonstrated that changes in lifestyle, including the frequent practice of physical exercise are able to prevent and treat not only obesity/metabolic disorders, but also to improve cognitive function and dementia. Several biochemical pathways and epigenetic mechanisms have been proposed to understand the beneficial effects of physical exercise on cognition. This manuscript revised central ongoing research on epigenetic mechanisms induced by exercise and the beneficial effects on obesity-associated cognitive decline, highlighting potential mechanistic mediators.
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Trastornos del Conocimiento/terapia , Epigénesis Genética , Terapia por Ejercicio/métodos , Ejercicio Físico/psicología , Obesidad/complicaciones , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Humanos , Obesidad/psicologíaRESUMEN
Xylan is one of the most abundant hemicellulose constituents in the plant kingdom. We extracted xylan from corn cobs (XCC) using ultrasound. The structure of XCC was determined by NMR analysis, which revealed a composition of xylose:glucose:arabinose:galactose:mannose:glucuronic acid in a molar percentage ratio of 48:21:16:10:2.5:2.5. XCC induced the proliferation of murine macrophage cells (RAW 264.7) and inhibited the proliferation of human lung adenocarcinoma epithelial cells (A549) by 20% and human cervical adenocarcinoma cells (HeLa) by 60%. Several cell death-associated morphological changes were observed after the exposure of HeLa cells to XCC for 24 h. In addition, by using fluorescent probes, we observed a larger number of irregular and pyknotic nuclei with condensed chromatin bodies (nuclear condensation). FACS analysis showed an increase in the number of annexin V-positive and propidium iodide (PI)-positive cells (37.0%) in the presence of XCC compared with that of the negative control cells (5.0%). XCC also increased the ratio of Bax:Bcl-2 (3.5:1) and the levels of cytochrome c, caspase 3, and apoptosis-inducing factor (AIF) in treated cells. Therefore, the results demonstrated the antiproliferative potential of XCC, which induced apoptosis in HeLa cells.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Xilanos/farmacología , Zea mays/química , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HeLa , HumanosRESUMEN
Shear stress changes are associated with a repertory of signaling cascade modulating vascular phenotype. As shear stress-related tensional forces might be associated with pathophysiological susceptibility, a more comprehensive molecular map needs to be addressed. Thus, we subjected human umbilical vein endothelial cells (HUVECs) to a circuit of different tensional forces in vitro considering the following three groups: (a) physiological blood flow shear stress condition (named Normo), (b) a hypertensive blood flow shear stress (named Hyper), and (c) these hyper-stressed cells were returned to Normo condition (named Return). The samples were properly collected to allow different methodologies analysis. Our data showed a pivotal involvement of c-Src on driving the mechanotransduction cascade by modulating signaling related with adhesion, survival (PI3K/Akt) and proliferative phenotype. Moreover, c-Src seems to develop important role during extracellular matrix remodeling. Additionally, proteomic analysis showed strong involvement of heat shock protein 70 (HSP70) in the hypertensive-stressed cells; it being significantly decreased in return phenotype. This result prompted us to investigate 20S proteasome as an intracellular proteolytic alternative route to promote the turnover of those proteins. Surprisingly, our data reveled significant overexpression of sets of proteasome subunit α-type (PSMA) and ß-type (PSMB) genes. In conjunction, our data showed c-Src as a pivotal protein to drive mechanotransduction in endothelial cells in a HSP70-dependent turnover scenario. Because shear patterns is associated with pathophysiological changes, such as atherosclerosis and hypertension, these results paved new road to understand the molecular mechanism on driving mechanotransduction in endothelial cells and, if drugable, these targets must be considered within pharmacological treatment optimization.
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Proteína Tirosina Quinasa CSK/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Mecanotransducción Celular/fisiología , Flujo Sanguíneo Regional/fisiología , Adhesión Celular/fisiología , Células Cultivadas , Hemodinámica/fisiología , Humanos , Hipertensión/fisiopatología , Complejo de la Endopetidasa Proteasomal/metabolismo , Transducción de Señal/fisiología , Estrés Mecánico , Estrés Fisiológico/fisiologíaRESUMEN
Chronic metabolic alterations may represent a risk factor for the development of cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and obesity are known to imprint epigenetic markers that compromise the proper expression of cell survival genes. Here, we showed that chronic hyperglycemia (60 days) induced by a single intraperitoneal injection of streptozotocin compromised cognition by reducing hippocampal ERK signaling and by inducing neurotoxicity in rats. The mechanisms appear to be linked to reduced active DNA demethylation and diminished expression of the neuroprotective transcription factor REST. The impact of the relationship between adiposity and DNA hypermethylation on REST expression was also demonstrated in peripheral blood mononuclear cells in obese children with reduced levels of blood ascorbate. The reversible nature of epigenetic modifications and the cognitive impairment reported in obese children, adolescents, and adults suggest that the correction of the anthropometry and the peripheral metabolic alterations would protect brain homeostasis and reduce the risk of developing neurodegenerative diseases.
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Trastornos del Conocimiento/etiología , Diabetes Mellitus Experimental/complicaciones , Hipocampo/metabolismo , Hiperglucemia/complicaciones , Proteínas Represoras/metabolismo , Animales , Reacción de Prevención/fisiología , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/metabolismo , Metilación de ADN , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Humanos , Hiperglucemia/genética , Hiperglucemia/metabolismo , Aprendizaje por Laberinto/fisiología , Ratas , Proteínas Represoras/genéticaRESUMEN
Resumo: O artigo analisa a defesa da liberdade sexual, da diversidade e dos direitos sexuais pela Defensoria Pública do Estado de São Paulo e pelos movimentos sociais no processo de inclusão da Profilaxia Pré-Exposição (PrEP) nos protocolos clínicos e diretrizes terapêuticas do Sistema Único de Saúde - SUS para HIV/Aids, enfatizando o contraponto feito nas atuações contra discursos e práticas institucionalizados heteronormativas e tecnocráticas.
Abstract: This article is a brief analysis on sexual freedom, diversity and sexual rights as sustained arguments by Brazilian Public Defense (Defensoria Pública do Estado de São Paulo) and social movements during the process of public consultation and further approval of Pre-Exposure Prophylaxis (PrEP) in the Brazilian Public Health System, emphasizing a substancial critique on technocracy and heteronormativity.
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Lipases are an economic important group of biocatalysts that can be produced by some fungal under solid-state fermentation. Orange wastes are source of lipases and potential substrates for lipases production. This work assessed 19 fugal strains cultivated in Citrus sinensis cv. Hamlin orange wastes (peel, frit and core) for production of lipases in order to generate compounds with antioxidant, antimicrobial and cytotoxic properties. Fifteen of those fungi grew and produced lipases, mainly the Aspergillus brasiliensis [National Institute of Quality Control (INCQS) 40036]/frit system, which showed 99.58 U/g total lipase. The substrate with the highest production of lipase was frit with 26.67 and 78.91 U/g of total lipases produced on average by the 15 microorganisms. Aspergillus niger 01/frit (33.53 U/g) and Aspergillus niger (INCQS 40015)/frit (34.76 U/g) systems showed the highest specificity values in all the herein tested synthetic substrates with 4, 12 and 16 carbons. Analysis of the fatty acid profile of hydrolysis products obtained in the most prominent systems applied to corn and sunflower oils showed: palmitic acid, linoleic acid, oleic acid, and stearic acid. These acids showed antioxidant capacity of up to 58% DPPH (2,2-diphenyl-1-pierylhydrazyl) radical reduction and antibacterial activity against Escherichia coli, Listeria monocytogenes, Pseudomonas aureginosa, Salmonella Enteritidis and Staphylococcus aureus, as well as cytotoxicity to SCC9 cells (squamous cancer cells).
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Parkinson's disease (PD), the second-most prevalent neurodegenerative disease, is primarily characterized by neurodegeneration in the substantia nigra pars compacta, resulting in motor impairment. Loss-of-function mutations in parkin are the major cause of the early onset familial form of the disease. Although rodents deficient in parkin (parkin(-/-) ) have some dopaminergic system dysfunction associated with central oxidative stress and energy metabolism deficiencies, these animals only display nigrostriatal pathway degeneration under inflammatory conditions. This study investigated the impact of the inflammatory stimulus induced by lypopolisaccharide (LPS) on tetrahydrobiopterin (BH4) synthesizing enzymes (de novo and salvage pathways), since this cofactor is essential for dopamine synthesis. The mitochondrial content and architecture was investigated in the striatum of LPS-exposed parkin(-/-) mice. As expected, the LPS (0.33 mg/kg; i.p.) challenge compromised spontaneous locomotion and social interaction with juvenile parkin(-/-) and WT mice. Moreover, the genotype impacted the kinetics of the investigation of the juvenile. The inflammatory scenario did not induce apparent changes in mitochondrial ultrastructure; however, it increased the quantity of mitochondria, which were of smaller size, and provoked the perinuclear distribution of the organelle. Furthermore, the BH4 de novo biosynthetic pathway failed to be up-regulated in the LPS challenge, a well-known stimulus for its activation. The LPS treatment increased sepiapterin reductase (SPR) expression, suggesting compensation by the salvage pathway. This might indicate that dopamine synthesis is compromised in parkin(-/-) mice under inflammatory conditions. Finally, this scenario impaired the striatal expression of the transcription factor BDNF, possibly favoring cell death.
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Biopterinas/análogos & derivados , Cuerpo Estriado/metabolismo , Ubiquitina-Proteína Ligasas/genética , Oxidorreductasas de Alcohol/metabolismo , Animales , Conducta Animal , Biopterinas/biosíntesis , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cuerpo Estriado/efectos de los fármacos , Dopamina/metabolismo , Lipopolisacáridos/farmacología , Locomoción , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Electrónica de Transmisión , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Plasticidad Neuronal/fisiología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/veterinaria , Ubiquitina-Proteína Ligasas/deficiencia , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The effect of LDH samples comprised of chloride anions intercalated between positive layers of magnesium/aluminum (Mg-Al LDH) or zinc/aluminum (Zn-Al LDH) chemical composition on pre-osteoblast performance is investigated. Non-cytotoxic concentrations of both LDHs modulated pre-osteoblast adhesion by triggering cytoskeleton rearrangement dependent on recruiting of Cofilin, which is modulated by the inhibition of the Protein Phosphatase 2A (PP2A), culminating in osteoblast differentiation with a significant increase of osteogenic marker genes. The alkaline phosphatase (ALP) and bone sialoprotein (BSP) are significantly up-modulated by both LDHs; however, Mg-Al LDH nanomaterial promoted even more significance than both experimental controls, while the phosphorylations of mitogen-activated protein kinase (MAPKs)- extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinase (JNK) significantly increased. MAPK signaling is necessary to activate Runt-related transcription factor 2 (RUNX2) gene. Concomitantly, it is also investigated whether challenged osteoblasts are able to modulate osteoclastogenesis by investigating both osteoprotegerin (OPG) and Receptor activator of nuclear factor kappa-ligand (RANKL) in this model; a dynamic reprogramming of both these genes is found, suggesting LDHs in modulating osteoclastogenesis. These results suggest that LDHs interfere in bone remodeling, and they can be considered as nanomaterials in graft-based bone healing or drug-delivery materials for bone disorders.
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Sustitutos de Huesos/química , Diferenciación Celular , Hidróxidos/química , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Osteogénesis , Aluminio/química , Animales , Sustitutos de Huesos/farmacología , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular , Matriz Extracelular/metabolismo , Magnesio/química , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Ratones , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteopontina/genética , Osteopontina/metabolismo , Ligando RANK/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Zinc/químicaRESUMEN
Exercise improves mental health and synaptic function in the aged brain. However, the molecular mechanisms involved in exercise-induced healthy brain aging are not well understood. Evidence supports the role of neurogenesis and neurotrophins in exercise-induced neuroplasticity. The gene silencing transcription factor neuronal RE1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) and an anti-inflammatory role of exercise are also candidate mechanisms. We evaluate the effect of 8weeks of physical activity on running wheels (RW) on motor and depressive-like behavior and hippocampal gene expression of brain-derived neurotrophic factor (BDNF), REST, and interleukins IL-1ß and IL-10 of adult and aged C57BL/6 mice. The aged animals exhibited impaired motor function and a depressive-like behavior: decreased mobility in the RW and open field and severe immobility in the tail suspension test. The gene expression of REST, IL-1ß, and IL-10 was increased in the hippocampus of aged mice. Physical activity was anxiolytic and antidepressant and improved motor behavior in aged animals. Physical activity also boosted BDNF and REST expression and decreased IL-1ß and IL-10 expression in the hippocampus of aged animals. These results support the beneficial role of REST in the aged brain, which can be further enhanced by regular physical activity.
Asunto(s)
Envejecimiento/metabolismo , Conducta Animal/fisiología , Depresión/metabolismo , Hipocampo/metabolismo , Inflamación/metabolismo , Actividad Motora/fisiología , Condicionamiento Físico Animal/fisiología , Afecto/fisiología , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Interleucina-10/sangre , Interleucina-1beta/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismoRESUMEN
Neglected agricultural products (NAPs) are defined as discarded material in agricultural production. Corn cobs are a major waste of agriculture maize. Here, a methanolic extract from corn cobs (MEC) was obtained. MEC contains phenolic compounds, protein, carbohydrates (1.4:0.001:0.001). We evaluated the in vitro and in vivo antioxidant potential of MEC. Furthermore, its antiproliferative property against tumor cells was assessed through MTT assays and proteins related to apoptosis in tumor cells were examined by western blot. MEC showed no hydroxyl radical scavenger capacity, but it showed antioxidant activity in Total Antioxidant Capacity and DPPH scavenger ability assays. MEC showed higher Reducing Power than ascorbic acid and exhibited high Superoxide Scavenging activity. In tumor cell culture, MEC increased catalase, metallothionein and superoxide dismutase expression in accordance with the antioxidant tests. In vivo antioxidant test, MEC restored SOD and CAT, decreased malondialdehyde activities and showed high Trolox Equivalent Antioxidant Capacity in animals treated with CCl4. Furthermore, MEC decreased HeLa cells viability by apoptosis due an increase of Bax/Bcl-2 ratio, caspase 3 active. Protein kinase C expression increased was also detected in treated tumor cells. Thus, our findings pointed out the biotechnological potential of corn cobs as a source of molecules with pharmacological activity.