RESUMO
Reactive oxygens species (ROS) are common byproducts of metabolic reactions and could be at the origin of many diseases of the elderly. Here we investigated the role of ROS in the renewal of the intestinal epithelium in mice lacking catalase (CAT) and/or nicotinamide nucleotide transhydrogenase (NNT) activities. Cat-/- mice have delayed intestinal epithelium renewal and were prone to develop necrotizing enterocolitis upon starvation. Interestingly, crypts lacking CAT showed fewer intestinal stem cells (ISC) and lower stem cell activity than wild-type. In contrast, crypts lacking NNT showed a similar number of ISCs as wild-type but increased stem cell activity, which was also impaired by the loss of CAT. No alteration in the number of Paneth cells (PCs) was observed in crypts of either Cat-/- or Nnt-/- mice, but they showed an evident decline in the amount of lysozyme. Cat deficiency caused fat accumulation in crypts, and a fall in the remarkable high amount of adipose triglyceride lipase (ATGL) in PCs. Notably, the low levels of ATGL in the intestine of Cat -/- mice increased after a treatment with the antioxidant N-acetyl-L-cysteine. Supporting a role of ATGL in the regulation of ISC activity, its inhibition halt intestinal organoid development. These data suggest that the reduction in the renewal capacity of intestine originates from fatty acid metabolic alterations caused by peroxisomal ROS.
Assuntos
Antioxidantes , Metabolismo dos Lipídeos , Humanos , Camundongos , Animais , Idoso , Metabolismo dos Lipídeos/genética , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Mucosa Intestinal/metabolismo , HomeostaseRESUMO
Invasive fungal disease accounts for about 3.8â million deaths annually, an unacceptable rate that urgently prompts the discovery of new knowledge-driven treatments. We report the use of camelid single-domain nanobodies (Nbs) against fungal ß-1,3-glucanosyltransferases (Gel) involved in ß-1,3-glucan transglycosylation. Crystal structures of two Nbs with Gel4 from Aspergillus fumigatus revealed binding to a dissimilar CBM43 domain and a highly conserved catalytic domain across fungal species, respectively. Anti-Gel4 active site Nb3 showed significant antifungal efficacy in vitro and in vivo prophylactically and therapeutically against different A. fumigatus and Cryptococcus neoformans isolates, reducing the fungal burden and disease severity, thus significantly improving immunocompromised animal survival. Notably, C. deneoformans (serotypeâ D) strains were more susceptible to Nb3 and genetic Gel deletion than C. neoformans (serotype A) strains, indicating a key role for ß-1,3-glucan remodelling in C. deneoformans survival. These findings add new insight about the role of ß-1,3-glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases.
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Aspergillus fumigatus , Domínio Catalítico , Anticorpos de Domínio Único , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/farmacologia , Aspergillus fumigatus/imunologia , Aspergillus fumigatus/enzimologia , Cryptococcus neoformans/enzimologia , Cryptococcus neoformans/imunologia , Antifúngicos/química , Antifúngicos/farmacologia , Animais , Camundongos , Glucana Endo-1,3-beta-D-GlucosidaseRESUMO
PURPOSE: To identify prognostic factors of failure in patients undergoing perineal urethrostomy (PU) with Blandy technique, with inverted U-shaped perineal flap. METHODS: This is a retrospective study of PU of non-oncological causes (2001-2017). Data of age, BMI, history of diabetes mellitus, etiology of urethral stricture, type of stricture, previous surgeries, dilatation and suprapubic catheter were collected. Failure was defined as the need for any instrumentation after surgery. Variables were analyzed by Cox regression and Kaplan-Meier curves were used for survival analysis. RESULTS: A total of 115 PU were performed. Median age was 61 years (IQR 53-68) and BMI 27.9 (IQR 25-30.9). The most frequent etiologies were: lichen sclerosus (30.4%), iatrogenic (27%), and idiopathic (25.7%). 62.6% had panurethral stricture. There were no complications in 73%. Clavien I complications occurred in 25.2%, Clavien II in 0.9% and Clavien IVa in 0.9%. The overall success rate was 51.3% with a median follow-up of 71 months. In the last 8 years, it was 75%. In the multivariate analysis, we found that age (p = 0.01), BMI (p = 0.01), date of surgery (p = 0.01), and suprapubic catheter (p = 0.003) were predictive variables. The voiding satisfaction rate was 88.7%. CONCLUSIONS: PU with Blandy technique is a surgery with low morbidity. During the entire study period, it had a failure rate of 48.7% but the failure rate decreased to 25% over the last 8 years. Age, BMI, date of surgery and suprapubic catheter are the most important prognostic factor of failure.
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Uretra , Estreitamento Uretral , Humanos , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Constrição Patológica/cirurgia , Prognóstico , Uretra/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Estreitamento Uretral/etiologia , Estreitamento Uretral/cirurgia , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/métodosRESUMO
Perennial grasses are potentially abundant sources of biomass for biorefineries, which can produce high yields with low input requirements, and many added environmental benefits. However, perennial grasses are highly recalcitrant to biodegradation and may require pretreatment before undergoing many biorefining pathways. Microbial pretreatment uses the ability of microorganisms or their enzymes to deconstruct plant biomass and enhance its biodegradability. This process can enhance the enzymatic digestibility of perennial grasses, enabling saccharification with cellulolytic enzymes to produce fermentable sugars and derived fermentation products. Similarly, microbial pretreatment can increase the methanation rate when the grasses are used to produce biogas through anaerobic digestion. Microorganisms can also increase the digestibility of the grasses to improve their quality as animal feed, enhance the properties of grass pellets, and improve biomass thermochemical conversion. Metabolites produced by fungi or bacteria during microbial pretreatment, such as ligninolytic and cellulolytic enzymes, can be further recovered as added-value products. Additionally, the action of the microorganisms can release chemicals with commercialization potential, such as hydroxycinnamic acids and oligosaccharides, from the grasses. This review explores the recent advances and remaining challenges in using microbial pretreatment for perennial grasses with the goal of obtaining added-value products through biorefining. It emphasizes recent trends in microbial pretreatment such as the use of microorganisms as part of microbial consortia or in unsterilized systems, the use and development of microorganisms and consortia capable of performing more than one biorefining step, and the use of cell-free systems based on microbial enzymes. KEY POINTS: ⢠Microorganisms or enzymes can reduce the recalcitrance of grasses for biorefining ⢠Microbial pretreatment effectiveness depends on the grass-microbe interaction ⢠Microbial pretreatment can generate value added co-products to enhance feasibility.
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Lignina , Poaceae , Animais , Lignina/química , Fermentação , Biocombustíveis , BiomassaRESUMO
AIMS: To evaluate the biological activity of extracts from cultures of marine bacteria against Toxoplasma gondii and Mycobacterium tuberculosis. METHODS AND RESULTS: Ethyl acetate extracts obtained from seven marine bacteria were tested against T. gondii GFP-RH and M. tuberculosis H37Rv. The cytotoxicity on HFF-1 cells was measured by a microplate resazurin fluorescent approach, and the haemolytic activity was determined photometrically. The extracts from Bacillus sp. (INV FIR35 and INV FIR48) affected the tachyzoite viability. The extracts from Bacillus, Pseudoalteromonas, Streptomyces and Micromonospora exhibited effects on infection and proliferation processes of parasite. Bacillus sp. INV FIR48 extract showed an minimum inhibitory concentration value of 50 µg ml-1 against M. tuberculosis H37Rv. All the extracts exhibited relatively low toxicity to HFF-1 cells and the primary culture of erythrocytes, except Bacillus sp. INV FIR35, which decreased cell viability under 20%. Liquid chromatography coupled to mass spectrometry analysis of the most active bacterial extract Bacillus sp. INV FIR48 showed the presence of peptide metabolites related to surfactin. CONCLUSIONS: The extract from culture of deep-sea Bacillus sp. INV FIR48 showed anti-T. gondii and anti-tuberculosis (TB) biological activity with low cytotoxicity. In addition, peptide metabolites were detected in the extract. SIGNIFICANCE AND IMPACT OF THE STUDY: Toxoplasmosis and TB are among the most prevalent diseases worldwide, and the current treatment drugs exhibit side effects. This study confirm that marine bacteria are on hand sources of anti-infective natural products.
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Mycobacterium tuberculosis , Toxoplasma , Tuberculose , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Tuberculose/tratamento farmacológicoRESUMO
The diversity of deep-sea cultivable bacteria was studied in seven sediment samples of the Colombian Caribbean. Three hundred and fifty two marine bacteria were isolated according to its distinct morphological character on the solid media, then DNA sequences of the 16S rRNA were amplified to identify the isolated strains. The identified bacterial were arranged in three phylogenetic groups, Firmicutes, Proteobacteria, and Actinobacteria, with 34 different OTUs defined at ≥ 97% of similarity and 70 OTUs at ≥ 98.65%, being the 51% Firmicutes, 34% Proteobacteria and 15% Actinobacteria. Bacillus and Fictibacillus were the dominant genera in Firmicutes, Halomonas and Pseudomonas in Proteobacteria and Streptomyces and Micromonospora in Actinobacteria. In addition, the strains were tested for biosurfactants and lipolytic enzymes production, with 120 biosurfactant producing strains (mainly Firmicutes) and, 56 lipolytic enzymes producing strains (Proteobacteria). This report contributes to the understanding of the diversity of the marine deep-sea cultivable bacteria from the Colombian Caribbean, and their potential application as bioremediation agents.
Assuntos
Bactérias , Biodiversidade , Biodegradação Ambiental , Colômbia , DNA Bacteriano/genética , Sedimentos Geológicos/microbiologia , Filogenia , RNA Ribossômico 16S/genéticaRESUMO
We present the case of a 57-year-old female with bloody diarrhea, fever and abdominal pain. Her medical history included human immunodeficiency virus (HIV) infection with an undetectable viral load and end-stage kidney disease secondary to HIV on dialysis. At admission, she had a painful abdomen, no skin lesions and bloody stools in the rectal examination. Laboratory findings included a white blood cell count of 12,900 x 103 cells/µl, CD4 counts of 243 cells/µl and C-reactive protein of 24.5 mg/dl. Serologies, cytomegalovirus and PCR SARS-CoV-2 were negative.
Assuntos
COVID-19 , Infecções por HIV , Falência Renal Crônica , Vasculite , Feminino , Infecções por HIV/complicações , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Pessoa de Meia-Idade , SARS-CoV-2 , Vasculite/complicaçõesRESUMO
The thermal mineral water of Peñón de los Baños spa (Mexico City) has been used for over 500 years starting in pre-Hispanic times and is famous for the treatment of various pathologies. It has a temperature of 45 °C, which is rich in HCO3-, and its main trace elements are B, Li and Fe, which confers healing effects. Concerns about the sustainability of this important spa have motivated this study to understand the thermal system, possible hydraulic and hydrochemical changes over time and its implications. Stable water isotope data indicate that the thermal water sources originate from local precipitation at Sierra de las Cruces with a recharge elevation of approximately 2770 m above sea level. The recharged water percolates through volcanic and carbonate rock formations and ascends via fault structure conduits, where it eventually is extracted 25 km downstream in Peñon de los Baños. During the gravity-driven deep circulation of up to 4.9 km, the groundwater is heated up to 136-160 °C. A comparison of past and current water levels and water chemical analyses indicates a water table drop and few variations in the chemical composition, confirming the presence of anthropic impact on water quality. Due to the heavy groundwater extractions in Mexico City, the spring water flow has ceased, and water must be pumped now from a 203-m deep well. In addition, the concentration of bicarbonate, sodium and chloride has been reduced by half since the onset of groundwater development. The therapeutic effects of this thermal mineral water are at risk due to the alteration of the chemical signature. However, new and different therapeutical uses may prevent a future deterioration or closure of this historically important thermal spa. It is crucial to establish a monitoring program of the thermal mineral water and reducing or minimizing nearby urban extractions which tap the regional flow component to preserve the properties of the thermal water.
Assuntos
Água Subterrânea , Águas Minerais , Poluentes Químicos da Água , Monitoramento Ambiental , Água Subterrânea/química , Isótopos/análise , Águas Minerais/análise , Poluentes Químicos da Água/análise , Qualidade da ÁguaRESUMO
The MAX network transcriptional repressor (MNT) is an MXD family transcription factor of the basic helix-loop-helix (bHLH) family. MNT dimerizes with another transcriptional regulator, MYC-associated factor X (MAX), and down-regulates genes by binding to E-boxes. MAX also dimerizes with MYC, an oncogenic bHLH transcription factor. Upon E-box binding, the MYC-MAX dimer activates gene expression. MNT also binds to the MAX dimerization protein MLX (MLX), and MNT-MLX and MNT-MAX dimers co-exist. However, all MNT functions have been attributed to MNT-MAX dimers, and no functions of the MNT-MLX dimer have been described. MNT's biological role has been linked to its function as a MYC oncogene modulator, but little is known about its regulation. We show here that MNT localizes to the nucleus of MAX-expressing cells and that MNT-MAX dimers bind and repress the MNT promoter, an effect that depends on one of the two E-boxes on this promoter. In MAX-deficient cells, MNT was overexpressed and redistributed to the cytoplasm. Interestingly, MNT was required for cell proliferation even in the absence of MAX. We show that in MAX-deficient cells, MNT binds to MLX, but also forms homodimers. RNA-sequencing experiments revealed that MNT regulates the expression of several genes even in the absence of MAX, with many of these genes being involved in cell cycle regulation and DNA repair. Of note, MNT-MNT homodimers regulated the transcription of some genes involved in cell proliferation. The tight regulation of MNT and its functionality even without MAX suggest a major role for MNT in cell proliferation.
Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Proteínas Repressoras/genética , Transcrição Gênica , Sequência de Aminoácidos/genética , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/química , Proliferação de Células/genética , Regulação da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Sequências Hélice-Alça-Hélice/genética , Humanos , Regiões Promotoras Genéticas , Multimerização Proteica/genética , Proteínas Proto-Oncogênicas c-myc/química , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Repressoras/químicaRESUMO
Electroencephalography (EEG) signal classification is a challenging task due to the low signal-to-noise ratio and the usual presence of artifacts from different sources. Different classification techniques, which are usually based on a predefined set of features extracted from the EEG band power distribution profile, have been previously proposed. However, the classification of EEG still remains a challenge, depending on the experimental conditions and the responses to be captured. In this context, the use of deep neural networks offers new opportunities to improve the classification performance without the use of a predefined set of features. Nevertheless, Deep Learning architectures include a vast number of hyperparameters on which the performance of the model relies. In this paper, we propose a method for optimizing Deep Learning models, not only the hyperparameters, but also their structure, which is able to propose solutions that consist of different architectures due to different layer combinations. The experimental results corroborate that deep architectures optimized by our method outperform the baseline approaches and result in computationally efficient models. Moreover, we demonstrate that optimized architectures improve the energy efficiency with respect to the baseline models.
Assuntos
Interfaces Cérebro-Computador , Algoritmos , Artefatos , Eletroencefalografia , Redes Neurais de Computação , Processamento de Sinais Assistido por ComputadorRESUMO
Seagrass meadows store globally significant organic carbon (Corg ) stocks which, if disturbed, can lead to CO2 emissions, contributing to climate change. Eutrophication and thermal stress continue to be a major cause of seagrass decline worldwide, but the associated CO2 emissions remain poorly understood. This study presents comprehensive estimates of seagrass soil Corg erosion following eutrophication-driven seagrass loss in Cockburn Sound (23 km2 between 1960s and 1990s) and identifies the main drivers. We estimate that shallow seagrass meadows (<5 m depth) had significantly higher Corg stocks in 50 cm thick soils (4.5 ± 0.7 kg Corg /m2 ) than previously vegetated counterparts (0.5 ± 0.1 kg Corg /m2 ). In deeper areas (>5 m), however, soil Corg stocks in seagrass and bare but previously vegetated areas were not significantly different (2.6 ± 0.3 and 3.0 ± 0.6 kg Corg /m2 , respectively). The soil Corg sequestration capacity prevailed in shallow and deep vegetated areas (55 ± 11 and 21 ± 7 g Corg m-2 year-1 , respectively), but was lost in bare areas. We identified that seagrass canopy loss alone does not necessarily drive changes in soil Corg but, when combined with high hydrodynamic energy, significant erosion occurred. Our estimates point at ~0.20 m/s as the critical shear velocity threshold causing soil Corg erosion. We estimate, from field studies and satellite imagery, that soil Corg erosion (within the top 50 cm) following seagrass loss likely resulted in cumulative emissions of 0.06-0.14 Tg CO2-eq over the last 40 years in Cockburn Sound. We estimated that indirect impacts (i.e. eutrophication, thermal stress and light stress) causing the loss of ~161,150 ha of seagrasses in Australia, likely resulted in the release of 11-21 Tg CO2 -eq since the 1950s, increasing cumulative CO2 emissions from land-use change in Australia by 1.1%-2.3% per annum. The patterns described serve as a baseline to estimate potential CO2 emissions following disturbance of seagrass meadows.
Assuntos
Carbono , Solo , Austrália , Carbono/análise , Dióxido de Carbono , Sequestro de Carbono , Sedimentos GeológicosRESUMO
Granulysin is a protein present in the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, with cytolytic activity against microbes and tumors. Previous work demonstrated the therapeutic effect of the intratumoral injection of recombinant granulysin and of the systemic injection of an immunotoxin between granulysin and the anti-carcinoembryonic antigen single-chain Fv antibody fragment MFE23, which were produced in the yeast Pichia pastoris. In the present work, we developed a second immunotoxin combining granulysin and the anti-Tn antigen single-chain Fv antibody fragment SM3, that could have a broader application in tumor treatment than our previous immunotoxin. In addition, we optimized a method based on electroporation by pulsed electric field (PEF) to extract the remaining intracellular protein from yeast, augmenting the production and purificiation yield. The immunotoxin specifically recognized the Tn antigen on the cell surface. We also compared the thermal stability and the cytotoxic potential of the extracellular and intracellular immunotoxins on Tn-expressing human cell lines, showing that they were similar. Moreover, the bioactivity of both immunotoxins against several Tn+ cell lines was higher than that of granulysin alone.
Assuntos
Antígenos de Diferenciação de Linfócitos T/genética , Antígenos Glicosídicos Associados a Tumores/imunologia , Imunotoxinas/farmacologia , Neoplasias/metabolismo , Saccharomycetales/crescimento & desenvolvimento , Anticorpos de Cadeia Única/genética , Células A549 , Antígenos de Diferenciação de Linfócitos T/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Eletroporação , Humanos , Células Jurkat , Células MCF-7 , Neoplasias/tratamento farmacológico , Engenharia de Proteínas , Proteínas Recombinantes/farmacologia , Saccharomycetales/genética , Anticorpos de Cadeia Única/farmacologiaRESUMO
Modulation of TCR signaling upon ligand binding is achieved by changes in the equilibrium between TCR degradation, recycling and synthesis; surprisingly, the molecular mechanism of such an important process is not fully understood. Here, we describe the role of a new player in the mediation of TCR degradation: the endocytic adaptor Numb. Our data show that Numb inhibition leads to abnormal intracellular distribution and defective TCR degradation in mature T lymphocytes. In addition, we find that Numb simultaneously binds to both Cbl and a site within CD3ε that overlaps with the Nck binding site. As a result, Cbl couples specifically to the CD3ε chain to mediate TCR degradation. The present study unveils a novel role of Numb that lies at the heart of TCR signaling initiation and termination.
Assuntos
Complexo CD3/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteólise , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Células HEK293 , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas Oncogênicas/metabolismo , Ligação Proteica/genética , Transporte Proteico/genética , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Deleção de Sequência/genéticaRESUMO
Stress response is associated with increased activity in the hypothalamic-pituitary-adrenocortical axis. Chronic stress-induced elevation in cortisol may alter its own negative regulation with multiple long-term consequences for physical and psychological health. One of the most reliable physical traits associated with mental, apparent physical health, and competitiveness is the degree of facial fluctuating asymmetry. However, to our knowledge there are no studies regarding the relationship between cortisol levels, facial symmetry and male competitiveness, and how cortisol changes after a stressful test depending on these traits. Here, a group of 100 college men were photographed to obtain their facial asymmetry levels. They then, answered the perceived stress scale and the intrasexual competition test and donated two saliva samples (pre-and post-test sample) to measure the change in their cortisol levels after a stressful test. We found that basal cortisol levels were positively correlated with both perceived stress and competitiveness, but not with facial fluctuating asymmetry. Cortisol levels increased in most symmetrical men after a short stressful test, but it decreased in most asymmetrical men. The results suggest differences in endocrine responses according to facial fluctuating asymmetry in men and how these responses could be related to the maintenance of social status.
Assuntos
Assimetria Facial/metabolismo , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Estresse Psicológico/metabolismo , Adolescente , Adulto , Humanos , Masculino , Saliva/química , Meio Social , Adulto JovemRESUMO
INTRODUCTION: Kidney transplantation (KT) is the preferred treatment for patients with end-stage renal disease (ESRD). To reduce the morbidity of the open surgery, a robotic-assisted approach has been recently introduced. Our aim is to evaluate surgical and functional results on 17 cases of robotic-assisted kidney transplantation (RAKT) performed at the same institution. MATERIALS AND METHODS: From July 2015 to June 2016, we performed 17 cases of RAKT from living donors in pre-emptive patients, who underwent laparoscopic nephrectomy. A prospective pilot study was made at Fundació Puigvert (Barcelona), evaluating functional and surgical outcomes. In this series, we considered the functional results, surgical outcomes and complications rates. RESULTS: Seventeen patients successfully underwent RAKT, in particular surgical console time was 181 min (150-200) with vascular suture time 42 min (32-48), and estimated blood loss <70 ml. Overall ischemia time was 98.9 min (84-140). No patient was converted to open transplantation. No major surgical intra-operative complications were observed. The mean post-operative serum creatinine level 160 µmol/L (81-479). We reported a case of delayed graft function (DGF), one case of graft arterial thrombosis and one case of intraperitoneal hematoma. No anastomosis revision and wounds infections occurred. CONCLUSION: RAKT with regional hypothermia appears to be a safe surgical procedure in a properly selected group of patients. The potential advantages of RAKT are related to the quality of the vascular anastomosis, the possible lower complication rate and the shorter recovery of the recipients.
Assuntos
Complicações Pós-Operatórias , Adulto , Feminino , Humanos , Falência Renal Crônica/cirurgia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Projetos Piloto , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Procedimentos Cirúrgicos Robóticos , Espanha , Resultado do TratamentoRESUMO
OBJECTIVE: Analyze results with respect to cortisol reactivity (CR) in experimental stress paradigms in adults with or without a psychiatric disorder who suffered violence in early developmental stages (infancy or early adolescence); and use these results to propose a clinical tool to determine biological stress indicators. METHODS: A systematic review was conducted using several databases and following PRISMA criteria; of a total of 231 articles, 16 satisfied the inclusion criteria and the results were analyzed qualitatively. RESULTS: Despite heterogeneity, the results suggested that the people who suffered violence at an early age present a pattern of low CR. In contrast, people who also developed symptoms of post-traumatic stress disorder and depression, regardless of the type of violence, showed increased CR. The majority of studies focused on people who suffered childhood sexual abuse and half of the articles supported the hypothesis that CR is more pronounced in men than in women. CONCLUSIONS: The results of this review suggest that cortisol hyperreactivity can be considered a biomarker for treatment and intervention in people with post-traumatic stress disorder and depression who suffered violence at an early age. The results also support evidence that experiencing violence alters stress response and mental health in the long term. However, it is necessary to conduct more studies, in particular studies on hyporeactivity and gender differences.
OBJETIVO: Analisar os resultados da reatividade do cortisol segundo um modelo de estresse experimental em adultos com ou sem transtorno psiquiátrico que foram precocemente expostos à violência durante o desenvolvimento (infância e início da adolescência) e propor um instrumento clínico para determinar indicadores biológicos de estresse. MÉTODOS: Uma revisão sistemática foi conduzida em diferentes bases de dados conforme os critérios PRISMA. Dos 231 artigos selecionados, 16 satisfizeram os critérios de inclusão. Foi realizada uma análise qualitativa dos resultados. RESULTADOS: Apesar de serem heterogêneos, os resultados indicam que adultos com exposição precoce à violência apresentam baixa reatividade do cortisol. De maneira oposta, os indivíduos que desenvolveram sintomas de transtorno de estresse pós-traumático e depressão, independentemente do tipo de violência sofrida, apresentaram elevada reatividade do cortisol. A maioria dos estudos se centrou em vítimas de abuso sexual na infância e, em metade dos artigos, sustentou-se a hipótese de que a reatividade do cortisol é mais acentuada no sexo masculino que no feminino. CONCLUSÕES: Os resultados deste estudo de revisão apontam que se pode considerar a hiper-reatividade do cortisol como biomarcador para o tratamento e a intervenção de pacientes que foram expostos precocemente à violência e que apresentam transtorno de estresse pós-traumático e depressão. Além disso, é reforçada a evidência de que sofrer violência afeta a resposta ao estresse e a saúde mental a longo prazo. Porém, fazem-se necessários mais estudos, sobretudo investigando hiporreatividade e diferenças de gênero.
RESUMO
Soon after the discovery of the Myc gene (c-Myc), it became clear that Myc expression levels tightly correlate to cell proliferation. The entry in cell cycle of quiescent cells upon Myc enforced expression has been described in many models. Also, the downregulation or inactivation of Myc results in the impairment of cell cycle progression. Given the frequent deregulation of Myc oncogene in human cancer it is important to dissect out the mechanisms underlying the role of Myc on cell cycle control. Several parallel mechanisms account for Myc-mediated stimulation of the cell cycle. First, most of the critical positive cell cycle regulators are encoded by genes induced by Myc. These Myc target genes include Cdks, cyclins and E2F transcription factors. Apart from its direct effects on the transcription, Myc is able to hyperactivate cyclin/Cdk complexes through the induction of Cdk activating kinase (CAK) and Cdc25 phosphatases. Moreover, Myc antagonizes the activity of cell cycle inhibitors as p21 and p27 through different mechanisms. Thus, Myc is able to block p21 transcription or to induce Skp2, a protein involved in p27 degradation. Finally, Myc induces DNA replication by binding to replication origins and by upregulating genes encoding proteins required for replication initiation. Myc also regulates genes involved in the mitotic control. A promising approach to treat tumors with deregulated Myc is the synthetic lethality based on the inhibition of Cdks. Thus, the knowledge of the Myc-dependent cell cycle regulatory mechanisms will help to discover new therapeutic approaches directed against malignancies with deregulated Myc. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.
Assuntos
Pontos de Checagem do Ciclo Celular/genética , Replicação do DNA/genética , Neoplasias/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proliferação de Células/genética , Quinases Ciclina-Dependentes/genética , Ciclinas/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Proteínas Proto-Oncogênicas c-myc/biossíntese , Quinases Ativadas por p21/genéticaRESUMO
Myc expression is deregulated in many human cancers. A yeast two-hybrid screen has revealed that the transcriptional repressor Sin3b interacts with Myc protein. Endogenous Myc and Sin3b co-localize and interact in the nuclei of human and rat cells, as assessed by co-immunoprecipitation, immunofluorescence, and proximity ligation assay. The interaction is Max-independent. A conserved Myc region (amino acids 186-203) is required for the interaction with Sin3 proteins. Histone deacetylase 1 is recruited to Myc-Sin3b complexes, and its deacetylase activity is required for the effects of Sin3b on Myc. Myc and Sin3a/b co-occupied many sites on the chromatin of human leukemia cells, although the presence of Sin3 was not associated with gene down-regulation. In leukemia cells and fibroblasts, Sin3b silencing led to Myc up-regulation, whereas Sin3b overexpression induced Myc deacetylation and degradation. An analysis of Sin3b expression in breast tumors revealed an association between low Sin3b expression and disease progression. The data suggest that Sin3b decreases Myc protein levels upon Myc deacetylation. As Sin3b is also required for transcriptional repression by Mxd-Max complexes, our results suggest that, at least in some cell types, Sin3b limits Myc activity through two complementary activities: Mxd-dependent gene repression and reduction of Myc levels.
Assuntos
Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Repressoras/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Progressão da Doença , Regulação para Baixo , Feminino , Genes myc , Células HEK293 , Histona Desacetilase 1/genética , Histona Desacetilase 1/metabolismo , Humanos , Células K562 , Pessoa de Meia-Idade , Modelos Biológicos , Domínios e Motivos de Interação entre Proteínas , Proteólise , Proteínas Proto-Oncogênicas c-myc/química , Proteínas Proto-Oncogênicas c-myc/genética , Ratos , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Ativação Transcricional , Técnicas do Sistema de Duplo-HíbridoRESUMO
A study about processing conditions of exportation coffee in 15 benefits located in Chiriqui, western region of Panama, was conducted. In addition, 21 samples of processed coffee (green beans), from the benefits, were analyzed. The samples were microbiologically tested in order to quantify total aflatoxins (B1, B2, G1 and G2) and Ochratoxin A (OTA), using the immunoaffinity ELISA method. A detection limit of 0.017 ng/mL, was determined for Ochratoxin A, which is equivalent to a concentration of 0.829 µg/kg, and a detection limit of 0.027 ng/mL, for total aflatoxins, which is equivalent to a concentration of 1.350 µg/kg. It was found that four (19%) out of the 21 samples were positive to the presence of Ochratoxin A and three (14%) to the presence of total aflatoxins. Samples showed levels of Ochratoxin A in the range 4.90 - 37.73 µg/kg; only three of them exceeded the maximum limit allowed by the European Union, for the concentration of Ochratoxin, which is of 5.0 µg/kg. Total aflatoxins were found in the range 1.51 - 1.93 µg/kg, below 10 µg/kg which is the maximum limit allowed for coffee by the European Union. The results indicate that the processing of coffee produced in Panama successfully meets international standards for postharvest handling, which leads to a low incidence ofmycotoxins and very low levels ofmycotoxin-producing fungi.
Assuntos
Aflatoxinas/análise , Café/química , Ocratoxinas/análise , Cromatografia Líquida de Alta Pressão , Comércio , Ensaio de Imunoadsorção Enzimática , Contaminação de Alimentos/análise , Panamá , Padrões de ReferênciaRESUMO
The island of Guam in the west Pacific has seen a significant decrease in coral cover since 2013. Lafac Bay, a marine protected area in northeast Guam, served as a reference site for benthic communities typical of forereefs on the windward side of the island. The staghorn coral Acropora abrotanoides is a dominant and characteristic ecosystem engineer of forereef communities on exposed shorelines. Photoquadrat surveys were conducted in 2015, 2017, and 2019, and a diver-operated hyperspectral imager (i.e., DiveRay) was used to survey the same transects in 2019. Machine learning algorithms were used to develop an automated pipeline to assess the benthic cover of 10 biotic and abiotic categories in 2019 based on hyperspectral imagery. The cover of scleractinian corals did not differ between 2015 and 2017 despite being subjected to a series of environmental disturbances in these years. Surveys in 2019 documented the almost complete decline of the habitat-defining staghorn coral Acropora abrotanoides (a practically complete disappearance from about 10% cover), a significant decrease (~75%) in the cover of other scleractinian corals, and a significant increase (~55%) in the combined cover of bare substrate, turf algae, and cyanobacteria. The drastic change in community composition suggests that the reef at Lafac Bay is transitioning to a turf algae-dominated community. However, the capacity of this reef to recover from previous disturbances suggests that this transition could be reversed, making Lafac Bay an excellent candidate for long-term monitoring. Community analyses showed no significant difference between automatically classified benthic cover estimates derived from the hyperspectral scans in 2019 and those derived from photoquadrats. These findings suggest that underwater hyperspectral imagers can be efficient and effective tools for fast, frequent, and accurate monitoring of dynamic reef communities.