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1.
RSC Adv ; 13(30): 21071-21079, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37448636

RESUMO

Today's rising energy costs, coupled with increasing energy demand, make it necessary to search for more efficient energy processes. In recent years, there have been increasing efforts to develop efficient catalysts based on waste-derived char, by a single step where the carbon precursor and the metallic active phase one undergo a single common thermal process under a reductant atmosphere at high temperature. The use of a reductant atmosphere drives the formation of carbonaceous materials with different characteristics than those obtained under the standard nitrogen-inert one. Our work evaluates the influence of the residence time and the heating rate on the physicochemical properties of the biochar obtained. Relatively long residence times and slow heating rates, improve the yield to the resulting biochar, without increasing production cost, making the subsequent char-based metallic catalyst synthesis more efficient. The heating rate was shown to be key in improving the properties of the char in a smoother and more controlled way, unlocking a new working pathway for the efficient design and production of char-based catalysts in a one-pot synthesis.

2.
Psychol Med ; 53(15): 7265-7276, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37185055

RESUMO

BACKGROUND: Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis. METHODS: The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use. RESULTS: After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1-3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2-2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (ß = -2.3; p ⩽ 0.001; 95% CI [-3.7 to -0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0-1.8]); however, these results were no longer significant after controlling for cannabis use. CONCLUSIONS: Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.


Assuntos
Cannabis , Transtornos Psicóticos , Esquizofrenia , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/diagnóstico , Esquizofrenia/epidemiologia , Uso de Tabaco/epidemiologia , Cannabis/efeitos adversos
3.
Sci Total Environ ; 847: 157647, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35907537

RESUMO

Nonylphenol (NP) is an anthropogenic pollutant frequently found in sewage sludge due to the insufficient degrading effectiveness of conventional WWTPs and has attracted attention as an endocrine disruptor. The aim of this study was to isolate specific NP-degrading bacteria from sewage sludge to be used in the degradation of this contaminant through bioaugmentation processes in aqueous solution and sewage sludge. Up to eight different bacterial strains were isolated, six of them not previously described as NP degraders. Bacillus safensis CN12 presented the best NP degradation in solution, and glucose used as an external carbon source increased its effect, reaching DT50 degradation values (time to decline to half the initial concentration of the pollutant) of only 0.9 days and a complete degradation in <7 days. Four NP metabolites were identified throughout the biodegradation process, showing higher toxicity than the parent contaminant. In sewage sludge suspensions, the endogenous microbiota was capable of partially degrading NP, but a part remained adsorbed as bound residue. Bioaugmentation was used for the first time to remove NP from sewage sludge to obtain more environmentally friendly biosolids. However, B. safensis CN12 was not able to degrade NP due to its high adsorption on sludge, but the use of a cyclodextrin (HPBCD) as availability enhancer allowed us to extract NP and degrade it in solution. The addition of glucose as an external carbon source gave the best results since the metabolism of the sludge microbiota was activated, and HPBCD was able to remove NP from sewage sludge to the solution to be degraded by B. safensis CN12. These results indicate that B. safensis CN12 can be used to degrade NP in water and sewage sludge, but the method must be improved using consortia of B. safensis CN12 with other bacterial strains able to degrade the toxic metabolites produced.


Assuntos
Ciclodextrinas , Disruptores Endócrinos , Poluentes Ambientais , Bactérias , Biodegradação Ambiental , Biossólidos , Carbono , Glucose , Fenóis , Esgotos/microbiologia , Água
5.
Artigo em Português | LILACS | ID: biblio-1353025

RESUMO

Fundamentos: Idosos que vivem na comunidade são propensos a desenvolver fragilidade, considerada como um estado clinicamente identificável que aumenta a vulnerabilidade a resultados adversos e prediz incapacidade e mortalidade na população idosa. Objetivo: Identificar a prevalência e fatores associados à fragilidade em idosos que vivem em uma comunidade. Método: Trata-se de um inquérito domiciliar transversal e analítico, de abordagem quantitativa realizado com 854 idosos que vivem na comunidade. A fragilidade foi mensurada pela Edmonton Frail Scale (EFS). A associação entre fragilidade e variáveis sociodemográficas e de condições clínicas foi mensurada pela análise múltipla por regressão logística. Resultados: A prevalência de fragilidade encontrada neste estudo foi de 12,3% (IC95%: 10,1 a 14,5). O modelo de regressão logística mostrou que as variáveis estatisticamente associadas à fragilidade foram: queda recorrente, uso de dispositivo para auxílio à marcha, polifarmácia, autopercepção ruim de saúde, dependência nas atividades básicas e instrumentais de vida diária. Conclusão: A prevalência de fragilidade em idosos foi baixa em comparação a outros estudos nacionais que empregaram a EFS. Os resultados indicaram múltiplos fatores associados à fragilidade modificáveis. Assim, a investigação da síndrome da fragilidade bem como dos seus fatores relacionados passíveis de prevenção são ações a serem incluídas na prática clínica. (AU)


Foundations: Elderly people living in the community are prone to developing frailty, considered as a clinically identifiable state that increases vulnerability to adverse events and predicts disability and mortality in the elderly population. Objective: To identify the prevalence and factors associated with frailty in the elderly living in the community. Materials and method: This is a cross-sectional and analytical household survey with a quantitative approach conducted with 854 elderly people living in the community. Frailty was measured by Edmonton Frail Scale (EFS). The association between frailty and sociodemographic and clinical condition variables was measured by multiple analysis using logistic regression. Results: The prevalence of frailty found in this study was 12.3% (95% CI: 10.1 to 14.5). The logistic regression model showed that the variables statistically associated with frailty were: recurrent fall, use of walking aids, polypharmacy, poor self-rated health, dependence on basic and instrumental activities of daily living. Conclusion: The prevalence of frailty in the elderly was low compared to other national studies that employed the SAI. Results indicated potentially modifiable factors associated with frailty. Thus, the investigation of frailty syndrome and its related preventable factors are actions to be included in clinical practice. (AU)


Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Atividades Cotidianas , Prevalência , Idoso Fragilizado , Prevenção de Doenças , Vulnerabilidade em Saúde , Fragilidade , Marcha , Instituição de Longa Permanência para Idosos , Métodos
6.
Public Health ; 201: 69-74, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34794094

RESUMO

OBJECTIVES: This study assessed the moderating role of education on the relationship between multimorbidity and mortality among older adults in Brazil. STUDY DESIGN: This was a cohort study. METHODS: This study used data from 1768 participants of the Health, Well-Being and Ageing Cohort Study (SABE) who were assessed between 2006 and 2015. The Cox Proportional Risks Model was used to evaluate the association between multimorbidity (two or more chronic diseases) and mortality. An interaction term between education and multimorbidity was included to test the moderating role of education in this association. RESULTS: The average follow-up time was 4.5 years, with a total of 589 deaths in the period. Multimorbidity increased the risk of mortality (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.27-1.91), and this association was not moderated by education (HR 1.06, 95% CI 1.00-1.13; P value = 0.07). CONCLUSIONS: The impact of education and multimorbidity on mortality emphasises the need for an integrated approach directed towards the social determinants of health to prevent multimorbidity and its burden among older adults.


Assuntos
Envelhecimento , Multimorbidade , Idoso , Doença Crônica , Estudos de Coortes , Humanos , Modelos de Riscos Proporcionais
7.
Braz J Med Biol Res ; 54(8): e11447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34320123

RESUMO

Knowledge about the needs of psychiatric patients is essential for mental health care planning. However, research on met and unmet needs is still scarce, particularly in low- and middle-income countries. This study aimed to describe the patients' needs (met and unmet) at least four years after their first psychiatric hospitalization and to verify the role of demographic and clinical features as possible predictors of these needs. Patients who had their first psychiatric admission between January 1, 2006 and December 31, 2007 at an inpatient unit in the city of Ribeirão Preto, Brazil, were eligible to participate in the study. Patients were contacted and face-to-face interviews were conducted by psychologists using the Camberwell Assessment of Need. Data were analyzed using zero-inflated negative binomial regression model. Of 933 eligible patients, 333 were interviewed. The highest level of needs was related to welfare benefits (32.4%, unmet=25.5%), followed by household skills (30.3%, unmet=3.0%), psychotic symptoms (29.4%, unmet=9.0%), psychological distress (27.6%, unmet=8.4%), physical health (24.3%, unmet=5.4%), daytime activities (19.5%, unmet=16.5%), and money (16.8%, unmet=9.0%). Fewer years of schooling, living with relatives, and unemployment at the moment of the first admission were significantly associated with a higher number of both met and unmet needs in the follow-up. Unmet needs were also more often reported by patients living alone. In conclusion, socioeconomic indicators were the best predictors of needs. The unmet needs related to welfare benefits point to the need for specific social and health policies.


Assuntos
Hospitalização , Pacientes Internados , Brasil , Estudos de Coortes , Humanos , Determinação de Necessidades de Cuidados de Saúde
9.
J Nutr Health Aging ; 25(2): 201-208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33491035

RESUMO

OBJECTIVES: Higher total energy expenditure in free living conditions, regardless of any activity, has been strongly associated with a lower risk of mortality in healthy older adults. Also, a good performance in physical and functional tests is a marker of good functional prognosis. However, it is not yet clear what is the association between total energy expenditure and the performance in physical and functional tests. The objective of this study was to verify the association between the total energy expenditure of older adults measured by doubly labelled water and the performance in functional tests. DESIGN: Cross-sectional study. SETTINGS AND PARTICIPANTS: Fifty-six older people were recruited from health services linked to the participating institutions. MEASUREMENTS: Socio-demographic, anthropometric and clinical characteristics were assessed through the application of a structured questionnaire. Body composition was evaluated by isotopic dilution of deuterium oxide and functional status was assessed by the gait speed test, 6-minute walk test and handgrip strength. Total energy expenditure (GET) was assessed using the doubly labelled water method and the physical activity profile was verified using an activity monitor based on accelerometery. RESULTS: The results showed that the highest total energy expenditure correlated with the best performance in the gait speed tests (r = 0.266; p = 0.047), 6-minute walk test (r = 0.424; p = 0.001) and maximum handgrip strength (r = 0.478; p = 0.000). Multivariate regression analysis in a model adjusted for sex and fat-free mass revealed an association between total energy expenditure and the 6-minute walk test (ß = 1.790; t = 2.080; p = 0.044) and the number of sedentary events ( ß = 6.389; t = 2.147; p = 0.038). CONCLUSION: The results of this study suggest that, in clinical practice, older individuals with lower gait speed, worse performance in the 6-minute walk test and lower handgrip strength, may have lower total energy expenditure, being the stimulus for its increase important for the prevention of possible problems related to low energy expenditure.


Assuntos
Antropometria/métodos , Metabolismo Energético/genética , Água/química , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino
10.
Phys Chem Chem Phys ; 23(4): 2836-2845, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33470998

RESUMO

Melanoma is a type of skin cancer with increasing incidence worldwide and high lethality. Conventional forms of treatment are not effective in advanced cancer stages. Hence, immunotherapeutic approaches have been tested to modulate immune response against tumor cells. Some vaccine models using tumor-associated antigens (TAAs) such as glycoprotein 100 (gp100) have been studied, but their expected effectiveness has not been shown until now. Antigen immunogenicity is a crucial point to improve the immune response, and therefore mutations are inserted in peptide sequences. It is possible to understand the interactions which occur between peptides and immune system molecules through computer simulation, and this is essential in order to guide efficient vaccine models. In this work, we have calculated the interaction binding energies of crystallographic data based on modified gp100 peptides and HLA-A*0201 using density functional theory (DFT) and the molecular fractionation with conjugated caps (MFCC) approach. Our results show the most relevant residue-residue interactions, the impact of three mutations in their binding sites, and the main HLA-A*0201 amino acids for peptide-HLA binding.


Assuntos
Antígeno HLA-A2/metabolismo , Antígeno gp100 de Melanoma/metabolismo , Simulação por Computador , Teoria da Densidade Funcional , Antígeno HLA-A2/química , Humanos , Modelos Químicos , Mutação , Fragmentos de Peptídeos , Ligação Proteica , Termodinâmica , Antígeno gp100 de Melanoma/química , Antígeno gp100 de Melanoma/genética
11.
Braz. j. med. biol. res ; 54(8): e11447, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1285673

RESUMO

Knowledge about the needs of psychiatric patients is essential for mental health care planning. However, research on met and unmet needs is still scarce, particularly in low- and middle-income countries. This study aimed to describe the patients' needs (met and unmet) at least four years after their first psychiatric hospitalization and to verify the role of demographic and clinical features as possible predictors of these needs. Patients who had their first psychiatric admission between January 1, 2006 and December 31, 2007 at an inpatient unit in the city of Ribeirão Preto, Brazil, were eligible to participate in the study. Patients were contacted and face-to-face interviews were conducted by psychologists using the Camberwell Assessment of Need. Data were analyzed using zero-inflated negative binomial regression model. Of 933 eligible patients, 333 were interviewed. The highest level of needs was related to welfare benefits (32.4%, unmet=25.5%), followed by household skills (30.3%, unmet=3.0%), psychotic symptoms (29.4%, unmet=9.0%), psychological distress (27.6%, unmet=8.4%), physical health (24.3%, unmet=5.4%), daytime activities (19.5%, unmet=16.5%), and money (16.8%, unmet=9.0%). Fewer years of schooling, living with relatives, and unemployment at the moment of the first admission were significantly associated with a higher number of both met and unmet needs in the follow-up. Unmet needs were also more often reported by patients living alone. In conclusion, socioeconomic indicators were the best predictors of needs. The unmet needs related to welfare benefits point to the need for specific social and health policies.


Assuntos
Humanos , Hospitalização , Pacientes Internados , Brasil , Estudos de Coortes , Determinação de Necessidades de Cuidados de Saúde
12.
Epidemiol Psychiatr Sci ; 29: e182, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200977

RESUMO

AIMS: Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum. METHODS: The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components). RESULTS: Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene-environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions. CONCLUSIONS: The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.


Assuntos
Herança Multifatorial , Transtornos Psicóticos/genética , Esquizofrenia/genética , Adulto , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Genômica , Humanos , Masculino , Transtornos Psicóticos/psicologia , Psicologia do Esquizofrênico
13.
Biomed Pharmacother ; 130: 110592, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763822

RESUMO

OBJECTIVES: The most recent survey conducted by the World Health Organization described Tuberculosis (TB) as one of the top 10 causes of death and the leading cause of death from a single infectious agent. The increasing number of TB-resistant cases has contributed to this scenario. In light of this, new strategies to control and treat the disease are necessary. Our research group has previously described furoxan derivatives as promising scaffolds to be explored as new antitubercular drugs. RESULTS: Two of these furoxan derivatives, (14b) and (14c), demonstrated a high selectivity against Mycobacterium tuberculosis. The compounds (14b) and (14c) were also active against a latent M. tuberculosis strain, with MIC90 values of 6.67 µM and 9.84 µM, respectively; they were also active against monoresistant strains (MIC90 values ranging from 0.61 to 20.42 µM) and clinical MDR strains (MIC90 values ranging from 3.09 to 42.95 µM). Time-kill experiments with compound (14c) showed early bactericidal effects that were superior to those of the first- and second-line anti-tuberculosis drugs currently used in therapy. The safety of compounds (14b) and (14c) was demonstrated by the Ames test because these molecules were not mutagenic under the tested conditions. Finally, we confirmed the safety, and high efficacy of compounds (14b) and (14c), which reduced M. tuberculosis to undetectable levels in a mouse aerosol model of infection. CONCLUSION: Altogether, we have identified two advanced lead compounds, (14b) and (14c), as novel promising candidates for the treatment of TB infection.


Assuntos
Antituberculosos/uso terapêutico , Oxidiazóis/uso terapêutico , Tuberculose/tratamento farmacológico , Animais , Antituberculosos/farmacologia , Antituberculosos/toxicidade , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Testes de Mutagenicidade , Mycobacterium tuberculosis/efeitos dos fármacos , Oxidiazóis/farmacologia , Oxidiazóis/toxicidade , Tuberculose/microbiologia
14.
Clin Transl Oncol ; 22(11): 2017-2025, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32253706

RESUMO

PURPOSE: Meningiomas are common brain tumors, the majority of which are considered benign. Despite surgery and/or radiation therapy, recurrence rates are approximately 8-10%. One likely cause is the dysregulation of cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma (Rb) pathway, which controls the cell cycle restriction point. This pathway is commonly dysregulated in anaplastic meningioma cell lines (AM) and radiation-induced meningioma cells (RIM), making it a rational target for anti-meningioma therapy. In this study, we investigate the effect of a CDK4/6 inhibitor, palbociclib, with radiation in relevant pre-clinical models. METHODS: In vitro cell culture, ex vivo slice culture and in vivo cell line-derived orthotopic xenograft animal models of AM/RIM were utilized to assess treatment efficacy with palbociclib plus radiation. Treatment effects were examined by immunoblot, cell viability, apoptosis, and cell cycle progression. RESULTS: The in vitro and ex vivo studies demonstrate that palbociclib plus radiation treatment reduced proliferation and has additional effects on cell cycling, including induction of an RB-associated G (1) arrest in Rb+ AM and RIM cells, but not in Rb- cells. Our results also demonstrated reduced CDK4 and CDK6 expression as well as reduced E2F target gene expression (CCNA2 and CCNE2) with the combination therapy. MRI results in vivo demonstrated reduced tumor size at 5 weeks when treated with 14 days palbociclib (10 mg/kg) plus 6 Gy radiation compared to saline-treated tumors. Finally, no hepatic toxicity was found after treatments. CONCLUSION: A pre-clinical murine model provides preclinical evidence for use of palbociclib plus radiation as a therapeutic agent for Rb+ meningiomas.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Meníngeas/terapia , Meningioma/terapia , Neoplasias Induzidas por Radiação/terapia , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Humanos , Masculino , Camundongos , Proteína do Retinoblastoma/metabolismo
15.
Clin Transl Oncol ; 22(7): 1138-1145, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31732915

RESUMO

PURPOSE: N-myc downstream-regulated gene 2 (NDRG2) is down-regulated in grade-III meningioma [anaplastic meningioma (AM)] and associated with clinically aggressive behavior. Current therapies in the treatment of high-grade meningioma are lacking with limited success. This study aims to validate the effect of NDRG2-targeted therapy using structurally related bioactive triterpene compounds derived from the edible mushroom Ganoderma lucidum (ganoderic acid A:GA-A/ganoderic acid DM:GA-DM) in human AM in relevant pre-clinical models. METHODS: Tissue samples from the AM tumor regions of three human patients and control non-tumor samples were used to analyze the expression pattern of NDRG2. In vitro cell culture and in vivo cell-line-derived orthotopic xenograft animal models of AM were utilized to assess efficacy of treatment with GA-A/DM. RESULTS: Downregulation of NDRG2 expression was observed in surgically resected high-grade meningiomas compared to normal brain. These results prompt us to use NDRG2-targeting agents GA-A/DM. In vitro results showed that 72-h treatments of 25 µM GA-A/DM induced AM cell death, upregulate NDRG2 protein expression, downregulate NDRG2 promoter methylation in meningioma cells as compared to azacitidine and decitabine, the most commonly used demethylating agents. Our results also demonstrated that GA-A/DM does not have any detrimental effect on normal human neurons and arachnoid cells. GA-A/DM promoted apoptotic factors (Bax) while suppressing MMP-9, p-P13K, p-AKT, p-mTOR, and Wnt-2 protein expression. RNAi-mediated knockdown of NDRG2 protein expression increased tumor proliferation, while forced expression of wt-NDRG2 decreased proliferation in an in vitro model. Magnetic resonance (MR) imaging and Hematoxylin (H&E) staining demonstrated gross reduction of tumor volume in GA-A/DM treated mice at 5 weeks when compared with saline-treated orthotopic AM xenografted controls. There was an overall decrease in tumor cell proliferation with increased survival in GA-A/DM-treated animals. Enzyme assays showed that GA-A/DM did not negatively impact hepatic function. CONCLUSION: GA-A/DM may be a promising natural therapeutic reagent in the treatment of AM by suppressing growth via NDRG2 modulation and altering of intracellular signal pathways. We have shown it could potentially be an effective treatment for AM with decreased cellular proliferation in vitro, decreased tumor volume and increased survival in vivo.


Assuntos
Ácidos Heptanoicos/farmacologia , Lanosterol/análogos & derivados , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Triterpenos/farmacologia , Proteínas Supressoras de Tumor/efeitos dos fármacos , Idoso , Anaplasia , Animais , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Azacitidina/farmacologia , Morte Celular/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Decitabina/farmacologia , Regulação para Baixo , Técnicas de Silenciamento de Genes , Humanos , Técnicas In Vitro , Lanosterol/farmacologia , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Meníngeas/patologia , Meningioma/patologia , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Gradação de Tumores , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteína Wnt2/efeitos dos fármacos , Proteína Wnt2/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
16.
Schizophr Res ; 211: 88-92, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31345706

RESUMO

The objective of the study was to examine the cognitive profile of Spanish patients with a first episode of schizophrenia (FESz) and to compare that to the profile of patients with a chronic schizophrenia (CSz) and non-psychiatric (NP) control subjects. The study included 106 FESz, 293 CSz, and 210 NP, assessed with the Spanish version of the MATRICS Consensus Cognitive Battery (MCCB). The MCCB cognitive profile in a Spanish sample of FESz was similar to the cognitive profile of CSz with some discrepancies in select domains. The scores of both patient samples were about 1-2 SD below the scores of non-psychiatric control subjects.


Assuntos
Disfunção Cognitiva/fisiopatologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Doença Aguda , Adulto , Estudos de Casos e Controles , Doença Crônica , Cognição , Disfunção Cognitiva/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha , Adulto Jovem
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 212: 246-254, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30641365

RESUMO

This work focused the implementation of FRET processes between CdTe quantum dots (QDs), acting as donors, and gold nanoparticles (AuNPs), behaving as acceptors, for the determination of several bioactive thiols such as captopril, glutathione, l-cysteine, thiomalic acid and coenzyme M. The surface chemistry of the QDs and AuNPs was adjusted with adequate capping ligands, i.e. mercaptopropionic acid and cysteamine, respectively, to guarantee the establishment of strong electrostatic interaction between them and promoting the formation of stable FRET assemblies. Under these circumstances the fluorescence emission of the QDs was completely suppressed by the AuNPs. The assayed target analytes were capable of disrupting the donor-acceptor assemblies yielding a concentration-related reversion of the FRET process and restoring QDs fluorescence emission. Distinct mechanisms, involving enhancing of the QDs quantum yield (QY), AuNPs agglomeration, nanoparticles detachment, etc., could be proposed to explain the referred FRET reversion. The developed approach assured good analytical working ranges and demonstrate adequate sensitivity for the assayed compounds, anticipating great prospective for implementing rapid, simple and reliable sensing methodologies for the monitoring of pharmaceutical, food and environmental species. However, selectivity could be a hindrance in the detection of these bioactive thiols in more complex matrices such as environmental and food samples. This problem could be circumvented through the employment of multivariate chemometric methods for the analysis and processing of whole fluorometric response. Moreover, the proposed methodology shows a great analytical versatility since it is possible to easily adapt the surface chemistry, of both QDs and AuNPs, to the chemical nature of the target analyte.


Assuntos
Compostos de Cádmio/química , Transferência Ressonante de Energia de Fluorescência/métodos , Ouro/química , Nanopartículas Metálicas/química , Pontos Quânticos/química , Compostos de Sulfidrila/análise , Telúrio/química , Ácido 3-Mercaptopropiônico/análise , Calibragem , Cisteamina/química , Modelos Lineares , Tamanho da Partícula
18.
Pediatr Obes ; 14(3): e12479, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30515969

RESUMO

BACKGROUND: While the genetic contribution to obesity is well established, few studies have examined how genetic variants influence standardized body mass index Z-score (BMIz) in Hispanics/Latinos, especially across childhood and adolescence. OBJECTIVES: We estimated the effect of established BMIz loci in Chilean children of the Santiago Longitudinal Study (SLS). METHODS: We examined associations with BMIz at age 10 for 15 loci previously identified in European children. For significant loci, we performed association analyses at ages 5 and 16 years, for which we have smaller sample sizes. We tested associations of unweighted genetic risk scores (GRSs) for previously identified tag variants (GRS_EUR) and from the most significant variants in SLS at each locus (GRS_SLS). RESULTS: We generalized five variants at age 10 (P < 0.05 and directionally consistent), including rs543874 that reached Bonferroni-corrected significance. The effect on BMIz was greatest at age 10 for all significant loci, except FTO, which exhibited an increase in effect from ages 5 to 16. Both GRSs were associated with BMIz (P < 0.0001), but GRS_SLS explained a much greater proportion of the variation (13.63%). CONCLUSION: Our results underscore the importance of conducting genetic investigations across life stages and selecting ancestry appropriate tag variants in future studies for disease prediction and clinical evaluation.


Assuntos
Índice de Massa Corporal , Obesidade Pediátrica/genética , Adolescente , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Chile , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Estudos Longitudinais , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco
19.
J Nutr Health Aging ; 22(1): 138-144, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29300433

RESUMO

BACKGROUND/OBJECTIVE: There is little epidemiological evidence demonstrating that dynapenic abdominal obesity has higher mortality risk than dynapenia and abdominal obesity alone. Our main aim was to investigate whether dynapenia combined with abdominal obesity increases mortality risk among English and Brazilian older adults over ten-year follow-up. DESIGN: Cohort study. SETTING: United Kingdom and Brazil. PARTICIPANTS: Data came from 4,683 individuals from the English Longitudinal Study of Ageing (ELSA) and 1,490 from the Brazilian Health, Well-being and Aging study (SABE), hence the final sample of this study was 6,173 older adults. MEASUREMENTS: The study population was categorized into the following groups: non-dynapenic/non-abdominal obese, abdominal obese, dynapenic, and dynapenic abdominal obese according to their handgrip strength (< 26 kg for men and < 16 kg for women) and waist circumference (> 102 cm for men and > 88 cm for women). The outcome was all-cause mortality over a ten-year follow-up. Adjusted hazard ratios by sociodemographic, behavioural and clinical characteristics were estimated using Cox proportional hazards models. RESULTS: The fully adjusted model showed that dynapenic abdominal obesity has a higher mortality risk among the groups. The hazard ratios (HR) were 1.37 for dynapenic abdominal obesity (95% CI = 1.12 - 1.68), 1.15 for abdominal obesity (95% CI = 0.98 - 1.35), and 1.23 for dynapenia (95% CI = 1.04 - 1.45). CONCLUSIONS: Dynapenia is an important risk factor for mortality but dynapenic abdominal obesity has the highest mortality risk among English and Brazilian older adults.


Assuntos
Obesidade Abdominal/complicações , Circunferência da Cintura/fisiologia , Idoso , Envelhecimento , Brasil , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Obesidade Abdominal/mortalidade , Obesidade Abdominal/patologia , Fatores de Risco , Análise de Sobrevida , Reino Unido
20.
Braz J Med Biol Res ; 50(12): e6211, 2017 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-29069223

RESUMO

Recent evidence suggests that cell-derived circulating miRNAs may serve as biomarkers of cardiovascular diseases. However, a few studies have investigated the potential of circulating miRNAs as biomarkers for left ventricular hypertrophy (LVH). In this study, we aimed to characterize the miRNA profiles that could distinguish hypertensive patients with LHV, hypertensive patients without LVH and control subjects, and identify potential miRNAs as biomarkers of LVH. LVH was defined by left ventricular mass indexed to body surface area >125 g/m2 in men and >110 g/m2 in women and patients were classified as hypertensive when presenting a systolic blood pressure of 140 mmHg or more, or a diastolic blood pressure of 90 mmHg or more. We employed miRNA PCR array to screen serum miRNAs profiles of patients with LVH, essential hypertension and healthy subjects. We identified 75 differentially expressed miRNAs, including 49 upregulated miRNAs and 26 downregulated miRNAs between LVH and control patients. We chose 2 miRNAs with significant differences for further testing in 59 patients. RT-PCR analysis of serum samples confirmed that miR-7-5p and miR-26b-5p were upregulated in the serum of LVH hypertensive patients compared with healthy subjects. Our findings suggest that these miRNAs may play a role in the pathogenesis of hypertensive LVH and may represent novel biomarkers for this disease.


Assuntos
Perfilação da Expressão Gênica/métodos , Hipertensão/sangue , Hipertrofia Ventricular Esquerda/sangue , MicroRNAs/sangue , Adulto , Idoso , Análise de Variância , Biomarcadores/sangue , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Humanos , Hipertensão/genética , Hipertrofia Ventricular Esquerda/genética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Padrões de Referência , Valores de Referência , Fatores de Risco , Regulação para Cima
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