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1.
Nutrients ; 15(21)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37960295

RESUMEN

The new coronavirus infection represents a serious threat to global health and economies. In this sense, it is paramount to know the nutritional factors that may be related to the prognosis of the disease. Evidence shows that vitamin A may play an important preventive and therapeutic role in supporting respiratory infections as in COVID-19. The aim of our study was to evaluate the association of vitamin A (retinol) status with the prognosis of the disease. A case-control study from a cohort study was conducted in Brazil between May and October 2020. The study population was chosen by convenience, consisting of participants diagnosed with COVID-19. Recruitment was carried out using different approaches, including through dissemination on social media and in four hospitals in the city of Natal/RN, Brazil, recruiting participants from the COVID-19 ward and hospitalized participants who tested positive for the disease. The participants were allocated into two groups according to severity, with a group of mild (n = 88) or critical (n = 106) patients and compared to a control group (selected before the pandemic, n = 46). The extraction of retinol serum was performed and analyzed using the high-performance liquid chromatography method (HPLC). The retinol level was calculated in mmol/L, and levels below 0.7 µmol/L (20 µg/dL) were considered to be a vitamin A deficiency. Our findings suggest that the participants with mild and critical COVID-19 had lower retinol levels compared to the healthy controls (p = 0.03). In addition, milder cases of COVID-19 were associated with increased symptoms and prolonged symptoms after 90 days since the beginning of infection. However, the survival analysis showed no association with higher cases of death among participants with vitamin A deficiency (p = 0.509). More studies are needed to understand how nutritional status, including vitamin A levels, can influence prognosis and is a risk factor for the development of long COVID syndrome.


Asunto(s)
COVID-19 , Deficiencia de Vitamina A , Humanos , Vitamina A , COVID-19/epidemiología , Deficiencia de Vitamina A/complicaciones , Deficiencia de Vitamina A/epidemiología , Estudios de Casos y Controles , Estudios de Cohortes , Síndrome Post Agudo de COVID-19
2.
Sci Rep ; 13(1): 13973, 2023 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-37633999

RESUMEN

Until January 2023, Brazil recorded 37 million COVID-19 cases despite the decrease in mortality due to mass vaccination efforts against COVID-19. The infection continues to challenge researchers and health professionals with the persistent symptoms and onset manifestations after the acute phase of the disease, namely Post-Covid Condition (PCC). Being one of the countries with the highest infection rate, Brazil must prepare for a growing number of patients with chronic health consequences of COVID-19. Longitudinal studies that follow patients over extended periods are crucial in understanding the long-term impacts of COVID-19, including potential health consequences and the effects on quality of life. We describe the clinical profile of a cohort of COVID-19 patients infected during the first year of the pandemic in Brazil and a follow-up after two years to investigate the health impacts of SARS-CoV-2 infection. The first wave of SARS-CoV-2 infection in Brazil featured extensive drug misuse, notably the ineffective COVID kit comprised of ivermectin, antimalarials and azithromycin, and elevated in-hospital mortality. In the second phase of the study, Post-Covid Condition was reported by symptomatic COVID-19 subjects across different severity levels two years after infection. Long haulers are more likely to be women, previously hospitalized, and reported a range of symptoms from muscle pain to cognitive deficit. Our longitudinal study is essential to inform public health authorities to develop strategies and policies to control the spread of the virus and mitigate its impacts on society.


Asunto(s)
COVID-19 , Síndrome Post Agudo de COVID-19 , Humanos , Femenino , Masculino , COVID-19/epidemiología , Brasil/epidemiología , Estudios de Seguimiento , Estudios Longitudinales , Calidad de Vida , SARS-CoV-2
3.
PLoS One ; 18(5): e0284497, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37167233

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the effectiveness of hand debridement (HD) versus ultrasonic dental scaler (UDS) for the treatment of experimental periodontitis (EP) in rats. MATERIAL AND METHODS: Thirty 3-month-old male rats were used. EP was induced around the mandibular first molars (right and left). Seven days after induction, the treatments with either HD (n = 30) or UDS (n = 30) were randomly performed in each molar. Euthanasia were performed at 7, 15, and 30 days after treatment. Histometric (percentage of bone in the furcation [PBF]), histopathological, and immunohistochemical (for detection of tartrate-resistant acid phosphatase [TRAP] and osteocalcin [OCN]). Parametric data (PBF and TRAP) was analyzed by One-way ANOVA followed by Tukey's post-test. OCN was analyzed by Kruskal-Wallis followed by Student-Newman-Keuls post-test. The level of significance was 5%. RESULTS: Group HD presented higher PBF and lower TRAP-immunolabeling at 30 days as compared with UDS in the same period (p≤0.05). Group HD presented higher OCN immunolabeling at 30 days as compared with 7 and 15 days (p≤0.05). Persistent and exacerbated inflammatory process was observed in some specimens from group UDS at 30 days, as well as the bone trabeculae presented irregular contour, surrounded by many active osteoclasts. CONCLUSION: Nonsurgical periodontal therapy with HD resulted in higher PBF and lower expression of TRAP as compared with UDS. Also, HD increased the expression of OCN over time.


Asunto(s)
Pérdida de Hueso Alveolar , Periodontitis , Ratas , Masculino , Animales , Ratas Wistar , Pérdida de Hueso Alveolar/patología , Ultrasonido , Periodontitis/patología , Proyectos de Investigación
5.
Am J Cancer Res ; 13(3): 976-991, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37034206

RESUMEN

Lung cancer is the leading cause of cancer-related deaths. Lung cancer cells develop resistance to apoptosis by suppressing the secretion of the tumor suppressor Par-4 protein (also known as PAWR) and/or down-modulating the Par-4 receptor GRP78 on the cell surface (csGRP78). We sought to identify FDA-approved drugs that elevate csGRP78 on the surface of lung cancer cells and induce Par-4 secretion from the cancer cells and/or normal cells in order to inhibit cancer growth in an autocrine or paracrine manner. In an unbiased screen, we identified crizotinib (CZT), an inhibitor of activated ALK/MET/ROS1 receptor tyrosine kinase, as an inducer of csGRP78 expression in ALK-negative, KRAS or EGFR mutant lung cancer cells. Elevation of csGRP78 in the lung cancer cells was dependent on activation of the non-receptor tyrosine kinase SRC by CZT. Inhibition of SRC activation in the cancer cells prevented csGRP78 translocation but promoted Par-4 secretion by CZT, implying that activated SRC prevented Par-4 secretion. In normal cells, CZT did not activate SRC and csGRP78 elevation but induced Par-4 secretion. Consequently, CZT induced Par-4 secretion from normal cells and elevated csGRP78 in the ALK-negative tumor cells to cause paracrine apoptosis in cancer cell cultures and growth inhibition of tumor xenografts in mice. Thus, CZT induces differential activation of SRC in normal and cancer cells to trigger the pro-apoptotic Par-4-GRP78 axis. As csGRP78 is a targetable receptor, CZT can be repurposed to elevate csGRP78 for inhibition of ALK-negative lung tumors.

6.
Microbiome ; 11(1): 90, 2023 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-37101209

RESUMEN

BACKGROUND: The continuous proliferation of intestinal stem cells followed by their tightly regulated differentiation to epithelial cells is essential for the maintenance of the gut epithelial barrier and its functions. How these processes are tuned by diet and gut microbiome is an important, but poorly understood question. Dietary soluble fibers, such as inulin, are known for their ability to impact the gut bacterial community and gut epithelium, and their consumption has been usually associated with health improvement in mice and humans. In this study, we tested the hypothesis that inulin consumption modifies the composition of colonic bacteria and this impacts intestinal stem cells functions, thus affecting the epithelial structure. METHODS: Mice were fed with a diet containing 5% of the insoluble fiber cellulose or the same diet enriched with an additional 10% of inulin. Using a combination of histochemistry, host cell transcriptomics, 16S microbiome analysis, germ-free, gnotobiotic, and genetically modified mouse models, we analyzed the impact of inulin intake on the colonic epithelium, intestinal bacteria, and the local immune compartment. RESULTS: We show that the consumption of inulin diet alters the colon epithelium by increasing the proliferation of intestinal stem cells, leading to deeper crypts and longer colons. This effect was dependent on the inulin-altered gut microbiota, as no modulations were observed in animals deprived of microbiota, nor in mice fed cellulose-enriched diets. We also describe the pivotal role of γδ T lymphocytes and IL-22 in this microenvironment, as the inulin diet failed to induce epithelium remodeling in mice lacking this T cell population or cytokine, highlighting their importance in the diet-microbiota-epithelium-immune system crosstalk. CONCLUSION: This study indicates that the intake of inulin affects the activity of intestinal stem cells and drives a homeostatic remodeling of the colon epithelium, an effect that requires the gut microbiota, γδ T cells, and the presence of IL-22. Our study indicates complex cross kingdom and cross cell type interactions involved in the adaptation of the colon epithelium to the luminal environment in steady state. Video Abstract.


Asunto(s)
Microbioma Gastrointestinal , Inulina , Humanos , Animales , Ratones , Inulina/farmacología , Dieta , Fibras de la Dieta , Celulosa , Epitelio , Comunicación Celular
7.
Nutr. hosp ; 40(2): 419-427, mar.-abr. 2023. ilus, tab, graf
Artículo en Inglés | IBECS | ID: ibc-219341

RESUMEN

Introduction: changes in dietary/energetic composition during the critical period of development (pregnancy/lactation) or even during meal times may contribute to changes in metabolic and behavioral parameters such as feeding behavior. Objective: the study aimed to examine the repercussions of time-restricted feeding on feeding behavior and on some parameters of glycemic and lipemic metabolism of the offspring of adult rats whose mothers were fed a westernized diet during pregnancy and lactation. Methods: initially, 43 male Wistar rats were used. At 60 days of life, the rats were divided into 4 groups: C: control group; RC: control group with time-restricted feeding; W: westernized diet during pregnancy/lactation group; RW: westernized diet group during pregnancy/lactation group with time-restricted feeding. The following parameters were evaluated: behavioral sequence of satiety (BSS), biochemical parameters, and abdominal fat. Results: findings highlighted a high level of abdominal fat in the groups whose mothers were submitted to a westernized diet, as well as hypertriglyceridemia, and clear differences in feed rate and meal length. This study showed that the westernized diet ingested by mothers during pregnancy and lactation induced hyperlipidemia and changes in the feeding behavior of their adult offspring. Conclusions: these changes may be responsible for eating disorders and risk factors for metabolism disturbance-related diseases. (AU)


Introducción: los cambios en la composición dietética/energética durante el período crítico de desarrollo (embarazo/lactancia) o incluso durante las comidas pueden contribuir a cambios en los parámetros metabólicos y conductuales como el comportamiento alimentario. Objetivo: el estudio tuvo como objetivo examinar las repercusiones de la alimentación restringida en el tiempo sobre el comportamiento alimentario y sobre algunos parámetros del metabolismo glucémico y lipémico de crías de ratas adultas cuyas madres fueron alimentadas con una dieta occidentalizada durante el embarazo y la lactancia. Métodos: inicialmente se utilizaron 43 ratas Wistar macho. A los 60 días de vida, las ratas se agruparon en 4 grupos: C: grupo de control; RC: grupo de control con alimentación restringida en el tiempo; W: grupo de dieta occidentalizada durante el embarazo/lactancia; RW: grupo de dieta occidentalizada durante el embarazo y la lactancia con alimentación restringida en el tiempo. Se evaluaron los siguientes parámetros: secuencia conductual de saciedad (BSS), parámetros bioquímicos y grasa abdominal. Resultados: destacó una grasa abdominal elevada en los grupos cuyas madres fueron sometidas a una dieta occidentalizada, así como hipertrigliceridemia y una diferencia evidente en la tasa de alimentación y la duración de la comida. Este estudio demostró que la dieta occidentalizada ingerida por las madres durante el embarazo y la lactancia induce hiperlipidemia y cambios en el comportamiento alimentario de las crías adultas. Conclusiones: estos cambios pueden ser responsables de trastornos alimentarios y factores de riesgo de enfermedades relacionadas con alteraciones del metabolismo. (AU)


Asunto(s)
Animales , Ratas , Fenómenos Fisiologicos Nutricionales Maternos , Efectos Tardíos de la Exposición Prenatal , Conducta Alimentaria , Ratas Wistar , Dieta Alta en Grasa , Dieta Occidental , Lactancia , Privación de Alimentos
8.
Nutr Hosp ; 40(2): 419-427, 2023 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-36880723

RESUMEN

Introduction: Introduction: changes in dietary/energetic composition during the critical period of development (pregnancy/lactation) or even during meal times may contribute to changes in metabolic and behavioral parameters such as feeding behavior. Objective: the study aimed to examine the repercussions of time-restricted feeding on feeding behavior and on some parameters of glycemic and lipemic metabolism of the offspring of adult rats whose mothers were fed a westernized diet during pregnancy and lactation. Methods: initially, 43 male Wistar rats were used. At 60 days of life, the rats were divided into 4 groups: C: control group; RC: control group with time-restricted feeding; W: westernized diet during pregnancy/lactation group; RW: westernized diet group during pregnancy/lactation group with time-restricted feeding. The following parameters were evaluated: behavioral sequence of satiety (BSS), biochemical parameters, and abdominal fat. Results: findings highlighted a high level of abdominal fat in the groups whose mothers were submitted to a westernized diet, as well as hypertriglyceridemia, and clear differences in feed rate and meal length. This study showed that the westernized diet ingested by mothers during pregnancy and lactation induced hyperlipidemia and changes in the feeding behavior of their adult offspring. Conclusions: these changes may be responsible for eating disorders and risk factors for metabolism disturbance-related diseases.


Introducción: Introducción: los cambios en la composición dietética/energética durante el período crítico de desarrollo (embarazo/lactancia) o incluso durante las comidas pueden contribuir a cambios en los parámetros metabólicos y conductuales como el comportamiento alimentario. Objetivo: el estudio tuvo como objetivo examinar las repercusiones de la alimentación restringida en el tiempo sobre el comportamiento alimentario y sobre algunos parámetros del metabolismo glucémico y lipémico de crías de ratas adultas cuyas madres fueron alimentadas con una dieta occidentalizada durante el embarazo y la lactancia. Métodos: inicialmente se utilizaron 43 ratas Wistar macho. A los 60 días de vida, las ratas se agruparon en 4 grupos: C: grupo de control; RC: grupo de control con alimentación restringida en el tiempo; W: grupo de dieta occidentalizada durante el embarazo/lactancia; RW: grupo de dieta occidentalizada durante el embarazo y la lactancia con alimentación restringida en el tiempo. Se evaluaron los siguientes parámetros: secuencia conductual de saciedad (BSS), parámetros bioquímicos y grasa abdominal. Resultados: destacó una grasa abdominal elevada en los grupos cuyas madres fueron sometidas a una dieta occidentalizada, así como hipertrigliceridemia y una diferencia evidente en la tasa de alimentación y la duración de la comida. Este estudio demostró que la dieta occidentalizada ingerida por las madres durante el embarazo y la lactancia induce hiperlipidemia y cambios en el comportamiento alimentario de las crías adultas. Conclusiones: estos cambios pueden ser responsables de trastornos alimentarios y factores de riesgo de enfermedades relacionadas con alteraciones del metabolismo.


Asunto(s)
Fenómenos Fisiologicos Nutricionales Maternos , Efectos Tardíos de la Exposición Prenatal , Embarazo , Femenino , Humanos , Ratas , Masculino , Animales , Ratas Wistar , Dieta , Conducta Alimentaria , Ingestión de Alimentos , Lactancia , Dieta Alta en Grasa
9.
Revisbrato ; 6(4): 1279-1294, 20220000.
Artículo en Portugués | LILACS | ID: biblio-1417886

RESUMEN

Introdução: O resgate da forma de pensamento e método críticos da Terapia Ocupacional, conhecida como Corrente Materialista Histórica da Terapia Ocupacional (CMHTO), advinda no Brasil nos idos de 1980, faz-se necessário ao debate franco que pretendemos contribuir sobre a perspectiva crítica da Terapia Ocupacional. Métodos: Estudo teórico sobre as obras nacionais centrais da discussão materialista histórica e dialética na Terapia Ocupacional. Objetivo: Apresentar as categorias fundamentais da CMHTO e parte da sua teorização no debate epistemológico da Terapia Ocupacional no Brasil. Resultados: O escopo epistemológico da Terapia Ocupacional, a finalidade e forma de intervenção profissional foram os objetos centrais do debate crítico da CMHTO a partir das obras de Karl Marx e Friedrich Engels sob as categorias trabalho, produção capitalista, mercadoria, alienação, hegemonia, ideologia, consciência de classe, práxis e luta de classes. A crise do papel profissional manifestou as contradições da profissão diante da incapacidade de responder às necessidades sociais e de saúde da classe trabalhadora. O método materialista histórico e dialético teorizado pela CMHTO, ainda que primário, aponta para a superação da abstração sobre a ocupação humana e o caráter funcionalista das práticas terapêuticas ocupacionais que sustentam a reprodução à ordem do capital. Conclusão: O debate crítico epistemológico da Terapia Ocupacional continua em aberto. A reconstrução da CMHTO responde ao chamado da nossa base profissional combativa à forma atual do capitalismo sob as novas e conhecidas questões e necessidades da classe trabalhadora.


Introduction: The updating of the Occupational Therapy's critical thinking and method, known as the Historical Materialism Current of Occupational Therapy (CMHTO), arising in Brazil in the 1980s, is necessary for the open debate that we intend to contribute to the critical perspective of Occupational Therapy. Methods: Theoretical study about historical and dialectical materialist discussion in brazilian Occupational Therapy. Objective: To present the fundamental categories of the CMHTO and part of its theorization in the epistemological debate of Occupational Therapy in Brazil. Results: The epistemological scope of Occupational Therapy, and the purpose and form of professional intervention were the central objects of the CMHTO debate from Karl Marx and Friedrich Engels under the categories work, capitalist production, commodity, alienation, hegemony, ideology, class consciousness, praxis and class struggle. The professional role crisis manifested the contradictions of the profession in the face of its inability to respond to the social Palavras-chave: Ensino Online. Terapia Ocupacional. Aprendizagem. COVID-19. and health needs of the working class. The historical and dialectical materialist method theorized by the CMHTO, although primary, point to the overcoming the abstraction about human occupation and the functionalist character of occupational therapy practices that sustain the reproduction to the capital. Conclusion: The critical epistemological debate in Occupational Therapy remains open. The reconstruction of brazilian CMHTO answers the call of our combative professional base to the current form of capitalism under the new and known social and health issues of the working class.


Introdución: El rescate de las formas críticas de pensamiento y método de la Terapia Ocupacional, conocida como la Corriente Materialista e Histórica de la Terapia Ocupacional (CMHTO) brasileña en la década de 1980, es necesaria para el debate franco que pretendemos contribuir a la perspectiva crítica de la Terapia Ocupacional. Objetivos: Presentar las categorías fundamentales del CMHTO y parte de su teorización en el debate epistemológico de la Terapia Ocupacional brasileña Método: Estudio teórico sobre las obras centrales de la discusión materialista histórica y dialéctica en Terapia Ocupacional. Resultados: El alcance epistemológico de la Terapia Ocupacional así como la finalidad y la forma de la intervención profesional fueron los objetos centrales del debate de la CMHTO a partir de Karl Marx y Friedrich Engels bajo las categorías trabajo, producción capitalista, mercancía, alienación, hegemonía, ideología, conciencia de clase, praxis y lucha de clases. La crisis del papel profesional puso de manifiesto las contradicciones de la profesión ante su incapacidad de respuesta social y sanitaria para la clase trabajadora. El método materialista histórico y dialéctico teorizado por el CMHTO, aunque primario, apunta superar la abstracción sobre la ocupación humana y el carácter funcionalista de las prácticas profesionales que sustentan la reproducción de la orden del capital. Conclusión: El debate epistemológico crítico de la Terapia Ocupacional sigue abierto. La reconstrucción de la CMHTO brasileña responde al llamado de nuestra base profesional combativa a la forma actual del capitalismo bajo las nuevas y conocidas cuestiones sociales y de salud de la clase trabajadora.


Asunto(s)
Terapia Ocupacional
10.
Mol Psychiatry ; 27(11): 4800-4808, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36071110

RESUMEN

Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE ε4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings, including the association between APOE ε4 risk and Alzheimer's disease (AD) pathology, the most frequent cause of dementia. We investigated the interaction between African ancestry, AD-related neuropathology, APOE genotype, and functional cognition in a postmortem sample of 400 individuals with a range of AD pathology severity and lack of comorbid neuropathology from a cohort of community-dwelling, admixed Brazilians. Increasing proportions of African ancestry (AFR) correlated with a lower burden of neuritic plaques (NP). However, for individuals with a severe burden of NP and neurofibrillary tangles (NFT), AFR proportion was associated with worse Clinical Dementia Rating sum of boxes (CDR-SOB). Among APOE ε4 carriers, the association between AFR proportion and CDR-SOB disappeared. APOE local ancestry inference of a subset of 309 individuals revealed that, in APOE ε4 noncarriers, non-European APOE background correlated with lower NP burden and, also, worse cognitive outcomes than European APOE when adjusting by NP burden. Finally, APOE ε4 was associated with worse AD neuropathological burden only in a European APOE background. APOE genotype and its association with AD neuropathology and clinical pattern are highly influenced by ancestry, with AFR associated with lower NP burden and attenuated APOE ε4 risk compared to European ancestry.


Asunto(s)
Enfermedad de Alzheimer , Apolipoproteína E4 , Humanos , Apolipoproteína E4/genética , Enfermedad de Alzheimer/patología , Ovillos Neurofibrilares/genética , Ovillos Neurofibrilares/patología , Placa Amiloide/genética , Placa Amiloide/patología , Genotipo , Factores Biológicos , Cognición
11.
Front Oncol ; 12: 860446, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35425699

RESUMEN

Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4-/- and AKO mice exhibit increased absorption and storage of fat in adipocytes. Mechanistically, Par-4 loss is associated with mdm2 downregulation and activation of p53. We identified complement factor c3 as a p53-regulated gene linked to fat storage in adipocytes. Par-4 re-expression in adipocytes or c3 deletion reversed the obese mouse phenotype. Moreover, obese human subjects showed lower expression of Par-4 relative to lean subjects, and in longitudinal studies, low baseline Par-4 levels denoted an increased risk of developing obesity later in life. These findings indicate that Par-4 suppresses p53 and its target c3 to regulate obesity.

12.
Trends Biochem Sci ; 47(9): 732-735, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35418348

RESUMEN

Alternative histone acylations integrate gene expression with cellular metabolic states. Recent measurements of cellular acyl-coenzyme A (acyl-CoA) pools highlight the potential that histone post-translational modifications (PTMs) contribute directly to the regulation of metabolite pools. A metabolite-centric view throws new light onto roles and evolution of histone PTMs.


Asunto(s)
Cromatina , Histonas , Acilcoenzima A/metabolismo , Acilación , Histonas/metabolismo , Procesamiento Proteico-Postraduccional
14.
Nat Commun ; 13(1): 1004, 2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-35246524

RESUMEN

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.


Asunto(s)
Genómica , Metagenómica , Anciano , Brasil/epidemiología , Genoma Humano/genética , Genómica/métodos , Humanos , Polimorfismo de Nucleótido Simple , Secuenciación Completa del Genoma
15.
Prep Biochem Biotechnol ; 52(4): 443-451, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34370621

RESUMEN

Chitooligosaccharides (COS) have a great potential to be used by pharmaceutical industry due to their many biological activities. The use of enzymes to produce them is very advantageous, however it still faces many challenges, such as discovering new strains capable to produce enzymes that are able to generate bioactive oligosaccharides. In the present study a purification protein protocol was performed to purify chitosanases produced by Bacillus toyonensis CCT 7899 for further chitosan hydrolysis. The produced chitooligosaccharides were characterized by mass spectroscopy (MS) and their antiedematogenic effect was investigated through carrageenan-induced paw edema model. The animals were treated previously to inflammation by intragastric route with COS at 30, 300 and 600 mg/kg. The purification protocol showed a good performance for the chitosanases purification using 0.20 M NaCl solution to elute it, with a 9.54-fold purification factor. The treatment with COS promoted a decrease of paw edema at all evaluated times and the AUC0-4h, proving that COS produced showed activity in acute inflammation like commercial anti-inflammatory Dexamethasone (corticosteroid). Therefore, the strategy used to purification was successfully applied and it was possible to generate bioactive oligosaccharides with potential pharmacological use.


Asunto(s)
Bacillus , Quitosano , Animales , Bacillus/metabolismo , Quitina/metabolismo , Quitosano/química , Edema/inducido químicamente , Edema/tratamiento farmacológico , Glicósido Hidrolasas/metabolismo , Inflamación , Oligosacáridos/metabolismo
16.
Environ Sci Pollut Res Int ; 29(1): 1199-1209, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34347241

RESUMEN

The production of personal hygiene and body products generates wastewater with a high load of surfactants, a high chemical oxygen demand (COD), and abundant oils and greases. Aluminum sulfate (AS) and two solutions of natural coagulant from Moringa oleifera Lam. seeds prepared with a 1M NaCl solution and 1.5M NaCl solution were used. Aluminum sulfate, Moringa oleifera Lam. in 1M NaCl, and Moringa oleifera Lam. in 1.5M NaCl solutions reduced turbidity at rates 94.48%, 98.07%, and 97.87%; reduced COD at rates 46.36%, 49.15%, and 42.7%; and reduced oil and grease at rates 98.72%, 78.65%, and 97.41%, respectively. Mutagenicity tests with guppies showed a lower toxicity of Moringa oleifera Lam. extract compared with aluminum sulfate. This work shows that Moringa oleifera Lam. extract has high potential for use as an alternative to aluminum sulfate; therefore, this study will contribute to proposals for the sustainable treatment of effluents from the cosmetic industry.


Asunto(s)
Compuestos de Alumbre , Moringa oleifera , Aguas Residuales/química , Purificación del Agua , Cosméticos , Extractos Vegetales , Semillas , Aguas Residuales/toxicidad
17.
Eur J Clin Nutr ; 76(3): 469-476, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34230633

RESUMEN

BACKGROUND/OBJECTIVES: Experimental and clinical studies have shown that vitamins A and E can inhibit cancer formation and progression. The unfavourable status of these vitamins can represent risk factors for the disease. This study aimed to evaluate the associations between the nutritional status of vitamins A and E (serum levels and dietary intake) and histopathological outcomes in Papillary Thyroid Carcinoma (PTC) patients. SUBJECTS/METHODS: We applied a cross-sectional study (2017-2018) and quantified retinol (ROH) and α-tocopherol (TOH) serum levels and vitamins dietary intake of 46 PTC patients. Serum vitamins were quantified by high efficiency liquid chromatography and vitamins dietary intake was analyzed by 24-hr dietary recalls. RESULTS: Patients with lower ROH serum levels were more likely to present lymph node metastasis and/or angiolymphatic invasion (p = 0.025). In addition, higher vitamin A and vitamin E intake are related to the absence of extrathyroidal extension (p = 0.013) and lymph node metastasis (p = 0.007), respectively. Our findings suggest that a ROH serum level greater than 2.65 µmol/L in PTC patients may be a protective factor against the presence of lymph node metastasis and angiolymphatic invasion. In addition, vitamin A and E intake may protect against extrathyroidal extension and lymph node metastasis. CONCLUSIONS: A favourable nutritional status (higher serum levels and/or intake) of vitamin A and E may be associated with less aggressive tumours in PTC patients.


Asunto(s)
Neoplasias de la Tiroides , Vitamina A , Estudios Transversales , Humanos , Estado Nutricional , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Vitaminas
18.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34638973

RESUMEN

The search for promising biomolecules such as chitooligosaccharides (COS) has increased due to the need for healing products that act efficiently, avoiding complications resulting from exacerbated inflammation. Therefore, this study aimed to produce COS in two stages of hydrolysis using chitosanases derived from Bacillus toyonensis. Additionally, this study aimed to structurally characterize the COS via mass spectrometry, to analyze their biocompatibility in acute toxicity models in vivo, to evaluate their healing action in a cell migration model in vitro, to analyze the anti-inflammatory activity in in vivo models of xylol-induced ear edema and zymosan-induced air pouch, and to assess the wound repair action in vivo. The structural characterization process pointed out the presence of hexamers. The in vitro and in vivo biocompatibility of COS was reaffirmed. The COS stimulated the fibroblast migration. In the in vivo inflammatory assays, COS showed an antiedematogenic response and significant reductions in leukocyte migration, cytokine release, and protein exudate. The COS healing effect in vivo was confirmed by the significant wound reduction after seven days of the experiment. These results indicated that the presence of hexamers influences the COS biological properties, which have potential uses in the pharmaceutical field due to their healing and anti-inflammatory action.


Asunto(s)
Antiinflamatorios/administración & dosificación , Materiales Biocompatibles/administración & dosificación , Quitosano/administración & dosificación , Enfermedades del Oído/tratamiento farmacológico , Edema/tratamiento farmacológico , Oligosacáridos/administración & dosificación , Cicatrización de Heridas/efectos de los fármacos , Células 3T3 , Animales , Antiinflamatorios/química , Bacillus/enzimología , Materiales Biocompatibles/química , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Citocinas/metabolismo , Modelos Animales de Enfermedad , Enfermedades del Oído/inducido químicamente , Edema/inducido químicamente , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Glicósido Hidrolasas/química , Hidrólisis , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Oligosacáridos/química
19.
Front Psychiatry ; 12: 665257, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34135785

RESUMEN

Background: Genetics influence the vulnerability to alcohol use disorders, and among the implicated genes, three previous studies have provided evidences for the involvement of LRRK2 in alcohol dependence (AD). LRRK2 expression is broadly dysregulated in postmortem brain from AD humans, as well as in the brain of mice with alcohol dependent-like behaviors and in a zebrafish model of alcohol preference. The aim of the present study was to evaluate the association of variants in the LRRK2 gene with AD in multiethnic populations from South and North America. Methods: Alcohol-screening questionnaires [such as CAGE and Alcohol Use Disorders Identification Test (AUDIT)] were used to determine individual risk of AD. Multivariate logistic regression analyses were done in three independent populations (898 individuals from Bambuí, Brazil; 3,015 individuals from Pelotas, Brazil; and 1,316 from the United States). Linkage disequilibrium and conditional analyses, as well as in silico functional analyses, were also conducted. Results: Four LRRK2 variants were significantly associated with AD in our discovery cohort (Bambuí): rs4768231, rs4767971, rs7307310, and rs1465527. Two of these variants (rs4768231 and rs4767971) were replicated in both Pelotas and US cohorts. The consistent association signal (at the LRRK2 locus) found in populations with different genetic backgrounds reinforces the relevance of our findings. Conclusion: Taken together, these results support the notion that genetic variants in the LRRK2 locus are risk factors for AD in humans.

20.
Nutr. hosp ; 38(2): 281-289, mar.-abr. 2021. tab, graf
Artículo en Inglés | IBECS | ID: ibc-201871

RESUMEN

BACKGROUND: the dietary pattern that characterizes western diet is strongly associated with metabolic diseases and excess weight, as well as chronic illnesses. Misaligned feeding schedules can lead to or aggravate the development of such conditions. AIM: this study evaluated the influence of dietary composition and/or time-restricted feeding on the anthropometric and biochemical profile of adult rats. METHODS: forty male rats, at 60 days of life, were divided into the following groups: Control (C), Restricted Control (RC), Westernized (W), and Restricted Westernized (RW). RESULTS: westernized groups, in spite of a low energy intake (C = 5399 ± 401.2 kcal; RC = 4279.0 ± 476.2 kcal; W = 4302 ± 619.8 kcal; RW = 4081.0 ± 404.4 kcal, p < 0.001), had a higher body weight (C = 404.6 ± 39.1 g; RC = 335.1 ± 36.5 g; W = 488.9 ± 51.2 g; RW = 438.8 ± 36.5 g, p < 0.001) as compared to their paired controls (RC and C) - around 30 % and 20 % more for RW and W, respectively. The westernized diet caused glucose intolerance and mixed hyperlipidemia, characterized by higher concentrations of cholesterol (C = 40.8 ± 7.4 mg/dL; RC = 76.7 ± 10.8 mg/dL; W = 61.3 ± 20.2 mg/dL; RW = 42.2 ± 8.2 mg/dL), LDLc (C = 17.4 ± 7.5 mg/dL; RC = 38.8 ± 7.2 mg/dL ; W = 45.3 ± 15.8 mg/dL; RW = 11.0 ± 5.8 mg/dL), and triacylglycerol (C = 45.2 ± 15.0 mg/dL; RC = 73.2 ± 21.5 mg/dL ; W = 83.6 ± 23.4 mg/dL; RW = 57.5 ± 13.6 mg/dL) in the serum (p < 0.05). CONCLUSION: the effect of time-restricted feeding on body weight was strongly dependent on diet composition. The glucose tolerance test showed an influence of the circadian cycle phase. Mixed hyperlipidemia varied according to the presence of westernized diet and/or time-restricted food


ANTECEDENTES: el patrón dietético que caracteriza a la dieta occidental está fuertemente asociado con las enfermedades metabólicas, así como con el sobrepeso y las enfermedades crónicas. Los horarios de alimentación desorganizados pueden conducir o agravar el desarrollo de tales trastornos. OBJETIVO: este estudio evaluó la influencia de la composición dietética y/o la alimentación restringida en el perfil antropométrico y bioquímico de ratas adultas. MÉTODOS: cuarenta ratas macho, a los 60 días de vida, se dividieron en los seguientes grupos: control (C); control restringido (RC); occidentalizado (W) y occidentalizado restringido (RW). RESULTADOS: los grupos occidentalizados, a pesar de la baja ingesta energética (C = 5399 ± 401,2 kcal; RC = 4279,0 ± 476,2 kcal; W = 4302 ± 619,8 kcal; RW = 4081,0 ± 404,4 kcal, p < 0,001), tuvieron mayor peso corporal (C = 404,6 ± 39,1 g; RC = 335,1 ± 36,5 g; W = 488,9 ± 51,2 g; RW = 438,8 ± 36,5 g, p < 0,001) que los respectivos grupos de control (RC y C): alrededor de un 30 % y un 20 % más para RW y W, respectivamente. La dieta occidentalizada provocó intolerancia a la glucosa e hiperlipidemia mixta, caracterizada por una mayor concentración de colesterol (C = 40,8 ± 7,4 mg/dL; RC = 76,7 ± 10,8 mg/dL; W = 61,3 ± 20,2 mg/dL; RW = 42,2 ± 8,2 mg/dL), cLDL (C = 17,4 ± 7,5 mg/dL; RC = 38,8 ± 7,2 mg/dL; W = 45,3 ± 15,8 mg/dL; RW = 11,0 ± 5,8 mg/dL) y triacilglicerol (C = 45,2 ± 15,0 mg/dL; RC = 73,2 ± 21,5 mg/dL; W = 83,6 ± 23,4 mg/dL; RW = 57,5 ± 13,6 mg/dL) en el suero (p < 0,05). CONCLUSIÓN: el efecto de la alimentación restringida en el tiempo sobre el peso corporal fue muy dependiente de la composición de la dieta. La prueba de tolerancia a la glucosa mostró la influencia de la fase del ciclo circadiano. La hiperlipidemia mixta varió según la presencia de la dieta occidentalizada y/o la comida con restricción de tiempo


Asunto(s)
Animales , Masculino , Ratas , Hiperlipidemias/dietoterapia , Composición de Alimentos , Composición Corporal , Ritmo Circadiano , Hiperlipidemias/veterinaria , Modelos Animales , Prueba de Tolerancia a la Glucosa/métodos , Antropometría
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