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1.
Gut Microbes ; 16(1): 2342497, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635321

RESUMO

Despite the potential protective role of the gut microbiome against COVID-19, specific microbes conferring resistance to COVID-19 have not yet been identified. In this work, we aimed to identify and validate gut microbes at the species level that provide protection against SARS-CoV-2 infection. To identify gut microbes conferring protection against COVID-19, we conducted a fecal microbiota transplantation (FMT) from an individual with no history of COVID-19 infection or immunization into a lethal COVID-19 hamster model. FMT from this COVID-19-resistant donor resulted in significant phenotypic changes related to COVID-19 sensitivity in the hamsters. Metagenomic analysis revealed distinct differences in the gut microbiome composition among the hamster groups, leading to the identification of two previously unknown bacterial species: Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, both associated with COVID-19 resistance. Subsequently, we conducted a proof-of-concept confirmation animal experiment adhering to Koch's postulates. Oral administration of this gut microbe pair, Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, to the hamsters provided complete protection against SARS-CoV-2 infection through the activation of CD8+ T cell mediated immunity. The prophylactic efficacy of the gut microbe pair against SARS-CoV-2 infection was comparable to, or even superior to, current mRNA vaccines. This strong prophylactic efficacy suggests that the gut microbe pair could be developed as a host-directed universal vaccine for all betacoronaviruses, including potential future emerging viruses.


Assuntos
COVID-19 , Microbioma Gastrointestinal , Animais , Cricetinae , Ruminococcus , SARS-CoV-2 , Clostridiales , Linfócitos T CD8-Positivos , Imunidade Celular
2.
Acta Radiol Open ; 10(2): 2058460120988097, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33786201

RESUMO

BACKGROUND: The pathology of Parkinson's disease leads to morphological changes in brain structure. Currently, the progressive changes in gray matter volume that occur with time and are specific to patients with Parkinson's disease, compared to healthy controls, remain unclear. High-tesla magnetic resonance imaging might be useful in differentiating neurological disorders by brain cortical changes. PURPOSE: We aimed to investigate patterns in gray matter changes in patients with Parkinson's disease by using an automated segmentation method with 7-tesla magnetic resonance imaging. MATERIAL AND METHODS: High-resolution T1-weighted 7 tesla magnetic resonance imaging volumes of 24 hemispheres were acquired from 12 Parkinson's disease patients and 12 age- and sex-matched healthy controls with median ages of 64.5 (range, 41-82) years and 60.5 (range, 25-74) years, respectively. Subgroup analysis was performed according to whether axial motor symptoms were present in the Parkinson's disease patients. Cortical volume, cortical thickness, and subcortical volume were measured using a high-resolution image processing technique based on the Desikan-Killiany-Tourville atlas and an automated segmentation method (FreeSurfer version 6.0). RESULTS: After cortical reconstruction, in 7 tesla magnetic resonance imaging volume segmental analysis, compared with the healthy controls, the Parkinson's disease patients showed global cortical atrophy, mostly in the prefrontal area (rostral middle frontal, superior frontal, inferior parietal lobule, medial orbitofrontal, rostral anterior cingulate area), and subcortical volume atrophy in limbic/paralimbic areas (fusiform, hippocampus, amygdala). CONCLUSION: We first demonstrated that 7 tesla magnetic resonance imaging detects structural abnormalities in Parkinson's disease patients compared to healthy controls using an automated segmentation method. Compared with the healthy controls, the Parkinson's disease patients showed global prefrontal cortical atrophy and hippocampal area atrophy.

3.
J Cereb Blood Flow Metab ; 39(9): 1864-1877, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-29673284

RESUMO

Myeloperoxidase (MPO) is a pro-inflammatory enzyme abundantly secreted by activated myeloid cells after stroke. We show that when MPO activity is either blocked by the specific inhibitor 4-aminobenzoic acid hydrazide (ABAH) in wildtype (WT) mice or congenitally absent (MPO-/-), there was decreased cell loss, including degenerating neurons and oligodendrocytes, in the ischemic brains compared to vehicle-treated WT mice after stroke. MPO inhibition also reduced the number of activated myeloid cells after ischemia. MPO inhibition increased cytoprotective heat shock protein 70 (Hsp70) by 70% and p-Akt by 60%, while decreased the apoptotic marker p53 level by 62%, compared to vehicle-treated mice after ischemia. Similarly, MPO inhibition increased the number of Hsp70+/NeuN+ cells after stroke by 60%. Notably, MPO inhibition significantly improved neurological outcome compared with the vehicle-treated group after stroke. We further found longer treatment periods resulted in larger reduction of infarct size and greater neurobehavioral improvement from MPO inhibition, even when given days after stroke. Therefore, MPO inhibition with ABAH or MPO deficiency creates a protective environment that decreased inflammatory cell recruitment and increased expression of survival factors to improve functional outcome. MPO inhibition may represent a promising therapeutic target for stroke therapy, possibly even days after stroke has occurred.


Assuntos
Compostos de Anilina/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Inibidores Enzimáticos/uso terapêutico , Peroxidase/metabolismo , Animais , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Deleção de Genes , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuroproteção/efeitos dos fármacos , Peroxidase/antagonistas & inibidores , Peroxidase/genética
4.
Nutrients ; 8(10)2016 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-27754404

RESUMO

Obesity is exponentially increasing regardless of its preventable characteristics. The current measures for preventing obesity have failed to address the severity and prevalence of obesity, so alternative approaches based on nutritional and diet changes are attracting attention for the treatment of obesity. Fruit contains large amounts of simple sugars (glucose, fructose, sucrose, etc.), which are well known to induce obesity. Thus, considering the amount of simple sugars found in fruit, it is reasonable to expect that their consumption should contribute to obesity rather than weight reduction. However, epidemiological research has consistently shown that most types of fruit have anti-obesity effects. Thus, due to their anti-obesity effects as well as their vitamin and mineral contents, health organizations are suggesting the consumption of fruit for weight reduction purposes. These contradictory characteristics of fruit with respect to human body weight management motivated us to study previous research to understand the contribution of different types of fruit to weight management. In this review article, we analyze and discuss the relationships between fruit and their anti-obesity effects based on numerous possible underlying mechanisms, and we conclude that each type of fruit has different effects on body weight.


Assuntos
Peso Corporal , Dieta , Comportamento Alimentar , Frutas , Obesidade/prevenção & controle , Carboidratos da Dieta , Frutose , Frutas/química , Humanos , Micronutrientes
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