RESUMO
Alzheimer's disease (AD) is a brain illness that affects learning and memory capacities over time. In recent investigations, acupuncture has been shown to be an effective alternative treatment for AD. We investigated the effect of acupuncture on learning and memory abilities using a water maze in APP/PS1 transgenic mice. The amounts of Aß and tau protein in mice's hippocampal tissue were determined using Western blot. The levels of IL-1ß, IL-10, LPS and TNF-α in mice's serum were measured using ELISA. The variations of gut microbiota in mice's feces were determined using the 16SrDNA technique, and the metabolites were examined using a untargeted metabolomics methodology. The results showed that acupuncture treatment improved mice's learning and memory abilities substantially. Acupuncture therapy regulated the Aß and tau protein concentration as well as the levels of IL-10 and LPS. Acupuncture treatment influenced the mouse microbiota and metabolites and had been linked to six biochemical pathways. This study adds to our understanding of the effect of acupuncture on AD and opens the door to further research into the alterations of intestinal bacteria in the presence of AD.
Assuntos
Terapia por Acupuntura , Doença de Alzheimer , Microbioma Gastrointestinal , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/farmacologia , Animais , Modelos Animais de Doenças , Microbioma Gastrointestinal/fisiologia , Humanos , Interleucina-10/farmacologia , Lipopolissacarídeos , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , Proteínas tau/genéticaRESUMO
Adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1) deficiency, an ultrarare autosomal recessive liver disease, includes severe and mild clinical forms, referred to as progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis type 1 (BRIC1), respectively. There is currently no practical method for determining PFIC1 or BRIC1 at an early disease course phase. Herein, we assessed the feasibility of developing a diagnostic method for PFIC1 and BRIC1. A nationwide Japanese survey conducted since 2015 identified 25 patients with cholestasis with ATP8B1 mutations, 15 of whom agreed to participate in the study. Patients were divided for analysis into PFIC1 (n = 10) or BRIC1 (n = 5) based on their disease course. An in vitro mutagenesis assay to evaluate pathogenicity of ATP8B1 mutations suggested that residual ATP8B1 function in the patients could be used to identify clinical course. To assess their ATP8B1 function more simply, human peripheral blood monocyte-derived macrophages (HMDMs) were prepared from each patient and elicited into a subset of alternatively activated macrophages (M2c) by interleukin-10 (IL-10). This was based on our previous finding that ATP8B1 contributes to polarization of HMDMs into M2c. Flow cytometric analysis showed that expression of M2c-related surface markers cluster of differentiation (CD)14 and CD163 were 2.3-fold and 2.1-fold lower (95% confidence interval, 2.0-2.5 for CD14 and 1.7-2.4 for CD163), respectively, in patients with IL-10-treated HMDMs from PFIC1 compared with BRIC1. Conclusion: CD14 and CD163 expression levels in IL-10-treated HMDMs may facilitate diagnosis of PFIC1 or BRIC1 in patients with ATP8B1 deficiency.
Assuntos
Adenosina Trifosfatases/deficiência , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Colestase/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Receptores de Superfície Celular/metabolismo , Adenosina Trifosfatases/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Colestase/diagnóstico , Colestase/patologia , Feminino , Humanos , Interleucina-10/farmacologia , Fígado/metabolismo , Fígado/patologia , Macrófagos/patologia , Masculino , Mutagênese/genética , Mutação , Adulto JovemRESUMO
Allergic and other immune-mediated diseases are complex disease states determined by interplay between host genetics and environmental factors. Environmental changes such as fewer infections and reduced exposure to microbial products have been suggested to have led to insufficient regulation of Th1 and Th2 immune responses, causing an increased incidence of inflammatory diseases. The objective of the present study was to investigate the effect of poor living environmental conditions on mitogen-induced production of cytokines (Th1 and Th2) by peripheral blood leukocytes in children living in urban Brazil and investigate the role of IL-10 in modifying this effect. Our data showed that the proportion of children producing Th1 and Th2 cytokines was lower among those with poor living conditions and that this finding was stronger in children producing IL-10. These results provide a possible biologic explanation for the temporal trends of increasing risk of inflammatory diseases observed in populations living in affluent countries.