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1.
Bull Tokyo Dent Coll ; 63(1): 41-51, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35173083

RESUMO

In Japan, domiciliary care fees are only covered by the public health insurance system if the clinic concerned is located within 16 km of the patient's residence. This nationwide rule does not take local conditions into account and therefore may not be appropriate. The goal of the present study was to assess the current state of domiciliary dental care nationwide in view of this restriction to clarify the current situation and any inherent problems. Six dental institutions providing domiciliary dental care were selected by location (urban or mountainous area) and size. Travel time from clinics to the 16 km points and the longest time required for the journey from clinics were investigated. Two of the dental clinics were located in depopulated areas with few dental institutions. These clinics had to provide domiciliary dental care not only in the 16-km area around the clinic, but also in areas over 16 km away. Travel time to the 16-km points was between 52 and 90 min. On the other hand, the longest time for actual visiting was between 30 and 60 min. In some areas, no domiciliary dental care was available within the 16 km limit. This indicates that the 16-km area is too wide to be covered by one dental institution alone and that it poses a problem in areas with few dental institutions. This suggests that it would be preferable to consider time required to visit rather than geographical distance in forming policy. The 16-km limit often spans multiple residential areas, indicating that greater coordination is needed between the Community-based Integrated Care System and dental offices.


Assuntos
Assistência Odontológica para Idosos , Serviços de Assistência Domiciliar , Idoso , Assistência Odontológica , Humanos , Japão , Inquéritos e Questionários
2.
Mucosal Immunol ; 15(2): 289-300, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35013573

RESUMO

Dietary ω3 fatty acids have important health benefits and exert their potent bioactivity through conversion to lipid mediators. Here, we demonstrate that microbiota play an essential role in the body's use of dietary lipids for the control of inflammatory diseases. We found that amounts of 10-hydroxy-cis-12-cis-15-octadecadienoic acid (αHYA) and 10-oxo-cis-12-cis-15-octadecadienoic acid (αKetoA) increased in the feces and serum of specific-pathogen-free, but not germ-free, mice when they were maintained on a linseed oil diet, which is high in α-linolenic acid. Intake of αKetoA, but not αHYA, exerted anti-inflammatory properties through a peroxisome proliferator-activated receptor (PPAR)γ-dependent pathway and ameliorated hapten-induced contact hypersensitivity by inhibiting the development of inducible skin-associated lymphoid tissue through suppression of chemokine secretion from macrophages and inhibition of NF-κB activation in mice and cynomolgus macaques. Administering αKetoA also improved diabetic glucose intolerance by inhibiting adipose tissue inflammation and fibrosis through decreased macrophage infiltration in adipose tissues and altering macrophage M1/M2 polarization in mice fed a high-fat diet. These results collectively indicate that αKetoA is a novel postbiotic derived from α-linolenic acid, which controls macrophage-associated inflammatory diseases and may have potential for developing therapeutic drugs as well as probiotic food products.


Assuntos
Dieta Hiperlipídica , Macrófagos , Tecido Adiposo , Animais , Dieta Hiperlipídica/efeitos adversos , Lipídeos , Macaca fascicularis/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama/metabolismo
3.
Sci Rep ; 11(1): 10426, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001916

RESUMO

Atherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by identifying anti-inflammatory lipid metabolite. Mice were exposed to a high-fat diet (HFD) supplemented with either conventional soybean oil or α-linolenic acid-rich linseed oil. We found that as mice became obese they also showed increased pulsatility and resistive indexes in the common carotid artery. In sharp contrast, the addition of linseed oil to the HFD improved pulsatility and resistive indexes without affecting weight gain. Histological analysis revealed that dietary linseed oil inhibited foam cell formation in the aortic valve. Lipidomic analysis demonstrated a particularly marked increase in the eicosapentaenoic acid-derived metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) in the serum from mice fed with linseed oil. When we gave 12-HEPE to mice with HFD, the pulsatility and resistive indexes was improved. Indeed, 12-HEPE inhibited the foamy transformation of macrophages in a peroxisome proliferator-activated receptor (PPAR)γ-dependent manner. These results demonstrate that the 12-HEPE-PPARγ axis ameliorates the pathogenesis of atherosclerosis by inhibiting foam cell formation.


Assuntos
Aterosclerose/prevenção & controle , Suplementos Nutricionais , Ácido Eicosapentaenoico/análogos & derivados , Células Espumosas/patologia , Obesidade/complicações , Animais , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Diferenciação Celular , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ácido Eicosapentaenoico/administração & dosagem , Células Espumosas/metabolismo , Humanos , Óleo de Semente do Linho/administração & dosagem , Óleo de Semente do Linho/química , Masculino , Camundongos , Obesidade/dietoterapia , PPAR gama/metabolismo , Óleo de Soja/administração & dosagem , Aumento de Peso
4.
FASEB J ; 35(4): e21354, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33749892

RESUMO

ω3 fatty acids show potent bioactivities via conversion into lipid mediators; therefore, metabolism of dietary lipids is a critical determinant in the properties of ω3 fatty acids in the control of allergic inflammatory diseases. However, metabolic progression of ω3 fatty acids in the skin and their roles in the regulation of skin inflammation remains to be clarified. In this study, we found that 12-hydroxyeicosapentaenoic acid (12-HEPE), which is a 12-lipoxygenase metabolite of eicosapentaenoic acid, was the prominent metabolite accumulated in the skin of mice fed ω3 fatty acid-rich linseed oil. Consistently, the gene expression levels of Alox12 and Alox12b, which encode proteins involved in the generation of 12-HEPE, were much higher in the skin than in the other tissues (eg, gut). We also found that the topical application of 12-HEPE inhibited the inflammation associated with contact hypersensitivity by inhibiting neutrophil infiltration into the skin. In human keratinocytes in vitro, 12-HEPE inhibited the expression of two genes encoding neutrophil chemoattractants, CXCL1 and CXCL2, via retinoid X receptor α. Together, the present results demonstrate that the metabolic progression of dietary ω3 fatty acids differs in different organs, and identify 12-HEPE as the dominant ω3 fatty acid metabolite in the skin.


Assuntos
Quimiocina CXCL1/metabolismo , Dermatite de Contato/prevenção & controle , Ácido Eicosapentaenoico/análogos & derivados , Queratinócitos/efeitos dos fármacos , Animais , Anticorpos Monoclonais/efeitos dos fármacos , Anticorpos Monoclonais/metabolismo , Células da Medula Óssea , Quimiocina CXCL1/genética , Dieta , Dinitrofluorbenzeno , Regulação para Baixo , Ácido Eicosapentaenoico/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células HaCaT , Humanos , Óleo de Semente do Linho/administração & dosagem , Óleo de Semente do Linho/metabolismo , Camundongos
5.
iScience ; 23(9): 101426, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32818907

RESUMO

Homeostatic generation of T cells, which occurs in the thymus, is controlled at least in part by endogenous cytokines and ligands. In addition, nutritional factors are other key regulators for the homeostasis of host immunity, but whether and how nutrition affects the homeostatic generation of thymocytes remains to be established. Here, we showed that vitamin B1 deficiency resulted in a bias toward the maturation of γδ thymocytes accompanied by decreased differentiation into double-positive thymocytes during thymic involution. These events were mediated through the increased production of TGF-ß superfamily members due to the accumulation of branched-chain α-keto acids in thymic stromal cells. These findings revealed essential roles of vitamin B1 in the appropriate differentiation of T cells through the metabolism of thymic stromal cells.

6.
FASEB Bioadv ; 2(1): 59-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32123857

RESUMO

Dietary intake of ω3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid is beneficial for health control. We recently identified 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) as a lipid metabolite endogenously generated from eicosapentaenoic acid that exhibits potent anti-allergic and anti-inflammatory properties. However, chemically synthesized 17,18-EpETE is enantiomeric due to its epoxy group-17(S),18(R)-EpETE and 17(R),18(S)-EpETE. In this study, we demonstrated stereoselective differences of 17(S),18(R)-EpETE and 17(R),18(S)-EpETE in amelioration of skin contact hypersensitivity and found that anti-inflammatory activity was detected in 17(S),18(R)-EpETE, but not in 17(R),18(S)-EpETE. In addition, we found that cytochrome P450 BM-3 derived from Bacillus megaterium stereoselectively converts EPA into 17(S),18(R)-EpETE, which effectively inhibited the development of skin contact hypersensitivity by inhibiting neutrophil migration in a G protein-coupled receptor 40-dependent manner. These results suggest the new availability of a bacterial enzyme to produce a beneficial lipid mediator, 17(S),18(R)-EpETE, in a stereoselective manner. Our findings highlight that bacterial enzymatic conversion of fatty acid is a promising strategy for mass production of bioactive lipid metabolites.

7.
Allergy ; 75(8): 1939-1955, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32027039

RESUMO

BACKGROUND: Maternal dietary exposures are considered to influence the development of infant allergies through changes in the composition of breast milk. Cohort studies have shown that ω3 polyunsaturated fatty acids (PUFAs) in breast milk may have a beneficial effect on the preventing of allergies in infants; however, the underlying mechanisms remain to be investigated. We investigated how the maternal intake of dietary ω3 PUFAs affects fatty acid profiles in the breast milk and their pups and reduced the incidence of allergic diseases in the pups. METHODS: Contact hypersensitivity (CHS) induced by 2,4-dinitrofluorobenzene (DNFB) and fluorescein isothiocyanate was applied to the skin in pups reared by mother maintained with diets mainly containing ω3 or ω6 PUFAs. Skin inflammation, immune cell populations, and expression levels of immunomodulatory molecules in pups and/or human cell line were investigated by using flow cytometric, immunohistologic, and quantitative RT-PCR analyses. ω3 PUFA metabolites in breast milk and infant's serum were evaluated by lipidomics analysis using LC-MS/MS. RESULTS: We show that maternal intake of linseed oil, containing abundant ω3 α-linolenic acid, resulted in the increased levels of ω3 docosapentaenoic acid (DPA) and its 14-lipoxygenation products in the breast milk of mouse dams; these metabolites increased the expression of TNF-related apoptosis-inducing ligand (TRAIL) on plasmacytoid dendritic cells (pDCs) in their pups and thus inhibited infant CHS. Indeed, the administration of DPA-derived 14-lipoxygenation products to mouse pups ameliorated their DNFB CHS. CONCLUSION: These findings suggest that an inhibitory mechanism in infant skin allergy is induced through maternal metabolism of dietary ω3 PUFAs in mice.


Assuntos
Ácidos Graxos Ômega-3 , Ligante Indutor de Apoptose Relacionado a TNF , Animais , Cromatografia Líquida , Células Dendríticas , Ácidos Graxos Insaturados , Camundongos , Espectrometria de Massas em Tandem
8.
Bull Tokyo Dent Coll ; 61(1): 37-42, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32074589

RESUMO

Maintaining dental and oral health and increasing healthy life expectancy are important issues for Japan as it deals with the rapid aging of its population. The purpose of this study was to determine effective dental health measures aimed at increasing the number of present teeth in the elderly. Change in the number of present teeth was determined based on data obtained from the 2009 and 2014 "Good Teeth Tokyo (Ii-ha Tokyo)" surveys carried out by the Tokyo Metropolitan Government. The number of present teeth and percentile curves were compared between these two time points. The number only showed a significant increase in individuals aged 60 years in 2014 (p<0.05). This may have been due to the establishment of a national public insurance system. The number of present teeth showed an increase in 2014 in the 25th, 50th, and 75th percentile curves. In the 75th and 90th percentile curves, tooth loss accelerated when the number of present teeth was fewer than 25. This finding is consistent with studies reporting that tooth loss itself is a risk for tooth loss. Tooth loss showed a slight acceleration between the ages of approximately 20 and 45 years in the 90th percentile curve. These results indicate that dental check-ups at universities and companies, periodontal disease check-ups performed by local governments, and health instruction at these check-ups are necessary to increase the number of present teeth in the elderly. They further suggest that implementing measures to promote periodic visits to dental clinics and providing incentives to undergo treatment for tooth defects are necessary in high-risk individuals. In conclusion, dental check-ups, health instruction, and strategies for high-risk individuals in their 20s and 40s are necessary to increase the number of present teeth in the elderly.


Assuntos
Perda de Dente , Adulto , Idoso , Humanos , Japão , Pessoa de Meia-Idade , Saúde Bucal , Inquéritos e Questionários , Tóquio , Adulto Jovem
9.
Nanomaterials (Basel) ; 9(12)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817823

RESUMO

A new concept of semiconductor wafer bonding, mediated by optical wavelength conversion materials, is proposed and demonstrated. The fabrication scheme provides simultaneous bond formation and interfacial function generation, leading to efficient device production. Wavelength-converting functionalized semiconductor interfacial engineering is realized by utilizing an adhesive viscous organic matrix with embedded fluorescent particles. The bonding is carried out in ambient air at room temperature and therefore provides a cost advantage with regard to device manufacturing. Distinct wavelength conversion, from ultraviolet into visible, and high mechanical stabilities and electrical conductivities in the bonded interfaces are verified, demonstrating their versatility for practical applications. This bonding and interfacial scheme can improve the performance and structural flexibility of optoelectronic devices, such as solar cells, by allowing the spectral light incidence suitable for each photovoltaic material, and photonic integrated circuits, by delivering the respective preferred frequencies to the optical amplifier, modulator, waveguide, and detector materials.

10.
Bull Tokyo Dent Coll ; 60(4): 297-302, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31761880

RESUMO

The purpose of this study was to investigate the effectiveness of the Communication Studies Program at Tokyo Dental College as a tool in behavioral education. The number of Patient Community members who had participated in multiple sets of the program for third-year students in the same year within the 3-year period spanning 2016 to 2018 (152, 148, and 129 students in 2016, 2017, and 2018 respectively), and the period during which they had participated in multiple sets were investigated. Comments on student behavior, including on hairstyle, clothes, and attitude, were also analyzed. The total number of members who had participated in multiple sets (1 set comprised 1 lecture and 2 training sessions) was 5; and their comments were more favorable during the second (sets 3 and 4) than the first half of the 1-month program (sets 1 and 2). During the first half, the students were criticized for speaking softly, having bad posture, not concentrating, and having an attitude inappropriate for a medical worker; but in the second half, they were praised for beginning to adopt the proper attitude for a medical worker, speaking louder, having better posture, and a very serious attitude. These findings suggest that the Communication Studies Program is effective in improving student behavior.


Assuntos
Faculdades de Odontologia , Humanos , Tóquio
11.
Nutrients ; 11(12)2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766714

RESUMO

The metabolism and generation of bioactive lipid mediators are key events in the exertion of the beneficial effects of dietary omega-3 fatty acids in the regulation of allergic inflammation. Here, we found that dietary linseed oil, which contains high amounts of alpha-linolenic acid (ALA) dampened allergic rhinitis through eosinophilic production of 15-hydroxyeicosapentaenoic acid (15-HEPE), a metabolite of eicosapentaenoic acid (EPA). Lipidomic analysis revealed that 15-HEPE was particularly accumulated in the nasal passage of linseed oil-fed mice after the development of allergic rhinitis with the increasing number of eosinophils. Indeed, the conversion of EPA to 15-HEPE was mediated by the 15-lipoxygenase activity of eosinophils. Intranasal injection of 15-HEPE dampened allergic symptoms by inhibiting mast cell degranulation, which was mediated by the action of peroxisome proliferator-activated receptor gamma. These findings identify 15-HEPE as a novel EPA-derived, and eosinophil-dependent anti-allergic metabolite, and provide a preventive and therapeutic strategy against allergic rhinitis.


Assuntos
Antialérgicos/farmacologia , Ácido Eicosapentaenoico/análogos & derivados , Eosinófilos/metabolismo , PPAR gama/metabolismo , Rinite Alérgica/tratamento farmacológico , Administração Intranasal , Animais , Antialérgicos/metabolismo , Modelos Animais de Doenças , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/farmacologia , Eosinófilos/efeitos dos fármacos , Feminino , Inflamação/tratamento farmacológico , Óleo de Semente do Linho/administração & dosagem , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL
12.
Mucosal Immunol ; 12(5): 1082-1091, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31142830

RESUMO

Leukotriene B4 receptor 1 (BLT1) triggers the migration of granulocytes and activated T cells; however, its role in B-cell function remains unclear. Here we report that BLT1 is required to induce the production of antigen-specific IgA against oral vaccine through mediating innate immune signals from commensal bacteria. B cells acquire BLT1 expression during their differentiation to IgA+ B cells and plasma cells in Peyer's patches and the small intestinal lamina propria, respectively. BLT1 KO mice exhibited impaired production of antigen-specific fecal IgA to oral vaccine despite normal IgG responses to systemically immunized antigen. Expression of MyD88 was decreased in BLT1 KO gut B cells and consequently led to diminished proliferation of commensal bacteria-dependent plasma cells. These results indicate that BLT1 enhances the proliferation of commensal bacteria-dependent IgA+ plasma cells through the induction of MyD88 and thereby plays a key role in the production of antigen-specific intestinal IgA.


Assuntos
Epitopos/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade Inata , Imunoglobulina A Secretora/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Receptores do Leucotrieno B4/genética , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Imunização , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/metabolismo , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/metabolismo , Plasmócitos/imunologia , Plasmócitos/metabolismo , Receptores do Leucotrieno B4/metabolismo , Transdução de Sinais , Vacinas/administração & dosagem , Vacinas/imunologia
13.
Allergy ; 74(8): 1522-1532, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30843234

RESUMO

Coconut oil is used as a dietary oil worldwide, and its healthy effects are recognized by the fact that coconut oil is easy to digest, helps in weight management, increases healthy cholesterol, and provides instant energy. Although topical application of coconut oil is known to reduce skin infection and inflammation, whether dietary coconut oil has any role in decreasing skin inflammation is unknown. In this study, we showed the impact of dietary coconut oil in allergic skin inflammation by using a mouse model of contact hypersensitivity (CHS). Mice maintained on coconut oil showed amelioration of skin inflammation and increased levels of cis-5, 8, 11-eicosatrienoic acid (mead acid) in serum. Intraperitoneal injection of mead acid inhibited CHS and reduced the number of neutrophils infiltrating to the skin. Detailed mechanistic studies unveiled that mead acid inhibited the directional migration of neutrophils by inhibiting the filamentous actin polymerization and leukotriene B4 production required for secondary recruitment of neutrophils. Our findings provide valuable insights into the preventive roles of coconut oil and mead acid against skin inflammation, thereby offering attractive therapeutic possibilities.


Assuntos
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Óleo de Coco/efeitos adversos , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Dermatite de Contato/imunologia , Dermatite de Contato/metabolismo , Gorduras Insaturadas na Dieta/efeitos adversos , Ácido 8,11,14-Eicosatrienoico/metabolismo , Actinas/metabolismo , Animais , Biomarcadores , Permeabilidade Capilar , Quimiotaxia/imunologia , Dermatite Atópica/diagnóstico , Dermatite de Contato/diagnóstico , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Imunofenotipagem , Leucotrieno B4/biossíntese , Metabolismo dos Lipídeos , Camundongos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Pele/imunologia , Pele/metabolismo , Pele/patologia
14.
Int Immunol ; 31(2): 91-100, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30329068

RESUMO

Food poisonings caused by Clostridium perfringens and Shiga toxin (Stx)-producing Escherichia coli (STEC) occur frequently worldwide; however, no vaccine is currently available. Therefore, we aimed to develop a bivalent vaccine against C. perfringens and STEC infections. Although it has been considered that the C-terminal region of C. perfringens enterotoxin (C-CPE) could be a good vaccine antigen to block the binding to its receptor, it was insufficient for induction of a protective immune response because of the low antigenicity. However, the fusion of C-CPE with Stx2 B subunit (Stx2B) augmented the antigenicity of C-CPE without affecting the antigenicity of Stx2B. Indeed, high levels of C-CPE-specific neutralizing IgG were found in the serum of mice immunized with the fusion protein Stx2B-C-CPE. Additionally, comparable and substantial levels of Stx2B-specific neutralizing IgG were induced in mice receiving Stx2B-C-CPE or Stx2B alone. These antibody responses against C-CPE and Stx2B lasted for at least 48 weeks, which were sufficient for protective immunity in vitro and in vivo, indicating that Stx2B-C-CPE could induce long-term protective immunity. As an underlying mechanism, ex vivo stimulation with Stx2B, but not with C-CPE, induced cytokine production from splenic T cells collected from mice immunized with Stx2B-C-CPE, suggesting that Stx2B-specific, but not C-CPE-specific, T cells were induced by the immunization with Stx2B-C-CPE and plausibly promoted immunoglobulin class switching of both Stx2B- and C-CPE-specific B cells from IgM to IgG. These findings collectively indicate that Stx2B-C-CPE is a T-cell-antigen-supplement-type bivalent vaccine, which could be an efficient against C. perfringens and STEC infections.


Assuntos
Clostridium perfringens/imunologia , Enterotoxinas/imunologia , Escherichia coli/imunologia , Doenças Transmitidas por Alimentos/imunologia , Imunogenicidade da Vacina/imunologia , Toxina Shiga II/imunologia , Vacinas/imunologia , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C
15.
Int Immunol ; 30(10): 471-481, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30011025

RESUMO

We previously reported that Ag85B-expressing human parainfluenza type 2 virus (Ag85B-rHPIV2) was effective as a nasal vaccine against tuberculosis in mice; however, the mechanism by which it induces an immune response remains to be investigated. In the present study, we found that organogenesis of inducible bronchus-associated lymphoid tissue (iBALT) played a role in the induction of antigen-specific T cells and IgA antibody responses in the lung of mice intra-nasally administered Ag85B-rHPIV2. We found that expression of Ag85B was dispensable for the development of iBALT, suggesting that HPIV2 acted as an iBALT-inducing vector. When iBALT organogenesis was disrupted in Ag85B-rHPIV2-immunized mice, either by neutralization of the lymphotoxin pathway or depletion of CD11b+ cells, Ag85B-specific immune responses (i.e. IFN γ-producing T cells and IgA antibody) were diminished in the lung. Furthermore, we found that immunization with Ag85B-rHPIV2 induced neutrophil and eosinophil infiltration temporally after the immunization in the lung. Thus, our results show that iBALT organogenesis contributes to the induction of antigen-specific immune responses by Ag85B-rHPIV2 and that Ag85B-rHPIV2 provokes its immune responses without inducing long-lasting inflammation.


Assuntos
Aciltransferases/imunologia , Antígenos de Bactérias/imunologia , Tecido Linfoide/imunologia , Mycobacterium tuberculosis/imunologia , Organogênese , Vírus da Parainfluenza 2 Humana/imunologia , Vacinas contra a Tuberculose/imunologia , Animais , Camundongos , Camundongos Endogâmicos C57BL
16.
J Allergy Clin Immunol ; 142(2): 470-484.e12, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29288079

RESUMO

BACKGROUND: Metabolites of eicosapentaenoic acid exert various physiologic actions. 17,18-Epoxyeicosatetraenoic acid (17,18-EpETE) is a recently identified new class of antiallergic and anti-inflammatory lipid metabolite of eicosapentaenoic acid, but its effects on skin inflammation and the underlying mechanisms remain to be investigated. OBJECTIVE: We evaluated the effectiveness of 17,18-EpETE for control of contact hypersensitivity in mice and cynomolgus macaques. We further sought to reveal underlying mechanisms by identifying the responsible receptor and cellular target of 17,18-EpETE. METHODS: Contact hypersensitivity was induced by topical application of 2,4-dinitrofluorobenzene. Skin inflammation and immune cell populations were analyzed by using flow cytometric, immunohistologic, and quantitative RT-PCR analyses. Neutrophil mobility was examined by means of imaging analysis in vivo and neutrophil culture in vitro. The receptor for 17,18-EpETE was identified by using the TGF-α shedding assay, and the receptor's involvement in the anti-inflammatory effects of 17,18-EpETE was examined by using KO mice and specific inhibitor treatment. RESULTS: We found that preventive or therapeutic treatment with 17,18-EpETE ameliorated contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques. 17,18-EpETE was recognized by G protein-coupled receptor (GPR) 40 (also known as free fatty acid receptor 1) and inhibited chemoattractant-induced Rac activation and pseudopod formation in neutrophils. Indeed, the antiallergic inflammatory effect of 17,18-EpETE was abolished in the absence or inhibition of GPR40. CONCLUSION: 17,18-EpETE inhibits neutrophil mobility through GPR40 activation, which is a potential therapeutic target to control allergic inflammatory diseases.


Assuntos
Antialérgicos/uso terapêutico , Anti-Inflamatórios/metabolismo , Ácidos Araquidônicos/metabolismo , Dermatite de Contato/tratamento farmacológico , Neutrófilos/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Animais , Antialérgicos/farmacologia , Ácidos Araquidônicos/farmacologia , Ácidos Araquidônicos/uso terapêutico , Movimento Celular , Células Cultivadas , Feminino , Macaca fascicularis , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pseudópodes/patologia , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais , Proteínas rac de Ligação ao GTP/metabolismo
17.
Allergol Int ; 66(4): 523-528, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28693971

RESUMO

The number of patients with allergic and inflammatory disorders has been increasing during the past several decades. Accumulating evidence has refined our understanding of the relationship between allergic diseases and the gut microbiome. In addition, the gut microbiome is now known to produce both useful and harmful metabolites from dietary materials. These metabolites and bacterial components help to regulate host immune responses and potentially affect the development of allergic diseases. Here, we describe recent findings regarding the immunologic crosstalk between commensal bacteria and dietary components in the regulation of host immunity and the influence of this relationship on the development of allergic diseases.


Assuntos
Suscetibilidade a Doenças , Microbioma Gastrointestinal , Hipersensibilidade/etiologia , Hipersensibilidade/metabolismo , Metaboloma , Aminoácidos/metabolismo , Animais , Bactérias/metabolismo , Ácidos Graxos/metabolismo , Humanos , Imunomodulação , Vitaminas/metabolismo
18.
Sci Rep ; 7(1): 4339, 2017 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-28659635

RESUMO

Metagenomic analysis based on the 16S rRNA gene is generally performed to examine the diversity and abundance of commensal bacteria in feces, which is now recognized to be associated with human health and diseases. Guanidine thiocyanate (GuSCN) solution is used as a less onerous way compared with a frozen method to transport and stock fecal samples at room temperature for DNA analysis; however, optimal methods to measure fecal bacterial composition in GuSCN solution remain to be investigated. Here, we examined the influence of various factors such as pretreatment (e.g., removing GuSCN solution and washing feces with phosphate-buffered saline (PBS) before mechanical lysis), fecal concentration in the GuSCN solution, storage time, and position of fecal subsampling on the 16S rRNA-based analysis of fecal bacteria in GuSCN solution. We found that pretreatment and fecal concentration affected the bacterial composition, and a little change was noted with subsampling position. Based on these results, we propose a basic protocol, including fecal sampling, sample storage, and DNA extraction, for the 16S rRNA-based analysis of bacterial composition in feces suspended in GuSCN solution.


Assuntos
Biodiversidade , Metagenoma , Metagenômica , Microbiota , Adulto , Bactérias/classificação , Bactérias/genética , Fezes/microbiologia , Feminino , Humanos , Masculino , Metagenômica/métodos , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Adulto Jovem
19.
Bull Tokyo Dent Coll ; 58(1): 33-40, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28381732

RESUMO

The purpose of the present study was to investigate the reasons governing selection of geographical location of workplace by postgraduate dental trainees. We believe that such data would aid in the development of measures aimed at reducing regional disparities in the number of dentists. A total of 10 dental colleges and faculties in Japan were invited to participate in the study. Anonymous, self-completed questionnaire surveys were given to 739 dentists at 13 clinical training facilities following training in 2012 and 2013; 713 responses were analyzed. The items surveyed included the local population in the area in which they wished to work and whether they wanted to work in rural areas or remote islands. The most common response to the question regarding population was "medium-size cities" with a population of 100,000 to 300,000 people (67.3%). The largest number of respondents stated that they hoped to work in their hometown or a neighboring area (49.9%). A large percentage wished to work in medium-size cities, which may reflect the population of their hometowns. The current system allows dentists a free choice in becoming practitioners or hospital dentists on completion of training. This may explain why so many expressed a preference to work in their hometown or a neighboring area here. These results suggest that policies relying on increasing the supply of dentists as the sole solution to rural shortages are flawed.


Assuntos
Escolha da Profissão , Odontólogos , Educação de Pós-Graduação em Odontologia , Local de Trabalho , Atitude do Pessoal de Saúde , Humanos , Intenção , Japão , População Rural , Inquéritos e Questionários
20.
Bull Tokyo Dent Coll ; 57(3): 189-93, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27665697

RESUMO

In 2009, the Ministry of Education, Culture, Sports, Science and Technology launched its "Program for Promoting University Education and Student Support, Theme A: Program for Promoting University Education Reform". The ministry's stated aims were to 1) enhance student training centered on the needs of the individual patient; 2) improve their ability to make comprehensive diagnosis and treatment plans; and 3) instill high ethical standards and good communication skills. One of the main pillars of this project was to establish an educational organization aimed at encouraging public participation, the "Patient Community". The aim was to have members of this community roleplay patients in the Communication Studies component of the 1st-4th years of dental school. It was hoped that they would be able to respond to the students in a more realistic manner than simulated patients. Here, the number of Patient Community members and number who attended Communication Studies classes in 2010, 2011, 2012, and 2014 were investigated. The results showed that the number registered in the Patient Community increased annually, as did the number participating in Communication Studies classes, which rose in accordance with the number of classes held. No difference was observed in the number of attendees per Communication Studies class by grade (years 1-4). The number of members never attending Community Studies classes increased annually, although some members repeatedly attended. These findings suggest that the members who regularly participate tend to remain the same.


Assuntos
Participação da Comunidade/estatística & dados numéricos , Educação em Odontologia/estatística & dados numéricos , Simulação de Paciente , Seleção de Pessoal/estatística & dados numéricos , Participação da Comunidade/métodos , Relações Dentista-Paciente , Educação em Odontologia/métodos , Feminino , Humanos , Masculino , Seleção de Pessoal/métodos , Avaliação de Programas e Projetos de Saúde/métodos , Faculdades de Odontologia , Tóquio
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