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1.
Nat Commun ; 14(1): 7396, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978297

RESUMO

Antiferromagnetic (AF) topological materials offer a fertile ground to explore a variety of quantum phenomena such as axion magnetoelectric dynamics and chiral Majorana fermions. To realize such intriguing states, it is essential to establish a direct link between electronic states and topology in the AF phase, whereas this has been challenging because of the lack of a suitable materials platform. Here we report the experimental realization of the AF topological-insulator phase in NdBi. By using micro-focused angle-resolved photoemission spectroscopy, we discovered contrasting surface electronic states for two types of AF domains; the surface having the out-of-plane component in the AF-ordering vector displays Dirac-cone states with a gigantic energy gap, whereas the surface parallel to the AF-ordering vector hosts gapless Dirac states despite the time-reversal-symmetry breaking. The present results establish an essential role of combined symmetry to protect massless Dirac fermions under the presence of AF order and widen opportunities to realize exotic phenomena utilizing AF topological materials.

2.
Nat Commun ; 12(1): 7070, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862386

RESUMO

The metal-insulator transition (MIT), a fascinating phenomenon occurring in some strongly correlated materials, is of central interest in modern condensed-matter physics. Controlling the MIT by external stimuli is a key technological goal for applications in future electronic devices. However, the standard control by means of the field effect, which works extremely well for semiconductor transistors, faces severe difficulties when applied to the MIT. Hence, a radically different approach is needed. Here, we report an MIT induced by resonant tunneling (RT) in double quantum well (QW) structures of strongly correlated oxides. In our structures, two layers of the strongly correlated conductive oxide SrVO3 (SVO) sandwich a barrier layer of the band insulator SrTiO3. The top QW is a marginal Mott-insulating SVO layer, while the bottom QW is a metallic SVO layer. Angle-resolved photoemission spectroscopy experiments reveal that the top QW layer becomes metallized when the thickness of the tunneling barrier layer is reduced. An analysis based on band structure calculations indicates that RT between the quantized states of the double QW induces the MIT. Our work opens avenues for realizing the Mott-transistor based on the wave-function engineering of strongly correlated electrons.

3.
J Nutr Health Aging ; 24(10): 1080-1086, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33244564

RESUMO

OBJECTIVES: Nutritional status affects cerebral circulation and cognitive function. More attention needs to be paid to nutritional status in coronary artery disease (CAD) patients, yet the relation between nutritional status or dietary intake (DI) and cognitive function or mild cognitive impairment (MCI) in CAD patients remain unclear. Thus, we examined the following relations: 1) that between nutritional status and cognitive function, and MCI and 2) that between DI and cognitive function, and MCI. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional study of 208 patients with CAD but without dementia. MEASUREMENTS: MCI was estimated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Nutritional status was assessed by the Geriatric Nutritional Risk Index (GNRI), and DI was assessed by total energy intake per day. We investigated the relation between nutritional status or DI and cognitive function by Pearson correlation analysis, and that between nutritional status or DI and MCI by multivariable logistic regression analysis. RESULTS: The GNRI and DI were positively associated with the MoCA-J score (r = 0.23, p < 0.001, and r = 0.24, p < 0.001, respectively), and both were independently associated with MCI in the multivariable logistic regression analysis (odds ratio, 0.96; p = 0.045, and odds ratio, 0.998; p = 0.020, respectively). CONCLUSIONS: Poor nutritional status and low DI were found to be significantly associated with cognitive function and MCI in CAD patients. Our findings regarding nutritional status and DI might be useful for clinicians to prevent or intervene in the early cognitive decline of inpatients with CAD.


Assuntos
Disfunção Cognitiva/etiologia , Doença da Artéria Coronariana/complicações , Desnutrição/etiologia , Estado Nutricional/fisiologia , Idoso , Disfunção Cognitiva/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Desnutrição/psicologia , Pessoa de Meia-Idade
4.
J AOAC Int ; 103(6): 1619-1624, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33112388

RESUMO

BACKGROUND: Lycopene has been the object of considerable research attention recently, and the effects of the intake of lycopene, or of tomato products, have been studied in various ways. In Japan, interest in the health-promoting function of food components has increased. OBJECTIVE: Developing a method to determine lycopene contents in tomato that meets the Japanese Agricultural Standard (JAS). METHOD: In the proposed JAS method, the test sample consists of fresh tomatoes; a hexane-acetone mixture is utilized as the extraction solvent. A collaborative study was conducted to evaluate the interlaboratory performance of the method. RESULTS: Ten laboratories participated and analyzed six test materials characterized by a lycopene content between 39 and 170 mg/kg as blind duplicates. After removing statistical outliers, RSDr ranged from 1.2 to 3.0% and RSDR ranged from 2.4 to 4.2%. The HorRat values were calculated and found to be in the 0.26-0.49 range. CONCLUSIONS: The method for determining the lycopene content in tomato was evaluated by means of a collaborative study, and the reproducibility of this method was found to be acceptable. HIGHLIGHTS: Intended for standardization in Japan, a method to determine lycopene content in tomato has been developed and shown to have acceptable precision in a collaborative study.


Assuntos
Licopeno , Solanum lycopersicum , Japão , Licopeno/análise , Reprodutibilidade dos Testes , Espectrofotometria
5.
Lupus ; 28(3): 295-303, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30700214

RESUMO

BACKGROUND: Lupus nephritis (LN) is a major determinant of mortality in systemic lupus erythematosus (SLE). Here we evaluated the association between complete renal response (CR) and mortality in LN. METHODS: We retrospectively analyzed the cases of 172 of 201 patients with LN for whom data on the therapeutic response at 6 and 12 months after induction therapy were available. The patients underwent a renal biopsy at Nagasaki University Hospital and community hospitals in Nagasaki between the years 1990 and 2016. We determined the CR rates at 6 and 12 months after induction therapy initiation and evaluated the predictive factors for CR and their relationship with mortality. We performed univariate and multivariable competing risks regression analyses to determine the factors predictive of CR. The patients' survival data were analyzed by the Kaplan-Meier method with a log-rank test. RESULTS: The median follow-up duration after renal biopsy was 120 months (interquartile range: 60.3-191.8 months). The 5-, 10-, 15- and 20-year survival rates of our cohort were 99.3, 94.6, 92.0 and 85.4%, respectively. During follow-up, nine patients (5.2%) died from cardiovascular events, infection, malignancy and other causes. The multivariate analysis revealed that the following factors were predictive of CR. At 6 months: male gender (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.08-0.65, p = 0.0028), proteinuria (g/gCr) (OR 0.83, 95% CI 0.71-0.97, p = 0.0098) and index of activity (0-24) (OR 0.84, 95% CI 0.71-0.99, p = 0.0382). At 12 months: male gender (OR 0.25, 95% CI 0.09-0.67, p = 0.0043) and index of activity (0-24) (OR 0.82, 95% CI 0.69-0.98, p = 0.0236). The Kaplan-Meier analysis showed that compared to not achieving CR at 12 months, achieving CR at 12 months was significantly correlated with the survival rate (OR 0.18, 95% CI 0.04-0.92, p = 0.0339). CONCLUSIONS: Our results suggest that the survival rate of patients with LN is associated with the achievement of CR at 12 months after induction therapy, and that male gender and a higher index of activity (0-24) are the common predictive factors for failure to achieve CR at 6 and 12 months.


Assuntos
Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/mortalidade , Prednisolona/uso terapêutico , Adulto , Idade de Início , Estudos de Casos e Controles , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Proteinúria , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais
6.
Lupus ; 28(4): 501-509, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30755146

RESUMO

BACKGROUND: Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE). METHODS: We retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993-2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares. RESULTS: Of the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5-154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01-1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44-0.90, p = 0.00048) and serum ß2 microglobulin (MG) (OR 0.26, 95% CI 0.06-0.74, p = 0.00098) levels. CONCLUSIONS: Among LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum ß2MG levels were negative predictive factors of CR at 12 months.


Assuntos
Hospitais Universitários , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/etiologia , Adulto , Autoantígenos/sangue , Nitrogênio da Ureia Sanguínea , Feminino , Seguimentos , Humanos , Japão , Estimativa de Kaplan-Meier , Rim/patologia , Modelos Logísticos , Nefrite Lúpica/sangue , Nefrite Lúpica/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fragmentos de Peptídeos/sangue , Modelos de Riscos Proporcionais , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Microglobulina beta-2/sangue
7.
Transplant Proc ; 50(10): 3496-3500, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577227

RESUMO

BACKGROUND: Despite reported associations between intrapulmonary vascular shunting (IPVS) and morbidity and mortality in pediatric liver transplantation (LT), there are no guidelines for screening. OBJECTIVE: To investigate IPVS before and after pediatric LT. METHODS: Retrospective records review of all pediatric LT (n = 370) from 2005 to 2015 at a single institute in Japan. All children with cirrhosis and clinical suspicion of IPVS without cardiac or pulmonary conditions were included. 99mTechnetium labelled macroaggregated albumin (99mTcMAA) scans were performed before and after LT. The severity of IPVS was graded using shunt ratios. RESULTS: Twenty-four children fulfilled inclusion criteria and underwent Tc99MAA scans. All revealed mild (<20%) to moderate (20%-40%) grades of IPVS. Following LT, the mean shunt ratio regressed from 20.69 ± 6.26% to 15.1 ± 3.4% (P = .06). The median (range) follow-up was 17 (4-85) months. Mortality was zero. The incidence of portal vein thrombosis (4.2%) biliary strictures (12.5%) and graft loss (4.1%) in the study group was not statistically significant compared to the remainder of the 370 transplants (3.2%, 9.4% and 3%, respectively). Sub-group analysis revealed hepatopulmonary syndrome (HPS) in 2 out of 24 children. The mean shunt ratios before and after LT were 39.2 ± 0.77% and 16.2 ± 8.5%, respectively (P = .08). There was 1 complication (intra-abdominal abscess). CONCLUSIONS: HPS is less likely in mild to moderate IPVS. LT may achieve comparable results when performed in the presence of mild to moderate IPVS.


Assuntos
Transplante de Fígado , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Síndrome Hepatopulmonar/etiologia , Humanos , Lactente , Japão , Transplante de Fígado/efeitos adversos , Pulmão/patologia , Masculino , Imagem de Perfusão/métodos , Estudos Retrospectivos , Resultado do Tratamento
8.
J Periodontal Res ; 53(2): 200-209, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29063603

RESUMO

BACKGROUND AND OBJECTIVE: Single nucleotide polymorphisms (SNPs) of paraoxonase 1 (PON1) are known to be associated with the pathogenesis of osteoporosis and periodontitis. However, the effects of PON1 on the osteoblastic differentiation of periodontal ligament (PDL) cells are unclear. In this study, we examined the effects of PON1 on the osteoblastic differentiation of PDL cells, and analysed the role of PON1 SNPs on the pathogenesis of aggressive periodontitis (AgP) in the Japanese population. MATERIAL AND METHODS: Human PDL (HPDL) cells were exposed to the PON1 plasmid and PON1 inhibitor, 2-hydroxyquinoline, and cultured in mineralization medium. Expression of calcification-related genes and calcified nodule formation were assessed by real-time PCR, an alkaline phosphatase (ALPase) activity assay and Alizarin red staining. Sanger sequencing was performed to evaluate whether PON1 SNPs are associated with the pathogenesis of AgP in Japanese people. RESULTS: During osteoblastic differentiation of HPDL cells, expression of PON1 mRNA increased in a time-dependent manner. PON1 stimulated an increase in expression of mRNA for calcification-related genes, as well as ALPase activity. In contrast, 2-hydroxyquinoline clearly inhibited the expression of calcification-related genes, ALPase activity and calcified nodule formation in HPDL cells. Moreover, there was a statistically significant difference in the minor allele frequency of PON1 SNP rs854560 between the Japanese control database and patients with AgP in the Japanese population (P = .0190). CONCLUSION: PON1 induced cytodifferentiation and mineralization of HPDL cells, and PON1 SNP rs854560 may be associated with the pathogenesis of AgP in the Japanese population.


Assuntos
Periodontite Agressiva/patologia , Arildialquilfosfatase/metabolismo , Arildialquilfosfatase/farmacologia , Diferenciação Celular/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/patologia , Adulto , Periodontite Agressiva/enzimologia , Fosfatase Alcalina/análise , Arildialquilfosfatase/genética , Reabsorção Óssea , Calcificação Fisiológica , Células Cultivadas , Feminino , Expressão Gênica , Frequência do Gene , Humanos , Hidroxiquinolinas/antagonistas & inibidores , Japão , Masculino , Osteoblastos/efeitos dos fármacos , Bolsa Periodontal , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/metabolismo
9.
J Dent Res ; 96(3): 339-346, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28221099

RESUMO

Sphingomyelin phosphodiesterase 3 ( Smpd3), which encodes neutral sphingomyelinase 2 (nSMase2), is a key molecule for skeletal development as well as for the cytodifferentiation of odontoblasts and alveolar bone. However, the effects of nSMase2 on the cytodifferentiation of periodontal ligament (PDL) cells are still unclear. In this study, the authors analyzed the effects of Smpd3 on the cytodifferentiation of human PDL (HPDL) cells. The authors found that Smpd3 increases the mRNA expression of calcification-related genes, such as alkaline phosphatase (ALPase), type I collagen, osteopontin, Osterix (Osx), and runt-related transcription factor (Runx)-2 in HPDL cells. In contrast, GW4869, an inhibitor of nSMase2, clearly decreased the mRNA expression of ALPase, type I collagen, and osteocalcin in HPDL cells, suggesting that Smpd3 enhances HPDL cytodifferentiation. Next, the authors used exome sequencing to evaluate the genetic variants of Smpd3 in a Japanese population with aggressive periodontitis (AgP). Among 44 unrelated subjects, the authors identified a single nucleotide polymorphism (SNP), rs145616324, in Smpd3 as a putative genetic variant for AgP among Japanese people. Moreover, Smpd3 harboring this SNP did not increase the sphingomyelinase activity or mRNA expression of ALPase, type I collagen, osteopontin, Osx, or Runx2, suggesting that this SNP inhibits Smpd3 such that it has no effect on the cytodifferentiation of HPDL cells. These data suggest that Smpd3 plays a crucial role in maintaining the homeostasis of PDL tissue.


Assuntos
Periodontite Agressiva/genética , Ligamento Periodontal/citologia , Esfingomielina Fosfodiesterase/fisiologia , Adulto , Periodontite Agressiva/enzimologia , Fosfatase Alcalina/metabolismo , Calcificação Fisiológica , Diferenciação Celular , Linhagem Celular , Células Cultivadas , Colágeno Tipo I/metabolismo , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Immunoblotting , Japão , Masculino , Osteocalcina/metabolismo , Osteopontina/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real , Esfingomielina Fosfodiesterase/genética
10.
J Periodontal Res ; 52(1): 114-121, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27028150

RESUMO

BACKGROUND AND OBJECTIVE: The association between periodontal disease and nutrient intake was examined using linked data from the 2005 National Health and Nutrition Survey, the Comprehensive Survey of Living Conditions and the Survey of Dental Diseases from the same year 'using linked data from the National Health and Nutrition Survey, the Comprehensive Survey of Living Conditions and the Survey of Dental Diseases, all from 2005'. There has been increasing focus on the importance of nutritional factors in disease in recent years, but very few studies in Japan have looked at the association between periodontal disease and nutrients. Therefore, in the present study we investigated factors associated with periodontal disease, particularly in terms of nutrient intake. MATERIAL AND METHODS: Data from 3043 individuals, ≥ 20 years of age (the original study sample comprised 4873 individuals, but those younger than 20 years of age and pregnant women were excluded from the present study) were compiled from linked responses to these three surveys from the same year. Permission to use the data was obtained from the Lifestyle-Related Diseases Control General Affairs Division of the Ministry of Health, Labor, and Welfare, Japan. Information including basic attributes, family structure, economic status, physical condition, lifestyle habits, diet, dental habits, blood data, intake of foods (including the categories of food) and nutrient-related information were obtained from the linked data. The individual maximum Community Periodontal Index (CPI) was used as an index of periodontal disease. Subjects were divided, according to maximum CPI, into groups in which CPI = 0-2 or CPI = 3-4, and associations between CPI and basic attributes, family structure, economic status, physical condition, lifestyle habits, diet, blood data and food intake were analyzed. RESULTS: Multivariate analysis revealed that the percentage of calories from fat was a nutrient factor associated with periodontal disease, with the percentage of calories from fat being significantly lower in the group with advanced periodontal disease. CONCLUSION: The results suggest that a low-fat, high-carbohydrate diet is related to periodontal disease. A more detailed analysis of this topic will be conducted in the future using different indices of periodontal disease.


Assuntos
Gorduras na Dieta/efeitos adversos , Doenças Periodontais/etiologia , Adulto , Complicações do Diabetes/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Estilo de Vida , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estado Nutricional , Doenças Periodontais/epidemiologia , Fatores de Risco , Adulto Jovem
11.
JDR Clin Trans Res ; 2(1): 87-92, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30938644

RESUMO

The 2004 Japanese National Health and Nutrition Survey collected data on several measures, including self-reported dental health. In addition, this was the first nationwide survey to focus on metabolic syndrome (MetS) in Japan. Therefore, the authors used this nationwide data set to assess the relationship between number of teeth present and MetS. Anonymized data were available with permission from the Ministry of Health, Labour and Welfare of Japan. Data from 3,195 men and women aged 35 to 99 y were examined, and logistic regression analyses were used to evaluate the association between number of teeth and MetS. Moreover, the authors performed an analysis of covariance to compare the mean number of teeth between those with and those without MetS, after adjusting for confounders. In comparison with those having ≥28 teeth, those with fewer remaining teeth demonstrated significantly higher odds of having MetS. Specifically, those having 1 to 9 teeth had higher odds of having MetS than those with more teeth and were more than twice as likely to be affected than those with ≥28 teeth. Furthermore, individuals with MetS in the age groups of 45 to 54, 55 to 64, and 65 to 74 y had significantly fewer teeth than those without MetS in the same age groups. These results suggest that the number of teeth present is associated with the prevalence of MetS in the Japanese population. Knowledge Transfer Statement: The results of this study can be used by clinicians when they examine patients with periodontal disease or extensive tooth loss to refer for a general medical examination.

12.
Oral Dis ; 22(6): 578-84, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27171647

RESUMO

OBJECTIVE: Diabetes is often associated with increased prevalence and severity of periodontal disease. We hypothesized that gingival epithelial cells modify periodontal disease progression and predicted that hyperglycemia would activate an inflammatory response in human gingival epithelial cells (HGECs). MATERIALS AND METHODS: We tested our hypothesis in immortalized HGECs (epi 4 cells) isolated from periodontal tissue and transfected with the simian virus 40 T antigen. The epi 4 cells were cultured in high (25 mM, HG) and normal (6 mM, NG) glucose conditions. RESULTS: The epi 4 cells showed increased interleukin-8 (IL-8) protein secretion and mRNA expression when cultured in HG, compared with in NG. These effects were not associated with increased cell proliferation and were not observed in a hyperosmolar control group (normal glucose with 19 mM mannitol). Increased IL-8 secretion in HG was inhibited by pretreatment with an antioxidant, N-acetylcysteine, or a protein kinase C inhibitor, Ro31-8220. Hyperglycemia did not affect IL-8 secretion by gingival fibroblasts or periodontal ligament cells. In epi 4 cells, hyperglycemia also induced expression of toll-like receptor 2 (TLR2) but not TLR4. CONCLUSION: These findings suggest a potential participation of epithelial cells in periodontal disease during diabetes by evoking an excessive host inflammatory response.


Assuntos
Células Epiteliais/fisiologia , Gengiva/citologia , Interleucina-8/biossíntese , Estresse Oxidativo/fisiologia , Células Cultivadas , Diabetes Mellitus/metabolismo , Humanos
13.
J Dent Res ; 94(10): 1417-24, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26239644

RESUMO

PLAP-1 is an extracellular matrix protein that is predominantly expressed in the periodontal ligament within periodontal tissue. It was previously revealed that PLAP-1 negatively regulates bone morphogenetic protein 2 and transforming growth factor ß activity through direct interactions. However, the interaction between PLAP-1 and other growth factors has not been defined. Here, we revealed that PLAP-1 positively regulates the activity of fibroblast growth factor 2 (FGF-2), a critical growth factor in tissue homeostasis and repair. In this study, we isolated mouse embryonic fibroblasts (MEFs) from Plap-1(-/-) mice generated in our laboratory. Interestingly, Plap-1(-/-) MEFs exhibited enhanced responses to bone morphogenetic protein 2 but defective responses to FGF-2, and Plap-1 transfection into Plap-1(-/-) MEFs rescued these defective responses. In addition, binding assays revealed that PLAP-1 promotes FGF-2-FGF receptor 1 (FGFR1) complex formation by direct binding to FGF-2. Immunocytochemistry analyses revealed colocalization of PLAP-1 and FGF-2 in wild-type MEFs and reduced colocalization of FGF-2 and FGFR1 in Plap-1(-/-) MEFs compared with wild-type MEFs. Taken together, PLAP-1 positively regulates FGF-2 activity through a direct interaction. Extracellular matrix-growth factor interactions have considerable effects; thus, this approach may be useful in several regenerative medicine applications.


Assuntos
Proteínas da Matriz Extracelular/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Animais , Western Blotting , Diferenciação Celular/fisiologia , Fibroblastos/fisiologia , Camundongos , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo Real , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/fisiologia
14.
Chem Commun (Camb) ; 51(66): 13110-2, 2015 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-26185913

RESUMO

A versatile method has been found to catalyze the dehydrogenative N-((triisopropylsilyl)oxy)carbonyl (Tsoc) protection of amines using Pd/C, volatile iPr3SiH and CO2 gas without the liberation of any salts. A simple filtration/evaporation process facilitates the easy isolation of the product, thereby enhancing the utility of Tsoc as an amine-protecting group in organic synthesis.


Assuntos
Aminas/química , Dióxido de Carbono/química , Compostos de Trimetilsilil/química , Catálise , Hidrogenação
15.
J Dent Res ; 94(8): 1149-57, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26045329

RESUMO

Damage-associated molecular patterns (DAMPs), endogenous molecules released from injured or dying cells, evoke sterile inflammation that is not induced by microbial pathogens. Periodontal diseases are infectious diseases caused by oral microorganisms; however, in some circumstances, DAMPs might initiate inflammatory responses before host cells recognize pathogen-associated molecular patterns. Here, we showed that the necrotic cell supernatant (NCS) functioned as an endogenous danger signal when released from necrotic epithelial cells exposed to repeat freeze thawing. The NCS contained RNA and stimulated the production of inflammatory cytokines interleukin 6 (IL-6) and IL-8 from gingival epithelial cells and gingival fibroblasts. Targeted knockdown of Toll-like receptor 3 (TLR3) in these cells significantly suppressed the ability of the NCS to induce IL-6 and IL-8 production. Epithelial cells and fibroblasts recognized the NCS from heterologous cells. Interestingly, the activation of TLR3, rather than other TLRs, induced TLR2 mRNA expression and proteins in gingival epithelial cells, and pretreatment with the NCS or polyinosinic:polycytidylic acid (Poly(I:C)), a strong TLR3 activator, enhanced inflammatory cytokine production induced by subsequent stimulation with Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide, a TLR2 agonist. Moreover, the NCS reduced the expression of epithelial tight junction molecules zona occludens 1 and occludin and increased the permeability of epithelial tight junctions. These findings suggest that endogenous danger signal molecules such as self-RNA released from necrotic cells are recognized by TLR3 and that a subsequent increase of TLR2 expression in periodontal compartments such as gingival epithelial cells and gingival fibroblasts may enhance the inflammatory response to periodontopathic microbes recognized by TLR2 such as P. gingivalis, which also disrupts epithelial barrier functions. Thus, DAMPs may be involved in the development and prolongation of periodontal disease.


Assuntos
Porphyromonas gingivalis/imunologia , Receptor 2 Toll-Like/metabolismo , Receptor 3 Toll-Like/metabolismo , Western Blotting , Células Cultivadas , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Citometria de Fluxo , Fluoresceína-5-Isotiocianato , Gengiva/citologia , Humanos , Lipopolissacarídeos/farmacologia , Necrose/metabolismo , Necrose/patologia , Reação em Cadeia da Polimerase em Tempo Real
16.
J Periodontal Res ; 50(2): 248-55, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24948468

RESUMO

BACKGROUND AND OBJECTIVE: The proteasome inhibitor, bortezomib, is known to induce osteoblastic differentiation in a number of cell lines, such as mesenchymal stem cells and osteoblastic precursor cells. As periodontal ligament (PDL) cells are multipotent, we examined whether bortezomib may induce the differentiation of PDL cells into hard-tissue-forming cells. MATERIAL AND METHODS: A mouse PDL clone cell line, MPDL22 cells, was cultured in mineralization medium in the presence or absence of bortezomib. Expression of calcification-related genes and calcified-nodule formation were evaluated by real-time PCR and Alizarin Red staining, respectively. RESULTS: Bortezomib increased the expression of calcification-related mRNAs, such as tissue nonspecific alkaline phosphatase isoenzyme (ALPase), bone sialoprotein (Bsp), runt-related transcription factor 2 (Runx2) and osteopontin, and calcified-nodule formation in MPDL22 cells. These effects were induced, in part, by increasing the cytosolic accumulation and nuclear translocation of ß-catenin, leading to an increase in expression of bone morphogenetic protein (Bmp)-2, -4 and -6 mRNAs. In addition, bortezomib enhanced BMP-2-induced expression of Bsp and osteopontin mRNAs and increased calcified-nodule formation in MPDL22 cells. CONCLUSION: Bortezomib induced cytodifferentiation and mineralization of PDL cells by enhancing the accumulation of ß-catenin within the cytosol and the nucleus and increasing the expression of Bmp-2, -4 and -6 mRNAs. Moreover, bortezomib enhanced the BMP-2-induced cytodifferentiation and mineralization of PDL cells, suggesting that bortezomib may be efficacious for use in periodontal regeneration therapy.


Assuntos
Bortezomib/farmacologia , Calcificação Fisiológica/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Inibidores de Proteassoma/farmacologia , Fosfatase Alcalina/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2/efeitos dos fármacos , Proteína Morfogenética Óssea 4/efeitos dos fármacos , Proteína Morfogenética Óssea 6/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Clonais/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/efeitos dos fármacos , Citosol/efeitos dos fármacos , Isoenzimas/efeitos dos fármacos , Camundongos , Osteopontina/efeitos dos fármacos , Ligamento Periodontal/citologia , beta Catenina/efeitos dos fármacos
17.
J Oral Rehabil ; 41(12): 912-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25056986

RESUMO

This cross-sectional study aimed to investigate the association of periodontal status with occlusal force and food acceptability. We hypothesised that mastication deteriorated with reduced periodontal support, even when posterior occlusal contacts with natural teeth were maintained and the patients remained clinically asymptomatic. Participants were 482 independently living 69-71-year-olds, classified as Eichner's group A, having no mobile teeth and no periodontal symptoms. The periodontal probing depth (PPD) and restoration status of each tooth were examined. Occlusal force in the intercuspal position was measured with pressure-sensitive films. Food acceptability was evaluated from the difficulty experienced in chewing apples, grilled beef, and hard rice crackers. Multivariate regression analysis was performed to investigate the association of periodontal status with occlusal force and food acceptability. A P-value of <0.05 was considered statistically significant. Multiple linear regression analysis showed that occlusal force had significant negative associations with maximal PPD (standardised partial regression coefficient (ß) = -0.121) after controlling for gender, handgrip strength, number of teeth, and percentage of restored teeth. Approximately 15% of participants were included in the compromised food acceptability group. Logistic regression analyses showed that compromised food acceptability was significantly associated with PPD, after controlling for gender, number of teeth, and percentage of restored teeth. Periodontal probing depth (PPD) was significantly correlated with occlusal force and self-rated food acceptability after controlling for the possible confounding factors in septuagenarians, even those with complete posterior occlusal contacts and no tooth mobility.


Assuntos
Força de Mordida , Preferências Alimentares , Mastigação/fisiologia , Doenças Periodontais/fisiopatologia , Idoso , Estudos Transversais , Índice CPO , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Satisfação Pessoal
18.
J Dent Res ; 93(1): 89-95, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24186558

RESUMO

We previously demonstrated that topical application of fibroblast growth factor (FGF)-2 enhanced periodontal tissue regeneration. Although angiogenesis is a crucial event for tissue regeneration, the mechanism(s) by which topically applied FGF-2 induces angiogenesis in periodontal tissues has not been fully clarified. In this study, we investigated whether FGF-2 could induce vascular endothelial growth factor (VEGF)-A expression in periodontal ligament (PDL) cells and whether cell-to-cell interactions between PDL cells and endothelial cells could stimulate angiogenesis. FGF-2 induced VEGF-A secretion from MPDL22 cells (mouse periodontal ligament cell line) in a dose-dependent manner. Transwell and wound-healing assays revealed that co-stimulation with FGF-2 plus VEGF-A synergistically stimulated the migration of MPDL22 cells. Interestingly, co-culture of MPDL22 cells with bEnd5 cells (mouse endothelial cell line) also stimulated VEGF-A production from MPDL22 cells and tube formation by bEnd5 cells. Furthermore, time-lapse analysis revealed that MPDL22 cells migrated close to the tube-forming bEnd5 cells, mimicking pericytes. Thus, FGF-2 induces VEGF-A expression in PDL cells and induces angiogenesis in combination with VEGF-A. Cell-to-cell interactions with PDL cells also facilitate angiogenesis.


Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacologia , Ligamento Periodontal/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/farmacologia , Animais , Comunicação Celular/efeitos dos fármacos , Técnicas de Cultura de Células , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Técnicas de Cocultura , Corantes , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Células Endoteliais/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Citometria de Fluxo , Humanos , Camundongos , Microscopia Confocal , Microtúbulos/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Pericitos/efeitos dos fármacos , Ligamento Periodontal/citologia , Proteínas Recombinantes , Regulação para Cima
19.
Oral Dis ; 20(3): e49-56, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23679350

RESUMO

OBJECTIVE: Periodontitis is a chronic inflammatory disease of the tissues supporting the teeth and is caused by subgingival plaque. Systemic increases in reactive oxygen species are involved in pathogenesis of periodontitis. This study addressed the relationship between levels of serum oxidative stress and antibodies against putative periodontopathic bacteria and their association with periodontal conditions, in a community-based study. SUBJECTS AND METHODS: Serum samples were measured for reactive oxygen metabolite (ROM) levels and anti-oxidant capacity. The serum levels of immunoglobulin G (IgG) antibodies to Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Aggregatibacter actinomycetemcomitans (Aa), and Eikenella corrodens (Ec) were determined by ELISA. RESULTS: The participants with greater clinical attachment loss had higher serum ROM levels and IgG antibody titers to Pg. Serum ROM levels were positively correlated with antibody titers to Pg, Pi, and Ec. When the participants with greater probing pocket depth and clinical attachment loss were used as the dependent variables, high ROM levels showed a statistically significant associations in multivariate logistic analyses; the adjusted odds ratios were 2.9 (95% confidence interval = 1.0-8.5) and 6.0 (95% confidence interval = 2.0-17.6), respectively. CONCLUSIONS: It was concluded that an increased oxidative stress may be detrimental to periodontitis in Japanese community-dwelling adults.


Assuntos
Anticorpos Antibacterianos/sangue , Imunoglobulina G/sangue , Estresse Oxidativo , Periodontite/microbiologia , Idoso , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade
20.
Infection ; 41(2): 415-23, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23471823

RESUMO

PURPOSE: In Japan, a national surveillance study of antimicrobial consumption has never been undertaken. This study aimed to describe antimicrobial consumption and resistance to Pseudomonas aeruginosa in 203 Japanese hospitals, to identify targets for quality improvement. METHODS: We conducted an ecological study using retrospective data (2010). Antimicrobial consumption was collected in the World Health Organization (WHO) anatomical therapeutic chemical/defined daily dose (ATC/DDD) format. Rates of imipenem (IPM), meropenem (MEPM), ciprofloxacin (CPFX), or amikacin (AMK) resistance were expressed as the incidence of non-susceptible isolates. Additionally, hospitals were asked to provide data concerning hospital characteristics and infection control policies. Hospitals were classified according to functional categories of the Medical Services Act in Japan. RESULTS: Data were collected from 203 Japanese hospitals (a total of 91,147 beds). The total antimicrobial consumption was 15.49 DDDs/100 bed-days (median), with consumptions for penicillins, carbapenems, quinolones, and glycopeptides being 4.27, 1.60, 0.41, and 0.49, respectively. The median incidences of IPM, MEPM, CPFX, and AMK resistance were 0.15, 0.10, 0.13, and 0.03 isolates per 1,000 patient-days, respectively. Antimicrobial notification and/or approval systems were present in 183 hospitals (90.1 %). In the multivariate analysis, the piperacillin/tazobactam, quinolones, and/or total consumptions and the advanced treatment hospitals showed a significant association with the incidence of P. aeruginosa resistant to IPM, MEPM, CPFX, and AMK [adjusted R (2) (aR (2)) values of 0.23, 0.30, 0.22, and 0.35, respectively). CONCLUSION: This is the first national surveillance study of antimicrobial consumption in Japan. A continuous surveillance program in Japan is necessary in order to evaluate the association among resistance, antimicrobial restriction, and consumption.


Assuntos
Farmacorresistência Bacteriana Múltipla , Uso de Medicamentos/estatística & dados numéricos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Amicacina/uso terapêutico , Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Revisão de Uso de Medicamentos/métodos , Hospitais/normas , Humanos , Imipenem/uso terapêutico , Incidência , Japão/epidemiologia , Meropeném , Testes de Sensibilidade Microbiana , Programas Nacionais de Saúde , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Inquéritos e Questionários , Tienamicinas/uso terapêutico
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