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BACKGROUND: Marital transitions are associated with adverse health events, such as mortality and cardiovascular disease. Since marital transitions (eg, becoming widowed) are unavoidable life events, it is necessary to identify modifiable intermediate outcomes. Thus, we examined the association between marital transitions and vegetable intake among middle-aged and older Japanese adults. METHODS: This longitudinal study included Japanese adults aged 40-79 years who received an annual health checkup between 2007 and 2011 (baseline) and 5 years later (follow-up). Marital transitions were classified as whether and what type of transition occurred during the 5-year period and comprised five groups: consistently married, married to widowed, married to divorced, not married to married, and remained not married. Changes in total vegetable, green and yellow vegetable, and light-colored vegetable intake from baseline to follow-up were calculated using the Food Frequency Questionnaire. RESULTS: Data from 4,813 participants were analyzed (mean age, 59.4 years; 44.1% women). Regarding marital transitions, 3,960 participants were classified as "consistently married," 135 as "married to widowed," 40 as "married to divorced," 60 as "not married to married," and 529 as "remained not married." Multivariable linear regression analysis revealed that compared to consistently married, married to widowed was inversely associated with the change in total vegetable intake (ß = -16.64, SE = 7.68, P = 0.030) and light-colored vegetable intake (ß = -11.46, SE = 4.33, P = 0.008). CONCLUSION: Our findings suggest that being widowed could result in a reduced intake of vegetables. Hence, dietary counseling according to marital situation is necessary.
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Matrimonio , Verduras , Adulto , Anciano , Femenino , Humanos , Japón , Estudios Longitudinales , Masculino , Estado Civil , Persona de Mediana EdadRESUMEN
INTRODUCTION: After the onset of bone metastasis, tumor cells appear to modify surrounding microenvironments for their benefit, and particularly, the levels of circulating fibroblast growth factor (FGF) 23 in patients with tumors have been highlighted. MATERIALS AND METHODS: We have attempted to verify if human breast carcinoma MDA-MB-231 cells metastasized in the long bone of nu/nu mice would synthesize FGF23. Serum concentrations of calcium, phosphate (Pi) and FGF23 were measured in control nu/nu mice, bone-metastasized mice, and mice with mammary gland injected with MDA-MB-231 cells mimicking primary mammary tumors. RESULTS AND CONCLUSIONS: MDA-MB-231 cells revealed intense FGF23 reactivity in metastasized lesions, whereas MDA-MB-231 cells cultured in vitro or when injected into the mammary glands (without bone metastasis) showed weak FGF23 immunoreactivity. Although the bone-metastasized MDA-MB-231 cells abundantly synthesized FGF23, osteocytes adjacent to the FGF23-immunopositive tumors, unlike intact osteocytes, showed no FGF23. Despite significantly elevated serum FGF23 levels in bone-metastasized mice, there was no significant decrease in the serum Pi concentration when compared with the intact mice and mice with a mass of MDA-MB-231 cells in mammary glands. The metastasized femora showed increased expression and FGFR1 immunoreactivity in fibroblastic stromal cells, whereas femora of control mice showed no obvious FGFR1 immunoreactivity. Taken together, it seems likely that MDA-MB-231 cells synthesize FGF23 when metastasized to a bone, and thus affect FGFR1-positive stromal cells in the metastasized tumor nest in a paracrine manner.
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Neoplasias de la Mama , Factores de Crecimiento de Fibroblastos , Animales , Huesos , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Ratones , Ratones Desnudos , Osteocitos , Microambiente TumoralRESUMEN
BACKGROUND AND AIM: A recent basic study identified that Dicer is contained in exosomes derived from cancer cells and plays crucial roles in microRNA maturation and cancer development. Based on this novel basic concept, we analyzed the usefulness of serum exosomal Dicer as a diagnostic biomarker for gastrointestinal cancers. METHODS: Enrolled participants (691) were categorized into 3 groups: gastric cancer (GC) cohort, 183 patients (90 healthy controls (HCs) and 93 GC patients); esophageal cancer (EC) cohort, 115 patients (90 HCs and 25 EC patients); and colorectal cancer (CRC) cohort, 188 patients (92 HCs and 96 CRC patients) after age- and sex matching using the propensity score. The quality of isolated serum exosomes was validated with an electron microscope, particle size analyzer, and exosome marker, CD63. RESULTS: Serum exosomal Dicer was significantly higher in the GC group than in the HC group (p = 0.004), whereas no significant differences were found in both EC and CRC cohorts. Serum exosomal Dicer was significantly higher in only differentiated gastric adenocarcinoma and not in the undifferentiated type. Moreover, serum exosomal Dicer showed no significant differences regardless of Helicobacter pylori (H. pylori) status. The biomarker panel combining serum exosomal Dicer with H. pylori status distinguished between HC and differentiated GC patients with an area under the curve (AUC) of 0.762. As for early-stage diagnosis, this combination distinguished between HC and stage I differentiated GC with an AUC = 0.758. CONCLUSIONS: Serum exosomal Dicer is a potential noninvasive diagnostic biomarker for early detection of differentiated gastric adenocarcinoma.
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Adenocarcinoma , ARN Helicasas DEAD-box , Exosomas , MicroARNs , Ribonucleasa III , Neoplasias Gástricas , Adenocarcinoma/diagnóstico , Biomarcadores de Tumor , ARN Helicasas DEAD-box/sangre , Humanos , Ribonucleasa III/sangre , Neoplasias Gástricas/diagnósticoRESUMEN
BACKGROUND: With the goal of discovering non-invasive biomarkers for early diagnosis of GC, we conducted a case-control study utilising urine samples from individuals with predominantly early GC vs. healthy control (HC). METHODS: Among urine samples from 372 patients, age- and sex-matched 282 patients were randomly divided into three groups: 18 patients in a discovery cohort; 176 patients in a training cohort and 88 patients in a validation cohort. RESULTS: Among urinary proteins identified in the comprehensive quantitative proteomics analysis, urinary levels of TFF1 (uTFF1) and ADAM12 (uADAM12) were significantly independent diagnostic biomarkers for GC, in addition to Helicobacter pylori status. A urinary biomarker panel combining uTFF1, uADAM12 and H. pylori significantly distinguished between HC and GC patients in both training and validation cohorts. On the analysis for sex-specific biomarkers, this combination panel demonstrated a good AUC of 0.858 for male GC, whereas another combination panel of uTFF1, uBARD1 and H. pylori also provided a good AUC of 0.893 for female GC. Notably, each panel could distinguish even stage I GC patients from HC patients (AUC = 0.850 for males; AUC = 0.845 for females). CONCLUSIONS: Novel urinary protein biomarker panels represent promising non-invasive biomarkers for GC, including early-stage disease.
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Biomarcadores de Tumor/orina , Detección Precoz del Cáncer/métodos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/orina , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Second-hand smoke exposure has been associated with poor mental health. However, among Japanese adults, little is known about the association between second-hand smoking and depressive symptoms. We examined this association in a cross-sectional study among a Japanese general adult population sample. METHODS: Japanese adults were recruited from the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2012 and 2017. Second-hand smoke exposure and smoking status were assessed using a self-administered questionnaire. Based on their frequency of exposure to second-hand smoke, non-smokers and smokers were categorized as "almost never," "sometimes," and "almost every day". Depressive symptoms were defined by a Kessler 6 score ≥5 points. We performed a multivariable Poisson regression analysis to obtain adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for depressive symptoms. RESULTS: Overall, 5,121 participants (4,547 non-smokers and 574 smokers) were included whose mean age was 63.6 (standard deviation [SD], 10.3) years for non-smokers and 59.33 (SD, 10.2) years for smokers. The association between second-hand smoking and depressive symptoms was significant among non-smokers, but not among smokers. Among non-smokers, PRs compared with "almost never" were 1.25 (95% CI, 1.09-1.42) for "sometimes" and 1.41 (95% CI, 1.09-1.84) for "almost every day" (P for trend <0.001); among smokers, PRs compared with "almost never" were 1.30 (95% CI, 0.82-2.06) for "sometimes" and 1.44 (95% CI, 0.90-2.33) for "almost every day" (P for trend = 0.144). CONCLUSIONS: Second-hand smoking and depressive symptoms were associated among non-smokers. Our findings indicate the importance of tobacco smoke control for mental health.
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Depresión/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Fumar/efectos adversos , Contaminación por Humo de Tabaco/efectos adversos , Adulto , Estudios de Cohortes , Estudios Transversales , Depresión/psicología , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Fumar/epidemiología , Encuestas y Cuestionarios , Contaminación por Humo de Tabaco/estadística & datos numéricosRESUMEN
BACKGROUND: It is known that physical activity affects glucose metabolism. However, there have been no reports on the influence of physical activity earlier in life on subsequent glucose metabolism. Therefore, we analyzed the influence of physical activity in earlier decades of life on insulin resistance in middle aged and older residents in Japan. METHODS: The subjects were 6,883 residents of Okazaki City between the ages of 40 and 79 years who underwent physical examinations at the Okazaki City Medical Association Public Health Center from April 2007 through August 2011. They gave informed consent for participation in the study. Data on individual characteristics were collected via a questionnaire and from the health examination records. Fasting blood glucose and insulin levels were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR). HOMA-IR >1.6 was considered to indicate insulin resistance for the purpose of logistic regression models. RESULTS: The study sample included 3,683 men and 3,200 women for whom complete information was available. For those who exercised regularly throughout their teens to their 30s-40s, the odds ratio for having insulin resistance was 0.75 (95% confidence interval [CI], 0.58-0.96) for men and 0.76 (95% CI, 0.58-0.99) for women after adjusting for other variables, including age, body mass index, and present physical activity. A linear trend was also observed in both men and women. CONCLUSIONS: Subjects who have exercised regularly in the early decades of life are less likely to have insulin resistance later in life.
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Ejercicio Físico , Resistencia a la Insulina , Adulto , Anciano , Femenino , Humanos , Japón , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: We aimed to examine missing data in FFQ and to assess the effects on estimating dietary intake by comparing between multiple imputation and zero imputation. DESIGN: We used data from the Okazaki Japan Multi-Institutional Collaborative Cohort (J-MICC) study. A self-administered questionnaire including an FFQ was implemented at baseline (FFQ1) and 5-year follow-up (FFQ2). Missing values in FFQ2 were replaced by corresponding FFQ1 values, multiple imputation and zero imputation. SETTING: A methodological sub-study of the Okazaki J-MICC study.ParticipantsOf a total of 7585 men and women aged 35-79 years at baseline, we analysed data for 5120 participants who answered all items in FFQ1 and at least 50% of items in FFQ2. RESULTS: Among 5120 participants, the proportion of missing data was 3·7%. The increasing number of missing food items in FFQ2 varied with personal characteristics. Missing food items not eaten often in FFQ2 were likely to represent zero intake in FFQ1. Most food items showed that the observed proportion of zero intake was likely to be similar to the probability that the missing value is zero intake. Compared with FFQ1 values, multiple imputation had smaller differences of total energy and nutrient estimates, except for alcohol, than zero imputation. CONCLUSIONS: Our results indicate that missing values due to zero intake, namely missing not at random, in FFQ can be predicted reasonably well from observed data. Multiple imputation performed better than zero imputation for most nutrients and may be applied to FFQ data when missing is low.
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Exactitud de los Datos , Encuestas sobre Dietas/normas , Dieta/estadística & datos numéricos , Alimentos/estadística & datos numéricos , Encuestas y Cuestionarios/normas , Adulto , Anciano , Estudios de Cohortes , Registros de Dieta , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
This study was designed to examine developing acellular cementum in rat molars by immunohistochemistry, to elucidate (1) how Hertwig's epithelial root sheath disintegrates and (2) whether epithelial sheath cells transform into cementoblasts through epithelial-mesenchymal transition (EMT). Initial acellular cementogenesis was divided into three developmental stages, which can be seen in three different portions of the root: portion 1, where the epithelial sheath is intact; portion 2, where the epithelial sheath becomes fragmented; and portion 3, where acellular cementogenesis begins. Antibodies against three kinds of matrix proteinases, which degrade epithelial sheath-maintaining factors, including basement membrane and desmosomes, were used to investigate proteolytic activity of the epithelial sheath. Tissue non-specific alkaline phosphatase (TNALP) and keratin were used to investigate EMT. Epithelial sheath cells showed immunoreactivity for all three enzymes at fragmentation, which suggests that epithelial sheath disintegration is enzymatically mediated. Dental follicle cells and cementoblasts showed intense immunoreactivity for TNALP, and from portion 1 through to 3, the reaction extended from the alveolar bone-related zone to the root-related zone. Cells possessing keratin/TNALP double immunoreactivity were virtually absent. Keratin-positive epithelial sheath cells showed negligible immunoreactivity for TNALP, and epithelial cells did not appear to migrate to the dental follicle. Together, these findings suggest that a transition phenotype between epithelial cells and cementoblasts does not exist in the developing dental follicle and hence that epithelial sheath cells do not undergo EMT during initial acellular cementogenesis. In brief, this study supports the notion that cementoblasts derive from the dental follicle.
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Cementogénesis , Células Epiteliales/citología , Diente Molar/citología , Raíz del Diente/citología , Animales , Células Epiteliales/metabolismo , Masculino , Diente Molar/metabolismo , Ratas , Ratas Wistar , Raíz del Diente/metabolismoRESUMEN
The association between blood glucose and fractures is not consistent across populations. Blood glucose was associated with fractures five years later in middle-aged and elderly men who underwent health examinations in Japan, respectively. Blood glucose-targeted fracture alerts are crucial for middle-aged and elderly individuals. OBJECTIVES: The evidence on blood glucose as a fracture risk marker has not been adequately examined in various populations, and there are no studies in middle-aged Japanese. We aimed to determine the association between blood glucose status and self-report fractures among middle-aged and elderly Japanese men. METHODS: The data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Okazaki Study were used. Hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) measured at baseline physical examinations were examined for association with fractures questioned five years later. Analyses were performed for the middle-aged and elderly respondents. RESULTS: The HbA1c was dichotomized into 290 (11.8%) with HbA1c ≥ 6.5% and 2165 (88.2%) with HbA1c < 6.5%. Compared to the group with an HbA1c < 6.5, the odds ratio for the risks of fracture among the group with an HbA1c ≥ 6.5% were 3.46 (95% confidence interval (CI), 1.75-6.84) in Model 1 (adjusted for age) and 3.60 (95% CI, 1.77-7.34) in Model 2 (adjusted for various confounding factors). These associations were also observed in both middle-aged and elderly generations, whereas no association was observed for FPG. CONCLUSIONS: Among Japanese men who have undergone physical examinations, those with an HbA1c of 6.5% or higher are at higher risk for fractures, and HbA1c-targeted fracture alerts are crucial for middle-aged and elderly individuals.
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Glucemia , Fracturas Óseas , Anciano , Humanos , Masculino , Persona de Mediana Edad , Hemoglobina Glucada , Japón , Estudios Multicéntricos como Asunto , Examen Físico , Estudios Prospectivos , AutoinformeRESUMEN
Despite encouraging multi-generational cohabitation, the population of Japanese people living alone has increased. However, little is known about the association between health and multigenerational cohabitation. This study examined the relationship between self-rated health and living arrangements among Japanese adults using data from the Japan Multi-Institutional Collaborative Cohort Study (2013-2017). The analysis employed multivariate logistic regression to examine the associations. Our results showed no association between living arrangements and self-rated health when stratified by gender. Living alone was found to be associated with poor self-rated health among women aged 65 and above. A similar association may exist among men in the same age group. Among women aged < 65 years, two-generation cohabitation was associated with a good self-rated health, similar to those living alone. Among men aged < 65 years, neither living alone nor two-generation cohabitation was significantly associated with good self-rated health. We found no association between three- or plus-generation cohabitation and self-rated health. Therefore, our findings indicate associations between multigenerational cohabitation and self-rated health, but they vary by gender and age. Invested stakeholders in the public health field should consider the potential impact of living arrangements on health based on gender and age.
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Estado de Salud , Humanos , Femenino , Masculino , Anciano , Japón , Persona de Mediana Edad , Factores Sexuales , Factores de Edad , Características de la Residencia , Estudios de Cohortes , AutoinformeRESUMEN
BACKGROUND: Currently utilized serum tumor markers and fecal immunochemical tests do not have sufficient diagnostic power for colorectal cancer (CRC) due to their low sensitivities. To establish non-invasive urinary protein biomarkers for early CRC diagnosis, we performed stepwise analyses employing urine samples from CRCs and healthy controls (HCs). METHODS: Among 474 urine samples, 363 age- and sex-matched participants (188 HCs, 175 stage 0-III CRCs) were randomly divided into discovery (16 HCs, 16 CRCs), training (110 HCs, 110 CRCs), and validation (62 HCs, 49 CRCs) cohorts. RESULTS: Of the 23 urinary protein candidates comprehensively identified from mass spectrometry in the discovery cohort, urinary levels of dipeptidase 1 (uDPEP1) and Trefoil factor1 (uTFF1) were the two most significant diagnostic biomarkers for CRC in both training and validation cohorts using enzyme-linked immunosorbent assays. A urinary biomarker panel comprising uDPEP1 and uTFF1 significantly distinguished CRCs from HCs, showing area under the curves of 0.825-0.956 for stage 0-III CRC and 0.792-0.852 for stage 0/I CRC. uDPEP1 and uTFF1 also significantly distinguished colorectal adenoma (CRA) patients from HCs, with uDPEP1 and uTFF1 increasing significantly in the order of HCs, CRA patients, and CRC patients. Moreover, expression levels of DPEP1 and TFF1 were also significantly higher in the serum and tumor tissues of CRC, compared to HCs and normal tissues, respectively. CONCLUSIONS: This study established a promising and non-invasive urinary protein biomarker panel, which enables the early detection of CRC with high sensitivity.
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Biomarcadores de Tumor , Neoplasias Colorrectales , Dipeptidasas , Detección Precoz del Cáncer , Factor Trefoil-1 , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/orina , Biomarcadores de Tumor/orina , Biomarcadores de Tumor/sangre , Masculino , Detección Precoz del Cáncer/métodos , Femenino , Factor Trefoil-1/orina , Persona de Mediana Edad , Anciano , Dipeptidasas/orina , Dipeptidasas/sangre , Estudios de Casos y Controles , Estadificación de Neoplasias , Ensayo de Inmunoadsorción Enzimática , Adulto , Sensibilidad y Especificidad , Adenoma/diagnóstico , Adenoma/orina , Proteínas Ligadas a GPIRESUMEN
The School of Dental Medicine in Japan nurtures well-trained professionals who are at the cutting edge of the present knowledge in the fields of Dentistry and Dental Technology. As an important part of its mission, many Schools of Dental Medicine in Japan, including Hokkaido University, also encourages dental students to pursue basic research in the many aspects of Dentistry. It is of importance to cultivate research-minded students in Dental Medicine. Laboratory assignment conducted by the School of Dental Medicine, Hokkaido University, is one process of education curriculum to assign students in the fifth and sixth grade to laboratories of basic sciences. Every dental student should belong to one laboratory, which accepts the fixed number of the students. By means of the research activity of the laboratory assignments, some students obtain new insights on their research projects, and will often have an opportunity for presenting their findings in some academic meetings. Meanwhile, many academic meetings in Japan, including The Japanese Association of Anatomists, often feature special sessions where undergraduate students can present their findings under the guidance of their mentors. Such initiatives led by the Dental School and the academic meetings are geared towards raising interest in research and preparing young investigators for the future.
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Investigación Biomédica , Educación en Odontología , Estudiantes de Odontología , Evaluación Educacional , Humanos , Japón , Facultades de Odontología , Estudiantes de Odontología/estadística & datos numéricosRESUMEN
Previous studies have reported that the signal attenuation of diffusion weighted magnetic resonance imaging for tumor tissues displays a non-monoexponential biexponential decay, and the apparent diffusion coefficients (ADCs) can be divided into a fast and slow diffusion component by using a simple biexponential decay model. The purpose of this study is to examine the non-monoexponential character of the diffusion weighted magnetic resonance imaging signal attenuations of breast cancers, estimate the fast and slow diffusion components, and compare them with the extra- and intracellular component information obtained from the pathological specimens. Twenty-two subjects having breast cancers underwent diffusion weighted magnetic resonance imaging using six b-values up to 3500 s/mm(2) and the signal attenuations were analyzed using the biexponential function. The derived slow component fraction correlated with the cellular fraction and the ADCs converged to 0.2-0.3 × 10(-3) mm(2) /s for the higher cellular fractions. The ADCs of the fast component ranged from 1.3 to 3.9 × 10(-3) mm(2) /s and showed no correlation with the extracellular components. This result suggests that the main reason for the decreasing ADC of a breast tumor is the decreasing fraction of the fast component and the increasing fraction of the slow component having a low ADC rather than the decreasing ADC of the fast component by the restricted water diffusion in the reduced extracellular spaces.
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Algoritmos , Neoplasias de la Mama/patología , Imagen de Difusión por Resonancia Magnética/métodos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Recent findings have focused attention on the molecular consequences of the microenvironment in tumor progression, but events occurring in cancer cells themselves in response to their ambient conditions remain obscure. Here, we identify receptor activator of nuclear factor κB ligand (RANKL) as a microenvironment-specific factor essential for tumorigenesis in vivo, using head and neck squamous cell carcinoma (HNSCC) as a model. In human HNSCC tissues, RANKL is abundantly expressed, and its expression level correlates with the histological grade of differentiation. RANKL levels are significantly higher in poorly differentiated SCCs than in well or moderately differentiated SCCs. In contrast, all HNSCC cell lines tested displayed extremely low RANKL expression; however, RANKL is efficiently up-regulated when these cell lines are inoculated in the head and neck region of mice. RANKL expression is restored in a microenvironment-specific manner, and cannot be observed when the cells are inoculated in the hindlimbs. Forced expression of RANKL compensates for tumor growth in the hindlimb milieu, promotes epithelial mesenchymal transition, and induces tumor angiogenesis, in a manner independent of vascular endothelial growth factor (VEGF). These results implicate RANKL expression causatively in tumor growth and progression in HNSCC in vivo. RANKL may provide a novel functional marker for biological malignancy and a therapeutic target based on the specific nature of the microenvironment.
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Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Neoplasias de Cabeza y Cuello/patología , Ligando RANK/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/irrigación sanguínea , Neoplasias de Cabeza y Cuello/genética , Miembro Posterior/patología , Humanos , Ratones , Neovascularización Patológica/complicaciones , Fenotipo , Lesiones Precancerosas/patología , Ligando RANK/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Microambiente Tumoral/genéticaRESUMEN
This study aimed at elucidating whether estrogen deficiency would affect the synthesis of an osteocyte-derived factor, sclerostin, in the mesial region of alveolar bone. Eight 9-week-old Wistar female rats were ovariectomized (OVX) and eight other rats were Sham-operated (Sham). After 4 weeks, the interradicular septa of mandibular first molar were embedded in paraffin and then histochemically examined. Sclerostin-positive osteocytes were located in the superficial layer of the mesial region of Sham bones, whereas the OVX mesial region showed less sclerostin-reactive osteocytes. There was no significant difference in the distribution of estrogen receptor α and terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling -positive cells in the groups studied. The Sham mesial region featured many osteoclasts, and OVX specimens showed numerous osteoclasts in association with intense immunolabeling of the receptor activator of the nuclear factor kB ligand. Contrary to the observations in Sham specimens, a complex meshwork of cement lines was seen in the OVX mesial region, accompanied by an irregularly distributed osteocytic lacunar-canalicular system. In conclusion, estrogen deficiency appears to inhibit osteocyte-derived sclerostin synthesis in the mesial region of the interradicular septum, in a process that seems to be mediated by accelerated bone remodeling rather than by direct effects on osteocytes.
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Proteínas Morfogenéticas Óseas/biosíntesis , Remodelación Ósea/efectos de los fármacos , Osteoclastos/metabolismo , Osteocitos/efectos de los fármacos , Osteocitos/metabolismo , Fosfatasa Ácida/metabolismo , Animales , Proteínas Morfogenéticas Óseas/genética , Huesos/metabolismo , Catepsina K/genética , Catepsina K/metabolismo , Estrógenos/deficiencia , Estrógenos/farmacología , Femenino , Marcadores Genéticos/genética , Etiquetado Corte-Fin in Situ , Isoenzimas/metabolismo , Ovariectomía , Ratas , Ratas Wistar , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Fosfatasa Ácida Tartratorresistente , Receptor Relacionado con Estrógeno ERRalfaRESUMEN
Parathyroid hormone (PTH) -driven anabolism in bone appears to involve the osteoblastic activation and the increased population of preosteoblastic lineages. Given that the activities of osteoclasts and osteoblasts are intertwined during normal bone remodeling, it is plausible that the anabolic action of PTH is either directly or indirectly related to the osteoclast. We have recently reported that the absence of osteoclasts in c-fos( - / - ) mice might hinder PTH-driven bone anabolism, and that osteoclastic presence may be necessary for full osteoblastic differentiation and enhanced bone formation seen after intermittent PTH administration. Alternatively, it was suggested that PTH administration inhibits sclerostin synthesis by osteocytes, thereby allowing for active bone formation. Taken together, PTH affects bone cells in a dual pathway - mediating osteoblastic (preosteoblastic) activities or osteocytic synthesis of sclerostin -.
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Huesos/metabolismo , Osteoblastos/citología , Osteogénesis/efectos de los fármacos , Hormona Paratiroidea/administración & dosificación , Hormona Paratiroidea/farmacología , Proteínas Adaptadoras Transductoras de Señales , Animales , Proteínas Morfogenéticas Óseas/biosíntesis , Remodelación Ósea , Diferenciación Celular , Marcadores Genéticos , Humanos , Ratones , Osteoclastos/fisiología , Osteocitos/metabolismo , Hormona Paratiroidea/fisiologíaRESUMEN
BACKGROUND: As the global population ages, the number of older adults working after retirement is increasing. However, knowledge regarding working conditions for health and happiness among this population is insufficient. Therefore, we examined the association between work-related factors (e.g., employment status, daily working time, work-related stress) and happiness among working older adults. METHODS: This cross-sectional study recruited Japanese older adults, aged 65 years and older, who were engaged in paid work, during their annual health checkups. Self-administered questionnaires were used to assess happiness, employment status, daily working time, and work-related stress (i.e., job strain, job control, job suitability, and relationships at work). RESULTS: The data of 520 men and 168 women were analyzed (mean ages, 68.5 years and 68.0 years, respectively). The results of the multivariable ordinal logistic regression analysis indicated that low job suitability was negatively associated with happiness in men (odds ratio [OR]=0.46; 95% confidence interval [CI], 0.28-0.78; p=0.004). In women, long working hours and low job control were negatively associated with happiness-working >8 hours daily (OR=0.29; 95% CI, 0.12-0.71; p=0.008) and low job control (OR=0.29; 95% CI, 0.12-0.72; p=0.009). CONCLUSION: The results showed that low job suitability for men and long daily working time and low job control for women were negatively associated with happiness. These findings suggest the need to improve working conditions to enhance the well-being of working older adults.
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Since noninvasive biomarkers as an alternative to invasive colonoscopy to detect colorectal cancer (CRC) are desired, we conducted this study to determine the urinary biomarker consisting of microRNAs (miRNAs). In total, 415 age- and sex-matched participants, including 206 patients with CRC and 209 healthy controls (HCs), were randomly divided into three groups: (1) the discovery cohort (CRC, n = 3; HC, n = 6); (2) the training cohort (140 pairs); and (3) the validation cohort (63 pairs). Among 11 urinary miRNAs with aberrant expressions between the two groups, miR-129-1-3p and miR-566 were significantly independent biomarkers that detect CRC. The panel consisting of two miRNAs could distinguish patients with CRC from HC participants with an area under the curve (AUC) = 0.811 in the training cohort. This panel showed good efficacy with an AUC = 0.868 in the validation cohort. This urinary biomarker combining miR-129-1-3p and miR-566 could detect even stage 0/I CRC effectively with an AUC = 0.845. Moreover, the expression levels of both miR-129-1-3p and miR-566 were significantly higher in primary tumor tissues than in adjacent normal tissue. Our established novel biomarker consisting of urinary miR-129-1-3p and miR-566 enables noninvasive and early detection of CRC.
RESUMEN
BACKGROUND: Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene-environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005. METHODS: We initiated a cross-sectional study to examine associations of genotypes with lifestyle and clinical factors, as assessed by questionnaires and medical examinations. The 4519 subjects were selected from among participants in the J-MICC Study in 10 areas throughout Japan. In total, 108 polymorphisms were chosen and genotyped using the Invader assay. RESULTS: The study group comprised 2124 men and 2395 women with a mean age of 55.8 ± 8.9 years (range, 35-69 years) at baseline. Among the 108 polymorphisms examined, 4 were not polymorphic in our study population. Among the remaining 104 polymorphisms, most variations were common (minor allele frequency ≥0.05 for 96 polymorphisms). The allele frequencies in this population were comparable with those in the HapMap-JPT data set for 45 Japanese from Tokyo. Only 5 of 88 polymorphisms showed allele-frequency differences greater than 0.1. Of the 108 polymorphisms, 32 showed a highly significant difference in minor allele frequency among the study areas (P < 0.001). CONCLUSIONS: This comprehensive data collection on lifestyle and clinical factors will be useful for elucidating gene-environment interactions. In addition, it is likely to be an informative reference tool, as free access to genotype data for a large Japanese population is not readily available.
Asunto(s)
Ambiente , Frecuencia de los Genes/genética , Estilo de Vida , Polimorfismo Genético/genética , Adulto , Anciano , Estudios de Cohortes , Estudios Transversales , Femenino , Genotipo , Humanos , Japón , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: It has been reported that kidney stones are linked to metabolic syndrome (MetS), which is characterized by insulin resistance. The aim of the present study was to examine the association of insulin resistance, insulin and adiponectin with kidney stones in a Japanese population. METHODS: From February 2007 to March 2008, 1036 (529 men and 507 women) apparently healthy Japanese subjects, aged 35-79 years, were analyzed. Weight, height, waist circumference and blood pressure were measured. Overnight fasting blood was collected to measure insulin and adiponectin levels. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to assess insulin resistance. Logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence intervals for a self-reported history of kidney stones across tertiles of HOMA-IR, insulin and adiponectin. RESULTS: Of the participants, 84 men (15.6%) and 35 women (6.9%) had a history of kidney stones. Age, body mass index, waist circumference, systolic and diastolic blood pressures, HOMA-IR and insulin were significantly higher in women with than in women without kidney stones. There was no difference in adiponectin level between subjects with and without a history of kidney stones in either sex. Furthermore, a significant positive trend was observed in the age-adjusted OR for a history of kidney stones across insulin tertiles (P-value for trend = 0.04) in women. CONCLUSIONS: For Japanese women, HOMA-IR and insulin are associated with a history of kidney stones. The findings suggest that MetS components could increase the risk of kidney stones through subclinical hyperinsulinemia and insulin resistance.