RESUMEN
OBJECTIVES: To investigate the relationship between cognitive performance and cognitive health appraisals across non-Hispanic White, non-Hispanic Black, and Hispanic older adults in the United States and to explore within-group variations by examining interactions between cognitive performance and background and health variables. METHOD: The sample (N = 3,099) included 2,260 non-Hispanic White, 498 non-Hispanic Black, and 341 Hispanic adults aged 65 or older, from the 2016-2017 Harmonized Cognitive Assessment Protocol. Regression models of cognitive health appraisals, indicated by self-rated cognitive health, were examined in the entire sample and in racial and ethnic subgroups to test direct and interactive effects of cognitive performance, indicated by the Mini-Mental State Examination (MMSE). RESULTS: The regression model for the entire sample showed direct effects of cognitive performance and race/ethnicity on cognitive health appraisals, as well as a significant interaction between cognitive performance and being non-Hispanic Black. Cognitive performance and cognitive health appraisals were positively associated in non-Hispanic Whites but not significantly associated in non-Hispanic Blacks. Our subsequent analysis within each racial/ethnic group showed that the effect of cognitive performance in non-Hispanic Blacks and Hispanics became either reversed or nonsignificant when background and health variables were considered. Modification by age or chronic medical conditions in each racial and ethnic group was also observed. CONCLUSION: Overall, these findings suggest that perceptions and appraisals of cognitive health vary by race and ethnicity and hold implications for how these differences should be considered in research and practice with diverse groups of older adults.
Asunto(s)
Etnicidad , Hispánicos o Latinos , Anciano , Enfermedad Crónica , Cognición , Humanos , Grupos Raciales , Estados UnidosAsunto(s)
Infecciones Relacionadas con Catéteres/complicaciones , Infecciones Relacionadas con Catéteres/terapia , Discectomía Percutánea/métodos , Trombectomía/métodos , Trombosis/complicaciones , Trombosis/terapia , Adulto , Ecocardiografía , Femenino , Corazón/diagnóstico por imagen , Humanos , VacioRESUMEN
Nitrogen-doped nano-onions (NNO) were prepared as electrocatalytic materials for the oxygen reduction reaction (ORR). The nano-onions (NO), spherical graphitic material particles, were prepared by pyrolysis of nanodiamonds (ND). Oxidized NO (ONO) was prepared from NO by a modified Hummers' method, and this was mixed with urea, followed by pyrolysis, resulting in the formation of NNO. The nitrogen content and molar ratio of nitrogen-containing groups in the NNOs were varied by controlling the oxygen content of ONO to explore the effect of nitrogen content on the ORR activity. The formation of NO was confirmed by Raman spectroscopy, X-ray diffraction analysis, and high-resolution transmission electron microscopy. X-ray photoelectron spectroscopy analyses were conducted to confirm the formation of the NNO and the structures of the nitrogen-containing groups in the NNOs. The ORR activities of the NNOs were investigated using a rotating disk electrode. The NNOs showed a higher onset potential than that of NO, and the ORR activity of the NNO could be improved by increasing the number of active sites (nitrogen-containing groups) in the NNO. In addition, the NNO exhibited better long-term stability and resistance toward methanol crossover in the ORR than the platinum-based catalysts.
RESUMEN
A hemicurcuminoid boron difluoride complex is used as an emitter in organic light-emitting diodes, showing far red/near-infrared electroluminescence with an external quantum efficiency as high as 2.1%. This dye blended in CBP thin films shows amplified spontaneous emission with a threshold of 22 µJ cm-2 at 750 nm, making this compound attractive for organic semiconductor lasers operating in the near-infrared region.
RESUMEN
This research analyzed the effect of ß-glucan that is expected to alleviate the production of the inflammatory mediator in macrophagocytes, which are processed by the lipopolysaccharide (LPS) of Escherichia. The incubated layer was used for a nitric oxide (NO) analysis. The DNA-binding activation of the small unit of nuclear factor-κB was measured using the enzyme-linked immunosorbent assay-based kit. In the RAW264.7 cells that were vitalized by Escherichia coli (E. coli) LPS, the ß-glucan inhibited both the combatant and rendering phases of the inducible NO synthase (iNOS)-derived NO. ß-Glucan increased the expression of the heme oxygenase-1 (HO-1) in the cells that were stimulated by E. coli LPS, and the HO-1 activation was inhibited by the tin protoporphyrin IX (SnPP). This shows that the NO production induced by LPS is related to the inhibition effect of ß-glucan. The phosphorylation of c-Jun N-terminal kinases (JNK) and the p38 induced by the LPS were not influenced by the ß-glucan, and the inhibitory κB-α (IκB-α) decomposition was not influenced either. Instead, ß-glucan remarkably inhibited the phosphorylation of the signal transducer and activator of transcription-1 (STAT1) that was induced by the E. coli LPS. Overall, the ß-glucan inhibited the production of NO in macrophagocytes that was vitalized by the E .coli LPS through the HO-1 induction and the STAT1 pathways inhibition in this research. As the host immune response control by ß-glucan weakens the progress of the inflammatory disease, ß-glucan can be used as an effective immunomodulator.
RESUMEN
BACKGROUND AND OBJECTIVE: Daidzein is an isoflavone abundant in soybeans, kudzu root and red clover, which have been widely studied for its therapeutic potential. The present study was designed to evaluate the effects of daidzein on alveolar bone loss and internal microstructures of bone in a rat model of experimental periodontitis by assessing morphological data obtained from micro-computed tomography (micro-CT). MATERIAL AND METHODS: Twenty-four male Sprague-Dawley rats were randomly assigned to the following three groups comprising eight animals each: the nonligation (NL) group; the ligation (L) group; and the ligation+daidzein (LD) group. To induce periodontitis, a 4-0 braided silk ligature was tied around the cervical area of the lower-right first molars of rats in groups L and LD. Rats in the LD group were given daily doses of daidzein (10 mg/kg of body weight) by intraperitoneal injection immediately after ligature placement. Two weeks after the placement of ligatures, mandibular block biopsies were scanned using a micro-CT system. RESULTS: Daily administration of daidzein strongly suppressed the ligature-induced loss of alveolar bone height. In addition, when rats were treated with daidzein, the ligature-induced decrease in the bone volume fraction was significantly recovered. Furthermore, daidzein significantly reversed ligature-induced deteriorations in the microarchitecture parameters of trabecular bone, such as trabecular thickness, bone mineral density, trabecular separation and structure model index. CONCLUSION: The study presented here demonstrates, for the first time, that daidzein effectively reduces alveolar bone destruction resulting from experimental periodontitis in rats. Further studies are necessary for the translation of this compound clinically to improve the outcomes of patients diagnosed with periodontitis.
Asunto(s)
Periodontitis , Pérdida de Hueso Alveolar/inducido químicamente , Animales , Densidad Ósea , Masculino , Ratas , Ratas Sprague-Dawley , Microtomografía por Rayos XRESUMEN
To understand the role of myeloid differentiation factor 88 (MyD88) expressed by donor bone marrow (BM) in the pathophysiology of graft-vs.-host disease (GVHD), we investigated the effects of transplantation of MyD88-deficient T cell-depleted BM (MyD88KO TCD-BM) on the severity of GVHD. Transplantation with MyD88KO TCD-BM aggravated GVHD; serious gut damage was evident, with high infiltration of T cells into the intestines of recipients and markedly reduced expansion of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs). MDSCs from MyD88KO mice were defective in inducing donor T-cell apoptosis and inhibiting T-cell proliferation. Supplementation of transplanted mice with MDSCs from wild-type mice, but not MyD88KO mice, attenuated GVHD severity with reduced intestinal T-cell infiltration in MyD88KO TCD-BM recipients. Pretreatment of BM donors with lipopolysaccharide to increase MDSC levels and MyD88 transcription in the TCD-BM transplant alleviated GVHD severity and intestinal T-cell infiltration. The T cell/MDSC ratios were correlated with intestinal GVHD severity in both animal models and human patients. This study indicates that MyD88-dependent MDSC expansion from donor BM is critical for protection against fatal intestinal GVHD.
Asunto(s)
Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped/inmunología , Intestinos/inmunología , Factor 88 de Diferenciación Mieloide/metabolismo , Células Supresoras de Origen Mieloide/inmunología , Complicaciones Posoperatorias/inmunología , Linfocitos T/inmunología , Enfermedad Aguda , Animales , Apoptosis , Proliferación Celular , Células Cultivadas , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Intestinos/patología , Depleción Linfocítica , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 88 de Diferenciación Mieloide/genética , Complicaciones Posoperatorias/prevención & controlRESUMEN
BACKGROUND: Decreased bone mineral density (BMD) in patients with obstructive lung disease (OLD) is well known. However, the relationship between BMD and asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is not yet known. OBJECTIVE: To determine the relationship between ACOS and decreased BMD. DESIGN: We evaluated the relationship between OLD phenotypes and decreased BMD in subjects from the Korean National Health and Nutrition Survey IV and V (2008-2011). Data on 979 subjects who underwent spirometry and dual-energy X-ray absorptiometry were included in the study. RESULTS: Patients with ACOS had lower femur, femur neck and lumbar T-scores than those with COPD (P = 0.048, P = 0.001 and P = 0.002, respectively). On multivariate logistic regression analysis, the ACOS group had a two-fold higher risk of developing osteopenia and low BMD compared to the COPD group (OR 1.960, 95%CI 1.011-3.800, P = 0.046; OR 1.974, 95%CI 1.019-3.824, P = 0.044). CONCLUSION: The rate of bone loss differed among subjects with the asthma, COPD and ACOS OLD phenotypes. In particular, patients with ACOS had a higher risk of developing osteopenia and low BMD than those with COPD.
Asunto(s)
Asma/fisiopatología , Densidad Ósea , Enfermedades Óseas Metabólicas/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Absorciometría de Fotón , Anciano , Asma/complicaciones , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Encuestas Nutricionales , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , República de Corea/epidemiología , Estudios Retrospectivos , Espirometría , SíndromeRESUMEN
SETTING: Hospitalised patients with community-acquired pneumonia (CAP) in a tertiary referral hospital in South Korea. OBJECTIVE: To determine the burden of vitamin D deficiency in patients hospitalised with CAP and to investigate whether vitamin D deficiency affected clinical outcomes. DESIGN: Serum 25-hydroxyvitamin D (25[OH]D) levels were measured at admission; vitamin D deficiency was defined as 25(OH)D <20 ng/ml. Data were retrospectively analysed for incidence of vitamin D deficiency. The primary outcome was the relationship between serum vitamin D concentration and 28-day all-cause mortality in CAP. RESULTS: The mean age was 68.1 years (standard deviation [SD] ± 14.6), and the mean pneumonia severity index was 98.0 (± SD 28.6). Of the 797 patients (males 66.0%), 641 (80.4%) had vitamin D deficiency. Overall mean serum 25(OH)D level was 14.0 ± 7.4 ng/ml. The 28-day all-cause mortality rate in vitamin D-deficient patients was significantly higher than in non-deficient patients (8.3% vs. 2.6%, P = 0.01), and serum vitamin D level was negatively associated with risk of 28-day mortality in CAP after adjustment for pneumonia severity index and serum lactate levels (OR 0.94, 95%CI 0.90-0.99, P < 0.01). CONCLUSION: The prevalence of vitamin D deficiency was ~80% in patients hospitalised with CAP. Vitamin D deficiency was also a significant predictor of increased 28-day all-cause mortality.
Asunto(s)
Infecciones Comunitarias Adquiridas/mortalidad , Neumonía/mortalidad , Deficiencia de Vitamina D/sangre , Vitamina D/análogos & derivados , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Infecciones Comunitarias Adquiridas/sangre , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/terapia , Comorbilidad , Femenino , Hospitalización , Humanos , Incidencia , Ácido Láctico/sangre , Masculino , Persona de Mediana Edad , Neumonía/sangre , Neumonía/diagnóstico , Neumonía/terapia , Prevalencia , Pronóstico , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Centros de Atención Terciaria , Factores de Tiempo , Vitamina D/sangre , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/mortalidadRESUMEN
BACKGROUND AND OBJECTIVE: Caffeic acid phenethyl ester (CAPE) has numerous potentially beneficial properties, including antioxidant, immunomodulatory and anti-inflammatory activities. However, the effect of CAPE on periodontal disease has not been studied before. This study was designed to investigate the efficacy of CAPE in ameliorating the production of proinflammatory mediators in macrophages activated by lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in periodontal disease. MATERIAL AND METHODS: LPS from P. intermedia ATCC 25611 was isolated by using the standard hot phenol-water method. Culture supernatants were assayed for nitric oxide (NO), interleukin (IL)-1ß and IL-6. We used real-time polymerase chain reaction to quantify inducible NO synthase, IL-1ß, IL-6, heme oxygenase (HO)-1 and suppressors of cytokine signaling (SOCS) 1 mRNA expression. HO-1 protein expression and levels of signaling proteins were assessed by immunoblot analysis. DNA-binding activities of NF-κB subunits were analyzed by using the enzyme-linked immunosorbent assay-based kits. RESULTS: CAPE exerted significant inhibitory effects on P. intermedia LPS-induced production of NO, IL-1ß and IL-6 as well as their mRNA expression in RAW264.7 cells. CAPE-induced HO-1 expression in cells activated with P. intermedia LPS, and selective inhibition of HO-1 activity by tin protoporphyrin IX attenuated the inhibitory effect of CAPE on LPS-induced NO production. CAPE did not interfere with IκB-α degradation induced by P. intermedia LPS. Instead, CAPE decreased nuclear translocation of NF-κB p65 and p50 subunits induced with LPS, and lessened LPS-induced p50 binding activity. Further, CAPE showed strong inhibitory effects on LPS-induced signal transducer and activator of transcription 1 and 3 phosphorylation. Besides, CAPE significantly elevated SOCS1 mRNA expression in P. intermedia LPS-stimulated cells. CONCLUSION: Modulation of host response by CAPE may represent an attractive strategy towards the treatment of periodontal disease. In vivo studies are required to appraise the potential of CAPE further as an immunomodulator in the treatment of periodontal disease.
Asunto(s)
Ácidos Cafeicos/metabolismo , Citocinas/metabolismo , Factores Inmunológicos/metabolismo , Lipopolisacáridos/metabolismo , Macrófagos/efectos de los fármacos , Óxido Nítrico/metabolismo , Alcohol Feniletílico/análogos & derivados , Animales , Perfilación de la Expresión Génica , Lipopolisacáridos/aislamiento & purificación , Ratones , FN-kappa B/metabolismo , Alcohol Feniletílico/metabolismo , Prevotella intermedia/química , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Lung cancer is the number one cancer killer, and metastasis is the main cause of high mortality in lung cancer patients. However, mechanisms underlying the development of lung cancer metastasis remain unknown. Using genome-wide transcriptional analysis in an experimental metastasis model, we identified laminin γ2 (LAMC2), an epithelial basement membrane protein, to be significantly upregulated in lung adenocarcinoma metastatic cells. Elevated LAMC2 increased traction force, migration, and invasion of lung adenocarcinoma cells accompanied by the induction of epithelial-mesenchymal transition (EMT). LAMC2 knockdown decreased traction force, migration, and invasion accompanied by EMT reduction in vitro, and attenuated metastasis in mice. LAMC2 promoted migration and invasion via EMT that was integrin ß1- and ZEB1-dependent. High LAMC2 was significantly correlated with the mesenchymal marker vimentin expression in lung adenocarcinomas, and with higher risk of recurrence or death in patients with lung adenocarcinoma. We suggest that LAMC2 promotes metastasis in lung adenocarcinoma via EMT and may be a potential therapeutic target.
Asunto(s)
Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Laminina/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Adenocarcinoma del Pulmón , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Transición Epitelial-Mesenquimal/genética , Transición Epitelial-Mesenquimal/fisiología , Femenino , Humanos , Laminina/genética , RatonesRESUMEN
Electro-optic switching of refraction is experimentally demonstrated in a phase-discontinuity complementary metasurface twisted nematic cell. The phase-discontinuity complementary metasurface is fabricated by focused-ion-beam milling, and a twisted nematic cell is constructed with complementary V-shape slot antenna metasurface. By application of an external voltage, switching is achieved between ordinary refraction and extraordinary refraction satisfying the generalized Snell's law. It has a strong implication for applications in spatial light modulation and wavelength division multiplexer/demultiplexer in a near-IR spectral range.
RESUMEN
We investigate the photophysical and amplified spontaneous emission properties of a series of monodisperse solution-processable oligofluorenes functionalized with hexyl chains at the C9 position of each fluorene unit. Thin films of these oligofluorenes are then used in organic field-effect transistors and their charge transport properties are examined. We have particularly focused our attention on the influence of oligofluorene length on the absorption and steady-state fluorescence spectra, on the HOMO/LUMO energy levels, on the photoluminescence lifetime and quantum yield as well as on the amplified spontaneous emission properties and the charge carrier mobilities. Differential scanning calorimetry and X-ray diffraction measurements demonstrate that, among all oligofluorene derivatives used in this study, only the structure and morphology of the pentafluorene film is significantly modified by a thermal treatment above the glass transition temperature, resulting in a 9 nm blue-shift of the fluorescence spectrum without significant changes in the photoluminescence quantum yield and in the amplified spontaneous emission threshold. In parallel, hole field-effect mobility is significantly increased from 8.6 × 10(-7) to 3.8 × 10(-5) cm(2) V(-1) s(-1) upon thermal treatment, due to an increase of crystallinity. This study provides useful insights into the morphological control of oligofluorene thin films and how it affects their photophysical and charge transport properties. Moreover, we provide evidence that, because of the low threshold, the tunability of the amplified spontaneous emission and the photostability of the films, these oligofluorenes are promising candidates for organic solid-state laser applications.
RESUMEN
Infertile men with azoospermia commonly have associated microdeletions in the azoospermia factor (AZF) region of the Y chromosome, sex chromosome mosaicism, or sex chromosome rearrangements. In this study, we describe an unusual 46,XX and 45,X mosaicism with a rare Y chromosome rearrangement in a phenotypically normal male patient. The patient's karyotype was 46,XX[50]/45,X[25]/46,X,der(Y)(pterâq11.222::p11.2âpter)[25]. The derivative Y chromosome had a deletion at Yq11.222 and was duplicated at Yp11.2. Two copies of the SRY gene were confirmed by fluorescence in situ hybridization analysis, and complete deletion of the AZFb and AZFc regions was shown by multiplex-PCR for microdeletion analysis. Both X chromosomes of the predominant mosaic cell line (46,XX) were isodisomic and derived from the maternal gamete, as determined by examination of short tandem repeat markers. We postulate that the derivative Y chromosome might have been generated during paternal meiosis or early embryogenesis. Also, we suggest that the very rare mosaicism of isodisomic X chromosomes might be formed during maternal meiosis II or during postzygotic division derived from the 46,X,der(Y)/ 45,X lineage because of the instability of the derivative Y chromosome. To our knowledge, this is the first confirmatory study to verify the origin of a sex chromosome mosaicism with a Y chromosome rearrangement.
Asunto(s)
Azoospermia/genética , Cromosomas Humanos X/genética , Cromosomas Humanos Y/genética , Mosaicismo , Aberraciones Cromosómicas Sexuales , Adulto , Deleción Cromosómica , Humanos , Cariotipo , Masculino , Meiosis/genética , Proteína de la Región Y Determinante del Sexo/genéticaRESUMEN
OBJECTIVE: The purposes of this study were to isolate and characterize stem cells from inflamed pulp tissue of human functional deciduous teeth (iSHFD) and to evaluate the influence of fibroblastic growth factor-2 (FGF-2) on the regenerative potential. MATERIALS AND METHODS: We successfully isolated mesenchymal stem cells (MSCs) from the inflamed dental pulp tissue of human deciduous teeth and demonstrated that their regenerative potential could be enhanced by the application of FGF-2 (20 ng ml(-1)) during ex vivo expansion. Isolated stem cells expanded in FGF-2 were characterized using a colony-forming assay, proliferation, migration, in vitro differentiation, in vivo ectopic transplantation assay, and gene expression profiling. RESULTS: MSCs isolated from the inflamed pulp tissue of functional deciduous teeth potentially possess the qualities of those from human exfoliated deciduous teeth. FGF-2 applied to iSHFD during expansion enhanced the colony-forming efficiency of these cells, increased their proliferation and migration potential, and reduced their differentiation potential in vitro. However, the ectopic transplantation of iSHFD/FGF-2 in vivo increased the formation of dentin-like material. CONCLUSION: FGF-2 expansion of stem cells from inflamed pulp tissues of human deciduous teeth can be a good source of stem cells for future clinical applications and a novel way of using discarded inflamed tissues.
Asunto(s)
Pulpa Dental/citología , Factor 2 de Crecimiento de Fibroblastos/fisiología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Pulpitis/patología , Diferenciación Celular , Células Cultivadas , Factor 2 de Crecimiento de Fibroblastos/farmacología , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Diente PrimarioRESUMEN
Electric switching of reflection resonances at near-IR spectral range is experimentally demonstrated in a reflective metamaterial twisted nematic liquid crystal cell. Reflective metamaterial composed of nano-sized double-split ring resonator aperture is fabricated by a focused ion beam milling. Two-fold rotational symmetry of double-split ring resonators allows for two orthogonal polarization-dependent reflection resonances in the reflective metamaterial. With an external voltage of 10V across 12µm cell gap, a full switching is achieved between two reflection resonances. Dynamic measurements show the time constants of switch-on and switch-off are in the order of 100ms and 10ms, respectively.
Asunto(s)
Cristales Líquidos/química , Cristales Líquidos/efectos de la radiación , Nanotecnología/instrumentación , Refractometría/instrumentación , Procesamiento de Señales Asistido por Computador/instrumentación , Resonancia por Plasmón de Superficie/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Luz , Dispersión de RadiaciónRESUMEN
BACKGROUND: Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy. METHODS: A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of their regulatory pathway. RESULTS: For cetuximab regimens, patients homozygous for the wild-type alleles (GG) of LIFR rs3729740 exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (GA and AA; P=0.022 and 0.027, respectively). For bevacizumab regimens, patients homozygous for the minor alleles (TT) of ANXA11 rs1049550 exhibited an ORR twice as high as those homozygous or heterozygous for the ancestral allele (CC and CT; P=0.031). Overall response rate gain was achieved up to 10% in patients with wild-type LIFR rs3729740 patients either with wild-type KRAS or skin toxicity (P=0.001) respectively. Specifically in clones treated with cetuximab and bevacizumab regimens, active p-ERK and MMP-9 expressions were significantly reduced in clones expressing wild-type LIFR rs3729740 (P=0.044) and in those expressing minor-type ANXA11 rs1049550 (P=0.007), respectively. CONCLUSION: LIFR rs3729740 and possibly ANXA11 rs1049550 may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed.
Asunto(s)
Anexinas/genética , Neoplasias Colorrectales/tratamiento farmacológico , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/genética , Terapia Molecular Dirigida , Metástasis de la Neoplasia/tratamiento farmacológico , Adulto , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab , Biomarcadores de Tumor/genética , Cetuximab , Neoplasias Colorrectales/genética , Supervivencia sin Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/biosíntesis , Quinasas MAP Reguladas por Señal Extracelular/genética , Femenino , Genotipo , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/genética , Persona de Mediana Edad , Metástasis de la Neoplasia/genética , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , Proteínas ras/genéticaRESUMEN
BACKGROUND AND OBJECTIVE: Interleukin-6 (IL-6) is a key proinflammatory cytokine that has been considered to be important in the pathogenesis of periodontal disease. Therefore, host-modulatory agents directed at inhibiting IL-6 appear to be beneficial in terms of attenuating periodontal disease progression and potentially improving disease susceptibility. In the current study, we investigated the effect of the flavonoid isorhamnetin on the production of IL-6 in murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. MATERIAL AND METHODS: Lipopolysaccharide from P. intermedia ATCC 25611 was isolated using the standard hot phenol-water method. Culture supernatants were collected and assayed for IL-6. We used real-time PCR to quantify IL-6 and heme oxygenase-1 (HO-1) mRNA expression. The expression of HO-1 protein and the levels of signaling proteins were monitored using immunoblot analyses. The DNA-binding activity of nuclear factor-κB (NF-κB) was analyzed using ELISA-based assay kits. RESULTS: Isorhamnetin significantly down-regulated P. intermedia LPS-induced production of IL-6 as well as its mRNA expression in RAW264.7 cells. Isorhamnetin up-regulated the expression of HO-1 at both gene transcription and translation levels in cells stimulated with P. intermedia LPS. In addition, inhibition of HO-1 activity by tin protoporphyrin IX blocked the inhibitory effect of isorhamnetin on IL-6 production. Isorhamnetin failed to prevent LPS from activating either c-Jun N-terminal kinase or p38 pathways. Isorhamnetin did not inhibit NF-κB transcriptional activity at the level of inhibitory κB-α degradation. Isorhamnetin suppressed NF-κB signaling through inhibition of nuclear translocation and DNA binding activity of NF-κB p50 subunit and attenuated signal transducer and activator of transcription 1 signaling. CONCLUSION: Although further research is required to clarify the detailed mechanism of action, we propose that isorhamnetin may contribute to blockade of the host-destructive processes mediated by IL-6 and could be a highly efficient modulator of the host response in the treatment of inflammatory periodontal disease. Further research in animal models of periodontitis is required to better evaluate, the potential of isorhamnetin as a novel agent for treating periodontal disease.
Asunto(s)
Antiinflamatorios/metabolismo , Antioxidantes/farmacología , Hemo-Oxigenasa 1/efectos de los fármacos , Interleucina-6/antagonistas & inhibidores , Lipopolisacáridos/antagonistas & inhibidores , Macrófagos/efectos de los fármacos , Proteínas de la Membrana/efectos de los fármacos , FN-kappa B/antagonistas & inhibidores , Prevotella intermedia/inmunología , Quercetina/análogos & derivados , Factor de Transcripción STAT1/antagonistas & inhibidores , Animales , Antiinflamatorios/antagonistas & inhibidores , Línea Celular , Regulación hacia Abajo , Inducción Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/biosíntesis , Proteínas I-kappa B/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/efectos de los fármacos , Macrófagos/inmunología , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/biosíntesis , Metaloporfirinas/farmacología , Ratones , Subunidad p50 de NF-kappa B/efectos de los fármacos , Biosíntesis de Proteínas/efectos de los fármacos , Protoporfirinas/farmacología , Quercetina/farmacología , Transcripción Genética/efectos de los fármacos , Regulación hacia Arriba , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacosRESUMEN
A total of 245 patients with confirmed 2009 H1N1 influenza were admitted to the intensive-care units of 28 hospitals (South Korea). Their mean age was 55.3 years with 68.6% aged >50 years, and 54.7% male. Nine were obese and three were pregnant. One or more comorbidities were present in 83.7%, and nosocomial acquisition occurred in 14.3%. In total, 107 (43.7%) patients received corticosteroids and 66.1% required mechanical ventilation. Eighty (32.7%) patients died within 30 days after onset of symptoms and 99 (40.4%) within 90 days. Multivariate logistic regression analysis showed that the clinician's decision to prescribe corticosteroids, older age, Sequential Organ Failure Assessment score and nosocomial bacterial pneumonia were independent risk factors for 90-day mortality. In contrast with Western countries, critical illness in Korea in relation to 2009 H1N1 was most common in older patients with chronic comorbidities; nosocomial acquisition occurred occasionally but disease in obese or pregnant patients was uncommon.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Enfermedad Crítica , Femenino , Humanos , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Factores de Riesgo , Adulto JovenRESUMEN
By focused ion beam milling, we fabricated near-IR reflective metamaterials consisting of nano-aperture arrays. Optimum parameters of ion beam current and accelerating voltage in the fabrication process are obtained. Nano-apertures constituting reflective metamaterial are successfully milled, and possess a reflective resonance in the near-IR spectral range. With a double-split-ring resonator structure for the nano-aperture, the intensity reflection at resonance is rendered polarization dependent. It is found that the point group symmetry of the nano-aperture array determines the amount of anisotropy in the intensity reflection. Finite-difference time-domain simulation was adopted to identify details of nano-aperture metastructures transferred from nano-aperture patterns by the focused ion beam milling.