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Acute kidney injury (AKI) is often accompanied by uremic encephalopathy resulting from accumulation of uremic toxins in brain possibly due to impaired blood-brain barrier (BBB) function. Anionic uremic toxins are substrates or inhibitors of organic anionic transporters (OATs). In this study we investigated the CNS behaviors and expression/function of BBB OAT3 in AKI rats and mice, which received intraperitoneal injection of cisplatin 8 and 20 mg/kg, respectively. We showed that cisplatin treatment significantly inhibited the expressions of OAT3, synaptophysin and microtubule-associated protein 2 (MAP2), impaired locomotor and exploration activities, and increased accumulation of uremic toxins in the brain of AKI rats and mice. In vitro studies showed that uremic toxins neither alter OAT3 expression in human cerebral microvascular endothelial cells, nor synaptophysin and MAP2 expressions in human neuroblastoma (SH-SY5Y) cells. In contrast, tumour necrosis factor alpha (TNFα) and the conditioned medium (CM) from RAW264.7 cells treated with indoxyl sulfate (IS) significantly impaired OAT3 expression. TNFα and CM from IS-treated BV-2 cells also inhibited synaptophysin and MAP2 expressions in SH-SY5Y cells. The alterations caused by TNFα and CMs in vitro, and by AKI and TNFα in vivo were abolished by infliximab, a monoclonal antibody designed to intercept and neutralize TNFα, suggesting that AKI impaired the expressions of OAT3, synaptophysin and MAP2 in the brain via IS-induced TNFα release from macrophages or microglia (termed as IS-TNFα axis). Treatment of mice with TNFα (0.5 mg·kg-1·d-1, i.p. for 3 days) significantly increased p-p65 expression and reduced the expressions of Nrf2 and HO-1. Inhibiting NF-κB pathway, silencing p65, or activating Nrf2 and HO-1 obviously attenuated TNFα-induced downregulation of OAT3, synaptophysin and MAP2 expressions. Significantly increased p-p65 and decreased Nrf2 and HO-1 protein levels were also detected in brain of AKI mice and rats. We conclude that AKI inhibits the expressions of OAT3, synaptophysin and MAP2 due to IS-induced TNFα release from macrophages or microglia. TNFα impairs the expressions of OAT3, synaptophysin and MAP2 partly via activating NF-κB pathway and inhibiting Nrf2-HO-1 pathway.
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Lesión Renal Aguda , Cisplatino , Indicán , Factor de Necrosis Tumoral alfa , Animales , Lesión Renal Aguda/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Humanos , Ratones , Masculino , Células RAW 264.7 , Ratas , Ratones Endogámicos C57BL , Transportadores de Anión Orgánico Sodio-Independiente/metabolismo , Ratas Sprague-Dawley , Sinaptofisina/metabolismo , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Uremia/metabolismo , Uremia/complicaciones , Línea Celular TumoralRESUMEN
Background and Purpose: The purpose of this study is to report the process of adapting the existing Lung Cancer Screening Health Belief Scale to be used in Chinese Americans. Methods: Guided by Flaherty et al.'s cross-cultural equivalency model, the methodology used in the adaptation process consists of four steps, including preliminary modification after a comprehensive literature review, forward and backward translation, expert review, and cognitive interviews among participants. Results: The modified culturally fitted Lung Cancer Screening Health Belief Scale included 57 items and 6 subscales, which proved highly reliable and valid through the expert review and participants' review. Conclusions: This study provided an example for a novice cross-cultural researcher to adapt an instrument to be used in another population with a different language. Further research is needed to work out a standard guideline for cross-cultural instrument adaptation.
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Comparación Transcultural , Neoplasias Pulmonares , Humanos , Detección Precoz del Cáncer , Neoplasias Pulmonares/diagnóstico , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , AsiáticoRESUMEN
OBJECTIVE: To discover novel serodiagnostic candidates for the serological diagnosis of syphilis. METHODS: Two recombinant Treponema pallidum proteins Tp0100 and Tp1016 were expressed, purified, and identified by Western Blotting. A total of 600 clinical serum samples were tested with the Tp0100-based ELISA, the Tp1016-based ELISA, and the commercial LICA Syphilis TP kit (ChIVD, Beijing, China). The sensitivities were determined by testing 340 samples from individuals with clinically diagnosed primary, secondary, latent, and tertiary syphilis. The specificities were determined by screening 260 samples from healthy controls and individuals with potentially cross-reactive infections, including leptospirosis, Lyme disease, hepatitis B, tuberculosis, rheumatoid arthritis, systemic lupus erythematosus. Kappa (κ) values were applied to compare the agreement between clinical syphilis diagnosis and the Tp0100-based ELISA, the Tp1016-based ELISA, or the LICA Syphilis TP test. RESULTS: Using clinical syphilis diagnosis as the gold standard, Tp0100 exhibited an overall sensitivity of 95.6% and specificity of 98.1% for testing IgG antibody while Tp1016 demonstrated only an overall sensitivity of 75.0% and specificity of 79.6%. In contrast, the LICA Syphilis TP test revealed an overall sensitivity of 97.6% and specificity of 96.2%. In addition, the overall percent agreement and corresponding κ values were 96.7% (95% CI 95.6%-97.8%) and 0.93 for the Tp0100-based ELISA, 77.0% (95% CI 74.3%-79.7%) and 0.54 for the Tp1016-based ELISA, and 97.0% (95% CI 96.0%-98.0%) and 0.94 for the LICA Syphilis TP test, respectively. CONCLUSION: The recombinant T. pallidum protein Tp0100 shows promise as a novel diagnostic antigen in the serological tests for syphilis.
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Sífilis , Treponema pallidum , Anticuerpos Antibacterianos , Antígenos Bacterianos , Ensayo de Inmunoadsorción Enzimática , Humanos , Proteínas Recombinantes , Sensibilidad y Especificidad , Pruebas Serológicas , Sífilis/diagnóstico , Serodiagnóstico de la Sífilis , Treponema pallidum/genéticaRESUMEN
Stimuli-responsive polymers with complicated but controllable shape-morphing behaviors are critically desirable in several engineering fields. Among the various shape-morphing materials, cross-linked polymers with exchangeable bonds in dynamic network topology can undergo on-demand geometric change via solid-state plasticity while maintaining the advantageous properties of cross-linked polymers. However, these dynamic polymers are susceptible to creep deformation that results in their dimensional instability, a highly undesirable drawback that limits their service longevity and applications. Inspired by the natural ice strategy, which realizes creep reduction using crystal structure transformation, we evaluate a dynamic cross-linked polymer with tunable creep behavior through topological alternation. This alternation mechanism uses the thermally triggered disulfide-ene reaction to convert the network topology - from dynamic to static - in a polymerized bulk material. Thus, such a dynamic polymer can exhibit topological rearrangement for thermal plasticity at 130°C to resemble typical dynamic cross-linked polymers. Following the topological alternation at 180°C, the formation of a static topology reduces creep deformation by more than 85% in the same polymer. Owing to temperature-dependent selectivity, our cross-linked polymer exhibits a shape-morphing ability while enhancing its creep resistance for dimensional stability and service longevity after sequentially topological alternation. Our design enriches the design of dynamic covalent polymers, which potentially expands their utility in fabricating geometrically sophisticated multifunctional devices.
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Shape-reconfigurable materials are crucial in many engineering applications. However, because of their isotropic deformability, they often require complex molding equipment for shaping. A polymeric origami structure that follows predetermined deformed and non-deformed patterns at specific temperatures without molding is demonstrated. It is constructed with a heterogeneous (dynamic and static) network topology via light-induced programming. The corresponding spatio-selective thermal plasticity creates varied deformability within a single polymer. The kinematics of site-specific deformation allows guided origami deployment in response to external forces. Moreover, the self-locking origami can fix its geometry in specific states without pressurization. These features enable the development of shape-reconfigurable structures that undergo on-demand geometry changes without requiring bulky or heavy equipment. The concept enriches polymer origamis, and could be applied with other polymers having similar chemistries. Overall, it is a versatile material for artificial muscles, origami robotics, and non-volatile mechanical memory devices.
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Polímeros , Robótica , Polímeros/química , TemperaturaRESUMEN
Liver failure is associated with increased levels of brain aromatic amino acids (AAAs), whose transport across the blood-brain barrier (BBB) is mainly mediated by L-amino acid transporter 1 (LAT1). We aimed to investigate whether liver failure induced by bile duct ligation (BDL) increases levels of brain AAAs by affecting the expression and function of LAT1. The LAT1 function was assessed using the brain distribution of gabapentin. It was found that BDL significantly increased levels of gabapentin, phenylalanine, and tryptophan in the cortex, hippocampus, and striatum of rats, and upregulated the expression of total LAT1 protein in hippocampus and striatum as well as cortex membrane LAT1 protein. HCMEC/D3 served as in vitro BBB model, and the data showed that both the serum of BDL rats and bilirubin induced LAT1 expression and function, while bilirubin oxidase almost abolished the upregulation of LAT1 protein by bilirubin and the serum of BDL rats. The enhanced function and expression of LAT1 were also observed in the hippocampus and striatum of hyperbilirubinemia rats. Both aryl hydrocarbon receptor (AhR) antagonist α-naphthoflavone and AhR silencing obviously attenuated the upregulation of LAT1 protein by bilirubin or omeprazole. This study provides the first evidence that BDL upregulates LAT1 at the rat BBB, attributed to the activation of AhR by the increased plasma bilirubin. The results highlight the mechanisms causing BDL-increased levels of brain AAAs and their physiological significance.
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Recycling of epoxy resin and its composites is extremely difficult due to its thermoset nature. In this study, we proposed the environmentally-friendly recycling system of epoxy resin with dynamic covalent bonding in the assistance of cysteine-containing tripeptide, so-called glutathione. The glutathione attached on the epoxy resin and resulted in the cleavage of dynamic disulfide bonds of epoxy resin through thiol-disulfide exchange reaction between the thiol group of glutathione and disulfide bonding of epoxy resin, followed by the scission of epoxy networks. Therefore, the degraded epoxy residue was dissolved into chloroform. Finally, this resulting product could be reused as reagent for preparation the new epoxy materials with approximately 90% of initial mechanical strength via regeneration of disulfide bonding through heating. This work demonstrated the different aspect to understand the decomposition and recycling of thermosetting networks and the wide application under more environmentally friendly condition.
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BACKGROUND: Iron overload, which is common in patients with haematological disorders, is known to have a suppressive effect on haematogenesis. However, the mechanism for this effect is still unclear. The antioxidant curcumin has been reported to protect against iron overload-induced bone marrow damage through an as-yet-unknown mechanism. METHODS: We established iron overload cell and mouse models. Mitochondrial reactive oxygen species (mROS) levels, autophagy levels and the SIRT3/SOD2 pathway were examined in the models and in the bone marrow of patients with iron overload. RESULTS: Iron overload was shown to depress haematogenesis and induce mitochondrion-derived superoxide anion-dependent autophagic cell death. Iron loading decreased SIRT3 protein expression, promoted an increase in SOD2, and led to the elevation of mROS. Overexpression of SIRT3 reversed these effects. Curcumin treatment ameliorated peripheral blood cells generation, enhanced SIRT3 activity, decreased SOD2 acetylation, inhibited mROS production, and suppressed iron loading-induced autophagy. CONCLUSIONS: Our results suggest that curcumin exerts a protective effect on bone marrow by reducing mROS-stimulated autophagic cell death in a manner dependent on the SIRT3/SOD2 pathway.
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Médula Ósea/patología , Curcumina/farmacología , Hematopoyesis , Sobrecarga de Hierro/metabolismo , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 3/metabolismo , Superóxido Dismutasa/metabolismo , Acetilación/efectos de los fármacos , Animales , Autofagia/efectos de los fármacos , Médula Ósea/efectos de los fármacos , Médula Ósea/metabolismo , Citoprotección/efectos de los fármacos , Hematopoyesis/efectos de los fármacos , Humanos , Sobrecarga de Hierro/patología , RatonesRESUMEN
The incidence of peri-implant bone loss is high, and is a difficult condition to treat. Previous studies have shown that titanium (Ti) ions released from implants can lead to osteoblast cell damage, but the specific mechanisms have not been elucidated. The present study established a Ti ion damage osteoblast cell model. The levels of mitochondrionderived reactive oxygen species (mROS) and autophagy, cell viability and the sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) pathway were examined in this model. It was found that Ti ions decreased osteoblast viability. Moreover, with increased Ti ion concentration, the expression levels of microtubule associated protein 1 light chain 3α (LC3) progressively increased, P62 decreased, autophagic flow increased and mROS levels increased. After the addition of an autophagy inhibitor Bafilomycin A1 and MitoTEMPO, a mitochondrial antioxidant, the production of mROS was inhibited, the level of autophagy was decreased and cell activity was improved. In addition, with increased Ti ion concentration, the activity of SOD2 decreased, the acetylation level of SOD2 increased, the SIRT3 mRNA and protein expression levels decreased, and the activity of SIRT3 was significantly decreased. Furthermore, it was demonstrated that SIRT3 overexpression reduced the acetylation of SOD2 and increased the activity of SOD2, as well as reducing the production of mROS and the expression level of LC3, thus increasing cell viability. Therefore, the present results suggested that excessive production of mROS induced by Ti ions led to autophagic cell death of osteoblasts, which is dependent on the SIRT3/SOD2 pathway.
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Muerte Celular Autofágica/genética , Mitocondrias/metabolismo , Osteoblastos/metabolismo , Sirtuina 3/metabolismo , Superóxido Dismutasa/metabolismo , Titanio/toxicidad , Acetilación , Antioxidantes/farmacología , Muerte Celular Autofágica/efectos de los fármacos , Autofagia/efectos de los fármacos , Autofagia/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Células Cultivadas , Humanos , Iones/metabolismo , Iones/toxicidad , Macrólidos/farmacología , Proteínas Asociadas a Microtúbulos/metabolismo , Compuestos Organofosforados/farmacología , Osteoblastos/efectos de los fármacos , Osteoblastos/enzimología , Piperidinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/genética , Sirtuina 3/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: Hypervitaminosis A, alcoholism or medical treatment for acute promyelocytic leukaemia may cause unphysiologically high accumulation of all-trans retinoic acid (ATRA), which could inhibit osteoblastogenesis, thereby triggering osteoporosis. We have shown that bone morphogenetic protein-2 (BMP-2) can only partially antagonize the inhibitive effects of ATRA. In this study, we hypothesized that antagonists of retinoic acid receptors (RARs) could further antagonize the inhibitive effect of ATRA and rescue BMP2-induced osteoblastogenesis. MATERIALS AND METHODS: We first screened the dose-dependent effects of the specific antagonists of RAR α, ß and γ and transforming growth factor-beta receptor (ER-50891, LE-135, MM11253, and SB-43142, respectively) on ATRA-induced inhibition of the total cell metabolic activity and proliferation of preosteoblasts. We selected ER-50891 and tested its effects on osteoblastogenesis with the presence or absence of 1 µM ATRA and/or 200 ng/mL BMP-2. We measured the following parameters: Alkaline phosphatase activity (ALP), osteocalcin (OCN) expression and extracellular matrix mineralization as well as the level of phosphorylated Smad1/5. RESULTS: ER-50891 but not LE-135, MM11253, or SB-431542 significantly antagonized the inhibition of ATRA and enhanced the total cell metabolic activity and proliferation of preosteoblasts. Dose-dependent assays show ER-50891 could also rescue ATRA inhibited OCN expression and mineralization with or without the induction of BMP. ER-50891 also suppressed the ALP activity that was synergistically enhanced by BMP and ATRA. Neither ATRA, nor ER-50891 or their combination significantly affected the level of BMP-induced phosphorylated Smad1/5. CONCLUSION: The antagonist of RARα, ER-50891 could significantly attenuate ATRA's inhibitive effects on BMP 2-induced osteoblastogenesis.
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Proteína Morfogenética Ósea 2/metabolismo , Diferenciación Celular/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Receptor alfa de Ácido Retinoico/antagonistas & inhibidores , Tretinoina/antagonistas & inhibidores , Células 3T3 , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Ratones , Receptor alfa de Ácido Retinoico/metabolismo , Tretinoina/farmacologíaRESUMEN
To determine the prognostic value of baseline mean platelet volume (MPV) in diffuse large B-cell lymphoma (DLBCL) patients. We retrospectively analyzed 161 DLBCL patients who received R-CHOP chemotherapy. The associations between MPV and clinicopathological factors were assessed. A low MPV (MPV ≤ 9.1 fl, cut-off was calculated by receiver operating characteristics) was not associated with any other clinicopathological factors. Patients with MPV ≤ 9.1 fl experienced a shorter progression-free survival (PFS) (2-year PFS rate, 60.6% vs 84.0%, P = 0.003) and overall survival (OS) (2-year OS rate, 70.4% vs 87.9%, P = 0.030), compared with those with MPV > 9.1 fl. The multivariate analysis demonstrated that MPV ≤ 9.1 fl was an independent prognostic factor of OS (Hazard Ratio [HR] = 0.588, P = 0.045) and PFS (HR = 0.456, P = 0.010). Therefore, we demonstrated that low baseline MPV is an independent prognostic marker of poor outcome in patients with DLBCL.
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Linfoma de Células B Grandes Difuso/sangre , Volúmen Plaquetario Medio/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Tasa de Supervivencia , Adulto JovenRESUMEN
It is generally believed that there is correlation between cancer prognosis and pretreatment PLR and NLR. However, there are limited data about their role in diffuse large B cell lymphoma (DLBCL). This study aims to determine the prognostic value of pretreatment PLR and NLR for patients who have DLBCL. The associations between clinical characteristics and NLR and PLR were evaluated among 182 DLBCL patients from January 2005 to June 2016. The optimal cutoff values for high PLR (⩾150) and NLR (⩾2.32) in prognosis prediction were determined. The effect of NLR and PLR on survival was evaluated through multivariate Cox regression analysis, univariate analysis, and log-rank test. According to the evaluation results, patients with high NLR and PLR had significantly shorter OS (P=0.026 and P=0.035) and PFS (P=0.024 and P=0.022) compared with those who have low PLR and NLR. On multivariate analyses, IPI>2, elevated LDH, and PLR⩾2.32 were prognostic factors for OS and PFS in DLBCL patients. Therefore, we demonstrated that high PLR and NLR predicted adverse prognostic factors in DLBCL patients.
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Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/mortalidad , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Plaquetas , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Humanos , Recuento de Linfocitos , Linfocitos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neutrófilos , Recuento de Plaquetas , Prednisona/administración & dosificación , Prednisona/efectos adversos , Rituximab , Tasa de Supervivencia , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
PURPOSE: This study investigated the effect of topography on cell behavior by screening polydimethylsiloxane (PDMS) molds with different nanoscale micropatterns to determine the ideal surface characteristics for attachment of human epithelial cells. MATERIALS AND METHODS: A soft PDMS mold with regular dot arrays was fabricated based on an aluminum oxide template with ordered nanotube arrays and used as a substrate for cell culture. Cell proliferation, spread, and morphology, as well as features of the extracellular matrix and the actin cytoskeleton were assessed. DISCUSSION: Cells grown on 100-nm regular dot arrays had the highest proliferation rate and spread, with the longest pseudopodia; they showed robust actin distribution relative to the control group. CONCLUSION: Three-dimensional PDMS microstructures with 100 nm regular dot arrays were the most effective surface for epithelial cell attachment. These findings can aid in the manufacture of superior materials for use in implants to better integrate into recipient tissue.
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Técnicas de Cultivo de Célula , Implantes Dentales , Células Epiteliales/citología , Encía/citología , Citoesqueleto de Actina/fisiología , Proliferación Celular/fisiología , Dimetilpolisiloxanos/farmacología , Matriz Extracelular/fisiología , Humanos , Inmunohistoquímica , Técnicas In Vitro , Microscopía Confocal , Microscopía Electrónica de Rastreo , Propiedades de SuperficieRESUMEN
PURPOSE: To investigate the feasibility of using sol gel technique to produce thin layer nano silicon dioxide on zirconia ceramic surface and the effect of improving shear bond strength between zirconia and veneer porcelain. METHODS: The presintered zirconia specimen was cut into a rectangle block piece (15 mm×10 mm×2.5 mm), a total of 40 pieces were obtained and divided into 4 groups, each group had 10 pieces. Four different treatments were used in each group respectively. Pieces in group A (control group) were only sintered at 1450°C to crystallization; pieces in group B underwent 30% nano silica sol infiltration first and then were sintered at 1450°C to crystallization; piece in group C underwent crystallization first at 1450°C, then 30% nano silica sol infiltration and were sintered at 1450°C again; pieces in group D was coated by nano silica sol and then sintered at 1450°C to crystallization; ten rectangle block pieces (12 mm×8 mm×2 mm) in group E were made. Cylinder veneers 5 mm in diameter and 4 mm in height were produced in each group and the shear bond strength was tested. Data were statistically analyzed by SPSS 19.0 software package. RESULTS: The shear bond strength of the 5 group specimens were: (28.12±2.95) MPa in group A, (31.09±3.94) MPa in group B, (25.60±2.45) MPa in group C, (31.75±4.90) MPa in group D, (28.67±3.95) MPa in group E, respectively. Significant differences existed between the 5 groups, and group C had significant difference compared with group B and D. CONCLUSIONSï¼â Use of nano silicon sol gel on presintered zirconia surface to make thin layer of nano silicon dioxide can improve the shear bond strength between zirconia and veneer; â¡Using nano silicon sol gel on crystallization zirconia surface to make thin layer of nano silicon dioxide will decrease the shear bond strength between zirconia and veneer; ⢠Zirconia veneer bilayer ceramic has the same shear bond strength with porcelain fused to Ni Cr alloy; â£Use of sol gel technique to produce thin layer nano silicon dioxide on zirconia ceramic surface is feasible and can improve shear bond strength between zirconia and veneer porcelain.
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Porcelana Dental/química , Coronas con Frente Estético , Ensayo de Materiales , Polimetil Metacrilato , Resistencia al Corte , Estrés Mecánico , Circonio , Óxido de Aluminio , Cerámica , Recubrimiento Dental Adhesivo , Materiales Dentales , Humanos , Dióxido de Silicio , Propiedades de SuperficieRESUMEN
BACKGROUND: Gut-derived bacteraemia is a major complication in patients with haematological malignancy after chemotherapy. OBJECTIVE: Our study aimed to investigate the role of proton pump inhibitors (PPIs) in the occurrence of gut-derived bacteraemia. METHODS: We compared data from 92 hospitalized haematological malignancy patients after chemotherapy with gut-derived bacteraemia, collected from January 2009 to July 2015, with those of 92 contemporaneous, hospitalized haematological malignancy patients without bacteraemia. We evaluated PPIs use and analysed the effects of covariates. RESULTS: Patients with gut-derived bacteraemia had a significantly higher incidence of PPIs use (69.6%) than that of controls (47.8%). Of the patients with gut-derived bacteraemia, only 44.6% had a documented indication for PPIs therapy. The antibacterial prophylaxis rate was 38.0% in the bacteraemia group and 58.7% in the non-antibacterial group. Based on multivariable logistic regression analysis, only PPIs use (P = 0.00, odds ratio (OR) = 0.546) was found to be associated with the risk of bacteraemia whereas antibacterial prophylaxis (P = 0.00, OR = 0.652) was protective. There were no significant differences in demographics, malignancy status, length of neutropenia, complications, or steroid use between the gut-derived bacteraemia and control group. CONCLUSIONS: This study suggests a potential association between PPIs use and development of gut-derived bacteraemia in haematological malignancy patients after chemotherapy.
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Antibacterianos/uso terapéutico , Bacteriemia/microbiología , Neoplasias Hematológicas/tratamiento farmacológico , Inhibidores de la Bomba de Protones/farmacología , Adulto , Estudios de Casos y Controles , Femenino , Neoplasias Hematológicas/complicaciones , Humanos , Masculino , Inhibidores de la Bomba de Protones/uso terapéutico , Estudios RetrospectivosRESUMEN
The gene for Small Adipocyte Factor 1, Smaf1 (also known as adipogenin, ADIG), encodes a â¼600 base transcript that is highly upregulated during 3T3-L1 in vitro adipogenesis and markedly enriched in adipose tissues. Based on the lack of an obvious open reading frame in the Smaf1 transcript, it is not known if the Smaf1 gene is protein coding or non-coding RNA. Using a peptide from a putative open reading frame of Smaf1 as antigen, we generated antibodies for western analysis. Our studies prove that Smaf1 encodes an adipose-enriched protein which in western blot analysis migrates at â¼10 kDa. Rapid induction of Smaf1 protein occurs during in vitro adipogenesis and its expression in 3T3-L1 adipocytes is positively regulated by insulin and glucose. Moreover, siRNA studies reveal that expression of Smaf1 in adipocytes is wholly dependent on PPARγ. On the other hand, use of siRNA for Smaf1 to nearly abolish its protein expression in adipocytes revealed that Smaf1 does not have a major role in adipocyte triglyceride accumulation, lipolysis or insulin-stimulated pAkt induction. However, immunolocalization studies using HA-tagged Smaf1 reveal enrichment at adipocyte lipid droplets. Together our findings show that Smaf1 is a novel small protein endogenous to adipocytes and that Smaf1 expression is closely tied to PPARγ-mediated signals and the adipocyte phenotype.
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Adipocitos/metabolismo , Adipogénesis/fisiología , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Gotas Lipídicas/metabolismo , Proteínas Nucleares/metabolismo , Células 3T3-L1 , Adipocitos/citología , Animales , Regulación de la Expresión Génica/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Peso Molecular , Proteínas Nucleares/química , PPAR gamma/metabolismoRESUMEN
A series of 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that the target compounds exhibited good acetylcholinesterase (AChE) inhibitory potencies, high selectivity toward AChE over butyrylcholinesterase (BuChE), potential antioxidant activities and significant inhibitory potencies of self-induced beta-amyloid peptide (Aß) aggregation. In particular, compound 14c had the strongest AChE inhibitory activity with IC50 value of 12.8 nM, potent inhibition of self-induced Aß1-42 aggregation with inhibition ratio of 33.8% at 25 µM. Moreover, compound 14c acted as an antioxidant, as well as a neuroprotectant. Furthermore, 14c could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 14c might be a potential multifunctional candidate for the treatment of AD.
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Enfermedad de Alzheimer/tratamiento farmacológico , Antioxidantes/farmacología , Inhibidores de la Colinesterasa/farmacología , Diseño de Fármacos , Flavonas/farmacología , Tacrina/análogos & derivados , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/síntesis química , Antioxidantes/química , Butirilcolinesterasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Relación Dosis-Respuesta a Droga , Electrophorus , Equidae , Flavonas/síntesis química , Flavonas/química , Estructura Molecular , Células PC12 , Ratas , Relación Estructura-Actividad , Tacrina/síntesis química , Tacrina/química , Tacrina/farmacologíaRESUMEN
AIM: Mussel-mimetic, bioadhesive polymers are synthesized from plant-derived sources. The strong adhesive action is caused by interactions between the catechol groups at the end of the polymer terminal chains and the substrate surface. Here, we present a preliminary study of the adhesion properties and a discussion of the adhesion mechanism. METHODS: Two bioadhesive polymers were synthesized from natural plant-derived monomers by the transesterification of: (a) caffeic acid (3,4-dihydroxycinnamic acid; DHCA) and p-coumaric acid (4-hydroxycinnamic acid; 4HCA) to produce poly(DHCA-co-4HCA); and (b) 4-dihydroxyhydrocinnamic acid (DHHCA) and 3-(3-hydroxyphenyl) propionic acid (3HPPA) to produce poly(DHHCA-co-3HPPA). Thermoplastic poly(DHCA-co-4HCA) or poly(DHHCA-co-3HPPA) was placed between glass, carbon, steel, or bovine dentin substrates, and a lap shear adhesion test was conducted to compare them using conventional cyanoacrylate glue and epoxy resin. RESULTS: The greatest adhesion for all tested substrates was exhibited by poly(DHHCA-co-3HPPA), followed by epoxy resin adhesive, poly(DHCA-co-4HCA), and cyanoacrylate adhesive. The adhesive strength of poly(DHHCA-co-3HPPA) was greater than 25.6 MPa for glass, 29.6 MPa for carbon, 15.7 MPa for steel, and 16.3 MPA for bovine dentin. CONCLUSION: The adhesion of poly(DHHCA-co-3HPPA) might be the strongest reported for a mussel-mimic adhesive system, and could be a feasible alternative to petroleum adhesives.
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Adhesivos/química , Materiales Biomiméticos/química , Biopolímeros/química , Preparaciones de Plantas/química , Adhesividad , Animales , Ácidos Cafeicos/química , Carbono/química , Catecoles/química , Bovinos , Cinamatos/química , Ácidos Cumáricos/química , Cianoacrilatos/química , Dentina/química , Resinas Epoxi/química , Esterificación , Vidrio/química , Polimerizacion , Propionatos , Proteínas/química , Acero/química , Estrés MecánicoRESUMEN
In good shape: The films of hyperbranched polycoumarate derivatives can undergo a reversible [2+2] cycloaddition under irradiation of UV light and behave like photomechanical elastomers. From a predetermined original shapeâ A the photonically and thermally memorized shapesâ B and C were obtained. The original shape was recovered by photoirradiation (see picture; Tg =glass transition temperature).
Asunto(s)
Ácidos Cumáricos/química , Polímeros/química , Diseño Asistido por Computadora , Ácidos Cumáricos/síntesis química , Procesos Fotoquímicos , Polímeros/síntesis químicaRESUMEN
In this paper, the carboxymethyl chitosan/oxidized dextran hydrogel was developed and its potency application in the prevention of postoperative adhesion was investigated. The developed hydrogel showed porous and interconnected interior structure with pore size about 250 µm, which was sensitive to lysozymic solution (1.5 µg/ml) with almost complete degradation after 4 weeks of in vitro incubation. In vivo study suggested that the developed hydrogel showed the great capacity on the prevention of postoperative adhesions in rat model. According to the result of histopathological examination, it clearly showed that the mesothelial cell layer of abdominal wall and cecum were completely recovered after 7 days of surgery in 3% carboxymethyl chitosan/oxidized dextran hydrogel group, while obvious adhesion between abdominal wall and cecum was observed as treatment with saline solution or 3% carboxymethyl chitosan solution after 1 day of surgery. All these results suggested that the developed biodegradable hydrogel might have potential application in the prevention of postoperative adhesion.