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Surface modification of cathodes using Ni-rich coating layers prevents bulk and surface degradation for the stable operation of Li-ion batteries at high voltages. However, insulating and dense inorganic coating layers often impede charge transfer and ion diffusion kinetics. In this study, the fabrication of dual functional coating materials using metal-organic polyhedra (MOP) with 3D networks within microporous units of Li-ion batteries for surface stabilization and facile ion diffusion is proposed. Zr-based MOP is modified by introducing acyl groups as a chemical linkage (MOPAC), and MOPAC layers are homogenously coated by simple spray coating on the cathode. The coating allow the smooth transport of electrons and ions. MOPAC effectively suppress side reactions between the cathode and electrolyte and protect active materials against aggressive fluoride ions by forming a Li-ion selective passivation film. The MOPAC-coated Ni-rich layered cathode exhibited better cycle retention and enhanced kinetic properties than pristine and MOP-coated cathodes. Reduction of undesirable gas evolution on the cathode by MOPAC is also verified. Microporous MOPAC coating can simultaneously stabilize both the bulk and surface of the Ni-rich layered cathode and maintain good electrochemical reaction kinetics for high-performance Li-ion batteries.
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Therapeutic iodoform (CHI3) is commonly used as a root-filling material for primary teeth; however, the side effects of iodoform-containing materials, including early root resorption, have been reported. To overcome this problem, a water-soluble iodide (NaI)-incorporated root-filling material was developed. Calcium hydroxide, silicone oil, and NaI were incorporated in different weight proportions (30:30:X), and the resulting material was denoted DX (D5~D30), indicating the NaI content. As a control, iodoform instead of NaI was incorporated at a ratio of 30:30:30, and the material was denoted I30. The physicochemical (flow, film thickness, radiopacity, viscosity, water absorption, solubility, and ion releases) and biological (cytotoxicity, TRAP, ARS, and analysis of osteoclastic markers) properties were determined. The amount of iodine, sodium, and calcium ion releases and the pH were higher in D30 than I30, and the highest level of unknown extracted molecules was detected in I30. In the cell viability test, all groups except 100% D30 showed no cytotoxicity. In the 50% nontoxic extract, D30 showed decreased osteoclast formation compared with I30. In summary, NaI-incorporated materials showed adequate physicochemical properties and low osteoclast formation compared to their iodoform-counterpart. Thus, NaI-incorporated materials may be used as a substitute for iodoform-counterparts in root-filling materials after further (pre)clinical investigation.
Assuntos
Materiais Restauradores do Canal Radicular , Hidróxido de Cálcio , Materiais Restauradores do Canal Radicular/farmacologia , Iodeto de Sódio , Dente Decíduo , ÁguaRESUMO
Colloidal clusters are prepared by assembling positively charged cross-linked polystyrene (PS) particles onto negatively charged liquid cores of swollen polymer particles. PS particles at the interface of the liquid core are closely packed around the core due to interfacial wetting. Then, by evaporating solvent in the liquid cores, polymers in the cores are solidified and the clusters are cemented. As the swelling ratio of PS cores increases, cores at the center of colloidal clusters are exposed, forming patchy colloidal clusters. Finally, by density gradient centrifugation, high-purity symmetric colloidal clusters are obtained. When silica-PS core-shell particles are swollen and serve as the liquid cores, hybrid colloidal clusters are obtained in which each silica nanoparticle is relocated to the liquid core interface during the swelling-deswelling process breaking symmetry in colloidal clusters as the silica nanoparticle in the core is comparable in size with the PS particle in the shell. The configuration of colloidal clusters is determined once the number of particles around the liquid core is given, which depends on the size ratio of the liquid core and shell particle. Since hybrid clusters are heavier than PS particles, they can be purified using centrifugation.
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Hypercholesterolemia is reported to increase reactive oxygen species (ROS) and to promote breast cancer progression. ROS play an important role in tumor biology, and xanthine oxidase (XO) is an enzyme that generates ROS. The effects of febuxostat (FBX), an XO inhibitor, on breast cancer cell migration under LDL stimulation in vitro and metastasis of breast cancer associated with hypercholesterolemia in vivo were studied. In vitro, FBX significantly inhibited LDL-induced ROS production and cell migration. Treatment of small interfering RNA against XO was consistent with the findings of FBX treatment. In vivo, a significant increase of tumor growth and pulmonary metastasis was observed in a xenograft mouse model with 4T1 cells on a high cholesterol diet (HCD), both of which were markedly inhibited by FBX or allopurinol treatment. Moreover, ERK represented the main target-signaling pathway that was affected by FBX treatment in a xenograft mouse model on an HCD evaluated by NanoString nCounter analysis. Consistently, MEK/ERK inhibitors directly decreased the LDL-induced cell migration in vitro. In conclusion, FBX mitigates breast cancer cell migration and pulmonary metastasis in the hyperlipidemic condition, associated with decreased ROS generation and MAPK phosphorylation. The inhibition of ERK pathways is likely to underlie the XO inhibitor-mediated suppression of breast cancer cell migration.-Oh, S.-H., Choi, S.-Y., Choi, H.-J., Ryu, H.-M., Kim, Y.-J., Jung, H.-Y., Cho, J.-H., Kim, C.-D., Park, S.-H., Kwon, T.-H., Kim, Y.-L. The emerging role of xanthine oxidase inhibition for suppression of breast cancer cell migration and metastasis associated with hypercholesterolemia.
Assuntos
Neoplasias da Mama/enzimologia , Hipercolesterolemia/complicações , Neoplasias Pulmonares/secundário , Proteínas de Neoplasias/antagonistas & inibidores , Xantina Oxidase/antagonistas & inibidores , Alopurinol/farmacologia , Alopurinol/uso terapêutico , Animais , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular , Colesterol na Dieta/toxicidade , Progressão da Doença , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Febuxostat/farmacologia , Febuxostat/uso terapêutico , Feminino , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/prevenção & controle , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Proteínas de Neoplasias/genética , RNA Interferente Pequeno/farmacologia , Distribuição Aleatória , Espécies Reativas de Oxigênio , Imagem com Lapso de Tempo , Xantina Oxidase/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In the present study, we investigated the effects of xanthine oxidase (XO) inhibition on cholesterol-induced renal dysfunction in chronic kidney disease (CKD) mice, and in low-density lipoprotein (LDL)-treated human kidney proximal tubule epithelial (HK-2) cells. ApoE knockout (KO) mice underwent uninephrectomy to induce CKD, and were fed a normal diet or high-cholesterol (HC) diet along with the XO inhibitor topiroxostat (1 mg/kg/day). HK-2 cells were treated with LDL (200 µg/mL) and topiroxostat (5 µM) or small interfering RNA against xanthine dehydrogenase (siXDH; 20 nM). In uninephrectomized ApoE KO mice, the HC diet increased cholesterol accumulation, oxidative stress, XO activity, and kidney damage, while topiroxostat attenuated the hypercholesterolemia-associated renal dysfunction. The HC diet induced cholesterol accumulation by regulating the expressions of genes involved in cholesterol efflux (Nr1h3 and Abca1) and synthesis (Srebf2 and Hmgcr), which was reversed by topiroxostat. Topiroxostat suppressed the expressions of genes related to hypercholesterolemia-associated inflammation and fibrosis in the unilateral kidney. LDL stimulation evoked changes in the cholesterol metabolism, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and NF-κB pathways in HK-2 cells, which were mitigated by XO inhibition with topiroxostat or siXDH. These findings suggest that XO inhibition exerts renoprotective effects against hypercholesterolemia-associated kidney injury. XO could be a novel therapeutic target for hypercholesterolemia-associated kidney injury in uninephrectomized patients.
Assuntos
Hipercolesterolemia/complicações , Hipercolesterolemia/metabolismo , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/metabolismo , Xantina Oxidase/metabolismo , Colesterol/metabolismo , Progressão da Doença , Suscetibilidade a Doenças , Fibrose , Humanos , Metabolismo dos Lipídeos , Lipoproteínas LDL/metabolismo , Estresse Oxidativo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Transdução de Sinais , Xantina Oxidase/genéticaRESUMO
The protective effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) 1 inhibition against kidney ischemia-reperfusion injury (IRI) remain uncertain. The bilateral kidney pedicles of C57BL/6 mice were clamped for 30 min to induce IRI. Madin-Darby Canine Kidney (MDCK) cells were incubated with H2O2 (1.4 mM) for 1 h to induce oxidative stress. ML171, a selective NOX1 inhibitor, and siRNA against NOX1 were treated to inhibit NOX1. NOX expression, oxidative stress, apoptosis assay, and mitogen-activated protein kinase (MAPK) pathway were evaluated. The kidney function deteriorated and the production of reactive oxygen species (ROS), including intracellular H2O2 production, increased due to IRI, whereas IRI-mediated kidney dysfunction and ROS generation were significantly attenuated by ML171. H2O2 evoked the changes in oxidative stress enzymes such as SOD2 and GPX in MDCK cells, which was mitigated by ML171. Treatment with ML171 and transfection with siRNA against NOX1 decreased the upregulation of NOX1 and NOX4 induced by H2O2 in MDCK cells. ML171 decreased caspase-3 activity, the Bcl-2/Bax ratio, and TUNEL-positive tubule cells in IRI mice and H2O2-treated MDCK cells. Among the MAPK pathways, ML171 affected ERK signaling by ERK phosphorylation in kidney tissues and tubular cells. NOX1-selective inhibition attenuated kidney IRI via inhibition of ROS-mediated ERK signaling.
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Peróxido de Hidrogênio/metabolismo , Nefropatias/enzimologia , Rim/enzimologia , Sistema de Sinalização das MAP Quinases , NADPH Oxidase 1/metabolismo , Traumatismo por Reperfusão/enzimologia , Animais , Cães , Rim/patologia , Nefropatias/patologia , Células Madin Darby de Rim Canino , Masculino , Camundongos , Traumatismo por Reperfusão/patologiaRESUMO
BACKGROUND: A single nutrient or dietary pattern has been associated with physical performance. However, little is still known about the association of overall dietary quality with physical performance. This study aimed to investigate the link between the recommended food score (RFS), defined as an indicator of overall diet quality, and physical performance among the Korean elderly aged over 65 years. METHODS: The study subjects consisted of 622 participants (294 men and 328 women) aged over 65 years from the 2014-2015 National Fitness Award project. RESULTS: The mean value of RFS was higher in elderly women (30.7 ± 7.6) than elderly men (29.5 ± 8.8), but the difference was only marginally significant (P = 0.065). In elderly women, multiple regression linear models, adjusted for potential confounders, showed that RFS was positively related to absolute hand grip strength (kg) (ß = 0.066, 95% CI = 0.010 to 0.122) and relative hand grip strength (%) (ß =0.109, 95% CI = 0.016 to 0.201); other physical performance indicators did not show any association with RFS. In elderly men, none of the physical performance indexes were associated with RFS. CONCLUSIONS: These results suggest that a better overall diet quality may be associated with improved grip strength among elderly women in Korea.
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Dieta/normas , Desempenho Físico Funcional , Idoso , Feminino , Força da Mão , Humanos , Masculino , República da CoreiaRESUMO
BACKGROUND: A healthy diet is a key determinant of an individual's health status and is closely related to mental health and quality of life (QoL); however, the exact nature of the relationship is unknown. This study hypothesized that a higher diet quality score is associated with a lower observance of symptoms of depression and anxiety and a higher QoL. METHODS: This study evaluated 1,295 adults (521 men; 774 women) aged 19-64 years, who participated in the 2014-2015 National Fitness Award Project. Diet quality was measured by the recommended food score (RFS), and mental health and QoL were assessed by the beck depression inventory (BDI), beck anxiety inventory (BAI), and the World Health Organization QoL-Brief (WHOQoL-BREF). RESULTS: After adjusting for covariates, the individuals with depression had a significantly lower RFS value compared to those without depression, and the group with a QoL score above the median had a higher RFS value than the group with a QoL score below the median. These trends occurred in both men and women. Subjects in the highest tertile of RFS showed a lower odds of depression (OR = 0.51, 95% CI = 0.32-0.81, p-trend = 0.0043) and a QoL score below the median (OR = 0.40, 95% CI = 0.30-0.54, p-trend < 0.0001) compared with those in the lowest tertile. The RFS was not associated with anxiety. CONCLUSIONS: Our data suggest that higher diet quality may be associated with lower depressive symptoms and a better QoL in Korean adults.
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Ansiedade/epidemiologia , Depressão/epidemiologia , Dieta/normas , Qualidade de Vida , Adulto , Distinções e Prêmios , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aptidão Física , República da Coreia/epidemiologia , Adulto JovemRESUMO
Endothelial cell injury and dysfunction caused by reactive oxygen species (ROS) are implicated in the pathogenesis of vascular diseases. ROS are generated and hypoxanthine is degraded by xanthine oxidase. Smoking and alcohol consumption are associated with an increased level of hypoxanthine. We aimed to study the direct role of hypoxanthine in endothelial dysfunction in human umbilical vascular endothelial cells (HUVECs). Hypoxanthine induced cell death and production of ROS. Furthermore, hypoxanthine induced apoptosis through regulation of protein expression related to apoptosis. When cells were pretreated with N-acetylcysteine or a pancaspase inhibitor (Z-VAD-fmk) and stimulated with hypoxanthine, Z-VAD-fmk and N-acetylcysteine prevented hypoxanthine-induced apoptosis by inhibiting the ROS production and caspase pathway. Thus, an increased extracellular concentration of hypoxanthine induces endothelial dysfunction through ROS production and regulates expression of apoptosis-related proteins in HUVECs. These effects are expected to be associated with some vascular diseases.
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Apoptose , Células Endoteliais/metabolismo , Hipoxantina/metabolismo , Estresse Oxidativo , Células Endoteliais/citologia , Células Endoteliais/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: To determine the in vivo cortical spreading pattern of tau and amyloid and to establish positron emission tomography (PET) image-based tau staging in the Alzheimer disease (AD) spectrum. METHODS: We included 195 participants (53 AD, 52 amnestic mild cognitive impairment [MCI], 23 nonamnestic MCI, and 67 healthy controls) who underwent 2 PET scans ((18) F-florbetaben for amyloid-ß and (18) F-AV-1451 for tau). We assumed that regions with earlier appearances of pathology may show increased binding in a greater number of participants and acquired spreading order of tau accumulation by sorting the regional frequencies of involvement. We classified each participant into image-based tau stage based on the Z score of the composite region for each stage. RESULTS: Tau accumulation was most frequently observed in the medial temporal regions and spread stepwise to the basal and lateral temporal, inferior parietal, posterior cingulate, and other association cortices, and then ultimately to the primary cortical regions. In contrast, amyloid accumulation was found with similar frequency in the diffuse neocortical areas and then finally spread to the medial temporal regions. The image-based tau stage correlated with the general cognitive status, whereas cortical thinning was found only in the advanced tau stages: medial temporal region in stage V and widespread cortex in stage VI. INTERPRETATION: Our PET study replicated postmortem spreading patterns of tau and amyloid-ß pathologies. Unlike the diffuse accumulation of amyloid throughout the neocortex, tau spreading occurred in a stepwise fashion through the networks. Image-based tau staging may be useful for the objective assessment of AD progression. Ann Neurol 2016;80:247-258.
Assuntos
Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Córtex Cerebral/metabolismo , Disfunção Cognitiva/metabolismo , Proteínas tau/metabolismo , Idoso , Doença de Alzheimer/patologia , Amnésia/complicações , Amnésia/metabolismo , Amnésia/patologia , Atrofia/patologia , Córtex Cerebral/patologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Testes Neuropsicológicos , Tomografia por Emissão de PósitronsRESUMO
BACKGROUND: Undirected graphical models or Markov random fields have been a popular class of models for representing conditional dependence relationships between nodes. In particular, Markov networks help us to understand complex interactions between genes in biological processes of a cell. Local Poisson models seem to be promising in modeling positive as well as negative dependencies for count data. Furthermore, when zero counts are more frequent than are expected, excess zeros should be considered in the model. METHODS: We present a penalized Poisson graphical model for zero inflated count data and derive an expectation-maximization (EM) algorithm built on coordinate descent. Our method is shown to be effective through simulated and real data analysis. RESULTS: Results from the simulated data indicate that our method outperforms the local Poisson graphical model in the presence of excess zeros. In an application to a RNA sequencing data, we also investigate the gender effect by comparing the estimated networks according to different genders. Our method may help us in identifying biological pathways linked to sex hormone regulation and thus understanding underlying mechanisms of the gender differences. CONCLUSIONS: We have presented a penalized version of zero inflated spatial Poisson regression and derive an efficient EM algorithm built on coordinate descent. We discuss possible improvements of our method as well as potential research directions associated with our findings from the RNA sequencing data.
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Algoritmos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Modelos Estatísticos , Análise de Sequência de RNA/métodos , Simulação por Computador , Feminino , Humanos , Masculino , Distribuição de PoissonRESUMO
Human respiratory syncytial virus (HRSV) is a main cause of lower respiratory tract infections in infants and the elderly. Glycoprotein (G) is major antigen on the viral surface, and plays a key role for virus entry. Therefore, purification of the glycoprotein of HRSV is critical for the development of HRSV vaccine and serological diagnosis. In this study, we report the design and characterization of glycoprotein engineered rationally to enhance the protein solubility and to facilitate efficient purification. We permuted HRSV glycoproteins with two tags: (i) an immunoglobulin (Ig) M signal peptide and a protein A B domain tag to render HRSV glycoprotein secret into the culture media and (ii) a foldon and 6 × histidine tag with or without transmembrane domain. Three recombinant baculoviruses were constructed: (i) transmembrane-truncated HRSV glycoprotein (amino acid positions 66-298) inserted with the N-terminal IgM signal peptide and protein A B domain (MG-GΔTM), (ii) truncated HRSV glycoprotein (amino acid positions 66-298) fused with a C-terminal foldon and 6 × histidine tag (GΔTM-FH), and (iii) full-length HRSV glycoprotein (amino acid positions 1-298) fused with a C-terminal foldon and 6 × histidine tag (G-FH). Highly soluble recombinant MG-GΔTM protein was clearly purified using one-step affinity chromatography with IgG-sepharose resin, whereas the recombinant G-FH protein and truncated GΔTM-FH were purified partially using nickel-resin. Although, the antigenicity of GΔTM-FH was stronger than highly mannose-rich MG-GΔTM protein, MG-GΔTM induced neutralizing antibodies efficiently in the mice to protect from infectious HRSV.
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Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Expressão Gênica , Glicoproteínas , Vírus Sinciciais Respiratórios/genética , Proteínas Virais , Animais , Feminino , Glicoproteínas/biossíntese , Glicoproteínas/genética , Glicoproteínas/imunologia , Glicoproteínas/isolamento & purificação , Humanos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Vírus Sinciciais Respiratórios/imunologia , Células Sf9 , Spodoptera , Proteínas Virais/biossíntese , Proteínas Virais/genética , Proteínas Virais/imunologia , Proteínas Virais/isolamento & purificaçãoRESUMO
BACKGROUND: In 2015, the largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside the Middle East occurred in South Korea. We summarized the epidemiological, clinical, and laboratory findings of the first Korean case of MERS-CoV and analyzed whole-genome sequences of MERS-CoV derived from the patient. CASE PRESENTATION: A 68-year-old man developed fever and myalgia 7 days after returning to Korea, following a 10-day trip to the Middle East. Before diagnosis, he visited 4 hospitals, potentially resulting in secondary transmission to 28 patients. On admission to the National Medical Center (day 9, post-onset of clinical illness), he presented with drowsiness, hypoxia, and multiple patchy infiltrations on the chest radiograph. He was intubated (day 12) because of progressive acute respiratory distress syndrome (ARDS) and INF-α2a and ribavirin treatment was commenced. The treatment course was prolonged by superimposed ventilator associated pneumonia. MERS-CoV PCR results converted to negative from day 47 and the patient was discharged (day 137), following rehabilitation therapy. The complete genome sequence obtained from a sputum sample (taken on day 11) showed the highest sequence similarity (99.59%) with the virus from an outbreak in Riyadh, Saudi Arabia, in February 2015. CONCLUSIONS: The first case of MERS-CoV infection had high transmissibility and was associated with a severe clinical course. The patient made a successful recovery after early treatment with antiviral agents and adequate supportive care. This first case in South Korea became a super-spreader because of improper infection control measures, rather than variations of the virus.
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Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/etiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Idoso , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Surtos de Doenças , Humanos , Controle de Infecções/métodos , Masculino , Oriente Médio , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Filogenia , República da Coreia/epidemiologia , Ribavirina/uso terapêutico , Arábia Saudita/epidemiologiaRESUMO
1. Drug efflux by P-glycoprotein (P-gp) is a common resistance mechanism of breast cancer cells to paclitaxel, the primary chemotherapy in breast cancer. As a means of overcoming the drug resistance-mediated failure of paclitaxel chemotherapy, the potential of Korean red ginseng extract (KRG) as an adjuvant chemotherapy has been reported only in in vitro. Therefore, we assessed whether KRG alters P-gp mediated paclitaxel efflux, and therefore paclitaxel efficacy in in vitro and vivo models. 2. KRG inhibited P-gp protein expression and transcellular efflux of paclitaxel in MDCK-mdr1 cells, but KRG was not a substrate of P-gp ATPase. In female rats with mammary tumor, the combination of paclitaxel with KRG showed the greater reduction of tumor volumes, lower P-gp protein expression and higher paclitaxel distribution in tumors, and greater oral bioavailability of paclitaxel than paclitaxel alone. 3. From these results, KRG increased systemic circulation of oral paclitaxel and its distribution to tumors via P-gp inhibition in rats and under the current study conditions.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Paclitaxel/metabolismo , Panax , Extratos Vegetais/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Disponibilidade Biológica , Neoplasias da Mama/metabolismo , Cães , Feminino , Células Madin Darby de Rim Canino , RatosRESUMO
Reactive oxygen species (ROS) generation during purine metabolism is associated with xanthine oxidase and uric acid. However, the direct effect of hypoxanthine on ROS generation and atherosclerosis has not been evaluated. Smoking and heavy drinking are associated with elevated levels of hypoxanthine. In this study, we investigated the role of hypoxanthine on cholesterol synthesis and atherosclerosis development, particularly in apolipoprotein E (APOE)-deficient mice. The effect of hypoxanthine on the regulation of cholesterol synthesis and atherosclerosis were evaluated in Apoe knockout (KO) mice and cultured HepG2 cells. Hypoxanthine markedly increased serum cholesterol levels and the atherosclerotic plaque area in Apoe KO mice. In HepG2 cells, hypoxanthine increased intracellular ROS production. Hypoxanthine increased cholesterol accumulation and decreased APOE and ATP-binding cassette transporter A1 (ABCA1) mRNA and protein expression in HepG2 cells. Furthermore, H2 O2 also increased cholesterol accumulation and decreased APOE and ABCA1 expression. This effect was partially reversible by treatment with the antioxidant N-acetyl cysteine and allopurinol. Hypoxanthine and APOE knockdown using APOE-siRNA synergistically induced cholesterol accumulation and reduced APOE and ABCA1 expression. Hypoxanthine induces cholesterol accumulation in hepatic cells through alterations in enzymes that control lipid transport and induces atherosclerosis in APOE-deficient cells and mice. These effects are partially mediated through ROS produced in response to hypoxanthine.
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Apolipoproteínas E/deficiência , Aterosclerose/patologia , Colesterol/metabolismo , Hipoxantina/farmacologia , Acetilcisteína/farmacologia , Alopurinol/farmacologia , Animais , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Colesterol/sangue , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Células Hep G2 , Humanos , Peróxido de Hidrogênio/toxicidade , Hipercolesterolemia/patologia , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Placa Aterosclerótica/sangue , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Regulação para Cima/efeitos dos fármacosRESUMO
An outbreak of nosocomial infections with Middle East respiratory syndrome coronavirus occurred in South Korea in May 2015. Spike glycoprotein genes of virus strains from South Korea were closely related to those of strains from Riyadh, Saudi Arabia. However, virus strains from South Korea showed strain-specific variations.
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Variação Genética/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Glicoproteína da Espícula de Coronavírus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/virologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Surtos de Doenças , Humanos , Masculino , República da Coreia/epidemiologia , Arábia Saudita/epidemiologiaRESUMO
Mumps is a vaccine-preventable viral disease. Despite vaccine coverage of >95%, the incidence of mumps has increased in Korea since 2007. This study aimed to genetically characterize mumps virus (MuV) strains that circulated in Korea between 2007 and 2012 to determine the factors underlying mumps outbreaks. MuV was isolated from 175 clinical specimens between 2007 and 2012 in Korea. Upon analysis of the SH gene in Korean mumps virus isolates, three different genotypes were identified: I, H, and F. The MuV genotypes I and H co-circulated in Korea, and eight isolates of Korean genotype F were found within the same time period in 2008. An analysis of HN amino-acid sequence data showed that Korean isolates had no changes in their glycosylation sites. At putative neutralizing epitope sites, the Jeryl-Lynn strain showed 4-5 different amino acid sequences from those observed in Korean isolates. Korean isolates of genotypes I and H shared distinctive point mutations on putative neutralizing epitope positions in each genotype. This report describes the genetic characteristics of MuV strains circulating in Korea and provides information on endemic mumps infections. This information may be important to help prevent mumps and control outbreaks of mumps in Korea. J. Med. Virol. 88:1479-1486, 2016. © 2016 Wiley Periodicals, Inc.
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Variação Genética , Vírus da Caxumba/genética , Caxumba/virologia , Surtos de Doenças , Epitopos/imunologia , Genótipo , Humanos , Caxumba/epidemiologia , Vírus da Caxumba/classificação , Vírus da Caxumba/isolamento & purificação , Filogenia , RNA Viral/genética , República da Coreia/epidemiologia , Alinhamento de Sequência , Proteínas Virais/genéticaRESUMO
BACKGROUND: Previous animal studies suggested that Chlorella, a unicellular green alga, has a preventive role in maintaining serum cholesterol levels against excess dietary cholesterol intake. This study aimed to conduct a pioneering investigation to clarify this issue in healthy subjects by adopting a dietary cholesterol challenge, which has not been used previously in similar studies of Chlorella in hypercholesterolemia. METHODS: In this double blind, randomized, placebo-controlled study, 34 participants ingested 510 mg of dietary cholesterol from three eggs concomitantly with a usual dose of Chlorella (5 g/d) or a matched placebo for 4 weeks. RESULTS: The dietary cholesterol challenge induced consistently higher concentrations of serum total cholesterol (TC, P < 0.001), LDL-C (P = 0.004), and HDL-C (P = 0.010) compared with baseline values, suggesting that the challenge was reliable. Thus, we observed a preventive action of Chlorella in maintaining serum TC versus placebo levels (3.5 % versus 9.8 %, respectively; P = 0.037) and LDL-C versus placebo levels (1.7 % versus 14.3 %, respectively; P = 0.012) against excessive dietary cholesterol intake and in augmenting HDL-C versus placebo levels (8.3 % versus 3.8 %, respectively). Furthermore, serum α-carotene showed the best separation between the placebo and Chlorella groups (R(2)X and R(2)Y > 0.5; Q(2) > 0.4). CONCLUSION: The results suggest that a fully replicated dietary cholesterol challenge may be useful in assessing the effectiveness of dietary supplements in maintaining the serum lipid profiles of adults whose habitual diets are high in cholesterol. TRIAL REGISTRATION: WHO International Clinical Trials Registry Platform ( KCT0000258 ).
Assuntos
Chlorella , Colesterol na Dieta/administração & dosagem , Lipídeos/sangue , Índice de Massa Corporal , Carotenoides/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta , Método Duplo-Cego , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/terapia , Masculino , Resultado do Tratamento , Triglicerídeos/sangue , Adulto JovemRESUMO
In May 2015, Middle East respiratory syndrome coronavirus infection was laboratory confirmed in South Korea. Patients were a man who had visited the Middle East, his wife, and a man who shared a hospital room with the index patient. Rapid laboratory confirmation will facilitate subsequent prevention and control for imported cases.
Assuntos
Infecções por Coronavirus/diagnóstico , Coronavirus/patogenicidade , Infecção Hospitalar/virologia , Viagem , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Infecção Hospitalar/transmissão , Humanos , Masculino , Oriente Médio , República da Coreia/epidemiologiaRESUMO
A technique for adequate flow control is important in the fields of science and engineering. In this study, we hypothesized that the unrestricted flow control inside a chamber containing 'schools of magnetic particles' might be possible through control of an external magnetic field, biomimicking the flow generated by schools of fish. Microgels based on superparamagnetic iron oxide nanoparticles (SPIONs) and poly(acrylic acid) hydrogels were employed. With an increase in the SPION content, the microgels responded more efficiently to the translational movement of the magnetic field. Rotational movement was more efficiently achieved with anisotropic distribution of SPIONs inside microgels, which was induced by applying a magnetic field immediately prior to crosslinking. The systems of the anisotropic microgels successfully provided microflow for effective mixing in a capillary. This biomimetic flow control may be useful for the control of fluid systems of any micro- or nano-size and any shape, regardless of the tortuosity.