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1.
Antioxidants (Basel) ; 12(8)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37627645

RESUMO

The aim of this study was to investigate the effects of different cooking methods on the hepatoprotective effects of purple sweet potatoes against alcohol-induced damage in HepG2 cells. Purple sweet potatoes (Ipomeoea batatas L. Danjami) were subjected to different cooking methods, including steaming, roasting, and microwaving. Steaming resulted in a higher cytoprotective effect against alcohol damage than the other cooking methods. Additionally, the highest inhibition of glutathione depletion and production of reactive oxygen species against alcohol-induced stress were observed in raw and/or steamed purple sweet potatoes. Compared to roasted and/or microwaved samples, steamed samples significantly increased the expression of NADPH quinone oxidoreductase 1, heme oxygenase 1, and gamma glutamate-cysteine ligase in alcohol-stimulated HepG2 cells via the activation of nuclear factor erythroid 2-related factor 2. Moreover, ten anthocyanins were detected in the raw samples, whereas five, two, and two anthocyanins were found in the steamed, roasted, and microwaved samples, respectively. Taken together, steaming purple sweet potatoes could be an effective cooking method to protect hepatocytes against alcohol consumption. These results provide useful information for improving the bioactive properties of purple sweet potatoes using different cooking methods.

2.
Materials (Basel) ; 16(5)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36903122

RESUMO

Defects on graphene over a micrometer in size were selectively blocked using polyvinyl alcohol through the formation of hydrogen bonding with defects. Because this hydrophilic PVA does not prefer to be located on the hydrophobic graphene surface, PVA selectively filled hydrophilic defects on graphene after the process of deposition through the solution. The mechanism of the selective deposition via hydrophilic-hydrophilic interactions was also supported by scanning tunneling microscopy and atomic force microscopy analysis of selective deposition of hydrophobic alkanes on hydrophobic graphene surface and observation of PVA initial growth at defect edges.

3.
Nano Lett ; 22(1): 286-293, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34978186

RESUMO

Self-assembled alkane layers are introduced between graphene layers to physically block nanometer size defects in graphene and lateral gas pathways between graphene layers. A well-defined hexatriacontane (HTC) monolayer on graphene could cover nanometer-size defects because of the flexible nature and strong intermolecular van der Waals interactions of alkane, despite the roughness of graphene. In addition, HTC multilayers between graphene layers greatly improve their adhesion. This indicates that HTC multilayers between graphene layers can effectively block the lateral pathway between graphene layers by filling open space with close-packed self-assembled alkanes. By these mechanisms, alternately stacked composites of graphene and self-assembled alkane layers greatly increase the gas-barrier property to a water vapor transmission rate (WVTR) as low as 1.2 × 10-3 g/(m2 day), whereas stacked graphene layers generally show a WVTR < 0.5 g/(m2 day). Furthermore, the self-assembled alkane layers have superior crystallinity and wide bandgap, so they have little effect on the transmittance.

4.
Antioxidants (Basel) ; 9(11)2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33182801

RESUMO

Excessive accumulation of melanin can cause skin pigmentation disorders, which may be accompanied by significant psychological stress. Although many natural and synthetic products have been developed for the regulation of melanogenesis biochemistry, the management of unwanted skin pigmentation remains challenging. Herein, we investigated the potential hypopigmenting properties of peptide sequences that originated from milk proteins such as ĸ-casein and ß-lactoglobulin. These proteins are known to inhibit melanogenesis and their hydrolysates are reported as antioxidant peptides. We synthesize tetrapeptide fragments of the milk protein hydrolysates and investigate the amino acids that are essential for designing peptides with tyrosinase inhibitory and antioxidant activities. We found that the peptide methionine-histidine-isoleucine-arginine amide sufficiently inhibits mushroom tyrosinase activity, shows potent antioxidant activity and effectively impedes melanogenesis in cultured melanocytes via cooperative biological activities. Our findings demonstrate the potential utility of the bioactive tetrapeptide from milk proteins as a chemical alternative to hypopigmenting agents.

5.
Adv Mater ; 32(22): e2000969, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32310332

RESUMO

Mimicking human skin sensation such as spontaneous multimodal perception and identification/discrimination of intermixed stimuli is severely hindered by the difficulty of efficient integration of complex cutaneous receptor-emulating circuitry and the lack of an appropriate protocol to discern the intermixed signals. Here, a highly stretchable cross-reactive sensor matrix is demonstrated, which can detect, classify, and discriminate various intermixed tactile and thermal stimuli using a machine-learning approach. Particularly, the multimodal perception ability is achieved by utilizing a learning algorithm based on the bag-of-words (BoW) model, where, by learning and recognizing the stimulus-dependent 2D output image patterns, the discrimination of each stimulus in various multimodal stimuli environments is possible. In addition, the single sensor device integrated in the cross-reactive sensor matrix exhibits multimodal detection of strain, flexion, pressure, and temperature. It is hoped that his proof-of-concept device with machine-learning-based approach will provide a versatile route to simplify the electronic skin systems with reduced architecture complexity and adaptability to various environments beyond the limitation of conventional "lock and key" approaches.


Assuntos
Materiais Biomiméticos/química , Técnicas Biossensoriais/instrumentação , Dispositivos Eletrônicos Vestíveis , Algoritmos , Materiais Revestidos Biocompatíveis/química , Humanos , Aprendizado de Máquina , Modelos Químicos , Nanofios/química , Percepção , Poliuretanos/química , Pressão , Prata/química , Temperatura , Tato
6.
Sensors (Basel) ; 20(4)2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32102360

RESUMO

A readily synthesizable fluorescent probe DMAT-π-CAP was evaluated for sensitive and selective detection of human serum albumin (HSA). DMAT-π-CAP showed selective turn-on fluorescence at 730 nm in the presence of HSA with more than 720-fold enhancement in emission intensity ([DMAT-π-CAP] = 10 µM), and rapid detection of HSA was accomplished in 3 seconds. The fluorescence intensity of DMAT-π-CAP was shown to increase in HSA concentration-dependent manner (Kd = 15.4 ± 3.3 µM), and the limit of detection of DMAT-π-CAP was determined to be 10.9 nM (0.72 mg/L). The 1:1 stoichiometry between DMAT-π-CAP and HSA was determined, and the displacement assay revealed that DMAT-π-CAP competes with hemin for the unique binding site, which rarely accommodates drugs and endogenous compounds. Based on the HSA-selective turn-on NIR fluorescence property as well as the unique binding site, DMAT-π-CAP was anticipated to serve as a fluorescence sensor for quantitative detection of the HSA level in biological samples with minimized background interference. Thus, urine samples were directly analyzed by DMAT-π-CAP to assess albumin levels, and the results were comparable to those obtained from immunoassay. The similar sensitivity and specificity to the immunoassay along with the simple, cost-effective, and fast detection of HSA warrants practical application of the NIR fluorescent albumin sensor, DMAT-π-CAP, in the analysis of albumin levels in various biological environments.


Assuntos
Albuminas/isolamento & purificação , Albuminúria/diagnóstico , Técnicas Biossensoriais , Albumina Sérica Humana/isolamento & purificação , Albuminas/química , Fluorescência , Corantes Fluorescentes , Humanos , Limite de Detecção , Albumina Sérica Humana/química
7.
J Hand Surg Am ; 44(6): 517.e1-517.e7, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30292716

RESUMO

PURPOSE: The biomechanical characteristics of anatomic radial head prostheses have not been completely investigated. We compared and analyzed the contact kinematic characteristics of the native radial head and radial head prostheses replicating the native head contour, using a real-time flexion simulation model. METHODS: Ten fresh-frozen cadavers were used in this pilot study. A simulating dynamic motion mode from 0° to 130° of elbow flexion was applied. Radiocapitellar contact pressure and area were measured using a real-time digitized pressure sensor. Further, contact area and pressure curves were obtained during flexion, using a motion-tracking device. RESULTS: The mean contact area, mean contact pressure, and peak contact pressure of the native radial head and radial head prosthesis were 39 mm2, 0.0078 kgf/mm2, 0.0123 kgf/mm2, and 33 mm2, 0.0093 kgf/dm2, 0.0148 kgf/mm2, respectively. The contact area and pressure curves were parabolic nonlinear for the radial head prosthesis and more linear for the native radial head. CONCLUSIONS: The radial head prosthesis mimics the mechanics of the native radial head in terms of mean contact area, mean contact pressure, and peak contact pressure; however, different patterns of contact pressure and area curves during elbow flexion-extension were observed. CLINICAL RELEVANCE: We found that the biomechanics of the anatomic radial head prostheses used in the study were similar to those of the native radial head.


Assuntos
Artroplastia de Substituição do Cotovelo , Articulação do Cotovelo/fisiologia , Prótese de Cotovelo , Rádio (Anatomia)/cirurgia , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos/fisiologia , Cadáver , Articulação do Cotovelo/cirurgia , Feminino , Humanos , Masculino , Modelos Biológicos , Projetos Piloto
8.
Materials (Basel) ; 11(10)2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30275425

RESUMO

A fiber-based single-walled carbon nanotube (SWCNT) thin-film-transistor (TFT) has been proposed. We designed complementary SWCNT TFT circuit based on SPICE simulations, with device parameters extracted from the fabricated fiber-based SWCNT TFTs, such as threshold voltage, contact resistance, and off-/gate-leakage current. We fabricated the SWCNTs CMOS inverter circuits using the selective passivation and n-doping processes on a fiber substrate. By comparing the simulation and experimental results, we could enhance the circuit's performance by tuning the threshold voltage between p-type and n-type TFTs, reducing the source/drain contact resistance and off current level, and maintaining a low output capacitance of the TFTs. Importantly, it was found that the voltage gain, output swing range, and frequency response of the fiber-based inverter circuits can be dramatically improved.

9.
Adv Mater ; : e1804120, 2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30152085

RESUMO

A new strategy is reported to achieve high-mobility, low-off-current, and operationally stable solution-processable metal-oxide thin-film transistors (TFTs) using a corrugated heterojunction channel structure. The corrugated heterojunction channel, having alternating thin-indium-tin-zinc-oxide (ITZO)/indium-gallium-zinc-oxide (IGZO) and thick-ITZO/IGZO film regions, enables the accumulated electron concentration to be tuned in the TFT off- and on-states via charge modulation at the vertical regions of the heterojunction. The ITZO/IGZO TFTs with optimized corrugated structure exhibit a maximum field-effect mobility >50 cm2 V-1 s-1 with an on/off current ratio of >108 and good operational stability (threshold voltage shift <1 V for a positive-gate-bias stress of 10 ks, without passivation). To exploit the underlying conduction mechanism of the corrugated heterojunction TFTs, a physical model is implemented by using a variety of chemical, structural, and electrical characterization tools and Technology Computer-Aided Design simulations. The physical model reveals that efficient charge manipulation is possible via the corrugated structure, by inducing an extremely high carrier concentration at the nanoscale vertical channel regions, enabling low off-currents and high on-currents depending on the applied gate bias.

10.
Biochem Biophys Res Commun ; 495(2): 1992-1997, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29180011

RESUMO

We recently showed that a 13-kDa protein (p13), the homolog protein of formation of mitochondrial complex V assembly factor 1 in yeast, acts as a potential protective factor in pancreatic islets under diabetes. Here, we aimed to identify known compounds regulating p13 mRNA expression to obtain therapeutic insight into the cellular stress response. A luciferase reporter system was developed using the putative promoter region of the human p13 gene. Overexpression of peroxisome proliferator-activated receptor gamma coactivator 1α, a master player regulating mitochondrial metabolism, increased both reporter activity and p13 expression. Following unbiased screening with 2320 known compounds in HeLa cells, 12 pharmacological agents (including 8 cardiotonics and 2 anthracyclines) that elicited >2-fold changes in p13 mRNA expression were identified. Among them, four cardiac glycosides decreased p13 expression and concomitantly elevated cellular oxidative stress. Additional database analyses showed highest p13 expression in heart, with typically decreased expression in cardiac disease. Accordingly, our results illustrate the usefulness of unbiased compound screening as a method for identifying novel functional roles of unfamiliar genes. Our findings also highlight the importance of p13 in the cellular stress response in heart.


Assuntos
Glicosídeos Cardíacos/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Glicoproteínas/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Chaperonas Moleculares/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/fisiologia , Mapeamento de Interação de Proteínas/métodos , Genes Reporter , Células HeLa , Humanos
11.
Clin Interv Aging ; 11: 1817-1822, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28008242

RESUMO

Early-onset Alzheimer's disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer's disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer's disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16-17), PSEN1 (exons 3-12), and PSEN2 (exons 3-12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We suggest early AD onset and not carrying APOE ε4 allele are more reliable factors for predicting an induced genetic mutation than the presence of the family history in Korean EOAD population.


Assuntos
Doença de Alzheimer/genética , Povo Asiático/genética , Mutação , Doença de Alzheimer/epidemiologia , Precursor de Proteína beta-Amiloide/genética , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Presenilina-1/genética , Presenilina-2/genética , República da Coreia/epidemiologia
12.
J Cell Biol ; 215(1): 121-138, 2016 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-27697926

RESUMO

The membrane fusion of secretory granules with plasma membranes is crucial for the exocytosis of hormones and enzymes. Secretion disorders can cause various diseases such as diabetes or pancreatitis. Synaptosomal-associated protein 23 (SNAP23), a soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor (SNARE) molecule, is essential for secretory granule fusion in several cell lines. However, the in vivo functions of SNAP23 in endocrine and exocrine tissues remain unclear. In this study, we show opposing roles for SNAP23 in secretion in pancreatic exocrine and endocrine cells. The loss of SNAP23 in the exocrine and endocrine pancreas resulted in decreased and increased fusion of granules to the plasma membrane after stimulation, respectively. Furthermore, we identified a low molecular weight compound, MF286, that binds specifically to SNAP23 and promotes insulin secretion in mice. Our results demonstrate opposing roles for SNAP23 in the secretion mechanisms of the endocrine and exocrine pancreas and reveal that the SNAP23-binding compound MF286 may be a promising drug for diabetes treatment.


Assuntos
Ilhotas Pancreáticas/citologia , Pâncreas Exócrino/citologia , Proteínas Qb-SNARE/metabolismo , Proteínas Qc-SNARE/metabolismo , Células Acinares/metabolismo , Células Acinares/ultraestrutura , Amilases/metabolismo , Animais , Fusão Celular , Exocitose , Transportador de Glucose Tipo 4/metabolismo , Insulina/metabolismo , Secreção de Insulina , Camundongos Knockout , Microscopia de Fluorescência por Excitação Multifotônica , Modelos Biológicos , Glândula Parótida/citologia , Transporte Proteico , Proteínas Qb-SNARE/deficiência , Proteínas Qc-SNARE/deficiência , Proteínas SNARE/metabolismo , Vesículas Secretórias/metabolismo , Proteína 25 Associada a Sinaptossoma/metabolismo
13.
Biomed Mater Eng ; 26 Suppl 1: S1193-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26405878

RESUMO

In this study, the radiation generated in the diagnosis of scoliosis, to solve the problems by using an infrared camera and an optical marker system that can diagnose scoliosis developed. System developed by the infrared camera attached to the optical spinal curvature is recognized as a marker to shoot the angle between the two optical markers are measured. Measurement of angle, we used the Cobb's Angle method used in the diagnosis of spinal scoliosis. We developed a software to be able to output to the screen using an infrared camera to diagnose spinal scoliosis. Software is composed of camera output unit was manufactured in Labview, angle measurement unit, in Cobb's Angle measurement unit. In the future, kyphosis, Hallux Valgus, such as the diagnosis of orthopedic disorders that require the use of a diagnostic system is expected case.


Assuntos
Pontos de Referência Anatômicos/patologia , Marcadores Fiduciais , Interpretação de Imagem Assistida por Computador/métodos , Fotografação/instrumentação , Fotografação/métodos , Escoliose/patologia , Adolescente , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Imageamento Tridimensional/métodos , Raios Infravermelhos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
Int J Geriatr Psychiatry ; 30(6): 551-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25060738

RESUMO

OBJECTIVE: Insulin resistance (IR) is a distinct and early feature of type 2 diabetes mellitus and metabolic syndrome. IR is thought to play a vital role in cognitive impairment. We conducted this study to understand the early characteristics of cognitive dysfunctions attributable to IR. METHODS: This study included 85 consecutive non-diabetic elderly participants with mild cognitive impairment (MCI). IR was estimated with the homeostasis model assessment of insulin resistance (HOMA-IR). Cognitive performances were analyzed as a function of scores on the HOMA-IR. RESULTS: The group analysis those with and without IR did not show any differences in the cognitive performance although higher HOMA-IR was closely associated with lower performances in immediate recall on the Seoul Verbal Learning Test (SVLT-I) (r = -0.244, p = 0.026) and Controlled Oral Word Association Test (COWAT) (r = -0.270, p = 0.013). In subgroup analysis by APOE status, SVLT-delayed (p = 0.027) and COWAT (p = 0.016) scores were found to be significantly lower in the IR than the non-IR among those with APOE ε4 allele. In multiple regression analysis, impairment on the COWAT remained significantly correlated with scores on HOMA-IR (ß = -0.271, t = -2.340, p = 0.022). However, IR status was identified to interact with APOE ε4 carriership toward poor performances in the COWAT (ß = -0.335, t = -2.285, p = 0.026). CONCLUSION: This study found a domain-specific impact of HOMA-IR scores on cognitive performances in non-diabetic patients with MCI. This association was profound only in APOE ε4carriers.


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Resistência à Insulina/fisiologia , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína E4/genética , Disfunção Cognitiva/genética , Feminino , Homeostase , Humanos , Masculino , Modelos Biológicos , Testes Neuropsicológicos , Análise de Regressão
15.
Allergy Asthma Immunol Res ; 6(2): 156-62, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24587953

RESUMO

PURPOSE: Identification of tolerable alternative analgesics is crucial for management in nonsteroidal anti-inflammatory drug (NSAID)-sensitive patients. We investigated cross-reactivity of acetaminophen and celecoxib according to the type of aspirin/NSAID hypersensitivity and aimed to determine the risk factors for cross-intolerance. METHODS: We retrospectively reviewed the medical records of patients intolerant to aspirin and NSAIDs who had undergone an acetaminophen and/or celecoxib oral provocation test. Aspirin/NSAID hypersensitivity was classified into 4 types according to a recently proposed classification: aspirin-exacerbated respiratory disease (AERD), aspirin-exacerbated chronic urticaria (AECU), aspirin-induced acute urticaria/angioedema (AIAU), and NSAID-induced blended reaction (NIRD). RESULTS: A total of 180 patients with hypersensitivity to aspirin and NSAIDs were enrolled; 149 acetaminophen provocation test results and 145 celecoxib provocation test results were analyzed. The overall cross-reaction rates to acetaminophen and celecoxib were 24.8% and 10.3%, respectively. There was a significant difference in the cross-reactivity to acetaminophen according to the type of NSAID hypersensitivity. Cross-reactivity to acetaminophen was highest in the AECU group (43.9%), followed by the AERD (33.3%), NIBR (16.7%), and AIAU (12.5%) groups. Underlying chronic urticaria was more prevalent in patients with cross-intolerance to both acetaminophen (P=0.001) and celecoxib (P=0.033). Intolerance to acetaminophen was associated with intolerance to celecoxib (P<0.001). CONCLUSIONS: Acetaminophen and celecoxib may induce adverse reactions in a non-negligible portion of aspirin/NSAID-sensitive patients. Physicians should be aware of the possible cross-reactions of these alternative drugs and consider an oral challenge test to confirm their tolerability.

16.
Exp Neurol ; 248: 441-50, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23906983

RESUMO

Aging increases the co-incidence of Alzheimer's disease (AD) and type 2 diabetes (T2DM). However, the critical factors that contribute to the age-related increase in AD-T2DM comorbidity have yet to be clarified. In this study, aging effects and their relationship to AD-related pathology and T2DM as well as the underlying mechanisms of this process were investigated using obese rats with chronic T2DM. Tau pathology and its associated signaling pathways in the brain were compared between Otsuka Long-Evans Tokushima Fatty (OLETF) rats and corresponding non-diabetic controls at various ages. Tau phosphorylation at AD-related epitopes, including Thr212, Thr231, Ser262, and Ser396, increased with age in the soluble brain extracts of chronic OLETF rats and were accompanied by synaptic protein loss. There was also a marked age-dependent accumulation of polyubiquitinated substances in diabetic rats. Accordingly, tau proteins were highly polyubiquitinated in aged OLETF rats and a strong degree of co-localization existed between p-tau and ubiquitin in these neurons. In addition, the mRNA and protein levels of p62, a known cargo molecule that transports polyubiquitinated tau to proteasomal and autophagic degradation systems, decreased robustly with age in OLETF rats and there was an inverse correlation between protein levels of p62 and p-tau. The impaired degradation of polyubiquitinated p-tau due to age- and T2DM-dependent decreases in p62 transcription is a primary mechanism underlying increased AD-like pathology in a T2DM rat model as age increases. These results provide novel insight into the mechanisms supporting the age-related increase in AD-T2DM comorbidity.


Assuntos
Envelhecimento/metabolismo , Encéfalo/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas tau/metabolismo , Fatores Etários , Animais , Diabetes Mellitus Tipo 2/complicações , Modelos Animais de Doenças , Epitopos , Neurônios/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Fosforilação , Ratos , Proteína Sequestossoma-1 , Transdução de Sinais/fisiologia
17.
BMC Med Genet ; 14: 39, 2013 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-23521807

RESUMO

BACKGROUND: Asthma is a common respiratory disease that is characterized by bronchial hyperresponsiveness and airway obstruction due to chronic airway inflammation. Atopic asthma is a typical IgE-mediated disease in which the enhanced production of IgE is driven by the activation of Th2 cells, which release a distinct pattern of cytokines, including interleukin 4 (IL4) and IL3, in response to specific antigen presentation. To evaluate the methylation status of the whole genomes of bronchial mucosa tissues from subjects who lacked or had sensitization to Dermatophagoides farina (Df) and Dermatophagoides pteronyssinus (Dp). METHODS: The genome-wide DNA methylation levels in the bronchial mucosa tissues of atopic asthmatics (N=10), non-atopic asthmatics (N=7), and normal controls (N=7) were examined using microarrays. RESULTS: In the bronchial mucosa of atopic asthmatics, hypermethylation was detected at 6 loci in 6 genes, while hypomethylation was detected at 49 loci in 48 genes compared to those of non-atopic asthmatics. Genes that were assigned the ontologies of multicellular organismal process, response to organic substance, hormone metabolic process, and growth factor receptor binding were hypomethylated. The methylation levels in the mucosa of asthmatics and normal controls were similar. CONCLUSIONS: The bronchial mucosa of asthmatics who are atopic to Df or Dp have characteristic methylation patterns for 52 genes. The genes and pathways identified in the present study may be associated with the presence of atopy in asthmatics and therefore represent attractive targets for future research.


Assuntos
Antígenos de Dermatophagoides/imunologia , Asma/metabolismo , Brônquios/citologia , Metilação de DNA/genética , Genoma Humano/genética , Mucosa Respiratória/metabolismo , Adulto , Idoso , Asma/etiologia , Asma/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Estatísticas não Paramétricas
18.
J Neurochem ; 123(5): 856-65, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23020770

RESUMO

Caspase cleavage of amyloid precursor protein (APP) has been reported to be important in amyloid beta protein (Aß)-mediated neurotoxicity. However, the underlying mechanisms are not clearly understood. In this study, we explored the effect of caspase cleavage of APP on tau phosphorylation in relation to Aß. We found that Asp664 cleavage of APP increased tau phosphorylation at Thr212 and Ser262 in N2A cells and primary cultured hippocampal neurons. Compared with wild-type APP, protein phosphatase 2A (PP2A) activity was significantly increased when Asp664 cleavage was blocked by the D664A point mutation. Furthermore, we found that over-expression of C31 reduced PP2A activity. C31 binds directly to the PP2A catalytic subunit, through the asparagine, proline, threonine, tyrosine (NPTY) motif, which is essential for C31-induced tau hyperphosphorylation. However, it appears that the other fragment produced by Asp664 cleavage, Jcasp, modulates neither PP2A activity nor tau hyperphosphorylation. Asp664 cleavage and accompanying tau hyperphosphorylation were remarkably diminished by blockage of Aß production using a γ-secretase inhibitor. Taken together, our results suggest that Asp664 cleavage of APP leads to tau hyperphosphorylation at specific epitopes by modulating PP2A activity as a downstream of Aß. Direct binding of C31 to PP2A through the C31-NPTY domain was identified as a mechanism underlying this effect.


Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Proteína Fosfatase 2/metabolismo , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Western Blotting , Células Cultivadas , Eletroforese em Gel de Poliacrilamida , Imuno-Histoquímica , Camundongos , Fosforilação , Ratos , Transfecção
19.
DNA Cell Biol ; 31(11): 1604-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22994212

RESUMO

The aim of the present study was to develop a diagnostic set of single-nucleotide polymorphisms (SNPs) for discriminating aspirin-exacerbated respiratory disease (AERD) from aspirin-tolerant asthma (ATA) using the genome-wide association study (GWAS) data; the GWAS data were filtered according to p-values and odds ratios (ORs) using PLINK software, and the 10 candidate SNPs most closely associated with AERD were selected, based on 100 AERD and 100 ATA subjects. Using multiple logistic regression and receiver-operating characteristic (ROC) curve analysis, eight SNPs were chosen as the best model for distinguishing between AERD and ATA. The relative risk for AERD in each subject was calculated based on the relative risk of each of the eight SNPs. Ten of the original 109,365 SNPs highly associated (filtered with p<0.001 and ORs) with the risk for AERD were selected. A combination model of the eight SNPs among the 10 SNPs showed the highest area under the ROC curve of 0.9. The overall relative risk for AERD based on the eight SNPs was significantly different between the AERD and ATA groups (p=2.802E-21), and the sensitivity and specificity were 78% and 88%, respectively. The candidate set of eight SNPs may be useful in predicting the risk for AERD.


Assuntos
Asma Induzida por Aspirina/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Alelos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/genética , Asma Induzida por Aspirina/diagnóstico , Feminino , Frequência do Gene , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Fatores de Risco , Software , Adulto Jovem
20.
Asia Pac Allergy ; 2(2): 161-4, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22701867

RESUMO

Food-dependent exercise-induced anaphylaxis (FDEIA) is a type of exercise-induced anaphylaxis associated with postprandial exercise. We describe a 19-year-old man with FDEIA. Our patient complained of urticaria, angioedema, dizziness and hypotension associated with exercise after ingestion of walnut-containing foods in a warm environment. Skin prick test and prick to prick test were positive for walnut antigen. The attack didn't occur by free running outside for 10 min 2 h after taking walnuts, and the temperature was about -2℃. Food-exercise test was done again in a warm environment based on prior history. Anaphylaxis was developed after exercise for 10 min in a warm environment after taking walnuts. Some environmental factors such as high temperature and high humidity or cold temperature may influence exercise-induced anaphylaxis. In our case, the cofactor was a warm environment: the challenge test done in a cold environment was negative, but positive in a warm environment. Physicians should be aware that the challenge test of FDEIA can show different results depending on temperature.

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