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1.
Nutr Res Pract ; 18(2): 180-193, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38584817

RESUMO

BACKGROUND/OBJECTIVES: Obesity is a major cause of metabolic disorders; to prevent obesity, research is ongoing to develop natural and safe ingredients with few adverse effects. In this study, we determined the anti-obesity effects of Rosa multiflora root extract (KWFD-H01) in 3T3-L1 adipocytes and Sprague-Dawley (SD) rats. MATERIALS/METHODS: The anti-obesity effects of KWFD-H01in 3T3-L1 adipocytes and SD rats were examined using various assays, including Oil Red O staining, gene expression analyses, protein expression analyses, and blood biochemical analyses. RESULTS: KWFD-H01 reduced intracellular lipid accumulation and inhibited the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins (C/EBPα), sterol regulatory element-binding transcription factor 1 (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) in 3T3-L1 cells. KWFD-H01 also reduced body weight, weight gain, and the levels of triglycerides, total and LDL-cholesterol, glucose, and leptin, while increasing high-density lipoprotein-cholesterol and adiponectin in SD rats. PPARγ, C/EBPα, SREBP-1c, ACC, and FAS protein expression was inhibited in the epididymal fat of SD rats. CONCLUSION: Overall, these results confirm the anti-obesity effects of KWFD-H01 in 3T3-L1 adipocytes and SD rats, indicating their potential as baseline data for developing functional health foods or pharmaceuticals to control obesity.

2.
Int J Mol Sci ; 24(19)2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37834275

RESUMO

Hepatic stellate cells (HSCs) are the main contributors to the development and progression of liver fibrosis. Parkin is an E3 ligase involved in mitophagy mediated by lysosomes that maintains mitochondrial homeostasis. Unfortunately, there is little information regarding the regulation of parkin by transforming growth factor-ß (TGF-ß) and its association with HSC trans-differentiation. This study showed that parkin is upregulated in fibrotic conditions and elucidated the underlying mechanism. Parkin was observed in the cirrhotic region of the patient liver tissues and visualized using immunostaining and immunoblotting of mouse fibrotic liver samples and primary HSCs. The role of parkin-mediated mitophagy in hepatic fibrogenesis was examined using TGF-ß-treated LX-2 cells with mitophagy inhibitor, mitochondrial division inhibitor 1. Parkin overexpression and its colocalization with desmin in human tissues were found. Increased parkin in fibrotic liver homogenates of mice was observed. Parkin was expressed more abundantly in HSCs than in hepatocytes and was upregulated under TGF-ß. TGF-ß-induced parkin was due to Smad3. TGF-ß facilitated mitochondrial translocation, leading to mitophagy activation, reversed by mitophagy inhibitor. However, TGF-ß did not change mitochondrial function. Mitophagy inhibitor suppressed profibrotic genes and HSC migration mediated by TGF-ß. Collectively, parkin-involved mitophagy by TGF-ß facilitates HSC activation, suggesting mitophagy may utilize targets for liver fibrosis.


Assuntos
Células Estreladas do Fígado , Fator de Crescimento Transformador beta , Animais , Humanos , Camundongos , Fígado/patologia , Cirrose Hepática/patologia , Mitofagia , Transdução de Sinais , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta1/genética , Ubiquitina-Proteína Ligases/genética
3.
Molecules ; 28(6)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36985813

RESUMO

Ultraviolet B (UVB) rays disrupt the skin by causing photodamage via processes such as reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, DNA damage, and/or collagen degradation. Castanopsis sieboldii is an evergreen tree native to the southern Korean peninsula. Although it is known to have antioxidant and anti-inflammatory effects, its protective effect against photodamage in keratinocytes has not been investigated. Thus, in the present study, we investigated the effect of 70% ethanol extract of C. sieboldii leaf (CSL3) on UVB-mediated skin injuries and elucidated the underlying molecular mechanisms. CSL3 treatment restored the cell viability decreased by UVB irradiation. Moreover, CSL3 significantly inhibited UVB- or tert-butyl hydroperoxide-mediated ROS generation in HaCaT cells. ER stress was inhibited, whereas autophagy was upregulated by CSL3 treatment against UVB irradiation. Additionally, CSL3 increased collagen accumulation and cell migration, which were decreased by UVB exposure. Notably, epigallocatechin gallate, the major component of CSL3, improved the cell viability decreased by UVB irradiation through regulation of ER stress and autophagy. Conclusively, CSL3 may represent a promising therapeutic candidate for the treatment of UVB-induced skin damage.


Assuntos
Queratinócitos , Pele , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Pele/metabolismo , Colágeno/metabolismo , Raios Ultravioleta/efeitos adversos
4.
Plants (Basel) ; 10(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34371643

RESUMO

Salt stress is a major constraint of crop productivity because it reduces yield and limits the expansion of agriculture. This study investigated salt tolerance in 26 cultivars of cut lilies (Lilium hybrids) by examining the effect of salt stress on the growth and morphological characteristics of flowers and leaves and their physiological properties (chlorophyll a fluorescence). Salt stress significantly affected the growth and development of cut lilies. Canonical discriminant analysis indicates that the middle leaf width, number of flowers, first flower diameter, petal width, and chlorophyll a fluorescence were correlated with salt stress, whereas plant height, the middle leaf length, days to flowering, and sepal width were less affected by the stress. The cultivars examined were divided into three groups: Group 1 included the salt-sensitive cultivars, which failed to develop normal flowers; Group 2 included cultivars sensitive to salt stress but tolerant to osmotic stress; and Group 3 was the salt-tolerant group, which developed commercially valuable flowers. In conclusion, the cultivars contained a variable range of cut flower characteristics and growth traits that can be employed for lily breeding programs and as material for molecular mechanisms and signaling networks under salt stress.

5.
Mol Ther ; 29(4): 1557-1571, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33359791

RESUMO

Aberrant expression of CA125/MUC16 is associated with pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. However, knowledge of the contribution of MUC16 to pancreatic tumorigenesis is limited. Here, we show that MUC16 expression is associated with disease progression, basal-like and squamous tumor subtypes, increased tumor metastasis, and short-term survival of PDAC patients. MUC16 enhanced tumor malignancy through the activation of AKT and GSK3ß oncogenic signaling pathways. Activation of these oncogenic signaling pathways resulted in part from increased interactions between MUC16 and epidermal growth factor (EGF)-type receptors, which were enhanced for aberrant glycoforms of MUC16. Treatment of PDAC cells with monoclonal antibody (mAb) AR9.6 significantly reduced MUC16-induced oncogenic signaling. mAb AR9.6 binds to a unique conformational epitope on MUC16, which is influenced by O-glycosylation. Additionally, treatment of PDAC tumor-bearing mice with either mAb AR9.6 alone or in combination with gemcitabine significantly reduced tumor growth and metastasis. We conclude that the aberrant expression of MUC16 enhances PDAC progression to an aggressive phenotype by modulating oncogenic signaling through ErbB receptors. Anti-MUC16 mAb AR9.6 blocks oncogenic activities and tumor growth and could be a novel immunotherapeutic agent against MUC16-mediated PDAC tumor malignancy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antígeno Ca-125/genética , Carcinogênese/genética , Carcinoma Ductal Pancreático/tratamento farmacológico , Receptores ErbB/genética , Proteínas de Membrana/genética , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Animais , Anticorpos Monoclonais/farmacologia , Antígeno Ca-125/imunologia , Carcinogênese/imunologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/imunologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/imunologia , Camundongos , Metástase Neoplásica , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Transdução de Sinais
6.
Oxid Med Cell Longev ; 2020: 5915481, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029281

RESUMO

Intervertebral disc degeneration (IVDD) is a common cause of lower back pain. Programmed cell death (PCD) including apoptosis and autophagy is known to play key mechanistic roles in the development of IVDD. We hypothesized that the nucleus pulposus cells that make up the center of the IVD can be affected by aging and environmental oxygen concentration, thus affecting the development of IVDD. Here, we evaluated the phenotype changes and PCD signaling in nucleus pulposus cells in two different oxygen percentages (5% (hypoxia) and 20% (normoxia)) up to serial passage 20. NP cells were isolated from the lumbar discs of rats, and the chondrogenic, autophagic, and apoptotic gene expressions were analyzed during cell culture up to serial passage 20. Hypoxia significantly increased the number of autophagosomes, as determined by monodansylcadaverine staining and transmission electron microscopy. Furthermore, hypoxia triggered the activation of autophagic flux (beclin-1, LC3-II/LC3-I ratio, and SIRT1) with a concomitant decrease in the expression of apoptotic proteins (Bax and caspase-3). Despite injury and age differences, no significant differences were observed between the ex vivo lumbar disc cultures of groups incubated in the hypoxic chamber. Our study provides a better understanding of autophagy- and apoptosis-related senescence in NP cells. These results also provide insight into the effects of aging on NP cells and their PCD levels during aging.


Assuntos
Apoptose/genética , Autofagia/genética , Hipóxia Celular , Animais , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Sobrevivência Celular , Células Cultivadas , Condrogênese/genética , Masculino , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Núcleo Pulposo/citologia , Núcleo Pulposo/metabolismo , Ratos , Ratos Sprague-Dawley , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
7.
Biosens Bioelectron ; 161: 112252, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32442107

RESUMO

In line with growing interest in obesity management, there has been an increase in the amount of research focused on highly sensitive analysis systems for a small number of biomarers. In this paper, we introduce the highly ordered nanopillar electrode, featuring a high aspect ratio surface area that enables enhanced electron transfer. For fabrication of the flexible electrode, gold was evaporated by electronic beam lithography on polyurethane (PU), which has high flexibility. The fabricated nanopillar is 500 nm in diameter and 1500 nm in height. Based on the highly ordered nanostructure electrode, insulin was selected as a biomarker to monitor the insulin resistance associated with obesity. To effectively analyze the insulin, the self-assembled monolayer chemical was used to introduce the enzyme catalysis-based electrochemical immunoassay, leading to the analysis of the insulin concentration range from 0.1 to 1.0 ng/mL in the real sample. The square wave voltammetry principle was used to measure HRP-based electrochemical signal both electrochemically and quantitatively. Based on the nanostructural properties of significant electrochemical behavior, we successfully analyzed insulin in the plasma sample with high sensitivity (LOD of 0.1 ng/mL) and with high reproducibility (<10%). The obtained sensitivity of nanopillar electrode is approximately 10 times (1020%) greater than that of commercial electrode. The results demonstrated that the nanopillar electrode is suitable for precise and sensitive analysis of low-level biomolecules in medical and commercial fields.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas/métodos , Insulina/isolamento & purificação , Nanopartículas Metálicas/química , Eletrodos , Ouro/química , Humanos , Insulina/química , Poliuretanos/química
8.
Int J Biol Macromol ; 146: 922-930, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31726172

RESUMO

Articular cartilage exhibits reduced self-healing following degeneration. This research evaluated the effects of hydrogels derived from various polysaccharides-gellan gum (GG), alginate, and agarose-on cartilage regeneration compared with that of hyaluronic acid (HA), which is commonly used in cartilage tissue engineering. Chondrocytes were isolated from the articular cartilage of New Zealand White (NZW) rabbits and stimulated with IL-1ß followed by incubation with polysaccharides. The expressions of NF-κB and Cox-2 were decreased and those of IκBα, Sox-9, aggrecan, and type II collagen were increased in HA, GG, and Alginate groups. Osteochondral defects in NZW rabbits were treated with intra-articular polysaccharide injections; all except alginate resulted in tissue regeneration. Significant improvements were observed in cartilage regeneration in the GG and agarose groups. These results show that GG and agarose improve cartilage regeneration by suppressing inflammatory mediators and inducing cartilage formation and autophagy-related gene expression, indicating their potential for cartilage tissue engineering.


Assuntos
Autofagia/genética , Cartilagem Articular/fisiologia , Condrogênese/genética , Regulação da Expressão Gênica , Polissacarídeos/farmacologia , Regeneração , Alginatos/farmacologia , Animais , Autofagia/efeitos dos fármacos , Biomarcadores/metabolismo , Cartilagem Articular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrogênese/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Hialurônico/farmacologia , Hidrogéis/química , Inflamação/genética , Inflamação/patologia , Masculino , Osteoartrite/patologia , Polissacarídeos Bacterianos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Coelhos , Regeneração/efeitos dos fármacos , Reologia , Sefarose/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
9.
Oncol Rep ; 41(5): 2625-2635, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896812

RESUMO

The majority of natural killer (NK) cells serve an important role in eliminating malignant cells. The cytotoxic effects of NK cells were first identified against leukemia cells, and it is now hypothesized that they may have a critical role in leukemia therapy. The cellular functions of NK cells are mediated by their cell surface receptors, which recognize ligands on cancer cells. The role of NK cells is specifically regulated by the activating or inhibitory killer cell immunoglobulin­like receptors (KIRs) on their surface, which bind to the human leukocyte antigen (HLA) class I ligands present on the target cells. The association between KIR and HLA is derived from the diversity of KIR/HLA gene profiles present in different individuals, and this determines the cytotoxic effect of NK cells on cancer cells. Chronic myeloid leukemia (CML) is a hematological leukemia characterized by the hyper­proliferation of myeloid cells, with the majority of patients with CML presenting with abnormal immune cells. Tyrosine kinase inhibitors are the present standard therapy for CML, but are associated with numerous adverse side effects. Various studies have proposed CML therapy by immunotherapeutic approaches targeting the immune cells. This review summarizes the contents of NK cells and the association between KIR/HLA and leukemia, especially CML. This is followed by a discussion on the development of NK cell immunotherapy in hematological malignancies and research into strategies to enhance NK cell function for CML treatment.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Imunoterapia/métodos , Células Matadoras Naturais/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Receptores KIR/antagonistas & inibidores , Antineoplásicos Imunológicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Ensaios Clínicos como Assunto , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Receptores KIR/imunologia , Receptores KIR/metabolismo
10.
Yonsei Med J ; 59(4): 519-523, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29749135

RESUMO

PURPOSE: Kawasaki disease (KD) is a mucocutaneous lymph node syndrome. It is mainly seen in young children under the age of five. KD is a multifactorial disorder that includes genetic variants. The present study investigated the association between KD and single nucleotide polymorphisms (SNPs) in the candidate gene early B cell factor 2 (EBF2), which is associated with inflammation markers. MATERIALS AND METHODS: An SNP analysis was performed by whole exon sequencing of the EBF2 gene. Our study comprised a total of 495 subjects (295 KD patients and 200 unrelated normal controls) from a Korean population. Tag SNPs were discovered using the Haploview program. Genotyping of the EBF2 gene was performed with the TaqMan® assay with real-time PCR methods. RESULTS: Polymorphism of rs10866845 showed a significant difference in allele frequency between KD patients and controls (p=0.040). The EBF2 gene polymorphisms were significantly associated with KD on logistic regression analysis. CONCLUSION: EBF2 gene variants can contribute to KD in the Korean population.


Assuntos
Povo Asiático/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Predisposição Genética para Doença/etnologia , Síndrome de Linfonodos Mucocutâneos/etnologia , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Genótipo , Humanos , Lactente
11.
Adv Healthc Mater ; 7(14): e1701496, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29761643

RESUMO

It is required to exfoliate and functionalize 2D transition metal dichalcogenides (TMDs) in an aqueous solution for biological and medical applications. Herein, the approach for the simultaneous exfoliation and functionalization of 2D WS2 nanosheets using boronic acid-modified poly(vinyl alcohol) (B-PVA) in an aqueous solution is reported, and the B-PVA-functionalized WS2 nanosheets (B-PVA-WS2 ) are exploited as a fluorescent biosensor for the detection of glycated hemoglobin, HbA1c. The synthetic B-PVA polymer facilitates the exfoliation and functionalization of WS2 nanosheets from the bulk counterpart in the aqueous solution via a pulsed sonication process, resulting in fluorescent B-PVA-WS2 nanohybrids with a specific recognition of HbA1c. The fluorescence of the B-PVA-WS2 is quenched in the presence of HbA1c, whereas PVA-functionalized WS2 (PVA-WS2 ), not bearing boronic acid as a recognition moiety, shows no fluorescence changes upon the addition of the target. The B-PVA-WS2 is able to selectively detect HbA1c at the concentration as low as 3.3 × 10-8 m based on its specific fluorescence quenching.


Assuntos
Técnicas Biossensoriais/métodos , Hemoglobinas Glicadas/análise , Nanoestruturas/química , Animais , Ácidos Borônicos/química , Humanos
12.
Immunol Lett ; 198: 44-51, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29608924

RESUMO

A20 is a zinc finger protein that effectively inhibits the activation of nuclear factor (NF)-κB to downregulate the expression of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-17. A20 also plays a crucial role as a feedback inhibitor of the inflammatory response. Due to its inhibitory role, A20 may be useful in regulating diseases resulting from chronic inflammation and excessive pro-inflammatory cytokine production, such as colitis. Patients with colitis produce high levels of pro-inflammatory cytokines in the intestine. Therefore, this study aimed to investigate whether A20 improves experimental colitis by reducing high levels of inflammation in the intestine. An A20 overexpression vector was administered to mice by intrarectal injection after colitis induction. Histological analysis by immunohistochemistry was used to score sections of the intestine. Confocal laser scanning microscopy was used to identify the expression of IL-17 and forkhead box p (FOXP) 3 protein in spleen tissues. Protein expression induced by STAT3 and NF-κB signaling was analyzed by western blot. We found that A20 reduced the colitis activity index score and the histological score of the intestine. A20 also decreased inflammatory cytokine levels in the intestine and increased colon length. Additionally, A20 overexpression downregulated the activation of NF-kB and STAT3. A20 also reduced IL-17 expression in CD4+ T cells from spleen sections. In contrast, A20 overexpression enhanced the expression of FOXP3 in CD4+ T cells. These results suggest that A20 may inhibit the progression of colitis by decreasing inflammation via inhibition of NF-κB, phosphorylated STAT3, and IL-17.


Assuntos
Doenças Inflamatórias Intestinais/metabolismo , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Animais , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Células HT29 , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/patologia , Intestinos/patologia , Masculino , Camundongos Endogâmicos C57BL , Fosforilação , Transdução de Sinais , Baço/citologia , Células Th17/citologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética
13.
Protein Expr Purif ; 143: 14-19, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28988144

RESUMO

A20 (also known as TNFAIP3) is a potent anti-inflammatory protein that suppresses many intracellular signaling pathways induced by inflammatory cytokines and bacterial and viral pathogens. The anti-inflammatory function of A20 depends on its modulation of or binding to polyubiquitin chains on key signaling proteins in the nuclear factor-κB (NF-κB) pathway. To test whether A20 can be used as therapeutic agent in these inflammatory diseases, we prepared a recombinant cell-penetrating form of A20 (TAT-A20) for intracellular delivery and examined its effect on tumor necrosis factor-α (TNFα)-induced NF-κB activation. We observed that TAT-A20 was effectively transduced into cells within 30 min, whereas A20 protein without TAT motive was not. TAT-A20 also inhibited NF-κB induction in fibroblasts stimulated with TNFα. These results suggest that increasing intracellular level of A20 can be an effective means to suppress NF-κB activation and treat inflammatory diseases.


Assuntos
Peptídeos Penetradores de Células/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/genética , Escherichia coli/genética , Células HEK293 , Humanos , Espaço Intracelular/metabolismo , Redobramento de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/química , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética
14.
BMB Rep ; 50(9): 472-477, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28855027

RESUMO

The transcription repressor Bach2 has been proposed as a regulator of T cell quiescence, but the underlying mechanism is not fully understood. Given the importance of interleukin-2 in T cell activation, we investigated whether Bach2 is a component of the network of factors that regulates interleukin-2 expression. In primary and transformed CD4+ T cells, Bach2 overexpression counteracted T cell receptor/CD28- or PMA/ionomycin-driven induction of interleukin-2 expression, and silencing of Bach2 had the opposite effect. Luciferase and chromatin immunoprecipitation assays revealed that Bach2 binds to multiple Maf-recognition element-like sites on the interleukin-2 proximal promoter in a manner competitive with AP-1, and thereby represses AP-1-driven induction of interleukin-2 transcription. Thus, this study demonstrates that Bach2 is a direct repressor of the interleukin-2 gene in CD4+ T cells during the immediate early phase of AP-driven activation, thereby playing an important role in the maintenance of immune quiescence in the steady state. [BMB Reports 2017; 50(9): 472-477].


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Interleucina-2/metabolismo , Fator de Transcrição AP-1/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Células Cultivadas , Camundongos , Camundongos Knockout , Regiões Promotoras Genéticas/genética
15.
Int J Biometeorol ; 61(2): 259-272, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27387542

RESUMO

Pollen is an important cause of respiratory allergic reactions. As individual sanitation has improved, allergy risk has increased, and this trend is expected to continue due to climate change. Atmospheric pollen concentration is highly influenced by weather conditions. Regression analysis and modeling of the relationships between airborne pollen concentrations and weather conditions were performed to analyze and forecast pollen conditions. Traditionally, daily pollen concentration has been estimated using regression models that describe the relationships between observed pollen concentrations and weather conditions. These models were able to forecast daily concentrations at the sites of observation, but lacked broader spatial applicability beyond those sites. To overcome this limitation, an integrated modeling scheme was developed that is designed to represent the underlying processes of pollen production and distribution. A maximum potential for airborne pollen is first determined using the Weibull probability density function. Then, daily pollen concentration is estimated using multiple regression models. Daily risk grade levels are determined based on the risk criteria used in Korea. The mean percentages of agreement between the observed and estimated levels were 81.4-88.2 % and 92.5-98.5 % for oak and Japanese hop pollens, respectively. The new models estimated daily pollen risk more accurately than the original statistical models because of the newly integrated biological response curves. Although they overestimated seasonal mean concentration, they did not simulate all of the peak concentrations. This issue would be resolved by adding more variables that affect the prevalence and internal maturity of pollens.


Assuntos
Alérgenos/análise , Modelos Biológicos , Modelos Estatísticos , Pólen , Poluentes Atmosféricos/análise , Previsões , Humulus , Quercus , Análise de Regressão , República da Coreia , Risco
16.
ACS Nano ; 10(5): 5346-53, 2016 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-27136042

RESUMO

It has been of great interest to measure the activity of acetylcholinesterase (AChE) and its inhibitor, as AChE is known to accelerate the aggregation of the amyloid beta peptides that underlie Alzheimer's disease. Herein, we report the development of graphene oxide (GO) fluorescence-based biosensors for the detection of AChE activity and AChE inhibitors. To this end, GO was non-covalently functionalized with phenoxy-modified dextran (PhO-dex-GO) through hydrophobic interaction; the resulting GO showed excellent colloidal stability and intense fluorescence in various aqueous solutions as compared to pristine GO and the GO covalently functionalized with dextran. The fluorescence of PhO-dex-GO remarkably increased as AChE catalyzed the hydrolysis of acetylthiocholine (ATCh) to give thiocholine and acetic acid. It was found that the turn-on fluorescence response of PhO-dex-GO to AChE activity was induced by protonation of carboxyl groups on it from the product of the enzymatic hydrolysis reaction, acetic acid. On the basis of its turn-on fluorescence response, PhO-dex-GO was able to report kinetic and thermodynamic parameters involving a maximum velocity, a Michaelis constant, and an inhibition dissociation constant for AChE activity and inhibition. These parameters enable us to determine the activity of AChE and the efficiency of the inhibitor.


Assuntos
Acetilcolinesterase/química , Peptídeos beta-Amiloides , Técnicas Biossensoriais , Grafite , Acetiltiocolina , Inibidores da Colinesterase , Óxidos
17.
Chem Commun (Camb) ; 52(36): 6150-3, 2016 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-27075825

RESUMO

Semiconducting WS2 nanohybrids with different sizes of silver nanoparticles are designed via amine-assisted in situ reduction and growth of Ag(+) ions. These nanohybrids exhibit characteristic photocatalytic activity for the reduction of 4-nitrophenol as a function of their structure.

18.
Biomaterials ; 85: 18-29, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26854388

RESUMO

Mesenchymal cells condensation is crucial in chondrogenic development. However current tissue-engineered scaffolds for chondrogenesis pay little attention to this phenomenon. In this study, we fabricate poly(l-lactide-co-glycolide) (PLGA)/poly(l-lactide) (PLLA) microfiber scaffolds and coat them with human fibroblast-derived matrix (hFDM) that is a decellularized extracellular matrix (ECM) obtained from in vitro cultured human lung fibroblasts (WI-38). Those scaffolds were then conjugated with heparin via EDC chemistry and subsequently immobilized with transforming growth factor (TGF)-ß1. The amount of TGF-ß1 was quantitatively measured and the release profile showed a continuous release of TGF-ß1 for 4 weeks. Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) were seeded in four different scaffolds; control, fibronectin (FN)-coated, hFDM-coated, hFDM/TGF-ß1 and subjected to chondrogenic differentiation in vitro for up to 28 days. Both hFDM and hFDM/TGF-ß1 groups exhibited significantly more synthesis of glycosaminoglycan (GAG) and much better upregulation of chondrogenic markers expression. Interestingly, MSCs condensation that led to cell aggregates was clearly observed with time in the two hFDM-coated groups and the quantitative difference was obvious compared to the control and FN group. A mechanistic study in gene and protein level indicated that focal adhesion kinase (FAK) was involved at the early stage of cell adhesion and cell-cell contact-related markers, N-cadherin and neural cell adhesion molecule (NCAM), were highly up-regulated at later time point. In addition histological analysis proved that hFDM/TGF-ß1 group was the most effective in forming neocartilage tissue in a rabbit articular cartilage defect model. Taken together, this study demonstrates not only the positive effect of hFDM on chondrogenesis of MSCs and cartilage repair but also provides an important insight toward the significance of in vitro mesenchymal condensation on chondrogenic development of MSCs.


Assuntos
Cartilagem Articular/crescimento & desenvolvimento , Células-Tronco Mesenquimais/citologia , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Caderinas/genética , Caderinas/metabolismo , Diferenciação Celular , Proliferação de Células , Condrogênese/fisiologia , Materiais Revestidos Biocompatíveis/química , Matriz Extracelular/química , Fibroblastos/citologia , Proteína-Tirosina Quinases de Adesão Focal/genética , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Glicosaminoglicanos/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Ácido Láctico/química , Pulmão/citologia , Pulmão/metabolismo , Masculino , Moléculas de Adesão de Célula Nervosa/genética , Moléculas de Adesão de Célula Nervosa/metabolismo , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima
19.
Int J Mol Sci ; 17(1)2016 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-26784189

RESUMO

Despite the susceptibility to frequent intrinsic and extrinsic injuries, especially in the inner zone, the meniscus does not heal spontaneously owing to its poor vascularity. In this study, the effect of platelet-rich plasma (PRP), containing various growth factors, on meniscal mechanisms was examined under normal and post-traumatic inflammatory conditions. Isolated primary meniscal cells of New Zealand white (NZW) rabbits were incubated for 3, 10, 14 and 21 days with PRP(-), 10% PRP (PRP(+)), IL(+) or IL(+)PRP(+). The meniscal cells were collected and examined using reverse-transcription polymerase chain reaction (RT-PCR). Culture media were examined by immunoblot analyses for matrix metalloproteinases (MMP) catabolic molecules. PRP containing growth factors improved the cellular viability of meniscal cells in a concentration-dependent manner at Days 1, 4 and 7. However, based on RT-PCR, meniscal cells demonstrated dedifferentiation, along with an increase in type I collagen in the PRP(+) and in IL(+)PRP(+). In PRP(+), the aggrecan expression levels were lower than in the PRP(-) until Day 21. The protein levels of MMP-1 and MMP-3 were higher in each PRP group, i.e., PRP(+) and IL(+)PRP(+), at each culture time. A reproducible 2-mm circular defect on the meniscus of NZW rabbit was used to implant fibrin glue (control) or PRP in vivo. After eight weeks, the lesions in the control and PRP groups were occupied with fibrous tissue, but not with meniscal cells. This study shows that PRP treatment of the meniscus results in an increase of catabolic molecules, especially those related to IL-1α-induced inflammation, and that PRP treatment for an in vivo meniscus injury accelerates fibrosis, instead of meniscal cartilage.


Assuntos
Desdiferenciação Celular , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Meniscos Tibiais/metabolismo , Plasma Rico em Plaquetas/metabolismo , Agrecanas/genética , Agrecanas/metabolismo , Animais , Condrócitos/citologia , Colágeno/genética , Colágeno/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Meniscos Tibiais/citologia , Coelhos
20.
Vet Clin Pathol ; 44(3): 410-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25970518

RESUMO

BACKGROUND: Performance evaluation of point-of-care (POC) electrolyte analyzers is essential for determining their precision and accuracy in clinical practice. OBJECTIVE: The purpose of this study was to validate the i-Smart 30 VET Electrolyte Analyzer for canine, feline, bovine, and porcine samples in comparison with the ion-selective electrolyte analyzer Roche 9180 electrolyte analyzer. METHODS: A total of 400 heparinized whole blood samples were collected and analyzed by both instruments for sodium, potassium, and chloride concentrations. Within-run, between-day, and total imprecision were evaluated. Statistical analyses included tests for correlation, regression, bias, and total error. RESULTS: The coefficients of variation (CV) of both within-run and between-day imprecisions in the i-Smart 30 VET ranged from 0.4-1.6%. In addition, total CV (0.3-1.7%) and total error (0.7-3.7%) of the i-Smart 30 VET were acceptable according to the ASVCP guidelines (< 5%). The correlation between the i-Smart 30 VET and the Roche 9180 was excellent (r > .98). There was no proportional error according to the regression (slope ranges 0.92-1.00, 95% CI includes 1.00), but a constant error was detected for sodium concentration in dogs (interval = 0.5), cattle (interval = 3.0), and pigs (interval = 4.0), and for chloride concentration in cats (interval = 1.0). Most of the bias was within 95% CI, and the total error range (0.8-3.5%) was acceptable according to ASVCP guidelines. CONCLUSION: The i-Smart 30 VET Electrolyte Analyzer provides precise and accurate measurements of sodium, potassium, and chloride concentrations in whole blood samples from dogs, cats, cattle, and pigs.


Assuntos
Análise Química do Sangue/veterinária , Gatos/fisiologia , Bovinos/fisiologia , Cães/fisiologia , Eletrólitos/sangue , Suínos/fisiologia , Animais , Análise Química do Sangue/instrumentação , Cloretos/sangue , Feminino , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Potássio/sangue , Reprodutibilidade dos Testes , Sódio/sangue
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