Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Mediators Inflamm ; 2021: 6660640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285659

RESUMO

Myopia is a highly prevalent refractive disorder. We investigated the effect of diacerein on monocular form deprivation (MFD) in hamsters as a possible therapeutic intervention. Diacerein is an anthraquinone derivative drug whose active metabolite is rhein. Diacerein or atropine was applied to the MFD hamsters, and their refractive error and axial length were measured after 21 days. The refractive error (control: -0.91 ± 0.023, atropine: -0.3 ± 0.08, and diacerein: -0.27 ± 0.07 D) and axial length (control: 0.401 ± 0.017, atropine: 0.326 ± 0.017, and diacerein: 0.334 ± 0.016 mm) showed statistically significant differences between control, atropine-treated, and diacerein-treated MFD eyes. Furthermore, we determined the level of transforming growth factor-beta- (TGF-) ß1, matrix metalloproteinase- (MMP-) 2, type I collagen, interleukin- (IL-) 6, IL-8, and monocyte chemoattractant protein- (MCP-) 1 in the retina. Atropine and diacerein suppressed levels of the myopia-related TGF-ß1 and MMP-2 while increasing type I collagen expression. They also inhibited the interleukin IL-6, IL-8, and MCP-1 levels. Diacerein reduced the IL-6, IL-8, and MCP-1 expression in ARPE-19 cells. Furthermore, diacerein inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. This suggests that diacerein has a therapeutic effect on myopia and is a potential treatment option.

2.
Curr Issues Mol Biol ; 43(2): 716-727, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34287272

RESUMO

Resveratrol is a key component of red wine and other grape products. Recent studies have characterized resveratrol as a polyphenol, and shown its beneficial effects on cancer, metabolism, and infection. This study aimed to obtain insights into the biological effects of resveratrol on myopia. To this end, we examined its anti-inflammatory influence on human retinal pigment epithelium cells and in a monocular form deprivation (MFD)-induced animal model of myopia. In MFD-induced myopia, resveratrol increased collagen I level and reduced the expression levels of matrix metalloproteinase (MMP)2, transforming growth factor (TGF)-ß, and nuclear factor (NF)-κB expression levels. It also suppressed the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. Resveratrol exhibited no significant cytotoxicity in ARPE-19 cells. Downregulation of inflammatory cytokine production, and inhibition of AKT, c-Raf, Stat3, and NFκB phosphorylation were observed in ARPE-19 cells that were treated with resveratrol. In conclusion, the findings suggest that resveratrol inhibits inflammatory effects by blocking the relevant signaling pathways, to ameliorate myopia development. This may make it a natural candidate for drug development for myopia.

3.
Sci Rep ; 10(1): 15702, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973190

RESUMO

To investigate the particle size distribution of particulate matter and the concentration of specific perfluorinated compounds in indoor dust samples from several locations. Then, we used cell-based assays to investigate the effect of perfluorinated compounds on human corneal epithelial (HCEpiC), endothelial cells (HCEC) and retinal pigment epithelial cells (RPE). Indoor dust samples were collected at five different locations and PM50-10, PM10-2.5, and PM2.5-1 were fractionized. The presence and levels of 8:2 fluorotelomer alcohol, 10:2 fluorotelomer alcohol, and perfluorooctanoic acid were detected by gas chromatography-mass spectrometry. The effect of perfluorooctanoic acid on the activation of reactive oxygen species, transepithelial resistance as well as the expression of interleukin (IL)-6 and IL-8 were determined. The basolateral media of human corneal epithelial or human corneal endothelial cells were used to treat human corneal endothelial or retinal pigment epithelial cells, respectively to indicate the potential of ocular surface inflammation may result in retinal inflammation. Among perfluorinated compounds, only perfluorooctanoic acid was detected in all indoor dust samples. Perfluorooctanoic acid had the highest concentration among all perfluorinated compounds in the samples. Exposure to perfluorooctanoic acid impaired tight junction sealing and increased the levels of reactive oxygen species in human corneal epithelial cells. In human corneal epithelial cells, secretion of IL-6 and IL-8 in both apical and basolateral media was promoted significantly by perfluorooctanoic acid treatment. Stimulation with the basolateral media from perfluorooctanoic acid-treated human corneal epithelial cells induced inflammation in human corneal endothelial cells. The treatment of retinal pigment epithelial cells with the basolateral media from stimulated human corneal endothelial cells also elicited the secretion of proinflammatory cytokines. The results indicate that perfluorooctanoic acid exposure impaired the tight junction of corneal cells and caused inflammatory reactions in the retina. Exposure of the cornea to perfluorooctanoic acid contained in particulate matter might induce oxidative stress and inflammation in the retina and represent a risk factor for age-related macular degeneration.


Assuntos
Caprilatos/farmacologia , Córnea/efeitos dos fármacos , Fluorcarbonetos/farmacologia , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/farmacologia , Retina/efeitos dos fármacos , Córnea/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Retina/metabolismo , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo
4.
Int J Mol Sci ; 21(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32752134

RESUMO

The formation of foam cells, which are macrophages that have engulfed oxidized low-density lipoprotein (OxLDL), constitutes the first stage in the development of atherosclerosis. Previously, we found that knocking down galectin-12, a negative regulator of lipolysis, leads to reduced secretion of monocyte chemoattractant protein-1 (MCP-1), a chemokine that plays an important role in atherosclerosis. This prompted us to study the role of galectin-12 in atherosclerosis. With that aim, we examined foam cell formation in Gal12‒/‒ murine macrophages exposed to OxLDL and acetylated LDL (AcLDL). Then, we generated an LDL receptor and galectin-12 double knockout (DKO) mice and studied the effect of galectin-12 on macrophage function and atherosclerosis. Lastly, we evaluated the role of galectin-12 in human THP-1 macrophages using a doxycycline-inducible conditional knockdown system. Galectin-12 knockout significantly inhibited foam cell formation in murine macrophages through the downregulation of cluster of differentiation 36 (CD36), and the upregulation of ATP Binding Cassette Subfamily A Member 1 (ABCA1), ATP Binding Cassette Subfamily G Member 1 (ABCG1), and scavenger receptor class B type 1 (SRB1). Consistent with this, galectin-12 knockdown inhibited foam cell formation in human macrophages. In addition, the ablation of galectin-12 promoted M2 macrophage polarization in human and murine macrophages as evidenced by the upregulation of the M2 marker genes, CD206 and CD163, and downregulation of the M1 cytokines, tumor necrosis factor α (TNF- α), interleukin-6 (IL-6), and MCP-1. Moreover, the ablation of galectin-12 decreased atherosclerosis formation in DKO mice. Based on these results, we propose galectin-12 as a potential therapeutic target for atherosclerosis.


Assuntos
Aterosclerose/genética , Proteínas de Ciclo Celular/genética , Galectinas/genética , Macrófagos/metabolismo , Receptores de LDL/genética , Transportador 1 de Cassete de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Antígenos CD36/genética , Polaridade Celular/genética , Modelos Animais de Doenças , Células Espumosas/metabolismo , Células Espumosas/patologia , Regulação da Expressão Gênica/genética , Humanos , Lipoproteínas LDL/genética , Lipoproteínas LDL/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Knockout , Receptores Depuradores Classe B/genética
5.
J Biomed Sci ; 27(1): 24, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31937306

RESUMO

BACKGROUND: Galectin-9 is a ß-galactoside-binding protein with two carbohydrate recognition domains. Recent studies have revealed that galectin-9 regulates cellular biological reactions and plays a pivotal role in fibrosis. The aim of this study was to determine the role of galectin-9 in the pathogenesis of bleomycin-induced systemic sclerosis (SSc). METHODS: Human galectin-9 levels in the serum of patients with SSc and mouse sera galectin-9 levels were measured by a Bio-Plex immunoassay and enzyme-linked immunosorbent assay. Lung fibrosis was induced using bleomycin in galectin-9 wild-type and knockout mice. The effects of galectin-9 on the fibrosis markers and signaling molecules in the mouse lung tissues and primary lung fibroblast cells were assessed with western blotting and quantitative polymerase chain reaction. RESULTS: Galectin-9 levels in the serum were significantly higher (9-fold) in patients compared to those of healthy individuals. Galectin-9 deficiency in mice prominently ameliorated epithelial proliferation, collagen I accumulation, and α-smooth muscle actin expression. In addition, the galectin-9 knockout mice showed reduced protein expression levels of fibrosis markers such as Smad2/3, connective tissue growth factor, and endothelin-1. Differences between the wild-type and knockout groups were also observed in the AKT, mitogen-activated protein kinase, and c-Jun N-terminal kinase signaling pathways. Galectin-9 deficiency decreased the signal activation induced by transforming growth factor-beta in mouse primary fibroblasts, which plays a critical role in fibroblast activation and aberrant catabolism of the extracellular matrix. CONCLUSIONS: Our findings suggest that lack of galectin-9 protects against bleomycin-induced SSc. Moreover, galectin-9 might be involved in regulating the progression of fibrosis in multiple pathways.


Assuntos
Galectinas/sangue , Galectinas/deficiência , Fibrose Pulmonar/tratamento farmacológico , Escleroderma Sistêmico/tratamento farmacológico , Fator de Crescimento Transformador beta/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Bleomicina/toxicidade , Fibroblastos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Camundongos , Camundongos Knockout , Fibrose Pulmonar/induzido quimicamente , Escleroderma Sistêmico/induzido quimicamente , Transdução de Sinais , Proteínas Smad/metabolismo
6.
Environ Pollut ; 254(Pt B): 113031, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31454569

RESUMO

Myopia is caused by complex genetic and environmental factors. However, information regarding the effect of long-term exposure to air pollutants on the risk of development of myopia is lacking. We collected data from two linked databases: the Taiwan National Health Insurance Research Database (NHIRD) and the Taiwan Air Quality-Monitoring Database (TAQMD). A total of 15,822 children (16.3%) were diagnosed with myopia within the cohort. The incidence rate of myopia increased with exposure to increasing concentrations of particulate matter (PM2.5) and nitrogen oxides (NOx), increasing from 15.8 to 24.5 and from 13.7 to 34.4, per 1000 person-years, respectively. The adjusted hazard ratio for myopia increased with elevated PM2.5 and NOx exposure concentrations in Q4 to 1.57 and 2.60, respectively, compared to those exposed to the corresponding concentrations in Q1. In the animal experiments, PM2.5 induced myopia in hamsters by enhancing inflammation and was inhibited by resveratrol treatment compared to the control group. The change in axial length in the PM2.5 group was 0.386 ± 0.069 mm versus 0.287 ± 0.086 mm in the control group and 0.257 ± 0.059 mm in the PM2.5 + resveratrol group. We provide both clinical and experimental correlations that exposure to ambient air pollutants is associated with the pathogenesis of myopia.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição Ambiental/efeitos adversos , Miopia/etiologia , Óxidos de Nitrogênio/efeitos adversos , Material Particulado/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Animais , Criança , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Miopia/epidemiologia , Óxidos de Nitrogênio/análise , Material Particulado/análise , Modelos de Riscos Proporcionais , Taiwan/epidemiologia
8.
J Clin Med ; 7(9)2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30205439

RESUMO

Atropine and orthokeratology (OK) are both effective in slowing the progression of myopia. In the current study, we studied the combined effects of atropine and OK lenses on slowing the progression of myopia. This retrospective study included 84 patients who wore OK lenses and received atropine treatment (OA) and 95 patients who wore OK lenses alone (OK) for 2 years. We stratified patients into low (<6 D, LM) and high (≥6 D, HM) myopia groups, as well as two different atropine concentrations (0.125% and 0.025%). Significantly better LM control was observed in OA1 patients, compared with OK1 patients. Axial length was significantly shorter in the OA1 group (24.67 ± 1.53 mm) than in the OK1 group (24.9 ± 1.98 mm) (p = 0.042); similarly, it was shorter in the OA2 group (24.73 ± 1.53 mm) than in the OK2 group (25.01 ± 1.26 mm) (p = 0.031). For the HM patients, OA3 patients compared with OK3 patients, axial length was significantly shorter in the OA3 group (25.78 ± 1.46 mm) than in the OK3 group (25.93 ± 1.94 mm) (p = 0.021); similarly, it was shorter in the OA4 patients (25.86 ± 1.21 mm) than in the OK4 patients (26.05 ± 1.57 mm) (p = 0.011). Combined treatment with atropine and OK lenses would be a choice of treatment to control the development of myopia.

9.
Am J Chin Med ; 46(5): 1045-1063, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29976086

RESUMO

Obesity is a significant risk factor for various diseases. It is a clinical condition caused by the excessive accumulation of fat, which has a negative impact on human health. Galactin-12 is an adipocyte-expressed protein and possesses adipocyte-inducing activity. We investigated the expression level of candidate proteins involved in galactin-12-mediated adipocyte differentiation pathway. We performed a high-throughput screening assay to monitor galectin-12 promoter activity using 105 traditional Chinese herbs. Corn silk extract and [Formula: see text]-sitosterol reduced the expression of galactin-12 promoter in 3T3-L1 cells. In addition, corn silk extract and [Formula: see text]-sitosterol decreased the level of lipid droplets and downregulated the gene and protein expression level of C/EBP[Formula: see text], C/EBP[Formula: see text], PPAR[Formula: see text], Ap2, and adipsin in 3T3-L1 pre-adipocytes via AKT and ERK1/2 inhibition. In vivo study with the oral administration of corn silk extract and [Formula: see text]-sitosterol in a mouse model showed a significant weight reduction and decrease in adipocytes in several organs such as the liver and adipose tissue. Taken together, corn silk extract and [Formula: see text]-sitosterol may effectively reduce pre-adipocyte differentiation by inhibiting galectin-12 activity and exerting anti-obesity effects. These findings highlight the potential use of corn silk extract and [Formula: see text]-sitosterol as potential candidates for the prevention and treatment of obesity.


Assuntos
Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Proteínas de Ciclo Celular/metabolismo , Galectinas/metabolismo , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Zea mays/química , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Proteínas de Ciclo Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Galectinas/genética , Humanos , Camundongos , Células NIH 3T3 , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/fisiopatologia , PPAR gama/genética , PPAR gama/metabolismo
10.
EBioMedicine ; 28: 274-286, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29398596

RESUMO

Myopia is a highly prevalent eye disease. There is limited information suggesting a relationship between myopia and inflammation. We found children with allergic conjunctivitis (AC) had the highest adjusted odds ratio (1.75, 95% confidence interval [CI], 1.72-1.77) for myopia among the four allergic diseases. A cohort study was conducted and confirmed that children with AC had a higher incidence and subsequent risk of myopia (hazard ratio 2.35, 95%CI 2.29-2.40) compared to those without AC. Lower refractive error and longer axial length were observed in an AC animal model. Myopia progression was enhanced by tumor necrosis factor (TNF)-α or interleukin (IL)-6 administration, two cytokines secreted by mast cell degranulation. The TNF-α or IL-6 weakened the tight junction formed by corneal epithelial (CEP) cells and inflammatory cytokines across the layer of CEP cells, which increased the levels of TNF-α, IL-6, and IL-8 secreted by retinal pigment epithelial cells. The expression levels of TNF-α, IL-6, IL-8, monocyte chemoattractant protein-1, and nuclear factor kappa B were up-regulated in eyes with AC, whereas IL-10 and the inhibitor of kappa B were down-regulated. In conclusion, the experimental findings in mice corroborate the epidemiological data showing that allergic inflammation influences the development of myopia.


Assuntos
Conjuntivite Alérgica/complicações , Progressão da Doença , Inflamação/complicações , Inflamação/etiologia , Miopia/etiologia , Miopia/patologia , Retina/patologia , Animais , Criança , Estudos de Coortes , Conjuntivite Alérgica/patologia , Córnea/patologia , Demografia , Células Epiteliais/metabolismo , Feminino , Humanos , Incidência , Inflamação/patologia , Interleucina-6/metabolismo , Masculino , Modelos Biológicos , Miopia/epidemiologia , Ovalbumina/administração & dosagem , Modelos de Riscos Proporcionais , Ratos Endogâmicos Lew , Fatores de Risco , Fator de Necrose Tumoral alfa/metabolismo
11.
Mol Nutr Food Res ; 62(6): e1700616, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29345776

RESUMO

SCOPE: The aim of this study is to investigate the signaling pathways by which allyl isothiocyanate (AITC) reduces adipocyte differentiation and the efficacy of AITC in suppressing galectin-12 levels as a therapeutic for high fat diet (HFD)-induced obesity. METHODS AND RESULTS: AITC presents anti-adipogenic effects on 3T3-L1 cells by decreasing lipid droplet accumulation in a dose-dependent manner. AITC suppresses 3T3-L1 differentiation into adipocytes by decreasing galectin-12 expression and by downregulating key adipogenic transcription factors. AITC influences the expression of 3T3-L1 pre-adipocytes by modulating adipokine expression (leptin and resistin) and by regulating the protein kinase B (PKB/Akt)/cAMP response element-binding protein (CREB) pathway. In HFD-fed mice, oral administration of AITC reduces the body weight, accumulation of lipid droplets in the liver, and white adipocyte size. CONCLUSION: In summary, the results indicate that AITC inhibits adipocyte differentiation by suppressing galectin-12 levels in 3T3L1 cells and has antiobesity effects in HFD-fed mice.


Assuntos
Adipócitos/efeitos dos fármacos , Galectina 2/antagonistas & inibidores , Isotiocianatos/uso terapêutico , Obesidade/tratamento farmacológico , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Adipocinas/genética , Animais , Aterosclerose/etiologia , Diferenciação Celular/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Isotiocianatos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
12.
Biomed Res Int ; 2017: 2657913, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28828383

RESUMO

The prevalence of myopia has rapidly increased in recent decades and has led to a considerable global public health concern. In this study, we elucidate the relationship between Kawasaki disease (KD) and the incidence of myopia. We used Taiwan's National Health Insurance Research Database to conduct a population-based cohort study. We identified patients diagnosed with KD and individuals without KD who were selected by frequency matched based on sex, age, and the index year. The Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence intervals for the comparison of the 2 cohorts. The log-rank test was used to test the incidence of myopia in the 2 cohorts. A total of 532 patients were included in the KD cohort and 2128 in the non-KD cohort. The risk of myopia (hazard ratio, 1.31; 95% confidence interval, 1.08-1.58; P < 0.01) was higher among patients with KD than among those in the non-KD cohort. The Cox proportional hazards regression model showed that irrespective of age, gender, and urbanization, Kawasaki disease was an independent risk factor for myopia. Patients with Kawasaki disease exhibited a substantially higher risk for developing myopia.


Assuntos
Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Miopia/epidemiologia , Miopia/fisiopatologia , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Miopia/complicações , Modelos de Riscos Proporcionais , Fatores de Risco , Taiwan/epidemiologia
13.
Chin J Physiol ; 59(6): 315-322, 2016 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-27817193

RESUMO

MicroRNAs (miRNAs) are ~22-nucleotide long RNAs that negatively regulate gene expression and inflammatory responses in eukaryotes. The aim of this work was to evaluate the roles of miRNA (miR)-155 on the interferon-γ (IFN-γ)-induced response in biliary atresia (BA), which is the most common form of pediatric chronic liver disease and a leading indication for pediatric liver transplantation. The expression of miR-155 and the suppressor of cytokine signaling 1 (SOCS1) gene in human and mice liver tissues of BA and healthy controls was evaluated. IFN-γ-induced expression of miR-155, inflammatory cytokines and chemokines was determined in bile duct cells. A miR-155 inhibitor was used to determine the influence in the IFN-γ-induced signaling pathway by western blot analysis. A strong up-regulation of miR-155 expression was observed in BA histologic sections and mouse bile duct cells treated with IFN-γ. miR-155 down-regulated SOCS1 protein expression by targeting its mRNA. Up-regulation of miR-155 expression by IFN-γ in bile duct cells led to the activation of signal transducers and activators of transcription 1 (Stat1) and inflammatory cytokines through the Janus kinase (Jak)/Stat pathway, whereas targeted inhibition of miR-155 expression by anti-miRNA oligonucleotides significantly decreased the mRNA or protein expression levels of these inflammatory cytokines and Stat1. Overall, our results suggest that miR-155 regulates the IFN-γ signaling pathway by targeting SOCS1 expression and may be a potential target in BA therapy.


Assuntos
Atresia Biliar/metabolismo , Interferon gama/metabolismo , MicroRNAs/metabolismo , Animais , Estudos de Casos e Controles , Citocinas/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Regulação para Cima
14.
EBioMedicine ; 10: 269-81, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27470424

RESUMO

Prevention and treatment of myopia is an important public problem worldwide. We found a higher incidence of myopia among patients with inflammatory diseases such as type 1 diabetes mellitus (7.9%), uveitis (3.7%), or systemic lupus erythematosus (3.5%) compared to those without inflammatory diseases (p<0.001) using data from children (<18years old) in the National Health Insurance Research database. We then examined the inhibition of myopia by atropine in Syrian hamsters with monocular form deprivation (MFD), an experimental myopia model. We found atropine downregulated inflammation in MFD eyes. The expression levels of c-Fos, nuclear factor κB (NFκB), interleukin (IL)-6, and tumor necrosis factor (TNF)-α were upregulated in myopic eyes and downregulated upon treatment with atropine. The relationship between the inflammatory response and myopia was investigated by treating MFD hamsters with the immunosuppressive agent cyclosporine A (CSA) or the inflammatory stimulators lipopolysaccharide (LPS) or peptidoglycan (PGN). Myopia progression was slowed by CSA application but was enhanced by LPS and PGN administration. The levels of c-Fos, NF-κB, IL-6, and TNF-α were upregulated in LPS- and PGN-treated eyes and downregulated by CSA treatment. These findings provide clinical and experimental evidence that inflammation plays a crucial role in the development of myopia.


Assuntos
Inflamação/complicações , Miopia/etiologia , Miopia/patologia , Adolescente , Animais , Anti-Inflamatórios/uso terapêutico , Atropina/uso terapêutico , Técnicas de Cultura de Células , Criança , Pré-Escolar , Estudos de Coortes , Comorbidade , Cricetinae , Modelos Animais de Doenças , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Incidência , Lactente , Inflamação/tratamento farmacológico , Inflamação/epidemiologia , Masculino , Miopia/diagnóstico , Miopia/epidemiologia , Vigilância da População , Taiwan/epidemiologia
15.
Cancer Lett ; 375(2): 303-312, 2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26945968

RESUMO

Type I IFN-induced STAT6 has been shown to have anti-proliferative effects in Daudi and B cells. IFN-sensitive (DS) and IFN-resistant (DR) subclones of Daudi cells were used to study the role of STAT6 in the anti-proliferative activities. Type I IFN significantly increased STAT6 mRNA and protein expression in DS but not DR cells. STAT6 knockdown significantly reduced the sensitivity to IFN in both cell lines. The molecular targets and functional importance of IFN-activated STAT6 were performed by chromatin immunoprecipitation-on-chip (ChIP-on-chip) experiments in type I IFN-treated Daudi cells. Two target genes (Sp1 and BCL6) were selected from the ChIP-on-chip data. IFN-induced STAT6 activation led to Sp1 upregulation and BCL6 downregulation in DS cells, with only minimal effects in DR cells. siRNA inhibition of STAT6 expression resulted in decreased Sp1 and BCL6 mRNA and protein levels in both DS and DR cells. IFN treatment did not increase Sp1 and BCL6 expression in a STAT2-deficient RST2 cell line, and this effect was mitigated by plasmid overexpression of STAT2, indicating that STAT2 is important for STAT6 activation. These results suggest that STAT6 plays an important role in regulating Sp1 and BCL6 through STAT2 to exert the anti-proliferative effects of type I IFN.


Assuntos
Proteínas de Ligação a DNA/biossíntese , Interferon-alfa/administração & dosagem , Neoplasias/genética , Fator de Transcrição STAT2/biossíntese , Fator de Transcrição STAT6/genética , Fator de Transcrição Sp1/biossíntese , Linfócitos B/efeitos dos fármacos , Linfócitos B/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Proteínas Proto-Oncogênicas c-bcl-6 , Fator de Transcrição STAT2/genética , Transdução de Sinais
16.
Exp Biol Med (Maywood) ; 241(13): 1374-85, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27013543

RESUMO

Mushrooms are used in traditional Chinese medicine to treat a variety of diseases. Grifola frondosa (GF) is an edible mushroom indigenous to many Asian countries with a large fruiting body characterized by overlapping caps. In particular, GF is known for its anti-tumor activity, which has been targeted by scientific and clinical research. This study aimed to investigate the effects of the cold-water extract of GF (GFW) and its active fraction (GFW-GF) on autophagy and apoptosis, and the underlying mechanisms in vitro and in vivo Our results revealed that GFW and GFW-GF inhibited phosphatidylinositol 3-kinase (PI3K) and stimulated c-Jun N-terminal kinase (JNK) pathways, thereby inducing autophagy. We also demonstrated that GFW and GFW-GF inhibited proliferation, induced cell cycle arrest, and apoptosis in Hep3B hepatoma cells. GFW and GFW-GF markedly arrested cells in S phase and promoted cleavage of caspase-3 and -9. In addition, GFW and GFW-GF decreased the expression levels of the anti-apoptotic proteins protein kinase B and extracellular signal-regulated kinase. We also found that GFW significantly inhibited tumor growth in nude mice implanted with Hep3B cells. Our work demonstrates that GF and its active fraction inhibit hepatoma growth by inducing autophagy and apoptosis.


Assuntos
Carcinoma Hepatocelular/patologia , Misturas Complexas/farmacologia , Grifola/química , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Misturas Complexas/isolamento & purificação , Humanos , Camundongos , Camundongos Nus
17.
Glycobiology ; 26(7): 732-744, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26873172

RESUMO

Galectin-12 is a member of an animal lectin family with affinity for ß-galactosides and containing consensus amino acid sequences. Here, we found that galectin-12 was expressed in macrophages and thus aimed to determine how galectin-12 affects inflammation and macrophage polarization and activation. The ablation of galectin-12 did not affect bone marrow cells to differentiate into macrophages, but reduced phagocytic activity against Escherichia coli and lowered the secretion of nitric oxide. The ablation of galectin-12 also resulted in the polarization of macrophages into the M2 direction, as indicated by increases in the levels of M2 markers, namely, resistin-like ß (FIZZ1) and chitinase 3-like 3 (Ym1), as well as a reduction in the expression levels of a number of M1 pro-inflammatory cytokines. We found that the diminished expression of pro-inflammatory cytokines in macrophages resulting from galectin-12 deletion was due to reduced activation of IKKα/ß, Akt and ERK, which in turn caused decreased activation of NF-κB and activator protein 1. The activation of STAT3 was much higher in Gal12(-/-) macrophages activated by lipopolysaccharide, which was correlated with higher levels of IL-10. Adipocytes showed higher insulin sensitivity when treated with Gal12(-/-) macrophage-conditioned media than those treated with Gal12(+/+) macrophages. We conclude galectin-12 negatively regulates macrophage polarization into the M2 population, resulting in enhanced inflammatory responses and also in turn causing decreased insulin sensitivity in adipocytes. This has implications in the treatment of a wide spectrum of metabolic disorders.


Assuntos
Proteínas de Ciclo Celular/genética , Galectinas/genética , Inflamação/genética , Interleucina-10/genética , Fator de Transcrição STAT3/genética , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Polaridade Celular/genética , Galectinas/antagonistas & inibidores , Galectinas/metabolismo , Regulação da Expressão Gênica , Humanos , Inflamação/patologia , Insulina/metabolismo , Resistência à Insulina/genética , Ativação de Macrófagos/genética , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos
18.
BMC Cancer ; 15: 958, 2015 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-26675309

RESUMO

BACKGROUND: Flavones found in plants display various biological activities, including anti-allergic, anti-viral, anti-inflammatory, anti-oxidation, and anti-tumor effects. In this study, we investigated the anti-tumor effects of flavone, apigenin and luteolin on human breast cancer cells. METHODS: The anti-cancer activity of flavone, apigenin and luteolin was investigated using the MTS assay. Apoptosis was analyzed by Hoechst 33342 staining, flow cytometry and western blot. Cell migration was determined using the culture inserts and xCELLigence real-time cell analyzer instrument equipped with a CIM-plate 16. Real-time quantitative PCR and western blot were used to determine the signaling pathway elicited by flavone, apigenin and luteolin. RESULTS: Flavone, apigenin and luteolin showed potent inhibitory effects on the proliferation of Hs578T, MDA-MB-231 and MCF-7 breast cancer cells in a concentration and time-dependent manner. The ability of flavone, apigenin and luteolin to inhibit the growth of breast cancer cells through apoptosis was confirmed by Hoechst33342 staining and the induction of sub-G1 phase of the cell cycle. Flavone, apigenin and luteolin induced forkhead box O3 (FOXO3a) expression by inhibiting Phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB)/Akt. This subsequently elevated the expression of FOXO3a target genes, including the Cyclin-dependent kinase inhibitors p21Cip1 (p21) and p27kip1 (p27), which increased the levels of activated poly(ADP) polymerase (PARP) and cytochrome c. CONCLUSION: Taken together, these data demonstrated that flavone, apigenin and luteolin induced cell cycle arrest and apoptosis in breast cancer cells through inhibiting PI3K/Akt activation and increasing FOXO3a activation, which suggest that flavone, apigenin and luteolin will be the potential leads for the preventing and treating of breast cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Flavonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/metabolismo , Humanos , Luteolina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
19.
Biomed Res Int ; 2015: 893796, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26273655

RESUMO

OBJECTIVES: MUTYH glycosylase involved in DNA repair pathways may be associated with the risk of autoimmune diseases such as rheumatoid arthritis (RA). Therefore, the association between polymorphisms in the MUTYH gene and RA was evaluated. METHODS: We recruited 192 RA patients and 192 healthy subjects in Taiwan. The 4 MUTYH polymorphisms (rs3219463, rs3219476, rs3219489, and rs3219493) were detected and haplotype analysis was performed using the Bayesian method. The genotype and allelic frequency distributions of the polymorphisms in both RA patients and healthy patients were compared by the chi-square test. RESULTS: Comparison of the genotype/allele frequencies between individuals with RA and the control groups revealed significant differences in 2 MUTYH gene polymorphisms, rs3219463 and rs3219476. After we performed a haplotype-specific analysis, the haplotypes Ht6-GTGC and Ht8-GGCG had lower presenting rates in RA patients than in the control groups. Furthermore, the genotype frequency of rs3219463 G/ was significantly increased among patients with immunoglobulin M rheumatoid factors, whereas that of rs3219476 was not. CONCLUSION: We demonstrated that the rs3219463 and rs3219476 polymorphisms in RA patients from a Taiwan Chinese population were associated with disease susceptibility. These data indicate that the MUTYH gene may play a role in the progression of RA.


Assuntos
Artrite Reumatoide/epidemiologia , Artrite Reumatoide/genética , DNA Glicosilases/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Artrite Reumatoide/diagnóstico , Sequência de Bases , Feminino , Marcadores Genéticos/genética , Haplótipos/genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Taiwan/epidemiologia
20.
Chin J Physiol ; 57(2): 69-75, 2014 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-24694201

RESUMO

Graves' disease (GD) is a complex, organ-specific autoimmune disease wherein the thyroid gland becomes enlarged and overactive. During GD progression, T cells secrete interleukin-16 (IL-16) to promote inflammation, act as chemoattractants that recruit more inflammatory cells, and activate target cells to enhance the development of GD. To investigate the role of IL-16 in GD, we genotyped 474 patients with GD at 8 single-nucleotide polymorphisms (SNPs) in the IL-16 gene. The IL-16 SNP rs8028364 was found to be associated with GD when compared with the control subjects (P = 2.93 × 10⁻¹7; CG genotype: odds ratio [OR] = 0.2 [0.07, 0.59]; CC genotype: OR = 0.03 [0.01, 0.09]). The rs1131445 polymorphism was found to be associated with GD under the allelic model (P = 0.01; G allele: OR = 1.97 [1.17, 3.32]). Sliding-window haplotype analysis by the PLINK program showed that the most significant haplotype was provided by the 6-SNP haplotype window, consisting of rs7182786, rs8028364, rs12907134, rs4128767, rs4072111 and rs8031107 (P = 2.31 × 10⁻5¹). We found 2 protective haplotypes: GCAAGG (P = 8.69 × 10⁻7; OR = 0.22 [0.12, 0.41]) and AGAAGG (P = 0.0012; OR = 0.26 [0.12, 0.6]). In addition, GGGGAA (P = 0.39; OR = 2.32 [1.08, 4.99]) and GGGAGA (P = 1.18 × 10⁻5; OR = 5.54 [2.50, 12.31]) were found to be the two high-risk haplotypes. These results suggest that polymorphisms in IL-16 may be used as genetic markers for the diagnosis and prognosis of GD.


Assuntos
Doença de Graves/genética , Interleucina-16/genética , Polimorfismo de Nucleotídeo Único , Genótipo , Haplótipos , Humanos , Taiwan
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...