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1.
Nature ; 584(7820): 279-285, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760005

RESUMO

In pathophysiology, reactive oxygen species oxidize biomolecules that contribute to disease phenotypes1. One such modification, 8-oxoguanine2 (o8G), is abundant in RNA3 but its epitranscriptional role has not been investigated for microRNAs (miRNAs). Here we specifically sequence oxidized miRNAs in a rat model of the redox-associated condition cardiac hypertrophy4. We find that position-specific o8G modifications are generated in seed regions (positions 2-8) of selective miRNAs, and function to regulate other mRNAs through o8G•A base pairing. o8G is induced predominantly at position 7 of miR-1 (7o8G-miR-1) by treatment with an adrenergic agonist. Introducing 7o8G-miR-1 or 7U-miR-1 (in which G at position 7 is substituted with U) alone is sufficient to cause cardiac hypertrophy in mice, and the mRNA targets of o8G-miR-1 function in affected phenotypes; the specific inhibition of 7o8G-miR-1 in mouse cardiomyocytes was found to attenuate cardiac hypertrophy. o8G-miR-1 is also implicated in patients with cardiomyopathy. Our findings show that the position-specific oxidation of miRNAs could serve as an epitranscriptional mechanism to coordinate pathophysiological redox-mediated gene expression.


Assuntos
Cardiomegalia/genética , Cardiomegalia/patologia , Inativação Gênica , MicroRNAs/química , MicroRNAs/metabolismo , Animais , Pareamento de Bases , Linhagem Celular , Modelos Animais de Doenças , Guanina/análogos & derivados , Guanina/análise , Guanina/química , Guanina/metabolismo , Humanos , Camundongos , MicroRNAs/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Oxirredução , Ratos , Transcrição Gênica/genética , Transcriptoma/genética
2.
Phytother Res ; 29(4): 549-53, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25640212

RESUMO

Five polyphenols were isolated and purified from a brown alga Ecklonia cava. These compounds showed diverse biological activities such as antioxidative, antiinflammatory, and enzyme inhibitory activities. This led us to investigate the potential of these compounds as Alzheimer's disease drugs. All of the compounds showed moderate acetylcholinesterase inhibitory activity in a micromolar range (IC50 from 16.0 to 96.3 µM). For butyrylcholinesterase, a new target for the treatment of Alzheimer's disease, phlorofucofuroeckol-A (PFF-A), showed a particularly potent inhibitory activity (IC50 0.95 µM), which is over 100-fold greater than for acetylcholinesterase. These compounds inhibited glycogen synthase kinase 3 beta, which is related to the formation of hyperphosphorylated tau and generation Aß. Bieckol and PFF-A inhibited amyloid precursor protein biosynthesis. PFF-A also showed very strong ß-secretase inhibitory activity with IC50 of submicromole. These results render these compounds as interesting potential drug candidates for Alzheimer's disease.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Benzofuranos/farmacologia , Inibidores da Colinesterase/farmacologia , Dioxinas/farmacologia , Phaeophyceae/química , Polifenóis/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/biossíntese , Butirilcolinesterase/metabolismo , Linhagem Celular , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta , Humanos
3.
Pediatr Hematol Oncol ; 32(2): 109-14, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24274666

RESUMO

There have been a number of animal studies on the immunological effects of mercury. However, there is a lack of studies investigating the effects of mercury in children. We investigated the association between serum mercury and leukocyte differential count in Korean children. The relationship between mercury and leukocyte differential count (segment, lymphocyte, monocyte, basophil, and eosinophil counts) was analyzed by multivariate linear analysis adjusted for sex, BMI, parental smoking, lead, cadmium, and allergic sensitization in 311 children. Mercury showed a positive correlation with lymphocyte count (coefficient 113.8, 95% confidence interval 26.7-200.9). However, mercury was not associated with total leukocyte, segment, monocyte, basophil, or eosinophil count. Mercury was associated with the increased of lymphocyte count in Korean children. Further studies will be required to ascertain the clinical significance of this association.


Assuntos
Leucócitos/imunologia , Leucócitos/metabolismo , Mercúrio/sangue , Adolescente , Criança , Feminino , Humanos , Contagem de Leucócitos , Masculino , República da Coreia
4.
Graefes Arch Clin Exp Ophthalmol ; 252(4): 609-18, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24562465

RESUMO

PURPOSE: To investigate the effect of porcine chondrocyte-derived extracellular matrix (PCDECM) on an experimental mouse model of human pterygial epithelial cells. METHODS: Cultured human pterygial epithelial cells (hPECs) were stained with pan-cytokeratin (CK), CK3/2p, vimentin, and CK13 antibodies to characterize the cells. A pterygium mouse model was developed by injecting 1X104 hPECs into the nasal subconjunctival space in athymic nude mice. PCDECM (25 mg/mL, 10 µL) was injected into the nasal subconjunctival space in the right eye 7, 10 and 14 days after the epithelial cell injection (PCDECM group). Image analysis was performed using ImageJ® to compare the lesion size. A histopathological analysis of the cornea was conducted to evaluate the state of the epithelium and the expression of pterygial epithelial cell markers. RESULTS: The isolated pterygial cells were positive for pan-CK, CK3/2p and vimentin, and they were negative for CK13 under immunofluorescence microscopy. On day 17 after epithelial cell injection, the size of the lesion compared to the entire cornea was increased to 37.1 % in the control group. However, in the PCDECM group, the lesion covered only 26.3 % of the entire cornea. The corneas of the pterygium mice showed an epithelium of irregular thickness, proliferation of the stroma, extracellular matrix breakdown and overexpression of pterygium-positive markers. However, these changes were significantly suppressed by the application of PCDEDM. CONCLUSIONS: Our findings suggest that PCDECM seems to suppress pterygial epithelial cell growth and it could be used as a promising biomaterial for the noninvasive treatment of pterygium.


Assuntos
Biomarcadores/metabolismo , Condrócitos/fisiologia , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Matriz Extracelular/fisiologia , Pterígio/metabolismo , Animais , Células Cultivadas , Células Epiteliais/patologia , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Queratina-13/metabolismo , Queratina-3/metabolismo , Masculino , Camundongos , Camundongos Nus , Pterígio/patologia , Suínos , Alicerces Teciduais , Vimentina/metabolismo
5.
Graefes Arch Clin Exp Ophthalmol ; 252(6): 951-61, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24789464

RESUMO

PURPOSE: We investigated the effect of a chondrocyte-derived extracellular matrix (CDECM) on experimental corneal alkaline burns in rabbits. METHODS: Corneal neovascularization (NV) was induced by applying an 8-mm filter paper soaked in 1 N NaOH to the right central corneas of rabbits for 1 minute. Ten days later, the rabbits were randomly divided into three groups: the alkaline burn group, the CDECM transplantation group, and the human amniotic membrane (HAM) transplantation group. The left eyes were used as controls. CDECM and HAM were transplanted onto the corneal surface to completely cover the resected area and were subsequently sutured. On the 10th day after transplantation, the structural changes of the cornea were analyzed histologically. We examined the effects of CDECM on clinical NV features and on the expression of corneal NV markers. RESULTS: The alkaline burn produced significant NV and increased the corneal thickness. On day 10 after transplantation, the thickness, NV and opacity of the cornea were markedly decreased in the CDECM group (p < 0.001). However, the HAM transplantation group did not exhibit improvements in these clinical parameters, and there were no significant differences relative to the burn group. In addition, the use of CDECM improved the healing of the cornea following the alkaline burn by disrupting the corneal epithelial proliferation and reducing the fibrotic changes of the stroma. The hallmarks of NV were significantly induced in the subepithelium by the alkaline burn, and these levels were also suppressed by CDECM. The CDECM suppressed corneal NV by inhibiting nuclear factor-kappa B (NF-κB) activation by blocking the PKC and Akt signaling pathways. CONCLUSIONS: CDECM transplantation was markedly effective in healing alkali-burned corneas by modulating the translocation of NF-κB to the nucleus, thereby representing a promising material for the noninvasive treatment of ocular surface disease.


Assuntos
Queimaduras Químicas/terapia , Condrócitos/transplante , Neovascularização da Córnea/terapia , Modelos Animais de Doenças , Matriz Extracelular/transplante , Queimaduras Oculares/induzido quimicamente , Âmnio/transplante , Animais , Biomarcadores/metabolismo , Queimaduras Químicas/metabolismo , Neovascularização da Córnea/metabolismo , Humanos , Técnicas Imunoenzimáticas , Masculino , NF-kappa B/metabolismo , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Coelhos , Hidróxido de Sódio
6.
Front Chem ; 11: 1204477, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37398983

RESUMO

Introduction: The product labels of veterinary disinfectants specify their expiration dates to prevent the use of outdated products, as these may result in disinfection and biosecurity failures during outbreak situations. However, a clear standard for the storage conditions of diluted disinfectant solutions has not yet been established, and the effects of storage conditions have scarcely been investigated. To fill this research gap, our study examined the stability of the active ingredients of diluted veterinary disinfectants based on their change in concentrations when stored at various temperatures for various time periods. Methods: Twenty veterinary disinfectants effective against either foot-and-mouth disease or avian influenza viruses were selected. The disinfectants were diluted to effective concentrations following the manufacturer's instructions. Using selective analytical techniques, the concentrations of the active ingredients of the samples that had been stored for varying intervals at different temperatures (4, 20, 30, and 45°C) were determined. These samples included soaps and detergents, acids, oxidizing agents, aldehydes, and copper compounds. The active ingredient concentrations of two of the samples were determined following freezing/thawing cycle, to establish their stability when exposed to simulated winter conditions. Results: Our results showed that most of the active ingredients had concentrations of 90% or greater of their initial concentrations, indicating ≥90% stability over a 21-day period under the experimental storage conditions. However, there were some exceptions. Glutaraldehyde, formaldehyde, and malic acid are over 90% stable at ≤ 30°C for 21 days, but their concentrations decreased to below 90% of their initial concentrations at 45°C, indicating a decline in stability when stored at 45°C for 21 days. The concentrations of potassium peroxymonosulfate and peracetic acid rapidly declined with increasing time and temperature to less than 90% of their initial concentrations. Discussion: Based on our findings, we propose that diluted disinfectant solutions should preferably be prepared daily. However, if the daily preparation of a diluted disinfectant solution is not feasible, then our results can be used as a reference, providing basic scientific data on the chemical stability of diluted disinfectant solutions commonly used in the veterinary field, thus indicating suitable storage conditions.

7.
Nat Cell Biol ; 25(9): 1369-1383, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37696949

RESUMO

Oxidative stress contributes to tumourigenesis by altering gene expression. One accompanying modification, 8-oxoguanine (o8G) can change RNA-RNA interactions via o8G•A base pairing, but its regulatory roles remain elusive. Here, on the basis of o8G-induced guanine-to-thymine (o8G > T) variations featured in sequencing, we discovered widespread position-specific o8Gs in tumour microRNAs, preferentially oxidized towards 5' end seed regions (positions 2-8) with clustered sequence patterns and clinically associated with patients in lower-grade gliomas and liver hepatocellular carcinoma. We validated that o8G at position 4 of miR-124 (4o8G-miR-124) and 4o8G-let-7 suppress lower-grade gliomas, whereas 3o8G-miR-122 and 4o8G-let-7 promote malignancy of liver hepatocellular carcinoma by redirecting the target transcriptome to oncogenic regulatory pathways. Stepwise oxidation from tumour-promoting 3o8G-miR-122 to tumour-suppressing 2,3o8G-miR-122 occurs and its specific modulation in mouse liver effectively attenuates diethylnitrosamine-induced hepatocarcinogenesis. These findings provide resources and insights into epitranscriptional o8G regulation of microRNA functions, reprogrammed by redox changes, implicating its control for cancer treatment.


Assuntos
Carcinoma Hepatocelular , Glioma , Neoplasias Hepáticas , MicroRNAs , Animais , Camundongos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/genética , MicroRNAs/genética , Carcinogênese/genética , Guanina , Oxirredução , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/genética
8.
Sci Rep ; 11(1): 19161, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580386

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with fatal pulmonary fibrosis. Small interfering RNAs (siRNAs) can be developed to induce RNA interference against SARS-CoV-2, and their susceptible target sites can be inferred by Argonaute crosslinking immunoprecipitation sequencing (AGO CLIP). Here, by reanalysing AGO CLIP data in RNA viruses, we delineated putative AGO binding in the conserved non-structural protein 12 (nsp12) region encoding RNA-dependent RNA polymerase (RdRP) in SARS-CoV-2. We utilised the inferred AGO binding to optimise the local RNA folding parameter to calculate target accessibility and predict all potent siRNA target sites in the SARS-CoV-2 genome, avoiding sequence variants. siRNAs loaded onto AGO also repressed seed (positions 2-8)-matched transcripts by acting as microRNAs (miRNAs). To utilise this, we further screened 13 potential siRNAs whose seed sequences were matched to known antifibrotic miRNAs and confirmed their miRNA-like activity. A miR-27-mimicking siRNA designed to target the nsp12 region (27/RdRP) was validated to silence a synthesised nsp12 RNA mimic in lung cell lines and function as an antifibrotic miR-27 in regulating target transcriptomes related to TGF-ß signalling. siRNA sequences with an antifibrotic miRNA-like activity that could synergistically treat COVID-19 are available online ( http://clip.korea.ac.kr/covid19 ).


Assuntos
Proteínas Argonautas/genética , COVID-19/prevenção & controle , MicroRNAs/genética , RNA Interferente Pequeno/genética , SARS-CoV-2/genética , Células A549 , Proteínas Argonautas/metabolismo , Sequência de Bases , Sítios de Ligação/genética , COVID-19/virologia , Linhagem Celular , RNA-Polimerase RNA-Dependente de Coronavírus/genética , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Perfilação da Expressão Gênica/métodos , Células HeLa , Humanos , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Interferência de RNA , RNA-Seq/métodos , SARS-CoV-2/fisiologia , Homologia de Sequência do Ácido Nucleico
9.
Vet Med Sci ; 7(2): 289-296, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33107216

RESUMO

Veterinary biocides used in animal husbandry have the potential to cause human health concerns. Biocidal products for veterinary use, which contain pesticides approved in Korea, comprise 49 active ingredients within 234 products. Within 17 of these products there are 3 ingredients which are highly hazardous pesticides: coumaphos, dichlorvos and methomyl. In this study, the content of the active ingredients of 160 products sold domestically was investigated. Samples were collected for 119 biocidal products for veterinary use. These were analysed by high-performance liquid chromatography (HPLC) and gas chromatography (GC). Seventeen products were noncompliant (insufficient or excess quantity of active ingredients). The ingredients that were below the stated concentrations were amitraz, chlorpyrifos-methyl, cypermethrin, cyromazine, dichlorvos, fipronil, muscamone and trichlorfon. The ingredients that exceeded the stated concentrations were abamectin, fluvalinate and pyriproxyfen. The noncompliance rate in biocidal products for veterinary use was 9.19%. The results of this study show that three highly hazardous pesticides (coumaphos, dichlorvos and methomyl) and 10 active ingredients (abamectin, amitraz, chlorpyrifos-methyl, cypermethrin, cyromazine, fipronil, fluvalinate, muscamone, pyriproxyfen and trichlorfon) deviated from the stated concentrations. Thus, management plans should be established to ensure compliant veterinary drugs by post-distribution quality control, such as planning for regular inspection.


Assuntos
Praguicidas/análise , Medicina Veterinária/estatística & dados numéricos , Cromatografia Líquida de Alta Pressão/veterinária , República da Coreia
10.
Mol Ther Nucleic Acids ; 23: 1172-1190, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33664996

RESUMO

Small interfering RNAs (siRNAs) therapeutically induce RNA interference (RNAi) of disease-causing genes, but they also silence hundreds of seed-matched off-targets as behaving similar to microRNAs (miRNAs). miRNAs control the pathophysiology of tumors, wherein their accessible binding sites can be sequenced by Argonaute crosslinking immunoprecipitation (AGO CLIP). Herein, based on AGO CLIP, we develop potent anticancer siRNAs utilizing miRNA-like activity (mi/siRNAs). The mi/siRNAs contain seed sequences (positions 2-7) of tumor-suppressive miRNAs while maintaining perfect sequence complementarity to the AGO-accessible tumor target sites. Initially, host miRNA interactions with human papillomavirus 18 (HPV18) were identified in cervical cancer by AGO CLIP, revealing tumor-suppressive activity of miR-1/206 and miR-218. Based on the AGO-miRNA binding sites, mi/siRNAs were designed to target E6 and E7 (E6/E7) transcript with seed sequences of miR-1/206 (206/E7) and miR-218 (218/E7). Synergistic anticancer activity of 206/E7 and 218/E7 was functionally validated and confirmed via RNA sequencing and in vivo xenograft models (206/E7). Other mi/siRNA sequences were additionally designed for cervical, ovarian, and breast cancer, and available as an online tool (http://ago.korea.ac.kr/misiRNA); some of the mi/siRNAs were validated for their augmented anticancer activity (206/EphA2 and 206/Her2). mi/siRNAs could coordinate miRNA-like activity with robust siRNA function, demonstrating the potential of AGO CLIP analysis for RNAi therapeutics.

11.
Biosci Biotechnol Biochem ; 74(2): 279-84, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20139626

RESUMO

In Leonurus sibiricus herb extract (LHE)-supplemented animals, plasma cholesterol decreased and high-density lipoprotein-cholesterol increased, resulting in a lowered atherogenic index. The plasma trolox equivalent antioxidant capacity, levels of hepatic thiobarbituric acid-reactive substances, and protein carbonyl values decreased significantly in LHE-supplemented mice (p<0.05), whereas the hepatic antioxidant indicators were all significantly elevated (p<0.05). In human umbilical vein endothelial cells stimulated with tumor necrosis factor alpha, LHE significantly suppressed intracellular reactive oxygen species, LOX-1, and adhesion molecules. LHE supplementation may modulate the lipoprotein composition and attenuate oxidative stress by elevated antioxidant processes, thus suppressing the activation of inflammatory mediators. This is a possible mechanism of the anti-atherogenic effect.


Assuntos
Moléculas de Adesão Celular/metabolismo , Células Endoteliais/efeitos dos fármacos , Hipercolesterolemia/metabolismo , Leonurus/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Receptores de LDL Oxidado/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Células Cultivadas , Feminino , Humanos , Lectinas/metabolismo , Camundongos , Veias Umbilicais/citologia
12.
J Enzyme Inhib Med Chem ; 25(5): 608-14, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20105050

RESUMO

The antioxidant activity of extracts from Caesalpinia sappan L. (CSL) was studied in vitro by evaluating the total phenolics, measuring the antioxidant activity by TEAC, measuring the scavenging effects on reactive oxygen species (ROS) and on reactive nitrogen species (RNS), and measuring the inhibitory effect on Cu(2+)-induced human low-density lipoprotein (LDL) oxidation. The CSL extracts were found to have a potent scavenging activity against all of the reactive species tested, as well as an inhibitory effect on LDL oxidation, especially in the ethyl acetate (EA) fraction. Therefore, we isolated and identified benzylchroman derivatives sappanchalcone (1) and 3'-deoxy-4-O-methylepisappanol (2) from the EA fraction of CSL and their antioxidant activities were evaluated. The studied CSL extracts and the compounds 1 and 2 were revealed to be very effective against the evaluated pro-oxidant species, including ROS and RNS.


Assuntos
Antioxidantes/química , Caesalpinia/química , Chalconas/química , Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Extratos Vegetais/química , Madeira/química , Antioxidantes/isolamento & purificação , Chalconas/isolamento & purificação , Fracionamento Químico , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/análise , Lipoproteínas LDL/química , Espectroscopia de Ressonância Magnética , Fenóis/análise , Fenóis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Nitrogênio/química , Espécies Reativas de Oxigênio/química , Espectrometria de Massas por Ionização por Electrospray
13.
J Enzyme Inhib Med Chem ; 25(5): 702-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20105051

RESUMO

In this study the potent scavenging activity of "Lycopi Herba" (LH) extract was studied using the following: evaluation of the total phenolics, measuring the antioxidant activity by Trolox equivalent antioxidant concentration, measuring the scavenging effects on reactive oxygen species, on reactive nitrogen species, and measuring the inhibitory effect on Cu(2+) induced human low-density lipoprotein oxidation in vitro. The ethyl acetate fraction from the LH extracts were found to have a potent scavenging activity against all of the reactive species tested, as well as an inhibitory effect on LDL oxidation. Therefore, we isolated and identified luteolin-7-O-beta-D-glucuronide methyl ester as the major compound from the ethyl acetate fraction of LH and their antioxidant activities were evaluated.


Assuntos
Sequestradores de Radicais Livres/química , Glucuronídeos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Luteolina/química , Lycopus/química , Extratos Vegetais/química , Espécies Reativas de Nitrogênio/química , Espécies Reativas de Oxigênio/química , Acetatos , Antioxidantes/análise , Antioxidantes/química , Fracionamento Químico , Sequestradores de Radicais Livres/análise , Sequestradores de Radicais Livres/isolamento & purificação , Glucuronídeos/análise , Glucuronídeos/isolamento & purificação , Humanos , Lipoproteínas LDL/análise , Lipoproteínas LDL/química , Luteolina/análise , Luteolina/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Fenóis/análise , Extratos Vegetais/isolamento & purificação , Solventes , Madeira/química
14.
J Enzyme Inhib Med Chem ; 25(5): 720-9, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20163327

RESUMO

In this study, the anti-oxidative activities of 70% ethanol extract from Curcuma aromatica Salisb. (CAS) and curcumin (CUR) were studied. The CAS extracts and CUR were both found to have a potent scavenging activity against the reactive species tested, as well as an inhibitory effect on LDL oxidation. Cultured human umbilical vein endothelial cells (HUVECs) were stimulated with tumour necrosis factor alpha (TNFalpha), expression of intracellular reactive oxygen species (ROS), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), lectin-like oxidised LDL receptor-1 (LOX-1), adhesion molecules, inhibitory kappa Balpha (IkappaBalpha) and nuclear factor kappa B (NFkappaB) were measured. In HUVECs stimulated with TNFalpha, CUR significantly suppressed expression of the intracellular ROS, LOX-1 and adhesion molecules, degradation of IkappaBalpha and translocation of NFkappaB, while inducing production of NO by phosphorylation of eNOS (p <0.05). In conclusion, CAS and CUR may modulate lipoprotein composition and attenuate oxidative stress by elevated antioxidant processes.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Curcumina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptores Depuradores Classe E/metabolismo , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Antioxidantes/efeitos adversos , Antioxidantes/química , Moléculas de Adesão Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/metabolismo , Curcuma/química , Curcumina/efeitos adversos , Curcumina/química , Endotélio Vascular/enzimologia , Humanos , Proteínas I-kappa B/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Transporte Proteico/efeitos dos fármacos , Espécies Reativas de Nitrogênio/química , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais/citologia
15.
Immunopharmacol Immunotoxicol ; 32(4): 671-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20230182

RESUMO

Oxidative stress and inflammatory mediators were measured in the plasma and livers of C57BL/6 mice fed a high-cholesterol diet for 14 weeks and in cultured human umbilical vein endothelial cells (HUVECs). Some of the mice fed with the atherogenic diet received drinking water supplemented with 0.01 g of a 70% ethanol extract of Caesalpinia sappan L. (CSLE) per 20 g of body weight. Numerous parameters were determined: concentrations of total, high-, and low-density cholesterol; atherogenic index; plasma trolox equivalent antioxidant capacity (TEAC); levels of hepatic thiobarbituric acid reactive substances (TBARS) and protein carbonyls; and the activities of hepatic antioxidant enzymes, including Cu·Zn-SOD, Mn-SOD, glutathione peroxidase, glutathione reductase, and catalase. HUVECs were stimulated with tumor necrosis factor α (TNFα) and the expression of intracellular reactive oxygen species (ROS), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), adhesion molecules, inhibitory κBα (IκBα), and nuclear factor κB (NFκB) were measured. Compared to mice fed a hypercholesterolemic diet alone, mice fed a hypercholesterolemic diet supplemented with CSLE exhibited decreased total plasma cholesterol and increased high-density lipoprotein cholesterol, and thus a lower atherogenic index. Furthermore, plasma TEAC and levels of hepatic TBARS and protein carbonyls were significantly decreased in CSLE-supplemented mice (P < 0.05), whereas all hepatic antioxidative indicators were significantly elevated (P < 0.05). In HUVECs stimulated with TNFα, CSLE significantly decreased the expression of intracellular ROS, LOX-1, and adhesion molecules; the degradation of IκBα; and the nuclear translocation of NFκB; in contrast, CSLE induced the expression of Nrf2 and HO-1 (P < 0.05 for all results).


Assuntos
Anti-Inflamatórios/farmacologia , Caesalpinia/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Hipercolesterolemia/prevenção & controle , Veias Umbilicais/citologia , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Sangue/efeitos dos fármacos , Sangue/metabolismo , Peso Corporal , Sobrevivência Celular/efeitos dos fármacos , Dieta Aterogênica , Ingestão de Alimentos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Feminino , Heme Oxigenase-1/metabolismo , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/patologia , Proteínas I-kappa B/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Tamanho do Órgão , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Depuradores Classe E/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Molécula 1 de Adesão de Célula Vascular/metabolismo
16.
Anticancer Res ; 29(5): 1817-22, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19443410

RESUMO

BACKGROUND: The frequency of epithelial cell adhesion molecule (EpCAM) expression was investigated in non-small cell lung cancer (NSCLC) cells and human tissues, and its clinicopathological significance in adenocarcinoma of the lung was evaluated. MATERIALS AND METHODS: EpCAM expression was analysed by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry in human NSCLC cells. EpCAM protein expression was evaluated in 234 adenocarcinoma tissues using immunohistochemistry. RESULTS: A high expression level of EpCAM was observed in human NSCLC cells by flow cytometry and RT-PCR. EpCAM overexpression was detected in 120/234 (51.3%) surgically resected adenocarcinoma tissues. EpCAM overexpression occurred significantly more frequently in adenocarcinoma than in bronchioloalveolar carcinoma (p=0.02). The overall survival did not differ significantly between EpCAM-overexpressing and EpCAM-negative patients (p=0.40). CONCLUSION: These findings suggest EpCAM plays a role in the carcinogenesis of adenocarcinoma of the lung and might provide a promising molecule for targeted therapy in NSCLC.


Assuntos
Adenocarcinoma/metabolismo , Antígenos de Neoplasias/metabolismo , Moléculas de Adesão Celular/metabolismo , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/patologia , Sequência de Bases , Linhagem Celular Tumoral , Primers do DNA , Molécula de Adesão da Célula Epitelial , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Molecules ; 14(11): 4300-11, 2009 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-19924065

RESUMO

Tumor necrosis factor (TNF)-alpha is one of the pro-inflammatory cytokines highly expressed in Helicobacter pylori that inhibits gastric acid secretion. In this study we determined the effect of silibinin on TNF-alpha-induced MMP-9 expression in gastric cancer cell lines. MMP-9 mRNA and protein expression was dose-dependently increased by TNF-alpha in SNU216 and SNU668 gastric cancer cells. On the other hand, TNF-alpha-induced MMP-9 expression was dose-dependently suppressed by silibinin. To verify the regulatory mechanism of silibinin on TNF-alpha-induced MMP-9 expression, the gastric cancer cell lines were pretreated with silibinin prior to TNF-alpha. TNF-alpha-induced MMP-9 expression was inhibited by the MEK1/2 specific inhibitor, UO126. Finally, we investigated the effect of adenoviral constitutively active (CA)-MEK and CA-Akt on MMP-9 expression. The expression of MMP-9 was significantly increased by CA-MEK overexpression, but not by CA-Akt overexpression. Taken together, we suggest that silibinin down-regulates TNF-alpha- induced MMP-9 expression through inhibition of the MEK/ERK pathway in gastric cancer cells.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Gástricas/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Silibina , Silimarina/farmacologia
18.
Stud Health Technol Inform ; 264: 1957, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438426

RESUMO

Malicious e-mails sent intentionally to institutions have caused an increase in data breaches. Measures against these methods must be taken by healthcare institutions to prevent leakage of sensitive personal medical information. As a form of training, we conducted a phishing simulation to gauge the response of the hospital staff to similar email attacks, and to raise awareness about information security protocols.


Assuntos
Correio Eletrônico , Hospitais
19.
PLoS One ; 14(1): e0210840, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30653594

RESUMO

INTRODUCTION: It is difficult to accurately predict the natural course of allergic rhinitis (AR), because it is affected by a wide variety of environmental influences, as well as genetic predisposition. Considering the high prevalence of allergic rhinitis in children and adolescents, caregivers should be given appropriate information regarding the disease course. This study aimed to understand the prognosis of allergic rhinitis by examining the relationship between allergic sensitization and rhinitis symptoms during this developmental period. METHODS: This cross-sectional study included 1069 children aged 9-16 years from the Korean International Study of Asthma and Allergies in Childhood Survey database who had completed health questionnaires, and for whom skin prick test results were available. Data were collected during May 2016. The distribution of sensitization and allergic symptoms was compared by age groups (elementary, middle, and high school). Data were analyzed using linear-by-linear analysis. RESULTS: Sensitization to at least one tested allergen differed by age (59.2%, 58.3%, 68.2%, in elementary, middle, and high school students, respectively; p = 0.025), and seasonal allergen sensitization (35.0%, 37.1%, 53.9%, respectively) increased with age (p < 0.001). Conversely, the proportion of rhinitis symptoms among sensitized children decreased as age increased (58.80%, 52.90%, 49.70%, respectively; p = 0.047). However, the rate of non-allergic rhinitis was age-independent. CONCLUSION: With increasing age during childhood and adolescence, symptomatic allergic rhinitis decreases; thus, subclinical allergic rhinitis increases. This suggests that the symptoms of later-sensitized children are less clearly manifested, or that the symptoms reduce as previously sensitized children mature. This should be clarified further in a longitudinal study.


Assuntos
Rinite Alérgica/epidemiologia , Adolescente , Fatores Etários , Alérgenos/imunologia , Criança , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Prevalência , Prognóstico , República da Coreia/epidemiologia , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Testes Cutâneos
20.
Int J Pediatr Otorhinolaryngol ; 101: 37-40, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28964307

RESUMO

OBJECTIVES: The prevalence of allergic rhinitis and the social burden related to the management of allergic rhinitis have persistently increased. There are many studies investigating the association between the allergic diseases of children and the stress of their parent. However, the relationship between parenting stress and the incidence of allergic rhinitis among children requires further investigation. We aimed to investigate the significance of parenting stress for mothers with children treated for allergic rhinitis. METHODS: The mothers of 250 children in the second and third grade of elementary school were involved in this study. The Parenting Stress Index-Short Form (PSI-SF) was used to measure parenting stress. Additionally, the monthly household income, treatment history for allergic diseases (atopic dermatitis, asthma, and allergic rhinitis) during the past 12 months, and maternal education status were investigated using the questionnaire. RESULTS: Parenting stress index score was significantly higher among the mothers of children treated for allergic rhinitis (76.41 ± 9.35) compared with the parents of children without treatment history for allergic rhinitis (70.06 ± 13.74). Nonetheless, there were no significant differences between the cases of children with atopic dermatitis and those with asthma. We analyzed the association between allergic rhinitis and parenting stress adjusted for the monthly household income, and maternal education status, and showed that a treatment history of allergic rhinitis was significantly associated with parenting stress (coefficient 7.477, 95% interval 1.703-13.252; p = 0.011). CONCLUSION: Treatment of the children for allergic rhinitis significantly affects the parenting stress of their mother. We recommend that mothers with children with allergic rhinitis should receive appropriate counseling about parenting stress.


Assuntos
Mães/psicologia , Poder Familiar/psicologia , Rinite Alérgica/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Masculino , Prevalência , Rinite Alérgica/psicologia , Fatores de Risco , Inquéritos e Questionários
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