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1.
Front Pharmacol ; 14: 1119607, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37256225

RESUMO

Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subvert host immune surveillance allowing cancer cells to become invisible to the immune system and, in turn, promote cancer metastasis. Here we describe and validate the first high-throughput cell-based screening assay to identify chemical extracts and unique chemical entities that reverse the downregulation of APM components in cell lines derived from metastatic tumours. Through the screening of a library of 480 marine invertebrate extracts followed by bioassay-guided fractionation, curcuphenol, a common sesquiterpene phenol derived from turmeric, was identified as the active compound of one of the extracts. We demonstrate that curcuphenol induces the expression of the APM components, TAP-1 and MHC-I molecules, in cell lines derived from both metastatic prostate and lung carcinomas. Turmeric and curcumins that contain curcuphenol have long been utilized not only as a spice in the preparation of food, but also in traditional medicines for treating cancers. The remarkable discovery that a common component of spices can increase the expression of APM components in metastatic tumour cells and, therefore reverse immune-escape mechanisms, provides a rationale for the development of foods and advanced nutraceuticals as therapeutic candidates for harnessing the power of the immune system to recognize and destroy metastatic cancers.

2.
J Phys Chem B ; 123(26): 5601-5607, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31187996

RESUMO

We investigated the intramolecular charge transfer characteristics in the S1 state of boron-dipyrromethene (BODIPY) derivatives with triphenylamine (TPA) substituents, depending on the substituted position and the number of substituents. Based on the spectroscopic and theoretical results, the ß-substitution of TPA on BODIPY hybridizes locally excited and intramolecular charge transfer characteristics in the S1 state because of strong coupling between the highest occupied molecular orbitals of BODIPY and TPA moieties, and consequently, the BODIPY derivatives with ß-substituted TPAs exhibit strong red-color fluorescence around 640 nm in nonpolar and moderately polar solvents. The TPA substituent with propeller-like nonplanar geometry could prevent H-type aggregation between neighboring BODIPY derivative units and induce aggregation-induced emission enhancement (AIEE) characteristics of the BODIPY derivatives with TPA substituents, which are helpful to maintain their emission efficiencies under highly concentrated and condensed conditions. Since the red-color emission and AIEE property of the BODIPY derivatives with ß-substituted TPAs are promising characteristics for a bioimaging application, we applied these derivatives to L-929 fibroblast cells for cellular imaging. The BODIPY derivative with a single ß-substituted TPA (compound 2) was effectively loaded into porous silica nanoparticles (SNPs). Consequently, we achieved good cellular uptake of 2-SNPs and good cellular imaging, which further confirmed the bioimaging ability of 2-SNPs.


Assuntos
Boro/química , Porfobilinogênio/análogos & derivados , Animais , Células Cultivadas , Teoria da Densidade Funcional , Camundongos , Estrutura Molecular , Processos Fotoquímicos , Porfobilinogênio/síntese química , Porfobilinogênio/química , Espectrofotometria Ultravioleta
3.
Nanomaterials (Basel) ; 8(9)2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30217046

RESUMO

Photodynamic therapy (PDT) is a promising alternative to conventional cancer treatment methods. Nonetheless, improvement of in vivo light penetration and cancer cell-targeting efficiency remain major challenges in clinical photodynamic therapy. This study aimed to develop multifunctional magnetic nanoparticles conjugated with a photosensitizer (PS) and cancer-targeting molecules via a simple surface modification process for PDT. To selectively target cancer cells and PDT functionality, core magnetic (Fe3O4) nanoparticles were covalently bound with chlorin e6 (Ce6) as a PS and folic acid (FA). When irradiated with a 660-nm long-wavelength light source, the Fe3O4-Ce6-FA nanoparticles with good biocompatibility exerted marked anticancer effects via apoptosis, as confirmed by analyzing the translocation of the plasma membrane, nuclear fragmentation, activities of caspase-3/7 in prostate (PC-3) and breast (MCF-7) cancer cells. Ce6, used herein as a PS, is thus more useful for PDT because of its ability to produce a high singlet oxygen quantum yield, which is owed to deep penetration by virtue of its long-wavelength absorption band; however, further in vivo studies are required to verify its biological effects for clinical applications.

4.
Nanomaterials (Basel) ; 8(9)2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30223553

RESUMO

In this study, a series of rationally designed emissive phenanthrene derivatives were synthesized and their aggregation-induced emission (AIE) properties in tetrahydrofuran (THF)/water mixtures were investigated. Two tetraphenylethene (TPE) segments were conjugated to both ends of the phenanthrene core at the para-positions and meta-positions, resulting in pTPEP and mTPEP derivatives, respectively. While the TPE-conjugated phenanthrene derivatives did not show any emission when dissolved in pure THF, they showed strong sky-blue emissions in water-THF mixtures, which is attributed to the restriction of intramolecular motions of TPE segments by aggregation. Furthermore, silica nanoparticles loaded with these AIE-active compounds were prepared and proved to be promising intracellular imaging agents.

5.
Nanomaterials (Basel) ; 7(11)2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29099064

RESUMO

In this study, we report a new multifunctional nanoparticle with antioxidative and antibacterial activities in vitro. ZnO@GA nanoparticles were fabricated by coordinated covalent bonding of the antioxidant gallic acid (GA) on the surface of ZnO nanoparticles. This addition imparts both antioxidant activity and high affinity for the bacterial cell membrane. Antioxidative activities at various concentrations were evaluated using a 2,2'-azino-bis(ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging method. Antibacterial activities were evaluated against Gram-positive bacteria (Staphylococcus aureus: S. aureus), including several strains of methicillin-resistant S. aureus (MRSA), and Gram-negative bacteria (Escherichia coli). The functionalized ZnO@GA nanoparticles showed good antioxidative activity (69.71%), and the bactericidal activity of these nanoparticles was also increased compared to that of non-functionalized ZnO nanoparticles, with particularly effective inhibition and high selectivity for MRSA strains. The results indicate that multifunctional ZnO nanoparticles conjugated to GA molecules via a simple surface modification process displaying both antioxidant and antibacterial activity, suggesting a possibility to use it as an antibacterial agent for removing MRSA.

6.
Food Nutr Res ; 61(1): 1361769, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28904529

RESUMO

Background: The consumption of fruits, vegetables, and dietary supplements correlate. Most previous studies have aimed to identify the determinants of supplement uses or the distinct features of supplement users; this literature lacks a discussion on dietary supplement consumption as a predictor of fruit and vegetable consumption. Objective: This study examines how dietary supplement consumption correlates with fruit and vegetable consumption by combining scanner data and surveys of Korean household grocery shopping. Methods: Propensity score matching (PSM) is used to identify the relationship between dietary supplement consumption and fruit and vegetable consumption in a household. A logit regression using supplement consumption as the dependent variable is used. Then, the supplement takers (the treatment group) are matched with non-takers (the control group) based on the propensity scores estimated in the logit regression. The fruit and vegetable consumption levels of the groups are then compared. Results: We found that dietary supplement use is associated with higher fruit and vegetable consumption. This supports the health consciousness hypothesis based on attention bias, availability heuristics, the focusing effect, and the consumption episode effect. It rejects the health substitute hypothesis based on economic substitutes and mental accounting. Conclusions: Future research on the health benefits of dietary supplements should address the complementary consumption of fruits/vegetables and their health benefits to avoid misstating the health effects of supplements.

7.
Nanomaterials (Basel) ; 7(6)2017 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-28604596

RESUMO

Photodynamic therapy (PDT) has been adopted as a minimally invasive approach for the localized treatment of superficial tumors, representing an improvement in the care of cancer patients. To improve the efficacy of PDT, it is important to first select an optimized nanocarrier and determine the influence of light parameters on the photosensitizing agent. In particular, much more knowledge concerning the importance of fluence and exposure time is required to gain a better understanding of the photodynamic efficacy. In the present study, we synthesized novel folic acid-(FA) and hematoporphyrin (HP)-conjugated multifunctional magnetic nanoparticles (CoFe2O4-HPs-FAs), which were characterized as effective anticancer reagents for PDT, and evaluated the influence of incubation time and light exposure time on the photodynamic anticancer activities of CoFe2O4-HPs-FAs in prostate cancer cells (PC-3 cells). The results indicated that the same fluence at different exposure times resulted in changes in the anticancer activities on PC-3 cells as well as in reactive oxygen species formation. In addition, an increase of the fluence showed an improvement for cell photo-inactivation. Therefore, we have established optimized conditions for new multifunctional magnetic nanoparticles with direct application for improving PDT for cancer patients.

8.
Nanomaterials (Basel) ; 7(6)2017 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-28621707

RESUMO

We report a novel zinc oxide (ZnO) nanoparticle with antioxidant properties, prepared by immobilizing the antioxidant 3-(3,4-dihydroxyphenyl)-2-propenoic acid (caffeic acid, CA) on the surfaces of micro-dielectric barrier discharge (DBD) plasma-treated ZnO nanoparticles. The microstructure and physical properties of ZnO@CA nanoparticles were characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), infrared spectroscopy, and steady state spectroscopic methods. The antioxidant activity of ZnO@CA nanoparticles was evaluated using an ABTS (3-ethyl-benzothiazoline-6-sulfonic acid) radical cation decolorization assay. ZnO@CA nanoparticles exhibited robust antioxidant activity. Moreover, ZnO@CA nanoparticles showed strong antibacterial activity against Gram-positive bacteria (Staphylococcus aureus) including resistant bacteria such as methicillin-resistant S. aureus and against Gram-negative bacteria (Escherichia coli). Although Gram-negative bacteria appeared to be more resistant to ZnO@CA nanoparticles than Gram-positive bacteria, the antibacterial activity of ZnO@CA nanoparticles was dependent on particle concentration. The antioxidant and antibacterial activity of ZnO@CA may be useful for various biomedical and nanoindustrial applications.

9.
ACS Appl Mater Interfaces ; 9(20): 16890-16899, 2017 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-28474514

RESUMO

Various types of commercialized wound dressings (e.g., films, foams, gels, and nanofiber meshes) have been clinically used as a physical barrier against bacterial invasion and as wound-healing materials. Although these dressings can protect the wounded tissue from the external environment, they cannot treat the wounds that are already infected with bacteria. Herein, we report in situ H2O2-releasing hydrogels as an active wound dressing with antibacterial properties for treatment of drug-resistant bacterial infection. In this study, H2O2 was used for two major purposes: (1) in situ gel formation via a horseradish peroxidase (HRP)/H2O2-triggered cross-linking reaction, and (2) antibacterial activity of the hydrogel via its oxidative effects. We found that there were residual H2O2 in the matrix after in situ HRP-catalyzed gelling, and varying the feed amount of H2O2 (1-10 mM; used to make hydrogels) enabled control of H2O2 release kinetics within a range of 2-509 µM. In addition, although the gelatin-hydroxyphenyl propionic acid (GH) gel called "GH 10" (showing the greatest H2O2 release, 509 µM) slightly decreased cell viability (to 82-84%) of keratinocyte (HaCaT) and fibroblast (L-929) cells in in vitro assays, none of the hydrogels showed significant cytotoxicity toward tissues in in vivo skin irritation tests. When the H2O2-releasing hydrogels that promote in vivo wound healing, were applied to various bacterial strains in vitro and ex vivo, they showed strong killing efficiency toward Gram-positive bacteria including Staphylococcus aureus, S. epidermidis, and clinical isolate of methicillin-resistant S. aureus (MRSA, drug-resistant bacteria), where the antimicrobial effect was dependent on the concentration of the H2O2 released. The present study suggests that our hydrogels have great potential as an injectable/sprayable antimicrobial dressing with biocompatibility and antibacterial activity against drug-resistant bacteria including MRSA for wound and infection treatment.


Assuntos
Peróxido de Hidrogênio/química , Antibacterianos , Infecções Bacterianas , Bandagens , Farmacorresistência Bacteriana , Hidrogéis , Staphylococcus aureus Resistente à Meticilina
10.
Molecules ; 21(9)2016 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-27607999

RESUMO

In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe2O4-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as a photosensitizer delivery agent for photodynamic therapy in cancer cells. To provide selective targeting of cancer cells and destruction of cancer cell functionality, basic cobalt ferrite (CoFe2O4) particles were covalently bonded with a photosensitizer (PS), which comprises hematoporphyrin (HP), and folic acid (FA) molecules. The magnetic properties of the CoFe2O4 particles were finely adjusted by controlling the size of the primary CoFe2O4 nanograins, and secondary superstructured composite particles were formed by aggregation of the nanograins. The prepared CoFe2O4-HP-FA exhibited high water solubility, good MR-imaging capacity, and biocompatibility without any in vitro cytotoxicity. In particular, our CoFe2O4-HP-FA exhibited remarkable photodynamic anticancer efficiency via induction of apoptotic death in PC-3 prostate cancer cells in a particle size- and concentration-dependent manner. This size-dependent effect was determined by the specific surface area of the particles because the number of HP molecules increased with decreasing size and increasing surface area. These results indicate that our CoFe2O4-HP-FA may be applicable for photodynamic therapy (PDT) as a PS delivery material and a therapeutic agent for MR-imaging based PDT owing to their high saturation value for magnetization and superparamagnetism.


Assuntos
Cobalto , Compostos Férricos , Campos Magnéticos , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes , Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cobalto/química , Cobalto/farmacologia , Meios de Contraste/química , Meios de Contraste/farmacologia , Compostos Férricos/química , Compostos Férricos/farmacologia , Ácido Fólico/química , Ácido Fólico/farmacologia , Hematoporfirinas/química , Hematoporfirinas/farmacologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
11.
Korean J Parasitol ; 54(3): 319-21, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27417087

RESUMO

In the present study, we intended to report a clinical pediatric case of thelaziasis in Korea. In addition, we briefly reviewed the literature on pediatric cases of thelaziasis in Korea. In the present case, 3 whitish, thread-like eye-worms were detected in a 6-year-old-boy living in an urban area and contracted an ocular infection known as thelaziasis incidentally during ecological agritainment. This is the first report of pediatric thelaziasis in Seoul after 1995.


Assuntos
Oftalmopatias/diagnóstico , Oftalmopatias/patologia , Infecções por Spirurida/diagnóstico , Infecções por Spirurida/patologia , Thelazioidea/isolamento & purificação , Animais , Criança , Oftalmopatias/parasitologia , Humanos , Masculino , Microscopia , Parasitologia , República da Coreia , Infecções por Spirurida/parasitologia
12.
Biomed Res Int ; 2016: 4318917, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27110564

RESUMO

We developed a two-step chemical bonding process using photosensitizer molecules to fabricate photofunctional nanolayer coatings on hematoporphyrin- (HP-) coated Ti substrates. In the first step, 3-aminopropyltriethoxysilane was covalently functionalized onto the surface of the Ti substrates to provide heterogeneous sites for immobilizing the HP molecules. Then, HP molecules with carboxyl groups were chemically attached to the amine-terminated nanolayer coatings via a carbodiimide coupling reaction. The microstructure and elemental and phase composition of the HP-coated Ti substrates were investigated using field-emission scanning electron microscopy and energy-dispersive X-ray spectrometry. The photophysical properties of the photofunctional nanolayer coatings were confirmed using reflectance ultraviolet-visible absorption and emission spectrophotometry. The singlet oxygen generation efficiency of the photofunctional nanolayer coatings was determined using the decomposition reaction of 1,3-diphenylisobenzofuran. The HP-coated Ti substrates exhibited good biocompatibility without any cytotoxicity, and these nanolayer coatings generated singlet oxygen, which can kill microorganisms using only visible light.


Assuntos
Materiais Revestidos Biocompatíveis/farmacologia , Hematoporfirinas/química , Fármacos Fotossensibilizantes/química , Titânio/química , Animais , Bactérias/efeitos dos fármacos , Benzofuranos/química , Carbodi-Imidas/química , Linhagem Celular , Materiais Revestidos Biocompatíveis/química , Hematoporfirinas/farmacologia , Camundongos , Microscopia Eletrônica de Varredura , Nanotecnologia , Fármacos Fotossensibilizantes/farmacologia , Propilaminas/química , Silanos/química , Oxigênio Singlete/química , Análise Espectral , Propriedades de Superfície
13.
J Biomed Nanotechnol ; 11(2): 226-35, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26349298

RESUMO

To develop novel multifunctional magnetic nanoparticles (MNPs) with good magnetic properties, biocompatibility, and anticancer activities by photodynamic therapy (PDT), we synthesized multifunctional cobalt ferrite (CoFe2O4) nanoparticles (CoFe2O4-HPs-FAs) functionalized by coating them with hematoporphyrin (HP) for introducing photo-functionality and by conjugating with folic acid (FA) for targeting cancer cells. We evaluated the activities of the CoFe2O4-HPs-FAs by checking magnetic resonance imaging (MRI) in vitro, its biocompatibility, and photodynamic anticancer activities on FA receptor (FR)-positive and FR-negative cancer cell lines, Hela, KB, MCF-7, and PC-3 cells, to use for clinical applications. In this study, we have demonstrated that the CoFe2O4-HPs-FAs have good MRI and biocompatibility with non-cytotoxicity, and remarkable photodynamic anticancer activities at very low concentrations regardless of cell types. Particularly, the photo-killing abilities in 3.13 µg/mL of CoFe2O4-HPs-FAs were measured to be 91.8% (p < 0.002) for Hela, 94.5% (p < 0.007) for KB, 79.1% (p < 0.003) for MCF-7, and 71.3% (p < 0.006) for PC-3. The photodynamic anticancer activities in 6.25 and 12.5 µg/mL of CoFe2O4-HPs-FAs were measured to be over 95% (p < 0.004) to almost 100% regardless of cell types. The newly developed multifunctional CoFe2O4-HPs-FAs are effective for PDT and have potential as therapeutic agents for MRI-based PDT, because they have a high saturation value of magnetization and superparamagnetism.


Assuntos
Antineoplásicos/uso terapêutico , Cobalto/química , Compostos Férricos/química , Nanopartículas Metálicas/uso terapêutico , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Cobalto/uso terapêutico , Compostos Férricos/uso terapêutico , Células HeLa , Humanos , Células MCF-7 , Nanopartículas Metálicas/química , Camundongos , Neoplasias/metabolismo , Neoplasias/patologia , Fármacos Fotossensibilizantes/química , Células Tumorais Cultivadas
14.
Aerosp Med Hum Perform ; 86(5): 445-51, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25945661

RESUMO

BACKGROUND: There is a high prevalence of neck pain in air force pilots; however, the causes are not clear and are considered work-related. Kyphotic changes in the cervical spine have been known to cause neck pain. In this study, we investigated the association between neck pain and cervical kyphosis in air force pilots. METHODS: This is a cross-sectional study of 63 Republic of South Korea Air Force pilots. We examined the C2-7 absolute rotation angle (ARA) using the posterior tangent method and other radiologic parameters on whole spine lateral radiographs. We divided the participants into a neck pain group (N = 32) and no neck pain group (N = 31), and subsequently analyzed the difference in radiographic parameters and clinical data between the two groups. RESULTS: There were no significant differences found in age, body mass index, total flight time, or aerobic or anaerobic exercise between the neck pain and control groups. The fighter pilots had higher 1-yr prevalence of neck pain than nonfighter pilots (84.4% vs. 15.6%). The lower C2-7 ARA (OR = 0.91, 95% CI 0.846, 0.979) and fighter type aircrafts (OR = 3.93, 95% CI 1.104, 13.989) were associated with neck pain. CONCLUSIONS: Fighter pilots experienced neck pain more frequently than the nonfighter pilots. Those fighter pilots suffering from neck pain were shown to have more kyphotic changes in the cervical spine than control pilots through evaluation of whole spine lateral radiographs using the posterior tangent method. These key findings suggest that the forces involved in flying a fighter type aircraft may affect cervical alignment and neck pain.


Assuntos
Militares/estatística & dados numéricos , Cervicalgia/epidemiologia , Doenças Profissionais/epidemiologia , Adulto , Vértebras Cervicais/diagnóstico por imagem , Estudos Transversais , Humanos , Masculino , Pescoço/diagnóstico por imagem , Prevalência , Radiografia , República da Coreia/epidemiologia , Adulto Jovem
15.
J Nanosci Nanotechnol ; 15(10): 7900-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26726437

RESUMO

This work reports the synthesis and the characterization of water-soluble and biocompatible photosensitizer (PS)-conjugated magnetic nanoparticles composed of a cobalt ferrite (CoFe2O4) magnetic core coated with a biocompatible hematoporphyrin (HP) shell. The photo-functional cobalt ferrite magnetic nanoparticles (CoFe2O4@HP) were uniform in size, stable against PS leaching, and highly efficient in the photo-generation of cytotoxic singlet oxygen under visible light. With the CoFe2O4@HP, we acquired in vitro MR images of cancer cells (PC-3) and confirmed good biocompatibility of the CoFe2O4@HP in both normal and cancer cells. In addition, we confirmed the potential of the CoFe2O4@HP as an agent for photodynamic therapy (PDT) applications. The photodynamic anticancer activities in 25, 50, and 100 µg/mL of CoFe2O4@HP were measured and found to exceed 99% (99.0, 99.4, and 99.5%) (p < 0.002). The photodynamic anticancer activity was 81.8% (p < 0.003). From these results, we suggest that our CoFe2O4@HP can be used safely as a type of photodynamic cancer therapy with potential as a therapeutic agent having good biocompatibility. Moreover, these photo-functional magnetic nanoparticles are highly promising for applications in versatile imaging diagnosis and as a therapy tool in biomedical engineering.


Assuntos
Cobalto , Compostos Férricos , Hematoporfirinas , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Animais , Linhagem Celular Tumoral , Cobalto/química , Cobalto/farmacologia , Compostos Férricos/química , Compostos Férricos/farmacologia , Hematoporfirinas/química , Hematoporfirinas/farmacologia , Humanos , Masculino , Camundongos , Neoplasias/metabolismo , Neoplasias/patologia
16.
ACS Chem Biol ; 10(3): 757-65, 2015 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-25458073

RESUMO

Reactive oxygen species (ROS) play an important role in cellular signaling as second messengers. However, studying the role of ROS in physiological redox signaling has been hampered by technical difficulties in controlling their generation within cells. Here, we utilize two inert components, a photosensitizer and light, to finely manipulate the generation of intracellular ROS and examine their specific role in activating dendritic cells (DCs). Photoswitchable generation of intracellular ROS rapidly induced cytosolic mobilization of Ca(2+), differential activation of mitogen-activated protein kinases, and nuclear translocation of NF-κB. Moreover, a transient intracellular ROS surge could activate immature DCs to mature and potently enhance migration in vitro and in vivo. Finally, we observed that intracellular ROS-stimulated DCs enhanced antigen specific T-cell responses in vitro and in vivo, which led to delayed tumor growth and prolonged survival of tumor-bearing mice when immunized with a specific tumor antigen. Therefore, a transient intracellular ROS surge alone, if properly manipulated, can cause immature DCs to differentiate into a motile state and mature forms that are sufficient to initiate adaptive T cell responses in vivo.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Antígenos de Neoplasias/administração & dosagem , Neoplasias do Colo/terapia , Células Dendríticas/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/imunologia , Espécies Reativas de Oxigênio/agonistas , Imunidade Adaptativa/efeitos da radiação , Animais , Cálcio/imunologia , Cálcio/metabolismo , Sinalização do Cálcio , Linhagem Celular Tumoral , Movimento Celular , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias do Colo/mortalidade , Células Dendríticas/imunologia , Células Dendríticas/patologia , Células Dendríticas/efeitos da radiação , Hematoporfirinas/farmacologia , Imunização , Luz , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/genética , NF-kappa B/imunologia , Fármacos Fotossensibilizantes/farmacologia , Cultura Primária de Células , Transporte Proteico , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Análise de Sobrevida , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
17.
Int J Infect Dis ; 28: 204-10, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25316331

RESUMO

OBJECTIVES: This phase III placebo-controlled study evaluated the immunogenicity and safety of MenACWY-CRM vaccination in healthy Korean adolescents and adults. METHODS: Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination against all four meningococcal serogroups. The IgG concentration specific for serogroup W capsular polysaccharide was measured in a subset of subjects in a post-hoc analysis. Adverse reactions were monitored throughout the study. RESULTS: Four hundred and fifty subjects were randomized 2:1 to receive MenACWY-CRM (N=297) or a saline placebo (N=153). MenACWY-CRM induced a good immune response against all four serogroups, with seroprotection rates (hSBA titers ≥8) of 79%, 99%, 98%, and 94% for serogroups A, C, W, and Y, respectively. Seroresponse rates were high for serogroups A, C, and Y, i.e. 76%, 86%, and 69%, respectively; the rate for serogroup W was 28%. MenACWY-CRM vaccine induced serum bactericidal antibodies against all four serogroups in a majority of subjects regardless of their baseline hSBA titers. MenACWY-CRM was generally well tolerated with most reactions being transient and mild to moderate in severity. CONCLUSIONS: Findings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects) and geometric mean titers (48, 231, 147, and 107) against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.


Assuntos
Vacinas Meningocócicas/efeitos adversos , Vacinas Meningocócicas/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neisseria meningitidis/imunologia , Sorogrupo , Adulto Jovem
18.
Clin Vaccine Immunol ; 21(5): 762-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24671555

RESUMO

With continuing occurrence of varicella despite increasing vaccine coverage for the past 20 years, a case-based study, a case-control study, and an immunogenicity and safety study were conducted to address the impact of varicella vaccination in South Korea. Varicella patients under the age of 16 years were enrolled for the case-based study. For the case-control study, varicella patients between 12 months and 15 years of age were enrolled with one control matched for each patient. For the immunogenicity and safety study, otherwise healthy children from 12 to 24 months old were immunized with Suduvax (Green Cross, South Korea). Fluorescent antibody to membrane antigen (FAMA) varicella-zoster virus (VZV) antibody was measured before and 6 weeks after immunization. In the case-based study, the median age of the patients was 4 years. Among 152 patients between 1 and 15 years of age, 139 children received varicella vaccine and all had breakthrough infections. Clinical courses were not ameliorated in vaccinated patients, but more vaccinated patients received outpatient rather than inpatient care. In the case-control study, the adjusted overall effectiveness of varicella vaccination was 54%. In the immunogenicity and safety study, the seroconversion rate and geometric mean titer for FAMA antibody were 76.67% and 5.31. Even with increasing varicella vaccine uptake, we illustrate no upward age shift in the peak incidence, a high proportion of breakthrough disease, almost no amelioration in disease presentation by vaccination, and insufficient immunogenicity of domestic varicella vaccine. There is need to improve the varicella vaccine used in South Korea.


Assuntos
Vacina contra Varicela/administração & dosagem , Vacina contra Varicela/imunologia , Varicela/epidemiologia , Varicela/prevenção & controle , Adolescente , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , Varicela/patologia , Vacina contra Varicela/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , República da Coreia/epidemiologia , Vacinação/efeitos adversos , Vacinação/estatística & dados numéricos
19.
Int J Oral Sci ; 6(3): 150-3, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24008270

RESUMO

All-trans retinoic acid (ATRA) inhibits matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fibroblasts, skin fibroblasts, bronchoalveolar lavage cells and cancer cells, but activates MMP-9 in neuroblast and leukemia cells. Very little is known regarding whether ATRA can activate or inhibit MMPs in human dental pulp cells (HDPCs). The purpose of this study was to determine the effects of ATRA on the production and secretion of MMP-2 and -9 in HDPCs. The productions and messenger RNA (mRNA) expressions of MMP-2 and -9 were accessed by gelatin zymography and real-time polymerase chain reaction (PCR), respectively. ATRA was found to decrease MMP-2 level in a dose-dependent manner. Significant reduction in MMP-2 mRNA expression was also observed in HDPCs treated with 25 µmol⋅L(-1) ATRA. However, HDPCs treated with ATRA had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions. Taken together, ATRA had an inhibitory effect on MMP-2 expression in HDPCs, which suggests that ATRA could be a candidate as a medicament which could control the inflammation of pulp tissue in vital pulp therapy and regenerative endodontics.


Assuntos
Polpa Dentária/enzimologia , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Tretinoína/farmacologia , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultivo Condicionados , Polpa Dentária/citologia , Polpa Dentária/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , RNA Mensageiro/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Gênica/efeitos dos fármacos , Tretinoína/administração & dosagem
20.
J Nanosci Nanotechnol ; 13(10): 7134-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24245210

RESUMO

The development and enlargement of addressable magnetic core-shell hetero-architectures in a simple and economic way still remain a synthetic challenge. Herein, photofunctional magnetic FT1 (Fe3O4@TiO2 particles with 120 nm size) and FT4 ((Fe3O4@TiO2 particles with 420 nm size) core-shell particles with controlled size were fabricated successfully via a simple surface modification process that induces the atomic layer deposition (ALD) method. The size control of photofunctional magnetic particles has been adjusted by controlling the ratio of V(EG)/V(DEG) during the solvothermal reaction. Photocatalytic ability examination of the FT1 and FT4 core-shell particles was carried out in Rhodamine B (RhB) solutions illuminated under Xe light in a photochemical reactor. The photocatalytic activity depending on particle size indicates that the small FT1 particles are superior to the large FT4 particles due to the large surface area.

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