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Control over particulate matter (PM) emission from grilling is required for improving public health and air quality. The performance of mirror-symmetrical multi-compartment scrubbers with an upflow (U-type) and downflow baffle (D-type) configuration was evaluated for PM emission control from grilling at a flow rate of 30 m3 min-1. The PM removal efficiency of the U-type scrubber was the highest when the water level was 8 cm (95.6%), and the pressure drops recorded at the water levels of 6, 8 and 10 cm were 103, 122 and 153 mmH2O, respectively. Although PM removal efficiency of the D-type scrubber was over 91.0% at the water levels of 8, 10 and 12 cm, the pressure drops were 124, 142 and 185 mmH2O, respectively. A comprehensive evaluation of the water volume, pressure drop and PM removal performance, as well as device size, revealed that the U-type scrubber with a PM removal efficiency of 92% or higher and a pressure drop of 122 mmH2O or lower at the water levels of 6-8 cm was more economical for removing PM from grilling gas than the D-type scrubber.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Material Particulado/análisisRESUMEN
[This corrects the article DOI: 10.1155/2014/934691.].
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Here, red phosphorescent platinum(II) complexes based on tetradentate pyridine-containing lig-ands are studied. To investigate their electroluminescent properties, multilayer devices were fabricated in the following sequence; ITO (180 nm)/4,4',4â³-Tris[2-naphthyl(phenyl)amino]triphenylamine (2-TNATA) (30 nm)/N, N'-di(1-naphthyl)-N,N'-diphenyl-1,1'-biphenyl)4,4'-diamine (NPB) (20 nm)/ Tris(4-carbazoyl-9-ylphenyl)amine (TCTA) (10 nm)/4,4'-Bis(N-carbazolyl)-1,1'-biphenyl (CBP) (20 nm)/Platinum(II) complex (20 nm)/1,3,5-Tris(1-Phenyl-1H-benzimidazol-2-yl)benzene) (TPBi) (40 nm)/Liq (2 nm)/Al (100 nm). In particularly, a device using platinum(II) complex based on N-(3,5-di-tert-butylphenyl)-3-(pyridin-2-yl)-N-(3-(pyridin-2-yl)phenyl)benzenamineligand showed the efficient red emission, with a luminous efficiency, power efficiency, and external quantum efficiency of, and the Commission International de LEclairge (CIE) coordinates of 27.26 cd/A, 10.54 lm/W, 8.50% at 20 mA/cm², and (0.65, 0.33) at 11.0 V, respectively.
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In this study, we designed and synthesized two phosphorescent emitting materials based on tetradentate pyridine-containing ligands. Their photophysical properties were examined for OLEDs and multilayer devices using these materials were fabricated in the following sequence; ITO (180 nm)/4,4',4â³-Tris[2-naphthyl(phenyl)amino]triphenylamine (2-TNATA) (30 nm)/N,N'-di(1-naphthyl)-N,N'-diphenyl-1,1'-biphenyl)4,4'-diamine (NPB) (20 nm)/Tris(4-carbazoyl-9-ylphenyl)amine (TCTA) (10 nm)/4,4'-Bis(N-carbazolyl)-1,1'-biphenyl(CBP): 5, 8, 15% Platinum (II) complexes (20 nm)/1,3,5-Tris(1-Phenyl-1H-benzimidazol-2-yl)benzene) (TPBi) (40 nm)/Liq (2 nm)/Al (100 nm). In particularly, a device using Platinum (II) complex based on A/-(3,5-di-tert-butylphenyl)-6-phenyl-N-(6-phenylpyridin-2-yl)pyridin-2-amine ligand showed the efficient emission, with luminous efficiency, power efficiency, and external quantum efficiency, and the Commission International de LEclairge (CIE) coordinates of 29.29 cd/A, 9.37 lm/W, 8.66% at 20 mA/cm2, and (0.32, 0.62) at 8.0 V, respectively.
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Phosphorescent Pt(II) complexes based on phenylbenzoazole ligands were synthesized and their photophysical properties were investigated for OLEDs. Multilayered OLEDs devices using these complexes as emitters showed the efficient emissions, which are very sensitive to the structural and photophysical properties of Pt(II) complexes. In particularly, a device C using Pt(II) complex 2 based on phenylbenzoazole ligand as the dopant exhibited efficient emission with a luminous efficiency, a power efficiency, an external quantum efficiency, and CIE coordinates of 8.03 cd/A, 2.79 lm/W, 4.84% at 20 mA/cm², and (0.63, 0.35) at 10.0 V, respectively.
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Two fluorescent benzo[g]quinoline derivatives were synthesized via Friedländer synthesis. Multilayered OLEDs using benzo[g]quinoline derivatives as the emitters showed unexpected emissions by electroplexes. Particularly, a device using 2-(naphthalen-3-yl)-4-phenylbenzo[g]quinoline as an emitting material exhibited efficient emission with a luminous efficiency, a power efficiency, an external quantum efficiency, and CIE coordinates of 3.58 cd/A, 1.11 lm/W, 1.08% at 20 mA/cm², and (0.36, 0.56) at 1,000 cd/m², respectively.
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Two blue fluorescent materials based on diphenylaminoarylvinyl-substituted diphenylanthracene have been synthesized. Multilayered organic light-emitting diodes (OLED) with the following sequence; ITO/NPB (50 nm)/Blue materials (30 nm)/Bphen (30 nm)/Liq (2 nm)/Al (100 nm) were fabricated using these materials as emitters. Two devices exhibited blue electroluminescence. Particularly, a device using 6-(4-(10-phenylanthracen-9-yl)styryl)-N,N-diphenylnaphthalen-2-amine (2) exhibited blue emission with a luminance efficiency, a power efficiency, an external quantum efficiency and CIE coordinates of 5.69 cd/A, 1.99 lm/W, 3.39% at 100 mA/cm² and (x = 0.19, y =0.31) at 8.0 V, respectively.
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OBJECTIVES: This placebo-controlled randomized double-blinded clinical study assessed the analgesic efficacy of intramuscular morphine in TMD patients with myofascial pain and sex-dependent responses of the morphine treatment. SUBJECTS AND METHODS: Men and women with TMD were treated with morphine (1.5 or 5 mg), lidocaine, or saline in the masseter muscle. VAS of pain intensity, PPT, and PPtol were compared between treatment groups and gender. An additional group was treated with morphine in the trapezius muscle to evaluate the systemic effect of morphine that may reduce pain in the masseter muscle. RESULTS: There was a significant difference in VAS scores between the morphine 5 mg group and the saline group favoring morphine, but not between the morphine 5 mg and lidocaine. Morphine 1.5 and 5 mg treatments led to consistently and significantly elevated PPT and PPtol measures in men, but not in women. Morphine administered in the trapezius muscle did not affect the outcome measures. CONCLUSION: A single dose intramuscular morphine produced analgesic effects up to 48 hr in patients with myofascial pain. Intramuscular morphine elevated mechanical pain threshold and tolerance in the masseter only in male patients, suggesting sex differences in local morphine effects. No systemic effect of intramuscular morphine was detected.
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Analgésicos Opioides/uso terapéutico , Dolor Facial/tratamiento farmacológico , Morfina/uso terapéutico , Umbral del Dolor/efectos de los fármacos , Trastornos de la Articulación Temporomandibular/tratamiento farmacológico , Adulto , Analgésicos Opioides/administración & dosificación , Anestésicos Locales/uso terapéutico , Método Doble Ciego , Dolor Facial/etiología , Femenino , Humanos , Inyecciones Intramusculares , Lidocaína/uso terapéutico , Masculino , Músculo Masetero , Morfina/administración & dosificación , Dimensión del Dolor , Proyectos Piloto , Presión/efectos adversos , Factores Sexuales , Trastornos de la Articulación Temporomandibular/complicaciones , Adulto JovenRESUMEN
The present study evaluated the protective effects of melatonin in ethanol (EtOH)-induced senescence and osteoclastic differentiation in human periodontal ligament cells (HPDLCs) and cementoblasts and the underlying mechanism. EtOH increased senescence activity, levels of reactive oxygen species (ROS) and the expression of cell cycle regulators (p53, p21 and p16) and senescence-associated secretory phenotype (SASP) genes (interleukin [IL]-1ß, IL-6, IL-8 and tumor necrosis factor-α) in HPDLCs and cementoblasts. Melatonin inhibited EtOH-induced senescence and the production of ROS as well as the increased expression of cell cycle regulators and SASP genes. However, it recovered EtOH-suppressed osteoblastic/cementoblastic differentiation, as evidenced by alkaline phosphatase activity, alizarin staining and mRNA expression levels of Runt-related transcription factor 2 (Runx2) and osteoblastic and cementoblastic markers (glucose transporter 1 and cementum-derived protein-32) in HPDLCs and cementoblasts. Moreover, it inhibited EtOH-induced osteoclastic differentiation in mouse bone marrowâ»derived macrophages (BMMs). Inhibition of protein never in mitosis gene A interacting-1 (PIN1) by juglone or small interfering RNA reversed the effects of melatonin on EtOH-mediated senescence as well as osteoblastic and osteoclastic differentiation. Melatonin blocked EtOH-induced activation of mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and Nuclear factor of activated T-cells (NFAT) c-1 pathways, which was reversed by inhibition of PIN1. This is the first study to show the protective effects of melatonin on senescence-like phenotypes and osteoclastic differentiation induced by oxidative stress in HPDLCs and cementoblasts through the PIN1 pathway.
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Cemento Dental/citología , Etanol/farmacología , Melatonina/farmacología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Ligamento Periodontal/citología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Senescencia Celular/efectos de los fármacos , Cemento Dental/metabolismo , Humanos , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoclastos/citología , Ligamento Periodontal/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Complex regional pain syndrome (CRPS) is one of the most challenging chronic pain conditions and is characterized by burning pain, allodynia, hyperalgesia, autonomic changes, trophic changes, edema, and functional loss involving mainly the extremities. Until recently, very few reports have been published concerning CRPS involving the orofacial area. We report on a 50-year-old female patient who presented with unbearable pain in all of her teeth and hypersensitivity of the facial skin. She also reported intractable pain in both extremities accompanied by temperature changes and orofacial pain that increased when the other pains were aggravated. In the case of CRPS with trigeminal neuropathic pain, protocols for proper diagnosis and prompt treatment have yet to be established in academia or in the clinical field. We performed functional magnetic resonance imaging for a thorough analysis of the cortical representation of the affected orofacial area immediately before and immediately after isolated light stimulus of the affected hand and foot and concluded that CRPS can be correlated with trigeminal neuropathy in the orofacial area. Furthermore, the patient was treated with carbamazepine administration and stellate ganglion block, which can result in a rapid improvement of pain in the trigeminal region.
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Síndromes de Dolor Regional Complejo/diagnóstico por imagen , Síndromes de Dolor Regional Complejo/fisiopatología , Dolor Facial/diagnóstico por imagen , Dolor Facial/fisiopatología , Imagen por Resonancia Magnética , Femenino , Humanos , Persona de Mediana Edad , Dimensión del Dolor , Radiografía PanorámicaRESUMEN
INTRODUCTION: N-methyl-d-aspartate (NMDA) is expressed in sensory neurons and plays important roles in peripheral pain mechanisms. The aim of this study was to examine the effects and molecular mechanisms of NMDA on C2C12 myoblast proliferation and differentiation. METHODS: Cytotoxicity and differentiation were examined by the MTT assay, reverse transcription-polymerase chain reaction, and immunofluorescence. RESULTS: NMDA had no cytotoxicity (10-500 µM) and inhibited myoblastic differentiation of C2C12 cells, as assessed by F-actin immunofluorescence and levels of mRNAs encoding myogenic markers such as myogenin and myosin heavy-chain 2. It inhibited phosphorylation of mammalian target of rapamycin (mTOR) by inactivating mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38. It induced reactive oxygen species production. Furthermore, NMDA-suppressed expression of F-actin was reversed by adding the antioxidant N-acetylcysteine. CONCLUSIONS: Collectively, these results indicate that NMDA impairs myogenesis or myogenic differentiation in C2C12 cells through the mTOR/MAPK signaling pathways and may lead to skeletal muscle degeneration. Muscle Nerve 56: 510-518, 2017.
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Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Desarrollo de Músculos/efectos de los fármacos , Mioblastos/efectos de los fármacos , N-Metilaspartato/toxicidad , Animales , Diferenciación Celular/fisiología , Línea Celular , Proliferación Celular/fisiología , Ratones , Desarrollo de Músculos/fisiología , Mioblastos/metabolismo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: Magnetic biomaterials have recently gained great attention due to their some intriguing cell and tissue responses. However, little attention has been given to the fields of dental tissue regeneration. In this sense, we aim to investigate the effects of magnetic nanofiber scaffolds on the human dental pulp cell (HDPC) behaviors and to elucidate the underlying signaling mechanisms in the events. METHODS: Magnetic nanofiber scaffolds incorporating magnetic nanoparticles at varying contents were prepared into nanofibrous matrices to cultivate cells. Cell growth by MTS assay, odontoblastic differentiation by alkaline phosphatase (ALP) activity, mineralization, and the mRNA expression of differentiation-related genes of HDPCs, in vitro angiogenesis by migration and capillary tube formation in endothelial cells on the conditioned medium obtained from HDPSCs in the presence or absence of scaffolds. Western blot analysis and confocal immunofluorescene were used to asses signaling pathways. RESULTS: The growth of HDPCs was significantly enhanced on the magnetic scaffolds with respect to the non-magnetic counterpart. The odontogenic differentiation of cells was significantly up-regulated by the culture with magnetic scaffolds. Furthermore, the magnetic scaffolds promoted the HDPC-induced angiogenesis of endothelial cells. The expression of signaling molecules, Wnt3a, phosphorylated GSK-3ß and nuclear ß-catenin, was substantially stimulated by the magnetic scaffolds; in parallel, the MAPK and NF-κB were highly activated when cultured on the magnetic nanofiber scaffolds. SIGNIFICANCE: This study is the first to demonstrate that magnetic nanofiber scaffolds stimulate HDPCs in the events of growth, odontogenic differentiation, and pro-angiogenesis, and the findings imply the novel scaffolds can be potentially useful as dentin-pulp regenerative matrices.
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Pulpa Dental/metabolismo , FN-kappa B/metabolismo , Nanofibras , Neovascularización Fisiológica , Odontogénesis , Diferenciación Celular , Humanos , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Proteínas Wnt/metabolismoRESUMEN
Cudraxanthone H (CH) is a natural compound isolated from a methanol extract of the root bark of Cudrania tricuspidata, a herbal plant also known as Moraceae. However, the effect of CH on human cancer cells has not been reported previously. The aim of this study was to investigate the anticancer effects and mechanism of action of CH on oral squamous cell carcinoma (OSCC) cells. CH exerted significant antiproliferative effects on OSCC cells in dose- and time-dependent manners. CH also induced apoptosis in OSCC cells, as evidenced by an increased percentage of cells in the sub-G1 phase of the cell cycle, annexin V-positive/propidium iodide-negative cells, and nuclear morphology. This antiproliferative effect of CH was associated with a marked reduction in the expression of cyclin D1 and cyclin E, with a concomitant induction of cyclin-dependent kinase inhibitor (CDKI) expression (p21 and p27). CH inhibited the phosphorylation and degradation of IκB-α and the nuclear translocation of NF-κB p65. Furthermore, CH treatment down-regulated PIN1 mRNA and protein expression in a dose-dependent manner. PIN1 overexpression by infection with adenovirus-PIN1 (Ad-PIN1) attenuated the CH-induced growth-inhibiting and apoptosis-inducing effects, blocked CH-enhanced CDKI expression and restored cyclin levels. In contrast, inhibiting PIN1 expression via juglone exerted the opposite effects. The present study is the first to demonstrate antiproliferative and apoptosis-inducing effects of CH, which exerts its effects by inhibiting NF-κB and PIN1. These data suggest that it might be a novel alternative chemotherapeutic agent for use in the treatment of oral cancer.
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Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , FN-kappa B/fisiología , Isomerasa de Peptidilprolil/fisiología , Fitoterapia , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Xantonas/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Línea Celular Tumoral , Humanos , Moraceae/química , Neoplasias de la Boca/tratamiento farmacológico , Peptidilprolil Isomerasa de Interacción con NIMA , Xantonas/aislamiento & purificaciónRESUMEN
Recent reports suggest that hypoxia inducible factor-2α (HIF-2α) is a key regulator of osteoarthritis cartilage destruction. However, the precise role of HIF-2α in the inflammatory response and osteoclast differentiation remains unclear. The purpose of this study was to investigate the effect of HIF-2α on inflammatory cytokines, extracellular matrix (ECM) destruction enzymes, and osteoclastic differentiation in nicotine and lipopolysaccharide (LPS)-stimulated human periodontal ligament cells (PDLCs). HIF-2α was upregulated in chronically inflamed PDLCs of periodontitis patients, and in nicotine- and LPS-exposed PDLC in dose- and time-dependent manners. HIF-2α inhibitor and HIF-2α siRNA attenuated the nicotine- and LPS- induced production of NO and PGE2 , upregulation of iNOS, COX-2, pro-inflammatory cytokines (IL-1ß, TNF-α, IL-1ß, IL-6, IL-8, IL-10, IL-11, and IL-17), and matrix metalloproteinases (MMPs; MMP-1, -8, -13, -2 and -9), and reversed the effect on TIMPs (TIMP-1 and -2) in PDLCs. The conditioned medium produced by nicotine and LPS-treated PDLCs increased the number of TRAP-stained osteoclasts, TRAP activity and osteoclast-specific genes, which has been blocked by HIF-2α inhibition and silencing. HIF-2α inhibitor and HIF-2α siRNA inhibited the effects of nicotine and LPS on the activation of Akt, JAK2 and STAT3, ERK and JNK MAPK, nuclear factor-κB, c-Jun, and c-Fos. Taken together, this study is the first to demonstrate that HIF-2α inhibition exhibits anti-inflammatory activity through the inhibition of inflammatory cytokines and impairment of ECM destruction, as well as blocking of osteoclastic differentiation in a nicotine- and periodontopathogen-stimulated PDLCs model. Thus, HIF-2α inhibition may be a novel molecular target for therapeutic approaches in periodontitis.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Osteoclastos/citología , Ligamento Periodontal/patología , Periodontitis/metabolismo , Factores de Transcripción/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos ICR , Nicotina/farmacología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Ligamento Periodontal/citología , Periodontitis/inducido químicamente , Periodontitis/patología , Regulación hacia ArribaRESUMEN
PURPOSE: The expression levels of intracellular pyrin domain-containing 3 (NLRP3) and microbial pattern-recognition receptors, such as nucleotide-binding oligomerization domain 2 (NOD2), have been reported in human dental pulp cells (HDPCs) and inflamed dental pulp tissue, but the role of NLRP3 and Toll-like receptors (TLRs) in the production of human beta defensin 2 (hBD2) and inflammatory cytokines against invading pathogens remains poorly defined. The aim of this study was to determine whether the NOD2 ligand muramyl dipeptide (MDP) upregulates hBD2 and inflammatory cytokines and whether this response is dependent on TLRs and NLRP inflammasomes in HDPCs. METHODOLOGY: The effects of MDP on the expression of hBD2, TLRs, inflammasomes, and pro-inflammatory mediators in HDPCs were examined using Western blotting and reverse transcription-polymerase chain reaction. Levels of pro-inflammatory cytokines, such as nitric oxide (NO) and prostaglandin E2 (PGE2), were determined by enzyme-linked immunosorbent assay. RESULTS: MDP upregulated hBD2, TLR2, and TLR4 mRNAs and protein levels in a dose- and time-dependent manner. TLR2 and TLR4 neutralizing blocking antibodies and NOD2- and hBD2-specific small interfering RNAs (siRNAs) attenuated the MDP-induced production of NO, PGE2, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-8 and upregulated inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) in HDPCs. Additionally, MDP activated inflammasome-related genes, such as NLRP3, caspase 1, apoptotic speck protein containing a caspase recruitment domain, and IL-1ß. Furthermore, silencing of the NLRP3 gene using a siRNA significantly decreased the MDP-induced expression of hBD2 and cytokines, such as iNOS-derived NO, COX2, PGE2, TNF-α, IL-6, and IL-8. CONCLUSION: These results suggest that NOD2 activates the TLR2, TLR4, and NLRP3 inflammasome-signaling pathways in HDPCs to induce the production of multiple inflammatory mediators and antimicrobial peptides, which in turn promote pulp immune defense against microbial challenge. CLINICAL RELEVANCE: The TLR and NLRP3 inflammasome pathways may represent an important modulatory mechanism of immune defense responses during the progression of pulpitis. Our results suggest that local inhibition of NLRP3 and TLRs may reduce the impact of cytokine-mediated host destructive processes in pulpitis.
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Acetilmuramil-Alanil-Isoglutamina/farmacología , Pulpa Dental/citología , Pulpa Dental/metabolismo , Inflamasomas/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Receptores Toll-Like/metabolismo , beta-Defensinas/metabolismo , Western Blotting , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia ArribaRESUMEN
INTRODUCTION: The objective of this study was to compare the cytotoxicity, inflammatory response, osteogenic effect, and the signaling mechanism of these biologic activities of 4 calcium compound-based root canal sealers (ie, Sealapex [Sybron Kerr, WA], apatite root sealer [ARS; Dentsply Sankin, Tokyo, Japan], MTA Fillapex [Angelus Indústria de Produtos Odontológicos S/A, Londrina, PR, Brazil], and iRoot SP [Innovative BioCreamix Inc, Vancouver, Canada]) in human periodontal ligament cells. METHODS: Cytotoxicity was assessed using the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide assay. Levels of inflammatory mediators were measured by enzyme-linked immunosorbent assay, reverse-transcription polymerase chain reaction, and Western blot analysis. Osteogenic potential was evaluated by alkaline phosphatase activity, alizarin red staining, and marker genes by reverse-transcription polymerase chain reaction. The signal transduction pathways were examined by Western blotting. RESULTS: None of the sealers were cytotoxic. ARS, MTA Fillapex, and iRoot SP induced a lower expression of proinflammatory mediators than Sealapex. All sealers increased ALP activity and the formation of mineralized nodules and up-regulated the expression of osteoblastic marker messenger RNA. ARS, MTA Fillapex, and iRoot SP showed superior osteogenic potential compared with Sealapex. The expression and/or activation of integrin receptors and downstream signaling molecules, including focal adhesion kinase, paxillin, Akt, mitogen-activated protein kinase, and nuclear factor κB, was induced by ARS, MTA Fillapex, and iRoot SP treatment but not by Sealapex treatment. CONCLUSIONS: We show for the first time that ARS, MTA Fillapex, and iRoot SP induce a lower expression of inflammatory mediators and enhance osteoblastic differentiation of PDLCs via the integrin-mediated signaling pathway compared with Sealapex.
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Materiales Biocompatibles/farmacología , Mediadores de Inflamación/farmacología , Osteogénesis/efectos de los fármacos , Materiales de Obturación del Conducto Radicular/farmacología , Fosfatasa Alcalina/análisis , Fosfatasa Alcalina/efectos de los fármacos , Compuestos de Aluminio/farmacología , Compuestos de Aluminio/toxicidad , Antraquinonas , Materiales Biocompatibles/toxicidad , Compuestos de Calcio/farmacología , Compuestos de Calcio/toxicidad , Hidróxido de Calcio/farmacología , Hidróxido de Calcio/toxicidad , Diferenciación Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Colorantes , Combinación de Medicamentos , Durapatita/farmacología , Durapatita/toxicidad , Quinasa 1 de Adhesión Focal/efectos de los fármacos , Humanos , Mediadores de Inflamación/toxicidad , Ensayo de Materiales , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , FN-kappa B/efectos de los fármacos , Nanopartículas , Osteoblastos/efectos de los fármacos , Óxidos/farmacología , Óxidos/toxicidad , Paxillin/efectos de los fármacos , Ligamento Periodontal/citología , Ligamento Periodontal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Materiales de Obturación del Conducto Radicular/toxicidad , Salicilatos/farmacología , Salicilatos/toxicidad , Transducción de Señal/efectos de los fármacos , Silicatos/farmacología , Silicatos/toxicidad , Sales de Tetrazolio , TiazolesRESUMEN
Isocudraxanthone K (IK) is a novel, natural compound from a methanol extract of the root bark of Cudrania tricuspidata. It has not been shown previously that IK possessed antitumor activity. We investigated the antitumor effects and molecular mechanism of IK and related signal transduction pathway(s) in oral squamous cell carcinoma cells (OSCCCs). The MTT assay revealed that IK had an antiproliferative effect on OSCCCs, in a dose- and time-dependent manner. IK induced apoptosis in OSCCCs, as identified by a cell-cycle analysis, annexin V-FITC and propidium iodide staining, and the nuclear morphology in cell death. IK caused time-dependent phosphorylation of Akt, p38, and ERK (extracellular signal-regulated kinase). In addition, IK increased the cytosolic to nuclear translocation of nuclear factor-κB (NF-κB) p65 and the degradation and phosphorylation of IκB-α in HN4 and HN12 cells. Furthermore, IK treatment downregulated hypoxia-inducible factor 1α (HIF-1α) and its target gene, vascular endothelial growth factor (VEGF). Cobalt chloride (CoCl2), a HIF-1α activator, attenuated the IK-induced growth-inhibiting and apoptosis-inducing effects, and blocked IK-induced expression of apoptosis regulatory proteins, such as Bax, Bcl-2, caspase-3, caspase-8, and caspase-9, and cytochrome c. Collectively, these data provide the first evidence of antiproliferative and apoptosis-inducing effects of IK as a HIF-1α inhibitor and suggest it may be a drug candidate for chemotherapy against oral cancer.
Asunto(s)
Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Moraceae/química , Neoplasias de la Boca , Corteza de la Planta/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Xantonas/farmacología , Caspasas/genética , Caspasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Citocromos c/genética , Citocromos c/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Extractos Vegetales/química , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo , Xantonas/química , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
The aim of this study is to determine the effects of the combination of recombinant human BMP-2 (rh-BMP-2) and dentin sialoprotein (rh-DSP) on growth and differentiation in human cementoblasts and determine the underlying signal transduction mechanism. Compared to treatment of cementoblasts with either rh-BMP-2 or rh-DSP alone, the combination of rh-BMP-2 and rh-DSP synergistically increased cell growth, ALP activity, nodule formation and expression of differentiation markers. The differentiation-promoting effect was also observed in periodontal ligament cells and an osteoblastic cell line. Likewise, combination of rh-DSP and rh-BMP-2 increased BMP-2 mRNA expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist noggin. The expression levels of α2ß1 integrin and RhoA, as well as the phosphorylation status of FAK and Akt, were increased by the combination of rh-BMP-2 and rh-DSP in a time-dependent manner. In addition, rh-BMP-2 and rh-DSP enhanced expression of Wnt ligands, ß-catenin activation and GSK-3ß phosphorylation, all of which were inhibited by the Wnt receptor antagonist DKK1. Furthermore, treatment with rh-DSP plus rh-BMP-2 resulted in phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 and also induced the nuclear translocation of the NF-κB p65 subunit, which was blocked by noggin. This study demonstrates for the first time that rh-DSP and rh-BMP-2 act synergistically, enhancing each other's ability to stimulate cementoblastic cell growth and differentiation in vitro via autocrine BMP, integrin, Wnt/ß-catenin, MAP kinase and NF-κB pathways. These results support the therapeutic potential of a combination strategy for aiding periodontal regeneration.
Asunto(s)
Proteína Morfogenética Ósea 2/farmacología , Cemento Dental/citología , Cemento Dental/efectos de los fármacos , Proteínas de la Matriz Extracelular/farmacología , Fosfoproteínas/farmacología , Sialoglicoproteínas/farmacología , Factor de Crecimiento Transformador beta/farmacología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Cemento Dental/metabolismo , Humanos , Ligamento Periodontal/citología , Ligamento Periodontal/efectos de los fármacos , Ligamento Periodontal/metabolismo , Proteínas Recombinantes/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
The goal of this study was to investigate the effect and molecular mechanism of cudraflavone B, a prenylated flavonoid isolated from the root bark of Cudrania tricuspidata, against oral squamous cell carcinoma cells. We observed that cudraflavone B inhibited proliferation of these cells in a time- and dose-dependent manner. At 15 µM, cudraflavone B induced cell death via apoptosis (characterized by the appearance of nuclear morphology) and increased the accumulation of the sub-G1 peak (portion of apoptotic annexin V positive cells). Treatment with cudraflavone B triggered the mitochondrial apoptotic pathway (indicated by induction of the proapoptotic protein p53 and the p21 and p27 effector proteins), downregulation of cell cycle regulatory proteins (e.g., p-Rb, changing Bax/Bcl-2 ratios, cytochrome-c release), and caspase-3 activation. Cudraflavone B time-dependently activated NF-κB, the MAP kinases p38, and ERK, and induced the expression of SIRT1. SIRT1 activator, resveratrol, dose-dependently attenuated the growth-inhibitory and apoptosis-inducing effect of cudraflavone B and blocked cudraflavone B-induced regulatory protein expressions in the mitochondrial pathway such as p53, p21, p27, Bax, caspase-3, and cytochrome-c. Conversely, treatment with SIRT1 inhibitor sirtinol caused opposite effects. These results demonstrate for the first time that the molecular mechanism underlying the antitumor effect in oral squamous cell carcinoma cells is related to the activation of MAPK/and NF-κB as well as of the SIRT1 pathway. Therefore, cudraflavone B may be a lead for the development of a potential candidate for human oral squamous cell carcinoma cells.
Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Flavonoides/uso terapéutico , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Moraceae/química , Neoplasias de la Boca/tratamiento farmacológico , FN-kappa B/metabolismo , Sirtuina 1/metabolismo , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/metabolismo , Caspasa 3/metabolismo , Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias de la Boca/metabolismo , Fitoterapia , Corteza de la Planta , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Raíces de Plantas , Proteínas Quinasas/metabolismo , Transducción de SeñalRESUMEN
A stem cell-based strategy for tissue engineering in regenerative medicine is crucial to produce and effective therapeutic replacement of injured or damaged tissues. This type of therapeutic replacement requires interaction with the cells and tissues via the incorporation of a beneficial physical microenvironment and cellular biochemical signals. Recently, we studied a cell-function modifying factor, core-shell nanoparticles consisting of an SPIO (superparamagnetic iron oxide) core covered with a photonic ZnO shell for human adipose tissue-derived stem cells (hATSCs) that regulate various cellular functions: self-renewal, neurogenesis, and dedifferentiation. We proposed an alternative method of stem cell culture that focuses on the use of Zn++ Finger nanoparticles for stem cell expansion and transdifferentiation modulation in vitro and in in vivo spinal cord injury models. Our study showed that treating hATSC cultures with nanoscale particles could lead to active cell proliferation and self-renewal and could promote nuclear Dicer-regulation of several functional molecules, Oct4 and Glutathione peroxidase 3 (GPx3), and the abundance of specific functional proteins that have been observed using biochemical analysis. These biochemical changes in hATSCs induced the functional development of multiple differentiation potencies such as ß-cells and neural cells; specifically, the ability to differentiation into GABA-secreting cells was significantly improved in in vitro- and in vivo-induced animal lesions with significantly improved therapeutic modality.