Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52
Filtrar
Más filtros











Base de datos
Intervalo de año de publicación
1.
Maxillofac Plast Reconstr Surg ; 46(1): 24, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38976106

RESUMEN

BACKGROUND: The management of internal derangement (ID) of the TMJ is challenging because of multiple etiologic factors and varying degrees of severity. The aim of this study was to evaluate the clinical outcomes of patients with unilateral ID treated with arthrocentesis and stabilization splint therapy during a 6-month period. METHODS: A total of 105 patients (87 females, 18 males) with unilateral ID were included in this study. Patients were divided into unilateral anterior disc displacement with reduction (ADDwR) and unilateral anterior disc displacement without reduction (ADDwoR). Patients with ADDwoR were subdivided according to the erosive bone changes. Objective parameters on mandibular movement and subjective parameters on pain were obtained and assessed. Their clinical outcomes before and after arthrocentesis and stabilization splint therapy were compared with the chi-square, Fisher's exact test, paired t-test, or Wilcoxon singed-rank test. RESULTS: All objective parameters of unilateral ID patients significantly increased at the 6-month follow-up. The differences in mean visual analog scale (VAS) pain scores were statistically significant in all subjective variables (p < 0.01). In joints with ADDwoR, preoperative maximal mouth opening, and maximal protrusive movement in both groups, with erosive and non-erosive changes were significantly increased after 6 months (p < 0.01). However, right and left maximal lateral movement increased after treatment in both groups but without significant differences. All VAS pain scores on jaw movement and palpation of associated muscles showed a significant decrease regardless of erosive changes. CONCLUSIONS: The combination of arthrocentesis and subsequent stabilization splint therapy was shown to be highly effective in pain reduction and improvement of mandibular movements in both unilateral ADDwR and ADDwoR, as well as in cases with both erosive and non-erosive bony changes associated with unilateral ADDwoR.

2.
Antioxidants (Basel) ; 13(4)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38671920

RESUMEN

Phosphatase and tensin homolog (PTEN) is a negative regulator of the phosphoinositide 3-kinases/protein kinase B (PI3K/AKT) signaling pathway. Notably, its active site contains a cysteine residue that is susceptible to oxidation by hydrogen peroxide (H2O2). This oxidation inhibits the phosphatase function of PTEN, critically contributing to the activation of the PI3K/AKT pathway. Upon the stimulation of cell surface receptors, the activity of NADPH oxidase (NOX) generates a transient amount of H2O2, serving as a mediator in this pathway by oxidizing PTEN. The mechanism underlying this oxidation, occurring despite the presence of highly efficient and abundant cellular oxidant-protecting and reducing systems, continues to pose a perplexing conundrum. Here, we demonstrate that the presence of bicarbonate (HCO3-) promoted the rate of H2O2-mediated PTEN oxidation, probably through the formation of peroxymonocarbonate (HCO4-), and consequently potentiated the phosphorylation of AKT. Acetazolamide (ATZ), a carbonic anhydrase (CA) inhibitor, was shown to diminish the oxidation of PTEN. Thus, CA can also be considered as a modulator in this context. In essence, our findings consolidate the crucial role of HCO3- in the redox regulation of PTEN by H2O2, leading to the presumption that HCO4- is a signaling molecule during cellular physiological processes.

3.
Antioxidants (Basel) ; 13(2)2024 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-38397797

RESUMEN

Phosphatase and tensin homolog (PTEN) is a tumor suppressor due to its ability to regulate cell survival, growth, and proliferation by downregulating the PI3K/AKT signaling pathway. In addition, PTEN plays an essential role in other physiological events associated with cell growth demands, such as ischemia-reperfusion, nerve injury, and immune responsiveness. Therefore, recently, PTEN inhibition has emerged as a potential therapeutic intervention in these situations. Increasing evidence demonstrates that reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), are produced and required for the signaling in many important cellular processes under such physiological conditions. ROS have been shown to oxidize PTEN at the cysteine residue of its active site, consequently inhibiting its function. Herein, we provide an overview of studies that highlight the role of the oxidative inhibition of PTEN in physiological processes.

4.
Antioxidants (Basel) ; 12(1)2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36670982

RESUMEN

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are becoming increasingly prevalent worldwide. Despite the different etiologies, their spectra and histological feature are similar, from simple steatosis to more advanced stages such as steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Studies including peroxiredoxin knockout models revealed that oxidative stress is crucial in these diseases, which present as consequences of redox imbalance. Protein tyrosine phosphatases (PTPs) are a superfamily of enzymes that are major targets of reactive oxygen species (ROS) because of an oxidation-susceptible nucleophilic cysteine in their active site. Herein, we review the oxidative inactivation of two tumor suppressor PTPs, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and T-cell protein tyrosine phosphatase (TCPTP), and their contribution to the pathogenicity of ALD and NAFLD, respectively. This review might provide a better understanding of the pathogenic mechanisms of these diseases and help develop new therapeutic strategies to treat fatty liver disease.

5.
Antioxidants (Basel) ; 10(2)2021 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-33669370

RESUMEN

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is known as a tumor suppressor gene that is frequently mutated in numerous human cancers and inherited syndromes. PTEN functions as a negative regulator of PI3K/Akt signaling pathway by dephosphorylating phosphatidylinositol (3, 4, 5)-trisphosphate (PIP3) to phosphatidylinositol (4, 5)-bisphosphate (PIP2), which leads to the inhibition of cell growth, proliferation, cell survival, and protein synthesis. PTEN contains a cysteine residue in the active site that can be oxidized by peroxides, forming an intramolecular disulfide bond between Cys124 and Cys71. Redox regulation of PTEN by reactive oxygen species (ROS) plays a crucial role in cellular signaling. Peroxiredoxins (Prxs) are a superfamily of peroxidase that catalyzes reduction of peroxides and maintains redox homeostasis. Mammalian Prxs have 6 isoforms (I-VI) and can scavenge cellular peroxides. It has been demonstrated that Prx I can preserve and promote the tumor-suppressive function of PTEN by preventing oxidation of PTEN under benign oxidative stress via direct interaction. Also, Prx II-deficient cells increased PTEN oxidation and insulin sensitivity. Furthermore, Prx III has been shown to protect PTEN from oxidation induced by 15s-HpETE and 12s-HpETE, these are potent inflammatory and pro-oxidant mediators. Understanding the tight connection between PTEN and Prxs is important for providing novel therapies. Herein, we summarized recent studies focusing on the relationship of Prxs and the redox regulation of PTEN.

6.
Redox Biol ; 34: 101553, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32413744

RESUMEN

Phosphatase and tensin homologs deleted on chromosome 10 (PTEN) is a potent tumor suppressor and often dysregulated in cancers. Cellular PTEN activity is restrained by the oxidation of active-site cysteine by reactive oxygen species (ROS). Recovery of its enzymatic activity predominantly depends on the availability of cellular thioredoxin (Trx) and peroxiredoxins (Prx), both are important players in cell signaling. Trx and Prx undergo redox-dependent conformational changes through the oxidation of cysteine residues at their active sites. Their dynamics are essential for protein functionality and regulation. In this review, we summarized the recent advances regarding the redox regulation of PTEN, with a specific focus on our current state-of-the-art understanding of the redox regulation of PTEN. We also proposed a tight association of the redox regulation of PTEN with Trx dimerization and Prx hyperoxidation, providing guidance for the identification of novel therapeutic targets.


Asunto(s)
Peroxirredoxinas , Tiorredoxinas , Cisteína , Oxidación-Reducción , Fosfohidrolasa PTEN , Peroxirredoxinas/metabolismo , Especies Reactivas de Oxígeno , Transducción de Señal , Tiorredoxinas/genética , Tiorredoxinas/metabolismo
7.
J Oral Rehabil ; 47(3): 307-312, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31557342

RESUMEN

The efficacy of a combination treatment of arthrocentesis and stabilisation splint for patients with bilateral anterior disc displacement without reduction (ADDWoR) and erosive change of the TMJ remains controversial. To evaluate clinical outcomes of patients with ADDWoR and erosive change of the TMJ after performance of unilateral arthrocentesis and stabilisation splint therapy. A retrospective study of 44 patients (37 females, 7 males, mean age of 34 years) with bilateral ADDWoR and erosive change of the TMJ were included in this study. Their clinical outcomes before and after arthrocentesis and stabilisation splint therapy were compared. Evaluation criteria were as follows: (a) Maximal mouth opening (MMO); (b) Right and left maximal lateral movement (RLM, LLM) and maximal protrusive movement (PM); (c) Visual analog scale (VAS) pain score during MMO, RLM, LLM and PM; and (d) VAS pain score during palpation of masticatory muscles. Wilcoxon signed-rank test, Mc Nemar test and paired t test were used for statistical analysis. Differences in VAS pain score between arthrocentesis and non-arthrocentesis sites were not statistically significant except MMO and LLM (P < .05) after 6 months. Differences in mean VAS pain scores for all variables between before arthrocentesis and 6 months follow-up in the arthrocentesis site were statistically significant. (P < .01). Unilateral arthrocentesis on more symptomatic TMJ and subsequent stabilisation splint therapy was highly successful for pain and achievement of normal range of mandibular movements in patients with both ADDWoR and bony change.


Asunto(s)
Luxaciones Articulares , Trastornos de la Articulación Temporomandibular , Adulto , Artrocentesis , Femenino , Humanos , Masculino , Dimensión del Dolor , Rango del Movimiento Articular , Estudios Retrospectivos , Férulas (Fijadores) , Articulación Temporomandibular , Resultado del Tratamiento
8.
Genes Genomics ; 41(3): 373-379, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30610621

RESUMEN

BACKGROUND: Nitric oxide synthases (NOSs) are a unique family of enzymes that catalyze the production of nitric oxide (NO) from L-arginine. Atherogenic action of oxidized low-density lipoproteins (oxLDL) may be mediated partly by the formation of NO in endothelial cells. OBJECTIVE: The objective of this study was to identify sources of reactive oxygen species (ROS) causing native LDL (nLDL)-induced senescence of cultured human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were treated with nLDL and NO production was assessed using Griess reagent as substrate and spectrophotometry in the absence or presence of specific inhibitors of endothelial NOS (eNOS) and inducible NOS (iNOS). In addition, expression levels of eNOS and iNOS were measured with ELISA and western blotting, and ROS was evaluated using 2',7'-dichlorofluorescin diacetate (DCF-DA) and a fluorescence microplate reader. RESULTS: NO formation in nLDL-treated HUVECs was significantly increased. Long-term treatment with nLDL up-regulated both eNOS and iNOS proteins. Such increase of NO production in HUVECs induced by nLDL was significantly suppressed by treatment with iNOS-selective inhibitor 1400 W, but not by the eNOS-selective inhibitor L-NIO. Native LDL treatment uncoupled Hsp90, the regulatory binding protein of eNOS, from the enzyme in HUVECs. Native LDL also significantly increased ROS production in HUVECs. CONCLUSION: These findings suggest that oxidative stress originated from induction of iNOS and eNOS could be a causative factor for nLDL-induced senescence of HUVECs.


Asunto(s)
Células Endoteliales de la Vena Umbilical Humana/metabolismo , Lipoproteínas LDL/metabolismo , Óxido Nítrico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Humanos , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo
9.
J Oral Maxillofac Surg ; 76(5): 963-971, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29425757

RESUMEN

PURPOSE: The aim of the present prospective and preliminary study was to compare the clinical and radiographic outcomes of 2 types of rough surfaced implants after implant placement in the atrophic posterior maxilla with sinus membrane elevation without bone grafting using the crestal approach. PATIENTS AND METHODS: All clinical and radiographic records for 28 patients who had received 40 implants were included in the present study. The patients returned for radiographic and clinical examinations at 1, 3, and 6 months and every 6 months thereafter after implantation. Cone-beam computed tomography images were taken to evaluate the amount of bone gain in the maxillary sinus. Standardized periapical digital radiographs were taken to evaluate the changes in the crestal peri-implant bone level and peri-implant fixture radiolucency. RESULTS: The Kaplan-Meier survival estimates demonstrated a 100% probability of survival to 24 months. No significant differences were found in cervical bone loss (CBL) or residual bone height (RBH) between the TS III CA group and the TS III SA group during the 2-year follow-up period after implant placement. The CBL values according to gender, implant placement region, prosthesis type, and the time of implantation were not significantly different between the 2 groups. CONCLUSIONS: The results of the present preliminary study demonstrate that 2 types of rough surfaced implants placed in the atrophic posterior maxilla with sinus membrane elevation without a bone graft have good clinical and radiographic outcomes.


Asunto(s)
Pérdida de Hueso Alveolar/cirugía , Implantación Dental Endoósea/instrumentación , Implantación Dental Endoósea/métodos , Implantes Dentales , Enfermedades Mandibulares/cirugía , Adulto , Anciano , Pérdida de Hueso Alveolar/diagnóstico por imagen , Diseño de Prótesis Dental , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Enfermedades Mandibulares/diagnóstico por imagen , Persona de Mediana Edad , Estudios Prospectivos , Radiografía , Resultado del Tratamiento
10.
J Prosthodont ; 27(5): 443-448, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27479462

RESUMEN

PURPOSE: To evaluate the influence of implant neck structures on marginal bone loss around intentionally exposed implant fixtures by histomorphometric analysis. MATERIALS AND METHODS: Twenty-four implants representing 3 implant systems were placed in three dogs; an implant system with SLA surface without microthreads (group A); one with SLA + calcium surface without microthreads (group B); and one with SLA surface with microthreads (group C). The histomorphometric analyses for vertical defect length (VDL), infrabony defect height (IDH), and defect depth (DD) were performed at the buccal and lingual sides of each fixture. RESULTS: The VDL was lower in group A relative to groups B and C on the buccal and lingual sides. The IDH and DD were higher in group A than group C on the buccal and lingual sides; however, no statistically significant differences were noted between the groups in VDL, IDH, and DD on the buccal and lingual sides of the fixtures. CONCLUSIONS: In this preliminary study, marginal bone resorption pattern in the canine mandible varied according to the neck design of each implant fixture. Further studies with larger sample size are needed to confirm the effect of microthreads and surface roughness on the marginal bone loss at the exposed implant fixture.


Asunto(s)
Pérdida de Hueso Alveolar/etiología , Implantación Dental Endoósea/métodos , Implantes Dentales , Diseño de Prótesis Dental , Animales , Perros , Masculino , Mandíbula/cirugía , Propiedades de Superficie
11.
Oxid Med Cell Longev ; 2017: 4576985, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29098060

RESUMEN

[This corrects the article DOI: 10.1155/2017/6487825.].

12.
Free Radic Biol Med ; 112: 277-286, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28774816

RESUMEN

Intracellular redox status influences the oxidation and enzyme activity of the tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN). Cumene hydroperoxide (CuHP), an organic hydroperoxide, is a known tumor promoter. However, molecular targets and action mechanism of CuHP in tumor promotion have not been well characterized. In this study, we investigated the effect of CuHP on the redox state of PTEN in HeLa cells. In addition, the intracellular reducing system of oxidized PTEN was analyzed using a biochemical approach and the effect of CuHP on this reducing system was also analyzed. While PTEN oxidized by hydrogen peroxide is progressively converted to its reduced form, PTEN was irreversibly oxidized by exposure to CuHP in HeLa cells. A combination of protein fractionation and mass analysis showed that the reducing system of PTEN was comprised of NADPH, thioredoxin reductase (TrxR), and thioredoxin (Trx). Although CuHP-mediated PTEN oxidation was not reversible in cells, CuHP-oxidized PTEN was reactivated by the exogenous Trx system, indicating that the cellular Trx redox system for PTEN is inactivated by CuHP. We present evidence that PTEN oxidation and the concomitant inhibition of thioredoxin by CuHP results in irreversible oxidation of PTEN in HeLa cells. In addition, ablation of peroxiredoxin (Prdx) enhanced CuHP-induced PTEN oxidation in cells. These results provide a new line of evidence that PTEN might be a crucial determinant of cell fate in response to cellular oxidative stress induced by organic hydroperoxides.


Asunto(s)
Derivados del Benceno/farmacología , Carcinógenos/farmacología , Fibroblastos/efectos de los fármacos , Fosfohidrolasa PTEN/química , Tiorredoxina Reductasa 1/metabolismo , Tiorredoxinas/metabolismo , Animales , Línea Celular , Embrión de Mamíferos , Fibroblastos/citología , Fibroblastos/metabolismo , Expresión Génica , Células HeLa , Humanos , Peróxido de Hidrógeno/farmacología , Ratones , NADP/metabolismo , Oxidación-Reducción , Estrés Oxidativo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Tiorredoxina Reductasa 1/genética , Tiorredoxinas/genética
13.
Clin Implant Dent Relat Res ; 19(4): 703-709, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28517552

RESUMEN

PURPOSE: The purpose of this retrospective study was to determine clinical and radiographic outcomes of immediate and delayed placement of dental implants in molar and premolar regions. MATERIALS AND METHODS: Clinical and radiographic records of 116 patients who received implants in molar and premolar regions were included in this study. After implantation, patients were recalled for assessments at 1 month, 3 months, 6 months, 1 year, and every year thereafter. In addition, anatomic location, type of prosthesis, gender, stage, diameter, and length of implants were analyzed. RESULTS: Of these 116 patients, 55 were males, and 61 were females. Their mean age was 50.9 years. They received 85 immediate implants and 147 delayed implants in molar and premolar regions. Gender, type of prosthesis, stage, implant diameter, and implant length were not significantly different between the immediate placement group and the delayed placement group, although anatomic locations were significantly different between the 2 groups. Their mean follow up time after dental implantation was 3 years (range, 6 months to 9 years). Kaplan-Meier survival estimates showed 97.8% probability of survival up to 9 years in the delayed placement group and 100% probability of survival up to 8 years in the immediate placement group. There was no significant difference in implant survival according to the time of implantation. No significant difference in cervical bone loss (CBL) at the mesial or distal side was found between the 2 groups. CBL according to anatomic location, the type of prosthesis, or gender was not significantly different either between the 2 groups. However, CBL at distal side of 1-stage approach was significantly (P < .05) smaller in the delayed placement group than that in the immediate placement group. CONCLUSION: This study showed that immediate dental implantation in molar and premolar regions had good clinical and radiographic outcomes.


Asunto(s)
Diente Premolar/cirugía , Implantación Dental Endoósea , Carga Inmediata del Implante Dental , Diente Molar/cirugía , Adolescente , Adulto , Anciano , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/patología , Diente Premolar/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diente Molar/diagnóstico por imagen , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
14.
Oxid Med Cell Longev ; 2017: 6487825, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28197300

RESUMEN

The study aimed to evaluate whether the treatment of primary cultured human endothelial cells with native low-density lipoprotein (nLDL) could induce their senescence and to uncover some of the putative mechanisms involved. For this purpose, human umbilical vein endothelial cells (HUVECs) were subcultured and/or continuously cultured with nLDL (0, 2, 5, and 10 µg protein/mL), for up to 9 days. The results indicated that nLDL inhibited the proliferation of HUVECs by arresting the cell cycle at G1 phase. The G1-arrested cells showed increase in cytosolic senescence-associated-ß-galactosidase (SA-ß-Gal) activity, a biomarker of cellular senescence. The causative factor of the cellular senescence was nLDL itself and not oxidized LDL (oxLDL), since blocking LDL receptor (LDLR) with the anti-LDLR antibody opposed the nLDL-induced increase of SA-ß-Gal activity and decrease of cellular proliferation. In addition, nLDL-induced cellular senescence by inhibiting the phosphorylation of pRb (G1 arrest) via p53 as well as p16 signal transduction pathways. G1 phase arrest of the senescent cells was not overcome by nLDL removal from the culture medium. Moreover, the nLDL-treated cells produced reactive oxygen species (ROS) dose- and time-dependently. These results suggested, for the first time, that long-term treatment of nLDL could induce the premature senescence of endothelial cells.


Asunto(s)
Ciclo Celular/fisiología , Proliferación Celular/fisiología , Senescencia Celular/fisiología , Lipoproteínas LDL/farmacología , Western Blotting , Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Senescencia Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Especies Reactivas de Oxígeno/metabolismo
15.
Maxillofac Plast Reconstr Surg ; 39(1): 1, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28101496

RESUMEN

BACKGROUND: Multiple myeloma (MM) is characterized by a neoplastic proliferation of plasma cells primarily in the bone marrow. Bisphosphonates (BP) are used as supportive therapy in the management of MM. This study aimed to analyze the incidence, risk factors, and clinical outcomes of medication-related necrosis of the jaw (MRONJ) in MM patients. METHODS: One hundred thirty MM patients who had previous dental evaluations were retrospectively reviewed. Based on several findings, we applied the staging and treatment strategies on MRONJ. We analyzed gender, age, type of BP, incidence, and local etiological factors and assessed the relationship between these factors and the clinical findings at the first oral examination. RESULTS: MRONJ was found in nine male patients (6.9%). The mean patient age was 62.2 years. The median BP administration time was 19 months. Seven patients were treated with a combination of IV zoledronate and pamidronate, and two patients received single-agent therapy. The lesions were predominantly located in the mandible (n = 8), and the most common predisposing dental factor was a history of prior extraction (n = 6). Half of the MRONJ were related to diseases found on the initial dental screen. Patients with MRONJ were treated with infection control and antibiotic therapy. When comparing between the MRONJ stage and each factor (sign, location, etiologic factor, BP type, treatment, and outcome), there were no significant differences between stages, except for between the stage and sign (with or without purulence). CONCLUSIONS: For prevention of MRONJ, we recommend routine dental examinations and treatment prior to starting BP therapy.

16.
Mol Carcinog ; 56(2): 664-680, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27377703

RESUMEN

Aberrant expression of urokinase-type plasminogen activator receptor (uPAR) has been observed in human gastric cancers. Prostaglandin E2 (PGE2 ), whose biosynthesis is catalyzed by cyclooxygenase-2 (COX-2), is implicated in cancer metastasis; however, the cellular and molecular mechanisms of PGE2 -driven uPAR expression are yet to be elucidated in human gastric cancer AGS cells. In this study, we showed that PGE2 induces uPAR expression in concentration- and time-dependent manners. Furthermore, using antagonists and siRNA, we found that among the four subtypes of PGE2 receptors, EP2 receptors are involved in PGE2 -induced uPAR expression. PGE2 induced the activation of Src, epidermal growth factor receptor (EGFR), c-Jun NH2 -terminal kinase (JNK), extracellular signal-regulated kinase (Erk), and p38 mitogen activated protein kinase (p38 MAPK). Specific inhibitor and mutagenesis studies showed that Src, EGFR, JNK1/2, and Erk1/2 are involved in PGE2 -induced uPAR expression. PGE2 induces EP2-dependent phosphorylation of Src, while the activation of Src-dependent EGFR leads to the phosphorylation of JNK1/2 and Erk1/2. Deletion and site-directed mutagenesis studies demonstrated the involvement of transcription factor activator protein (AP)-1 and nuclear factor-kappa B (NF-κB) in PGE2 -induced uPAR expression. EGFR-dependent MAPKs (JNK1/2 and Erk1/2) function as the upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. AGS cells pre-treated with PGE2 showed remarkably enhanced invasiveness, which was partially abrogated by uPAR-neutralizing antibodies. To the best of our knowledge, this is the first report that PGE2 -induced uPAR expression, which stimulates invasiveness of human gastric cancer AGS cells, is mediated by the EP2 receptor-dependent Src/EGFR/JNK1/2, Erk1/2/AP-1, and Src/EGFR/JNK1/2, Erk1/2/NF-κB cascades. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Dinoprostona/metabolismo , Subtipo EP2 de Receptores de Prostaglandina E/metabolismo , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Transducción de Señal , Neoplasias Gástricas/metabolismo , Línea Celular Tumoral , Receptores ErbB/metabolismo , Mucosa Gástrica/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas , FN-kappa B/metabolismo , Estómago/patología , Neoplasias Gástricas/patología , Factor de Transcripción AP-1/metabolismo
17.
PLoS One ; 11(9): e0163395, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27654969

RESUMEN

The overexpression of urokinase-type plasminogen activator receptor (uPAR) is associated with inflammation and virtually all human cancers. Despite the fact that docosahexaenoic acid (DHA) has been reported to possess anti-inflammatory and anti-tumor properties, the negative regulation of uPAR by DHA is still undefined. Here, we investigated the effect of DHA on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced uPAR expression and the underlying molecular mechanisms in ECV304 human endothelial cells. DHA concentration-dependently inhibited TPA-induced uPAR. Specific inhibitors and mutagenesis studies showed that PKCδ, JNK1/2, Erk1/2, NF-κB, and AP-1 were critical for TPA-induced uPAR expression. Application of DHA suppressed TPA-induced translocation of PKCδ, activation of the JNK1/2 and Erk1/2 signaling pathways, and subsequent AP-1 and NF-κB transactivation. In conclusion, these observations suggest a novel role for DHA in reducing uPAR expression and cell invasion by inhibition of PKCδ, JNK1/2, and Erk1/2, and the reduction of AP-1 and NF-κB activation in ECV304 human endothelial cells.

18.
Toxicology ; 361-362: 24-38, 2016 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-27393034

RESUMEN

Carbon monoxide (CO), a byproduct of heme oxygenase (HO), presents antioxidant, anti-inflammatory, and anti-tumor properties. Accumulating evidence supports that interleukin (IL)-8 contribute to the vascularity of human gastric cancer. However, the inhibition of IL-8 expression by CO is yet to be elucidated. Here, we utilized CO releasing molecule-2 (CORM-2) to investigate the effect of CO on IL-1ß-induced IL-8 expression and the underlying molecular mechanisms in human gastric cancer AGS cells. CORM-2 dose-dependently suppressed IL-1ß-induced IL-8 mRNA and protein expression as well as IL-8 promoter activity. IL-1ß induced the translocation of p47(phox) to activate reactive oxygen species (ROS)-producing NADPH oxidase (NOX). Moreover, IL-1ß activated MAPKs (Erk1/2, JNK1/2, and p38 MAPK) and promoted nuclear factor (NF)-кB and activator protein (AP)-1 binding activities. Pharmacological inhibition and mutagenesis studies indicated that NOX, ROS, Erk1/2, and p38 MAPK are involved in IL-1ß-induced IL-8 expression. Transient transfection of deletion mutant constructs of the IL-8 promoter in cells suggested that NF-кB and AP-1 are critical for IL-1ß-induced IL-8 transcription. NOX-derived ROS and MAPKs (Erk1/2 and p38 MAPK) functioned as upstream activators of NF-κB and AP-1, respectively. CORM-2 pretreatment significantly mitigated IL-1ß-induced activation of ROS/NF-кB and Erk1/2/AP-1 cascades, blocking IL-8 expression and thus significantly reducing endothelial cell proliferation in the tumor microenvironment.


Asunto(s)
Interleucina-1beta/toxicidad , Interleucina-8/antagonistas & inhibidores , Compuestos Organometálicos/farmacología , Neoplasias Gástricas/metabolismo , Inhibidores de la Angiogénesis/farmacología , Antimetabolitos/toxicidad , Monóxido de Carbono/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , NADPH Oxidasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción AP-1/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
19.
Int J Oral Maxillofac Implants ; 31(2): 318-23, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27004279

RESUMEN

PURPOSE: The purpose of this study was to histomorphometrically compare the effects of the bilayer bone augmentation technique for the treatment of dehiscence-type defects around implants and evaluate the role as a membrane of the xenogeneic bone positioned as the outer layer in the bilayer bone augmentation technique. MATERIALS AND METHODS: Four standardized dehiscence defects measuring 5 mm in height from the crestal bone, 3 mm in width mesiodistally, and 4 mm in depth from the surface of the buccal bone were prepared on each mandible unilaterally in three dogs, and one implant was placed per defect, where each defect was treated with autograft, xenograft, the bilayer bone augmentation technique, or negative control without a membrane. The animals were sacrificed after an 8-week healing interval for histomorphometric analyses. The measurements of newly formed bone height, newly formed bone height contacting the implant, newly formed bone area, and the width of newly formed bone were made using incandescent and polarized light microscopy. RESULTS: Bone height and newly formed bone height contacting the implant in the autograft group were higher than in the xenograft, bilayer bone augmentation, and control groups. Newly formed bone area in the bilayer bone augmentation and autograft groups was higher than in the xenograft and control groups. The width of newly formed bone at 4.5 mm apically from the implant shoulder was greater in the xenograft and bilayer bone augmentation groups than in the control and autograft groups. However, the differences between the groups in bone height, newly formed bone height contacting the implant, newly formed bone area, and width of newly formed bone were not statistically significant in the histomorphometric examinations (P < .05). Data were verified with the Kruskal-Wallis test. CONCLUSION: The results of this study show the osteogenic effect of autogenous bone and the effect of mechanical support for prolonged space maintenance of xenogeneic bone for the treatment of dehiscence-type defects around implants. Further studies with a larger sample size are needed to confirm the efficacy of the bilayer bone augmentation technique.


Asunto(s)
Aumento de la Cresta Alveolar/métodos , Regeneración Ósea/fisiología , Trasplante Óseo/métodos , Implantes Dentales , Dehiscencia de la Herida Operatoria/cirugía , Animales , Autoinjertos/trasplante , Implantación Dental Endoósea/métodos , Perros , Xenoinjertos/trasplante , Mandíbula/patología , Mandíbula/cirugía , Enfermedades Mandibulares/patología , Enfermedades Mandibulares/cirugía , Osteogénesis/fisiología , Factores de Tiempo , Alveolo Dental/patología , Alveolo Dental/cirugía , Cicatrización de Heridas/fisiología
20.
Tissue Eng Regen Med ; 13(3): 304-310, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30603412

RESUMEN

The purpose of this preliminary study was to compare the effects of the bilayer bone augmentation technique (BBA) for the treatment of dehiscence-type defects around implants and evaluate the role as a membrane of the xenogenic bone positioned as the outer layer in the BBA technique using a micro-computed tomography (micro-CT). Four standardized dehiscence defects were prepared on each mandible bilaterally in 3 dogs and 1 implant was placed per defect, where each defect was treated with autograft (AB), xenograft (XB), BBA technique, or negative control without a membrane. Two months post-regenerative surgery, sectioned bone blocks were obtained. The image acquisitions were then scanned by micro-CT. Bone volume (BV), horizontal bone width (HBW) and vertical bone height (VBH) were measured through the analyses program. The BV were 11.08 mm3, 10.42 mm3, 8.1 mm3, and 7.01 mm3 in XB, BBA, control, and AB group in sequence of high value, respectively. HBW were 1.33 mm, 1.3 mm, 1.06 mm, and 1.03 mm in XB, BBA, AB, and control group, respectively. VBH were 4.88 mm, 4.85 mm, 4.74 mm, and 4.67 mm in XB, BBA, AB, and control group, respectively. However, there was no significant difference between the 4 groups. VBH tended to be higher in sequence of control, AB, BBA, and XB group (p for trend <0.05). The results showed the usefulness of the BBA technique involving mechanical support for prolonged space maintenance of xenogenic bone, for the treatment of dehiscence-type defects around implants. However, further studies with a larger sample size are required to confirm the results.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA