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1.
Acta Pharmacol Sin ; 40(5): 589-598, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30030529

RESUMO

High-mobility group box 1 (HMGB1) exhibits various functions according to its subcellular location, which is finely conditioned by diverse post-translational modifications, such as acetylation. The nuclear HMGB1 may prevent from cardiac hypertrophy, whereas its exogenous protein is proven to induce hypertrophic response. This present study sought to investigate the regulatory relationships between poly(ADP-ribose) polymerase 1 (PARP1) and HMGB1 in the process of pathological myocardial hypertrophy. Primary-cultured neonatal rat cardiomyocytes (NRCMs) were respectively incubated with three cardiac hypertrophic stimulants, including angiotensin II (Ang II), phenylephrine (PE), and isoproterenol (ISO), and cell surface area and the mRNA expression of hypertrophic biomarkers were measured. the catalytic activity of PARP1 was remarkably enhanced, meanwhile HMGB1 excluded from the nucleus. PARP1 overexpression by infecting with adenovirus PARP1 (Ad-PARP1) promoted the nuclear export of HMGB1, facilitated its secretion outside the cell, aggravated cardiomyocyte hypertrophy, which could be alleviated by HMGB1 overexpression. PE treatment led to the similar results, while that effect was widely depressed by PARP1 silencing or its specific inhibitor AG14361. Moreover, SD rats were intraperitoneally injected with 3-aminobenzamide (3AB, 20 mg/kg every day, a well-established PARP1 inhibitor) 7 days after abdominal aortic constriction (AAC) surgery for 6 weeks, echocardiography and morphometry of the hearts were measured. Pre-treatment of 3AB relieved AAC-caused the translocation of nuclear HMGB1 protein, cardiac hypertrophy, and heart dysfunction. Our research offers a novel evidence that PARP1 combines with HMGB1 and accelerates its translocation from nucleus to cytoplasm, and the course finally causes cardiac hypertrophy.


Assuntos
Cardiomegalia/etiologia , Núcleo Celular/metabolismo , Proteína HMGB1/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Angiotensina II/farmacologia , Animais , Isoproterenol/farmacologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Fenilefrina/farmacologia , Ratos Sprague-Dawley
2.
Acta Pharmacol Sin ; 39(2): 184-194, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28816235

RESUMO

The RasGAP SH3 domain-binding proteins (G3BPs) are a family of RNA-binding proteins that can co-ordinate signal transduction and post-transcriptional gene regulation. G3BPs have been shown to be involved in mediating a great diversity of cellular processes such as cell survival, growth, proliferation and apoptosis. But the potential roles of G3BPs in the pathogenesis and progression of cardiovascular diseases remain to be clarified. In the present study, we provide the first evidence that suggests the participation of G3BP2 in cardiac hypertrophy. In cultured neonatal rat cardiomyocytes (NRCMs), treatment with isoproterenol (ISO, 0.1-100 µmol/L) significantly elevated the mRNA and protein levels of G3BP2. Similar results were observed in the hearts of rats subjected to 7D-injection of ISO, accompanied by obvious heart hypertrophy and elevated the expression of hypertrophy marker genes ANF, BNP and ß-MHC in heart tissues. Overexpression of G3BP2 in NRCMs led to hypertrophic responses evidenced by increased cellular surface area and the expression of hypertrophy marker genes, whereas knockdown of G3BP2 significantly attenuated ISO-induced hypertrophy of NRCMs. We further showed that G3BP2 directly interacted with IκBα and promoted the aggregation of the NF-κB subunit p65 in the nucleus and increased NF-κB-dependent transcriptional activity. NF-κB inhibition with PDTC (50 µmol/L) or p65 knockdown significantly decreased the hypertrophic responses in NRCMs induced by ISO or G3BP2 overexpression. These results give new insight into the functions of G3BP2 and may help further elucidate the molecular mechanisms underlying cardiac hypertrophy.


Assuntos
Cardiomegalia/metabolismo , Reguladores de Proteínas de Ligação ao GTP/metabolismo , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Núcleo Celular/metabolismo , Modelos Animais de Doenças , Reguladores de Proteínas de Ligação ao GTP/genética , Técnicas de Silenciamento de Genes , Isoproterenol , Masculino , Miócitos Cardíacos/patologia , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/antagonistas & inibidores , Pirrolidinas/farmacologia , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Tiocarbamatos/farmacologia , Fator de Transcrição RelA/metabolismo
3.
Surg Endosc ; 31(8): 3203-3209, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27864725

RESUMO

BACKGROUND: A few modified approaches have been reported for performing endoscope-assisted dissections of benign parotid tumors, but none that use incisions totally hidden in a natural furrow. This study evaluated the feasibility of performing endoscope-assisted extracapsular dissections of benign parotid tumors using a single cephaloauricular furrow incision. METHODS: Forty-six patients with benign parotid superficial lobe tumors were randomly divided into two groups: an endoscope-assisted (21 patients) group or a conventional (25 patients) surgery group. Perioperative and postoperative outcomes of the patients were evaluated, including the maximum diameter of the tumors, length of the incision, operating time, estimated blood loss during the operation, amount and duration of drainage, satisfaction scores based on the cosmetic results, perioperative complications, and follow-up information. RESULTS: The diameters of the tumors were comparable between the groups, and all operations were successfully performed as planned. The mean length of the incision in the endoscope-assisted group (3.6 ± 0.5 cm) was significantly shorter than that in the conventional group (9.1 ± 1.9). Meanwhile, the intraoperative blood loss, amount of drainage, perioperative complications, and cosmetic outcomes were all improved in the endoscope-assisted group. No tumor recurrence was found during 11-40 months of follow-up. CONCLUSIONS: Cephaloauricular furrow incisions were totally and naturally hidden in this procedure. Endoscope-assisted extracapsular dissections of benign parotid tumors via a small cephaloauricular furrow incision were found to be feasible and reliable, providing a minimally invasive approach and a satisfactory appearance.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Neoplasias Parotídeas/cirurgia , Adulto , Perda Sanguínea Cirúrgica , Pavilhão Auricular/cirurgia , Endoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Resultado do Tratamento , Adulto Jovem
4.
J Prosthodont ; 26(3): 201-205, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26375868

RESUMO

PURPOSE: The focus of this study was to evaluate the effect of reading aloud on masticatory performance and patient satisfaction of patients rehabilitated with conventional complete dentures for the first time. MATERIALS AND METHODS: Sixty-two edentulous patients who received conventional complete denture treatment for the first time were randomly divided into two equal groups. After insertion of the dentures, patients in group I were asked to read a news report three times per day for 4 weeks, while those in group II did not read. The reading duration increased by 5 minutes per week, from 5 minutes in the first week to 20 minutes in the fourth week. The patients' mouth opening during reading aloud was advised to gradually increase throughout the training project. Two and four weeks after insertion of the dentures, masticatory performance was assessed using the sieving method, and patient satisfaction was measured using a visual analogue scale, which combined the patient's perceptions in relation to comfort, esthetics, stability, ability to talk, and ability to chew. RESULTS: There were significant improvements in masticatory performance with reading aloud exercises after the insertion of complete dentures (p < 0.001) at the 2- and 4-week follow-up visits. Masticatory performance also showed significant improvement within each group in the follow-up periods (p < 0.001). No significant differences were found between the two groups in patient satisfaction (p > 0.05) at 2 weeks, but at 4 weeks, patient satisfaction regarding stability, ability to talk, and ability to chew was significantly higher for group I (p < 0.001). CONCLUSIONS: The results of this study suggest that reading aloud exercises significantly improved early masticatory performance and patient satisfaction for denture wearers who were treated with conventional complete dentures for the first time, and may be a useful clinical application for more effective denture treatment.


Assuntos
Prótese Total , Terapia por Exercício/métodos , Boca Edêntula/reabilitação , Satisfação do Paciente , Leitura , Idoso , Retenção de Dentadura , Estética Dentária , Feminino , Humanos , Masculino , Mastigação/fisiologia , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
5.
J Oral Maxillofac Surg ; 74(6): 1255-64, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26851316

RESUMO

PURPOSE: Reconstruction of maxillary and midfacial defects due to tumor ablation is challenging to conventional operation. The purposes of this study are to evaluate the precise 3-dimensional position of the fibular flap in reconstruction of maxillary defects assisted by virtual surgical planning and to assess the postoperative outcomes compared with conventional surgery. MATERIALS AND METHODS: We retrospectively reviewed 18 consecutive patients who underwent maxillary reconstruction with a vascularized fibular flap assisted by virtual surgical planning after maxillary or midfacial tumor ablation. Conventional surgery was performed in another 15 patients. Proplan CMF surgical planning (Materialise, Leuven, Belgium) was performed preoperatively in the virtual planning group. Fibular flaps were harvested and underwent osteotomy assisted by prefabricated cutting guides, and the maxilla and midface were resected and reconstructed assisted by the prefabricated cutting guides and templates in the virtual planning group. The operative time and fibular flap positions were evaluated in the 2 groups. Postoperative fibular positions of the maxillary reconstruction were compared with virtual plans in the virtual planning group. The postoperative facial appearance and occlusal function were assessed. RESULTS: The operations were performed successfully without complications. The ischemia time and total operative time were shorter in the virtual planning group than those in the conventional surgery group (P < .05). High precision of the cutting guides and templates was found on both the fibula and maxilla in the virtual planning group. The positions of the fibular flaps, including the vertical and horizontal positions, were more accurate in the virtual planning group than those in the conventional surgery group (P < .05). Bone-to-bone contact between the maxilla and fibular segments was more precise in the virtual planning group (P < .05). Postoperative computed tomography scans showed excellent contour of the fibular flap segments in accordance with the virtual plans in the virtual planning group. All patients were alive with no evidence of disease. Functional mandibular range of motion, good occlusion, and an ideal facial appearance were observed in the virtual planning group. CONCLUSIONS: Virtual surgical planning appears to achieve precise maxillary reconstruction with a vascularized fibular flap after tumor ablation, as well as an ideal facial appearance and function after dental rehabilitation. The use of prefabricated cutting guides and plates eases fibular flap molding and placement, minimizes operating time, and improves clinical outcomes.


Assuntos
Fíbula/transplante , Reconstrução Mandibular/métodos , Maxila/cirurgia , Neoplasias Maxilares/cirurgia , Cirurgia Assistida por Computador/métodos , Retalhos Cirúrgicos , Técnicas de Ablação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Head Neck ; 38 Suppl 1: E607-12, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-25783596

RESUMO

BACKGROUND: The reconstruction of bilateral osteoradionecrosis (ORN) of mandibular defects using a single free bone flap is rarely performed because extensively radiated neck tissue with severe fibrosis is usually unsuitable for vascularized reconstruction. METHODS: Thirty-one patients with nasopharyngeal carcinoma (NPC) underwent bilateral reconstruction of advanced ORN in the mandible using a single fibular osteocutaneous flap. Clinical factors associated with the operation were assessed, including classification of mandible defects, types of recipient vessels, perioperative complications, and postoperative outcomes. RESULTS: All of the fibular osteocutaneous flaps survived completely, with the exception of 1 inner skin paddle that presented partial necrosis in a reconstruction of through-and-through defects. All patients experienced an improvement in cosmetic results 6 months after the reconstruction, whereas 23 patients experienced improved mouth opening compared to the preoperative condition. CONCLUSION: Advanced bilateral ORN in patients with NPC could be synchronously reconstructed with a single fibular osteocutaneous flap. © 2015 Wiley Periodicals, Inc. Head Neck 38: E-E, 2016.


Assuntos
Carcinoma/cirurgia , Fíbula/transplante , Mandíbula/cirurgia , Neoplasias Nasofaríngeas/cirurgia , Osteorradionecrose/cirurgia , Procedimentos Cirúrgicos Reconstrutivos , Adolescente , Adulto , Feminino , Retalhos de Tecido Biológico/transplante , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Estudos Prospectivos , Adulto Jovem
7.
PLoS One ; 10(12): e0144744, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26659581

RESUMO

BACKGROUND: Stress on the bone surrounding dental micro-implants affects implant success. PURPOSE: To compare the stress on the bone surrounding a micro-implant after application of a single force (SF) of 200 g or a composite force (CF) of 200 g and 6 N.mm torque. MATERIALS AND METHODS: Finite element models were developed for micro-implant diameters of 1.2, 1.6, and 2.0 mm, and lengths of 6, 8, 10, and 12 mm and either a SF or CF was applied. The maximum equivalent stress (Max EQS) of the bone surrounding the micro-implant was determined, and the relationships among type of force, diameter, and length were evaluated. RESULTS: The Max EQS of the CF exceeded that of the SF (P< 0.05). The effect of force on stress was related to implant diameter, but not to implant length. The larger CF led to greater instability of the micro-implant and the effect was most pronounced at an implant diameter of 1.2 mm. The use of implant diameters of 1.6 mm and 2.0 mm produced no significant difference in implant stability when either a CF or SF was applied. CONCLUSION: When considering the use of an implant to perform three-dimensional control on the teeth, the implant diameter chosen should be > 1.2 mm.


Assuntos
Implantes Dentários , Análise do Estresse Dentário , Análise de Elementos Finitos , Modelos Anatômicos , Fenômenos Biomecânicos , Força Compressiva , Planejamento de Prótese Dentária , Humanos , Mandíbula/anatomia & histologia , Mandíbula/cirurgia , Maxila/anatomia & histologia , Maxila/cirurgia , Estresse Mecânico , Torque
8.
J Prosthet Dent ; 114(5): 715-24, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26213266

RESUMO

STATEMENT OF PROBLEM: The effects of different heat treatments on the internal oxidation and metal-ceramic bond in Pd-Ag alloys with different trace elements require further documentation. PURPOSE: The purpose of this in vitro study was to determine whether heat treatment affects the metal-ceramic bond strength of 2 Pd-Ag alloys containing different trace elements. MATERIAL AND METHODS: Thirteen cast specimens (25×3×0.5 mm) from each of 2 Pd-Ag alloy groups (W-1 and Argelite 61+3) were allocated to heat treatments before porcelain application: heating under reduced atmospheric pressure of 0.0014 MPa and 0.0026 MPa and heating under normal atmospheric pressure. Bond strengths were evaluated using a 3-point bending test according to ISO9693. Results were analyzed using 2-way ANOVA and Tukey HSD test (α=.05). Visual observation was used to determine the failure types of the fractured specimens. Scanning electron microscopy and energy dispersive spectroscopy were used to study morphologies, elemental compositions, and distributions in the specimens. RESULTS: The W-1 group had a mean bond strength significantly higher than that of Argelite 61+3 (P<.001). Heating under reduced atmospheric pressures of 0.0014 MPa and 0.0026 MPa resulted in similar bond strengths (P=.331), and both pressures had significantly higher bond strengths than that of heating under normal atmospheric pressure (P=.002, P<.001). Heating under different air pressures resulted in Pd-Ag alloys that contained either Sn or In and Ga, with various degrees of internal oxidation and different quantities of metallic nodules. CONCLUSIONS: Heating under reduced atmospheric pressure effectively improved the bond strength of the ceramic-to-Pd-Ag alloys.


Assuntos
Materiais Dentários/efeitos da radiação , Temperatura Alta , Ligas Metalo-Cerâmicas/efeitos da radiação , Paládio/efeitos da radiação , Resistência ao Cisalhamento/efeitos da radiação , Prata/efeitos da radiação , Materiais Dentários/química , Calefação , Teste de Materiais , Ligas Metalo-Cerâmicas/química , Microscopia Eletroquímica de Varredura , Espectrometria por Raios X , Estresse Mecânico
9.
Br J Pharmacol ; 172(11): 2852-63, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25625556

RESUMO

BACKGROUND AND PURPOSE: The orphan nuclear receptor NOR1 belongs to the NR4A subfamily of the nuclear hormone receptor superfamily, and is involved in glucose and fat metabolism. However, its potential contribution to cardiovascular diseases remains to be assessed. Here, the roles of NOR1 in cardiac hypertrophy induced by isoprenaline and the underlying molecular mechanisms were investigated. EXPERIMENTAL APPROACH: NOR1 was expressed in cardiomyocytes treated with isoprenaline. After NOR1 overexpression or knockdown in neonatal rat cardiomyocytes, cellular hypertrophy was monitored by measuring cell surface area and the mRNA of hypertrophic biomarkers. Interactions between NOR1 and PARP-1 were investigated by co-immunoprecipitation. NOR1 expression and PARP-1 activity were measured in rats with cardiac hypertrophy induced by isoprenaline. KEY RESULTS: Treatment with isoprenaline significantly up-regulated NOR1 expression and PARP-1 activity both in vivo and in vitro. Specific gene silencing of NOR1 attenuated isoprenaline-induced cardiomyocyte hypertrophy, whereas NOR1 overexpression exacerbated cardiac hypertrophy. We identified a physical interaction between NOR1 and PARP-1, which was enhanced by NOR1 transfection and thereby led to PARP-1 activation. Overexpression of NOR1, but not C293Y, a NOR1 mutant lacking the PARP-1 binding activity, increased cellular surface area and the mRNA levels of atrial natriuretic factor and brain natriuretic polypeptide, effects blocked by the PARP-1 inhibitor 3-aminobenzamide or siRNA for PARP-1. CONCLUSIONS AND IMPLICATIONS: This is the first evidence that NOR1 was involved in isoprenaline-induced cardiac hypertrophy. The pro-hypertrophic effect of NOR1 can be partly attributed to its regulation of PARP-1 enzymic activity.


Assuntos
Cardiomegalia/genética , Proteínas de Ligação a DNA/efeitos dos fármacos , Isoproterenol/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Proteínas do Tecido Nervoso/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Simpatomiméticos/farmacologia , Animais , Fator Natriurético Atrial/efeitos dos fármacos , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Células Cultivadas , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Técnicas de Introdução de Genes , Técnicas de Silenciamento de Genes , Imunoprecipitação , Técnicas In Vitro , Isoproterenol/toxicidade , Miócitos Cardíacos/metabolismo , Peptídeo Natriurético Encefálico/efeitos dos fármacos , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , RNA Mensageiro/metabolismo , Ratos , Simpatomiméticos/toxicidade , Regulação para Cima
10.
J Mol Cell Cardiol ; 79: 92-103, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25446184

RESUMO

BACKGROUND: α-Enolase is a glycolytic enzyme with "second jobs" beyond its catalytic activity. However, its possible contribution to cardiac dysfunction remains to be determined. The present study aimed to investigate the role of α-enolase in doxorubicin (Dox)-induced cardiomyopathy as well as the underlying mechanisms. EXPERIMENTAL APPROACHES: The expression of α-enolase was detected in rat hearts and primary cultured rat cardiomyocytes with or without Dox administration. An adenovirus carrying short-hairpin interfering RNA targeting α-enolase was constructed and transduced specifically into the heart by intramyocardial injection. Heart function, cell apoptosis and mitochondrial function were measured following Dox administration. In addition, by using gain- and loss-of-function approaches to regulate α-enolase expression in primary cultured rat cardiomyocytes, we investigated the role of endogenous, wide type and catalytically inactive mutant α-enolase in cardiomyocyte apoptosis and ATP generation. Furthermore, the involvement of α-enolase in AMPK phosphorylation was also studied. KEY RESULTS: The mRNA and protein expression of cardiac α-enolase was significantly upregulated by Dox. Genetic silencing of α-enolase in rat hearts and cultured cardiomyocytes attenuated Dox-induced apoptosis and mitochondrial dysfunction. In contrast, overexpression of wide-type or catalytically inactive α-enolase in cardiomyocytes mimicked the detrimental role of Dox in inducing apoptosis and ATP reduction. AMPK dephosphorylation was further demonstrated to be involved in the proapoptotic and ATP-depriving effects of α-enolase. CONCLUSION: Our findings provided the evidence that α-enolase has a catalytically independent role in inducing cardiomyocyte apoptosis and mitochondrial dysfunction, which could be at least partially contributed to the inhibition of AMPK phosphorylation.


Assuntos
Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Mitocôndrias/metabolismo , Miócitos Cardíacos/enzimologia , Fosfopiruvato Hidratase/metabolismo , Trifosfato de Adenosina/metabolismo , Adenoviridae/metabolismo , Adenilato Quinase/metabolismo , Animais , Biocatálise/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Miocárdio/enzimologia , Miócitos Cardíacos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
11.
Neurochem Res ; 40(1): 186-94, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25424966

RESUMO

Oxidative stress and blood-brain barrier (BBB) disruption play important roles in cerebral ischemic pathogenesis and may represent targets for treatment. Earlier studies have shown that osthole, a main active constituent isolated from Cnidium monnieri (L.) Cusson, could be considered as an attractive therapeutic agent in the treatment of ischemic stroke. However, the mechanism underlying the protective effect remains vague. In this study we aimed to investigate the effect of osthole on transient cerebral ischemia as well as its mechanism(s) in C57 BL/6 J mice. Mice were subjected to transient global cerebral ischemia induced by bilateral common carotid artery occlusion for 25 min. Behavioral test was performed at 4 days after ischemia, followed by assessment of neuronal loss in hippocampal CA1 region. Osthole significantly improved the cognitive ability and enhanced the survival of pyramidal neurons in the CA1 region of mice after lesion. Further studies showed that osthole attenuated the permeation of BBB, which may contribute to antioxidative effect by increasing the superoxide dismutase activity and decreasing the malondialdehyde level in model mice. Further studies revealed that osthole obviously up-regulated the protein levels of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 in HT22 cells. In conclusion, our findings indicated that osthole exerts neuroprotective effects against global cerebral ischemia injury by reducing oxidative stress injury and reserving the disruption of BBB, which may be attributed to elevating the protein levels of Nrf2 and HO-1.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Cumarínicos/farmacologia , Ataque Isquêmico Transitório/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Nootrópicos/farmacologia , Animais , Células Cultivadas , Heme Oxigenase-1/metabolismo , Hipocampo/patologia , Ataque Isquêmico Transitório/patologia , Ataque Isquêmico Transitório/psicologia , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Superóxido Dismutase/metabolismo
12.
Mol Cell Endocrinol ; 392(1-2): 14-22, 2014 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-24859603

RESUMO

Poly(ADP-ribose) polymerase-1 (PARP-1) enzyme, as a sensor of DNA damage, could convert nicotinamide adenine dinucleotide (NAD) into long poly(ADP-ribose) chains and regulate many cellular processes, including DNA repair, gene transcription, cell survival and chromatin remodeling. However, excessive activation of PARP-1 depletes its substrate NAD and leads to cell death. Mounting evidences have shown that PARP-1 overactivation plays a pivotal role in the pathogenesis of cardiac hypertrophy and heart failure. In present study, a novel PARP-1 inhibitor AG-690/11026014 (6014) was identified based on virtual screening and validated by bioassay. Our results further showed that 6014 prevented the cardiomyocytes from AngII-induced hypertrophy, accompanying attenuation of the mRNA and protein expressions of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), and reduce in the cell surface area. Additionally, 6014 reversed the depletion ofcellular NAD and SIRT6 deacetylase activity induced by AngII in cardiomyocytes. These observations suggest that anti-hypertrophic effect of 6014 might be partially attributed to the rescue of NAD depletion and subsequent restoring of SIRT6 activity by inhibition of PARP-1. Moreover, 6014 attenuated the generation of oxidative stress via suppression of NADPH oxidase 2 and 4, which might probably contribute to the inhibition of PARP-1.


Assuntos
Cardiomegalia/enzimologia , Cardiomegalia/prevenção & controle , Cardiotônicos/uso terapêutico , Citoproteção/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Miócitos Cardíacos/patologia , Inibidores de Poli(ADP-Ribose) Polimerases , Tioglicolatos/farmacologia , Xantinas/farmacologia , Angiotensina II , Animais , Cardiotônicos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/análise , Inibidores Enzimáticos/química , Humanos , Concentração Inibidora 50 , Glicoproteínas de Membrana/metabolismo , Simulação de Acoplamento Molecular , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/enzimologia , NAD/metabolismo , NADPH Oxidase 2 , NADPH Oxidase 4 , NADPH Oxidases/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/metabolismo , Sirtuínas/metabolismo , Tioglicolatos/análise , Tioglicolatos/química , Regulação para Cima/efeitos dos fármacos , Xantinas/análise , Xantinas/química
13.
Pharmazie ; 69(3): 163-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24716403

RESUMO

We synthesized eight tanshinone anhydrides and the alcoholytic derivatives through a mild oxygen-insertion under Pd/C catalytic hydrogenation conditions. The suppressive effects of the anhydrides on the oxidized low-density lipoprotein (oxLDL) uptake and the oxLDL-induced macrophage-derived foam cell formation were studied. Our results revealed that both anhydrides 1a and 2a could significantly suppress the oxLDL uptake in macrophages and the foam cell formation at micromolar level, which might be partially attributed to their inhibition of oxLDL-induced LOX-1 expression in macrophages.


Assuntos
/síntese química , Antineoplásicos Fitogênicos/síntese química , Células Espumosas/metabolismo , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Anidridos/síntese química , Animais , Compostos Azo , Catálise , Linhagem Celular Tumoral , LDL-Colesterol/metabolismo , Corantes , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Camundongos , Sais de Tetrazólio , Tiazóis
14.
J Dent ; 42(3): 319-28, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24316343

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the efficacy of surface treatments on the bonding properties between a metal and ceramic. METHODS: Sixty metal specimens were divided equally into four groups of 15 samples each. These groups received different treatments (Gr1: 250µm Al2O3+preoxidation; Gr2: 250µm Al2O3+degassing; Gr3: 120µm Al2O3+preoxidation; Gr4: 120µm Al2O3+degassing). Bond strengths were evaluated using a three-point bending test. The results were analyzed using 2-way ANOVA and Tukey's test. Scanning electron microscopy and energy dispersive spectroscopy were used to observe the microscopic features, elemental compositions and distributions, and diffusion in the specimens. Mechanical profiler was used to measure the roughness of metal surface. RESULTS: The bond strengths of the four groups ranged from 45.00±3.63MPa to 51.61±5.91MPa, with significant differences (P<.05). The specimen that received the pretreatment of 250µm Al2O3 air-particle abrasion+degassing had the highest bond strength. Heating under different oxygen partial pressures caused the final Pd-Ag alloys to have varying degrees of internal oxidation and different quantities of metallic nodules. None of the elements in either the ceramic or the Pd-Ag alloy layer diffused into the other layer. CONCLUSIONS: The metal-ceramic specimen subjected to air-particle abrasion with 250µm Al2O3 and degassed before porcelain firing had significantly higher bond strength than specimens treated differently.


Assuntos
Colagem Dentária , Corrosão Dentária/métodos , Porcelana Dentária/química , Ligas de Ouro/química , Ligas Metalo-Cerâmicas/química , Paládio/química , Óxido de Alumínio/química , Materiais Dentários/química , Difusão , Temperatura Alta , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Oxirredução , Oxigênio/química , Pressão Parcial , Tamanho da Partícula , Maleabilidade , Espectrometria por Raios X , Estresse Mecânico , Propriedades de Superfície
15.
Bioorg Chem ; 52: 24-30, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24300390

RESUMO

A series of diacyltanshinol derivatives were synthesized by esterifying the corresponding o-hydroquinones of tanshinones. The suppressive effects of the synthesized compounds on oxidized low-density lipoprotein (oxLDL) uptake and oxLDL-induced macrophage-derived foam cell formation were evaluated. Our results indicated that the nicotinate derivatives 1a and 2a, modified from tanshinone IIA and cryptotanshinone, showed stronger suppressive activity on oxLDL uptake and the resultant foam cell formation relative to tanshinone IIA. Western Blot analysis indicated that derivatives 1a and 2a could dose-dependently inhibit the expression of oxLDL-induced LOX-1, implying that the suppressive effects of 1a and 2a on oxLDL uptake and foam cell formation could be at least partially attributed to the inhibition of LOX-1 expression in macrophages.


Assuntos
Ácidos Cafeicos/química , Células Espumosas/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , /química , Animais , Linhagem Celular , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Células Espumosas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Camundongos , Substâncias Protetoras/síntese química , Receptores Depuradores Classe E/antagonistas & inibidores
16.
Arch Biochem Biophys ; 542: 46-55, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24361255

RESUMO

α-Enolase is a metabolic enzyme in the catabolic glycolytic pathway. In eukaryotic cells, the subcellular compartmentalization of α-enolase as well as its multifaceted functions has been identified. Here, we report that α-enolase is a regulator of cardiac mitochondria; it partially located in the mitochondria of rat cardiomyocytes. Doxorubicin treatment displaced α-enolase from mitochondria, accompanied by activation of mitochondrial cell death pathway. Furthermore, in isolated mitochondria, recombinant α-enolase significantly alleviated Ca(2+)-induced loss of membrane potential, swelling of matrix and permeabilization of membrane. In contrast, mitochondria from α-enolase knockdown H9c2 myoblasts underwent more severe membrane depolarization and swelling after Ca(2+) stimulation. In addition, α-enolase was further identified to interact with voltage dependent anion channel 1 in the outer membrane of mitochondria, which was weakened by doxorubicin. Collectively, the present study indicates that mitochondria-located α-enolase has a beneficial role in stabilizing mitochondrial membrane. In cardiomyocytes, the displacement of α-enolase from mitochondria by doxorubicin may involve in activation of the intrinsic cell death pathway.


Assuntos
Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , Miócitos Cardíacos/citologia , Fosfopiruvato Hidratase/metabolismo , Animais , Cálcio/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Fosfopiruvato Hidratase/farmacologia , Transporte Proteico/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Canal de Ânion 1 Dependente de Voltagem/metabolismo
17.
Int Immunopharmacol ; 15(4): 743-51, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23499680

RESUMO

Flavonoids are a class of compounds that exist in nature with the structure of 2-phenyl-chromone. In Chinese traditional medicine, herbal drugs containing flavonoids are widely used for the treatment of inflammation, cardiovascular disease, tumor and so on. In this study, we investigated the anti-inflammatory effect and related mechanisms of a novel synthetic flavonoid, (E)-1-(4-ethoxyphenyl)-3-(4-nitrophenyl)-prop-2-en-1-one (ETH) in lipopolysaccharide (LPS) stimulated macrophages. Our results showed that ETH inhibited LPS-induced TNF-α and IL-6 release in a dose-dependent manner, and decreased TNF-α, IL-1ß, IL-6 and iNOS mRNA production. LPS-induced expression of cyclooxygenase-2 (COX-2) was also significantly attenuated by ETH. Pretreatment with ETH reduced the I-κBα phosphorylation, p65 nuclear translocation as well as NF-κB-dependent transcriptional activity. In addition, ETH exhibited a significant protection against LPS-induced inflammatory mortality in mice. Taken together, these findings suggest that ETH can inhibit LPS-induced inflammation via suppressing NF-κB signaling pathway, indicating that ETH may be a potential anti-inflammatory agent.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Chalconas/farmacologia , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , NF-kappa B/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/química , Western Blotting , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Chalconas/química , Relação Dose-Resposta a Droga , Flavonoides/química , Interleucina-1beta/genética , Interleucina-6/genética , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Estrutura Molecular , NF-kappa B/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Transporte Proteico , Reação em Cadeia da Polimerase em Tempo Real , Choque Séptico/prevenção & controle , Análise de Sobrevida , Fator de Necrose Tumoral alfa/genética
18.
J Prosthet Dent ; 109(2): 106-12, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23395336

RESUMO

STATEMENT OF PROBLEM: The creation of high bond strength between machined computer-manufactured pure titanium and porcelain remains a problem. However, machined titanium does not form the thick titanium oxide film found in cast titanium. PURPOSE: The purpose of this study was to investigate the effects of different preoxidation treatments on the bond strength of a machined pure titanium ceramic system. MATERIAL AND METHODS: Specimens of commercially pure titanium (25 × 3 × 0.5 mm) were divided equally into 6 groups (n=8), which received different preoxidation treatments (3 hour natural oxidation; 600°C, 650°C, 700°C, 750°C, and 800°C for 3 minutes). Bond strengths were evaluated by using a 3-point bend test. The results were analyzed by using 1-way ANOVA and the least significant difference test. Twelve additional specimens of commercially pure titanium (15 × 3 × 0.5 mm) were cut for interface observation and divided equally into 6 groups that received the preoxidation treatments described previously. Scanning electron microscopy and energy dispersive spectrum were used to observe microscopic features of the interface between Ti and ceramic. RESULTS: The bond strength values of the 6 groups ranged from 23.72 ±2.53 MPa to 36.99 ±3.92 MPa, with significant differences (P<.05). The specimen that received 750°C preoxidation had the highest bond strength. The main interface elements of the 6 groups were O, Si, Ti, Sn, Al, Na, and K. Ti showed a sigmoidal diffusion curve in each group, and Si showed a sigmoidal diffusion curve in most groups. Sn was enriched in each group's interface. CONCLUSIONS: Preoxidation under vacuum before porcelain firing can effectively improve the bond strength of machined pure titanium-porcelain systems.


Assuntos
Colagem Dentária , Materiais Dentários/química , Porcelana Dentária/química , Titânio/química , Alumínio/análise , Difusão , Microanálise por Sonda Eletrônica , Temperatura Alta , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Oxirredução , Oxigênio/análise , Maleabilidade , Potássio/análise , Silício/análise , Sódio/análise , Estresse Mecânico , Propriedades de Superfície , Fatores de Tempo , Estanho/análise , Titânio/análise , Vácuo
19.
Phytomedicine ; 20(2): 106-13, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23141425

RESUMO

Connective tissue growth factor (CTGF) has been reported to play an important role in tissue fibrosis and presents a promising therapeutic target for fibrotic diseases. In heart, inappropriate increase in level of CTGF promotes fibroblast proliferation and extracellular matrix (ECM) accumulation, thereby exacerbating cardiac hypertrophy and subsequent failure. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac fibrosis. However, the molecular mechanism by which EGCG exerts its anti-fibrotic effects has not been well investigated. In this study, we found that EGCG could significantly reduce collagen synthesis, fibronectin (FN) expression and cell proliferation in rat cardiac fibroblasts stimulated with angiotensinII (AngII). It also ameliorated cardiac fibrosis in rats submitted to abdominal aortic constriction (AAC). Moreover, EGCG attenuated the excessive expression of CTGF induced by AAC or AngII, and reduced the nuclear translocation of NF-κB p65 subunit and degradation of IκB-α. Subsequently, we demonstrated that in cardiac fibroblasts NF-κB inhibition could suppress AngII-induced CTGF expression. Taken together, these findings provide the first evidence that the effect of EGCG against cardiac fibrosis may be attributed to its inhibition on NF-κB activation and subsequent CTGF overexpression, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.


Assuntos
Catequina/análogos & derivados , Fator de Crescimento do Tecido Conjuntivo/antagonistas & inibidores , Fibroblastos/metabolismo , Miocárdio/metabolismo , NF-kappa B/antagonistas & inibidores , Chá/química , Animais , Catequina/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno/biossíntese , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Modelos Animais de Doenças , Fibroblastos/patologia , Fibronectinas/biossíntese , Fibrose/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley
20.
Br J Pharmacol ; 168(1): 117-28, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22335191

RESUMO

BACKGROUND AND PURPOSE: Sirtuin 6 (SIRT6) is involved in regulation of glucose and fat metabolism. However, its possible contribution to cardiac dysfunction remains to be determined. In the present study, the effect of SIRT6 on cardiac hypertrophy induced by angiotensin II (AngII) and the underlying molecular mechanisms were investigated. EXPERIMENTAL APPROACH: The expression and deacetylase activity of SIRT6 were measured in hypertrophic cardiomyocytes induced by AngII. After SIRT6 overexpression by transfection, or depletion by RNA interference in neonatal rat cardiomyocytes, cellular hypertrophy was monitored by measuring cell surface area and the mRNA levels of hypertrophic biomarkers. Further, the interaction between SIRT6 and the transcription factor NF-κB was investigated by co-immunoprecipitation, confocal immunofluorescence microscopy and luciferase reporter gene assay. The expression and deacetylase activity of SIRT6 were measured in vivo, using the abdominal aortic constriction (AAC) model of cardiac hypertrophy in rats. KEY RESULTS: In AngII-induced hypertrophic cardiomyocytes and also in AAC-induced hypertrophic hearts, the expression of SIRT6 protein was upregulated, while its deacetylase activity was decreased. Overexpression of wild-type SIRT6 but not its catalytically inactive mutant, attenuated AngII-induced cardiomyocyte hypertrophy. We further demonstrated a physical interaction between SIRT6 and NF-κB catalytic subunit p65, whose transcriptional activity could be repressed by SIRT6 overexpression. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that SIRT6 suppressed cardiomyocyte hypertrophy in vitro via inhibition of NF-κB-dependent transcriptional activity and that this effect was dependent on its deacetylase activity.


Assuntos
Cardiomegalia/metabolismo , Miócitos Cardíacos/metabolismo , Sirtuínas/metabolismo , Angiotensina II , Animais , Aorta Abdominal/diagnóstico por imagem , Cardiomegalia/induzido quimicamente , Cardiomegalia/etiologia , Células Cultivadas , Constrição Patológica/complicações , Constrição Patológica/diagnóstico por imagem , Masculino , NAD/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Interferência de RNA , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Sirtuínas/genética , Transcrição Genética/fisiologia , Ultrassonografia , Regulação para Cima
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