RESUMO
OBJECTIVES: Bonded restorations using self-etch (SE) systems exhibit a limited lifespan due to their susceptibility to hydrolytic, enzymatic or fatigue degradation and poor performance on enamel. This study was conducted to develop and assess the performance of a two-step SE system using a functional monomer bis[2-(methacryloyloxy)ethyl]phosphate (BMEP) and demonstrate a strategy to enhance stability of bonded resin composite restorations to both enamel and dentine. METHODS: A two-step SE system was formulated with a primer containing BMEP, with an adhesive with or without BMEP, and compared to a commercial 10-MDP-containing system, ClearfilTM SE Bond 2 (CFSE). The systems were evaluated on enamel for surface roughness and microshear bond strength (µSBS) and on dentine for microtensile bond strength (µTBS), nanoleakage, MMP inhibition and cyclic flexural fatigue. RESULTS: Whilst all bonding systems resulted in statistically similar µSBS, BMEP-based primers yielded greater enamel surface roughness than the CFSE primer. The BMEP-free adhesives resulted in statistically similar or higher µTBS and lower nanoleakage compared to CFSE. In situ zymography revealed minimal to no MMP activity within the hybrid layer of BMEP-based systems. The BMEP-free adhesive exhibited flexural strength and fatigue resistance statistically similar to CFSE. CONCLUSIONS: Incorporation of BMEP in the primer led to satisfactory bond strengths with both enamel and dentine, potentially eliminating the need for selective enamel etching. Combined with an adhesive formulation that is solvent-free and hydrophobic, and confining the acidic functional monomer in the primer resulted in minimal interfacial leakage, and resistance to proteolytic degradation and the cyclic nature of chewing. CLINICAL SIGNIFICANCE: The SE bonding system containing BMEP combines the potent etching of phosphoric acid with the therapeutic function of the phosphate-based monomer in creating a homogenous hybrid layer with protection against endogenous proteolytic enzymes. This strategy may overcome current challenges that arise during selective enamel etching.
Assuntos
Colagem Dentária , Cimentos Dentários , Adesivos Dentinários/química , Cimentos de Resina/química , Propriedades de Superfície , Peptídeo Hidrolases , Fosfatos , Teste de Materiais , Resistência à TraçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Alternanthera brasiliana L. is a flowering plant belonging to the family Amaranthaceae and is popularly known as "penicillin". It is used in folk medicine to treat infections, coughs, wound healing, and inflammatory diseases. AIM OF THE STUDY: We investigated the effect of Alternanthera brasiliana L. leaves hydroalcoholic extract (AB) against oxidative stress, inflammation, and fibrotic changes in an experimental model of carbon tetrachloride (CCl4)-induced liver injury and fibrosis in mice. MATERIALS AND METHODS: Thirty-six male Balb/C mice were randomized into five groups: normal control, AB control, CCl4 control, CCl4 + AB-200 mg/kg, and CCl4 + AB-400 mg/kg. In mice, liver injury was induced by intraperitoneal injection of CCl4 (20% in corn oil, 5 ml/kg body weight) thrice a week for six consecutive weeks. AB extract at two doses (200 mg/kg and 400 mg/kg body weight) was administered orally for six consecutive weeks. Liver injury-related serum markers (ALT, AST, ALP), antioxidants (GSH, GST, SOD, and vitamin C), pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-18, ultrasonographic and histological alterations, proteins of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinase-1 (TIMP-1), nuclear factor-κB (p65) (NF-κB), nod-like receptor protein 3 (NLRP3), and TGF-ß/Smad signaling were accessed. LC-Q-TOF-MS/MS analysis of AB was performed. RESULTS: AB treatment significantly decreased the CCl4-induced rise in serum ALT, AST, and ALP activities and improved the histological alterations. Compared with the CCl4-treated group, treatment with AB significantly restored the hepatic antioxidants and reduced the pro-inflammatory cytokines in the liver. The antioxidant activity of AB may be attributed to its terpenoid constituents, which was confirmed by LC-Q-TOF-MS/MS analysis. The CCl4-induced rise in expression of MMP-2 and MMP-9 and decrease in TIMP-1 were markedly restored in the AB-treated groups. Further findings revealed a significant reduction in the protein levels of phospho-NF-κB (p65), NLRP3, TGF-ß, pSmad2/3, collagen I, and α-smooth muscle actin (α-SMA) in the AB treatment groups. CONCLUSIONS: The hepatoprotective effect of AB may be attributed to the high content of terpenoid compounds and alleviates liver injury and associated fibrotic changes through modulating MMPs, NF-κB (p65), and the TGF-ß/Smad axis.
Assuntos
Antioxidantes , Doença Hepática Crônica Induzida por Substâncias e Drogas , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Fator de Crescimento Transformador beta/metabolismo , NF-kappa B/metabolismo , Tetracloreto de Carbono/efeitos adversos , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espectrometria de Massas em Tandem , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fígado , Cirrose Hepática/tratamento farmacológico , Citocinas/metabolismo , Estresse Oxidativo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/metabolismo , Peso CorporalRESUMO
INTRODUCTION: Metalloproteinases play key roles in health and disease, by generating novel proteoforms with variable structure and function. Areas covered: This review focuses on the role of endogenous [a Disintegrin and Metalloproteinase (ADAMs), ADAMs with thrombospondin motifs (ADAMTS), and matrix metalloproteinases (MMPs)] and exogenous metalloproteinases in various disease conditions, and describes the application of mass spectrometry-based proteomics to detect qualitative and quantitative changes in protein profiles in tissues and body fluids in disease. Emphasis is placed on the proteomic analysis of exudates collected from affected tissues, including methods that enrich newly generated protein fragments derived from proteolysis in cells, stroma, or extracellular matrix. The use of proteomic analysis of exudates in the study of the local tissue damage induced by metalloproteinases derived from viperid snake venoms is discussed, particularly in relation to extracellular matrix degradation and to the overall pathology of these envenomings. Expert commentary: The information provided by these proteomics approaches is paving the way for the identification of biomarkers based on particular proteolytic signatures associated with different pathologies. Together with other methodological approaches, a comprehensive view of the mechanisms and dynamics of diseases can be achieved. Such basis of knowledge allows for the design of novel diagnostic and therapeutic approaches within the frame of 'precision' or 'personalized' medicine.
Assuntos
Metaloproteases/análise , Técnicas de Diagnóstico Molecular/métodos , Proteômica/métodos , Mordeduras de Serpentes/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Exsudatos e Transudatos/química , Exsudatos e Transudatos/metabolismo , Humanos , Metaloproteases/metabolismo , Mordeduras de Serpentes/patologiaRESUMO
OBJECTIVE: To evaluate fibrosis and fibrosis-related gene expression in the myocardium of pediatric subjects with single ventricle with right ventricular failure. STUDY DESIGN: Real-time quantitative polymerase chain reaction was performed on explanted right ventricular myocardium of pediatric subjects with single ventricle disease and controls with nonfailing heart disease. Subjects were divided into 3 groups: single ventricle failing (right ventricular failure before or after stage I palliation), single ventricle nonfailing (infants listed for primary transplantation with normal right ventricular function), and stage III (Fontan or right ventricular failure after stage III). To evaluate subjects of similar age and right ventricular volume loading, single ventricle disease with failure was compared with single ventricle without failure and stage III was compared with nonfailing right ventricular disease. Histologic fibrosis was assessed in all hearts. Mann-Whitney tests were performed to identify differences in gene expression. RESULTS: Collagen (Col1α, Col3) expression is decreased in single ventricle congenital heart disease with failure compared with nonfailing single ventricle congenital heart disease (P = .019 and P = .035, respectively), and is equivalent in stage III compared with nonfailing right ventricular heart disease. Tissue inhibitors of metalloproteinase (TIMP-1, TIMP-3, and TIMP-4) are downregulated in stage III compared with nonfailing right ventricular heart disease (P = .0047, P = .013 and P = .013, respectively). Matrix metalloproteinases (MMP-2, MMP-9) are similar between nonfailing single ventricular heart disease and failing single ventricular heart disease, and between stage III heart disease and nonfailing right ventricular heart disease. There is no difference in the prevalence of right ventricular fibrosis by histology in subjects with single ventricular failure heart disease with right ventricular failure (18%) compared with those with normal right ventricular function (38%). CONCLUSIONS: Fibrosis is not a primary contributor to right ventricular failure in infants and young children with single ventricular heart disease. Additional studies are required to understand whether antifibrotic therapies are beneficial in this population.
Assuntos
Regulação para Baixo , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/patologia , Miocárdio/patologia , Criança , Pré-Escolar , Feminino , Fibrose , Marcadores Genéticos , Insuficiência Cardíaca/congênito , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/genética , Síndrome do Coração Esquerdo Hipoplásico/patologia , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic loxoscelism, the latter of which includes renal failure. Although incidence of renal failure is low, it is the main cause of death, occurring mainly in children. The sphingomyelinase D (SMase D) is the main component in Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous metalloproteinases (MMP). Results demonstrated that venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and MMP synthesis and secretion can be prevented by tetracycline. In a mouse model of systemic loxoscelism, Loxosceles venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in Loxosceles venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism.
Assuntos
Diester Fosfórico Hidrolases/toxicidade , Substâncias Protetoras/uso terapêutico , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/tratamento farmacológico , Venenos de Aranha/toxicidade , Tetraciclina/uso terapêutico , Animais , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Substâncias Protetoras/farmacologia , Proteinúria/induzido quimicamente , Insuficiência Renal/patologia , Aranhas , Tetraciclina/farmacologiaRESUMO
Ovarian cancer is one of the most malignant genital cancers, with a high mortality rate. Many researchers have suggested that matrix metalloproteinases (MMPs) have remarkably high expression in ovarian cancer tissues. MMPs are considered to be related to the occurrence, development, invasion and metastasis of ovarian cancer. Moreover, some studies have discovered that the unbalance between MMPs and tissue inhibitor of metalloproteinases (TIMPs) are associated with the malignant phenotype of tumors. This review summarizes the latest research progress of MMPs in ovarian cancer. The investigation of MMP mechanism in ovarian cancer will facilitate the development of effective anti-tumor drugs, and thereby improve the survival rate of patients with ovarian cancer.
Assuntos
Humanos , Feminino , Biomarcadores Tumorais/metabolismo , Metaloproteinases da Matriz/metabolismo , Neoplasias Ovarianas/enzimologia , Expressão Gênica/genética , Inibidores de Metaloproteinases de Matriz/metabolismo , Metaloproteinases da Matriz/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/secundário , Inibidores Teciduais de Metaloproteinases/metabolismoRESUMO
La adhesión con sistemas adhesivos resinosos en dentina está siendo cuestionada, los estudios longitudinales in vivo y de envejecimiento in vitro al respecto demuestran que existe una degradación de la capa híbrida a nivel de las paredes pulpares del diseño cavitario. El presente artículo plantea una síntesis de numerosas conclusiones obtenidas de diversas investigaciones, para dar a entender la realidad de la adhesión en dentina y despertar una actitud restauradora diferente más allá del empleo único de sistemas adhesivos resinosos para pretender una unión adhesiva longeva en la dentina.
The adhesion with resinous adhesive systems in dentine has been questioned. Longitudinal studies in vivo and in vitro have demonstrated degradation of the hybrid layer at the level of the pulpar walls. The present article summarizes numerous conclusions obtained from different investigations, to explain the updates of adhesion in dentine and to promote a different restoring attitude that goes beyond the resinous adhesive systems alone.