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Bol. latinoam. Caribe plantas med. aromát ; 20(3): 315-323, may. 2021. ilus, tab
Article in English | LILACS | ID: biblio-1343489


To investigate effectsof Yangyinyiqi Mixture on pulmonary fibrosis caused by bleomycin. SD ratswere divided randomly into: model group(distilled water,1 mL·0.1 kg-1), dexamethasone acetate group (dexamethasone acetate, the dosage was reduced gradually), low-dose group (Yangyinyiqi Mixture, 11 g·kg-1), moderate-dose group (Yangyinyiqi Mixture, 22 g·kg-1), high-dose group (Yangyinyiqi Mixture, 44 g·kg-1) and control group (distilled water, 1 mL·0.1 kg-1). Yangyinyiqi Mixture and dexamethasone acetate were intragastrically administrated. Lung tissue was collected for histopathological examination. Compared with control group, collagen markedly increased and HYP content significantly increased on 7th day in model group (p<0.01). On 28th day, collagen was diffusely deposited, alveolar was destroyed, and HYP content significantly increased (p<0.01). Compared with model group, bleomycin-induced suffering injury caused MMP-9 expression levels to rapidly increase (7and 14 days, p<0.01). TIMP-1 markedly increased (7and 14 days, p<0.01) and stayed at a high level to28th day. Yangyinyiqi Mixture exerted an effect against pulmonary fibrosis, which could involved prevention of collagen deposition through inhibitingMMP-9 and TIMP-1 expression.

El trabajo investiga los efectos de la mezcla Yangyinyiqi sobre la fibrosis pulmonary causada por bleomicina. Ratas SD se dividieron aleatoriamente en: grupo modelo (agua destilada, 1 mL·0.1 kg-1), grupo acetate de dexametasona (acetate de dexametasona, la dosis se redujo gradualmente), grupo de dosis baja (mezcla Yangyinyiqi, 11 g·kg-1), grupo de dosis moderada (mezcla Yangyinyiqi, 22 g·kg-1), grupo de dosis alta (mezcla Yangyinyiqi, 44 g·kg-1) y grupo control (agua destilada, 1 Ml·0.1 kg-1). La mezcla de Yangyinyiqi y el acetate de dexametasona se administraron por vía intragástrica. Se recolectó tejido pulmonary para examen histopatológico. En comparación con el grupo control, el colágeno aumentó notablemente y el contenido de HYP aumentó significativamente el séptimo día en el grupo modelo (p<0.01). El día 28, el colágeno se depositó difusamente, se produjo destrucción alveolar y el contenido de HYP aumento significativamente (p<0.01). En comparación con el grupo modelo, la lesión inducida por bleomicina causó que los niveles de expression de MMP-9 aumentaron rápidamente (7 y 14 días, p<0.01). TIMP-1 aumentó notablemente (7 y 14 días, p<0.01) y se mantuvo en un nivel alto hasta el día 28. La mezcla Yangyinyiqi ejerció un efecto contra la fibrosis pulmonary, lo que podría implicar la prevención del deposito de colágenio mediante la inhibición de la expression de MMP-9 y TIMP-1.

Animals , Male , Rats , Pulmonary Fibrosis/drug therapy , Drugs, Chinese Herbal/administration & dosage , Tissue Inhibitor of Metalloproteinases/metabolism , Matrix Metalloproteinase 9/metabolism , Bleomycin , Dexamethasone/administration & dosage , Blotting, Western , Rats, Sprague-Dawley , Matrix Metalloproteinase 1 , Disease Models, Animal , Hydroxyproline/analysis
Arq. bras. cardiol ; 114(1): 100-105, Jan. 2020. tab, graf
Article in English | LILACS | ID: biblio-1055084


Abstract Background: The emergence of coronary heart disease is increased with menopause, physical inactivity and with dyslipidemia. Physical training is known to promote the improvement of cardiovascular functions. Objective: To investigate the effects of aerobic physical training on the left ventricle in ovariectomized LDL knockout mice. Methods: Thirty animals were divided into 6 groups (n = 5): Sedentary non-ovariectomized control; Sedentary ovariectomized control; Trained ovariectomized control; Sedentary non-ovariectomized LDL-knockout, sedentary ovariectomized LDL-knockout and trained ovariectomized LDL-knockout. We analyzed the average parameters of apparent density of collagen fibers types I and III, and metalloproteinase type 2 and type 9, were considered significant p < 0.05. Results: The results showed that the proposed exercise protocol altered the volume of type I collagen fibers, altered collagen remodeling parameters (MMP-2), and also reduced the 8-hydroxy-2'-deoxyguanosine (8OHdG) oxidative stress parameter. Conclusion: Moderate intensity aerobic training acts on collagen fiber volume, on collagen remodeling with the reduction of oxidative stress in the left ventricles of ovariectomized LDL-knockout mice.

Resumo Fundamento: O surgimento da doença cardíaca coronariana aumenta com a menopausa, inatividade física e dislipidemia. Sabe-se que o treinamento físico promove a melhora das funções cardiovasculares Objectivo: Investigar os efeitos do treinamento físico aeróbico sobre o ventrículo esquerdo em camundongos LDL knockout ovariectomizadas. Métodos: Trinta animais foram divididos em 6 grupos (n = 5): controle sedentário não ovariectomizado, controle sedentário ovariectomizado, controle treinado ovariectomizado, sedentário LDL-knockout não ovariectomizado, sedentário LDL-knockout ovariectomizado e treinado LDL-knockout ovariectomizado. Analisamos os parâmetros médios da densidade de volume de fibras colágenas tipo I e III, e metaloproteinases 2 e 9. Valores de p < 0,05 foram considerados significativos. Resultados: Os resultados mostram que o protocolo de exercício proposto alterou o volume de fibras colágenas do tipo I e os parâmetros de remodelamento do colágeno (MMP-2), e ainda reduziu o parâmetro de estresse oxidativo do 8-hidroxi-2'-deoxiganosina (8-OhdG). Conclusão: O treinamento aeróbico de intensidade moderada age sobre o volume das fibras colágenas e sobre o remodelamento de colágeno, com redução do estresse oxidativo em ventrículos esquerdos de camundongos ovariectomizados LDLr Knockout.

Animals , Female , Rats , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Collagen Type I/metabolism , Collagen Type III/metabolism , Inflammation/physiopathology , Myocardium/metabolism , Physical Conditioning, Animal/physiology , Immunohistochemistry , Ovariectomy , Mice, Knockout , Oxidative Stress/physiology , Models, Animal
Rev. bras. ginecol. obstet ; 41(7): 449-453, July 2019. tab
Article in English | LILACS | ID: biblio-1020606


Abstract Objective To analyze the effects of estrogen alone or in combination with progestogens and tibolone (TIB) on the expression of the extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), of perlecan, and of heparanase (HPSE) of the vascular walls of the carotid arteries. Methods A total of 30 250-day-old ovariectomized Wistar rats were orally treated for 5 weeks with: a) 1 mg/kg of estradiol benzoate (EB); b) EB + 0.2 mg/kg of medroxyprogesterone acetate (MPA); c) EB + 0.2mg/kg of norethisterone acetate (NETA); d) EB + 2 mg/kg of dydrogesterone (DI); e) 1 mg/kg of TIB; f) placebo (CTR). Following treatment, the expression of mRNA for MMP-2, MMP-9, and HPSE was analyzed by realtime polymerase chain-reaction (PCR), and the expression of MMP-2, of MMP-9, of tissue inhibitor of metalloproteinase 2 (TIMP-2), and of perlecan was quantified by immunohistochemistry in the carotid arteries. Results The groups showed significant differences on mRNA HPSE expression (p = 0.048), which was higher in the EB, EB + MPA, and TIB groups. There was no statistically significant difference in mRNA MMP-2 or MMP-9 expression. The immunohistochemical expression of MMP-2, of TIMP-2, of MMP-9, of HPSE, and of perlecan showed no differences between groups. Conclusion Estradiol alone or associated with MPA and TIB treatment can increase mRNA HSPE expression of the walls of the carotid arteries in ovariectomized rats.

Resumo Objetivo Analisar os efeitos do estrogênio isolado ou em combinação com progestogênios e tibolona (TIB) na expressão das metaloproteinases 2 e 9 da matriz extracelular (MMP-2 e MMP-9), da perlecan e da heparanase (HPSE) das paredes vasculares das artérias carótidas. Métodos Trinta ratas Wistar ovariectomizadas com 250 dias de idade foram tratadas oralmente por 5 semanas com: a) 1 mg/kg de benzoato de estradiol (EB); b) EB + 0,2 mg/kg de acetato de medroxiprogesterona (MPA); c) EB + 0,2mg/kg de acetato de noretisterona (NETA); d) EB + 2 mg/kg de didrogesterona (DI); e) 1 mg/kg de TIB; f) placebo (CTR). Após o tratamento, a expressão de mRNA para MMP-2, MMP- 9, e HPSE foi analisada por reação em cadeia da polimerase (RCP) em tempo real, e a expressão de MMP-2, MMP-9, inibidor tecidual de metaloproteinase 2 (TIMP-2), e de perlecan foi quantificado por imunohistoquímica em artérias carótidas. Resultados Os grupos apresentaram diferenças significativas na expressão do mRNA HPSE (p = 0,048), sendo maiores nos grupos EB, EB + MPA e TIB. Não houve diferença estatisticamente significativa nas expressões de mRNA MMP-2 ou MMP-9. A expressão imunohistoquímica de MMP-2, TIMP-2, MMP-9, HPSE e perlecan não mostrou diferenças entre os grupos. Conclusão O estradiol isolado ou associado ao tratamento com MPA e TIB pode aumentar a expressão de mRNA HSPE nas paredes das artérias carótidas em ratas ovariectomizadas.

Animals , Female , Rats , Progestins/pharmacology , Carotid Arteries/enzymology , Heparin Lyase/drug effects , Estradiol/analogs & derivatives , Contraceptive Agents, Hormonal/pharmacology , Norpregnenes/pharmacology , Progestins/administration & dosage , Ovariectomy , Carotid Arteries/drug effects , Estrogen Replacement Therapy , Gene Expression Regulation, Enzymologic/drug effects , Administration, Oral , Rats, Wistar , Heparin Lyase/genetics , Heparin Lyase/metabolism , Heparan Sulfate Proteoglycans/genetics , Heparan Sulfate Proteoglycans/metabolism , Matrix Metalloproteinase 2/drug effects , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/drug effects , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Models, Animal , Estradiol/administration & dosage , Estradiol/pharmacology , Contraceptive Agents, Hormonal/administration & dosage , Norpregnenes/administration & dosage
Braz. j. med. biol. res ; 52(1): e7567, 2019. graf
Article in English | LILACS | ID: biblio-974265


Cervical cancer is one of the most common cancers among women around the world. However, the underlying mechanism involved in cervical cancer progression is incompletely known. In the present study, we determined the role of glycoprotein nonmetastatic melanoma protein B (GPNMB) in tumorigenesis of cervical cancer. According to the GEO database, we found that GPNMB expression was significantly higher in cervical cancer than in normal cervix epithelium. A similar pattern was observed in GPNMB expression in cultured cervical cancer cells and normal cervical epithelial cells. Compared with the control, GPNMB knockdown significantly decreased the proliferation and migration capacity, but enhanced the apoptosis capacity of SiHa and HeLa cells. Additionally, the activity of MMP-2 and MMP-9 were aberrantly increased in SiHa and HeLa cells compared with normal cervical epithelial cells, whereas their activities were strongly inhibited by GPNMB siRNA. Furthermore, Wnt/β-catenin signaling was activated by GPNMB in SiHa and HeLa cells. Increased MMP-2/MMP-9 expression was suppressed by Dkk-1, inhibitor of Wnt/β-catenin signaling, while it was enhanced by stimulator BIO. The proliferation, migration, and apoptosis capacity of HeLa cells were found to be affected by Dkk-1 and BIO to different extents. In conclusion, we demonstrated that GPNMB contributed to the tumorigenesis of cervical cancer, at least in part, by regulating MMP-2/MMP-9 activity in tumor cells via activation of canonical Wnt/β-catenin signaling. This might be a potential therapeutic target for treating human cervical cancer.

Humans , Female , Membrane Glycoproteins/metabolism , Gene Expression Regulation, Neoplastic/genetics , Uterine Cervical Neoplasms/metabolism , beta Catenin/metabolism , Wnt Signaling Pathway/genetics , Membrane Glycoproteins/genetics , Cell Movement , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Blotting, Western , Apoptosis , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , RNA, Small Interfering/metabolism , Cell Line, Tumor , Cell Proliferation , beta Catenin/genetics
Rev. Assoc. Med. Bras. (1992) ; 64(4): 361-367, Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-956455


SUMMARY OBJECTIVE: This study aims at investigating the expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)/ tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary disease (COPD) and their relationships with pulmonary vascular remodelling (PVR). METHODS: 60 para-tumour tissues were divided into the COPD group and the control group (n=30); the inflammations, pulmonary artery wall area/total artery area (WA%), and wall thickness/vascular outer diameter (WT%) were compared. The expressions of TLR-4, MMP-9/TIMP-1, and PCNA in pulmonary vascular smooth muscle cells were detected, and their relationships with PVR were then analysed. RESULTS: The inflammations (1.6±0.8), WA% (44.0±6.4), and WT% (27.3±3.3) in the COPD group were higher than in the control group (0.3±0.5, 26.1±2.8, 15.6±1.8), and the expressions of TLR-4 (31.4±147) and MMP-9/TIMP-1 (2.2±2.6) were increased compared to the control group (4.7±4.5, 1.9±12). Correlation analysis: TLR-4 and MMP-9/TIMP-1 were positively correlated with the inflammations (r=0.18, P<0.01), WA% (r=0.68, P<0.01), and WT% (r=0.73, P<0.01), as well as positively correlated with the expression of PCNA (r=0.44, P<0.01); the upregulation of TLR-4 was positively correlated with the expressions of MMP-9 and TIMP-1. CONCLUSIONS: The upregulation of TLR-4 in the pulmonary arterial smooth muscle cells of COPD patients could promote the inflammations and the MMP-9 expression, thus causing abnormal degradation of extracellular matrix, so it played an important role in the process of PVR.

RESUMO OBJETIVO: Este estudo tem como objetivo investigar as expressões de TOLL-like receptor 4 (TLR-4) e metaloproteinase 9 da matriz (MMP-9)/inibidor de tecido da metaloproteinase 1 (TIMP-1) em vasos sanguíneos pulmonares com doença pulmonar obstrutiva crônica (DPOC) e suas relações com o remodelamento vascular pulmonar (PVR). MÉTODOS: Sessenta tecidos paratumorais foram divididos em grupo COPD e o grupo controle (n = 30). Foram comparadas as inflamações, área da parede da artéria pulmonar/área da artéria total (WA%) e espessura da parede/diâmetro externo vascular (WT%). As expressões de TLR-4, MMP-9/TIMP-1 e PCNA em células de músculo liso vascular pulmonar foram detectadas, e suas relações com PVR foram então analisadas. RESULTADOS: As inflamações (1,6 ± 0,8), WA% (44,0 ± 6,4) e WT% (27,3 ± 3,3) no grupo COPD foram maiores que no grupo controle (0,3 ± 0,5; 26,1 ± 2,8; 15,6 ± 1,8). E as expressões de TLR-4 (31,4 ± 14,7) e MMP-9/TIMP-1 (2,2 ± 2,6) foram aumentadas em relação ao grupo controle (4,7 ± 4,5, 1,9 ± 1,2). Na análise de correlação, TLR-4 e MMP-9/TIMP-1 foram positivamente correlacionadas com as inflamações (r = 0,18; P <0,01), WA% (r = 0,68; P <0,01) e WT% (r = 0,73; P <0,01), bem como correlacionadas positivamente com a expressão de PCNA (r = 0,44; P <0,01). A elevação da TLR-4 foi correlacionada positivamente com as expressões de MMP-9 e TIMP-1. CONCLUSÕES: A regulação positiva do TLR-4 nas células do músculo liso arterial pulmonar de pacientes com DPOC poderia promover as inflamações e a expressão de MMP-9, causando assim uma degradação anormal da matriz extracelular, por isso desempenhou um papel importante no processo de PVR.

Humans , Male , Pulmonary Artery/metabolism , Tissue Inhibitor of Metalloproteinase-1/metabolism , Matrix Metalloproteinase 9/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Toll-Like Receptor 4/metabolism , Vascular Remodeling , Reference Values , Immunohistochemistry , Case-Control Studies , Vital Capacity/physiology , Forced Expiratory Volume/physiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Myocytes, Smooth Muscle/metabolism , Hematoxylin , Lung/blood supply , Middle Aged
Int. j. odontostomatol. (Print) ; 12(1): 51-56, Mar. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-893303


RESUMEN: El odontólogo como profesional integral del área de la salud, debe tener conocimiento acerca de distintas manifestaciones bioquímicas que pueden tener repercusión en la cavidad oral. El objetivo del trabajo fue determinar las manifestaciones bioquímicas y alteraciones en biomarcadores salivales en la cavidad oral producto de la fibrosis quística o del consumo crónico de medicamentos para el tratamiento de la FQ. Se seleccionó un total de cinco personas con fibrosis quística y cuatro personas sanas, pertenecientes a la ciudad de Concepción en la Octava Región de Chile. Se midió pH salival, capacidad buffer, concentración de proteínas totales, tasa de flujo salival estimulado y se determinó presencia de ciertas enzimas salivales en pacientes que padecen la enfermedad. Se pudo evidenciar que el pH salival en sujetos con fibrosis quística tiende a ser mayor a los valores de referencia, la tasa de flujo salival es mucho menor al igual que la capacidad buffer, la concentración de proteínas totales en saliva se encuentra igual a los valores de referencia y se determinó la presencia biomarcadores salivales a través de la técnica de electroforesis. La fibrosis quística afecta de muchas formas a las personas que la padecen, genera cambios a nivel de los biomarcadores salivales como también en la cavidad oral, por lo que el odontólogo debe estar capacitado para identificar estos cambios y poder tratar de la mejor manera a todo tipo de paciente.

ABSTRACT: The dentist as an integral health professional must have knowledge of various biochemical manifestations that may have repercussions on the oral cavity. The objective of the study was to determine the biochemical manifestations and salivary biomarker alterations in the oral cavity resulting from cystic fibrosis or chronic consumption of drugs for the treatment of CF. We selected a total of five people with cystic fibrosis and four healthy people, from the city of Concepcion in the eighth region of Chile. Salivary pH, buffer capacity, total protein concentration, stimulated salivary flow rate and the presence of certain salivary enzymes were measured in patients suffering from the disease. It was observed that the salivary pH in subjects with cystic fibrosis tends to be higher than the reference values, the salivary flow rate and buffer capacity are less than normal, the total protein concentration in saliva is equal to the reference values and the presence of salivary biomarkers was determined through the electrophoresis technique. Cystic fibrosis affects those who suffer the disease in many ways, it generates changes at the salivary biomarker level, as well as in the oral cavity. The dentist must therefore, be able to identify these changes in order to treat them in the best possible approach for all types of patients.

Humans , Male , Female , Child , Adolescent , Adult , Interleukin-8/metabolism , Matrix Metalloproteinase 9/metabolism , Cystic Fibrosis/physiopathology , Cystic Fibrosis/metabolism , Vascular Endothelial Growth Factor A/metabolism , Epidermal Growth Factor/metabolism , Chemokine CXCL10/metabolism , Saliva/chemistry , Biomarkers/metabolism , Proteins , Chile , Electrophoresis , Hydrogen-Ion Concentration , Informed Consent
Braz. dent. j ; 29(1): 43-47, Jan.-Feb. 2018. tab, graf
Article in English | LILACS | ID: biblio-888722


Abstract The aim of this study was to evaluate the expression of MMP2 and MMP9 during apical periodontitis (AP) progression in TLR2 (TLR2 KO) and in MyD88 (MyD88 KO) knockout mice compared to wild type (WT) mice. AP was induced in mandibular first molars of TLR2 KO (n= 18), MyD88 KO (n= 18), and WT mice (n= 18). After 7, 21, and 42 days, the animals were euthanized and the jaws were dissected and subjected to histotechnical processing. Subsequent sections were stained by immunohistochemistry and evaluated for detection of MMP2 and MMP9. Statistical analysis of the semi-quantitative analysis of immunohistochemistry was performed using chi-square test (α = 0.05). In the initial periods of AP progression, an increased expression of MMP9 in the TLR2 KO and MyD88 KO mice was observed. In the final periods of AP progression, a reduction of MMP2 expression and an increase of MMP9 expression in the TLR2 KO mice were observed. MMP2 and MMP9 production was modulated for TLR2 and MyD88 during apical periodontitis progression.

Resumo O objetivo deste estudo foi avaliar a expressão de MMP2 e MMP9 durante a progressão da periodontite apical (AP) em camundongos knockout para TLR2 (TLR2 KO) e MyD88 (MyD88 KO) comparados aos camundongos wild type (WT). A AP foi induzida nos primeiros molares inferiores dos camundongos TLR2 KO (n = 18), MyD88 KO (n = 18) e WT (n = 18). Após 7, 21 e 42 dias, os animais foram eutanaziados e as mandíbulas foram dissecadas e submetidas a processamento histotécnico. As lâminas foram coradas por imuno-histoquímica e analisadas para a detecção de MMP2 e MMP9. A análise estatística semi-quantitativa da imuno-histoquímica foi realizada pelo teste qui-quadrado (α = 0,05). Nos períodos iniciais de progressão AP, foi observada uma expressão aumentada de MMP9 nos camundongos TLR2 KO e MyD88 KO. Nos períodos finais de progressão AP, observou-se uma redução da expressão de MMP2 e um aumento da expressão de MMP9 nos camundongos TLR2 KO. A produção de MMP2 e MMP9 foi modulada por TLR2 e MyD88 durante a progressão da periodontite apical.

Animals , Mice , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Myeloid Differentiation Factor 88/physiology , Periapical Periodontitis/enzymology , Toll-Like Receptor 2/physiology , Disease Progression , Immunohistochemistry , Mice, Inbred C57BL , Mice, Knockout , Myeloid Differentiation Factor 88/genetics , Periapical Periodontitis/metabolism , Periapical Periodontitis/pathology
Braz. j. med. biol. res ; 51(12): e7862, 2018. graf
Article in English | LILACS | ID: biblio-974259


Although the effects of low-intensity pulsed ultrasound (LIPUS) on diverse cell types have been fully studied, the functional role of LIPUS in keratinocytes remains poorly understood. This study aimed to investigate the effects of LIPUS on proliferation and migration of HaCaT cells as well as the regulatory mechanisms associated with signaling pathways. Human HaCaT cells were exposed or not to LIPUS, and cell proliferation and migration were measured by BrdU incorporation assay and Transwell assay, respectively. Expression of proteins associated with proliferation and migration was evaluated by western blot analysis. Expression of key kinases in the PI3K/AKT and JNK pathways was also evaluated by western blot analysis. Effects of LIPUS on the PI3K/AKT and JNK pathways, and whether LIPUS affected HaCaT cells via these two pathways were finally explored. When the parameter of LIPUS (number of cycles) was set at 300, cell viability was the highest after LIPUS stimulation. We then found that the percentage of BrdU positive cells was enhanced by LIPUS, along with up-regulation of cyclinD1, CDK6, CDK4, and VEGF. LIPUS promoted migration, as well as up-regulation of MMP-2 and MMP-9. Phosphorylation levels of key kinases in the PI3K/AKT and JNK pathways were increased by LIPUS. Inhibition of either PI3K/AKT pathway or JNK pathway attenuated effects of LIPUS on HaCaT cells, and co-inhibition of these two pathways showed augmented effects. LIPUS promoted proliferation and migration of HaCaT cells through activating the PI3K/AKT and JNK pathways.

Keratinocytes/radiation effects , Cell Movement/radiation effects , Phosphatidylinositol 3-Kinases/radiation effects , MAP Kinase Signaling System/radiation effects , Cell Proliferation/radiation effects , Ultrasonic Waves , Bromodeoxyuridine , Cell Line, Transformed , Signal Transduction/radiation effects , Keratinocytes/metabolism , Up-Regulation , Cell Survival/radiation effects , Blotting, Western , Reproducibility of Results , Analysis of Variance , Phosphatidylinositol 3-Kinases/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism
Rev. Assoc. Med. Bras. (1992) ; 63(1): 78-84, Jan. 2017. tab, graf
Article in English | LILACS | ID: biblio-842523


Summary Zinc is the catalytic component of proteins that regulate responses to DNA damage, intracellular signaling enzymes, and matrix metalloproteinases, which are important proteins in carcinogenesis. The objective of this review is to bring current information on the participation of zinc and matrix metalloproteinases types 2 and 9 in mechanisms involved in the pathogenesis of breast cancer. We conducted a literature review, in consultation with the PubMed, Lilacs, and Scielo databases. The zinc and cysteine residues are structural elements shared by all members of the family of matrix metalloproteinases, and these proteins appear to be involved in the propagation of various types of neoplasms, including breast cancer. Moreover, transported zinc is likely to be used for the metalation of the catalytic domain of the newly synthesized metalloproteinases before the latter are secreted. Accordingly, increase in zinc concentrations in cellular compartments and the reduction of this trace element in the blood of patients with breast cancer appear to alter the activity of metalloproteinases 2 and 9, contributing to the occurrence of malignancy. Thus, it is necessary to carry out further studies with a view to clarify the role of zinc and metalloproteinases 2 and 9 in the pathogenesis of breast cancer.

Resumo O zinco é componente catalítico de proteínas que regulam respostas a danos no DNA, enzimas de sinalização intracelular e metaloproteinases de matriz, proteínas importantes na carcinogênese. O objetivo desta revisão é trazer informações atualizadas sobre a participação do zinco e das metaloproteinases de matriz dos tipos 2 e 9 em mecanismos envolvidos na patogênese do câncer de mama. Realizou-se um levantamento bibliográfico, mediante consulta às bases de dados PubMed, Scielo e Lilacs. O zinco e os resíduos de cisteína são elementos estruturais compartilhados por todos os membros da família das metaloproteinases de matriz, as quais parecem estar envolvidas na propagação de vários tipos de neoplasias, incluindo o câncer de mama. Além disso, é provável que o zinco transportado seja utilizado para metalação do domínio catalítico das metaloproteinases recentemente sintetizadas antes de serem segregadas. Nesse sentido, o aumento das concentrações de zinco em compartimentos celulares e a redução desse oligoelemento no sangue de pacientes com câncer de mama parecem alterar a atividade das metaloproteinases 2 e 9, contribuindo para a ocorrência de tumor maligno. Assim, faz-se necessária a realização de novos estudos na perspectiva de esclarecer o papel do zinco e das metaloproteinases 2 e 9 na patogênese do câncer de mama.

Humans , Female , Zinc/physiology , Breast Neoplasms/etiology , Matrix Metalloproteinase 2/physiology , Matrix Metalloproteinase 9/physiology , Zinc/metabolism , Breast Neoplasms/enzymology , Breast Neoplasms/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism
Braz. j. med. biol. res ; 50(6): e5868, 2017. tab, graf
Article in English | LILACS | ID: biblio-839308


We aimed to investigate the effect of etanercept, a tumor necrosis factor-α (TNF-α) inhibitor, on rat cardiomyocyte hypertrophy and its underlying mechanism. Primary neonatal rat cardiomyocytes were isolated from Sprague-Dawley rats. The model of rat cardiomyocyte hypertrophy was induced by endothelin, and then treated with different concentrations of etanercept (1, 10, and 50 μM). After treatment, cell counts, viability and cell apoptosis were evaluated. The mRNA levels of myocardial hypertrophy marker genes, including atrial natriuretic factor (ANF), matrix metalloproteinase (MMP)-9 and MMP-13, were detected by qRT-PCR, and the expressions of apoptosis-related proteins (Bcl-2 and Bax) were measured by western blotting. The protein levels of transforming growth factor-β1 (TGF-β1), interleukin (IL)-1β, IL-6, leukemia inhibitory factor (LIF) and cardiotrophin-1 (CT-1) were determined using enzyme linked immunosorbent assay (ELISA) kits. In the present study, TNF-α level in cardiomyocytes with hypertrophy was significantly enhanced (P<0.05). Compared to the model group, cell number and viability were significantly increased and ratio of apoptotic cells was reduced by etanercept (P<0.05, P<0.01, or P<0.001). In addition, etanercept remarkably reduced the mRNA levels of ANF, MMP-9 and MMP-13, inhibited the expression of Bax, and increased the expression of Bcl-2 compared to the model group (P<0.05). ELISA results further showed that etanercept lowered the levels of IL-1β, IL-6, LIF and CT-1 but not TGF-β1 compared to the model group (P<0.05). Etanercept may protect rat cardiomyocytes from hypertrophy by inhibiting inflammatory cytokines secretion and cell apoptosis.

Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cardiomegaly/metabolism , Etanercept/pharmacology , Myocytes, Cardiac/drug effects , Protective Agents/pharmacology , Animals, Newborn , Apoptosis/drug effects , Atrial Natriuretic Factor/metabolism , Cardiomegaly/chemically induced , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Cytokines/drug effects , Disease Models, Animal , Inflammation/metabolism , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 9/metabolism , Myocytes, Cardiac/metabolism , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/metabolism
Acta cir. bras ; 31(6): 382-388, graf
Article in English | LILACS | ID: lil-785018


ABSTRACT PURPOSE: To investigate the regulatory roles of neutrophil elastase (NE) and matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS: To construct LPS-induced ALI mouse models, wild-type C57BL/6 mice were administered 5.0 mg/kg of LPS through endotracheal, and/or 1.0 mg/kg of ONO-5046, and/or 20.0 mg/kg of chemically modified tetracycline-3 (CMT-3) by gavage. The levels of MMP-9, tissue inhibitor of metalloprotease-1, interleukin (IL)-6 were detected by real time RT-PCR at 6 h, 24 h and 48 h, and tumor necrosis factor (TNF), lung wet-dry weight ratio, white blood cell (WBC) count and polymorphonuclear (PMN) count in bronchoalveolar lavage fluid (BALF) were tested at 48 h after administration. The 5-day survival analysis of the ALI mice was also performed. RESULTS: Both ONO-5046 and CMT-3, regardless of being used individually or combined, significantly reduced the levels of MMP-9, IL-6, and TNF in lung tissue as well as in BALF, and the WBC and PMN count in BALF. Combined treatment with ONO-5046 and CMT-3 remarkably improved the survival rate of ALI mice. CONCLUSION: Neutrophil elastase synergizes with matrix metalloproteinase-9 to promote and regulate the release of inflammatory mediators and the infiltration of inflammatory cells, consequently affecting the survival of lipopolysaccharide-induced acute lung injury mice.

Animals , Sulfonamides/administration & dosage , Tetracyclines/administration & dosage , Leukocyte Elastase/metabolism , Matrix Metalloproteinase 9/metabolism , Acute Lung Injury/enzymology , Glycine/analogs & derivatives , Time Factors , Bronchoalveolar Lavage Fluid/cytology , Survival Analysis , Lipopolysaccharides , Interleukin-6/metabolism , Inflammation Mediators/metabolism , Leukocyte Elastase/drug effects , Tissue Inhibitor of Metalloproteinase-1/metabolism , Matrix Metalloproteinase 9/analysis , Matrix Metalloproteinase 9/drug effects , Tumor Necrosis Factors/metabolism , Disease Models, Animal , Acute Lung Injury/chemically induced , Acute Lung Injury/blood , Glycine/administration & dosage , Leukocyte Count , Mice, Inbred C57BL , Neutrophils
Acta cir. bras ; 31(5): 320-326, May 2016. tab, graf
Article in English | LILACS | ID: lil-783801


ABSTRACT PURPOSE : To compare ileal anastomoses in the immediate postoperative healing period after meloxicam use. METHODS: Forty two male Wistar rats were randomly divided into two groups of 21, COX and control group. To COX meloxicam in combination with morphine was given in 3 days period. Control group received only morphine during the same period. Each group was divided into three sub-groups of 7, which were euthanized at 5, 10, and 21 days postoperatively. Comparison was based in histological evaluation of collagen type I and III using sirius red, immunohistochemical through vascular endothelial growth factor and matrix metalloproteinase-9. RESULTS: Healing process in scheduled periods did not show significant differences (p>0.05) between the COX and control groups during any of the periods. CONCLUSION: The use of meloxicam in the postoperative period following ileal anastomosis did not affect healing.

Animals , Male , Thiazines/pharmacology , Thiazoles/pharmacology , Wound Healing/drug effects , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Ileum/surgery , Postoperative Period , Time Factors , Anastomosis, Surgical , Random Allocation , Rats, Wistar , Neovascularization, Physiologic/drug effects , Matrix Metalloproteinase 9/drug effects , Matrix Metalloproteinase 9/metabolism , Models, Animal , Collagen Type I/metabolism , Collagen Type III/metabolism , Receptors, Vascular Endothelial Growth Factor/drug effects , Receptors, Vascular Endothelial Growth Factor/metabolism , Ileum/blood supply
Braz. j. med. biol. res ; 49(12): e5717, 2016. graf
Article in English | LILACS | ID: biblio-828174


Propofol is one of the most commonly used intravenous anesthetic agents during cancer resection surgery. A previous study has found that propofol can inhibit invasion and induce apoptosis of ovarian cancer cells. However, the underlying mechanisms are not known. miR-9 has been reported to be little expressed in ovarian cancer cells, which has been related to a poor prognosis in patients with ovarian cancer. Studies have also demonstrated that propofol could induce microRNAs expression and suppress NF-κB activation in some situations. In the present study, we assessed whether propofol inhibits invasion and induces apoptosis of ovarian cancer cells by miR-9/NF-κB signaling. Ovarian cancer ES-2 cells were transfected with anti-miR-9 or p65 cDNA or p65 siRNA for 24 h, after which the cells were treated with different concentrations of propofol (1, 5, and 10 μg/mL) for 24 h. Cell growth and apoptosis were detected using MTT assay and flow cytometry analysis. Cell migration and invasion were detected using Transwell and Wound-healing assay. Western blot and electrophoretic mobility shift assay were used to detect different protein expression and NF-κB activity. Propofol inhibited cell growth and invasion, and induced cell apoptosis in a dose-dependent manner, which was accompanied by miR-9 activation and NF-κB inactivation. Knockdown of miR-9 abrogated propofol-induced NF-κB activation and MMP-9 expression, reversed propofol-induced cell death and invasion of ES-2 cells. Knockdown of p65 inhibited NF-κB activation rescued the miR-9-induced down-regulation of MMP-9. In addition, overexpression of p65 by p65 cDNA transfection increased propofol-induced NF-κB activation and reversed propofol-induced down-regulation of MMP-9. Propofol upregulates miR-9 expression and inhibits NF-κB activation and its downstream MMP-9 expression, leading to the inhibition of cell growth and invasion of ES-2 cells.

Humans , Female , MicroRNAs/drug effects , Neoplasm Invasiveness/prevention & control , NF-kappa B/drug effects , Ovarian Neoplasms/drug therapy , Propofol/therapeutic use , Protective Agents/therapeutic use , Apoptosis/drug effects , Blotting, Western , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Matrix Metalloproteinase 9/metabolism , MicroRNAs/genetics , NF-kappa B/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Polymerase Chain Reaction
Arq. bras. oftalmol ; 78(3): 141-145, May-Jun/2015. tab, graf
Article in English | LILACS | ID: lil-753022


ABSTRACT Purposes: To evaluate the effects of nalbuphine 1% on the expression of metalloproteinase 1 (MMP-1), metalloproteinase 9 (MMP-9), and opioid growth factor (OGF) in rabbit corneas after lamellar keratectomy. Methods: The rabbits were assigned to two groups: group nalbuphine (GN, n=30), which received 30 µL of nalbuphine 1% in 4 daily applications at regular intervals until corneal epithelialization, and group control (GC, n=30), which received physiological saline solution under the same conditions adopted in GN. The corneas were collected for immunohistochemistry on days 1, 3, 5, 7, and 9 after lamellar keratectomy, and the expressions of MMP-1, MMP-9, and OGF were analyzed. Results: The expressions of MMP-1 and MMP-9 increased until day 5 of the evaluation, with no differences observed between GN and GC (p>0.05). On days 7 and 9, significant reductions were observed in the expression of MMP-1 (p<0.01), with no differences observed between GN and GC (p>0.05). The expression of OGF was constant in all periods (p>0.05), restricted to the corneal epithelium, and there was no difference between the groups (p>0.05). Conclusions: The study results showed that nalbuphine 1% did not alter the expression patterns of MMP-1, MMP-9, and OGF in rabbit corneas after lamellar keratectomy. .

RESUMO Objetivos: Avaliar os efeitos da nalbufina 1% sobre a expressão da metaloproteinase 1 (MMP-1), da metaloproteinase 9 (MMP-9) e do fator de crescimento opióide (OGF), em córneas de coelhos submetidas à ceratectomia lamelar. Métodos: Constituíram-se dois grupos: grupo nalbufina (GN, n=30), que recebeu 30 µL de nalbufina 1% em 4 aplicações diárias, a intervalos regulares, até a epitelização corneal; controle (GC, n=30), que recebeu solução salina nas mesmas condições adotadas no GN. As córneas foram colhidas para imuno-histoquímica decorridos 1, 3, 5, 7 e 9 dias das ceratectomias lamelares, visando a se avaliarem as MMP-1, MMP-9 e OGF. Resultados: A expressão das MMP-1 e de MMP-9 se elevou até o quinto dia de avaliação, sem diferença entre GN e GC (p>0,05). Nos dias 7 e 9, observou-se redução significativa na expressão das enzimas (p<0,01), sendo que diferenças não foram observadas entre os grupos (p>0,05). O OGF exibiu imunomarcação constante em todos os períodos (p>0,05), restrita ao epitélio corneal. Não foram encontradas diferenças entre os grupos (p>0,05). Conclusões: Com base dos resultados obtidos, há como admitir que a nalbufina 1% não alterou o padrão de expressão da MMP-1, da MMP-9 e do OGF em córneas de coelhos submetidas à ceratectomia lamelar. .

Animals , Male , Rabbits , Analgesics, Opioid/pharmacology , Epithelium, Corneal/drug effects , Matrix Metalloproteinase 1/drug effects , Matrix Metalloproteinase 9/drug effects , Nalbuphine/pharmacology , Receptors, Opioid/drug effects , Analgesics, Opioid/administration & dosage , Corneal Stroma/metabolism , Corneal Stroma/pathology , Epithelium, Corneal/metabolism , Immunohistochemistry , Models, Animal , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 9/metabolism , Nalbuphine/administration & dosage , Receptors, Opioid/metabolism , Refractive Surgical Procedures/methods
Dental press j. orthod. (Impr.) ; 20(1): 66-73, Jan-Feb/2015. tab, graf
Article in English | LILACS | ID: lil-741440


OBJECTIVE: To determine by means of a systematic review the best treatment, whether interproximal wear or incisor extraction, to correct anterior lower crowding in Class I patients in permanent dentition. METHODS: A literature review was conducted using MEDLINE, Scopus and Web of Science to retrieve studies published between January 1950 and October 2013. In selecting the sample, the following inclusion criteria were applied: studies involving interproximal wear and/or extraction of mandibular incisors, as well as Class I cases with anterior lower crowding in permanent dentition. RESULTS: Out of a total of 943 articles found after excluding duplicates, 925 were excluded after abstract analysis. After full articles were read, 13 were excluded by the eligibility criteria and one due to methodological quality; therefore, only fours articles remained: two retrospective and two randomized prospective studies. Data were collected, analyzed and organized in tables. CONCLUSION: Both interproximal wear and mandibular incisor extraction are effective in treating Class I malocclusion in permanent dentition with moderate anterior lower crowding and pleasant facial profile. There is scant evidence to determine the best treatment option for each case. Clinical decision should be made on an individual basis by taking into account dental characteristics, crowding, dental and oral health, patient's expectations and the use of set-up models. .

OBJETIVO: determinar, por meio de uma revisão sistemática, o melhor tratamento entre desgastes interproximais e extração de incisivos para a correção de apinhamento anteroinferior em pacientes Classe I com dentição permanente. MÉTODOS: foram feitas buscas nas bases de dados eletrônicas MEDLINE, Scopus e Web of Science por artigos publicados de janeiro de 1950 até outubro de 2013. Os critérios de inclusão foram estudos que abordassem tratamentos com desgastes interproximais e/ou extração de incisivos inferiores, de casos Classe I com apinhamento anteroinferior na dentição permanente. RESULTADOS: dos 943 artigos encontrados após a remoção dos duplicados, 925 foram excluídos após a leitura dos resumos. Após leitura dos artigos completos, 13 foram excluídos pelos critérios de eligibilidade e um pela qualidade metodológica, restando quatro artigos, sendo dois retrospectivos e dois prospectivos randomizados. Os dados foram coletados, analisados e organizados em tabelas. CONCLUSÕES: tanto o desgaste interproximal quanto a extração de incisivo inferior são tratamentos eficazes em Classe I na dentição permanente, com apinhamento anteroinferior moderado e perfil facial agradável. Há fracas evidências para determinar a escolha do melhor tratamento para cada caso. A decisão clínica deve ser tomada em bases individuais, considerando as características anatômicas dentárias, da severidade do apinhamento, condições de saúde dentária e bucal, expectativas dos pacientes e ensaio em modelos (set-up). .

Animals , Female , Pregnancy , Maternal Nutritional Physiological Phenomena/physiology , Myocardium/pathology , Obesity/pathology , Blotting, Western , Fibrosis , Heart/embryology , Matrix Metalloproteinase 9/metabolism , Myocardium/metabolism , Obesity/metabolism , Phosphorylation , Reverse Transcriptase Polymerase Chain Reaction , Sheep , Signal Transduction , /metabolism , Transforming Growth Factor beta/metabolism , /metabolism
Article in English | WPRIM | ID: wpr-186437


Leptin is a peptide hormone, which has a central role in the regulation of body weight; it also exerts many potentially atherogenic effects. Ferulic acid ethyl ester (FAEE) has been approved for antioxidant properties. The aim of this study was to investigate whether FAEE can inhibit the atherogenic effects of leptin and the possible molecular mechanism of its action. Both of cell proliferation and migration were measured when the aortic smooth muscle cell (A10 cell) treated with leptin and/or FAEE. Phosphorylated p44/42MAPK, cell cycle-regulatory protein (for example, cyclin D1, p21, p27), beta-catenin and matrix metalloproteinase-9 (MMP-9) proteins levels were also measured. Results demonstrated that leptin (10, 100 ng ml-1) significantly increased the proliferation of cells and the phosphorylation of p44/42MAPK in A10 cells. The proliferative effect of leptin was significantly reduced by the pretreatment of U0126 (0.5 muM), a MEK inhibitor, in A10 cells. Meanwhile, leptin significantly increased the protein expression of cyclin D1, p21, beta-catenin and decreased the expression of p27 in A10 cells. In addition, leptin (10 ng ml-1) significantly increased the migration of A10 cells and the expression of MMP-9 protein. Above effects of leptin were significantly reduced by the pretreatment of FAEE (1 and 10 muM) in A10 cells. In conclusion, FAEE exerts multiple effects on leptin-induced cell proliferation and migration, including the inhibition of p44/42MAPK phosphorylation, cell cycle-regulatory proteins and MMP-9, thereby suggesting that FAEE may be a possible therapeutic approach to the inhibition of obese vascular disease.

Animals , Antioxidants/pharmacology , Aorta/cytology , Caffeic Acids/pharmacology , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Leptin/metabolism , Matrix Metalloproteinase 9/metabolism , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/cytology , Rats , beta Catenin/metabolism
Biol. Res ; 48: 1-8, 2015. ilus, graf
Article in English | LILACS | ID: biblio-950824


BACKGROUND: The aberrant expression of microRNAs (miRNAs) has been found in various types of cancer. miR-205 was reported to be upregulated in laryngeal squamous cell carcinoma (LSCC) tissues, however, the mechanisms by which miR-205 functions as a regulator of LSCC are largely unknown. RESULTS: In this study, Real-time qPCR and Western blot assay showed that expression of miR-205 was upregulated and expression of cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) was downregulated in LSCC tissues. The expression levels of miR-205 were negatively related to those of CDK2AP1 in LSCC tissues and cell lines. Moreover, we found that miR-205 was the upstream regulator of CDK2AP1 and could suppress the CDK2AP1 expression in LSCC cells. 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyl-tetrazolium bromide assays and transwell invasion assay were performed to test the proliferation and invasion of LSCC cells. Gelatin zymography was used to detect the activity of MMP2 and MMP9. CDK2AP1, c-Myc and CyclinD1 expression in cells was assessed with Western blotting. We found that miR-205 was the upstream regulator of CDK2AP1 and could suppress the expression of CDK2AP1 in LSCC cells. In addition, miR-205 significantly induced cell proliferation and invasion by suppressing CDK2AP1 expression. Consistent with miR-205 inhibitors, overexpressed CDK2AP1 suppressed the activity of MMP2 and MMP9 and c-Myc and CyclinD1 expression in LSCC cells. CONCLUSION: These findings help us to better elucidate the molecular mechanisms of LSCC progression and provide a new theoretical basis to further investigate miR-205 as a potential biomarker and a promising approach for LSCC treatment.

Humans , Suppression, Genetic/genetics , Carcinoma, Squamous Cell/pathology , Laryngeal Neoplasms/pathology , Tumor Suppressor Proteins/genetics , MicroRNAs/genetics , Cell Proliferation/genetics , Carcinoma, Squamous Cell/enzymology , Biomarkers, Tumor , Down-Regulation , Gene Expression Regulation, Neoplastic , Blotting, Western , Genes, myc/genetics , Cyclin D1/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Tumor Suppressor Proteins/metabolism , MicroRNAs/metabolism , Hep G2 Cells , Primary Cell Culture , Real-Time Polymerase Chain Reaction , Neoplasm Invasiveness/genetics
São Paulo; s.n; 2015. [129] p. ilus, tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-870998


Introdução e Objetivo: A doença mixomatosa da valva mitral leva ao comprometimento de sua matriz devido à alteração em sua composição tecidual provocada pelo desequilíbrio na quantidade de ácidos mucopolissacarídeos ou glicosaminoglicanos. Sua etiologia ainda não está totalmente esclarecida, podendo ocorrer em formas familiares com transmissão autossômica dominante de penetrância variável, que pode ser dependente do tempo ou de prováveis fatores ambientais, situações em que a interação de agentes infecciosos necessita de maiores esclarecimentos. O objetivo deste estudo é a análise dos produtos dos patógenos da Chlamydophila pneumoniae, Mycoplasma pneumoniae e Borrelia burgdorferi em segmentos de cúspide retirados da valva mitral com degeneração mixomatosa, comparada ao grupo controle e a relação dos produtos bacterianos com aumento de marcadores inflamatórios (CD20, CD48, CD68) e de metaloproteinase (MMP9) na etiopatogenia da degeneração mixomatosa da valva mitral. Método: Estudo observacional, analítico, tipo caso-controle, que analisou 2 grupos contendo 20 pacientes cada e divididos em grupo 1, composto por fragmentos de tecido valvar mitral com diagnóstico de degeneração mixomatosa extraídos em procedimentos de troca ou plásticas valvares mitrais; e grupo 2, formado por segmentos de valvas mitrais sem valvopatia retirados no serviço de verificação de óbito. Foram realizadas colorações de hematoxilina e eosina e Movat para diagnóstico histológico da degeneração mixomatosa e técnica de imunohistoquímica para detecção de antígenos da Borrelia burgdorferi, Mycoplasma pneumoniae, mediadores inflamatórios (CD20, CD45, CD68) e marcadores de metaloproteinase (MMP9). A presença de antígenos da Chlamydophila pneumonia e foi pesquisada pela técnica de hibridização in situ. A análise quantitativa dos aspectos microscópicos foi realizada com o analisador de imagens Aperio. A pesquisa de elementos bacterianos foi feita através de microscopia eletrônica...

Background: The myxomatous mitral valve disease leads to impairment due to changes in their tissue composition caused by the imbalance in the amount of acid mucopolysaccharides or glycosaminoglycans. Its etiology is not yet fully understood and may occur in familial forms of autosomal dominant trait with variable penetrance that can be time-dependent or probable environmental factors, where the interaction of infectious agents requires further elucidation. The purpose of this study is the analysis of the pathogens products of Chlamydophila pneumoniae, Mycoplasma pneumoniae and Borrelia burgdorferi in removed cusp segments of the mitral valve with myxoid degeneration, compared to the control group and the ratio of bacterial products with increased inflammatory markers (CD20, CD48, CD68) and metalloproteinase (MMP9) in the pathogenesis of myxomatous degeneration of the mitral valve. Method: Observational, analytical, case-control study which analyzed 2 groups of 20 patients each and divided in group 1, consisting of fragments of mitral valve tissue with diagnosis of myxomatous degeneration extracted in replacement procedures or mitral valve repair; group 2, formed by segments of mitral valves without valvolpaty clinial disease removed in the coroner service. Hematoxylin and eosin and Movat stains were done for histological diagnosis of myxoid degeneration and immunohistochemical technique for the detection of Borrelia burgdorferi, Mycoplasma pneumonia antigens, inflammatory mediators (CD20, CD45, CD68) and markers of metalloproteinase (MMP9). The presence of Chlamydophila pneumonia antigens was verified through an in situ hybridization technique. The quantitative analysis of the microscopic aspects was performed with the Aperio image analyzer. The research of bacterial elements was performed by a transmission electron microscopy. Results: In group 1, 14 (70%) patients were male and 6 (30%) were female. The mean age was (51 to 79 years, sd...

Humans , Adult , Borrelia burgdorferi , Chlamydophila pneumoniae , Mitral Valve , Mitral Valve Insufficiency , Mitral Valve Prolapse , Mycoplasma pneumoniae , Matrix Metalloproteinase 9/metabolism , Myxoma/metabolism , Myxoma/pathology
Article in Spanish | LILACS | ID: lil-746942


OBJETIVO: Los procesos destructivos del periodonto apical están en su mayoría mediados por proteasas específicas. Existe evidencia de que los niveles de metaloproteinasa de matriz extracelular-9 (MMP-9) en el fluido crevicular gingival (FCG) podrían reflejar la presencia de periodontitis apical asintomática (PAA). El objetivo de este estudio fue evaluar la actividad de MMP-9 durante la respuesta reparativa periapical en controles postendodóncicos entre una semana y 6 meses y en controles sanos. MATERIALES Y MÉTODOS: En este estudio prospectivo se incluyeron 28 pacientes con periodontitis apical asintomática, y se tomaron muestras de FCG a partir de dientes con PAA en línea base y controles postendodóncicos de una semana, uno, 3 y 6 meses. Adicionalmente se incluyeron controles contralaterales sanos. Las muestras se eluyeron y analizaron mediante gelatinogramas y densitometría. RESULTADOS: En pacientes con periodontitis apical asintomática se identificaron tanto la proforma como la forma activa de la MMP-9. Estas presentaron aumentos significativos en controles postendodóncicos de 3 y 6 meses con signos de reparación periapical. CONCLUSIONES: Los niveles de MMP-9 aumentaron significativamente en dientes con diagnóstico de PAA durante la fase reparativa. Estos resultados sugieren que MMP-9 también cumpliría un papel fisiológico durante la reparación periapical, que es susceptible de ser evaluado a través del análisis del FCG.

OBJECTIVE: Apical destructive periodontal processes are largely mediated by specific proteases. Evidence supports that the levels of extracellular matrix metalloproteinase-9 (MMP-9) could reflect the presence of asymptomatic apical periodontitis (AAP) in gingival crevicular fluid (GCF). The aim of this study was to evaluate the activity of MMP-9 during reparative response in periapical post endodontic controls between 1 week and 6 months later and in healthy controls. MATERIALS AND METHODS: A prospective study was performed on 28 patients with a diagnosis of AAP. GCF samples were taken from AAP teeth at baseline and post-endodontic controls at 1 week, 1, 3 and 6 months. Additional healthy contralateral controls were obtained, and samples were eluted and analyzed by densitometric scanning and gelatin zymography. RESULTS: In patients with asymptomatic apical periodontitis, both the pro form and the active form of MMP-9 were identified. These showed significant increases in post-endodontic controls at three and six months, with signs of periapical repairing. CONCLUSIONS: MMP-9 levels significantly increased in teeth diagnosed with AAP during the reparative phase. These results suggest that MMP-9 might be involved in the healing of apical tissues that might be reflected in GCF.

Humans , Male , Adolescent , Adult , Periapical Periodontitis/enzymology , Periapical Periodontitis/therapy , Gingival Crevicular Fluid/enzymology , Matrix Metalloproteinase 9/metabolism
Braz. j. med. biol. res ; 46(8): 659-669, ago. 2013. graf
Article in English | LILACS | ID: lil-684523


Chronic inflammation induced by amyloid-beta (Aβ) plays a key role in the development of age-related macular degeneration (AMD), and matrix metalloproteinase-9 (MMP-9), interleukin (IL)-6, and IL-8 may be associated with chronic inflammation in AMD. Sirtuin 1 (SIRT1) regulates inflammation via inhibition of nuclear factor-kappa B (NF-κB) signaling, and resveratrol has been reported to prevent Aβ-induced retinal degeneration; therefore, we investigated whether this action was mediated via activation of SIRT1 signaling. Human adult retinal pigment epithelial (RPE) cells were exposed to Aβ, and overactivation and knockdown of SIRT1 were performed to investigate whether SIRT1 is required for abrogating Aβ-induced inflammation. We found that Aβ-induced RPE barrier disruption and expression of IL-6, IL-8, and MMP-9 were abrogated by the SIRT1 activator SRT1720, whereas alterations induced by Aβ in SIRT1-silenced RPE cells were not attenuated by SRT1720. In addition, SRT1720 inhibited Aβ-mediated NF-κB activation and decrease of the NF-κB inhibitor, IκBα. Our findings suggest a protective role for SIRT1 signaling in Aβ-dependent retinal degeneration and inflammation in AMD.

Adult , Humans , Amyloid beta-Peptides/metabolism , Inflammation/chemically induced , Macular Degeneration/prevention & control , NF-kappa B/metabolism , Retinal Pigment Epithelium/drug effects , Signal Transduction/physiology , Sirtuin 1/physiology , Antioxidants/pharmacology , Blood-Retinal Barrier/physiopathology , Cell Survival/drug effects , Enzyme Assays/methods , Gene Silencing , /pharmacology , /metabolism , /metabolism , Macular Degeneration/chemically induced , Macular Degeneration/physiopathology , Matrix Metalloproteinase 9/metabolism , NF-kappa B/drug effects , Primary Cell Culture , Real-Time Polymerase Chain Reaction , RNA Interference , Retinal Pigment Epithelium/metabolism , Stilbenes/pharmacology