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1.
Medicine (Baltimore) ; 99(9): e19394, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118792

RESUMO

This study aimed to investigate the expression of c-Fos and matrix metallopeptidase 9 (MMP-9) in dental pulp of patients receiving orthodontic treatment via wire appliance.Fifteen patients (30 teeth in total) were randomly assigned to five groups: t = 0, t = 1, t = 4, t = 8 and t = 12 (n = 6). The first maxillary premolars of patients in the t = 0 group were extracted without any orthodontic treatment. An intrusive force of 300 g was applied on first maxillary premolars in the other four groups via wire appliances. This force was maintained for 1 week for t = 1 group, 4 weeks for t = 4 group, 8 weeks for t = 8 group, or 12 weeks for t = 12 group, before the teeth were extracted.The expression of c-Fos and MMP-9 in the pulps of each group was analyzed by immunohistochemical staining and real-time PCR. The relationship in the protein expression between c-Fos and MMP-9 in the dental pulp was analyzed by Pearson correlation analysis.Intrusive force of 300 g increased the expression of both c-Fos and MMP-9 in the dental pulp. The protein expression of MMP-9 in the dental pulp was significantly correlated with the expression of c-Fos (P < .001).Extreme intrusive force upregulates c-Fos and MMP-9 expression in the dental pulp. Moreover, protein expression of c-Fos and MMP-9 is significantly correlated under intrusive force.


Assuntos
Polpa Dentária/lesões , Metaloproteinase 9 da Matriz/análise , Proteínas Proto-Oncogênicas c-fos/análise , Estresse Mecânico , Adulto , Análise de Variância , China , Polpa Dentária/patologia , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/genética , Proteínas Proto-Oncogênicas c-fos/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos
2.
Braz Oral Res ; 34: e015, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130362

RESUMO

We sought to compare the characteristics and clinical significance of neutrophil extracellular traps in gingival samples from patients with periodontitis and those with gingivitis. The clinical indexes of gingival samples from patients with periodontitis and gingivitis were measured; the expression of TNF-alpha and IL-8 was measured by real-time fluorescent quantitative PCR; and the expression of TLR-8 and MMP-9 was measured by western blotting assays. Chemotaxis, phagocytosis and phagocytic activity of neutrophils were measured. Compared with the healthy group, the expression of TNF-α and IL-8 in the periodontitis group and the gingivitis group increased significantly (p < 0.05), and TNF-α in the gingivitis group was significantly lower than that in the healthy group (p < 0.05). The expression of IL-8 in the periodontitis group was significantly higher than that in the periodontitis group (p < 0.05). Furthermore, the expression of TLR-8 and MMP-9 in the periodontitis group was different from that in the gingivitis group and the healthy group, and the expression of TLR-8 and MMP-9 in the gingivitis group was significantly different from that in the healthy group (p < 0.05). In addition, the neutrophil mobility index in healthy people was 3.02 ± 0.53, that in the periodontitis group was 2.21 ± 0.13, and that in the gingivitis group was 2.31 ± 0.12. In conclusion, the chemotaxis of neutrophils in gingival samples of patients with periodontitis and gingivitis was decreased, the phagocytotic ability and activity of neutrophils were reduced, and the release of the extracellular trap-releasing inducible factors TNF-alpha and IL-8 also declined.


Assuntos
Armadilhas Extracelulares , Gengivite/patologia , Neutrófilos/patologia , Periodontite/patologia , Actinas/análise , Adulto , Western Blotting , Estudos de Casos e Controles , Eletroforese em Gel de Ágar , Feminino , Humanos , Interleucina-8/análise , Masculino , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Índice Periodontal , RNA/análise , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Receptor 8 Toll-Like/análise , Fator de Necrose Tumoral alfa/análise , Adulto Jovem
3.
Medicine (Baltimore) ; 98(48): e18244, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770287

RESUMO

BACKGROUND: We investigated the effects of propofol vs desflurane on ischemia and reperfusion injury (IRI)-induced inflammatory responses, especially in matrix metalloproteinase-9 (MMP-9) downregulation and heme oxygenase-1 (HO-1) upregulation, which may result in different clinical outcomes in liver transplant recipients. METHODS: Fifty liver transplant recipients were randomized to receive propofol-based total intravenous anesthesia (TIVA group, n = 25) or desflurane anesthesia (DES group, n = 25). We then measured the following: perioperative serum cytokine concentrations (interleukin 1 receptor antagonist [IL-1RA], IL-6, IL-8, and IL-10); MMP-9 and HO-1 mRNA expression levels at predefined intervals. Further, postoperative outcomes were compared between the 2 groups. RESULTS: The TIVA group showed a significant HO-1 level increase following the anhepatic phase and a significant MMP-9 reduction after reperfusion, in addition to a significant increase in IL-10 levels after the anhepatic phase and IL-1RA levels after reperfusion. Compared to DES patients, TIVA patients showed a faster return of the international normalized ratio to normal values, lower plasma alanine aminotransferase concentrations 24 hours after transplantation, and fewer patients developing acute lung injury. Moreover, compared with DES patients, TIVA patients showed a significant reduction in serum blood lactate levels. However, there were no differences in postoperative outcomes between the two groups. CONCLUSION: Propofol-based TIVA attenuated inflammatory response (elevated IL-1RA and IL-10 levels), downregulated MMP-9 response, and increased HO-1 expression with improved recovery of graft function and better microcirculation compared with desflurane anesthesia in liver transplant recipients.


Assuntos
Desflurano , Transplante de Fígado , Propofol , Traumatismo por Reperfusão , Adulto , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/efeitos adversos , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/efeitos adversos , Desflurano/administração & dosagem , Desflurano/efeitos adversos , Feminino , Heme Oxigenase-1/análise , Humanos , Proteína Antagonista do Receptor de Interleucina 1/análise , Interleucina-10/análise , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Metaloproteinase 9 da Matriz/análise , Período Pós-Operatório , Propofol/administração & dosagem , Propofol/efeitos adversos , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/etiologia , Imunologia de Transplantes
4.
Anticancer Res ; 39(11): 6403-6412, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704874

RESUMO

BACKGROUND: Cytokines, metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) take part in many processes involved in tumor progression and invasion such as degradation of the extracellular matrix, influence on immune cells associated with tumor tissue, and angiogenesis. Thus, the aim of this study was to compare the concentration of plasma levels and tissue expression of macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2 and MMP9, and their tissue inhibitors TIMP1 and TIMP2 in patients with cervical cancer, patients with high-grade cervical intraepithelial dysplasia (CIN3) and patients with ectropion. PATIENTS AND METHODS: Concentration and expression of all tested parameters was measured in serum with enzyme-linked immunosorbent assay (ELISA) and in tissue with immunohistochemistry method. RESULTS: The epithelial expression of M-CSF and TIMP1 in cancer tissue was much stronger as compared to that in ectropion and CIN3. In the case of MMP2, lack of or weak expression in epithelial cells was observed in all tested groups. Our studies showed statistical differences of tested parameters in tissue expression and in plasma concentrations in patients with cervical cancer, patients with CIN3 and patients with ectropion. Moreover, data revealed positive correlation between plasma level and cervical cancer cell expression of VEGF. CONCLUSION: Our findings indicate a potential role of all the proteins tested here in cervical cancer diagnosis, especially VEGF. However, further studies will show whether they play a role in the progression of cancerous changes in epithelial tissue of the cervix.


Assuntos
Fator Estimulador de Colônias de Macrófagos/análise , Metaloproteases/análise , Inibidores Teciduais de Metaloproteinases/análise , Displasia do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/química , Fator A de Crescimento do Endotélio Vascular/análise , Adenocarcinoma/sangue , Adenocarcinoma/química , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/química , Citocinas/análise , Citocinas/sangue , Feminino , Humanos , Fator Estimulador de Colônias de Macrófagos/sangue , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/sangue , Metaloproteases/sangue , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/sangue , Inibidores Teciduais de Metaloproteinases/sangue , Displasia do Colo do Útero/sangue , Neoplasias do Colo do Útero/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
5.
Plast Surg Nurs ; 39(3): 87-94, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31441788

RESUMO

Pressure injuries are a common kind of skin lesion that may be difficult to treat. The objective of this study was to analyze the effect of hydrogel enriched with alginate, fatty acids, and vitamins A and E in the treatment of pressure injuries. This case series with 12-week follow-up included applying daily dressings with hydrogel, maintaining a photographic record, using planimetry to calculate the lesion area, and classifying the healing process using the Pressure Ulcer Scale for Healing (PUSH). In addition, exudate collection from the ulcers was performed in the beginning and after 12 weeks of treatment to determine the dosage of metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1). Of the 13 patients included in the study, 2 died and 11 were monitored for 12 weeks. Only 1 patient showed full wound healing, but all patients showed a significant 12.19% (p = .023) reduction in the lesion area. The PUSH score was also significantly reduced from 15.9 to 10.54 (p = .0052). Relative to the dosage of metalloproteinase and its inhibitor, there was a reduction in the level of MMP9 and there was no change in the level of TIMP1. This study showed that hydrogel enriched with alginate, fatty acids, and vitamins A and E provided promising results for the treatment of pressure injuries by reducing the lesion area, the general PUSH score, and the amount of MMP9 in the wounds' microenvironment.


Assuntos
Alginatos/farmacologia , Ácidos Graxos/farmacologia , Lesão por Pressão/tratamento farmacológico , Vitamina A/farmacologia , Vitamina E/farmacologia , Idoso , Alginatos/uso terapêutico , Exsudatos e Transudatos/microbiologia , Ácidos Graxos/uso terapêutico , Feminino , Seguimentos , Humanos , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Masculino , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Lesão por Pressão/fisiopatologia , Inibidor Tecidual de Metaloproteinase-1/análise , Vitamina A/uso terapêutico , Vitamina E/uso terapêutico , Cicatrização/efeitos dos fármacos
6.
Arterioscler Thromb Vasc Biol ; 39(8): 1652-1666, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31294623

RESUMO

OBJECTIVE: We examined the pathogenic significance of VEGF (vascular endothelial growth factor)-A in experimental abdominal aortic aneurysms (AAAs) and the translational value of pharmacological VEGF-A or its receptor inhibition in aneurysm suppression. Approaches and Results: AAAs were created in male C57BL/6J mice via intra-aortic elastase infusion. Soluble VEGFR (VEGF receptor)-2 extracellular ligand-binding domain (delivered in Ad [adenovirus]-VEGFR-2), anti-VEGF-A mAb (monoclonal antibody), and sunitinib were used to sequester VEGF-A, neutralize VEGF-A, and inhibit receptor tyrosine kinase activity, respectively. Influences on AAAs were assessed using ultrasonography and histopathology. In vitro transwell migration and quantitative reverse transcription polymerase chain reaction assays were used to assess myeloid cell chemotaxis and mRNA expression, respectively. Abundant VEGF-A mRNA and VEGF-A-positive cells were present in aneurysmal aortae. Sequestration of VEGF-A by Ad-VEGFR-2 prevented AAA formation, with attenuation of medial elastolysis and smooth muscle depletion, mural angiogenesis and monocyte/macrophage infiltration. Treatment with anti-VEGF-A mAb prevented AAA formation without affecting further progression of established AAAs. Sunitinib therapy substantially mitigated both AAA formation and further progression of established AAAs, attenuated aneurysmal aortic MMP2 (matrix metalloproteinase) and MMP9 protein expression, inhibited inflammatory monocyte and neutrophil chemotaxis to VEGF-A, and reduced MMP2, MMP9, and VEGF-A mRNA expression in macrophages and smooth muscle cells in vitro. Additionally, sunitinib treatment reduced circulating monocytes in aneurysmal mice. CONCLUSIONS: VEGF-A and its receptors contribute to experimental AAA formation by suppressing mural angiogenesis, MMP and VEGF-A production, myeloid cell chemotaxis, and circulating monocytes. Pharmacological inhibition of receptor tyrosine kinases by sunitinib or related compounds may provide novel opportunities for clinical aneurysm suppression.


Assuntos
Aneurisma da Aorta Abdominal/etiologia , Elastase Pancreática/farmacologia , Receptores de Fatores de Crescimento do Endotélio Vascular/fisiologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Animais , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aneurisma da Aorta Abdominal/metabolismo , Quimiotaxia/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 9 da Matriz/análise , Camundongos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Sunitinibe/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
7.
Chem Commun (Camb) ; 55(49): 7085-7088, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31150032

RESUMO

A luminescent biosensor has been developed for matrix metalloproteinase 9 (MMP-9) assays based on the selective interaction between an Ir(iii) solvent complex and a histidine-rich peptide, which avoids the complicated double labeling of substrate polypeptides commonly-used in FRET MMP detections and provides a promising strategy for MMP detection in clinical applications.


Assuntos
Técnicas Biossensoriais , Complexos de Coordenação/química , Histidina/química , Irídio/química , Metaloproteinase 9 da Matriz/análise , Peptídeos/química , Complexos de Coordenação/metabolismo , Transferência Ressonante de Energia de Fluorescência , Histidina/metabolismo , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Peptídeos/metabolismo , Solventes/química
8.
Chem Commun (Camb) ; 55(41): 5817-5820, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31041939

RESUMO

A novel Au-Se nanoprobe with remarkable anti-interference ability for glutathione was developed for real-time in situ monitoring of the upstream and downstream regulatory relationship between uPA and MMP-9 proteins in the pathway.


Assuntos
Ouro/química , Metaloproteinase 9 da Matriz/análise , Nanoestruturas/química , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Selênio/química , Ativador de Plasminogênio Tipo Uroquinase/análise , Glutationa/química , Humanos , Células MCF-7 , Nanoestruturas/ultraestrutura , Neoplasias/enzimologia
9.
Med Sci Monit ; 25: 2835-2844, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30995213

RESUMO

BACKGROUND This study aims to demonstrate the underlying correlation between the resolution of liver fibrosis induced by Gexia-Zhuyu decoction (GZD) treatment and myeloid cell-mediated angiogenesis. MATERIAL AND METHODS A liver fibrosis mouse model induced by carbon tetrachloride (CCl4) intervention was employed in this study. Dynamics of blood liver function parameters were followed. The liver pathology was detected by Sirius Red and Masson staining. Matrix metalloproteinase (MMP) 2/9, tissue inhibitors of metalloproteinase (TIMP)-1/2, and vascular endothelial growth factor (VEGF)-A expression levels were measured. Bone marrow chimera mice were generated by transfer of bone morrow cells from green fluorescent protein (GFP)-knockin mice into irradiated wild-type mice, and were used it to visualize the role of myeloid cells on the fibrosis resolution induced by GZD treatment. RESULTS The result of Sirius Red and Masson staining and the dynamics of blood liver function parameters showed that 5 weeks of GZD treatment attenuated the severity of liver fibrosis with continual CCl4 administration. GZD treatment promoted the expression of MMP2/9 and repressed the heightened level of TIMP-1/2 in the recovery phase. More notably, the increased VEGF-A and augmented endothelial progenitor cells were observed in the liver and blood in mice that received GZD, and contributed to the remodeling of hepatic vascular though the CXCL12/CXCR4 axis. Then, chimera mice with GFP-positive bone marrow cells were used to show angiogenesis driven by GZD-induced myeloid cell motivation. We found that GZD facilitated myeloid cells binding to the vascular CXCR4 and induced the resolution of fibrosis. CONCLUSIONS This study shows that activation of myeloid cells induced by GZD administration accelerates the functional angiogenesis, which benefits the resolution of CCl4-induced liver fibrosis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática/tratamento farmacológico , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Indutores da Angiogênese/farmacologia , Animais , Células da Medula Óssea/citologia , Tetracloreto de Carbono/farmacologia , Modelos Animais de Doenças , Feminino , Fígado/química , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/metabolismo , Medicina Tradicional Chinesa/métodos , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/efeitos dos fármacos , Neovascularização Patológica/metabolismo , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Lab Chip ; 19(7): 1267-1276, 2019 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-30821304

RESUMO

To elucidate the secretary function of immune cells, we develop a nanoplasmonic circular interferometric biosensor based on intensity interrogation for label-free and dynamic sensing of molecular secretion. Exceptional sensitivity has been demonstrated through coupling free light and surface plasmon polariton (SPPs) waves, which generates a constructive and deconstructive interference pattern with high contrast and narrow linewidth when illuminated by white light. Alternatively, by adopting a narrow-band LED source and a CCD camera in this work, the transmission intensity of multiple sensing units is monitored simultaneously with a simple collinear optical setup. This intensity-modulated sensing platform yields a resolution of 4.1 × 10-5 refractive index unit (RIU) with a high temporal resolution of 1 s and a miniaturized footprint as small as 9.8 × 9.8 µm2 for a single sensing unit. By integrating the signals from multiple sensor units, the resolution of a 12 × 12 sensor array was found to reach 7.3 × 10-6 RIU. We apply this sensor array to detect matrix metalloproteinase 9 (MMP-9) secretion from human monocytic cells, THP-1, at different time points after lipopolysaccharide (LPS) simulation and the results are in good agreement with enzyme-linked immunosorbent assay (ELISA) tests, but without the need for labeling. The spatial, temporal and mass resolutions of the sensor array are found to exceed other label-free technologies. These biomolecular arrays, incorporated in a microfluidic sensor platform, hold great potential for the study the dynamics and interplay of cell secretion signals and achieving a better understanding of single cell functions.


Assuntos
Técnicas Biossensoriais/instrumentação , Interferometria/instrumentação , Dispositivos Lab-On-A-Chip , Metaloproteinase 9 da Matriz/análise , Linhagem Celular , Humanos
11.
Anat Histol Embryol ; 48(4): 306-314, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30907032

RESUMO

The tortuous nature of the ovine cervix restricts the transcervical passage of the cannula, and many studies have aimed to understand the endocrine mechanism of the remodelling of cervical tissue in adult ewe. However, little is known about the remodelling of the cervical tissue during the prepubertal development of the lambs. To obtain histochemical and biochemical evidence about the nature of the prepubertal development of the cervix of the ewe, cervices of Corriedale lambs obtained at 0, 1, 2, 4, 6 and 8 months of age (n = 5 to 6 in each) were processed. Neutral and acidic glycosaminoglycans (by PAS-Alcian stain) were weakly in the cervical stroma and not shown change during the development, whereas the percentage volume of fibrillar collagen (by van Gieson stain) increases throughout the experimental period in the superficial fold stroma and deep wall stroma (p < 0.05). The relative cervical weight (g/kg of body weight) and the collagen concentration (by spectrophotometry, mg/mg wet tissue) showed an early decreasing phase from months 0 to 4 and a later increasing phase from months 4 to 8 (p < 0.05). The latent form of matrix metalloproteinase-2 (MMP-2) detected by gelatin zymography (ng/mg protein) decreased from months 0 to 2 and increased from months 4 to 8, whereas the activated form decreased from months 0 to 2, remained low until month 6 and then recovered on month 8 (p < 0.0001). Data suggest that the relative cervical weight biphasic pattern during the development is related to MMP-2-dependent changes in the collagen content.


Assuntos
Colo do Útero/química , Colágeno/análise , Glicosaminoglicanos/análise , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 9 da Matriz/análise , Ovinos/crescimento & desenvolvimento , Animais , Peso Corporal , Colo do Útero/enzimologia , Colo do Útero/crescimento & desenvolvimento , Feminino , Histocitoquímica/veterinária , Tamanho do Órgão , Inclusão em Parafina/veterinária , Espectrofotometria/veterinária , Coloração e Rotulagem/veterinária
12.
Cardiovasc Pathol ; 40: 24-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30797186

RESUMO

Coronary high-signal-intensity plaques (HIPs) detected by T1-weighted magnetic resonance imaging are associated with future cardiovascular events. This study aimed to identify pathological findings reflecting HIPs in coronary arteries obtained from autopsy cases. Formalin-fixed hearts were imaged with noncontrast T1-weighted imaging with a 1.5-T magnetic resonance system. We defined HIPs or non-HIPs as a coronary plaque to myocardial signal intensity ratio (PMR) of ≥1.4 or <1.4, respectively. We found HIPs in 4 of 37 (10.8%) hearts and analyzed 7 hearts in detail. The corresponding sections to HIPs (n=11) or non-HIPs (n=25) were histologically and immunohistochemically analyzed. We calculated the T1 relaxation time of human venous blood in vitro. Plaque and necrotic core areas, and the frequency of intraplaque hemorrhage in HIPs were significantly larger/higher than those in non-HIPs. HIPs were immunopositive for CD68 (11/11), glycophorin A (10/11), and fibrin (11/11). Glycophorin-A-, matrix metalloprotease 9 (MMP9)-, and tissue factor-immunopositive areas were larger in HIPs than in non-HIPs. The PMR was positively correlated with glycophorin-A-, fibrin-, MMP9-, and tissue factor-immunopositive areas. Blood coagulation shortened the T1 relaxation time of the blood and plasma, and the T1 relaxation times in coagulated whole blood and erythrocyte-rich blood were significantly shorter than those in plasma. Coronary HIPs may reflect intraplaque hemorrhage and may be a novel marker for plaque instability and thrombogenic potential.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Hemorragia/diagnóstico por imagem , Imagem por Ressonância Magnética , Placa Aterosclerótica , Idoso , Idoso de 80 Anos ou mais , Autopsia , Coagulação Sanguínea , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Vasos Coronários/química , Vasos Coronários/patologia , Eritrócitos/química , Feminino , Fibrina/análise , Hemorragia/sangue , Hemorragia/patologia , Humanos , Imuno-Histoquímica , Masculino , Metaloproteinase 9 da Matriz/análise , Necrose , Valor Preditivo dos Testes , Tromboplastina/análise
13.
Pathol Oncol Res ; 25(2): 447-453, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30712193

RESUMO

Whole saliva is mainly composed of fluid produced by major and minor salivary glands. Major salivary glands including parotid, submandibular, and sublingual glands, are known to secrete fluid transported from serum as well as surrounding glandular tissues [1]. Beside the secretions from salivary glands, oral mucosa, periodontium, as well as oral microflora also contribute to the final content of whole saliva [1]. Whole saliva therefore represents a complex balance among local and systemic sources [2]. This allows for the application of saliva in the diagnosis not only for salivary gland disorders but also for oral diseases and systemic conditions [2]. The role of saliva as a diagnostic tool in detecting Oral Squamous Cell Carcinoma. Articles published in PUBMED, EMBASE, COCHRANE, GOOGLE, manual search and back references of the articles for last 5 years extracted 77 articles. Studies which considered saliva as a diagnostic tool were included. Statistical analysis with Receivers Operating Curve to establish sensitivity and specificity of the salivary biomarkers as a diagnostic tool to detect Oral Squamous Cell Carcinoma were included for meta analysis. The measure of effect with 95% confidence interval were meta analysed for 9 articles in which 308 healthy individuals compared with 340 patients with Oral Squamous Cell Carcinoma. Highly sensitive salivary biomarkers for detecting Oral Squamous Cell Carcinoma were MMP-9, Chemerin, Choline + Betaine + Pipecolinic Acid + I - Carnitine(confidence interval ranges from 0.83-1.0). The narrow confidence interval of 0.95 + (0.88-1.00) was seen for MMP-9 followed by 1.00 + (0.78-1.00) for chemerin. Highly specific biomarkers for Oral Squamous Cell Carcinoma were MMP-9 (specificity -100%,), Chemerin(specificity-100%), over expressed mi RNA 136 with specificity of 0.88(0.69-0.97), under expressed mi RNA 27B with specificity of 1.0(0.66-1.00). Saliva can be used as a diagnostic tool with highly sensitive and specific markers namely MMP-9, Chemerin for early detection of Oral Squamous Cell Carcinoma.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Bucais/diagnóstico , Saliva/química , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Quimiocinas/análise , Quimiocinas/biossíntese , Detecção Precoce de Câncer/métodos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/biossíntese , Sensibilidade e Especificidade
14.
World J Surg Oncol ; 17(1): 25, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30704487

RESUMO

BACKGROUND: The abnormal expression of activator protein-1(AP-1) has recently been investigated in a variety of tumors. While the relationship between AP-1 and thyroid cancer is poorly studied, our study was to evaluate the protein expression and clinical value of AP-1 in papillary thyroid carcinoma (PTC). METHODS: The expression of AP-1 was examined by immunohistochemistry on paraffin-embedded tissues obtained from PTC and correspondent paracancerous tissues of 82 patients. RESULTS: Compared with paracancerous tissues, AP-1 expression was significantly elevated in PTC tissues and the positive rate was 79.3% (65/82). Our study found a linear trend relationship between the expression of AP-1 and tumor size. However, the differences in AP-1 expression among gender, age, lymph node metastasis, number of lesions, location of the lesion, and extrathyroid invasion are not statistically significant. CONCLUSIONS: The expression of AP-1 plays an important role in the proliferation process of PTC.


Assuntos
Câncer Papilífero da Tireoide/química , Neoplasias da Glândula Tireoide/química , Fator de Transcrição AP-1/análise , Adolescente , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Proteínas Quinases JNK Ativadas por Mitógeno/fisiologia , Masculino , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Fator de Transcrição AP-1/fisiologia , Adulto Jovem
15.
Ann Vasc Surg ; 57: 210-219, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30684630

RESUMO

BACKGROUND: In abdominal aortic aneurysm (AAA), pathophysiology deterioration of the medial aortic layer plays a critical role. Key players in vessel wall degeneration are reactive oxygen species (ROS), smooth muscle cell apoptosis, and extracellular matrix degeneration by matrix metalloproteinase-9 (MMP-9). Lipocalin-2, also neutrophil gelatinase-associated lipocalin (NGAL), is suggested to be involved in these degenerative processes in other cardiovascular diseases. We aimed to further investigate the role of NGAL in AAA development and rupture. METHODS: In this observational study, aneurysm tissue and blood of ruptured (n = 13) AAA patients were investigated versus nonruptured (n = 26) patients. Nondilated aortas (n = 5) from deceased patients and venous blood from healthy volunteers (n = 10) served as controls. NGAL concentrations in tissue and blood were measured by enzyme-linked immunosorbent assay and immunofluorescence microscopy. Nitrotyrosine (marker of ROS), MMP-9, and caspase-3 (marker of apoptosis) in aneurysm tissue were measured by immunofluorescence microscopy. AAA expansion rates were calculated retrospectively. RESULTS: NGAL (in µg/mL) blood concentration in ruptured AAA was 46 (range 22-122) vs. 26 (range 6-55) in nonruptured AAA (P < 0.01) and 14 (range 12-22) in controls (P < 0.01). In the aneurysm wall of ruptured AAA, NGAL concentration was 4.7 (range 1.4-25) vs. 4.4 (range 0.2-14) in nonruptured AAA (not significant) and 1.8 (range 1.2-2.7) in nondilated aortas (P = 0.04). In the medial layer, NGAL correlated positively with nitrotyrosine (Rs = 0.80, P < 0.01), MMP-9 (Rs = 0.56, P = 0.02), and caspase-3 (Rs = 0.75, P = 0.01). NGAL did not correlate to AAA expansion rate in blood or tissue (P = 0.34 and P = 0.95, respectively). CONCLUSIONS: This study demonstrates that NGAL blood concentration is higher in ruptured AAA patients than in nonruptured AAA. NGAL expression in the AAA wall is also higher than in nondilated aorta. Furthermore, its expression is associated with factors of vessel wall deterioration. Based on our study results, we could not determine NGAL as a biomarker for AAA growth or rupture. However, our findings do support a potential role of NGAL in the development of AAA.


Assuntos
Aorta Abdominal/química , Aneurisma da Aorta Abdominal/sangue , Ruptura Aórtica/sangue , Lipocalina-2/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/patologia , Ruptura Aórtica/patologia , Apoptose , Biomarcadores/sangue , Caspase 3/análise , Dilatação Patológica , Progressão da Doença , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Estresse Oxidativo , Estudos Retrospectivos , Tirosina/análogos & derivados , Tirosina/análise , Regulação para Cima , Remodelação Vascular
16.
Int J Oral Sci ; 11(1): 7, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30602733

RESUMO

Proteases are important molecules that are involved in many physiological and pathological processes of the human body, such as growth, apoptosis and metastasis cancer cells. They are potential targets in cancer diagnosis and biotherapy. In this study, we analyzed the salivary protease spectrum of patients with oral squamous cell carcinoma (OSCC), oral benign masses and chronic periodontitis, as well as that of health, using human protease array kits, enzyme-linked immunosorbent assay, western blot and immunofluorescence. The salivary protease spectrum was found to be associated with oral diseases. For example, the saliva of patients with OSCC contained increased numbers of proteases than those of other oral diseases and health. The levels of matrix metalloproteinase (MMP)-1, MMP-2, MMP-10, MMP-12, A disintegrin and metalloprotease (ADAM)9, A disintegrin and metalloprotease with thrombospondin type 13 motifs (ADAMST13), cathepsin V and kallikrein 5 in the saliva of patients with OSCC were significantly increased compared with those of other groups. Taking MMP-1, cathepsin V, kallikrein 5 and ADAM9 as biomarkers of OSCC, cutoff values were199, 11.34, 9.29 and 202.55 pg·mL-1, respectively. From the area under the curve, sensitivity and specificity, the combination of cathepsin V/kallikrein5/ADAM9 was an optimal biomarker for diagnosing OSCC. Thus, analysis of the salivary protease spectrum may be an innovative and cost-efficient approach to evaluating the health status of the oral cavity. Specifically, increases in cathepsin V, kallikrein 5 and ADAM9 may be useful biomarkers in the screening and diagnosis of OSCC.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Metaloproteinase 9 da Matriz/análise , Neoplasias Bucais/diagnóstico , Saliva/química , Proteínas ADAM , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/metabolismo , Humanos , Proteínas de Membrana , Neoplasias Bucais/metabolismo
17.
Life Sci ; 217: 212-221, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30550883

RESUMO

AIMS: Cerebral ischemia reperfusion (I/R) is a neurovascular disease leading to cerebral damage. It was found that postmenopausal women are liable to more dangerous effects than men at same age in stroke. The objective of this study is to investigate the neuroprotective effect of zeranol against cerebral ischemia reperfusion in ovariectomized rats. MAIN METHODS: 36 female wistar rats divided in to 3 groups: sham group, I/R group (where I/R was induced 7 weeks after ovariectomy), zeranol group (0.5 mg/kg every 3 days for 5 weeks before I/R). Cerebral ischemia reperfusion (I/R) was performed by bilateral common carotid artery occlusion then de-ligated to restore blood flow. After 24 h of reperfusion, rats performed cylinder test to evaluate behavioral dysfunction followed by decapitation. Brain tissues were collected for biochemical measures such as oxidative stress marker malondialdehyde, antioxidant markers reduced glutathione, inflammatory markers (interleukin-1 beta, tumor necrosis factor alpha, and inducible nitric oxide synthase), matrix metalloproteinase-9, adenosine triphosphate, brain derived neurotrophic factor, glucose transporter-3, phosphorylated c-AMP response element binding protein and finally nissl staining for histopathological examination. KEY FINDINGS: The zeranol administered group showed a reversal of neuronal damage caused by ischemia evidenced by the decrease in MDA, IL-1ß, TNF-α, and MMP-9 levels, increase GSH, and ATP levels, decrease expression of iNOS in both regions cortex and hippocampus, increase protein level of p-CREB, GLUT-3 and BDNF, increase number of intact neuron cells in both regions and attenuated histological changes in both cortex and hippocampus regions. SIGNIFICANCE: Zeranol has neuroprotective potential against cerebral ischemia reperfusion in ovariectomized rats.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fitoestrógenos/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Zeranol/uso terapêutico , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/análise , Feminino , Mediadores da Inflamação/análise , Mediadores da Inflamação/metabolismo , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/metabolismo , Neurogênese/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/análise , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia
18.
Arq Bras Cardiol ; 112(2): 180-188, 2019 02.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30570072

RESUMO

BACKGROUND: In menopause, there is greater cellular exposure to oxidative stress, related to the decreased antioxidative effects of estrogen. These metabolic changes favor the progression of cardiovascular diseases, such as atherosclerosis. Abnormal function of the aorta - the most important artery - is associated with many cardiovascular diseases. Collagen, especially types I and III, is one of the most important aortic wall components and it can be affected by many factors, including menopause. The 8-OHdG is one of the main markers of DNA oxidative damage induced by reactive oxygen species (ROS). OBJECTIVE: We aimed to investigate effects of moderate aerobic training on the ascending aorta of LDL-knockout (LDL-KO) and ovariectomized female mice. METHODS: A total of 15 C57BL/6 mice and 15 LDL-KO mice were divided into experimental groups. The thickness and volume density of types I and III collagen fibers were performed by morphoquantitative analysis, whereas the MMP-2 and MMP-9 and 8-OHdG were detected by immunohistochemistry and apoptosis was detected by the TUNEL assay. The significance level for all tests was p < 0.05. RESULTS: Exercise causes an increase in the thickness of the aorta in LDL-KO groups, particularly accentuated in the ovariectomized groups. The type I collagen fibers showed an increase in volume density influenced by training in both Control groups and in the LDL-KO group. Type III collagen density decreased in both groups. The MMP-2 showed moderade immunostaining in the tunica media in LDL-KO groups, which did not occur in the control groups and the MMP-9 stained irregularly in all tissues. The marker 8-OhdG was stronger in the exercise training groups. Additionally, the ovariectomy, the exercise training and the LDL-KO treatments increased apoptosis. CONCLUSION: These results suggest that moderate-intensity aerobic exercise in ovariectomized mice associated to an increase in LDL rate possibly increases oxidative stress and apoptosis induction.


Assuntos
/análise , Aorta/metabolismo , Colágeno/análise , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 9 da Matriz/análise , Ovariectomia , Condicionamento Físico Animal/fisiologia , Animais , Aorta/patologia , Apoptose/fisiologia , Feminino , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Menopausa/metabolismo , Camundongos , Camundongos Knockout , Estresse Oxidativo/fisiologia , Receptores de LDL/sangue , Comportamento Sedentário , Túnica Média/patologia
19.
Breast Cancer Res ; 20(1): 154, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30558648

RESUMO

BACKGROUND: The role of tumor-associated macrophages (TAMs) in the cancer immune landscape and their potential as treatment targets or modulators of response to treatment are gaining increasing interest. TAMs display high molecular and functional complexity. Therefore their objective assessment as breast cancer biomarkers is critical. The aims of this study were to objectively determine the in situ expression and significance of TAM biomarkers (CD68, CD163, and MMP-9) in breast cancer and to identify subclasses of patients who could benefit from TAM-targeting therapies. METHODS: We measured CD68, CD163, and MMP-9 protein expression in formalin-fixed paraffin-embedded tissues of breast carcinomas represented in tissue microarray format using multiplexed quantitative immunofluorescence (QIF) in two independent Yale cohorts: cohort A-n = 398, estrogen receptor-positive (ER+) and ER- cases-and the triple-negative breast cancer (TNBC)-only cohort B (n = 160). Associations between macrophage markers, ER status, and survival were assessed. Protein expression measured by QIF was compared with mRNA expression data from the METABRIC study. RESULTS: All three macrophage markers were co-expressed, displaying higher expression in ER- cancers. High pan-macrophage marker CD68 correlated with poorer overall survival (OS) only in ER- cases of cohort A (P = 0.02). High expression of CD163 protein in TAMs was associated with improved OS in ER- cases (cohort A, P = 0.03 and TNBC cohort B, P = 0.04, respectively) but not in ER+ cancers. MMP-9 protein was not individually associated with OS. High expression of MMP-9 in the CD68+/CD163+ TAMs was associated with worse OS in ER+ tumors (P <0.001) but not in ER- cancers. In the METABRIC dataset, mRNA levels followed the co-expression pattern observed in QIF but did not always show the same trend regarding OS. CONCLUSIONS: Macrophage activity markers correlate with survival differently in ER+ and ER- cancers. The association between high co-expression and co-localization of MMP-9/CD163/CD68 and poor survival in ER+ cancers suggests that these cancers may be candidates for macrophage-targeted therapies.


Assuntos
Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Metaloproteinase 9 da Matriz/análise , Receptores de Superfície Celular/análise , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/imunologia , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Metaloproteinase 9 da Matriz/imunologia , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Seleção de Pacientes , Prognóstico , Receptores de Superfície Celular/imunologia , Receptores de Superfície Celular/metabolismo , Receptores Estrogênicos/metabolismo , Estudos Retrospectivos , Análise de Sobrevida , Análise Serial de Tecidos , Microambiente Tumoral/imunologia
20.
Rev Bras Ginecol Obstet ; 40(11): 705-712, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30485900

RESUMO

OBJECTIVE: To characterize the patterns of cell differentiation, proliferation, and tissue invasion in eutopic and ectopic endometrium of rabbits with induced endometriotic lesions via a well- known experimental model, 4 and 8 weeks after the endometrial implantation procedure. METHODS: Twenty-nine female New Zealand rabbits underwent laparotomy for endometriosis induction through the resection of one uterine horn, isolation of the endometrium, and fixation of tissue segment to the pelvic peritoneum. Two groups of animals (one with 14 animals, and the other with15) were sacrificed 4 and 8 weeks after endometriosis induction. The lesion was excised along with the opposite uterine horn for endometrial gland and stroma determination. Immunohistochemical reactions were performed in eutopic and ectopic endometrial tissues for analysis of the following markers: metalloprotease (MMP-9) and tissue inhibitor of metalloprotease (TIMP-2), which are involved in the invasive capacity of the endometrial tissue; and metallothionein (MT) and p63, which are involved in cell differentiation and proliferation. RESULTS: The intensity of the immunostaining for MMP9, TIMP-2, MT, and p63 was higher in ectopic endometria than in eutopic endometria. However, when the ectopic lesions were compared at 4 and 8 weeks, no significant difference was observed, with the exception of the marker p63, which was more evident after 8 weeks of evolution of the ectopic endometrial tissue. CONCLUSION: Ectopic endometrial lesions seem to express greater power for cell differentiation and tissue invasion, compared with eutopic endometria, demonstrating a potentially invasive, progressive, and heterogeneous presentation of endometriosis.


Assuntos
Coristoma/metabolismo , Endometriose/metabolismo , Endométrio/metabolismo , Metaloproteinase 9 da Matriz/biossíntese , Proteínas de Membrana/biossíntese , Metalotioneína/biossíntese , Inibidor Tecidual de Metaloproteinase-2/biossíntese , Animais , Diferenciação Celular , Proliferação de Células , Coristoma/patologia , Modelos Animais de Doenças , Endometriose/patologia , Endométrio/química , Endométrio/patologia , Feminino , Metaloproteinase 9 da Matriz/análise , Proteínas de Membrana/análise , Metalotioneína/análise , Coelhos , Inibidor Tecidual de Metaloproteinase-2/análise
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