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1.
Medicine (Baltimore) ; 98(47): e17950, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764795

RESUMO

OBJECTIVE: To investigate the role of YKL-40 in ST segment elevation myocardial infarction (STEMI) and its relationship to C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9). METHODS: This prospective study included 358 STEMI patients who were sent to the Emergency Department of our hospital from April 2014 to December 2017. Serum levels of YKL-40, CRP and MMP-9 were determined using commercially available Enzyme linked immunosorbent assay (ELISA) kits. Major adverse cardiovascular events (MACE) and overall survival time were analyzed. RESULTS: GRACE scores (P < .001) and the levels of YKL-40 (P < .001), MMP-9 (P < .001), and CRP (P < .001) were significantly higher in deceased patients compared to those that survived. The levels of CRP (P = .007) and MMP-9 (P = .022) were significantly higher in the high YKL-40 group. The GRACE scores were also significantly elevated (P = .011, 95% CI 2.1 (-9.7 to -1.3)). Cumulative MACE rates and cardiac death rates were significantly higher in the high YKL-40 group (P < .001, 95% CI 3.9 (1.9-8.2)). Overall survival times were significantly longer in patients with lower YKL-40 levels (P < .0001). CONCLUSION: Elevated YKL-40 levels positively correlate with CRP and MMP-9 levels and are associated with clinical outcomes including MACE and 6-month survival in STEMI patients.


Assuntos
Proteína C-Reativa/análise , Proteína 1 Semelhante à Quitinase-3/sangue , Metaloproteinase 9 da Matriz/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Doença Aguda , Correlação de Dados , Tratamento de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
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
3.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414760

RESUMO

BACKGROUND: The current study aims to investigate the expression of antisense noncoding RNA in the INK4 locus (ANRIL) in serum of patients with ischemic stroke and its correlation with high-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). METHODS: Real time PCR analysis was carried out to evaluate the level of ANRIL. The levels of hs-CRP and MMP-9 were evaluated using ELISA. ROC analysis was carried out to evaluate the diagnostic value of ANRIL, hs-CRP and MMP-9. Pearson's correlation analysis was carried out to evaluate the expression of ANRIL in serum of hs-CRP and MMP-9. RESULTS: Our data showed that the expression levels of ANRIL, hs-CRP, and MMP-9 in serum of the patients were significantly higher than those of the control group (p < 0.05). Pearson's correlation analysis showed that there was a positive correlation between the expression of ANRIL and hs-CRP and MMP-9. Meanwhile, serum levels of ANRIL, hs-CRP, and MMP-9 in patients with severe neurological deficits were significantly higher than those in patients with moderate and mild neurological deficits (p < 0.05). Moreover, the expression levels of ANRIL, hs-CRP, and MMP-9 in serum of patients with different degrees of neurological impairment have different correlations. More importantly, ROC analysis demonstrated that the combined use of ANRIL, hs-CRP, and MMP-9 demonstrated higher diagnostic value for stroke patients. CONCLUSIONS: Serum ANRIL may be used as a molecular marker in the diagnosis of ischemic stroke and may play an important role in the pathogenesis and development of ischemic stroke in cooperation with hs-CRP and MMP-9.


Assuntos
Biomarcadores/sangue , Isquemia Encefálica/sangue , RNA Longo não Codificante/sangue , Acidente Vascular Cerebral/sangue , Idoso , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/genética , Proteína C-Reativa/análise , Proteína C-Reativa/genética , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Curva ROC , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/genética
4.
Clin Appl Thromb Hemost ; 25: 1076029619871359, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31434498

RESUMO

Recombinant tissue plasminogen activator (rt-PA) can be utilized to treat ischemic stroke with safety and effectiveness but limited by a narrow therapeutic window. In the present clinical trial among patients with stroke, we sought to evaluate the potential of fisetin to extend the therapeutic window of rt-PA treatment. Patients with stroke were divided based on their onset-to-treatment time (OTT) and then randomly assigned to receive the rt-PA treatment combined with fisetin or placebo. Primary outcome was evaluated using the National Institutes of Health Stroke scale (NIHSS), and secondary outcome was assessed by serum levels of matrix metalloproteinase (MMP) 2, MMP 9, and C-reactive protein (CRP). Fisetin dramatically improved the treatment outcomes of the patients with stroke in the delayed OTT strata, as revealed by lower NIHSS scores. The beneficial effect of fisetin was likely attributable to reduced levels of MMP-2, MMP-9, and CRP in the serum, as evidenced by strong linear correlations between serum levels of such markers with the NIHSS scores in all enrolled patients. Fisetin may possess the potential to supplement traditional rt-PA treatments among patients with stroke, particularly for those with delayed OTT, and thereby extend the otherwise narrow therapeutic window and improve the treatment outcomes.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Flavonoides/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Tempo para o Tratamento , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Proteína C-Reativa/análise , Feminino , Flavonoides/farmacologia , Humanos , Masculino , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
5.
Nord J Psychiatry ; 73(8): 515-521, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31464540

RESUMO

The purpose of the article: Brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) are involved in the processes of neurogenesis, synaptic plasticity, learning and memory. Growing number of studies shows a relationship between BDNF or MMP-9 and schizophrenia. Also, BDNF and MMP-9 levels may be affected by metabolic parameters, such as obesity or dyslipidemia. Our hypothesis is that alterations of BDNF or MMP-9 levels in schizophrenia might be secondary to metabolic abnormalities, often found among schizophrenia patients. Materials and methods: We have compared BDNF and MMP-9 between patients with schizophrenia (n = 64, age 49 ± 8.2 y) and healthy controls (n = 32, age 51 ± 8.9 y) in the context of cardio-metabolic parameters. Serum levels of BDNF and MMP-9 were measured using ELISA test, body composition parameters were determined using bioelectric impedance analysis. Results and conclusions: Our results showed significantly lowered serum BDNF concentration in the schizophrenia group (schizophrenia: 23.8 ± 7.83 ng/mL, control: 27.69 ± 8.11 ng/mL, p = 0.03). Serum MMP-9 concentration in schizophrenia group did not differ compared with the control group (schizophrenia: 456.8 ± 278.4 ng/mL, control: 341.5 ± 162.4 ng/mL, p = 0.07). After adjusting for age, all anthropometric parameters, body composition and laboratory tests BDNF were still significantly lower in the schizophrenia group. However, MMP-9 became significantly elevated in the schizophrenia group after adjusting for several anthropometric and body composition covariates. Our results confirmed reduced serum BDNF concentration in patients with schizophrenia. Also, this reduction seems to be independent of metabolic abnormalities. On the other hand, our hypothesis that MMP-9 level in schizophrenia is altered due to metabolic abnormalities might be true.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Metaloproteinase 9 da Matriz/sangue , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
BMC Neurol ; 19(1): 167, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319804

RESUMO

BACKGROUND: Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 early after ischemic stroke have been associated with lower survival. The objectives of this study were to determine serum TIMP-1 levels during the first week of a severe cerebral infarction in surviving and non-surviving patients, and whether those levels during the first week could be used as a mortality biomarker for these patients. METHODS: We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as computer tomography showing ischaemic changes in more than 50% of the middle cerebral artery territory and Glasgow Coma Scale (GCS) ≤ 8. We measured serum levels of matrix metalloproteinases (MMP)-9 and TIMP-1. End-point study was 30-day mortality. RESULTS: We found higher TIMP-1 concentrations at days 1 (p < 0.001), 4 (p = 0.001), and 8 (p = 0.03) of MMCAI in non- urviving (n = 34) than in surviving (n = 34) patients. We found lower serum MMP-9 concentrations at day 1 (p = 0.03) of MMCAI and no significant differences at days 4 and 8. ROC curve analysis of TIMP-1 concentrations performed at days 1, 4, and 8 of MMCAI showed an area under curve to predict 30-day mortality of 81% (p < 0.001), 80% (p < 0.001) and 72% (p = 0.07) respectively. CONCLUSIONS: The new findings of our study were that non-surviving MMCAI patients showed higher serum TIMP-1 levels during the first week of MMCAI that surviving patients, and those levels during the first week of MMCAI could be used as mortality biomarkers.


Assuntos
Infarto da Artéria Cerebral Média/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Idoso , Biomarcadores/sangue , Feminino , Escala de Coma de Glasgow , Humanos , Infarto da Artéria Cerebral Média/mortalidade , Masculino , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Acidente Vascular Cerebral/sangue
7.
Clin Lab ; 65(7)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31307174

RESUMO

BACKGROUND: The current study aims to investigate the expression of miR-599 in serum of patients with ischemic stroke and its correlation with high sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). METHODS: The expression level of miR-24 in serum was detected by real-time PCR, and the expression levels of hs-CRP and MMP-9 were detected by ELISA. Partial correlation analysis was used to explore the correlation be-tween the expression of miR-24 in serum and hs-CRP and MMP-9. ROC analysis was carried out to evaluate the potential diagnostic value. RESULTS: Our data showed that the expression levels of miR-599, hs-CRP, and MMP-9 in serum of the patients were significantly higher than those of the control group (p < 0.05). Partial correlation analysis showed that there was a positive correlation between the expression of miR-599 and hs-CRP and MMP-9 (r = 0.718, p = 0.000; r = 0.658, p = 0.000; r = 0.878, p = 0.000). Meanwhile, serum levels of miR-599, hs-CRP, and MMP-9 in patients with severe neurological deficit were significantly higher than those in patients with moderate and mild neurological deficit (p < 0.05). Moreover, the expression levels of miR-599, hs-CRP, and MMP-9 in serum of patients with dif-ferent degrees of neurological impairment have different correlations. More importantly, ROC analysis demon-strated that combined use of miR-599, hs-CRP, and MMP-9 demonstrated higher diagnostic value for stroke pa-tients. CONCLUSIONS: Serum miR-599 may be used as a molecular marker in the diagnosis of ischemic stroke and may play an important role in the pathogenesis and development of ischemic stroke in cooperation with hs-CRP and MMP-9.


Assuntos
Biomarcadores/sangue , Isquemia Encefálica/sangue , MicroRNAs/sangue , Acidente Vascular Cerebral/sangue , Idoso , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/genética , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Curva ROC , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/genética
8.
J Zhejiang Univ Sci B ; 20(8): 687-692, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273966

RESUMO

The objective of this study was to assess the angiogenic potential expressed as a quotient of vascular endothelial growth factor A (VEGF-A), as an indicator of proangiogenic activity, and the circulating receptors (soluble VEGF receptor protein R1 (sVEGFR-1) and sVEGFR-2), as indicators of the effect of angiogenic inhibition, depending on the concentrations of matrix metalloproteinase 2 (MMP-2) and MMP-9 and their tissue inhibitor 1 (TIMP-1) and TIMP-2 in the plasma of patients with lower extremity artery disease (LEAD). These blood parameters in patients with intermittent claudication (IC) and critical limb ischemia (CLI) were compared for select clinical and biochemical features. Stimulation of angiogenesis in the plasma of individuals with LEAD was evident as indicated by the significant increase in VEGF-A concentration along with reduced inhibition depending on circulating receptors sVEGFR-1 and sVEGFR-2. Critical ischemia was associated with higher VEGF-A, MMP-9, TIMP-1, and TIMP-2 concentrations than in the case of IC.


Assuntos
Claudicação Intermitente/sangue , Isquemia/sangue , Extremidade Inferior/irrigação sanguínea , Metaloproteinase 9 da Matriz/sangue , Neovascularização Patológica , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/sangue , Idoso , Inibidores da Angiogênese/farmacologia , Feminino , Regulação da Expressão Gênica , Humanos , Claudicação Intermitente/tratamento farmacológico , Isquemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue
9.
Dis Markers ; 2019: 1242964, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191742

RESUMO

Background: Malignant mesothelioma (MM) is a rare, but fatal disease with few treatment options. The diagnosis and treatment response are challenging in MM. Therefore, the search for novel diagnostic and prognostic biomarkers is ongoing. The aim of our study was to investigate matrix metalloproteinase 9 (MMP9) as a potential serum biomarker of treatment response and survival in MM. We also investigated the influence of genetic polymorphisms on MMP9 serum levels. Methods: We included 110 patients with MM that have been previously genotyped for common MMP9 polymorphisms. Serum samples were collected before treatment, at the end of chemotherapy, and at the time of progression. MMP9 serum levels were measured using enzyme-linked immunosorbent assay kits. The role of serum MMP9 and MMP9 polymorphisms in treatment response was determined using the nonparametric tests and logistic or Cox regression. Results: Median serum MMP9 was 706.7 (499.6-1224.9) ng/ml before treatment, 440.5 (255.9-685.2) ng/ml after chemotherapy, and 502.8 (307.2-851.4) ng/ml at disease progression. After chemotherapy, 87 (79.8%) patients had lower serum MMP9, with the median change of -286.3 (-607.3 to -70.2) ng/ml (P < 0.001). At disease progression, 47 (65.3%) patients had lower serum MMP9 compared to pretreatment values, with the median change of -163.7 (-466.6 to 108.6) ng/ml (P = 0.001). Patients with higher performance status had higher serum MMP9 before treatment (P = 0.010). Among investigated polymorphisms, only rs17576 was associated with serum MMP9 levels before treatment (P = 0.041). Conclusion: Median serum MMP9 levels differed significantly before and after treatment of MM, but failed to reach significance as a standalone biomarker. The contribution of MMP9 serum levels and MMP9 polymorphisms to a composite diagnostic and prognostic biomarker should be further tested.


Assuntos
Metaloproteinase 9 da Matriz/sangue , Mesotelioma/sangue , Neoplasias Peritoneais/sangue , Neoplasias Pleurais/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Eur J Vasc Endovasc Surg ; 57(6): 768-777, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31164272

RESUMO

OBJECTIVE: Neutrophil gelatinase associated lipocalin (NGAL) and matrix metalloproteinase (MMP)-9/NGAL complex were investigated in asymptomatic patients with carotid artery stenosis including gender specific differences aiming at vulnerable plaques prone to embolisation. METHODS: Serum NGAL and MMP-9/NGAL levels were analysed in 83 patients with asymptomatic carotid artery stenosis. Pre-operative ultrasound and post-endarterectomy histology of carotid atherosclerotic lesions were evaluated. RESULTS: Patients with vulnerable plaques, as determined by ultrasound (plaques with decreased echogenicity) and histological analysis (type VI according to the classification of the American Heart Association), displayed the highest levels of NGAL and MMP-9/NGAL complex (p = .0003 and p = .0078, respectively). Grade VI plaques were primarily detected in patients with "soft" plaques (12 type VI plaques in 25 patients), but also in patients with mixed (four of 19) and calcified (three of 39) plaques according to ultrasound. Higher grade carotid artery stenosis (≥90%) was not associated with elevated NGAL levels. The receiver operating characteristic curve analysis detecting grade VI lesions yields an area under the curve (AUC) = 0.85, with respect to soft plaque on ultrasound the AUC = 0.86. There were no gender specific differences in levels of NGAL 80.9 (37.7) ng/mL in women vs. 76.7 (36.3) ng/mL in men, p = .607) nor of MMP-9/NGAL 33.0 (18.2-55.5) ng/mL in women vs. 36.7 (20.2-54.0) ng/mL in men, p = .969. Likewise, there were no gender associated differences in vulnerable plaque characteristics: either for grade VI plaques (17.9% vs. 27.3%, p = .582) or for the presence of soft plaques as evaluated by ultrasound (35.9% vs. 25%, p = .503). CONCLUSION: Circulating NGAL and MMP-9/NGAL are significantly increased in asymptomatic patients with vulnerable carotid atherosclerotic plaques independent of gender. Accordingly, serum NGAL may be proposed as a valuable biomarker for the detection of unstable carotid plaques in asymptomatic patients, who can then be selected for early carotid endarterectomy or stenting.


Assuntos
Estenose das Carótidas/sangue , Lipocalina-2/sangue , Placa Aterosclerótica , Idoso , Doenças Assintomáticas , Biomarcadores/sangue , Biópsia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Risco , Ruptura Espontânea , Ultrassonografia Doppler Dupla , Regulação para Cima
11.
Int J Cardiovasc Imaging ; 35(11): 1971-1978, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31218524

RESUMO

Normalized optical density (NOD) measured by optical coherence tomography represents neointimal maturity after coronary stent implantation and is correlated with morphologic information provided by both light and electron microscopy. We aimed to test the hypothesis that even second generation drug-eluting stents (DESs) are problematic in terms of neointimal maturity. We implanted bare-metal stents (BMS: n = 14), everolimus-eluting stents (EESs: n = 15) or zotarolimus-eluting stents (ZESs: n = 12) at 41 sites in 32 patients with stable coronary artery disease. OCT was performed at up to 12 months of follow-up, and the average optical density of neointima covering struts was evaluated. NOD was calculated as the optical density of stent-strut covering tissue divided by the optical density of the struts. We also measured circulating CD34+ /CD133+ /CD45low cells, and serum levels of stromal cell-derived factor (SDF)-1, interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 at baseline and follow-up. NOD was lower in the EES (0.70 ± 0.06) group than in the BMS (0.76 ± 0.07, P < 0.05) and ZES (0.76 ± 0.06, P < 0.05) groups. The mean neointimal area (R = 0.33, P < 0.05) and mean neointimal thickness (R = 0.37, P < 0.05) were correlated with NOD. Although NOD was not correlated with percent changes in circulating endothelial progenitor cells, and the levels of SDF-1 and IL-8, it was negatively correlated with the change in MMP-9 level (R = - 0.51, P < 0.01). Neointimal maturity might be lower at EES sites than BMS or ZES sites. This might lead to impaired neointimal tissue growth and matrix degradation. These results suggest a specific pathophysiology after DES implantation.


Assuntos
Doença da Artéria Coronariana/terapia , Vasos Coronários/diagnóstico por imagem , Stents Farmacológicos , Neointima , Intervenção Coronária Percutânea/instrumentação , Tomografia de Coerência Óptica , Idoso , Idoso de 80 Anos ou mais , Fármacos Cardiovasculares/administração & dosagem , Quimiocina CXCL12/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/metabolismo , Vasos Coronários/fisiopatologia , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Everolimo/administração & dosagem , Feminino , Humanos , Interleucina-8/sangue , Masculino , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Desenho de Prótese , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Fatores de Tempo , Resultado do Tratamento , Remodelação Vascular
12.
Cell Mol Biol Lett ; 24: 43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236121

RESUMO

Background: Impairment of the blood-brain barrier (BBB) could result in secondary cerebral edema and life-threatening pancreatic encephalopathy in patients with severe acute pancreatitis (SAP). Mesenchymal stem cells (MSCs) have been widely adopted in clinical research because of their pleiotropic functions. The aim of this study was to investigate the impact of MSCs on BBB permeability in SAP and the potential mechanisms driving these effects. Methods: Sprague-Dawley rats were randomly assigned to the control, SAP and SAP+MSCs groups. Pancreatic impairment was assessed. The serum levels of amylase, TNF-α and IL-10, expression levels of claudin-5, Bax, Bcl-2 and MMP-9, and the BBB permeability were measured. Endothelial cell apoptosis was evaluated. Results: SAP rats showed BBB impairment with increased permeability and secondary cerebral edema, which was confirmed using the Evans blue assay and the calculation of the brain dry/wet ratio. Treatment with MSCs decreased the serum levels of amylase and TNF-α, increased the serum levels of IL-10, attenuated the apoptosis of brain microvascular endothelial cells, upregulated claudin-5 expression and downregulated MMP-9 expression. This treatment attenuated the increased BBB permeability in SAP rats. Conclusions: MSCs attenuated the impairment of the BBB and decreased its permeability, producing protective effects in SAP rats.


Assuntos
Barreira Hematoencefálica/metabolismo , Transplante de Células-Tronco Mesenquimais , Pancreatite/metabolismo , Pancreatite/terapia , Doença Aguda/terapia , Amilases/sangue , Animais , Apoptose , Claudina-5/sangue , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Interleucina-10/sangue , Masculino , Metaloproteinase 9 da Matriz/sangue , Pancreatite/sangue , Permeabilidade , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
13.
Immunopharmacol Immunotoxicol ; 41(2): 224-230, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31046512

RESUMO

Objective: The aim of this work was to compare matrix metalloproteinase-9 and -12, tissue inhibitor of metalloproteinase-1 and -4, and neutrophil elastase in exhaled breath condensate (EBC) and peripheral blood of patients with COPD. Methods: Peripheral blood and EBC samples from COPD patients and healthy donors were collected. In serum and EBC, MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 proteins were detected by ELISA. The mRNA expression levels of MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 in peripheral blood mononuclear cells (PBMCs) were analyzed by qRT-PCR. Results: The protein levels of MMP-9 (p=.034) and MMP-12 (p=.041) in the EBC of COPD smokers were higher than those of COPD never-smokers. The concentrations of TIMP-1 (p=.072) and TIMP-4 (p=.084) in the EBC of COPD smokers were higher than those of COPD never-smokers; however, the difference was not statistically significant. MMP-9 (r=-0.78, p<.0001) and TIMP-1 (r=-0.71, p<.0001) levels in EBC were significantly negatively correlated with pulmonary function FEV1%pred. The protein levels of MMP-12 (r=-0.37, p=.034) and TIMP-4 (r=-0.34, p=.041) were also negatively correlated with FEV1%pred. The expression of MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 in PBMCs and serum of COPD smokers were significantly higher than those of control never-smokers (p<.05). Conclusions: Exhaled MMP-9, MMP-12, TIMP-1, and TIMP-4 levels increased in stable COPD patients and were negatively correlated with FEV1%pred, which suggests the usefulness of their measurement in EBC for the monitoring of airway inflammation. However, to better assess their diagnostic or prognostic value, larger studies are necessary.


Assuntos
Expiração , Mediadores da Inflamação/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Idoso , Biomarcadores/sangue , Testes Respiratórios , Estudos Transversais , Feminino , Humanos , Masculino , Metaloproteinase 12 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidores Teciduais de Metaloproteinases/sangue
14.
BMC Pharmacol Toxicol ; 20(1): 23, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053170

RESUMO

BACKGROUND: The activation of neurohumoral compensatory mechanisms is a common physiological phenomenon in heart failure in order to make up for a failing heart, which will usually have a deteriorating effect on overall health condition. Many medications, such as neprilysin and angiotensin inhibitors, have recently been introduced to remediate neurohumoral changes. This study was conducted to evaluate the efficacy of the sacubitril-aliskiren combination versus the sacubitril-ramipril combination in the treatment of neurohumoral changes in rats with experimentally induced heart failure. METHOD: Thirty Wister rats were randomly assigned into five groups each of six rats, the first group was the control group. Intraperitoneal isoprenaline injections of 5 mg/kg/day for 1 week were used to induce experimental models of heart failure in rats of the rest of experimental groups. The second group served as a positive control. Rats in the third, fourth, and fifth groups received oral daily dose of sacubitril 30 mg/kg/day, sacubitril-aliskiren 30,10 mg/kg/day, and sacubitril-ramipril 30/10 mg/kg/day respectively, for 2 weeks. RESULTS: Induction of heart failure in rats has significantly increased circulating NT-proBNP (980 ± 116.71 pg/ml), MMP9 (15.85 ± 0.57 ng/ml), troponin-I (3.09 ± 0.147 ng/ml), CK-MB (31.55 ± 1.69 ng/ml), renin (736 ± 45.8 pg/ml), urea (52.1 ± 1.57 mg/dl), and creatinine (0.92 ± 0.04 mg/dl). Significant decreases in glomerular filtration rate (7.031 ± 1.6 ml/hr./kg), urine flow (0.2761 ± 0.06 ml/h/kg), total solute excretion (0.11 ± 0.03 meq/m), and mean blood pressure (83.5 ± 2.6 mm hg) were seen in rats with heart failure. Rats treated with sacubitril combined with aliskiren or ramipril showed a statistically significant reduction of NT-proBNP, MMP9, troponin serum urea, and serum creatinine. Sacubitril-aliskiren or sacubitril-ramipril administration produced a significant increase in renin plasma level, total solute excretion, urine flow, and glomerular filtration rate. CONCLUSION: Sacubitril in combination with aliskiren or with ramipril effectively reduced plasma cardiac biomarkers, such as CK-MB, MMP9, and NT-proBNP, in rats with heart failure. Both combinations showed significant remediation of renal function through increasing GFR, urine flow, and total solute excretion, as well as reducing plasma level of renin. Net results revealed that the sacubitril-aliskiren combination has similar remediating effects on neurohumoral changes compared to the sacubitril-ramipril combination.


Assuntos
Amidas/farmacologia , Aminobutiratos/farmacologia , Antagonistas de Receptores de Angiotensina/farmacologia , Creatina Quinase Forma MB/sangue , Fumaratos/farmacologia , Insuficiência Cardíaca/sangue , Metaloproteinase 9 da Matriz/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Ramipril/farmacologia , Tetrazóis/farmacologia , Angiotensinas/antagonistas & inibidores , Animais , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Combinação de Medicamentos , Feminino , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/fisiologia , Neprilisina/antagonistas & inibidores , Ratos Wistar , Renina/antagonistas & inibidores , Renina/sangue , Troponina I/sangue
15.
PLoS One ; 14(5): e0215825, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31042729

RESUMO

Although mother-to-child transmission of HIV has dramatically declined, the number of in utero HIV-exposed, uninfected infants is on the increase. HIV-exposed infants are at an increased risk of mortality, morbidity and slower early growth than their non-HIV exposed counterparts. Maternal HIV increases the risk of having preterm deliveries, intrauterine growth restriction and low birth weight babies. However, the mechanism underlying dysregulation of fetal growth in HIV-infected pregnant women is unknown. We sought to determine whether maternal HIV is associated with dysregulation of the insulin-like growth factor (IGF) axis, some angiogenic factors or other related biomarkers that regulate fetal growth. A total of 102 normotensive pregnant women were enrolled in a small cross-sectional study. Amongst these were thirty-one HIV-1 positive women receiving combination antiretroviral therapy (cART) (Mean age: 30.0 ± 5.1 years; % on ART: 83.9%; median plasma viral load: 683 copies/ml; median CD4 count: 350 cells/ul) and 71 HIV uninfected women (mean age: 27.3 ± 5.8) recruited at delivery. A panel of biomarkers including IGF1 and IGF binding proteins (IGFBP1, IGFBP3), angiopoietins (ANG) 1 and 2, matrix metalloproteinases (MMP) 2 and 9, and galectin 13, was measured in plasma collected from the placental intervillous space. The levels of IGF1, IGFBP1, ANG1, ANG2, MMP2, MMP9 and Gal-13 were not affected by maternal HIV, even when adjusted for maternal factors in linear regression models (all p>0.05). It was observed that HIV-infection in pregnancy did not significantly affect key markers of the IGF axis and angiogenic factors. If anything, it did not affect women. These findings highlight the importance of the use of ART during pregnancy, which maintains factors necessary for fetal development closer to those of healthy women. However, decrease in IGF1 levels might be exacerbated in women con-infected with HIV and malaria.


Assuntos
Angiopoietinas/sangue , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Fator de Crescimento Insulin-Like I/metabolismo , Adulto , Biomarcadores/sangue , Camarões , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Malária/complicações , Malária/diagnóstico , Metaloproteinase 9 da Matriz/sangue , Placenta/metabolismo , Placenta/patologia , Gravidez , Adulto Jovem
16.
Acta Cir Bras ; 34(4): e201900409, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31038586

RESUMO

PURPOSE: To analyze the preoperative serum matrix metalloproteinase-9 (MMP-9) levels and prognosis of patients with hilar cholangiocarcinoma (HC) undergoing radical resection. METHODS: Preoperative serum MMP-9 levels in patients with HC undergoing radical resection were detected by enzyme-linked immunosorbent assay (ELISA). The ROC curve assay was used to analyze the preoperative serum MMP-9 level to determine the most valuable cut-off point. The relationship between MMP-9 and clinicopathological features of HC patients was analyzed. Kaplan-Meier method was used to analyze the prognostic factors, and COX regression model was used to analyze the independent risk factors affecting prognosis. RESULTS: Preoperative serum MMP-9 levels were significantly elevated in the death patients compared with the survival patients. The most valuable cut-off point for preoperative serum MMP-9 for prognosis was 201.93 ng/mL. Preoperative serum MMP-9 was associated with Bismuth-Corlette classification) and lymph node metastasis. Kaplan-Meier analysis showed that MMP-9, Bismuth-Corlette classification, Lymph node metastasis, Portal vein invasion, Hepatic artery invasion, Liver invasion, Incised margin, and Preoperative biliary drainage were related to prognosis. Cox regression model confirmed that hepatic artery invasion, liver invasion, incised margin, and MMP-9 have the potential to independence predicate prognosis in HC patients. CONCLUSION: Preoperative serum MMP-9 has high predictive value for prognosis and is an independent influencing factor for the prognosis of patients with hilar cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares/sangue , Neoplasias dos Ductos Biliares/cirurgia , Tumor de Klatskin/sangue , Tumor de Klatskin/cirurgia , Metaloproteinase 9 da Matriz/sangue , Adulto , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Tumor de Klatskin/mortalidade , Tumor de Klatskin/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Período Pós-Operatório , Período Pré-Operatório , Prognóstico , Curva ROC , Valores de Referência , Fatores de Risco , Fatores de Tempo
17.
Horm Metab Res ; 51(6): 389-395, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31075797

RESUMO

The association between obesity and cardiovascular diseases has a multifactorial pathogenesis, including the synthesis of inflammatory molecules, the increase in oxidative stress and the dysregulation of the matrix metalloprotease (MMP) concentration and activity. In a group of adults with obesity, divided in 2 subgroups according to the body mass index (BMI), we examined lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), protein oxidation, expressed as protein carbonyl groups (PCs), plasma gelatinases (MMP-2 and MMP-9), and their tissue inhibitors (TIMP-1 and TIMP-2). In the whole group, as well as in the 2 subgroups (with BMI 30-35 or BMI>35) of obese subjects, we observed an increase in TBARS, PCs, MMP-2, and MMP-9, and also TIMP-1 and TIMP-2 in comparison with the control group. A positive correlation between TBARS and PCs emerged in obese subjects and persisted after dividing obese subjects according to BMI. The correlation between MMP-2 and TIMP-2 was not statistically significant, while a significant correlation was present between MMP-9 and TIMP-1. The correlations between the markers of oxidative stress (TBARS and PCs) and those of the MMP/TIMP profile indicated a more marked influence of protein oxidation on MMPs and TIMPs in comparison with TBARS. The innovative aspect of our study was the simultaneous evaluation of oxidative stress markers and MMP/TIMP profile in adult obese subjects. We observed significant alterations and correlations that may negatively influence the clinical course of the disease.


Assuntos
Peroxidação de Lipídeos , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Obesidade/fisiopatologia , Proteínas/química , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/sangue , Adulto , Biomarcadores/análise , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Oxirredução , Estresse Oxidativo , Proteólise
18.
Dis Markers ; 2019: 3136792, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31143300

RESUMO

The aim of this study was to assess the expression of MMP-9 and TIMP-1 in cancerous tissue as well as in the serum and plasma concentrations of these proteins in patients with laryngeal cancer and compare the results to the inflammatory reaction in healthy subjects. Twenty-seven patients who were diagnosed with laryngeal carcinoma and selected for total laryngectomy were included in the study group. MMP-9 and TIMP-1 expression in tissues was assessed using immunohistochemical assays. Immunoenzymatic ELISA methods were used to measure MMP-9 and TIMP-1 concentrations in serum and plasma. MMP-9 and TIMP-1 were identified in tumor cells and in the tumor stroma compartment, as well as in macroscopically healthy mucous membrane. MMP-9 expression was more significant in tumor stroma than in the perimatrix of the mucous membrane (p = 0.047). TIMP-1 expression was significantly higher in the matrix and perimatrix of the mucous membrane than in cancer tissue (p = 0.0093) and the tumor stroma compartment (p < 0.0001). Expression of TIMP-1 was observed more frequently in tumors without infiltrated lymph nodes (p = 0.009). Serum concentrations of MMP-9 and TIMP-1 as well as plasma TIMP-1 concentration were significantly higher in the study group than in the control group (p = 0.0004, p = 0.002, and p = 0.0001, respectively). A significantly higher TIMP-1 level in plasma was found in patients with poorly differentiated tumors compared to G1 and G2 (p = 0.046). MMP-9/TIMP-1 rate in serum was significantly higher in the study group than in the control group. The balance between the level of MMP-9 and TIMP-1 is disrupted in laryngeal cancer. The significant correlation between TIMP-1 expression and the presence of lymph node metastases, as well as that between TIMP-1 plasma concentration and stage of cancer histological differentiation, might indicate the importance of this molecule as a prognostic factor during carcinogenesis.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias Laríngeas/metabolismo , Metaloproteinase 9 da Matriz/genética , Inibidor Tecidual de Metaloproteinase-1/genética , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , Metástase Linfática , Masculino , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-1/metabolismo
19.
Zhongguo Zhong Yao Za Zhi ; 44(8): 1696-1703, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31090337

RESUMO

To study the effect of modified Buyang Huanwu Decoction on the hemorrhagic transformation after intravenous thrombolysis of recombinant tissue type plasminogen activator(rt-PA) in patients with super early(onset time<4. 5 h) cerebral infarction. From March 2016 to July 2018,at the brain disease zone of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,212 cases of super early cerebral infarction were selected and divided into two group according to the randomized complete blocks designs: control group(106 cases) and traditional Chinese medicine group(106 cases). The control group was treated with rt-PA intravenous thrombolysis,while the traditional Chinese medicine group was treated with modified Buyang Huanwu Decoction in addition to the therapy of the control group. Both groups were treated for 14 days. Neurological deficit score,serum matrix metalloproteinase-9(MMP-9),neuron specific enolase(NSE),vascular endothelial growth factor(VEGF) and plasma cellular fibronectin(c-FN) levels,the incidence of hemorrhagic transformation,clinical efficacy and adverse drug reactions before and after treatment were compared between the two groups. According to the findings,at the 14 thday after treatment,the rank sum test of the grade data showed that the clinical efficacy of the traditional Chinese medicine group was better than that of the control group(Z =-2. 033,P = 0. 042); on the basis of χ2 test,the total efficiency of the traditional Chinese medicine group was higher than that of the control group(χ2= 4. 895,P =0. 027); the hemorrhagic transformation rate of the traditional Chinese medicine group was lower than that of the control group within14 days of treatment(χ2= 3. 962,P = 0. 047). MMP-9 levels in the traditional Chinese medicine group were lower than those in the control group at the 3 rd,5 th,7 th,10 th,14 thd after treatment(t =-2. 474,-3. 022,-5. 163,-6. 998,-9. 821; P = 0. 014,0. 003,0,0,0). The improvement of c-FN,NSE,VEGF and NIHSS scores in the traditional Chinese medicine group was superior to that of the control group after 14 days of treatment(t =-2. 343,-3. 187,-2. 129,-3. 105; P = 0. 020,0. 002,0. 034,0. 002). No obvious adverse reactions of modified Buyang Huanwu Decoction were observed during 14 days of treatment. Modified Buyang Huanwu Decoction could reduce the expressions of MMP-9,c-FN,NSE and VEGF after rt-PA intravenous thrombolysis in patients with super early cerebral infarction,and decrease the hemorrhagic transformation rate after thrombolysis,with high safety.


Assuntos
Infarto Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Ativador de Plasminogênio Tecidual/uso terapêutico , Fibronectinas/sangue , Humanos , Metaloproteinase 9 da Matriz/sangue , Medicina Tradicional Chinesa , Fosfopiruvato Hidratase/sangue , Proteínas Recombinantes/uso terapêutico , Terapia Trombolítica , Fator A de Crescimento do Endotélio Vascular/sangue
20.
Biomolecules ; 9(4)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934954

RESUMO

We sought to investigate whether levels of matrix metalloproteinases (MMPs) and their inhibitors predict coronary atherosclerotic plaque instability, as assessed by intravascular ultrasound (IVUS) virtual histology during coronary angiography. Blood samples were collected before angiography in 32 subjects (mean age 56 ± 8 years) with stable coronary heart disease (CHD) and elevated lipoprotein(a) (Lp(a), 94 ± 35 mg/dL). Levels of high-sensitivity C-reactive protein (hsCRP), apolipoprotein B100 (apoB100), MMP-7, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 were determined using commercially available enzyme-linked immunosorbent assay kits. Results. The morphology of a total of sixty coronary lesions was assessed by virtual histology IVUS imaging. Eleven (18%) plaques in nine (28%) patients were classified as plaques with an unstable phenotype or a thin-cap fibroatheroma. Age, low-density lipoprotein cholesterol, apoB100, MMP-7, and MMP-9 levels were positively associated with necrotic core volume. Conversely, there was a negative relationship between MMP-7 and -9 levels and fibrous and fibro-fatty tissue volume. Multivariate regression analysis revealed that MMP-9 is a strong independent predictor of atherosclerotic plaque instability in stable CHD patients. In stable CHD patients with elevated Lp(a), MMP-9 levels are positively associated with the size of the necrotic core of coronary atherosclerotic plaques.


Assuntos
Angiografia Coronária , Doença das Coronárias/enzimologia , Lipoproteína(a)/sangue , Metaloproteinase 9 da Matriz/sangue , Placa Aterosclerótica/enzimologia , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Doença das Coronárias/sangue , Doença das Coronárias/metabolismo , Feminino , Humanos , Lipoproteína(a)/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/metabolismo , Software
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