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1.
Adv Clin Chem ; 91: 163-179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31331488

RESUMO

Pentraxin 3 (PTX3) is involved in vascular inflammation and endothelial dysfunction through various mechanisms. Until now, most studies confirmed an important link between PTX3 and endothelial dysfunction and identified several pathogenetic pathways. PTX3 modulates inflammatory cells, thus stimulating vascular inflammation. Within endothelial cells, it decreases nitric oxide (NO) synthesis, inhibits cell proliferation and alters their functions. PTX3 blocks the effect of fibroblast growth factor 2 (FGF2) by making a molecular complex with these molecules inactivating them. However, there are substances like the tumor necrosis factor-inducible gene 6 protein (TSG-6) that block the PTX3-FGF2 interaction. Interacting with P-selectin, it promotes vascular inflammatory response and endothelial dysfunction. PTX3 also increases the matrix metalloproteinases synthesis directly or by blocking NO synthesis. From a clinical point of view, PTX3 positively correlates with arterial hypertension, flow mediated dilation and, with intima media thickness. Therefore, the involvement of PTX3 in the pathogenesis and evaluation of endothelial dysfunction is clear, and it may become a biomarker in this direction, but further studies are needed to determine its reliability in this direction. Last but not least, PTX3 could become an effective therapeutic target for preventing this dysfunction, but further research needs to be conducted.


Assuntos
Aterosclerose/metabolismo , Proteína C-Reativa/metabolismo , Células Endoteliais/metabolismo , Inflamação/metabolismo , Componente Amiloide P Sérico/metabolismo , Aterosclerose/etiologia , Aterosclerose/patologia , Proteína C-Reativa/genética , Regulação da Expressão Gênica , Humanos , Componente Amiloide P Sérico/genética
2.
J Sci Food Agric ; 99(15): 6663-6670, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31259415

RESUMO

There is little evidence about whether eggs affect inflammation. The aim of this meta-analysis was to explore the effects of egg consumption on inflammation. A systematic search of online databases (Institute for Scientific Information (ISI), Scopus, Ovid, PubMed, Cochrane) was used to gather clinical trials that assessed the effect of egg consumption on circulating inflammatory biomarkers. Using a random-effects model, pooled weighted mean differences (WMD) and corresponding standard deviations (SD) were calculated. Of the 21 eligible studies found, nine trials were eligible for analysis. Eight trials assessed high-sensitivity C-reactive protein (hs-CRP), four trials assessed interleukin-6 (IL-6), and five trials assessed tumor necrosis factor-alpha (TNF-α). Egg consumption did not affect hs-CRP (WMD 0.24 mg/L; 95% CI: -0.43, 0.90; I2  = 53.8; P = 0.48), IL-6 (WMD 0.20 pg/mL; 95% CI: -0.71, 1.11; I2 = 69.3; P = 0.50), and TNF-α (WMD: -0.38 pg/mL; 95% CI: -0.87, 0.10; I2 = 0.00; P = 0.12) relative to controls. Overall, this meta-analysis revealed that egg consumption had no significant effect on serum biomarkers of inflammation in adults. © 2019 Society of Chemical Industry.


Assuntos
Biomarcadores/análise , Ovos/análise , Inflamação/dietoterapia , Adulto , Idoso , Animais , Proteína C-Reativa/genética , Proteína C-Reativa/imunologia , Galinhas , Feminino , Humanos , Inflamação/genética , Inflamação/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
3.
J Biol Regul Homeost Agents ; 33(3): 675-685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31189490

RESUMO

Endometrial cells undergo very specific changes associated with reproductive processes. Cells prepare for embryo development by increasing their volume. Then, if fertilization fails, endometrial cells are liable for apoptosis, preparing new cells that are ready for subsequent processes related to the possibility of embryo implantation and the development of pregnancy. PTX3 and TNFAIP6 are absent or reduced in cultured COCs, resulting in a functional change in COC in vitro. In this work, we want to check how PTX3, HAS2 and TNFAIP6 behave in luminal epithelium primary cell culture. Cells obtained during slaughter from porcine specimens were cultured primarily in vitro for 7 days. Their proliferation patterns were then analysed using RTCA, with the expression of genes of interest evaluated with the use of immunofluorescence and RT-qPCR. The results of these changes in the expression of the genes of interest were analysed on each of the seven days of the porcine luminal primary cell culture. Our study showed the increased level of PTX3, HAS2 and TN¬FAIP6 expression at the same hours of primary culture. Rt-qPCR showed a higher level of expression of the PTX3 gene in the first 72 h, at the end of the lag phase (in the phase of stasis in which the cells adapt to the new environment and often die). In contrast, TNFAIP6 expression increases about 96 hours when the cells are in the full log phase (logarithmic phase growth) and continue this trend in the plateau phase. We did not observe such drastic changes in the HAS2 expression pattern, which leads us to hypothesize that PTX3 and TNFAIP6 are designed to maintain a constant level of HAS2 in the cell throughout its lifetime. The obtained results could become a point of reference for further in vivo and clinical research.


Assuntos
Proteína C-Reativa/genética , Moléculas de Adesão Celular/genética , Endométrio/citologia , Células Epiteliais/citologia , Hialuronan Sintases/genética , Componente Amiloide P Sérico/genética , Animais , Proliferação de Células , Feminino , Cultura Primária de Células , Suínos
4.
DNA Cell Biol ; 38(7): 688-699, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31188028

RESUMO

This study was aimed to identify hub genes associated with the development of glioblastoma (GBM) by conducting a bioinformatic analysis. The raw gene expression data were downloaded from the Gene Expression Omnibus database and The Cancer Genome Atlas project. After the differentially expressed genes (DEGs) were identified, the functional enrichment analysis of DEGs was conducted. Subsequently, the protein-protein interaction (PPI) network, molecular complex detection clusters, and transcriptional factor (TF)-miRNA-target regulatory network were constructed, respectively. Furthermore, the survival analysis of prognostic outcomes and genes was analyzed. In addition, the expression of key genes was validated by quantitative real-time PCR (qRT-PCR) analysis. A total of 884 DEGs, including 418 upregulated and downregulated genes, were identified between GBM and normal samples. The PPI network comprised a set of 3418 pairs involving 751 nodes, and AKT1 and CDK2 were the critical genes in the network. A total of seven clusters were identified, the genes in which were intensively associated with cell cycle, cholinergic synapse, and extracellular matrix (ECM)-receptor interaction. qRT-PCR analysis indicated that AKT1 and CDK2 were significantly upregulated, and NRXN3 and NPTX2 were significantly downregulated in GBM samples. The TF-miRNA-target regulatory networks were built, in which CCNB1, RFC5, microRNA524, and microRNA34b were key regulators. There were 43 genes, including NPTX2 and NRXN3, significantly related to the prognostic outcomes of GBM patients. These crucial genes might be promising options for GBM treatment.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , MicroRNAs/genética , Transcriptoma , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Células Cultivadas , Ciclina B1/genética , Ciclina B1/metabolismo , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína de Replicação C/genética , Proteína de Replicação C/metabolismo
5.
Gene ; 710: 145-147, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31141720

RESUMO

AIM: The present study was conducted to analyze the relationship between c-reactive protein (CRP) gene +1444C/T, 3407T/C (rs2808630) polymorphisms and colorectal cancer susceptibility. METHODS: A total of 142 colorectal cancer patients and 127 healthy controls were recruited into this case-control study. The genotypes of CRP gene +1444C/T, rs2808630 polymorphisms were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the genotypes distributions of polymorphisms in controls was assessed whether conformed to Hardy-Weinberg equilibrium (HWE). The calculation of odds ratio (OR) with its 95% confidence interval (95% CI) is used for evaluating the association strength of gene polymorphism and disease. RESULTS: Through the testing of χ2, the genotypes distributions were consistent with HWE in the control group. We identified that only CC genotype frequency in CRP rs2808630 had a significant difference in cases and controls (P = 0.03) and people who carried CC genotype had a low risk suffering from colorectal cancer, compared with TT genotype carriers (OR = 0.35, 95% CI = 0.14-0.90). However, the other genotypes in rs2808630 and even the genotypes CRP +1444C/T polymorphism were all not associated with the generation of colorectal cancer. CONCLUSION: CRP rs2808630 polymorphism was related to the decreased risk of colorectal cancer, but not +1444C/T polymorphism.


Assuntos
Proteína C-Reativa/genética , Neoplasias Colorretais/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo Genético , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
6.
Inflamm Res ; 68(5): 347-349, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30903199

RESUMO

OBJECTIVE: CRP gene polymorphism is common in inflammatory diseases, but such association has not been reported in periodontitis. Our objective was to interrogate SNPs of crp in chronic periodontitis in a case-control manner. METHODS: DNAs were extracted from mouthwash samples of 116 volunteers using salting-out method. Selected 12 5'UTR SNPs of crp were genotyped using ARMS-PCR. RESULTS: TC genotype of - 757T > C polymorphism (rs3093059) showed protective association (OR- 0.29, 95%CI-0.12-0.68, and p-0.004), and wild type - 757TT showed susceptible association with a p value of 0.008 (OR-3.09, 95%CI-1.33-7.15). CONCLUSION: The observation of protective and susceptible association of crp - 757T > C polymorphism may be useful for better management and prophylaxis of periodontitis.


Assuntos
Proteína C-Reativa/genética , Periodontite Crônica/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Índia , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único
7.
Anticancer Res ; 39(3): 1287-1292, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842160

RESUMO

Independently of tumour and treatment modulation, the host immune response status plays an important role in the clinical outcome of patients with cancer. The influence of single nucleotide polymorphisms (SNPs) and adjuvant radiotherapy (RT) on the systemic immune response status of patients with breast cancer was investigated. MATERIALS AND METHODS: Eighty-six female patients recovering from breast cancer surgery were investigated. As a control cohort, 82 healthy female blood donors were used. Blood-based SNPs, plasma C-reactive protein (CRP), cytokines and chemokines were analyzed for this purpose. RESULTS: Independently of tumour stage and hormone receptor status, dysregulation of plasma CRP, chemokine (C-C motif) ligand 4 (CCL4) and interleukin 2 (IL2), but not CCL5, CCL2, platelet-derived growth factor, IL6, IL10, IL12, interferon-gamma or tumour necrosis factor alpha were detected in the patients when compared to controls. The extent of alteration in plasma levels of CRP and IL2 patients was significantly associated with SNPs in CRP rs1800947 and IL2 rs6822844, respectively. These SNPs had no influence on the levels of corresponding plasma biomarkers in the healthy controls. Adjuvant RT reduced plasma CRP and CCL5 levels in patients with regards to CRP rs1800947CC, CCL5 rs2107538GG and CCL5 rs2280789AA sequences. CONCLUSION: Dysregulation of immune responses, as indicated by plasma levels of CRP, CCL4 and IL2 were found in patients with breast cancer despite the removal of the tumour mass. The benefit of adjuvant RT, as indicated by reduced plasma amounts of inflammatory protein CRP and chemokine CCL5 were based on the SNPs of the patients. Analyses of blood-based SNPs, plasma CRP, IL2 and CCL5 are low cost, rapid and can be carried out using general laboratory facilities while requiring only a peripheral blood sample. The possibility of using these blood-based biomarkers as an indicator of patient immune status for selection of individual patient treatment warrants further investigation.


Assuntos
Neoplasias da Mama , Proteína C-Reativa/análise , Citocinas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Proteína C-Reativa/genética , Citocinas/genética , Feminino , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Radioterapia Adjuvante
8.
Biomed Res Int ; 2019: 3793840, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863777

RESUMO

Background: The safety of cervical rotatory manipulation (CRM) is still controversial, especially in patients with carotid artery atherosclerosis (CAS). The study aimed to investigate the effects of CRM on carotid plaques in vulnerability. Methods: 50 rabbits were randomly divided into four groups: model rabbits with CRM [CAS-CRM (n=15)]; model rabbits without CRM [CAS (n=15)]; normal rabbits with CRM [Normal-CRM (n=10)]; and Blank-control group (n=10). CAS disease models were induced by carotid artery balloon injury combined with a high-fat diet for 12 weeks. Then, CRM technique was performed in CAS-CRM and Normal-CRM groups for 3 weeks. In the end, determination of serum level of hs-CRP and Lp-PLA2, histological analysis under HE and Masson trichromic staining, and immunohistochemical analysis with CD34 and CD68 antibody were completed in order. Results: Carotid stenosis rates on successful model rabbits ranged from 70% to 98%. The CAS-CRM group had an increased level of hs-CRP (P<0.05), in comparison with the CAS group, whereas effects were not significant between the Normal-CRM group and Blank-control group. In comparison with the CAS group, the positive expression of CD34 and CD68 in the CAS-CRM group increased significantly (P<0.05). Conclusion: CRM therapy may increase the vulnerability of carotid plaque in rabbits with severe CAS.


Assuntos
Oclusão com Balão/efeitos adversos , Proteína C-Reativa/genética , Doenças das Artérias Carótidas/cirurgia , Manipulação da Coluna/efeitos adversos , Placa Aterosclerótica/cirurgia , Animais , Antígenos CD34/genética , Proteína C-Reativa/metabolismo , Artérias Carótidas/metabolismo , Artérias Carótidas/fisiopatologia , Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/fisiopatologia , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/fisiopatologia , Lesões das Artérias Carótidas/cirurgia , Dieta Hiperlipídica , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Humanos , Placa Aterosclerótica/sangue , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/fisiopatologia , Coelhos
9.
Rev Soc Bras Med Trop ; 52: e20180455, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30810658

RESUMO

INTRODUCTION: The present study investigated the association of the rs2794521 polymorphism in the CRP gene in individuals with chronic hepatitis B and C, correlating it with markers of hepatic inflammation, fibrosis scores, viral load, and plasma protein levels. METHODS: The study analyzed 185 blood samples obtained from patients with hepatitis B (n=74) and hepatitis C (n=111) and 300 samples from healthy donors. Genotyping was performed by real-time polymerase chain reaction, and protein levels were quantified using the automated immunoturbidimetric method. RESULTS: The TT genotype was the most frequent in all studied groups and was associated with higher plasma levels of the protein but not with the progression of liver disease. Low levels of C-reactive protein were associated with increased viremia and scores indicative of severe fibrosis and cirrhosis. CONCLUSIONS: The present results demonstrated a close relationship between the ability of the virus to replicate and cause liver damage and low serum concentrations of C-reactive protein. Future research may determine if these results can be interpreted as a possible form of escape for the virus by decreasing its action as an opsonin and decreasing phagocytosis, which are functions of C-reactive protein in the immune response.


Assuntos
Proteína C-Reativa/análise , Hepatite B Crônica/sangue , Hepatite C Crônica/sangue , Cirrose Hepática/virologia , Biomarcadores/sangue , Proteína C-Reativa/genética , Estudos de Casos e Controles , Estudos Transversais , Feminino , Genótipo , Hepatite B Crônica/genética , Hepatite C Crônica/genética , Humanos , Cirrose Hepática/sangue , Masculino , Índice de Gravidade de Doença , Carga Viral
10.
Toxicol In Vitro ; 56: 10-18, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30599190

RESUMO

Leishmaniasis is one of the most important parasitic diseases after malaria. The standard treatment of leishmaniasis includes pentavalent antimonials (SbV); however, these drugs are associated with serious adverse effects. There have been very few studies pertaining to their side effects and mechanism of action in the fetus. This investigation examines the effects of meglumine antimoniate (MA) on the survival rate, angiogenesis and cellular apoptosis in the human umbilical vein endothelial cells (HUVECs). HUVECs were treated with varying doses of MA (100-800 µg/ml) for 24, 48 and 72 h and the survival rate was studied by colorimetric assay, flow cytometry, immunocytochemistry, migration (scratch) assay and tube formation assay. The results of quantitative real-time PCR (qPCR) studies indicated that the most important genes involved in presenting angiogenesis included VEGF and its receptors (Kdr and Flt-1), NP1 and Hif-1α genes including the anti-apoptotic gene of Bcl2, were significantly reduced compared to the control group (p < 0.05). In contrast, the most leading genes involved in the phenomenon of apoptosis were P53, Bax, Bak, Apaf-1 and caspases 3, 8 and 9, which were significantly up regulated compared to the control group (p < 0.05).


Assuntos
Antiprotozoários/toxicidade , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Antimoniato de Meglumina/toxicidade , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteína C-Reativa/genética , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neovascularização Fisiológica/efeitos dos fármacos , Proteínas do Tecido Nervoso/genética , Proteína Supressora de Tumor p53/genética , Fator A de Crescimento do Endotélio Vascular/genética
11.
Adv Med Sci ; 64(1): 85-89, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30572222

RESUMO

PURPOSE: Pentraxin 3 (PTX-3) is an acute phase protein that belongs to the pentraxin superfamily. It is synthesized locally at the site of inflammation and its levels are related to the damage of blood vessels. There are only a few studies examining the relationship between PTX-3 and chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the serum levels of PTX-3 and relative PTX-3 gene expression in COPD patients and their correlations with cigarette smoking history and lung function. MATERIALS/METHODS: A total number of 34 participants were enrolled into this study. Only stable patients without comorbidities were recruited. After obtaining written informed consent all planned procedures were performed (pre- and post-bronchodilator spirometry, blood samples for PTX-3 serum levels and PTX-3 gene expression measurements, demographical data, medical history, COPD patients were also asked for CAT and MMRC questionnaires). RESULTS: PTX-3 serum levels were significantly higher in the COPD group (29.22 (5.47) ng/ml vs. 14.64 (3.64) ng/ml). PTX-3 gene relative quantification (RQ) values were also significantly higher in the COPD group (0.15 (1.33) vs. -2.80 (1.99)). No differences in CRP serum levels were found between the control group and the COPD group. CONCLUSIONS: Our study demonstrates that serum levels of PTX-3 and the relative expression values of its gene are elevated in COPD, and can be related to cigarette smoking history.


Assuntos
Proteína C-Reativa/genética , Regulação da Expressão Gênica , Doença Pulmonar Obstrutiva Crônica/sangue , Componente Amiloide P Sérico/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/sangue , Fumar/genética
12.
In Vivo ; 33(1): 31-40, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30587599

RESUMO

BACKGROUND/AIM: Gestational diabetes mellitus (GDM) is a common pregnancy complication, characterized by insulin resistance and low-grade systemic inflammation with a pro-inflammatory immune system response. Our objective was to study the peripheral Th1, Th2, Th17 and Treg response in GDM compared to normal pregnancy. MATERIALS AND METHODS: Th1, Th2, Th17 and Treg subsets was determined by flow cytometry based on staining for specific intracellular cytokines, as well as C-reactive protein (CRP) and total IgE circulating levels. The health status of all offspring was also assessed 6 months post-delivery. RESULTS: A total of 49 Caucasian adult pregnant women were enrolled into a GDM (n=26) and Control (n=23) group. At the third trimester of pregnancy, the GDM group had a higher proportion of Th2, Th17 and Treg cells compared to control. Contrary to the control group, the GDM group exhibited no significant change in the Th1/Th2/Th17/Treg profile postpartum. Furthermore, higher circulating CRP and total IgE levels were noted in the GDM group compared to controls. At the 6-month post-delivery assessment, 30.8% of the offspring from the GDM group were found to have developed atopic dermatitis, food allergy or allergic proctocolitis compared to none from the control group. CONCLUSION: Compared to an uncomplicated pregnancy, GDM exhibits a significantly different peripheral T-cell profile at the third pregnancy trimester characterized by higher proportion of Th2, Th17 and Treg cells which persist six months post-delivery, while the increased high sensitivity CRP (hsCRP) levels stressed the low-grade inflammatory profile of this disease.


Assuntos
Proteína C-Reativa/genética , Diabetes Gestacional/imunologia , Sistema Imunitário , Linfócitos T/imunologia , Adulto , Citocinas , Diabetes Gestacional/genética , Diabetes Gestacional/patologia , Feminino , Citometria de Fluxo , Humanos , Gravidez , Linfócitos T/classificação , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia
13.
Lipids Health Dis ; 17(1): 173, 2018 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-30049280

RESUMO

BACKGROUND: Hypercholesterolemia is a well-established risk factor for cardiac damage, which can lead to cardiovascular diseases. Many studies have shown that thymoquinone protected rats from doxorubicin-induced cardiotoxicity and cardiac damage. The aim of this study was to investigate the possible protective effects of thymoquinone against cardiac damage in apolipoprotein E knockout (ApoE-/-) mice. METHODS: Eight-week-old male ApoE-/- mice were randomly divided into three groups: control group fed a normal diet (ND group), a high cholesterol diet (HD group) or HD mixed with thymoquinone (HD + TQ group). All groups were fed the different diets for 8 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at - 80 °C until used. Coronal sections of heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the heart tissues was snap-frozen in liquid nitrogen for mRNA or immunohistochemical analysis. RESULTS: The metabolic characteristics of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-sensitivity C-reactive protein (hs-CRP) were lower in ApoE-/-HD + TQ mice than in ApoE-/- HD mice. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) gene and protein expression was lower in the heart tissue of ApoE-/-HD + TQ mice than in those of ApoE-/-HD mice. Furthermore, the levels of macrophages and pro-inflammatory cytokines were lower in the cardiac tissues of ApoE-/-HD + TQ mice than in those of ApoE-/-HD mice. CONCLUSIONS: These results indicate that thymoquinone may provide a potential therapeutic target for cardiac damage caused by hypercholesterolemia.


Assuntos
Anticolesterolemiantes/farmacologia , Apolipoproteínas E/deficiência , Aterosclerose/tratamento farmacológico , Benzoquinonas/farmacologia , Cardiotônicos/farmacologia , Hipercolesterolemia/tratamento farmacológico , Miocárdio/metabolismo , Animais , Apolipoproteínas E/genética , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta Hiperlipídica , Regulação da Expressão Gênica , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Interleucina-6/genética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Knockout , Miocárdio/patologia , Receptores Depuradores Classe E/sangue , Receptores Depuradores Classe E/genética , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética
14.
Cell Physiol Biochem ; 48(2): 741-752, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30025407

RESUMO

BACKGROUND/AIMS: C reactive protein (CRP) levels are elevated in many diseases, including malignant tumors and cardiovascular disorders. In this study, the protein interaction network for CRP was evaluated to determine the importance of CRP and its interacting proteins in the molecular pathogenesis of hepatocellular carcinoma (HCC). METHODS: Isobaric tags for relative and absolute quantitation (iTRAQ) and mass spectrometry were used to identify CRP interacting proteins in SMMC7721 cells. Moreover, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to evaluate enriched genes and pathways for differentially expressed genes using DAVID and WebGestalt. Co-immunoprecipitation and western blot analyses were employed to assess interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1. RESULTS: In total, 52 proteins that interact with CRP were identified. A GO analysis suggested that most of the interacting proteins were involved in CRP complexes and regulated metabolic processes. A KEGG pathway analysis suggested that most CRP-interacting proteins contribute to the TRAIL signaling pathway, Class I PI3K/Akt signaling pathway, plasma membrane estrogen receptor signaling, Nectin adhesion pathway, and S1P1 pathway. Immunoprecipitation and western blot analyses revealed interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1. CONCLUSIONS: iTRAQ based proteomic profiling revealed the network of CRP interacting proteins. This network may activate the PI3K/Akt signaling pathway, thereby contributing to the pathogenesis of HCC.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteômica , Anexina A2/metabolismo , Proteína C-Reativa/antagonistas & inibidores , Proteína C-Reativa/genética , Carcinoma Hepatocelular/metabolismo , Perfilação da Expressão Gênica , Humanos , Queratina-8/metabolismo , Neoplasias Hepáticas/metabolismo , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Nectinas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Mapas de Interação de Proteínas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
15.
Reprod Biol Endocrinol ; 16(1): 69, 2018 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-30031399

RESUMO

BACKGROUND: In an article published in 2017, we discussed the results of the first part of our study into the morphokinetic development of embryos in relation to follicle diameter and homogeneity of follicular development. Our findings showed that embryos coming from small follicles in heterogeneous cycles had significantly higher rates of arrest or failure to reach blastocyst than embryos coming from large follicles in homogenous cycles. The aim of this further study was to investigate the relationship between follicular size and gene expression of cumulus cells (CCs) and evaluate whether gene expression could be an indicator of embryo development. METHODS: This study was based on 2495 COCs from 184 patients. CC expressions of five genes (TNFAIP6, PTGS2, HAS2, PTX3 and GDF9) were studied by generalized linear mixed models (GLMMs) regarding follicular size. CC expressions were then separately analysed regarding patient-specific variables (age, BMI, AMH and follicular size) in relation to embryos reaching blastocyst (eRB) or top or good quality blastocysts (TQ + GQ) using GLMMs with logit link. RESULTS: Follicular size significantly correlated with the potential of an oocyte to develop into a blastocyst: oocytes developing from large follicles were more than twice as likely to develop into an eRB than oocytes from small follicles (p < 0.001). Gene expression of HAS2 and GDF9 correlated with blastocyst quality when separately evaluated with follicular size and the patient specific variables of age, BMI and AMH. However, no such correlation was found in other gene expressions studied. CONCLUSIONS: Our findings suggest that differences in the expression of genes studied could be related to follicular size rather than to embryo quality. Although gene expression of HAS2 and GDF9 correlated with blastocyst quality, the only variable correlating with eRB and TQ and GQ blastocysts for each of these five models was follicular size. TRIAL REGISTRATION: This prospective cohort study was registered at clinicaltrials.gov (NCT02230449).


Assuntos
Células do Cúmulo/metabolismo , Desenvolvimento Embrionário/genética , Expressão Gênica , Folículo Ovariano/anatomia & histologia , Adulto , Fatores Etários , Hormônio Antimülleriano/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Estudos de Coortes , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Feminino , Fator 9 de Diferenciação de Crescimento/genética , Fator 9 de Diferenciação de Crescimento/metabolismo , Humanos , Hialuronan Sintases/genética , Hialuronan Sintases/metabolismo , Oócitos/citologia , Oócitos/crescimento & desenvolvimento , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/metabolismo , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/metabolismo
16.
Biomed Res Int ; 2018: 8535091, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854799

RESUMO

This study aimed to investigate the characteristics of Chinese patients with Behçet disease (BD) and myelodysplastic syndrome (MDS) and explore the role played by trisomy 8. This was a retrospective study of patients with BD and MDS from the Shanghai Behçet's disease database who were diagnosed between October 2012 and July 2017. There were 805 patients with BD and 16 also had MDS. Trisomy 8 was examined in patients with BD-MDS and some patients with gastrointestinal (GI) BD. Patients with BD and MDS (16/805; 2%) were more likely to be female and older; display fever and intestinal lesions; have lower leukocyte count, hemoglobin, platelet count; and show higher C-reactive protein and erythrocyte sedimentation rate (ESR) than patients with BD without MDS (all P < 0.05). Trisomy 8 was common (81.3%) in patients with BD-MDS. Ulcers in the ileocecal region were more frequently seen in intestinal patients with BD-MDS than in BD without MDS (90.0% versus 48.9%; P = 0.032). GI ulceration is common in patients with BD-MDS. Cytogenetic aberrations, especially trisomy 8, may play a role in the pathogenesis of intestinal involvement in patients with BD-MDS.


Assuntos
Síndrome de Behçet/genética , Síndromes Mielodisplásicas/genética , Trissomia/genética , Úlcera/genética , Adulto , Idoso , Síndrome de Behçet/complicações , Síndrome de Behçet/epidemiologia , Síndrome de Behçet/patologia , Sedimentação Sanguínea , Proteína C-Reativa/genética , China/epidemiologia , Aberrações Cromossômicas , Cromossomos Humanos Par 8/genética , Feminino , Gastroenteropatias/complicações , Gastroenteropatias/genética , Gastroenteropatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/patologia , Trissomia/patologia , Úlcera/complicações , Úlcera/patologia
17.
PLoS One ; 13(5): e0198375, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29851992

RESUMO

The conformational conversion of pentameric C-reactive protein (pCRP) to monomeric CRP (mCRP) has been shown to play important roles in the action of CRP in inflammation regulation. In vivo studies revealed the origin of mCRP and provided insights into how pCRP dissociation affected its functions. However, the interplay and exact bioactivities of CRP isoforms still remain uncertain due to the rapid conformational conversion and complex milieu in vivo. Herein, we have used surface-immobilization of pCRP to generate a preservable intermediate with dual antigenicity expression of both pCRP and mCRP. The intermediate has been further shown to exhibit modified bioactivities, such as a high affinity with solution-phase pCRP and an enhanced capacity of complement interaction. These results thus not only provide the conformational conversion details of CRP, but also propose a simple way in vitro to study how the functions of CRP are tuned by distinct isoforms.


Assuntos
Proteína C-Reativa/química , Proteína C-Reativa/metabolismo , Proteínas Imobilizadas/química , Proteínas Imobilizadas/metabolismo , Proteína C-Reativa/genética , Proteína C-Reativa/imunologia , Regulação da Expressão Gênica , Humanos , Proteínas Imobilizadas/genética , Proteínas Imobilizadas/imunologia , Inflamação/metabolismo , Modelos Moleculares , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Multimerização Proteica , Estrutura Quaternária de Proteína
18.
Dev Comp Immunol ; 87: 1-11, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29777721

RESUMO

Pentraxins are fluid phase pattern recognition molecules that form an important part of the innate immune defence and are conserved between fish and human. In Atlantic cod (Gadus morhua L.), two pentraxin-like proteins have been described, CRP-I and CRP-II. Here we show for the first time that these two CRP forms are post-translationally deiminated (an irreversible conversion of arginine to citrulline) and differ with respect to tissue specific localisation in cod ontogeny from 3 to 84 days post hatching. While both forms are expressed in liver, albeit at temporally differing levels, CRP-I shows a strong association with nervous tissue while CRP-II is strongly associated to mucosal tissues of gut and skin. This indicates differing roles for the two pentraxin types in immune responses and tissue remodelling, also elucidating novel roles for CRP-I in the nervous system. The presence of deimination positive bands for cod CRPs varied somewhat between mucus and serum, possibly facilitating CRP protein moonlighting, allowing the same protein to exhibit a range of biological functions and thus meeting different functional requirements in different tissues. The presented findings may further current understanding of the diverse roles of pentraxins in teleost immune defences and tissue remodelling, as well as in various human pathologies, including autoimmune diseases, amyloidosis and cancer.


Assuntos
Proteína C-Reativa/imunologia , Proteínas de Peixes/imunologia , Gadus morhua/imunologia , Animais , Arginina/genética , Arginina/imunologia , Arginina/metabolismo , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Citrulina/genética , Citrulina/imunologia , Citrulina/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Gadus morhua/genética , Gadus morhua/metabolismo , Humanos , Membrana Mucosa/imunologia , Membrana Mucosa/metabolismo , Tecido Nervoso/imunologia , Tecido Nervoso/metabolismo , Especificidade de Órgãos/genética , Especificidade de Órgãos/imunologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional/imunologia
19.
Cell Physiol Biochem ; 47(1): 266-278, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29768263

RESUMO

BACKGROUND/AIMS: Atherosclerosis is a chronic inflammatory disease in the artery walls. Fibrinopeptide A (FPA) is a biomarker of the activation of coagulation system, and a high concentration of FPA in blood occurs in patients with ischemic heart disease etc. However, there exist few studies on the pathological effects of FPA in cardiovascular system. Therefore, the present study examined the effect of FPA on CRP expression in VSMCs and the molecular mechanisms. METHODS: mRNA and protein expression was identified by quantitative real-time PCR and Western blot, respectively. Reactive oxygen species (ROS) and the immunofluorescence staining were observed by a fluorescence microscope. Plasma FPA and CRP level was determined by ELISA. RESULTS: FPA induced the expressions of CRP, IL-1ß and IL-6 in VSMCs, and anti-IL-1ß and anti-IL-6 neutralizing antibodies partially reduced FPA-induced CRP expression in VSMCs. The subchronic administration of FPA to rats increased FPA level in plasma and CRP expression in the aortic artery walls. The further studies showed that FPA promoted superoxide anion generation in VSMCs. Antioxidant NAC antagonized FPA-stimulated superoxide anion generation and inhibited FPA-induced CRP expression in VSMCs. FPA activated ERK1/2 and p38 phosphorylation, and PD98059 and SB203580 reduced FPA-induced CRP expression. Moreover, NAC inhibited the activation of ERK1/2 and p38. In addition, FPA enhanced NF-κB level in the nuclei of VSMCs, and PDTC reduced FPA-induced expression of CRP. CONCLUSIONS: FPA induces CRP expression in VSMCs via ROS-ERK1/2/p38-NF-κB signal pathway. This finding for the first time provides an experimental evidence for pro-inflammatory effect of FPA.


Assuntos
Proteína C-Reativa/genética , Fibrinopeptídeo A/imunologia , Músculo Liso Vascular/citologia , NF-kappa B/imunologia , Espécies Reativas de Oxigênio/imunologia , Transdução de Sinais , Regulação para Cima , Animais , Células Cultivadas , Sistema de Sinalização das MAP Quinases , Masculino , Músculo Liso Vascular/imunologia , Músculo Liso Vascular/metabolismo , RNA Mensageiro/genética , Ratos Sprague-Dawley
20.
Inflammation ; 41(4): 1477-1487, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29687414

RESUMO

Arterial macrophages comprise a heterogeneous population: pro-inflammatory (M1) and anti-inflammatory (M2). Since C-reactive protein (CRP) is produced by macrophages in atherosclerotic lesions, understanding of CRP regulation in macrophages could be crucial to decipher inflammatory patterns in atherogenesis. We aimed to analyze CRP expression in M1/M2 macrophages and to question whether it involves NFκB signaling pathway. Furthermore, we questioned whether oxidative stress affect macrophage phenotype and modulate macrophage CRP expression. M1/M2 macrophage polarization was validated using THP-1 macrophages. CRP mRNA and protein expression were determined using real-time PCR and immunohistochemistry. Involvement of NFκB was determined by nuclear translocation of p50 subunit and the use of NFκB inhibitor. Involvement of oxidative stress in macrophage phenotypes induction was studied using oxidized-LDL (Ox-LDL) and antioxidants. M1 macrophages were characterized by elevated CRP mRNA expression (by 67%), CRP protein levels (by 108%), and upregulation of NFκB activation compared to control, but these features were not shared by M2 macrophages. Macrophages incubation with Ox-LDL led to a moderate M1 phenotype combined with a M2 phenotype, correlated with increased CRP mRNA expression. Antioxidants inhibited by up to 86% IL6 expression but did not significantly affect IL10 secretion. Antioxidants significantly inhibited CRP expression in M1 macrophages, but not in M2 macrophages. Elevated expression of CRP was characteristic of M1 macrophages rather than M2 through NFκB activation. Oxidative stress could be one of the endogenous triggers for macrophage activation to a mixed M1 and M2 phenotype, in association with increased expression of CRP.


Assuntos
Proteína C-Reativa/metabolismo , Macrófagos/imunologia , NF-kappa B/metabolismo , Aterosclerose/patologia , Proteína C-Reativa/genética , Humanos , Inflamação , Lipoproteínas LDL/imunologia , Macrófagos/metabolismo , Estresse Oxidativo , Células THP-1 , Regulação para Cima
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