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1.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(5): 637-643, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33210493

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disease of child-bearing period women and one of the main causes of infertility in women. Pentraxin 3 (PTX3) is a multifunctional protein with a series of biological activities. PTX3 participates in the regulation of insulin secretion and glucose metabolism, ovarian cumulus cell function, inflammatory factor activity, androgen metabolism, lipid absorption and transport, and endothelial cell function, thereby improving insulin resistance, promoting follicular development and ovulation, reducing chronic inflammation, inhibiting androgen levels, improving lipid metabolism abnormalities and preventing atherosclerosis and cardiovascular diseases, thus participating in the occurrence of PCOS and its complications. This article reviews the mechanism of PTX3 in PCOS and its complications, trying to provide new ideas and directions for the study of PCOS pathogenesis and its clinical diagnosis and treatment.


Assuntos
Proteína C-Reativa , Síndrome do Ovário Policístico , Componente Amiloide P Sérico , Proteína C-Reativa/metabolismo , Criança , Feminino , Humanos , Resistência à Insulina , Síndrome do Ovário Policístico/fisiopatologia , Componente Amiloide P Sérico/metabolismo
2.
Gene ; 762: 145056, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32805313

RESUMO

BACKGROUND: Abdominal aortic aneurysm (AAA) is a disease characterized by weakening arterial wall and permanent expansion with high mortality once rupture, which was involved with immune system activation. However, owing to technical difficulties, previous research has limited the impact of one or limited immune cells on AAA. METHODS: We analyzed the composition of immune cells using the CIBERSORT algorithm through transcriptome sequencing data from patients with stable (eAAA) and ruptured aneurysms (rAAA). The whole transcriptome sequencing data, including 17 patients with ruptured AAA and 31 patients with stable AAA were downloaded from Gene Expression Omnibus (GEO, GSE98278). After normalizing and data processing, five rAAA and seventeen eAAA patients entered the follow-up analysis. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to identify several pathways that were significantly enriched in rAAA compared to eAAA tissues. RESULTS: We demonstrated that the compositions of infiltrative immune cell in eAAA and rAAA were different. Naïve B cells, both resting and activated CD4+ memory T cells were found significantly higher in ruptured AAA, while memory B cells and activated mast cells were much less in ruptured AAA than that in stable AAA. Besides, PTX3 was significantly highly expressed in rAAA, which might be associated with the complement system and polarization of macrophages. Finally, differentially expressed genes and the related immune cells were mapped in a network to reveal the relationship between gene expression and infiltrative immune cells. CONCLUSION: We identified the infiltrated immune cell profile of eAAA and rAAA patients, which might be the potential target of AAA treatment.


Assuntos
Aneurisma da Aorta Abdominal/genética , Ruptura Aórtica/genética , Linfócitos B/metabolismo , Linfócitos T/metabolismo , Transcriptoma , Animais , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Ruptura Aórtica/metabolismo , Ruptura Aórtica/patologia , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Células Dendríticas/metabolismo , Humanos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/metabolismo
3.
Cardiovasc Ther ; 2020: 9397109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821285

RESUMO

Chronic systemic inflammation contributes to cardiovascular disease (CVD) and correlates with the abundance of acute phase response (APR) proteins in the liver and plasma. Bromodomain and extraterminal (BET) proteins are epigenetic readers that regulate inflammatory gene transcription. We show that BET inhibition by the small molecule apabetalone reduces APR gene and protein expression in human hepatocytes, mouse models, and plasma from CVD patients. Steady-state expression of serum amyloid P, plasminogen activator inhibitor 1, and ceruloplasmin, APR proteins linked to CVD risk, is reduced by apabetalone in cultured hepatocytes and in humanized mouse liver. In cytokine-stimulated hepatocytes, apabetalone reduces the expression of C-reactive protein (CRP), alpha-2-macroglobulin, and serum amyloid P. The latter two are also reduced by apabetalone in the liver of endotoxemic mice. BET knockdown in vitro also counters cytokine-mediated induction of the CRP gene. Mechanistically, apabetalone reduces the cytokine-driven increase in BRD4 BET occupancy at the CRP promoter, confirming that transcription of CRP is BET-dependent. In patients with stable coronary disease, plasma APR proteins CRP, IL-1 receptor antagonist, and fibrinogen γ decrease after apabetalone treatment versus placebo, resulting in a predicted downregulation of the APR pathway and cytokine targets. We conclude that CRP and components of the APR pathway are regulated by BET proteins and that apabetalone counters chronic cytokine signaling in patients.


Assuntos
Anti-Inflamatórios/farmacologia , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Citocinas/metabolismo , Endotoxemia/tratamento farmacológico , Epigênese Genética/efeitos dos fármacos , Proteínas Nucleares/metabolismo , Quinazolinonas/farmacologia , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação , Proteína C-Reativa/genética , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Células Cultivadas , Ceruloplasmina/genética , Ceruloplasmina/metabolismo , Citocinas/genética , Modelos Animais de Doenças , Endotoxemia/genética , Endotoxemia/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas Nucleares/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Regiões Promotoras Genéticas , Componente Amiloide P Sérico/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , alfa-Macroglobulinas/genética , alfa-Macroglobulinas/metabolismo
4.
J Steroid Biochem Mol Biol ; 202: 105722, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32565247

RESUMO

PTX3, a member of the pentraxin protein family, plays important roles in ovulation as a marker of cumulus cell-oocyte complex expansion. However, the expression and function of PTX3 in goat ovarian GCs remain unclear. We isolated GCs from small and large follicles and found that PTX3 expression was significantly decreased and miR-29 mRNA expression was significantly increased during the growth of antral follicles. MiR-29 decreased PTX3 expression by targeting its 3' untranslated. Furthermore, miR-29 promoted GC proliferation, suppressed steroidogenesis and apoptosis by targeting PTX3 via the activation of the PI3K/AKT/mTOR and Erk1/2 signaling pathways. Treatment with inhibitors also verified these results. Meanwhile, we found that PI3K/AKT/mTOR and Erk1/2 signaling pathways had different role in secretion of E2 and P4 by regulating differently various steroidogenic enzyme (CYP19A1, CYP11A1, StAR and HSD3B) expression. These outcomes indicate the potential role of PTX3 in goat follicular growth and atresia.


Assuntos
Proteína C-Reativa/metabolismo , Células da Granulosa/metabolismo , MicroRNAs/genética , Componente Amiloide P Sérico/metabolismo , Animais , Apoptose , Proteína C-Reativa/genética , Proliferação de Células , Estradiol/metabolismo , Feminino , Cabras , Células HEK293 , Humanos , Sistema de Sinalização das MAP Quinases , Fosfatidilinositol 3-Quinases/metabolismo , Progesterona/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Componente Amiloide P Sérico/genética , Serina-Treonina Quinases TOR/metabolismo
5.
Medicine (Baltimore) ; 99(22): e20495, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481464

RESUMO

Biomarkers are valuable tools for the prediction of mortality in patients with sepsis. However, the use of a single biomarker to predict patient outcomes is challenging owing to the complexity and redundancy of the immune response to infections.We aimed to conduct a prospective observational analysis to investigate the prognostic value of pentraxin 3, interleukin 6, procalcitonin, and lactate combined in predicting the 28-day mortality rate in patients with sepsis or septic shock (n = 160; sepsis, 78; sepsis shock, 82). Two methods (the frequency sum of values above the cutoff, and the multivariate logistic regression model) were used to assess the prognostic value of the biomarker combination.In the receiver operating characteristic curve analyses, the combination of the 4 biomarkers was better than the Sequential Organ Failure Assessment (SOFA) score in predicting the 28-day mortality rate, regardless of whether the frequency sum of values above the cutoff or the multivariate logistic model was used for the analysis. The addition of the SOFA score to the biomarker combination did not result in a better performance for the prediction of mortality.The combined biomarker approach showed good performance in predicting 28-day all-cause mortality among patients diagnosed with either sepsis or septic shock according to the Sepsis-3 definitions. Furthermore, it was superior to the SOFA score in predicting mortality.


Assuntos
Biomarcadores/sangue , Escores de Disfunção Orgânica , Sepse/mortalidade , Choque Séptico/mortalidade , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Feminino , Humanos , Interleucina-6/sangue , Lactatos/sangue , Masculino , Valor Preditivo dos Testes , Pró-Calcitonina/sangue , Prognóstico , Estudos Prospectivos , Componente Amiloide P Sérico/metabolismo
6.
Arch Gynecol Obstet ; 301(6): 1569-1578, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32372340

RESUMO

PURPOSE: Pentraxin 3 (PTX3) is a locally secreted, quicker responsive pro-inflammatory protein than C-reactive protein (CRP). We evaluated the value of PTX3 in the prediction of ovarian hyperstimulation syndrome (OHSS), a severe complication of in vitro fertilization (IVF). METHODS: This two-year prospective follow-up study included 27 women with uncomplicated IVF-cycles (IVF group) and 31 patients diagnosed with moderate or severe early OHSS (OHSS group). PTX3 was analysed from follicular fluid (FF) and serial blood samples with enzyme-linked immunoassay and CRP with particle-enhanced immunoturbidimetric assay. The value of PTX3 and CRP in detecting OHSS was examined with receiver operating characteristic (ROC) curve analysis and expressed as the area under the curve (AUC). RESULTS: The circulating PTX3 level peaked at two days after oocyte pick-up (OPU2), and in the OHSS group the level was 1.9 times higher (P = 0.006) than in the IVF group. However, in ROC curve analysis PTX3 (AUC 0.79, best cut off 1.1 µg/L) was not superior to CRP (AUC 0.87; best cut off 9.5 mg/L) in predicting early OHSS. In the IVF group, the FF-PTX3 concentration was 15-20 times higher than in the plasma. PTX3 level at OPU2 correlated with the number of punctured follicles (r = 0.56, n = 22, P = 0.006). Triggering with human chorionic gonadotrophin or early pregnancy had no effect on PTX3 level. CONCLUSION: The elevated PTX3 concentration in OHSS at OPU2, when freeze-all embryos strategy is still possible to consider, indicates that PTX3 level could provide additional benefit in the risk assessment for early OHSS.


Assuntos
Proteína C-Reativa/metabolismo , Fertilização In Vitro/métodos , Síndrome de Hiperestimulação Ovariana/sangue , Componente Amiloide P Sérico/metabolismo , Adulto , Feminino , Seguimentos , Humanos , Síndrome de Hiperestimulação Ovariana/etiologia , Gravidez , Estudos Prospectivos
7.
Nat Commun ; 11(1): 2487, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427938

RESUMO

Cancer stem-like cells (CSCs) are the tumorigenic cell subpopulation and contribute to cancer recurrence and metastasis. However, the understanding of CSC regulatory mechanisms remains incomplete. By transcriptomic analysis, we identify a scaffold protein SH3RF3 (also named POSH2) that is upregulated in CSCs of breast cancer clinical tumors and cancer cell lines, and enhances the CSC properties of breast cancer cells. Mechanically, SH3RF3 interacts with the c-Jun N-terminal kinase (JNK) in a JNK-interacting protein (JIP)-dependent manner, leading to enhanced phosphorylation of JNK and activation of the JNK-JUN pathway. Further the JNK-JUN signaling expands CSC subpopulation by transcriptionally activating the expression of Pentraxin 3 (PTX3). The functional role of SH3RF3 in CSCs is validated with patient-derived organoid culture, and supported by clinical cohort analyses. In conclusion, our work elucidates the role and molecular mechanism of SH3RF3 in CSCs of breast cancer, and might provide opportunities for CSC-targeting therapy.


Assuntos
Neoplasias da Mama/genética , Proteína C-Reativa/genética , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Células-Tronco Neoplásicas/metabolismo , Componente Amiloide P Sérico/genética , Ubiquitina-Proteína Ligases/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proteína C-Reativa/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Ativação Enzimática , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Fosforilação , Componente Amiloide P Sérico/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Regulação para Cima
8.
PLoS One ; 15(1): e0227227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978114

RESUMO

Many conflicting reports about the involvement of serum amyloid P component (SAP) in amyloid diseases have been presented over the years; SAP is known to be a universal component of amyloid aggregates but it has been suggested that it can both induce and suppress amyloid formation. By using our Drosophila model of systemic lysozyme amyloidosis, SAP has previously been shown to reduce the toxicity induced by the expression of the disease-associated lysozyme variant, F57I, in the Drosophila central nervous system. This study further investigates the involvement of SAP in modulating lysozyme toxicity using histochemistry and spectral analyses on the double transgenic WT and F57I lysozyme flies to probe; i) formation of aggregates, ii) morphological differences of the aggregated lysozyme species formed in the presence or absence of SAP, iii) location of lysozyme and iv) co-localisation of lysozyme and SAP in the fly brain. We found that SAP can counteract the toxicity (measured by the reduction in the median survival time) induced by F57I lysozyme by converting toxic F57I species into less toxic amyloid-like structures, as reflected by the spectral changes that p-FTAA undergoes when bound to lysozyme deposits in F57I-F57I-SAP flies as compared to F57I-F57I flies. Indeed, when SAP was introduced to in vitro lysozyme fibril formation, the endpoint fibrils had enhanced ThT fluorescence intensity as compared to lysozyme fibrils alone. This suggests that a general mechanism for SAP's role in amyloid diseases may be to promote the formation of stable, amyloid-like fibrils, thus decreasing the impact of toxic species formed along the aggregation pathway.


Assuntos
Amiloidose/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Muramidase/metabolismo , Componente Amiloide P Sérico/metabolismo , Amiloide/genética , Amiloide/metabolismo , Amiloide/ultraestrutura , Amiloidose/genética , Amiloidose/patologia , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Humanos , Muramidase/genética , Agregados Proteicos , Agregação Patológica de Proteínas/genética , Agregação Patológica de Proteínas/metabolismo , Agregação Patológica de Proteínas/patologia
9.
Obesity (Silver Spring) ; 28(2): 323-332, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898407

RESUMO

OBJECTIVE: This study investigates the role of pentraxin 3 (PTX3) in the regulation of inflammatory homeostasis involving anti-inflammatory miR-21 during lipopolysaccharide (LPS) stimulation in adipocytes. METHODS: Using PTX3 knockout (PTX3 KO) mouse and primary stromal vascular cell models, this study determined the effect of PTX3 deficiency on the expression and secretion of miR-21 in brown adipose tissue (BAT) and brown adipocytes as well as the rescue effect of recombinant PTX3 on miR-21 during LPS-induced inflammation. RESULTS: Among three fat depots, BAT was the major tissue and fully differentiated brown adipocytes were the major cells that expressed miRNA-processing enzymes and produced miRNA. Moreover, brown adipocytes, but not stromal vascular cells, were the LPS-responsive cells in miR-21 production. PTX3 deficiency attenuated LPS-stimulated upregulation of miR-21 in sera and BAT. In wild-type brown adipocytes, LPS stimulation significantly upregulated cellular miR-21. Interestingly, this stimulatory effect of LPS was attenuated, and cellular and secreted miR-21 levels were reduced in PTX3 KO cells upon LPS stimulation. Treatment of recombinant PTX3 reversed the cellular and secreted levels of miR-21 and attenuated an LPS-stimulated increase in the expression of Tnf-α and Mcp1 genes in PTX3 KO adipocytes. CONCLUSIONS: PTX3 plays an anti-inflammatory role, in part through regulating miR-21 expression and secretion.


Assuntos
Proteínas da Fase Aguda/metabolismo , Adipócitos Marrons/metabolismo , Proteína C-Reativa/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/metabolismo , MicroRNAs/metabolismo , Componente Amiloide P Sérico/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Diferenciação Celular , Camundongos
10.
J Leukoc Biol ; 107(3): 497-508, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30934147

RESUMO

Calcineurin (CN) inhibitors are effective clinical immunosuppressants but leave patients vulnerable to potentially fatal fungal infections. This study tested the hypothesis that CN inhibition interferes with antifungal immune defenses mediated by monocytes. We showed that NFAT is expressed by human monocytes, and is activated by exposure to fungal ligands. We confirmed that NFAT translocation potently activated target gene transcription using a human monocytic reporter cell line. Inhibition of CN-NFAT by cyclosporine A significantly reduced monocyte production of TNF-α, IL-10, and MCP-1 proteins in response to pattern recognition receptor ligands as well as to Aspergillus fumigatus conidia. Moreover, we revealed that human monocytes express the antifungal protein pentraxin-3 under control of NFAT. In conclusion, clinical CN inhibitors have the potential to interfere with the novel NFAT-dependent pentraxin-3 pathway as well as antifungal cytokine production in human monocytes, thereby impeding monocyte-mediated defenses against fungal infection in immune-suppressed patients.


Assuntos
Antifúngicos/metabolismo , Proteína C-Reativa/metabolismo , Inibidores de Calcineurina/farmacologia , Monócitos/metabolismo , Fatores de Transcrição NFATC/metabolismo , Componente Amiloide P Sérico/metabolismo , Animais , Aspergillus fumigatus/efeitos dos fármacos , Sequência de Bases , Sítios de Ligação , Quimiocinas/metabolismo , Ciclosporina/farmacologia , Humanos , Interleucina-10/metabolismo , Camundongos , Monócitos/efeitos dos fármacos , Células Mieloides/efeitos dos fármacos , Células Mieloides/metabolismo , Transporte Proteico/efeitos dos fármacos , Homologia de Sequência de Aminoácidos , Transdução de Sinais/efeitos dos fármacos , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismo
11.
Am J Emerg Med ; 38(1): 38-42, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30961918

RESUMO

OBJECTIVES: We investigated the state of inflammation, PTX3 level and other routine inflammatory markers (high sensitivity C-reactive protein [hsCRP], and white blood cells [WBC]), in patients who presented to the emergency department (ED) with migraine. We also investigated the relationship between the clinical presentation, PTX3 level, and other routine inflammatory markers in the emergency management of these patients. METHODS: The study included 44 patients (group 1) who presented to the ED due to a migraine attack with aura and 44 controls (group 2) with similar demographic characteristics. RESULTS: The WBC count was 8.82 ±â€¯2.10 × 109/L in group 1 and 7.85 ±â€¯2.04 × 109/L in group 2. The mean PTX3 level was 11.57 ±â€¯3.99 ng/mL in patients who presented at the ED with a migraine attack, and 4.59 ±â€¯1.28 ng/mL in controls. The differences values of WBC and PTX3 between the two groups were significant (respectively; P = 0.031, P < 0.001). ROC analyses indicated significant results for PTX3 as a marker for acute migraine attack. It had a sensitivity of 93% and specificity of 84% at a cut-off value of 5.80 ng/mL. CONCLUSION: This is the first study to investigate plasma levels of PTX3 in patients with acute migraine. PTX3 as a biomarker may be used as an additional examination to the current subjective criteria to support the diagnosis of patients presenting to the ED with an acute migraine attack.


Assuntos
Proteína C-Reativa/metabolismo , Serviço Hospitalar de Emergência , Enxaqueca com Aura/sangue , Enxaqueca com Aura/diagnóstico , Componente Amiloide P Sérico/metabolismo , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Ferritinas/sangue , Humanos , Contagem de Leucócitos , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade
12.
Cell Mol Life Sci ; 77(18): 3627-3642, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31768607

RESUMO

Hypoxia-inducible factor (HIF), an αß dimer, is the master regulator of oxygen homeostasis with hundreds of hypoxia-inducible target genes. Three HIF isoforms differing in the oxygen-sensitive α subunit exist in vertebrates. While HIF-1 and HIF-2 are known transcription activators, HIF-3 has been considered a negative regulator of the hypoxia response pathway. However, the human HIF3A mRNA is subject to complex alternative splicing. It was recently shown that the long HIF-3α variants can form αß dimers that possess transactivation capacity. Here, we show that overexpression of the long HIF-3α2 variant induces the expression of a subset of genes, including the erythropoietin (EPO) gene, while simultaneous downregulation of all HIF-3α variants by siRNA targeting a shared HIF3A region leads to downregulation of EPO and additional genes. EPO mRNA and protein levels correlated with HIF3A silencing and HIF-3α2 overexpression. Chromatin immunoprecipitation analyses showed that HIF-3α2 binding associated with canonical hypoxia response elements in the promoter regions of EPO. Luciferase reporter assays showed that the identified HIF-3α2 chromatin-binding regions were sufficient to promote transcription by all three HIF-α isoforms. Based on these data, HIF-3α2 is a transcription activator that directly regulates EPO expression.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Eritropoetina/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/genética , Proteína Morfogenética Óssea 6/genética , Proteína Morfogenética Óssea 6/metabolismo , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Cromatina/metabolismo , Dimerização , Eritropoetina/análise , Eritropoetina/genética , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Humanos , Regiões Promotoras Genéticas , Ligação Proteica , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Interferência de RNA , Processamento de RNA , RNA Interferente Pequeno/metabolismo , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/metabolismo , Ativação Transcricional
13.
Saudi Med J ; 40(12): 1202-1208, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31828271

RESUMO

OBJECTIVES: To assess the prognostic value of pentraxin 3 (PTX3) in patients with ST-elevation myocardial infarction (STEMI) after bare-metal stent (BMS) implantation. METHODS: In this prospective study, PTX3, interleukin (IL-6), IL-10, high-sensitivity c-reactive protein  (hsCRP), and cardiac troponin I (cTnI) plasma values were determined before and 24 hours after BMS implantation in 97 consecutively enrolled patients with STEMI who were admitted to University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina between February 2016 and February 2017. Patients were followed for 24 months to assess major adverse cardiovascular events (MACEs). RESULTS: At 24 hours after percutaneous coronary intervention (PCI), plasma values of  PTX3, IL-6, hsCRP, and cTnI were significantly increased; and IL-10 levels were significantly decreased compared with the values determined before PCI. Patients with MACEs had significantly higher plasma PTX3 levels at 24 hours after BMS-PCI than in patients without MACEs. Patients with PTX3 plasma values ≥5042 ng/ml had a significantly higher risk of MACEs than patients with PTX3 levels <5.042 ng/mL. Pentraxin 3 levels exhibited strong and significant correlations with IL-6 and IL-10 levels. Pentraxin 3, cTnI, and IL-6, but not hsCRP levels have showed independent association with MACEs, according to the multivariate Cox regression analysis. CONCLUSION: Pentraxin 3 might be better serum prognostic marker than IL-6, IL-10 or high sensitivity CRP for MACEs after BMS-PCI. It might help to make better risk stratification of those patients who are undergoing BMS-PCI.


Assuntos
Proteína C-Reativa/metabolismo , Interleucina-10/sangue , Interleucina-6/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Componente Amiloide P Sérico/metabolismo , Stents , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia
14.
Int J Mol Sci ; 20(23)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31795454

RESUMO

: (1) Background: Age-related macular degeneration (AMD) is closely related with retinal pigment epithelial (RPE) cell dysfunction. Although the exact pathogenesis of AMD remains largely unknown, oxidative stress-induced RPE damage is believed to be one of the primary causes. We investigated the molecular mechanisms of pentraxin 3 (PTX3) expression and its biological functions during oxidative injury. (2) Methods: Using enzyme-linked immunosorbent assays and real-time reverse transcription-polymerase chain reaction, we analyzed mRNA and protein levels of PTX3 in the presence or absence of oxidative stress inducer, sodium iodate (NaIO3), in primary human H-RPE and ARPE-19 cells. Furthermore, we assessed cell death, antioxidant enzyme expression, and AMD-associated gene expression to determine the biological functions of PTX3 under oxidative stress. (3) Results: NaIO3 increased PTX3 expression, in a dose- and time-dependent manner, in H-RPE and ARPE-19 cells. We found phosphorylated Akt, a downstream target of the PI3 kinase pathway, phosphor- mitogen-activated protein kinase kinase 1/2 (ERK), and intracellular reactive oxygen species (ROS) were predominantly induced by NaIO3. NaIO3-induced PTX3 expression was decreased in the presence of phosphoinositide 3 (PI3) kinase inhibitors, ERK inhibitors, and ROS scavengers. Furthermore, NaIO3 enhanced mRNA expression of antioxidant enzymes such as glucose-6-phosphate dehydrogenase (G6PDH), catalase (CAT), and glutathione S-reductase (GSR) in the control shRNA expressing RPE cells, but not in hPTX3 shRNA expressing RPE cells. Interestingly, NaIO3 did not induce mRNA expression of AMD marker genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), and toll-like receptor 4 (TLR4) in hPTX3 shRNA expressing RPE cells. 4) Conclusions: These results suggest that PTX3 accelerates RPE cell death and might be involved in AMD development in the presence of oxidative stress.


Assuntos
Proteína C-Reativa/metabolismo , Degeneração Macular/metabolismo , Estresse Oxidativo , Epitélio Pigmentado da Retina/metabolismo , Componente Amiloide P Sérico/metabolismo , Proteína C-Reativa/genética , Morte Celular , Linhagem Celular , Humanos , Sistema de Sinalização das MAP Quinases , Degeneração Macular/genética , Degeneração Macular/patologia , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/patologia , Componente Amiloide P Sérico/genética , Regulação para Cima
15.
BMC Med Res Methodol ; 19(1): 222, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31795933

RESUMO

BACKGROUND: The recent progress in medical research generates an increasing interest in the use of longitudinal biomarkers for characterizing the occurrence of an outcome. The present work is motivated by a study, where the objective was to explore the potential of the long pentraxin 3 (PTX3) as a prognostic marker of Acute Graft-versus-Host Disease (GvHD) after haematopoietic stem cell transplantation. Time-varying covariate Cox model was commonly used, despite its limiting assumptions that marker values are constant in time and measured without error. A joint model has been developed as a viable alternative; however, the approach is computationally intensive and requires additional strong assumptions, in which the impacts of their misspecification were not sufficiently studied. METHODS: We conduct an extensive simulation to clarify relevant assumptions for the understanding of joint models and assessment of its robustness under key model misspecifications. Further, we characterize the extent of bias introduced by the limiting assumptions of the time-varying covariate Cox model and compare its performance with a joint model in various contexts. We then present results of the two approaches to evaluate the potential of PTX3 as a prognostic marker of GvHD after haematopoietic stem cell transplantation. RESULTS: Overall, we illustrate that a joint model provides an unbiased estimate of the association between a longitudinal marker and the hazard of an event in the presence of measurement error, showing improvement over the time-varying Cox model. However, a joint model is severely biased when the baseline hazard or the shape of the longitudinal trajectories are misspecified. Both the Cox model and the joint model correctly specified indicated PTX3 as a potential prognostic marker of GvHD, with the joint model providing a higher hazard ratio estimate. CONCLUSIONS: Joint models are beneficial to investigate the capability of the longitudinal marker to characterize time-to-event endpoint. However, the benefits are strictly linked to the correct specification of the longitudinal marker trajectory and the baseline hazard function, indicating a careful consideration of assumptions to avoid biased estimates.


Assuntos
Proteína C-Reativa/metabolismo , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Modelos de Riscos Proporcionais , Componente Amiloide P Sérico/metabolismo , Viés , Biomarcadores/metabolismo , Simulação por Computador , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Estudos Longitudinais , Prognóstico , Análise de Sobrevida , Fatores de Tempo
16.
Acta Vet Hung ; 67(4): 505-516, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842598

RESUMO

The aim of this study was to evaluate the biomarkers of cardiac damage such as heart-type fatty acid-binding protein (H-FABP), pentraxin-3 (PTX-3), and thrombomodulin (TM) for the detection and prognosis of bovine traumatic pericarditis (TP). Spontaneous TP was diagnosed on the basis of history, clinical signs, complete blood count, glutaraldehyde test, ultrasonography, and pericardiocentesis findings. H-FABP, PTX-3 and TM levels in serum were compared between 25 Holstein cows diagnosed with spontaneous TP and 10 healthy control cows using bovine-specific ELISA kits. Serum H-FABP in cattle with TP was significantly (P < 0.05) higher than in the control group and positively correlated with cardiac troponin-I (cTnI), creatine kinase myocardial band (CK-MB), PTX-3 and TM (r = 0.683, 0.342, 0.448 and 0.424, respectively; P < 0.05). The serum levels of PTX-3 (P < 0.05) and TM (P < 0.05) in cattle with TP were significantly higher than in the control group. Cardiac damage biomarkers H-FABP, PTX-3 and TM may be useful in the diagnosis of bovine TP.


Assuntos
Proteína C-Reativa/metabolismo , Doenças dos Bovinos/genética , Proteína 3 Ligante de Ácido Graxo/sangue , Pericardite/veterinária , Componente Amiloide P Sérico/metabolismo , Trombomodulina/sangue , Animais , Biomarcadores/metabolismo , Bovinos , Doenças dos Bovinos/metabolismo , Feminino , Pericardite/genética , Pericardite/metabolismo
17.
Neuro Endocrinol Lett ; 40(2): 85-92, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31785215

RESUMO

OBJECTIVES: Sleep apnea syndrome affects approximately 4% of adult males and 2% of adult females. It is associated with significant cardio-, cerebrovascular, metabolic and hormonal comorbidities and ranks among the more expensive medical specialties due to the requirement of high-quality technical diagnostic and therapeutic equipment as well as well-educated and experienced personnel. The aim of this study is to detect the relationship between C-reactive protein (CRP), pentraxin-3 (PTX-3), interleukin 6 (IL6), high-sensitivity troponin I (hsTnI), brain natriuretic protein (BNP) and galectin-3 serum levels and obstru-ctive sleep apnea syndrome. DESIGN: Prospective cohort study. MATERIAL AND METHODS: A group of 146 patients with middle to severe obstructive sleep apnea syndrome (OSAS) were monitored, and the results were compared with the results from a control group of healthy individuals. RESULTS: We assessed serum levels of the following biomarkers: CRP, PTX-3, IL6, hsTnI, BNP, and galectin-3. PTX-3 serum levels were statistically significantly higher (p<0.0001) in patients with OSAS, compared to controls. Statistical results related to the other biomarkers did not suggest any clinical value. ROC analysis showed that PTX-3 might be able to distinguish patients with OSAS from healthy individuals (AUC=7438). CONCLUSION: The elevation of PTX-3 serum levels is significantly associated with middle to severe obstructive sleep apnea syndrome. The PTX-3 biomarker appears to be a promising alternative method for sleep apnea syndrome investigations.


Assuntos
Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Monitorização Fisiológica/métodos , Componente Amiloide P Sérico/metabolismo , Síndromes da Apneia do Sono/diagnóstico , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Proteína C-Reativa/análise , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Interleucina-6/análise , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Componente Amiloide P Sérico/análise , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/sangue , Síndromes da Apneia do Sono/terapia , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/terapia
18.
PLoS One ; 14(11): e0224818, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31703088

RESUMO

Information about the tissue characteristics of abdominal aortic aneurysms (AAAs), some of which may be reflected in the serum, can help to elucidate AAA pathogenesis and identify new AAA biomarkers. This information would be beneficial not only for diagnostics and follow-up but also for potential therapeutic intervention. Therefore, the aim of our study was to compare the expression of structural proteins, immune factors (T and B lymphocytes, macrophages, neutrophils and pentraxin 3 (PTX3)), osteoprotegerin (OPG), microvessels and hypoxic cells in AAA and nonaneurysmal aortic walls. We examined specimens collected during surgery for AAA repair (n = 39) and from the abdominal aortas of kidney donors without AAA (n = 8). Using histochemical and immunohistochemical methods, we quantified the areas positive for smooth muscle actin, desmin, elastin, collagen, OPG, CD3, CD20, MAC387, myeloperoxidase, PTX3, and hypoxia-inducible factor 1-alpha and the density of CD31-positive microvessels. AAA samples contained significantly less actin, desmin, elastin and OPG, more collagen, macrophages, neutrophils, T lymphocytes, B lymphocytes, hypoxic cells and PTX3, and a greater density of vasa vasorum (VV) than those in non-AAA samples. Hypoxia positively correlated with actin and negatively correlated with collagen. Microvascular density was related to inflammatory cell infiltrates, hypoxia, PTX3 expression and AAA diameter. The lower OPG expression in AAAs supports the notion of its protective role in AAA remodeling. AAA contained altered amounts of structural proteins, implying reduced vascular elasticity. PTX3 was upregulated in AAA and colocalized with inflammatory infiltrates. This evidence supports further evaluation of PTX3 as a candidate marker of AAA. The presence of aortic hypoxia, despite hypervascularization, suggests that hypoxia-induced neoangiogenesis may play a role in AAA pathogenesis. VV angiogenesis of the AAA wall increases its vulnerability.


Assuntos
Aneurisma da Aorta Abdominal/etiologia , Aneurisma da Aorta Abdominal/metabolismo , Proteína C-Reativa/metabolismo , Hipóxia/metabolismo , Inflamação/complicações , Neovascularização Patológica/metabolismo , Osteoprotegerina/metabolismo , Componente Amiloide P Sérico/metabolismo , Adulto , Idoso , Aneurisma da Aorta Abdominal/patologia , Biomarcadores , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade
19.
Mediators Inflamm ; 2019: 9893682, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780874

RESUMO

Background/Aims: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Calcium dobesilate (CaD) is widely used to treat diabetic retinopathy. Recent studies have demonstrated that CaD exerts protective effects against diabetic nephropathy. The aim of this study was to elucidate the molecular and cellular mechanisms underlying the protective effects of CaD. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured with different D-glucose concentrations to determine the effects of high glucose on HUVEC gene expression. HUVECs were also incubated with CaD (25 µM, 50 µM, and 100 µM) for 3 days to determine the effects of CaD on HUVEC viability. db/db mice were treated with CaD. 2-[(Aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) blocked the nuclear factor-κB (NF-κB) pathway in HUVECs. A pentraxin 3 (PTX3) small interfering RNA (siRNA) intervention experiment was performed in the cells. An adenovirus-encapsulated PTX3 siRNA intervention experiment was performed in db/db mice. Western blot and real-time PCR analyses were used to detect PTX3, p-IKBa/IKBa (I-kappa-B-alpha), and p-eNOS/eNOS (endothelial nitric oxide synthase) expression in mice and HUVECs. Hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining were used to observe renal tissue damage in mice. PTX3 expression was observed by immunohistochemical staining. Results: CaD downregulated the expression of PTX3 and p-IKBa/IKBa and upregulated the expression of p-eNOS/eNOS in vitro. When TPCA-1 was used, high glucose induced high PTX3 expression, and the expression of p-eNOS/eNOS increased. After PTX3 gene silencing, the expression of p-eNOS/eNOS also increased. In vivo, CaD reduced the expression of PTX3 and p-IKBa/IKBa in the kidneys of db/db mice and increased the expression of p-eNOS/eNOS. After PTX3 gene silencing, the urine protein and renal function of db/db mice were ameliorated, the glomerular extracellular matrix was decreased, and the expression of p-eNOS/eNOS was increased. Conclusions: Our results suggested that CaD may inhibit the expression of PTX3 by altering the IKK/IKB/NF-κB pathway, thereby improving endothelial dysfunction in HUVECs. PTX3 may be a potential therapeutic target for DKD.


Assuntos
Dobesilato de Cálcio/uso terapêutico , Glucose/farmacologia , Células Endoteliais da Veia Umbilical Humana/patologia , Amidas/farmacologia , Proteína C-Reativa/metabolismo , Humanos , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Componente Amiloide P Sérico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tiofenos/farmacologia
20.
Int J Mol Sci ; 20(22)2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31744201

RESUMO

Pentraxin-3 (PTX3) is recognized as a modulator of inflammation and a mediator of tissue repair. In this study, we characterized the role of PTX3 on some biological functions of human dental pulp stem cells (HDPSCs). The expression level of PTX3 significantly increased during osteogenic/odontogenic differentiation of HDPSCs, whereas the knockdown of PTX3 decreased this differentiation. Silencing of PTX3 in HDPSCs inhibited their migration and C-X-C chemokine receptor type 4 (CXCR4) expression. Our present study indicates that PTX3 is involved in osteogenic/odontogenic differentiation and migration of HDPSCs, and may contribute to the therapeutic potential of HDPSCs for regeneration and repair.


Assuntos
Proteína C-Reativa/metabolismo , Diferenciação Celular , Movimento Celular , Odontogênese/fisiologia , Osteogênese/fisiologia , Componente Amiloide P Sérico/metabolismo , Proteína C-Reativa/genética , Polpa Dentária/crescimento & desenvolvimento , Polpa Dentária/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Receptores CXCR4/metabolismo , Componente Amiloide P Sérico/genética , Células-Tronco/fisiologia
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