In preovulatory follicles, after the endogenous gonadotropin surge, the oocyte-cumulus complexes (OCCs) produce hyaluronan (HA) in a process called "cumulus expansion". During this process, the heavy chains (HCs) of the serum-derived inter-alpha-trypsin inhibitor (IαI) family bind covalently to synthesized HA and form a unique structure of the expanded cumulus HA-rich extracellular matrix. Understanding the biochemical mechanism of the covalent linkage between HA and the HCs of the IαI family is one of the most significant discoveries in reproductive biology, since it explains basis of the cumulus expansion process running in parallel with the oocyte maturation, both essential for ovulation. Two recent studies have supported the above-mentioned findings: in the first, seven components of the extracellular matrix were detected by proteomic, evolutionary, and experimental analyses, and in the second, the essential role of serum in the process of cumulus expansion in vitro was confirmed. We have previously demonstrated the formation of unique structure of the covalent linkage of HA to HCs of IαI in the expanded gonadotropin-stimulated OCC, as well as interactions with several proteins produced by the cumulus cells: tumor necrosis factor-alpha-induced protein 6, pentraxin 3, and versican. Importantly, deletion of these genes in the mice produces female infertility due to defects in the oocyte-cumulus structure.
- MeSH
- alfa-globuliny metabolismus MeSH
- C-reaktivní protein metabolismus MeSH
- extracelulární matrix * metabolismus MeSH
- kumulární buňky * metabolismus MeSH
- kyselina hyaluronová * metabolismus MeSH
- lidé MeSH
- myši MeSH
- oocyty * metabolismus MeSH
- ovariální folikul * metabolismus MeSH
- sérový amyloidový protein metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: The current obstructive sleep apnea (OSA) diagnostic uses polysomnography or limited polygraphy and requires specialized personnel and technical equipment. Glycoprotein biomarkers and microRNAs are being explored as a possible new method for screening. We aimed to evaluate whether certain biomarkers and microRNA, previously identified as related to OSA, could be influenced by factors such as gender, age, and obesity level in patients with OSA. METHODS: In this retrospective analytical study, patients with moderate to severe OSA (n = 130) were compared with the control group. Serum levels of selected biomarkers and microRNA were taken from both groups. The group of OSA patients was then stratified by gender, obesity level, and age to see the possible influence of those variables on biomarker levels. RESULTS: Levels of all studied biomarkers - C-reactive protein (CRP), high-sensitivity troponin I (hsTnI), pentraxin-3 (PTX-3), and microRNA-499 were significantly higher in patients with OSA compared to the control group. In the OSA group only hsTnI showed a statistically significant relationship with gender. Levels of CRP and hsTnI showed a significant dependence on the level of obesity. Dependency on age was proven for hsTnI. CRP, PTX-3, and microRNA-499 did not have any statistically significant relationship with age. CONCLUSION: We found that serum levels of pentraxin-3 and microRNA-499 in patients with moderate to severe obstructive sleep apnoea are independent of gender, obesity, and age. CRP was affected by the level of obesity and hsTnI was influenced by all 3 variables. We consider these findings important for further research of OSA biomarkers.
- MeSH
- biologické markery * krev MeSH
- C-reaktivní protein * analýza metabolismus MeSH
- dospělí MeSH
- glykoproteiny krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- obezita * krev genetika MeSH
- obstrukční spánková apnoe * krev genetika MeSH
- retrospektivní studie MeSH
- senioři MeSH
- sérový amyloidový protein metabolismus analýza genetika MeSH
- sexuální faktory MeSH
- troponin I krev MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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.
- MeSH
- antifungální látky metabolismus MeSH
- Aspergillus fumigatus účinky léků MeSH
- C-reaktivní protein metabolismus MeSH
- chemokiny metabolismus MeSH
- cyklosporin farmakologie MeSH
- inhibitory kalcineurinu farmakologie MeSH
- interleukin-10 metabolismus MeSH
- lidé MeSH
- monocyty účinky léků metabolismus MeSH
- myeloidní buňky účinky léků metabolismus MeSH
- myši MeSH
- sekvence nukleotidů MeSH
- sekvenční homologie aminokyselin MeSH
- sérový amyloidový protein metabolismus MeSH
- signální transdukce účinky léků MeSH
- THP-1 buňky MeSH
- TNF-alfa metabolismus MeSH
- transkripční faktory NFATC metabolismus MeSH
- transport proteinů účinky léků MeSH
- vazebná místa MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
- MeSH
- biologické markery analýza krev MeSH
- C-reaktivní protein analýza metabolismus MeSH
- dospělí MeSH
- interleukin-6 analýza krev MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- monitorování fyziologických funkcí metody MeSH
- obstrukční spánková apnoe krev diagnóza terapie MeSH
- prospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sérový amyloidový protein analýza metabolismus MeSH
- studie případů a kontrol MeSH
- stupeň závažnosti nemoci MeSH
- syndromy spánkové apnoe krev diagnóza terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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.
- MeSH
- aneurysma břišní aorty etiologie metabolismus patologie MeSH
- biologické markery MeSH
- C-reaktivní protein metabolismus MeSH
- dospělí MeSH
- hypoxie metabolismus MeSH
- imunohistochemie MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- osteoprotegerin metabolismus MeSH
- patologická angiogeneze metabolismus MeSH
- senioři MeSH
- sérový amyloidový protein metabolismus MeSH
- studie případů a kontrol MeSH
- zánět komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PROBLEM: To determine the changes of pentraxin 3 (PTX3) level in noninvasively obtained cervical fluid samples from women with preterm prelabor rupture of membranes (PPROM) based on the presence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI), and intra-amniotic infection (the presence of both MIAC and IAI). METHODS OF STUDY: A total of 160 women with PPROM were included. Cervical fluid samples were obtained using a Dacron polyester swab and amniotic fluid samples were obtained by transabdominal amniocentesis. Cervical fluid PTX3 levels were assessed using enzyme-linked immunosorbent assay. RESULTS: PTX3 was found in all the cervical fluid samples and its levels were higher in women with MIAC, IAI, and intra-amniotic infection than in women without these conditions. When the women were categorized into four subgroups based on the presence of MIAC and/or IAI, women with intra-amniotic infection had higher cervical fluid PTX3 levels than those with sterile IAI (IAI alone), colonization (MIAC alone), or no MIAC or IAI. A cervical fluid PTX3 level of 11 ng/mL was the best value for identifying the presence of intra-amniotic infection in women with PPROM. CONCLUSIONS: PTX3 is a constituent of cervical fluid of women with PPROM. Cervical fluid PTX3 level reflects the situation in the intra-amniotic compartments of women with PPROM. Cervical fluid PTX3 is a potential marker for the noninvasive identification of intra-amniotic infection in PPROM.
- MeSH
- biologické markery metabolismus MeSH
- C-reaktivní protein metabolismus MeSH
- cervix uteri metabolismus MeSH
- chorioamnionitida diagnóza metabolismus mikrobiologie MeSH
- ELISA MeSH
- lidé MeSH
- plodová voda mikrobiologie MeSH
- předčasný odtok plodové vody diagnóza metabolismus mikrobiologie MeSH
- prediktivní hodnota testů MeSH
- retrospektivní studie MeSH
- sérový amyloidový protein metabolismus MeSH
- těhotenství MeSH
- upregulace MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The expression level of acute phase proteins (APPs) mirrors the health status of an individual. In human medicine, C-reactive protein (CRP), and other members of the pentraxin family are of significant relevance for assessing disease severity and prognosis. In chickens, however, which represent the most common livestock species around the world, no such marker has yet gained general acceptance. The aim of this study was therefore, to characterize chicken pentraxin 3 (chPTX3) and to evaluate its applicability as a general marker for inflammatory conditions. The mammalian and chicken PTX3 proteins were predicted to be similar in sequence, domain organization and polymeric structure. Nevertheless, some characteristics like certain sequence sections, which have varied during the evolution of mammals, and species-specific glycosylation patterns, suggest distinct biological functions. ChPTX3 is constitutively expressed in various tissues but, interestingly, could not be found in splenic tissue samples without stimulation. However, upon treatment with lipopolysaccharide (LPS), PTX3 expression in chicken spleens increased to 95-fold within hours. A search for PTX3 reads in various publicly available RNA-seq data sets of chicken spleen and bursa of Fabricius also showed that PTX3 expression increases within days after experimental infection with viral and bacterial pathogens. An experimental infection with avian pathogenic E.coli and qPCR analysis of spleen samples further established a challenge dose-dependent significant up-regulation of chPTX3 in subclinically infected birds of up to over 150-fold as compared to untreated controls. Our results indicate the potential of chPTX3 as an APP marker to monitor inflammatory conditions in poultry flocks.
- MeSH
- biologické markery metabolismus MeSH
- C-reaktivní protein genetika imunologie metabolismus MeSH
- Escherichia coli fyziologie MeSH
- infekce vyvolané Escherichia coli diagnóza MeSH
- kultivované buňky MeSH
- kur domácí imunologie MeSH
- lidé MeSH
- nemoci ptáků diagnóza MeSH
- proteiny akutní fáze genetika imunologie metabolismus MeSH
- ptačí proteiny genetika imunologie metabolismus MeSH
- sekvenční seřazení MeSH
- sérový amyloidový protein genetika imunologie metabolismus MeSH
- upregulace MeSH
- zánět diagnóza MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
In this study, pentraxin 3 (PTX3), C-reactive protein (CRP), and serum amyloid P component (SAP) concentrations in the amniotic fluid of women with preterm pre-labor rupture of membranes (PPROM) were evaluated based on evidence of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI. A total of 149 women with PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid PTX3, SAP, and CRP concentrations were assessed using enzyme-linked immunosorbent assay. PTX3 and CRP concentrations were higher in women with MIAC, IAI, and microbial-associated IAI than in women without these conditions. SAP concentrations were only higher in the presence of IAI and microbial-associated IAI. Amniotic fluid PTX3 concentrations of 11 ng/mL were found to be the best value for identifying the presence of microbial-associated IAI and IAI in women with PPROM. To conclude, amniotic fluid pentraxins are involved in intra-amniotic inflammatory responses in pregnancies complicated by PPROM.
- MeSH
- amniocentéza metody MeSH
- biologické markery metabolismus MeSH
- C-reaktivní protein metabolismus MeSH
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- plodová voda metabolismus MeSH
- předčasná porodní činnost metabolismus MeSH
- předčasný odtok plodové vody metabolismus MeSH
- retrospektivní studie MeSH
- sérový amyloidový protein metabolismus MeSH
- těhotenství MeSH
- zánět metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Fertilization of the mammalian oocyte requires interactions between spermatozoa and expanded cumulus extracellular matrix (ECM) that surrounds the oocyte. This review focuses on key molecules that play an important role in the formation of the cumulus ECM, generated by the oocyte-cumulus complex. In particular, the specific inhibitors (AG1478, lapatinib, indomethacin and MG132) and progesterone receptor antagonist (RU486) exerting their effects through the remodeling of the ECM of the cumulus cells surrounding the oocyte have been described. After gonadotropin stimulus, cumulus cells expand and form hyaluronan (HA)-rich cumulus ECM. In pigs, the proper structure of the cumulus ECM depends on the interaction between HA and serum-derived proteins of the inter-alpha-trypsin inhibitor (IαI) protein family. We have demonstrated the synthesis of HA by cumulus cells, and the presence of the IαI, tumor necrosis factor-alpha-induced protein 6 and pentraxin 3 in expanding oocyte-cumulus complexes (OCC). We have evaluated the covalent linkage of heavy chains of IαI proteins to HA, as the principal component of the expanded HA-rich cumulus ECM, in porcine OCC cultured in medium with specific inhibitors: AG1478 and lapatinib (both inhibitors of epidermal growth factor receptor tyrosine kinase activity); MG132 (a specific proteasomal inhibitor), indomethacin (cyclooxygenase inhibitor); and progesterone receptor antagonist (RU486). We have found that both RU486 and indomethacin does not disrupt the formation of the covalent linkage between the heavy chains of IαI to HA in the expanded OCC. In contrast, the inhibitors AG1478 and lapatinib prevent gonadotropin-induced cumulus expansion. Finally, the formation of oocyte-cumulus ECM relying on the covalent transfer of heavy chains of IαI molecules to HA has been inhibited in the presence of MG132.
- MeSH
- C-reaktivní protein metabolismus MeSH
- extracelulární matrix účinky léků metabolismus MeSH
- kumulární buňky cytologie účinky léků metabolismus MeSH
- kyselina hyaluronová metabolismus MeSH
- mifepriston farmakologie MeSH
- molekuly buněčné adheze metabolismus MeSH
- oocyty cytologie metabolismus MeSH
- rozmnožování účinky léků MeSH
- sérový amyloidový protein metabolismus MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVES: The aim was to evaluate the association between perioperative inflammatory biomarkers and atrial fibrillation (AF) in cardiac surgical patients. METHODS: Forty-two patients undergoing cardiac surgery were divided into three groups according to the occurrence of AF: Group A (n = 22) - patients with no AF, Group B (n = 11) - patients with new onset AF postoperatively and Group C (n = 9) - patients with preoperative history of atrial fibrillation. The serum levels of PTX3, CRP, TLR2, IL-8, IL-18, sFas, MMP-7 and MMP-8 were measured at the following time points: before surgery, immediately and 6 h after surgery and on the 1(st), 3(rd) and 7(th) postoperative days (POD). RESULTS: Serum levels of PTX3 showed a significant difference between Groups A and C on the 3(rd) POD (p<0.05) and on the 7(th) POD (p<0.0001). IL-8 levels were different between Groups A and C immediately after surgery (p<0.05), 6 hours after surgery (p<0.05) and on the 3(rd) POD (p<0.05). There was a difference between Groups B and C on the 1(st) POD in IL-8 levels (p<0.05). The sFas levels differed between Groups A and C on the 3(rd) POD (p<0.01) and the 7(th) POD (p<0.05). There was also a difference on the 7(th) POD (p<0.05) between the Groups B and C. No significant differences between the groups was seen for other biomarkers. CONCLUSION: This study demonstrates significantly different dynamics of PTX3, IL-8 and sFas levels after cardiac surgery in relation to AF.
- MeSH
- biologické markery krev MeSH
- C-reaktivní protein metabolismus MeSH
- fibrilace síní krev chirurgie MeSH
- kardiochirurgické výkony MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- sérový amyloidový protein metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH