Autoimmune thyroiditis (AIT) and type 2 diabetes mellitus (DM2) are the most common endocrinological diseases worldwide. Relation between these diseases explains several hypotheses. One of them is influence of some adipocytokines. This study evaluated association between three adipocytokines (adiponectin, resistin and visfatin) and thyroid and glycid status in patients with DM2 and AIT compared to the control group (CG). The group consisted of four subgroups: patients with DM2 without thyreopathies, patients with AIT on substitution therapy without diabetes and prediabetes, patients with DM2 and AIT on substitution therapy and healthy subjects as the CG. We investigated parameters of thyroid and glucose metabolism and serum levels of three adipocytokines. The mean level of resistin in the group of patients with diabetes and thyroiditis was significantly higher than in patients with thyroiditis without diabetes and than in the CG. We found a weak negative correlation between visfatin and fasting glucose levels in patients with thyroiditis without diabetes. We detected a weak negative correlation between resistin and glycated haemoglobin and a weak negative correlation between visfatin and thyroid gland volume in patients with diabetes without thyroiditis. In the CG we determined a weak positive correlation between visfatin and free thyroxin. Our results are consistent with several studies, which confirmed association between AIT and adipocytokines.

• MeSH
• Adipokines blood   MeSH
• Thyroiditis, Autoimmune blood   complications   diagnostic imaging   MeSH
• Cytokines blood   MeSH
• Diabetes Mellitus, Type 2 blood   complications   MeSH
• Adult MeSH
• Glycated Hemoglobin metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Nicotinamide Phosphoribosyltransferase blood   MeSH
• Aged MeSH
• Thyroid Gland diagnostic imaging   MeSH
• Case-Control Studies MeSH
• Ultrasonography MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Introduction: The amniotic fluid nicotinamide phosphoribosyltransferase (NAMPT) levels have not been compared among women with preterm prelabor rupture of membranes (PPROM) comorbid with intra-amniotic infection, sterile intra-amniotic inflammation (IAI), colonization, or without IAI and microbial invasion of the amniotic cavity (MIAC). Therefore, the main aim was to quantify the amniotic fluid NAMPT in women with PPROM complicated by intra-amniotic infection, sterile IAI, or colonization. The second aim was to characterize the diagnostic indices of NAMPT to reveal IAI. The third aim was to determine whether the cervical fluid and maternal serum NAMPT quantitation might be of value in the identification of intra-amniotic inflammatory complications in PPROM.Methods of study: NAMPT levels in amniotic fluid, cervical fluid, and maternal serum were assessed in three independent cohorts of women with singleton pregnancies complicated by PPROM between 24+0 and 36+6 weeks of gestation consisting of 88, 121, and 88 women, respectively. Amniotic fluid samples were obtained by transabdominal amniocentesis, cervical fluid samples were obtained using a Dacron polyester swab and maternal blood was obtained by venipuncture of the cubital vein. The NAMPT levels were measured by an enzyme-linked immunosorbent assay. Testing for MIAC and IAI was performed on all women, who were then categorized into four subgroups: intra-amniotic infection (MIAC and IAI), sterile IAI (IAI alone), colonization (MIAC alone), and without MIAC and IAI.Results: Women with intra-amniotic infection and women with sterile IAI had higher NAMPT levels than did women with colonization and women without MIAC and IAI (intra-amniotic infection: median 73.6 ng/mL, sterile IAI: median 55.5 ng/mL, colonization: median 12.1 ng/mL, without MIAC and IAI: 10.6 ng/mL; p < .0001). An amniotic fluid NAMPT level of 37 ng/mL was the best value for the detection of intra-amniotic infection in women with PPROM. Cervical fluid (p = .51) and maternal serum (p = .50) NAMPT levels did not reflect intra-amniotic inflammatory complications in women with PPROM.Conclusions: Intra-amniotic infection and sterile IAI are associated with higher NAMPT levels in amniotic fluid but not in cervical fluid or maternal serum in women with PPROM. Amniotic fluid NAMPT might be a marker for invasive identification of IAI in PPROM.

• MeSH
• Chorioamnionitis * diagnosis   MeSH
• Gestational Age MeSH
• Humans MeSH
• Nicotinamide Phosphoribosyltransferase MeSH
• Infant, Newborn MeSH
• Amniotic Fluid MeSH
• Fetal Membranes, Premature Rupture * MeSH
• Pregnancy MeSH
• Inflammation MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Serrated adenocarcinoma (SAC) and colorectal carcinomas showing histological and molecular features of high-level of microsatellite instability (hmMSI-H) are both end points of the serrated pathway of colorectal carcinogenesis. Despite common features (right-sided location, CpG island methylation phenotype and BRAF mutation) there are no studies comparing the microRNA (miRNA) expression profiles in SACs and hmMSI-H. The microtranscriptome from 12 SACs and 8 hmMSI-H were analysed using Affymetrix GeneChip miRNA 3.0 arrays and differentially enriched functions involving immune response were observed from this comparison. miR-181a-2* was found significantly more expressed in hmMSI-H than in SAC and higher expression of this miRNA in microsatellite unstable colorectal cancer were corroborated by Real-Time PCR in an extended series (61 SAC, 21 hmMSI-H). An analysis of genes possibly regulated by miR-181a-2* was carried out and, amongst these, an inverse correlation of NAMPT with miR-181a-2* expression was observed, whereas, for TRAF1 and SALL1, additional regulation mechanisms involving CpG island methylation were observed. miR-181a-2* is associated with particular histological and molecular features of colorectal carcinomas within the serrated pathological pathway and might play a role in the immune responses of microsatellite instability carcinomas.

• MeSH
• CpG Islands MeSH
• Cytokines genetics   metabolism   MeSH
• TNF Receptor-Associated Factor 1 genetics   metabolism   MeSH
• Gene Ontology MeSH
• Carcinoma genetics   metabolism   physiopathology   MeSH
• Colorectal Neoplasms genetics   metabolism   physiopathology   MeSH
• Humans MeSH
• DNA Methylation MeSH
• MicroRNAs genetics   metabolism   MeSH
• Microsatellite Instability * MeSH
• Cell Line, Tumor MeSH
• Nicotinamide Phosphoribosyltransferase genetics   metabolism   MeSH
• Gene Expression Regulation, Neoplastic genetics   MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Aged MeSH
• Transcription Factors genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The purpose of this cross-sectional study was to assess the visfatin levels in patients with axial spondyloarthritis (axSpA) and to investigate the association between visfatin, disease activity and radiographic spinal damage. Serum visfatin levels were determined by enzyme-linked immunosorbent assay in 64 patients with axSpA (46 with radiographic axSpA (r-axSpA) and 18 with non-radiographic axSpA (nr-axSpA)) and 61 age-/sex-matched healthy individuals. Patients with r-axSpA were further divided into two subsets based on radiographic spinal damage using modified Stoke Ankylosing Spondylitis Spine Score (mSASSS = 0 and mSASSS ≥ 1). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess disease activity. C-reactive protein (CRP) levels and human leukocyte antigen (HLA)-B27 were determined. Visfatin levels were significantly higher in patients with axSpA and in the subgroup of patients with r-axSpA than in healthy individuals (p = 0.010 and p = 0.005, respectively), with no difference between patients with r-axSpA and with nr-axSpA. In general, disease activity was high (mean BASDAI 5.01) and was moderately correlated with visfatin levels (r = 0.585; p = 0.011) in patients with nr-axSpA. Visfatin levels correlated with mSASSS (r = 0.281; p = 0.026) and were significantly higher in axSpA patients with mSASSS ≥ 1 than in those with mSASSS = 0 (p = 0.025). Our study showed that circulating visfatin levels are elevated in axSpA patients, may be associated with disease activity in early phase of the disease and with the degree of radiographic spinal involvement.

• MeSH
• Lumbar Vertebrae diagnostic imaging   MeSH
• Cytokines blood   MeSH
• Adult MeSH
• Cervical Vertebrae diagnostic imaging   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Nicotinamide Phosphoribosyltransferase blood   MeSH
• Spine diagnostic imaging   MeSH
• Cross-Sectional Studies MeSH
• Sacroiliac Joint diagnostic imaging   MeSH
• Spondylarthropathies blood   diagnostic imaging   physiopathology   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVES: Little is known about the role of adipokines in the pathogenesis of coronary artery disease in young patients. The aims of this study were to compare serum levels of adipokines and expression of adipokines in peripheral blood leukocytes in patients with premature coronary artery disease (CAD), metabolic syndrome and healthy individuals. DESIGN AND METHODS: Sixty-five patients with premature CAD (men 18-45years old and women 18-55years old) formed the study group. The control groups were 75 patients with metabolic syndrome and 50 healthy individuals. For each group, RNA expression in peripheral blood leukocytes was determined for 24 different adipokines and 11 adipokines were examined in serum. RESULTS: In individuals with CAD, serum visfatin levels were significantly higher than in metabolic syndrome and healthy controls (2.3 vs. 1.6 vs. 0.7µg/L, P<0.001) while both omentin-1 (92.9 vs. 587.0 vs. 552.3µg/L, P<0.001) and ZAG2 (45.5 vs. 72.5 vs. 77.1mg/L, P<0.001) levels were lower. The receiver operating curve (ROC) analysis for testing the validity of these adipokines in the diagnosis of CAD compared to control groups provided the following areas under the curve (AUC): omentin-1 AUC 0.97 (cut-off ≤222µg/L), ZAG2 AUC 0.89 (cut-off ≤51.7mg/L) and visfatin AUC 0.74 (cut-off ≥1.0µg/L) (P<0.001 in all cases). Visfatin and omentin-1 serum levels did not differ between the acute phase of myocardial infarction and the chronic phase of CAD. In patients with CAD, we found no significant relation between mRNA expression and adipokine concentration. CONCLUSION: Serum omentin-1, visfatin and ZAG2 could serve as biomarkers of premature CAD in young apparently healthy people.

• MeSH
• Adipokines blood   genetics   metabolism   MeSH
• Cytokines blood   genetics   MeSH
• Adult MeSH
• GPI-Linked Proteins blood   genetics   MeSH
• Myocardial Infarction blood   genetics   MeSH
• Cohort Studies MeSH
• Lectins blood   genetics   MeSH
• Leukocytes metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA, Messenger blood   MeSH
• Metabolic Syndrome blood   genetics   MeSH
• Adolescent MeSH
• Coronary Artery Disease blood   genetics   MeSH
• Nicotinamide Phosphoribosyltransferase blood   genetics   MeSH
• Subcutaneous Fat metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Nicotinamide phosphoribosyltransferase (NAMPT) is located in both the nucleus and cytoplasm and has multiple biological functions including catalyzing the rate-limiting step in NAD synthesis. Moreover, up-regulated NAMPT expression has been observed in many cancers. However, the determinants and regulation of NAMPT's nuclear transport are not known. Here, we constructed a GFP-NAMPT fusion protein to study NAMPT's subcellular trafficking. We observed that in unsynchronized 3T3-L1 preadipocytes, 25% of cells had higher GFP-NAMPT fluorescence in the cytoplasm, and 62% had higher GFP-NAMPT fluorescence in the nucleus. In HepG2 hepatocytes, 6% of cells had higher GFP-NAMPT fluorescence in the cytoplasm, and 84% had higher GFP-NAMPT fluorescence in the nucleus. In both 3T3-L1 and HepG2 cells, GFP-NAMPT was excluded from the nucleus immediately after mitosis and migrated back into it as the cell cycle progressed. In HepG2 cells, endogenous, untagged NAMPT displayed similar changes with the cell cycle, and in nonmitotic cells, GFP-NAMPT accumulated in the nucleus. Similarly, genotoxic, oxidative, or dicarbonyl stress also caused nuclear NAMPT localization. These interventions also increased poly(ADP-ribosyl) polymerase and sirtuin activity, suggesting an increased cellular demand for NAD. We identified a nuclear localization signal in NAMPT and amino acid substitution in this sequence (424RSKK to ASGA), which did not affect its enzymatic activity, blocked nuclear NAMPT transport, slowed cell growth, and increased histone H3 acetylation. These results suggest that NAMPT is transported into the nucleus where it presumably increases NAD synthesis required for cell proliferation. We conclude that specific inhibition of NAMPT transport into the nucleus might be a potential avenue for managing cancer.

• MeSH
• Acrylamides pharmacology   MeSH
• Active Transport, Cell Nucleus MeSH
• Cell Nucleus metabolism   MeSH
• 3T3-L1 Cells MeSH
• Hep G2 Cells MeSH
• Cytoplasm metabolism   MeSH
• Histones metabolism   MeSH
• Cell Cycle Checkpoints MeSH
• Humans MeSH
• Mutagenesis, Site-Directed MeSH
• Mice MeSH
• NAD metabolism   MeSH
• Nicotinamide Phosphoribosyltransferase chemistry   genetics   metabolism   MeSH
• Oxidative Stress MeSH
• Piperidines pharmacology   MeSH
• Poly(ADP-ribose) Polymerases metabolism   MeSH
• Cell Proliferation MeSH
• Recombinant Fusion Proteins chemistry   genetics   metabolism   MeSH
• Sirtuins metabolism   MeSH
• Cell Survival drug effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVES: The aim of the study is to investigate differences in visfatin concentrations between mothers with term and preterm birth (PTB) and between mothers who delivered within seven days and after more than seven days following admission for PTB/preterm premature rupture of membranes (PPROMs). METHODS: Maternal peripheral blood and cord blood were collected from 56 mothers with PTB (31 with PPROM) and 71 mothers with term delivery (three with PPROM). RESULTS: Maternal visfatin concentration was significantly higher for given gestational age in PTBs compared to term deliveries (p = .021) and also in mothers who delivered within seven days after admission for PTB or PPROM, compared to those who delivered after more than seven days (p = .027; p = .039). Cord blood visfatin concentration was found to be decreased in preterm compared to term infants (p = .007). CONCLUSIONS: Visfatin in both maternal and fetal circulation may play an important role in the pathogenesis of PTB/PPROM and could be used to distinguish between women who will deliver in a short period of time after clinical presentation of PTB/PPROM and those who deliver later. Nevertheless, additional research is necessary in order to identify its direct involvement in PTB/PPROM.

• MeSH
• Cytokines blood   genetics   MeSH
• Adult MeSH
• Fetal Blood chemistry   MeSH
• Genotype MeSH
• Polymorphism, Single Nucleotide MeSH
• Humans MeSH
• Nicotinamide Phosphoribosyltransferase blood   genetics   MeSH
• Fetal Membranes, Premature Rupture blood   genetics   MeSH
• Premature Birth blood   genetics   MeSH
• Case-Control Studies MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Dizertační práce, která se zaměřila na výzkum idiopatických zánětlivých myopatií a roli BAFF, interferonu alfa, visfatinu a autoprotilátek.

• MeSH
• Autoantibodies MeSH
• B-Cell Activating Factor MeSH
• Phenotype MeSH
• Immunologic Tests MeSH
• Interferon-alpha MeSH
• RNA, Messenger MeSH
• Myositis MeSH
• Nicotinamide Phosphoribosyltransferase MeSH
• B-Cell Activation Factor Receptor MeSH
• Publication type
• Academic Dissertation MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• alergologie a imunologie
• ortopedie

Visfatin is a multi-functional molecule that can act intracellularly and extracellularly as an adipokine, cytokine and enzyme. One of the main questions concerning visfatin is the mechanism of its secretion; whether, how and from which cells visfatin is released. The objective of this in vitro study was to observe the active secretion of visfatin from 3T3-L1 preadipocytes and adipocytes, HepG2 hepatocytes, U-937, THP-1 and HL-60 monocytes and macrophages. The amount of visfatin in media and cell lysate was always related to the intracellular enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), to exclude the passive release of visfatin. Visfatin was not found in media of 3T3-L1 preadipocytes. In media of 3T3-L1 adipocytes and HepG2 hepatocytes, the ratio of visfatin to the amount of GAPDH was identical to cell lysates. Hence, it is likely that these cells do not actively secrete visfatin in a significant manner. However, we found that significant producers of visfatin are differentiated macrophages and that the amount of secreted visfatin depends on used cell line and it is affected by the mode of differentiation. Results show that 3T3-L1 adipocytes and HepG2 hepatocytes released visfatin only passively during the cell death. U-937 macrophages secrete visfatin in the greatest level from all of the tested cell lines.

• MeSH
• 3T3-L1 Cells MeSH
• Hep G2 Cells MeSH
• Hepatocytes secretion   MeSH
• Humans MeSH
• Macrophages secretion   MeSH
• Mice MeSH
• Nicotinamide Phosphoribosyltransferase secretion   MeSH
• Adipocytes secretion   MeSH
• U937 Cells MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Přesná úloha visfatinu v průběhu patologických kloubních onemocnění není doposud zcela objasněna. Grantový projekt je zaměřen na zhodnocení podílu visfatinu na imunitní odpovědi v průběhu RA. Pomocí cytometrických metod budou blíže typizovány buňky periferní krve a synoviální tekutiny produkující visfatin. Pomocí genové interference bude sledována intracelulární role visfatinu v těchto buňkách a bude hodnocen vliv farmakologické intervence biologickou léčbou na hladiny visfatinu s cílem blíže charakterizovat visfatin jako potenciální prognostický marker revmatoidní artritidy a dále prostudovat potenciální terapeutické využití jeho inhibice u autoimunitních onemocnění.; The exact role of visfatin in the processes of pathological joint diseases has not yet been fully explained. The grant project focuses upon the evaluation of the function visfatin fulfils in the immune response in the course of RA. Using cytometry methods, visfatin-producing cells of the peripheral blood and synovial fluid will be characterised in more detail. Using gene interference, the intracellular role of visfatin in these cells will be monitored and the impact of biotherapeutic pharmacological intervention upon visfatin levels will be monitored in order to obtain a more detailed characteristics of visfatin as a potential prognostic marker for rheumatoid arthritis, and, furthermore, to study the potential therapeutic application of its inhibition in autoimmune diseases.

• MeSH
• Antigens, CD20 blood   drug effects   MeSH
• Biological Therapy MeSH
• Biomarkers analysis   MeSH
• Nicotinamide Phosphoribosyltransferase MeSH
• Prognosis MeSH
• Flow Cytometry MeSH
• Arthritis, Rheumatoid physiopathology   MeSH
• RNA Interference MeSH
• Synovial Fluid MeSH
• Tumor Necrosis Factor-alpha antagonists & inhibitors   blood   drug effects   MeSH

• Conspectus
• Biochemie. Molekulární biologie. Biofyzika
• NML Fields
• biochemie
• farmacie a farmakologie
• alergologie a imunologie
• revmatologie
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR