Intra-amniotic infections (IAI) are one of the reasons for preterm birth. High mobility group box 1 (HMGB1) is a nuclear protein with various physiological functions, including tissue healing. Its excessive extracellular release potentiates inflammatory reaction and can revert its action from beneficial to detrimental. We infected the amniotic fluid of a pig on the 80th day of gestation with 1 × 104 colony forming units (CFUs) of E. coli O55 for 10 h, and evaluated the appearance of HMGB1, receptor for glycation endproducts (RAGE), and Toll-like receptor (TLR) 4 in the amniotic membrane and fluid. Sham-infected amniotic fluid served as a control. The expression and release of HMGB1 were evaluated by Real-Time PCR, immunofluorescence, immunohistochemistry, and ELISA. The infection downregulated HMGB1 mRNA expression in the amniotic membrane, changed the distribution of HMGB1 protein in the amniotic membrane, and increased its level in amniotic fluid. All RAGE mRNA, protein expression in the amniotic membrane, and soluble RAGE level in the amniotic fluid were downregulated. TLR4 mRNA and protein expression and soluble TLR4 were all upregulated. HMGB1 is a potential target for therapy to suppress the exaggerated inflammatory response. This controlled expression and release can, in some cases, prevent the preterm birth of vulnerable infants. Studies on suitable animal models can contribute to the development of appropriate therapy.

• MeSH
• amnion imunologie   mikrobiologie   patologie   MeSH
• Escherichia coli růst a vývoj   patogenita   MeSH
• infekce vyvolané Escherichia coli genetika   imunologie   mikrobiologie   veterinární   MeSH
• infekční komplikace v těhotenství genetika   imunologie   mikrobiologie   veterinární   MeSH
• interakce hostitele a patogenu genetika   imunologie   MeSH
• lidé MeSH
• messenger RNA genetika   imunologie   MeSH
• modely nemocí na zvířatech MeSH
• plodová voda imunologie   mikrobiologie   MeSH
• prasata MeSH
• předčasný porod prevence a kontrola   MeSH
• protein HMGB1 genetika   imunologie   MeSH
• receptor pro konečné produkty pokročilé glykace genetika   imunologie   MeSH
• regulace genové exprese MeSH
• signální transdukce MeSH
• těhotenství MeSH
• toll-like receptor 4 genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The receptor for the advanced glycation end products (RAGE) is a multiligand transmembrane receptor involved in chronic inflammation whose specific polymorphisms of the promoter gene were found to increase its transcriptional activity. We investigated the association of both allelic and genotypic -374T/A and -429T/C polymorphisms with inflammatory bowel disease. The STREGA guidelines were applied for planning and reporting. We enrolled 133 patients with Crohn's disease (CD), 149 with ulcerative colitis (UC), and 128 blood donors. Genomic DNA was extracted from peripheral blood leukocytes collected from each patient and control. RAGE polymorphisms were analyzed by PCR-restriction fragment length polymorphism assay. The Hardy-Weinberg equilibrium was first assessed, and then, the Kruskal-Wallis test and the Fisher exact test were used for etiologic group comparisons. Distribution of patients' characteristics across genotypes was evaluated by the Fisher exact test, while that across alleles was analyzed with a probit model. A 2-sided value of p < 0.05 was considered significant. Following the evidence of the Hardy-Weinberg equilibrium, we found a higher prevalence of the allele A of the -374T/A haplotype in UC (p = 0.043), and of the allele C of the -429T/C haplotype in CD (p < 0.001) with respect to the other groups. Moreover, the homozygous AA genotype of the -374T/A polymorphism resulted associated with late onset of CD, while its TT genotype with early onset (p = 0.049). The allele C of the 429T/C haplotype was associated with early onset of UC (p = 0.03), while a higher frequency of the heterozygous TC haplotype was found in those with pancolitis (p = 0.026). The differing distribution of these polymorphisms in healthy donors and CD/UC patients suggests a role in the development and outcome of these pathological conditions.

• MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci * MeSH
• genotyp MeSH
• genotypizační techniky MeSH
• idiopatické střevní záněty genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• polymorfismus délky restrikčních fragmentů MeSH
• prevalence MeSH
• promotorové oblasti (genetika) * MeSH
• receptor pro konečné produkty pokročilé glykace genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Receptor for advanced glycation end products and glyoxalase I metabolizing advanced glycation end product precursors may play important role in the pathogenesis and progression of cancer. Potential relation between soluble forms of receptor for advanced glycation end products (sRAGE), receptor for advanced glycation end products, glyoxalase I polymorphisms, and long-term outcome (median follow-up of 10.3 years) was studied in 116 patients with breast cancer. Gly82Ser and 2184 A/G RAGE polymorphisms were related to the mortality due to the breast cancer and -419 A/C glyoxalase I polymorphism was related to the overall mortality of the patients suggesting their role not only in the risk of breast cancer but also in the outcome of patients with breast cancer.

• MeSH
• dospělí MeSH
• jednonukleotidový polymorfismus MeSH
• Kaplanův-Meierův odhad MeSH
• laktoylglutathionlyasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu genetika   mortalita   patologie   MeSH
• receptor pro konečné produkty pokročilé glykace genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Patients with type 2 diabetes (T2DM) are at increased risk of fractures. The aim of this study is to analyze the prevalence and risk factors of osteoporosis and osteoporosis related fractures in postmenopausal women with T2DM. METHODS: A total of 112 postmenopausal women with T2DM and 171 control nondiabetic women received a standardized questionnaire on osteoporosis risk factors, and were evaluated for bone mineral density (BMD, by using a dual energy X-ray absorptiometry), biochemical markers of bone and glucose metabolism, soluble receptor for advanced glycation end products (sRAGE) and its gene polymorphisms (rs1800625 or rs2070600). RESULTS: In T2DM patients the prevalence of osteoporosis was 25% and low trauma vertebral (Vfx) and non-vertebral fractures were found in 8% and 19% women, respectively. When compared between subjects with and without fractures, there were no significant differences in BMD at any site between the groups, except for distal radius, which was significantly lower in T2DM women with Vfx (p<0.05 vs.non-fractured without osteoporosis). We found no associations between bone and glucose metabolism variables, sRAGE and BMD. No significant differences were observed in sRAGE levels according to their rs1800625, rs 2070600 genotype or fracture prevalence. Serum osteocalcin was significantly lower in T2DM women (p<0.01 vs. controls) and in T2DM women with Vfx (p<0.05) vs. non-fractured without osteoporosis. T2DM women with low daily walking activity (< 2 h daily) had significantly higher serum sclerostin levels (p<0.05 vs. those who were walking > 2 h daily). CONCLUSION: Diabetes-specific parameters as well as RAGE polymorphisms did not associate with BMD or fractures in T2DM postmenopausal women. Lower levels of osteocalcin, namely in those with Vfx and higher sclerostin levels in those with low daily walking activity suggest lower bone remodeling and/or decreased bone quality in T2DM.

• MeSH
• absorpční fotometrie MeSH
• biologické markery krev   MeSH
• diabetes mellitus 2. typu epidemiologie   MeSH
• genetické markery MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus MeSH
• kostní denzita MeSH
• kostní morfogenetické proteiny krev   MeSH
• krevní glukóza metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteokalcin krev   MeSH
• osteoporotické fraktury epidemiologie   MeSH
• postmenopauzální osteoporóza epidemiologie   MeSH
• prevalence MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• receptor pro konečné produkty pokročilé glykace krev   genetika   MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

BACKGROUND AND AIMS: Activation of RAGE due to its increased expression in cancer cells or its stimulation by multiple ligands (AGEs, HMGB1, S100 proteins, etc.) may contribute to the proliferation, invasiveness of tumor cells and formation of distant metastases and also to the resistance of cancer to treatment. RAGE ligands could thus become both useful markers of disease severity and its outcome and, a potential therapeutic target. CONCLUSIONS: Better understanding of the role of RAGE activation in different types of cancer may help to define the role of ligand/RAGE antagonists as promising cancer treatment.

• MeSH
• karcinogeneze genetika   metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• metastázy nádorů MeSH
• mutace genetika   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory diagnóza   terapie   MeSH
• polymorfismus genetický genetika   MeSH
• produkty pokročilé glykace genetika   metabolismus   MeSH
• protein HMGB1 metabolismus   MeSH
• proteiny S100 metabolismus   MeSH
• receptor pro konečné produkty pokročilé glykace antagonisté a inhibitory   genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH