Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study evaluated the role of amino acids supplementation on the heart's adaptation under extensive training conditions. Sixty active athletes (bicyclists and swimmers) were separated into 2 groups: 30 were given amino acid mixture (1 g per 10 kg of body weight) for a period of 1 month, and the other 30 were given placebo for the same duration (control group). In the same time period, 20 subjects of similar age not engaged in physical training or sports activities were used as the additional control group. Blood concentrations of alanine transaminase (ALT), asparagine transaminase, lactate dehydrogenase (LDH), gamma-glutamil transpeptidase, alkaline phosphatase (ALP), amylase, triglycerides, albumin, interleukin-6 (IL-6), and interleukin-10 (IL-10) were determined for all subjects before and after the intervention period. Concentrations of LDH and ALP were increased, but concentrations of ALT, albumin, and triglycerides were decreased in the blood of trained athletes compared with healthy subjects not engaged in sports activities. In the athletes, some increases in IL-6 levels were noted; however, they were significantly (p < 0.05) lower than in patients with myocardiodystrophy. The values of IL-10 in athletes were higher than concentrations of IL-10 in patients with myocardiodystrophy but still lower than the normal values. The inhibition of IL-10 in blood may play an important role in the induction of apoptosis in cells of the heart muscle. After amino acid supplementation, the athletes' values for albumin, triglycerides, IL-10, LDH, and ALP were significantly increased compared with the post-placebo control groups. Enzyme activities of other enzymes remained unchanged in all groups. Histological data from a secondary study of actual heart tissue showed that the amino acids supplementation may have inhibiting effects on myocardial apoptosis. The criteria of efficiency of the amino acids supplementation were defined by the albumin, IL-6, and IL-10 concentrations.
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PMID:Biochemical and heart adaptations to physical training and supplementation with amino acids. 1557 76

Serum concentrations of interleukin-6 (IL-6), IL-6-soluble receptor (sIL-6R), IL-6 gp130-soluble receptor (sgp130), ligand of receptor activator of nuclear factor (NF)-kappaB (RANKL), and osteoprotegerin (OPG) were determined in 42 patients with polyostotic Paget's disease of bone (PDB) and acquired resistance to clodronate (M/F ratio 23:19; mean age 58.5 +/- 9.4 years) in acute phase of disease and after oral risedronate treatment (30 mg/day for 8 weeks). At baseline, pagetic patients showed higher levels of OPG, sIL-6R, and IL-6 with lower levels of sgp130 compared to 24 age- and sex-matched controls (respectively, 4.69 +/- 1.27 vs. 2.87 +/- 0.54 pmol/L; 40.89 +/- 8.61 vs. 30.98 +/- 4.24 ng/ml; 3.59 +/- 0.97 vs. 1.8 +/- 0.9 pg/ml; 327.34 +/- 43.41 vs. 411.7 +/- 79.5 ng/ml). Response to treatment is related to a significant increase of OPG levels in all patients (from 4.69 +/- 1.27 to 5.48 +/- 1.31 pmol/L). The disease remission, that is, total alkaline phosphatase (tALP) levels within the normal range after therapy, was associated with a simultaneous increase in OPG and sgp130 levels. In patients with tALP higher than the normal range after therapy, the OPG increase was associated with a parallel increase in RANKL levels. Our data suggest that serum levels of components of RANKL/OPG and IL-6 systems, before and after treatment, may be used to better define a therapeutical strategy in pagetic patients.
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PMID:Interleukin-6 and osteoprotegerin systems in Paget's disease of bone: relationship to risedronate treatment. 1577 35

Proinflammatory and anti-inflammatory cytokine balance and associated changes in pulmonary bronchoalveolar lavage fluid (BALF) of unleaded gasoline exhaust (GE) exposed mice were investigated. Animals were exposed to GE (1 L/min of GE mixed with 14 L/min of compressed air) using a flow-past, nose-only, dynamic inhalation exposure chamber for different durations (7, 14, and 21 days). The particulate content of the GE was found to be 0.635, +/-0.10 mg PM/m3. Elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were observed in BALF of GE-exposed mice, but interleukin 1beta(IL-1beta) and the anti-inflammatory cytokine interleukin-10 (IL-10) remained unaffected. GE induced higher activities of alkaline phosphatase (ALP), gamma-glutamyl transferase (gammaGT), and lactate dehydrogenase (LDH) in the BALF, indicating Type II alveolar epithelial cell injury, Clara-cell injury, and general toxicity, respectively. Total protein in the BALF increased after 14 and 21 days of exposure, indicating enhanced alveolar-capillary permeability. However, the difference in the mean was found statistically insignificant in comparison to the compressed air control. Total cell count in the BALF of GE-exposed mice ranged between 0.898 and 0.813x10(6) cells/ml, whereas the compressed air control showed 0.65x10(6) cells/mL. The histopathological changes in GE-exposed lung includes perivascular, and peribronchiolar cuffing of mononuclear cells, migration of polymorphonuclear cells in the alveolar septa, alveolar thickening, and mild alveolar edematous changes indicating inflammation. The shift in pro- and anti-inflammatory cytokine balance and elevation of the pulmonary marker enzymes indicate toxic insult of GE. This study will help in our understanding of the mechanism of pulmonary injury by GE in the light of cytokine profiles, pulmonary marker enzymes, and lung architecture.
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PMID:Proinflammatory and anti-inflammatory cytokine balance in gasoline exhaust induced pulmonary injury in mice. 1578 77

This structured review discusses the current literature on selected biomarkers and their ability to predict preterm delivery (PTD). Among symptomatic women, the likelihood ratio (LR+) for the prediction of PTD was found to be greater than 10 using amniotic fluid (AF) interleukin-6 (IL-6), AF Ureaplasma urealyticum, as well as a multi-marker consisting of cervical IL-6, cervical IL-8, and cervical length (CL). The LR+ was found to be between 5 and 10 for serum C-reactive protein (CRP). An LR+ between 2.5 and 5 was recorded for serum corticotropin-releasing hormone (CRH), cervical fetal fibronectin (fFN), cervical IL-6, serum relaxin, and a multi-marker consisting of fFN and CL. CL and bacterial vaginosis (BV) both predicted PTD in women with preterm labor with an LR+ of less than 2.5. In asymptomatic women, AF U. urealyticum and a multimarker consisting of five individual markers [fFN, CL, serum alpha-fetoprotein (AFP), serum alkaline phosphatase, and serum granulocyte colony-stimulating factor (G-CSF)] predicted PTD with an LR+ greater than 10. The LR+ was between 5 and 10 for serum relaxin and CL. LRs+ recorded for serum alkaline phosphatase, salivary estriol, serum CRH, serum G-CSF, cervical IL-6, AF IL-6, cervical fFN, AFP, and Chlamydia all ranged between 2.5 and 5. Finally, an LR+ below 2.5 has been documented for serum ferritin, serum CRP, BV, and cervical ferritin.
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PMID:Biomarkers for the prediction of preterm delivery. 1590 Dec 57

Certain plant-derived compounds show selective estrogen receptor modulator (SERM) activity and may therefore be an alternative to the conventional hormone replacement therapy, which prevents osteoporosis but is also associated with an increased risk of breast and endometrial cancers. In the current study, we tested the effects of the hop-derived compounds 8-prenylnaringenin, 6-prenylnaringenin, xanthohumol and isoxanthohumol (1) to modulate markers of differentiation and gene expression in osteoblasts and (2) to regulate proliferation in MCF-7 breast cancer cells. Additionally, we analyzed the ER-binding affinities of these hop compounds as well as the ER-mediation of their effects. Bone-forming activity and ER-subtype specificity were investigated by measuring alkaline phosphatase (AP) activity in hFOB/ERalpha cells and regulation of gene transcription for AP, interleukin-6, pS2 and von Willebrand factor (VWF) in U-2 OS/ERalpha and U-2 OS/ERbeta cells. Our results demonstrate that AP, pS2 and VWF mRNA levels are significantly increased by the compounds in an estrogen-like manner via both ERalpha and ERbeta, while IL-6 is down-regulated in U-2 OS/ERalpha cells. Consistently, AP enzymatic activity is up-regulated by all compounds in hFOB/ERalpha9 cells. Depending on their concentration, all compounds show proliferative effects in MCF-7 cells. Except for 8-PN the hop constituents display an ERbeta-preference. Reversal of estrogen-specific AP-induction in Ishikawa cells indicates an ER-regulated mechanism. Finally, the flavonoids display cytotoxic effects only at high concentrations (> or =10(-4)M). In summary, we have demonstrated for the first time that specific phytoestrogen compounds found in hop extracts exert estrogen-like activities on bone metabolism. Regarding a potential for use in osteoporosis-prevention therapy, the dosage of a phytoestrogen, which is taken, will play an important role concerning a desired in vivo profile.
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PMID:Regulation of osteoblastic phenotype and gene expression by hop-derived phytoestrogens. 1601 5

The aim of the study was to determine factors of risk and progress of aortal valvular calcinosis (AVC) and aortic ostium stenosis (AOS). The subjects were 85 patients with AVC (42--with aortic valvular stenosis (AVS), and 43--without AOS). The study, which included analysis of the lipid and mineral metabolism, and immunological tests, shows that potential factors of AVC are: age (p < 0. 001), osteoporosis (p < 0.03), mitral ring calcification (p = 0.047), dislipidemia (high serum level of total cholesterol, cholesterol of low density lipoproteins, and apoB, atherogenic shift of apoB/apoA-1 ratio, low level of cholesterol of high density lipoproteins (CHDLP)), disbalance between intecellular matrix synthesis and destruction (high concentration of alkaline phosphatase and its bone fraction, and accelerated deoxypyridinoline excretion), inflammation (high concentration of C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6)). The factors of AOS were: age (p < 0.001), smoking (p < 0.001), osteoporosis (p = 0.004), AVC (p < 0.001), mitral ring calcinosis (p = 0.033), dislipidemia (high levels of cholesterol of low density and very low density lipoproteins, low concentrations of CHDLP, and apoA-1), degradation of extracellular matrix, and inflammation (high concentrations of CRP, fibrinogen, IL-6, and IL-8). Thus, atherogenic dislipidemia and mineral dysmetabolism disorder facilitate AVC. The revealed immune status changes imply the role of inflammation in the development and progress of AVS.
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PMID:[Factors facilitating development of degenerative aortic valvular stenosis]. 1607 46

This study was conducted to identify bone resorption and anti-inflammatory effects with intermittent cyclical etidronate therapy (ICET) in patients with rheumatoid arthritis, and anti-inflammatory effect of etidronate in vitro. We compared bone mineral density (BMD), urinary deoxypyridinoline (DPD) level, bone alkaline phosphatase (BAP) level and Larsen damage scores between the ICET and the non-ICET groups for 3 years. The levels of interleukin-6 (IL-6), prostaglandin E2 (PGE2), substance P and vascular endothelial growth factor (VEGF) in synovial cells from arthritis models were measured following the addition of etidronate. In the ICET group, BMD and BAP levels increased. Urinary DPD level and the Larsen damage score were significantly lower than that in the non-ICET group. In the in vitro study, the production of IL-6, PGE2, substance P and VEGF were inhibited in a dose-dependent manner. Bone resorption and destruction inhibition effect of etidronate remained for 3 years. In vitro study showed that the production of inflammatory cytokines and an angiogenesis factor were inhibited.
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PMID:Inhibitory effect of bone resorption and inflammation with etidronate therapy in patients with rheumatoid arthritis for 3 years and in vitro assay in arthritis models. 1613 81

Tissue formation and repair are dependent upon cascades of biological events, but the signals involved and the possible gene coexpression patterns during intramembranous bone repair are only poorly understood. We sought to place this mode of regeneration in context by profiling quantitative gene expression for a panel of 39 genes between days 1 and 14 following rat femoral marrow ablation. In situ hybridization was employed to localize a subset of genes. Additionally, principal components analysis was conducted to identify underlying factors suggestive of coexpression patterns. During inflammation (days 1-5), several genes, including cyclooxygenase-1 and -2, showed downregulation. Other proinflammatory cytokines, tumor necrosis factor-alpha and interleukin-1beta, exhibited increasing levels around day 5. During repair (days 3-10), growth factors, receptors, and inhibitor genes for transforming growth factor- beta; basic fibroblast growth factor; bone morphogenetic proteins 2, 4, and 7; vascular endothelial growth factor; and insulin-like growth factor-I were upregulated. In addition, the gene for core binding factor-alpha1 and markers of osteoblast function such as alkaline phosphatase, collagen type I, osteonectin, osteopontin, and osteocalcin had peak expression at day 5 or 7. The remodeling phase (days 10-14) was characterized by peaks for cytokines associated with osteoclastic activity including receptor activator of nuclear factor-kappaB, receptor activator of nuclear factor-kappaB ligand (RANKL), cathepsin K, tumor necrosis factor-alpha, interleukin-6, and cyclooxygenase-2. In situ hybridization showed that the most common sites of increased signal were within osteoblastic cells on trabecular and endosteal surfaces. Principal components analysis identified eight underlying factors that together explained over 80% of the variance in the data.
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PMID:Patterns and localization of gene expression during intramembranous bone regeneration in the rat femoral marrow ablation model. 1619 34

Fish oil supplementation is associated with lower risk of coronary artery disease in humans, and it has been shown to reduce ectopic calcification in an animal model. However, whether N-3 fatty acids, active ingredients of fish oil, have direct effects on calcification of vascular cells is not clear. In this report, we investigated the effects of eicosapentaenoic acid and docosahexaenoic acid (DHA) on osteoblastic differentiation and mineralization of calcifying vascular cells (CVCs), a subpopulation of bovine aortic medial cells that undergo osteoblastic differentiation and form calcified matrix in vitro. Results showed that N-3 fatty acids inhibited alkaline phosphatase (ALP) activity and mineralization of vascular cells, suggesting that they directly affect osteoblastic differentiation in vascular cells. By Western blot analysis, DHA activated p38-mitogen-activated protein kinase (MAPK) but not extracellular-regulated kinase (ERK) or Akt. An inhibitor of p38-MAPK partially reversed the inhibitory effects of DHA on osteoblastic differentiation and mineralization. Transient transfection experiments showed that DHA also activated peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Both p38-MAPK activator and PPAR-gamma agonists reproduced the inhibitory effects of DHA on CVC mineralization. Pretreatment with DHA also inhibited interleukin-6-induced ALP activity and mineralization. Together, these results suggest that N-3 fatty acids directly inhibit vascular calcification, and that the inhibitory effects are mediated by the p38-MAPK and PPAR-gamma pathways.
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PMID:N-3 fatty acids inhibit vascular calcification via the p38-mitogen-activated protein kinase and peroxisome proliferator-activated receptor-gamma pathways. 1651 67

Although recombinant human bone morphogenetic proteins (BMPs) are used locally for treating bone defects in humans, their systemic effect on bone augmentation has not been explored. We have previously demonstrated that demineralized bone (DB) from ovariectomized (OVX) rats cannot induce bone formation when implanted ectopically at the subcutaneous site. Here we showed in vitro that 17beta-estradiol (E2) specifically induced expression of Bmp6 mRNA in MC3T3-E1 preosteoblastic cells and that bone extracts from OVX rats lack BMPs. Next we demonstrated that 125I-BMP-6 administered systemically accumulated in the skeleton and also restored the osteoinductive capacity of ectopically implanted DB from OVX rats. BMP-6 applied systemically to aged OVX rats significantly increased bone volume and mechanical characteristics of both the trabecular and cortical bone, the osteoblast surface, serum osteocalcin and osteoprotegerin levels, and decreased the osteoclast surface, serum C-telopeptide, and interleukin-6. E2 was significantly less effective, and was not synergistic with BMP-6. Animals that discontinued BMP-6 therapy maintained bone mineral density gains for another 12 weeks. BMP-6 increased in vivo the bone expression of Acvr-1, Bmpr1b, Smad5, alkaline phosphatase, and collagen type I and decreased expression of Bmp3 and BMP antagonists, chordin and cerberus. These results show, for the first time, that systemically administered BMP-6 restores the bone inductive capacity, microarchitecture, and quality of the skeleton in osteoporotic rats.
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PMID:Systemically administered bone morphogenetic protein-6 restores bone in aged ovariectomized rats by increasing bone formation and suppressing bone resorption. 1679 45


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