In vivo bone regeneration using a bioactive nanocomposite scaffold and human mesenchymal stem cells

Cell and Tissue Banking - Due to the osteoconductive role of bioceramics, use of these bioactive nanocomposite scaffolds that can maintain their structural integrity during bone tissue...     

Highly perturbed genes and hub genes associated with type 2 diabetes in different tissues of adult humans: a bioinformatics analytic workflow

Functional & Integrative Genomics - Type 2 diabetes (T2D) has a complex etiology which is not yet fully elucidated. The identification of gene perturbations and hub genes of T2D may deepen our...     

Expression and localization of plasma transglutaminase factor XIIIA in bone.

Transglutaminases (TGs) are protein crosslinking enzymes involved in cell adhesion and signaling and matrix stabilization and maturation, in many cell types and tissues. We previously described that in addition to transglutaminase 2 (TG2), cultured MC3T3-E1 osteoblasts also express the plasma TG Factor XIIIA (FXIIIA). Here we report on the expression and localization of FXIIIA in bone in vivo and provide confirmatory in vitro data. Immunohistochemistry and in situ hybridization demonstrated that FXIIIA is expressed by osteoblasts and osteocytes in long bones formed by endochondral ossification (femur) and flat bones formed primarily by intramembranous ossification (calvaria and mandible). FXIIIA immunoreactivity was localized to osteoblasts, osteocytes, and the osteoid. RT-PCR analysis revealed FXIIIA expression by both primary osteoblasts and by the MC3T3-E1 osteoblast cell line. Western blot analysis of bone and MC3T3-E1 culture extracts demonstrated that FXIIIA is produced mainly as a small, 37-kDa form. Sequential RT-PCR analysis using overlapping PCR primers spanning the full FXIIIA gene showed that the entire FXIIIA gene is expressed, thus indicating that the 37-kDa FXIIIA is not a splice variant but a product of posttranslational proteolytic processing. Forskolin inhibition of osteoblast differentiation revealed that FXIIIA processing is regulated by the protein kinase A pathway.     

Long-term exposure to outdoor VOCs and lung function in urban adults: a cross-sectional study in Tabriz an industrialized city in the northwest of Iran

Abstract

This study aimed to evaluate the effects of outdoor benzene, toluene, xylenes, and styrene (BTXS) on respiratory system performance in adults living in an industrialized city. The concentration of BTXS was measured in the three selected areas (low traffic, high traffic and industrial). Pulmonary function of totally 219 participants who have lived in the selected areas for at least five years, were evaluated through the spiromertry. Based on the results, significant differences were observed between the mean concentrations of BTXS (industrial area?>?high traffic area?>?low traffic area). Considerable decline of 0.46?L, 0.41?L, 2.99%, 0.9?L/min, and 0.59?L/s for Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV₁), FEV₁/FVC, Peak Expiratory Flow (PEF) and Forced Expiratory Flow between 25% and 75% of vital capacity (FEF_25–75%), respectively, were detected in industrial area residents compared to the low traffic region. In addition, some spirometric parameters were different between the other sampling sites. In conclusion, the results showed that the long term exposure to higher concentrations of BTXS increases respiratory dysfunction risks in industrial and high traffic areas respectively, as compared with living in the low traffic region.     

Prolonged intermittent footschock stress decreases Met and Leu enkephalin levels in brain with concomitant decreases in pain threshold

The influence of a 21 day intermittent footshock regimen upon enkephalin levels in brain and adrenals was examined in the rat. Changes in pain sensitivity as well as analgesic and hyperthermic responsiveness to morphine (7.5 mg/kg) were also monitored. Following the stress regimen, Met and Leu enkephalin levels were decreased by 40 to 50% in brain, but were unchanged in adrenals. Post-stress pain thresholds were markedly decreased in stressed animals while the analgesic properties of morphine were enhanced. Core body temperature of stressed animals was significantly raised, but the hyperthermic response to morphine was unchanged.     

Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure

Carnosine-like peptides (carnosine-LP) are a family of histidine derivatives that are present in the nervous system of various species and that exhibit antioxidant, anti-matrix-metalloproteinase, anti-excitotoxic, and free-radical scavenging properties. They are also neuroprotective in animal models of cerebral ischemia. Although the function of carnosine-LP is largely unknown, the hypothesis has been advanced that they play a role in the developing nervous system. Since the zebrafish is an excellent vertebrate model for studying development and disease, we have examined the distribution pattern of carnosine-LP in the adult and developing zebrafish. In the adult, immunoreactivity for carnosine-LP is specifically concentrated in sensory neurons and non-sensory cells of the olfactory epithelium, the olfactory nerve, and the olfactory bulb. Robust staining has also been observed in the retinal outer nuclear layer and the corneal epithelium. Developmental studies have revealed immunostaining for carnosine-LP as early as 18 h, 24 h, and 7 days post-fertilization in, respectively, the olfactory, corneal, and retinal primordia. These data suggest that carnosine-LP are involved in olfactory and visual function. We have also investigated the effects of chronic (7 days) exposure to carnosine on embryonic development and show that 0.01 μM to 10 mM concentrations of carnosine do not elicit significant deleterious effects. Conversely, treatment with 100 mM carnosine results in developmental delay and compromised larval survival. These results indicate that, at lower concentrations, exogenously administered carnosine can be used to explore the role of carnosine in development and developmental disorders of the nervous system. This research was supported in part by an Intramural Research Grant Program Award from Michigan State University (no. 06-IRGP-899 to M.C.S.) and a grant from the National Institutes of Health (no. DC-03112 to F.L.M.).     

Synthesis and pharmacology of modified amidine isoxazoline glycoprotein IIb/IIIa receptor antagonists

Selective antagonism of the platelet GPIIb/IIIa receptor represents an attractive mechanism for the prevention and treatment of a number of thrombotic disease states. The antiplatelet activity of the oral GPIIb/IIIa receptor antagonists DMP 754 and DMP 802 have been disclosed. In this paper, the synthesis and biological evaluation of a series of potent N-substituted benzamidine isoxazolines are explored. The effect of benzamidine substitution on the duration of antiplatelet efficacy in dog is presented.     

Chemoattraction of human T cells by IL-18

Cell locomotion is crucial to the induction of an effective immune response. We report here the chemoattraction of CD4(+) T cells by IL-18, a member of the IL-1 cytokine family. Recombinant IL-18 increased the proportion of T cells in polarized morphology in vitro and stimulated their subsequent invasion into collagen gels in an IL-18 concentration gradient-dependent manner. Immunofluorescent microscopy studies determined that the major cell type responding to IL-18 was IL-18R(+)CD4(+). Importantly, synovial CD4(+) T cells from patients with rheumatoid arthritis responded to IL-18, adopting polarized morphology and gel invasion without further activation ex vivo, indicating the physiologic relevance of our observations. Finally, injection of rIL-18 into the footpad of DBA/1 mice led to local accumulation of inflammatory cells. These data therefore demonstrate for the first time lymphocyte chemoattractant properties of a member of the IL-1 cytokine family and its relevance in inflammatory diseases.