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CD40 is a member of the growing tumor necrosis factor receptor (TNF-R) family of molecules, and has been shown to play important roles in T cell-mediated B lymphocyte activation. Ligation of B cell CD40 by CD154 expressed on activated T cells stimulates B cell proliferation, differentiation, isotype switching, upregulation of surface molecules contributing to antigen presentation, development of the germinal center, and the humoral memory response. The present review will summarize recent literature data on the various CD40 signalling pathways, which involve both the TNF-R associated factors (TRAFs) and additional signalling proteins, and lead to activation of kinases and transcription factors
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Taurine is a sulfur amino acid (2-amino ethane sulfonic acid) and has been claimed for a number of beneficial actions ranging from anti-epilepsy to anti-hypertension. Taurine in diabetes has an age old story; taurine is involved in the development and protection of insulin apparatus. Taurine and insulin both have mutual stimulating actions with hypoglycemic properties. On the clinical front, taurine supplementation has an acceptable beneficial effect in platelet aggregation and, to name few more, in neuropathy, cardiomyopathy, and nephropathy to retinopathy. Recent studies have provided a role for taurine in fetal development and in blocking the transfer of diabetes from diabetic mother to offspring. A number of mechanisms for the actions of taurine have been advocated, from osmoregulation to anti-oxidation. Though sulfonylurea and recently introduced thiazolidinediones are effective, however they are not free from complications, thus there is a need to design new therapeutics. As taurine is also a sulfonyl derivative, it will be of great interest to develop taurine analogues as an alternative therapy. Considering the great involvement of taurine in diabetes, this review may provide a holistic view of taurine in diabetes and in its prevention in this century
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To overcome the limitation of the currently adopted direct method to detect recombinant Human Erythropoietin (rHuEpo) abuse in sport, indirect analysis of blood parameters are increasingly used as part of the anti-doping strategies. The aim of the present work is to identify whether immunophenotype modifications on erythroid cells may be indicative of previous rHuEPO administration. The study was conducted on dialyzed patients under treatment with rHuEPO (DPT). Dialyzed patients without rHuEPO therapy (DP) and volunteer donors (H) were used as controls. The analysis of erythroid cells immunophenotype, performed using a multiparametric flow cytometry technique, showed a peculiar pattern of CD71 expression following rHuEPO treatment. In particular CD71 showed an increased expression in mature and intermediate reticulocytes and a surprisingly decreased expression in immature reticulocytes. In conclusion, the analysis of reticulocyte maturation stages with TO/CD71 double staining may be considered as a valid alternative indirect method for the detection of rHuEPO abuse
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Free radical damage to many cellular components has been proposed as the main mechanism underlying the aging process. In the liver, NO can be generated by iNOS, but also by the constitutively expressed endothelial NOS (eNOS). iNOS enzyme appears to be expressed in liver disease such as cirrhosis and fulminant hepatitis, while the eNOS is expressed in physiological conditions. Ten young and ten old Wistar rats were sacrificed and their livers were excised. Liver sections were incubated with an anti-iNOS antibody of rabbit origin. RT-PCR and Western blot analysis were performed and nitric oxide activity was calculated. A significant increase of iNOS immunoreactivity was seen in the aged liver sections versus young liver sections. iNOS protein is expressed in greater quantities in the aged group, compared to the young group. In this study we show, for the first time, that aging in the rat liver is accompanied by a spontaneous induction of iNOS mRNA, high levels of iNOS protein and immunohistochemistry/image analysis
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The small dimension and particle shape of silica in gypsum used to prepare moulds for lost wax casting might be responsible for the high prevalence of silicosis in gold jewellery. To test this hypothesis, human pulmonary epithelial cell (BEAS-2B) cultures were exposed to two samples of silica with different crystal micro-morphologies: Silica Powder (Silica P) which is used in casting gold jewellery, and no powder Silica (Silica F). Extracellular matrix (ECM) production was evaluated using radio-labelled precursors and quantified by RT-PCR analysis. Expression of basic fibroblast growth factor (FGF2) and its receptor (FGFR2) was also evaluated. The results demonstrated Silica P particles had a very fine lamellar crystalline structure while Silica F was characterized by larger rounded crystals. Silica P stimulated collagen production significantly more than Silica F and downregulated laminin and metalloprotease expression. Both silica samples down-regulated FGF2 but only Silica F enhanced FGF2 receptor expression. In conclusion each Silica sample promoted a profibrotic lung microenvironment in a different manner and also elicited different FGF2 signalling pathways. The data confirm that different micromorphology of Silica particles affects the fibrogenic potential and the molecular mechanisms of dust pathogenicity
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Periodontal disease (Pd) is characterized by extensive alveolar bone loss, that occurs as a consequence of the impairment of the normal bone remodelling. Bone remodelling is regulated by the correct balance between osteoclast and osteoblast formation and activity. Alveolar bone loss could be due to an increased bone resorption by osteoclasts or a decreased bone formation by osteoblasts (OBs) or both. Although the role played by osteoclasts in increasing bone resorption in Pd is already known, the behaviour of OBs in this disease is poorly understood. In the present study we hypothesized that activity and survival of OBs, locally present in alveolar bone of Pd patients, are altered. Thus, we studied the activity and survival of OBs obtained from alveolar bone fragments of Pd patients. The results, obtained in OBs from the patients were compared with those from OBs obtained from healthy donors. We demonstrated that OBs from Pd patients weakly express OB phenotype in respect to the control cells. In particular, the alkaline phosphatase activity and the collagen type I production, as well as the formation of mineralized nodules, typical markers of differentiated OBs, were significantly lower in Pd patients. Interestingly, we also demonstrated that OBs from the patients were more sensitive to the apoptotic effect induced by TNF-related apoptosis-inducing ligand (TRAIL). TRAIL, a member of the TNF superfamily, induces apoptosis by interacting with its death receptors, (DR4, DR5). However, its activity can be modulated by two decoy receptors, DcR1 and DcR2. Thus, the sensitiveness of TRAIL induced apoptosis is determined by the ratio of death and decoy receptor. We demonstrated that OBs from Pd patients showed an imbalanced ratio between death and decoy TRAIL receptors due to the down-regulation of DcR2 expression. Furthermore, the levels of TRAIL in the serum of the same patients were significantly higher than those detected in the controls. In conclusion, we show for the first time that the alveolar bone loss in Pd patients could be due to the increased TRAIL-mediated apoptosis of OBs
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Orexin A is a member of a wider family of orexigenic neuropeptides that have been recently discovered. They are produced by a small group of neurons located in the area of the brain, round the nucleus of the fornix (posterior hypothalamus), in the paraventricular nucleus, the dorsomedial nucleus, the ventromedial hypothalamus, as well as in the lateral hypothalamic region; these are sites that are known to be involved in regulating feeding in mammals. Orexin A is a neuropeptide, which is involved in appetite regulation and energy homeostasis. An intracerebroventricular (i.c.v.) injection of Orexin A in the brain of rats causes an impressive increase in food consumption. In addition, a subcutaneous or intravenous (IV) injection of Orexin A produces changes on insulin plasma concentrations in rats. Recent research suggests that Orexin A is also involved in regulating many other physiological functions. In this study, we examined the potential effects of the central administration of porcine Orexin A on insulin plasma concentrations in pigs, and whether these changes are connected with the possible effect of the neuropeptide on the enteroinsular axis
