The pathophysiological function of peroxisome proliferator-activated receptor-γ in lung-related diseases

Research into respiratory diseases has reached a critical stage and the introduction of novel therapies is essential in combating these debilitating conditions. With the discovery of the peroxisome proliferator-activated receptor and its involvement in inflammatory responses of cardiovascular disease and diabetes, attention has turned to lung diseases and whether knowledge of this receptor can be applied to therapy of the human airways. In this article, we explore the prospect of peroxisome proliferator-activated receptor-γ as a marker and treatment focal point of lung diseases such as asthma, chronic obstructive pulmonary disorder, lung cancer and cystic fibrosis. It is anticipated that peroxisome proliferator-activated receptor-γ ligands will provide not only useful mechanistic pathway information but also a possible new wave of therapies for sufferers of chronic respiratory diseases

Decrease of CD68 Synovial Macrophages in Celastrol Treated Arthritic Rats

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments) and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA).FCT fellowship: (SFRH/BPD/92860/2013)

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Osteoporosis and Fragility in Elderly Patients

Osteoporosis is a systemic bone disease affecting numerous people all over the world, causing fragility fractures, especially among the elderly. In order to reach a complete diagnosis before a fragility fracture occurs, it is necessary, according to the main international guidelines, to perform a dual X-ray absorptiometry (DXA) to evaluate bone mineral density (BMD), an X-ray of the dorsal and lumbar spine to investigate the presence of asymptomatic vertebral fractures, laboratory tests to exclude secondary forms of osteoporosis, and draw up an accurate medical history, since several risk factors may be involved. The general management of this pathology includes prevention of further falls as well as the administration of calcium, vitamin D and protein supplements. Many drugs that permit a customised strategy—fundamental to improving treatment-adherence rates, frequently low in elderly patients—are available for the pharmacological treatment of this pathology

Generation of myeloid-derived suppressor cells using prostaglandin E2

Myeloid-derived suppressor cells (MDSCs) are natural immunosuppressive cells and endogenous inhibitors of the immune system. We describe a simple and clinically-compatible method of generating large numbers of MDSCs, using the cultures of peripheral blood-isolated monocytes supplemented with prostaglandin E2 (PGE2). We observed that PGE2 induces endogenous COX2 expression in cultured monocytes, blocking their differentiation into CD1a+ DCs and inducing the expression of IDO1, IL-4Ralpha, NOS2 and IL-10, typical MDSC-associated suppressive factors. The establishment of a positive feedback loop between PGE2 and COX2, the key regulator of PGE2 synthesis is necessary and sufficient to promote the development of CD1a+ DCs to CD14+CD33+CD34+ monocytic MDSCs in GM-CSF/IL-4-supplemented monocyte cultures, for their stability, production of multiple immunosuppressive mediators and CTL-suppressive function. In addition to PGE2, also selective EP2- and EP4-agonists, but not EP3/1 agonists, induce the MDSCs development, suggesting that other activators of the EP2- and EP2-driven signaling pathway (adenylate cyclase/cAMP/PKA/CREB) may be used to promote the development of suppressive cells. Our observations provide for a simple method to generate large numbers of MDSCs for the immunotherapy of autoimmune diseases, chronic inflammatory disorders and transplant rejection