General Nano (United States)

T regulatory cells (Tregs) generated in the periphery (pTregs) are initially unstable, but some of them stabilize with time. The stabilization signals, however, are poorly understood. We have previously reported that the treatment of mice with poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) decorated with anti-CD2 antibodies and encapsulating IL-2 and TGF-β induced tolerogenic CD4+ and CD8+ pTregs that protected mice from fatal graft-versus-host disease (GvHD). These NPs also induced TGF-β-producing NK cells. Here we show that initially unstable Tregs are stabilized and maintained by NK-cell derived TGF-β. Blockade of TGF-β signaling or NK cell depletion hindered the induction of Tregs and converted tolerogenic responses into immunogenic responses, leading to an accelerated demise of the mice. IL-2 from the NPs and TGF-β from NP-induced NK cells were sufficient for the maintenance of the Tregs, making the encapsulated TGF-β unnecessary. These results identify a new non-redundant cellular source of TGF-β required for the support of newly induced Tregs. NPs inducing cross-communicating innate and adaptive tolerogenic cells can represent a new cell-targeted approach to induce and maintain long-term immune tolerance in immune-mediated diseases.

Autoimmune diseases are disorders of immune regulation where the mechanisms responsible for self-tolerance break down and pathologic T cells overcome the protective effects of T regulatory cells (Tregs) that normally control them. The result can be the initiation of chronic inflammatory diseases. Systemic lupus erythematosus (SLE) and other autoimmune diseases are generally treated with pharmacologic or biological agents that have broad suppressive effects. These agents can halt disease progression, yet rarely cure while carrying serious adverse side effects. Recently, nanoparticles have been engineered to correct homeostatic regulatory defects and regenerate therapeutic antigen-specific Tregs. Some approaches have used nanoparticles targeted to antigen presenting cells to switch their support from pathogenic T cells to protective Tregs. Others have used nanoparticles targeted directly to T cells for the induction and expansion of CD4+ and CD8+ Tregs. Some of these T cell targeted nanoparticles have been formulated to act as tolerogenic artificial antigen presenting cells. This article discusses the properties of these various nanoparticle formulations and the strategies to use them in the treatment of autoimmune diseases. The restoration and maintenance of Treg predominance over effector cells should promote long-term autoimmune disease remission and ultimately prevent them in susceptible individuals.

This chapter is an attempt to introduce NanoArt as a visual aid for education in Nanoscience and Nanotechnology and support the understanding of the benefits the integration of this new artistic-scientific discipline creates in a future academic curriculum. The evolution of the visibility power, advances in the visual theory which made all these developments possible, and a short primer on electron microscopy are also presented. The chapter informs about the international juried NanoArt competitions and festivals organized by NanoArt 21 and other organizations, the NanoArt presence at International Art-Science-Technology and STEAM conferences, the NanoArt K12 program, the Academy of NanoArt recently founded, and finally the Moon Museum (part of the MoonArk project) that include NanoArt works authored by 47 nanoartists from NanoArt 21 group.

The aim of this study was to examine the outcomes related to analgesia, function, mortality, and adverse effects of oral opioid analgesics and spinal steroid injections on low back pain syndromes. Databases including Medline, EMBASE, PubMed, and Cochrane Library were searched in September 2009 using combinations of terms related to spinal pain and its treatment. A systematic review was performed of randomized controlled trials that enrolled patients with low back pain syndromes and that evaluated patient outcomes after intervention using either oral opioids or spinal steroid injections. Eight high-quality and ten moderate-quality randomized controlled trials were identified. One high-quality study on oral opioid therapy showed significant improvements in pain relief and patient function. Those on spinal steroid injections had a decreased Visual Analog Scale pain score by 7.18 (95% confidence interval, 2.21-12.1) points more than the control group at 1 mo or less and by 0.429 (95% confidence interval, -4.41 to 5.27) points at 1-3 mos. At more than 6 mos, there was no significant benefit: 0.930 (95% confidence interval, -5.03 to 6.89). Spinal steroids decreased the Oswestry Disability Index by 3.53 (95% confidence interval, 0.480-6.57) at 1 mo or less, by -0.281 (95% confidence interval, -3.18 to 2.62) at 1-3 mos, by -11.0 (95% confidence interval, -14.8 to -7.16) at 3-6 mos, and by -0.205 (95% confidence interval, -3.50 to 3.09) compared with the control group at 6 mos or more, suggesting that there was improvement in function. All-cause mortality was low in our analysis of patients attending specialty clinics. It was difficult to assess the adverse effects of opioid therapy because they influenced up to 28% of patients to withdraw from the original studies. In terms of spinal steroid injections, headache appeared to be the most common adverse effect. However, there was no significantly increased risk of headaches associated with spinal steroids compared with control injections: odds ratio, 1.29 (95% confidence interval, 0.69-2.39). Oral opioid therapy may be helpful for the treatment of low back pain, but it is unclear from the high-quality literature whether there are limitations from adverse effects. Spinal steroid injections are beneficial for low back pain and disability in the short-term. The high dropout rates caused by insufficient pain relief and adverse effects suggest that opioids may not be as effective as spinal steroid injections. There is more high-quality literature to support the use of spinal steroid injections compared with oral opioids in this condition.