The immunomodulatory effects of mesenchymal stromal cell-based therapy in human and animal models of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune inflammatory disease with no absolute cure. Although the exact etiopathogenesis of SLE is still enigmatic, it has been well demonstrated that a combination of genetic predisposition and environmental factors trigger a disturbance in immune responses and thereby participate in the development of this condition. Almost all available therapeutic strategies in SLE are primarily based on the administration of immunosuppressive drugs and are not curative. Mesenchymal stromal cells (MSCs) are a subset of non-hematopoietic adult stem cells that can be isolated from many adult tissues and are increasingly recognized as immune response modulating agents. MSC-mediated inhibition of immune responses is a complex mechanism that involves almost every aspect of the immune response. MSCs suppress the maturation of antigen-presenting cells (DC and MQ), proliferation of T cells (Th1, T17, and Th2), proliferation and immunoglobulin production of B cells, the cytotoxic activity of CTL and NK cells in addition to increasing regulatory cytokines (TGF-ß and IL10), and decreasing inflammatory cytokines (IL17, INF-ϒ, TNF-α, and IL12) levels. MSCs have shown encouraging results in the treatment of several autoimmune diseases, in particular SLE. This report aims to review the beneficial and therapeutic properties of MSCs; it also focuses on the results of animal model studies, preclinical studies, and clinical trials of MSC therapy in SLE from the immunoregulatory aspect.

Curcumin nano-micelle induced testicular toxicity in healthy rats; evidence for oxidative stress and failed homeostatic response by heat shock proteins 70-2a and 90.

This study explores the effect of curcumin nano-micelle (NCMN) on the testicular anti-oxidant status and heat shock proteins (Hsp) 70-2a and Hsp 90 expression. Therefore, 24 male Wistar rats were divided into control, 7.50 mg/kg, 15 mg/kg, and 30 mg/kg of NCMN-received groups. Following 48 days, the testicular total anti-oxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA) and glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPX) activities, immunoreactivity of 8-oxodG, Hsp70-2a and Hsp90 expressions, germ cell's DNA and mRNA damages, the spermatozoa count, motility and DNA integrity were assessed. With no change in the testicular TAC level, the TOS, MDA and GSH contents were increased in the NMC-received groups. However, CAT and GPX activities were decreased. The NCMN suppressed spermatogenesis, increased immunoreactivity of 8-oxodG, stimulated the Hsp70-2a and Hsp90 expressions, and resulted in severe DNA and mRNA damages. Moreover, the NCMN-received animals exhibited remarkable reductions in the spermatozoa count, motility and DNA integrity. In conclusion, chronic and high dose consumption of NCMN initiates OS, and in response to OS, the Hsp70-2a and Hsp90 expression increases. However, considering enhanced DNA and mRNA damages and suppressed spermatogenesis, HSPs over-expression can neither boost the anti-oxidant system nor overcome the NCMN-induced OS-related damages.