STAT3 siRNA, HO-1 siRNA and control siRNA were purchased from Santa Cruz

abnormal glucose tolerance in two separate studies. 3) ISO-092 Testing of a potent MIF inhibitor was proposed by Tom Coleman and Yousef Al-Abed at the Feinstein Institute for Medical Research in Manhasset, New York. The small molecule MIF inhibitor ISO-092 is a fluorinated analog of ISO-1 with oral bioavailability. MIF has been 6 Efficacy Testing in Rodent Models of T1D doi: 10.1371/journal.pone.0072989.g004 shown to enhance beta cell destruction in mice and to increase diabetes incidence in NOD mice. Non-diabetic NOD mice at 12 weeks of age were treated daily for 14 days or until diabetes onset with 25mg/kg, or drug vehicle by oral gavage. Pilot studies had indicated that the drug was well-tolerated, and no adverse events were observed in this study. Animals were observed for diabetes onset through 25 weeks of age. The agent provided no protection from progression to diabetes. NOD mice at 14 weeks of age and with abnormal glucose tolerance, were treated daily for 14 days with ISO 92 25mg/kg, or drug vehicle, by oral gavage. Pilot studies had indicated that the drug was well-tolerated, and no adverse events were observed in this study. Animals were observed for diabetes 10336542 onset through 25 weeks of age. The agent provided 2173565 no protection from progression to diabetes. Subsequent PK studies performed by BRM showed that ISO-092 had a half-life in vivo of approximately 1 hour whether administered via IP or PO injection, suggesting that one cause of lack of efficacy could have been inadequate dosing. A follow-up study using osmotic pumps to deliver a continuous dose of ISO-092 at 1.3, 3.9, or 11.7 mg/kg/day was performed. For this study, the KRV and poly inducible diabetes model in MAD rats was used. In agreement with earlier work, dexamethasone treatment could prevent diabetes in this model; however, continuously delivered IS0-092 at multiple concentrations did not. 4) Cis-Tetracosenoyl Sulfatide Vipin Kumar of Torrey Pines Institute for Molecular Studies requested that we test a synthetic sulfatide known to activate CD1drestricted type II NKT cells and impact T1D by regulating type I NKT cells. Prior studies had shown that treatment of animals with brain-derived sulfatide as well as synthetic long chain sulfatides could protect against experimental autoimmune encephalomyelitis and a model of induced autoimmune hepatitis, as well as reducing incidence of T1D in the NOD mouse. Since there was significant preliminary data on acute effects of drug treatment in the NOD mouse, we decided to test our dosing regimen. Two pilot studies were performed in which the synthetic sulfatide or the brain derived mixture was injected into mice and IL-12 and IFN production were measured. C57Bl/6 mice were used since that was the strain which had been shown to previously respond to the drug. However, in neither study were IFN- and IL-12 produced in response to the injection of sulfatide products, in contrast to what was previously published. As a result, no further experiments using these drugs were performed, but further studies in the requestor’s lab confirmed that the sulfatide preparations used showed reduced biological potency in other studies. 5) Celastrol Celastrol is a natural triterpene compound isolated from Tripterygium wilfordii, with in vitro and in vivo antiinflammatory Aphrodine price properties, treating rodent models of arthritis as well as anti-cancer properties, and has been shown to impact hematopoiesis in the mouse. Preliminary data from the requestor suggest