Synthesis and Preclinical Evaluation of a Novel Oxy133-Infused Biomimetic Bone Graft Using a Rat Model of Posterolateral Spinal Fusion.

Objective: To 1) create a novel tissue-engineered bone graft comprising the osteoinductive oxysterol Oxy133 and 2) compare the osteogenic capability of this novel bone graft with bone graft substitutes previously examined.

Methods: Oxy133 was homogeneously incorporated into a biomimetic (BioMim) bone graft substitute comprising extracellular matrix and calcium phosphates. Two iterations of the graft were created: one corresponding to an implant-dose of 2.

Selective inhibition of hepatitis B virus internalization by oxysterol derivatives.

Given that the current approved anti-hepatitis B virus (HBV) drugs suppress virus replication and improve hepatitis but cannot eliminate HBV from infected patients, new anti-HBV agents with different mode of action are urgently needed. In this study, we identified a semi-synthetic oxysterol, Oxy185, that can prevent HBV infection in a HepG2-based cell line and primary human hepatocytes. Mechanistically, Oxy185 inhibited the internalization of HBV into cells without affecting virus attachment or replication.

Oxy210, a Semi-Synthetic Oxysterol, Inhibits Profibrotic Signaling in Cellular Models of Lung and Kidney Fibrosis.

Oxy210, a semi-synthetic oxysterol derivative, displays cell-selective inhibition of Hedgehog (Hh) and transforming growth factor beta (TGF-β) signaling in epithelial cells, fibroblasts, and macrophages as well as antifibrotic and anti-inflammatory efficacy in models of liver fibrosis. In the present report, we examine the effects of Oxy210 in cellular models of lung and kidney fibrosis, such as human lung fibroblast cell lines IMR-90, derived from healthy lung tissue, and LL97A, derived from an idiopathic pulmonary fibrosis (IPF) patient. In addition, we examine the effects of Oxy210 in primary human renal fibroblasts, pericytes, mesangial cells, and renal tubular epithelial cells, known for their involvement in chronic kidney disease (CKD) and kidney fibrosis.

Oxysterol derivatives Oxy186 and Oxy210 inhibit WNT signaling in non-small cell lung cancer.

Background: Developmental signaling pathways such as those of Hedgehog (HH) and WNT play critical roles in cancer stem cell self-renewal, migration, and differentiation. They are often constitutively activated in many human malignancies, including non-small cell lung cancer (NSCLC). Previously, we reported that two oxysterol derivatives, Oxy186 and Oxy210, are potent inhibitors of HH/GLI signaling and NSCLC cancer cell growth.