Structure-Activity Relationships of Ligand Binding to Oxysterol-Binding Protein (OSBP) and OSBP-Related Protein 4.

Oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4) have emerged as potentially druggable targets in antiviral and precision cancer drug development. Multiple structurally diverse small molecules function through targeting the OSBP/ORP family of proteins, including the antiviral steroidal compounds OSW-1 and T-00127-HEV2. Here, the structure-activity relationships of oxysterols and related compound binding to human OSBP and ORP4 are characterized. Oxysterols with hydroxylation at various side chain positions (i.e., C-20, C-24, C-25, and C-27)─but not C-22─confer high affinity interactions with OSBP and ORP4. A library of 20(S)-hydroxycholesterol analogues with varying sterol side chains reveal that side chain length modifications are not well tolerated for OSBP and ORP4 interactions. This side chain requirement is contradicted by the high affinity binding of T-00127-HEV2, a steroidal compound lacking the side chain. The binding results, in combination with docking studies using homology models of OSBP and ORP4, suggest multiple modes of steroidal ligand binding to OSBP and ORP4.

Human Gut Microbiota: Toward an Ecology of Disease.

Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics.

Extrapleural Solitary Fibrous Tumor of the Foot A Case Report.

Solitary fibrous tumors are uncommon mesenchymal neoplasms that were initially described as pleural tumors, but in recent years, numerous extrapleural sites have been reported. A solitary fibrous tumor is characterized as a circumscribed, painless mass with a patternless growth pattern, positive CD34 spindle-shaped cells, bcl-2, and dense keloidal collagen with areas of hypercellularity and hypocellularity. This case report describes a 55-year-old male veteran who presented with a rare manifestation of an extrapleural solitary fibrous tumor of the medial right hallux. Microscopic and immunohistochemical findings were consistent with the previously documented characteristics of solitary fibrous tumors. Complete surgical excision of the tumor is the treatment of choice.