Infectious Uveitis in Horses and New Insights in Its Leptospiral Biofilm-Related Pathogenesis.

Uveitis is a sight-threatening eye disease in equids known worldwide that leads to considerable pain and suffering. By far the most common type of uveitis in Germany and neighboring countries is classical equine recurrent uveitis (ERU), which is caused by chronic intraocular leptospiral infection and is the main cause of infectious uveitis in horses. Other infectious causes are extremely rare and are usually clinically distinguishable from ERU.

In Vivo Biofilm Formation of Pathogenic spp. in the Vitreous Humor of Horses with Recurrent Uveitis.

Equine recurrent uveitis (ERU) causes painful inflammatory attacks and oftentimes blindness in the affected eyes. The disease is considered a late sequela of systemic leptospirosis. The most effective therapy is the surgical removal of the vitreous (vitrectomy), which is not only therapeutic, but provides vitreous material that can be assessed diagnostically.

Sorafenib inhibits macrophage-induced growth of hepatoma cells by interference with insulin-like growth factor-1 secretion.

Background & Aims: Hepatocellular carcinoma (HCC) associated macrophages accelerate tumor progression by growth factor release. Therefore, tumor-associated macrophages (TAM) and their initiated signaling cascades are potential therapeutic targets. Aiming at understanding anticancer effects of systemic HCC therapy, we investigated the impact of sorafenib on macrophage function, focusing on macrophage-related growth factor secretion.

Sorafenib perpetuates cellular anticancer effector functions by modulating the crosstalk between macrophages and natural killer cells.

Unlabelled: Alternatively polarized macrophages (Mϕ) shape the microenvironment of hepatocellular carcinoma (HCC) and temper anticancer immune responses. We investigated if sorafenib alters the HCC microenvironment by restoring classical macrophage polarization and triggering tumor-directed natural killer (NK) cell responses. In vivo experiments were conducted with sorafenib (25 mg/kg)-treated C57BL/6 wildtype as well as hepatitis B virus (HBV) and lymphotoxin transgenic mice with and without HCC.

Severe acute respiratory syndrome coronavirus replication is severely impaired by MG132 due to proteasome-independent inhibition of M-calpain.

The ubiquitin-proteasome system (UPS) is involved in the replication of a broad range of viruses. Since replication of the murine hepatitis virus (MHV) is impaired upon proteasomal inhibition, the relevance of the UPS for the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) was investigated in this study. We demonstrate that the proteasomal inhibitor MG132 strongly inhibits SARS-CoV replication by interfering with early steps of the viral life cycle.

Proteasomal dysfunction and endoplasmic reticulum stress enhance trafficking of prion protein aggregates through the secretory pathway and increase accumulation of pathologic prion protein.

A conformational change of the cellular prion protein (PrP(c)) underlies formation of PrP(Sc), which is closely associated with pathogenesis and transmission of prion diseases. The precise conformational prerequisites and the cellular environment necessary for this post-translational process remain to be completely elucidated. At steady state, glycosylated PrP(c) is found primarily at the cell surface, whereas a minor fraction of the population is disposed of by the ER-associated degradation-proteasome pathway.