Volume 100 Issue 8, August 2020

The authors observed an increase of talin-vinculin spatial proximities in the livers of spotted fever Rickettsia australis or Ebola virus-infected mice when compared to mock mice. Furthermore, using EPAC1 knockout mice, they found that deletion of EPAC1 suppresses the formation of spatial proximal complex of talin-vinculin in rickettsial infections.

Matricellular protein SPOCK1 expression positively correlates with liver fibrosis and hepatic stellate cell activation. SPOCK1 is upregulated by PDGF-BB via the PI3K/Akt/FoxM1 signaling pathway and induces pro-fibrogenic responses. Additionally, it promotes stellate cell pro-fibrogenic responses through the integrin α5β1/PI3K/Akt signaling pathway. SPOCK1 is therefore a promising therapeutic target for liver fibrosis.

The thrombin receptor PAR1 and mechanosensitve ion channel TRPV4 are known to modulate endothelial barriers and contribute to edema, but functional interactions between these targets are not well understood. Utilizing cell signalling studies and in vivo models, the authors have demonstrated that PAR1 activation leads to functional upregulation of endothelial TRPV4 activity, to promote vascular leakage in airways and the gastrointestinal system.

Adeno-associated virus type 2 encoding the prolactin fragment vasoinhibin (AAV2 vasoinhibin) reduces joint inflammation and bone loss in antigen-induced arthritis in mice by inhibiting pannus angiogenesis and vasopermeability via the blockage of VEGF-induced eNOS activation. These findings suggest the potential benefit of vasoinhibin gene therapy in arthritis.

Increased levels of histone H2B (H2B), a damage-associated protein, are found in the vitreous of patients with acute primary angle closure. Elevated H2B causes severe inflammation and subsequent retinal ganglion cell death through toll-like receptor 4 (TLR4) signaling. These results provide new insight for the mechanism of retinal ganglia degeneration.

The interaction of genetic and epigenetic mechanisms is one of the underlying causes of phenotypic variability in diseases like type 2 diabetes. The authors identified the methylation-dependent CpG-SNP in the MTHFD1 gene as a regulator of allele-specific gene expression in peripheral blood mononuclear cells, which may perturb one-carbon metabolism in diabetes.

Mucus was tested as a potential biological material for screening/early diagnosis of colorectal cancer using infrared spectroscopy. Based on a digital histopathology and statistical modeling approach, cancerous and non-cancerous samples were classified with an area under the curve performance of 95% based on mucus spectral profiles, indicating changes in the glycan component of mucins.

The ability to characterize the cellular composition and spatial organization of the tumor microenvironment has been limited by the techniques available to image the necessary number of biomarkers for broad phenotyping at a subcellular resolution. This study demonstrates the capabilities of Multiplexed Ion Beam Imaging (MIBI) for cell phenotype identification and their spatial relationships across multiple tumor types.

Brightfield multiplex immunohistochemistry (IHC) is improved by replacing broadly absorbing chromogens with narrowband covalently deposited chromogens, and sequentially illuminating with light channels matched to chromogen absorbance bands, synchronized with monochromatic image acquisition. Light emitting diodes provide a path to rapid multispectral imaging. Spectral unmixing provided accurate representations of biomarkers that faithfully reproduced 3,3′-diaminobenzidine IHC.