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Thrombospondin-1 (TSP1) is a matrix protein that binds it high affinity receptor CD47. Both TSP1 and CD47 are upregulated in the kidney in response to injury and this promotes the development of fibrosis by inducing transforming growth factor-β and other fibrogenic factors. The authors were able to block or eliminate CD47-based signal transduction to reduce renal fibrosis.
The authors developed nervous-system-specific Nrbf2 knockout mice and found that they exhibited profound learning and memory deficits. RNAseq analyses have identified altered expression of genes related to protein folding and quality control. Aberrant aggregates of some of these key proteins are evident in the hippocampus.
This study on myxoid liposarcoma, based on mass spectrometry imaging of N-glycans, has revealed that increases in high-mannose-type as well as tri- and tetra-antennary complex-type N-glycans are associated with morphological progression of the disease. The increased abundance of tri-antennary complex-type glycans was also associated with a poor disease-specific survival for the patients.
This study reports laboratory data and disease outcome of 54 severe- and critical-type COVID-19 hospitalized adult patients in Wuhan, China. Decreased peripheral blood lymphocyte count, prolonged PT, increased secondary fibrinolytic activity, and significantly increased inflammatory factors sIL-2R and IL-6 correlated with the severity of the disease.
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.
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.
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.
Traditional RNA sequencing data may fail to detect the exact cellular changes in tumor cells. With comprehensively single-cell and traditional RNA-seq data, these authors detected and compared differentially expressed genes in lung adenocarcinoma. These results may improve our understanding of cellular and molecular differences between cancerous and non-malignant tissue and provide tumor markers as well as potential therapeutic targets.
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.
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.
Digital spatial profiling is a new high-plex technology with potential to multiplex hundreds of proteins on a single slide. Here the authors validate the digital aspect of the technology on a control tissue microarray with known amounts of PD-L1 expression to show it has quantitative capacity comparable to quantitative immunofluorescence.
Synovial mesenchymal stem cells (MSCs) are an attractive cell source for transplantation in the meniscus of the knee because of their high chondrogenic potential. This study describes the morphological features of synovial MSC adhesion to the meniscus and provides ways to increase the number of adherent MSCs so that clinical outcomes can be improved.
The authors observed an increase of talin-vinculin spatial proximities in the livers of spotted fever Rickettsiaaustralis 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.
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.
SiO2-mediated epithelial–mesenchymal transition via the nuclear transcription factor Ets-like protein-1 (ELK-1) due to oxidative stress and the downstream signaling of ZC3H4 expression. These findings suggest that the nuclear transcription factor ELK-1 may be useful as a novel target for the treatment of pulmonary fibrosis.
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.
Glycodelin is a major endometrial glycoprotein. The authors analyzed glycan structures of endometrial carcinoma associated glycodelin and established a novel glycodelin-glycoform specific histochemical staining method. With this, they showed that glycodelin is differentially glycosylated in endometrial carcinoma tissue, as compared to normal endometrium, representing a neoantigen with potential clinical applications.
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.