The Role of Von Willebrand Factor in the Pathogenesis of Pulmonary Vascular Thrombosis in COVID-19

The increased plasma levels of von Willebrand factor (VWF) in patients with COVID-19 was reported in many studies, and its correlation with disease severity and mortality suggest its important role in the pathogenesis of thrombosis in COVID-19. We performed histological and immunohistochemical studies of the lungs of 29 patients who died from COVID-19. We found a significant increase in the intensity of immunohistochemical reaction for VWF in the pulmonary vascular endothelium when the disease duration was more than 10 days. In the patients who had thrombotic complications, the VWF immunostaining in the pulmonary vascular endothelium was significantly more intense than in nonsurvivors without thrombotic complications. Duration of disease and thrombotic complications were found to be independent predictors of increased VWF immunostaining in the endothelium of pulmonary vessels. We also revealed that bacterial pneumonia was associated with increased VWF staining intensity in pulmonary arterial, arteriolar, and venular endothelium, while lung ventilation was an independent predictor of increased VWF immunostaining in arterial endothelium. The results of the study demonstrated an important role of endothelial VWF in the pathogenesis of thrombus formation in COVID-19.     

An extensive tumor array analysis supports tumor suppressive role for nucleophosmin in breast cancer

Nucleophosmin (NPM) is a multifunctional protein involved in a complex network of interactions. The role of NPM in oncogenesis is controversial. The NPM gene (NPM1) is mutated or rearranged in a number of hematological disorders, but such changes have not been detected in solid cancers. However, experiments with cultured NPM-null cells and with mice carrying a single inactivated NPM allele indicate a tumor suppressor function for NPM. To resolve the role of NPM in solid cancers, we examined its expression and localization in histologically normal breast tissue and a large array of human breast carcinoma samples (n = 1160), and also evaluated its association with clinicopathological variables and patient survival. The intensity and localization (nucleolar, nuclear, cytoplasmic) of NPM varied across clinical samples. No mutations explaining the differences were found, but the present findings indicate that expression levels of NPM affected its localization. Our study also revealed a novel granular staining pattern for NPM, which was an independent prognostic factor of poor prognosis. In addition, reduced levels of NPM protein were associated with poor prognosis. Furthermore, luminal epithelial cells of histologically normal breast displayed high levels of NPM and overexpression of NPM in the invasive MDA-MB-231 cells abrogated their growth in soft agar. These results support a tumor suppressive role for NPM in breast cancer.     

Immunoreactivity of calcium binding protein secretagogin in the human hippocampus is restricted to pyramidal neurons

Disturbed calcium homeostasis plays a crucial role in the aetiology of Alzheimer's disease (AD) and the aging process. We evaluated immunoreactivity of secretagogin, a recently cloned calcium binding protein, in hippocampus and adjacent entorhinal cortex of 30 neuropathologically examined post mortem brains (m:f=12:18; mean age, 79.8+/-15.1 years). The study group consisted of 15 cases fulfilling the criteria for high probability of AD according to the NIA-Reagan Institute Criteria and 15 cases with no to medium probability. Sections were incubated with secretagogin-specific antibodies and the number of immunoreactive neurons as well as staining intensities in both neurons and neuropil were assessed. Both cellular and neuropil immunoreactivity were restricted to subiculum and Ammons horn. Cellular immunoreactivity was further restricted to pyramidal neurons and showed a hierarchical distribution: the mean percentage of immunoreactive neurons was highest in sector CA3 (64.41%), followed by CA2 (44.09%), CA4 (34.38%), CA1 (10.9%), and the subiculum (2.92%; P<0.001, except CA2-CA4, P>0.05), while it did not differ significantly between groups with different degrees of AD pathology. The pattern of secretagogin immunoreactivity resembles that of calcium sensor proteins as it is restricted to a subset of neurons and therefore secretagogin could serve highly specialized tasks in neuronal calcium signalling.     

Cellular internalization and morphological analysis after intravenous injection of a highly hydrophilic octahedral rhenium cluster complex – a new promising X‐ray contrast agent

The octahedral cluster compound Na₂H₈[{Re₆Se₈}(P(C₂H₄CONH₂)(C₂H₄COO)₂)₆] has been shown to be highly radio dense, thus becoming a promising X‐ray contrast agent. It was also shown that this compound had low cytotoxic effect in vitro, low acute toxicity in vivo and was eliminated rapidly from the body through the urinary tract. The present contribution describes a more detailed cellular internalization assay and morphological analysis after intravenous injection of this hexarhenium cluster compound at different doses. The median lethal dose (LD₅₀) of intravenously administrated compound was calculated (4.67 ± 0.69 g/kg). Results of the study clearly indicated that the cluster complex H_n[{Re₆Se₈}(P(C₂H₄CONH₂)(C₂H₄COO)₂)₆]^n–10 was not internalized into cells in vitro and induced only moderate morphological alterations of kidneys at high doses without any changes in morphology of liver, spleen, duodenum, or heart of mice. Copyright © 2016 John Wiley & Sons, Ltd.