Gut Microbiome Multiple Sclerosis and Cancer

Thanks to their influence on the owner’s gut microbiome, dogs may be beneficial in reducing cardiovascular, diabetes, multiple sclerosis and cancer risk by providing a non-human form of social support and increasing physical activity. Ownership of hunting dog breeds was associated with a decreased risk of CVD, and ownership of all purebred breeds was associated with lower risk of all-cause mortality. Dog ownership has also been associated with elevated parasympathetic and diminished sympathetic nervous system activity, lower reactivity to stress, and faster recovery of blood pressure following stressful activity. We provide evidence that supports epsilon toxin’s ability to cause BBB permeability and show that epsilon toxin kills the brain’s myelin producing cells, oligodendrocytes; the same cells die in multiple sclerosis (MS) lesions. A new study has identified how the environment surrounding a tumor can stimulate metastatic behavior in the individual cancer cells. Researchers found that the tumor cells activate a particular set of genes and begin form blood vessel-like structure when they are confined in densely packed environment.

Host-Derived Pericytes and Sca-1+ Cells Predominate in the MART-1− Stroma Fraction of Experimentally Induced Melanoma

Identification of cell types in tumor-associated stroma that are involved in the development of melanoma is hampered by their heterogeneity. The authors used flow cytometry and immunohistochemistry to demonstrate that anti–MART-1 antibodies can discriminate between melanoma and stroma cells. They investigated the cellular composition of the MART-1−, non-hematopoietic melanoma-associated stroma, finding it consisted mainly of Sca-1+ and CD146+ cells. These cell types were also observed in the skin and muscle adjacent to developing melanomas. The Sca-1+ cell population was observed distributed in the epidermis, hair follicle bulges, and tumor capsule. The CD146+ population was found distributed within the tumor, mainly associated with blood vessels in a perivascular location. In addition to a perivascular distribution, CD146+ cells expressed α-smooth muscle actin, lacked expression of endothelial markers CD31 and CD34, and were therefore identified as pericytes. Pericytes were found to be associated with CD31+ endothelial cells; however, some pericytes were also observed associated with CD31−, MART-1+ B16 melanoma cells that appeared to form blood vessel structures. Furthermore, the authors observed extensive nuclear expression of HIF-1α in melanoma and stroma cells, suggesting hypoxia is an important factor associated with the melanoma microenvironment and vascularization. The results suggest that pericytes and Sca-1+ stroma cells are important contributors to melanoma development.

A colorimetric assay for releasable plasminogen activator.

We describe an equilibrium assay for measuring release of plasminogen activator form blood-vessel walls and report data from 125 individuals free of overt thromboembolic disease. Excess human plasminogen is added to the euglobulin fraction of plasma obtained before and after venous occlusion at mean systolic pressure. To measure plasmin generation in these samples, we used the chromogenic plasmin substrate D-Val-Leu-Lys-p-nitroanilide, which liberates p-nitroaniline upon cleavage. Releasable plasminogen activator in 24 subjects was determined by this colorimetric assay and by the radiocasein assay previously reported by this laboratory (Am. J. Clin. Pathol. 76,403-409, 1981), and the results were compared. The correlation coefficient was 0.97. The colorimetric assay offers several advantages over the radiocasein assay: shorter incubation (6 vs 16 h) and no preparation or quantification of a radioactive substrate and its cleavage products.