Head Aagesen (burstgum90)

Caveolin-1 (CAV1) is a well-established nitric oxide synthase inhibitor, whose function as a tumor suppressor is favored by, but not entirely dependent on, the presence of E-cadherin. Tumors are frequently hypoxic and the activation of the hypoxia-inducible factor-1α (HIF1α) promotes tumor growth. HIF1α is regulated by several post-translational modifications, including S-nitrosylation. Here, we evaluate the mechanisms underlying tumor suppression by CAV1 in cancer cells lacking E-cadherin in hypoxia. Our main findings are that CAV1 reduced HIF activity and Vascular Endothelial Growth Factor expression in vitro and in vivo. This effect was neither due to reduced HIF1α protein stability or reduced nuclear translocation. Instead, HIF1α S-nitrosylation observed in hypoxia was diminished by the presence of CAV1, and nitric oxide synthase (NOS) inhibition by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) reduced HIF1α transcriptional activity in cells to the same extent as observed upon CAV1 expression. Additionally, arginase inhibition by (S)-(2-Boronoethyl)-L-cysteine (BEC) partially rescued cells from the CAV1-mediated suppression of HIF1α transcriptional activity. In vivo, CAV1-mediated tumor suppression was dependent on NOS activity. In summary, CAV1-dependent tumor suppression in the absence of E-cadherin is linked to reduced HIF1α transcriptional activity via diminished NOS-mediated HIF1α S-nitrosylation.There are a several emerging and re-emerging RNA viruses that are prevalent around the world for which there are no licensed vaccines or antiviral drugs. Staurosporine mouse Zika virus (ZIKV) is an example of an emerging virus that has become a significant concern worldwide because of its association with severe congenital malformations and neurological disorders in adults. Several polyphenol-rich extracts from plants were used as nutraceuticals which exhibit potent in vitro antiviral effects. Here, we demonstrated that the papaya pulp extracted from Carica papaya fruit inhibits the infection of ZIKV in human cells without loss of cell viability. At the non-cytotoxic concentrations, papaya pulp extract has the ability to reduce the virus progeny production in ZIKV-infected human cells by at least 4-log, regardless of viral strains tested. Time-of-drug-addition assays revealed that papaya pulp extract interfered with the attachment of viral particles to the host cells. With a view of preserving the properties of papaya pulp over time, lactic fermentation based on the use of bacterial strains Weissella cibaria 64, Lactobacillus plantarum 75 and Leuconostoc pseudomesenteroides 56 was performed and the resulting fermented papaya pulp samples were tested on ZIKV. We found that lactic fermentation of papaya pulp causes a moderate loss of antiviral activity against ZIKV in a bacterial strain-dependent manner. Whereas IC50 of the papaya pulp extract was 0.3 mg/mL, we found that fermentation resulted in IC50 up to 4 mg/mL. We can conclude that papaya pulp possesses antiviral activity against ZIKV and the fermentation process has a moderate effect on the antiviral effect.The extracellular matrix (ECM) spatiotemporally controls cell fate; however, dysregulation of ECM remodeling can lead to tumorigenesis and cancer development by providing favorable conditions for tumor cells. Proteoglycans (PGs) and glycosaminoglycans (GAGs) are the major macromolecules composing ECM. They influence both cell behavior and matrix properties through direct and indirect interactions with various cytokines, growth factors, cell surface receptors, adhesion molecules, enzymes, and glycoproteins within the ECM. The classical features of PGs/GAGs play well-known roles in cancer angiogenesis, proliferation, invasion, and metastasis. Several lines of evidence suggest that PGs/GAGs critically affect broader aspects in cancer initiation and the progression process, including regulation of cell metabolism, serving as a sensor of ECM's mechanical prope