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Fight Aging! Newsletter, May 2nd 2022
In this study, we tested the therapeutic potential of VHHASC and a newly generated VHH against murine ASC (VHHmASC) to target ASC specks in vitro and in vivo. We show that pre-incubation of extracellular ASC specks with VHHASC abrogated their inflammatory functions in vitro. Recombinant VHHASC rapidly disassembled pre-formed ASC specks and thus inhibited their ability to seed the nucleation of soluble ASC. Notably, VHHASC required prior cytosolic access to prevent inflammasome activation within cells, but it was effective against extracellular ASC specks released following caspase-1-dependent loss of membrane integrity, an...
Source: Fight Aging! - May 1, 2022 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

DNMT Inhibitors Increase Methylation in the Cancer Genome
In conclusion, we showed hypermethylation of CpGs as a novel mechanism of action for DNMTi agents and identified 638 hypermethylated molecular targets (CpGs) common to decitabine and azacytidine therapy. These novel results suggest that hypermethylation of CpGs should be considered when predicting the DNMTi responses and side effects in cancer patients. Introduction DNA methyltransferase inhibitors (DNMTi) are widely used as chemical tools for hypomethylating the genome, with an aim to understand the role of DNA methylation in multiple processes (e.g., X-chromosome inactivation and DNA imprinting) and as an anti-ca...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Identification of a Novel Bcl-2 Inhibitor by Ligand-Based Screening and Investigation of Its Anti-cancer Effect on Human Breast Cancer Cells
Conclusions In this study, a virtual screening process including RF classification and regression models was applied to identify the novel Bcl-2 inhibitors. We finally screened out the compound M1 as a novel Bcl-2 small molecule inhibitor, which binds to and down-regulates Bcl-2, has significant cytotoxic effect by inducing mitochondria-mediated apoptosis. Compound M1 could be a novel and promising hit or lead compound for further structural optimization in drug discovery. Ethics Statement We have explored the anti-tumor effect of Compound M1 in vitro. The human breast cancer cell lines MDA-MB-231, T47D, and BT549, were...
Source: Frontiers in Pharmacology - April 16, 2019 Category: Drugs & Pharmacology Source Type: research