Category Health/Medical

CDK8 is asymmetrically loaded at SEs in MOLM-14 cells.

“Once we learned this molecule named cortistatin A was very potent and selective in terms of inhibiting the growth of AML cells, we tested it in mouse models of AML and found that it was as efficacious as any other molecule we had seen, without having deleterious effects,” Shair said. “This suggests we have identified a promising new therapeutic approach.” It’s one that could be available to test in patients relatively soon.
“We synthesized cortistatin A and we are working to develop novel therapeutics based on it by optimizing its drug-like properties,” Shair said.

MOA: The molecule inhibits a pair of nearly identical kinases, called CDK8 and CDK19, that his work indicates play a key role in the growth of AML cells...

The protein/peptide system can grow on demand by simply displacing the interface. Credit: QMUL

Researchers have developed a way of assembling organic molecules into complex tubular tissue-like structures without the use of moulds or techniques like 3-D printing. The study describes how peptides and proteins can be used to create materials that exhibit dynamic behaviors found in biological tissues like growth, morphogenesis, and healing.

The method uses solutions of peptide and protein molecules that, upon touching each other, self-assemble to form a dynamic tissue at the point at which they meet. As the material assembles itself it can be easily guided to grow into complex shapes.

This discovery could lead to the engineering of tissues like veins, arteries, or even the blood-brain barrier,...

GATA4 functions as a key switch in the senescence regulatory network to activate the SASP. The nonsenescent state is maintained by inhibitory barriers that prevent cell cycle arrest and inflammation. Upon senescence-inducing signals, ATM and ATR relieve inhibition of the p53 and p16INK4a pathways to induce growth arrest and also block p62-dependent autophagic degradation of GATA4, resulting in NF-κB activation and SASP induction.

A team of researchers from Harvard Medical School and Buck Institute for Research on Aging has conducted a study that has revealed that GATA4 (a transcription factor) plays a significant role in cell senescence.

Cell senescence is a state that cells enter as they age or react to damage or other problems—once in this state they no longer progress through the cel...

Intracellular tumour necrosis factor receptor-2 (TNFR2) signalling. Binding of tumour necrosis factor (TNF) to TNFR2 results in activation and recruitment of intracellular adaptor proteins that induce signal transduction promoting cell proliferation and survival via phosphorylation of endothelial/epithelial nonreceptor tyrosine kinase (Etkp40), which in turn transactivates vascular endothelial growth factor receptor-2 (VEGFR2p1054–1059), leading to phosphatidylinositol 3-kinase (PI3K)-Akt/PKB pathway.

This discovery could lead to new treatment options for the 65% of individuals with IBD who do not respond or become resistant to anti-TNF medications...