Empowering AlphaFold2 for protein conformation selective drug discovery with AlphaFold2-RAVE [PDF]
Small molecule drug design hinges on obtaining co-crystallized ligand-protein structures. Despite AlphaFold2's strides in protein native structure prediction, its focus on apo structures overlooks ligands and associated holo structures. Moreover, designing selective drugs often benefits from the targeting of diverse metastable conformations. Therefore,
arxiv +1 more source
Influence of epidermal growth factor receptor (EGFR), p53 and intrinsic MAP kinase pathway status of tumour cells on the antiproliferative effect of ZD1839 (‘Iressa’) [PDF]
ZD1839 (‘Iressa’) is an orally active, selective epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR–TKI), which blocks signal transduction pathways implicated in proliferation and survival of cancer cells, and other host-dependent processes
Dubreuil, A+6 more
core +2 more sources
Exogenously-added copper/zinc superoxide dismutase rescues damage of endothelial cells from lethal irradiation [PDF]
The vascular endothelium is important for the early and late effects observed in lethally irradiated tissue and organs. We examined the effects of exogenously added superoxide dismutase on cell survival and angiogenesis in lethally irradiated human ...
Akashi, Makoto+5 more
core +2 more sources
In mice challenged with lipopolysaccharide/D‐galactosamine (L/G), Mas signaling increased SHP2 in hepatic Col4a1+ endothelial cells, inhibiting farnesoid X receptor (FXR), potentially due to enterogenic deoxycholic acid. This inhibition activates sphingosine‐1‐phosphate‐induced Raf/MEK/ERK signaling in Cldn1+CD177+ neutrophils, causing neutrophil ...
Bo Yang+11 more
wiley +1 more source
The role of PAF in immunopathology: From immediate hypersensitivity reactions to fungal defense
Abstract Platelet‐activating factor (PAF, 1‐alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphorylcholine) was discovered when the mechanisms involved in the deposition of immune complex in tissues were being scrutinized in the experimental model of rabbit serum sickness.
Mariano Sánchez Crespo+2 more
wiley +1 more source
Gene amplifications associated with the development of hormone- resistant prostate cancer [PDF]
Purpose: Hormone resistance remains a significant clinical problem in prostate cancer with few therapeutic options. Research into mechanisms of hormone resistance is essential.
Bartlett, J.M.S.+3 more
core
P38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level [PDF]
The cytokine tumor necrosis factor (TNF) alpha was found to stimulate the p38 mitogen activated protein (MAP) kinase signalling cascade in human umbilical vein endothelial cells.
Gaestel, M. (Matthias)+6 more
core +2 more sources
NRAS mutations are widespread in hematologic malignancies. Our study shows that GOLGA7 serves as a safe and effective therapeutic target for NRAS‐driven leukemia. Loss of Golga7 in adult mice effectively suppresses NrasG12D‐driven myeloproliferative neoplasm by disrupting its PM localization and impairing subsequent MAPK signaling, without affecting ...
Bo Jiao+18 more
wiley +1 more source
Activated mutant NRasQ61K drives aberrant melanocyte signaling, survival, and invasiveness via a rac1-Dependent mechanism [PDF]
Around a fifth of melanomas exhibit an activating mutation in the oncogene NRas that confers constitutive signaling to proliferation and promotes tumor initiation.
Abraham+52 more
core +1 more source
High Fat Low Carbohydrate Diet Is Linked to CNS Autoimmunity Protection
Mapping global epidemiological data to macronutrient supply reveals high carbohydrate, in contrast to high fat supply, associates with increased multiple sclerosis (MS) prevalence and incidence. This is confirmed in a mouse MS model, experimental autoimmune encephalomyelitis (EAE), using isocaloric diets: a high carbohydrate diet aggravates, a high ...
Duan Ni+15 more
wiley +1 more source