DYRK1A modulates c-MET in pancreatic ductal adenocarcinoma to drive tumour growth.

Background And Aims: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumour with a poor prognosis using current treatments. Targeted therapies may offer a new avenue for more effective strategies. Dual-specificity tyrosine regulated kinase 1A (DYRK1A) is a pleiotropic kinase with contradictory roles in different tumours that is uncharacterised in PDAC.

DYRK1A Kinase Positively Regulates Angiogenic Responses in Endothelial Cells.

Angiogenesis is a highly regulated process essential for organ development and maintenance, and its deregulation contributes to inflammation, cardiac disorders, and cancer. The Ca/nuclear factor of activated T cells (NFAT) signaling pathway is central to endothelial cell angiogenic responses, and it is activated by stimuli like vascular endothelial growth factor (VEGF) A. NFAT phosphorylation by dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) is thought to be an inactivating event.

Palm oil tocotrienol rich fraction reduces extracellular matrix production by inhibiting transforming growth factor-β1 in human intestinal fibroblasts.

Background & Aims: Extracellular matrix deposition is key event for the development of bowel stenosis in Crohn's disease patients. Transforming growth factor-β plays a key role in this process. We aimed at characterizing the effects of tocotrienol rich fraction on ECM proteins production and molecules that regulate the synthesis and degradation of extracellular matrix, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1, in human intestinal fibroblasts, and at elucidating whether the effects of tocotrienol rich fraction (TRF) are mediated through inhibition of TGF-β1.

Mesenchymal cell proliferation and programmed cell death: key players in fibrogenesis and new targets for therapeutic intervention.

An exquisite equilibrium between cell proliferation and programmed cell death is required to maintain physiological homeostasis. In inflammatory bowel disease, and especially in Crohn's disease, enhanced proliferation along with defective apoptosis of immune cells are considered key elements of pathogenesis. Despite the relatively limited attention that has been given to research efforts devoted to intestinal fibrosis to date, there is evidence suggesting that enhanced proliferation along with defective programmed cell death of mesenchymal cells can significantly contribute to the development of excessive fibrogenesis in many different tissues.

Tocotrienols have potent antifibrogenic effects in human intestinal fibroblasts.

Background: Excessive fibroblast expansion and extracellular matrix (ECM) deposition are key events for the development of bowel stenosis in Crohn's disease (CD) patients. Tocotrienols are vitamin E compounds with proven in vitro antifibrogenic effects on rat pancreatic fibroblasts. We aimed at investigating the effects of tocotrienols on human intestinal fibroblast (HIF) proliferation, apoptosis, autophagy, and synthesis of ECM.