Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the ageing population. Without effective treatment strategies that can prevent disease progression, there is an urgent need for novel therapeutic interventions to reduce the burden of vision loss and improve patients' quality of life. Dysfunctional innate immune responses to oxidative stress observed in AMD can be caused by the formation of oxidised lipids, whilst polyunsaturated fatty acids have shown to increase the risk of AMD and disease progression in affected individuals.

Ponatinib Tyrosine Kinase Inhibitor Induces a Thromboinflammatory Response.

Both nilotinib, a second-generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukaemia (CML), and ponatinib, a third-generation TKI used in CML and Philadelphia positive acute lymphocytic leukaemia, have been associated with an increase in arterial occlusive events, in contrast to other TKIs such as imatinib and dasatinib. We have previously demonstrated evidence of a pro-thrombotic state associated with nilotinib, using microvascular and arterial thrombosis C57BL/6 mouse models. In this study, we examined ponatinib and determined if a calcium channel blocker could ameliorate the pro-thrombotic and pro-inflammatory phenotypes.

The tyrosine kinase inhibitor, nilotinib potentiates a prothrombotic state.

Tyrosine kinase inhibitors (TKI) such as imatinib, nilotinib and dasatinib are now established as highly effective frontline therapies for chronic myeloid leukaemia (CML). Disease control is achieved in the majority of patients and survival is excellent such that recent focus has been on toxicities of these agents. Cumulative data have reported an excess of serious vascular complications, including arterial thrombosis and peripheral arterial occlusive disease, in patients receiving nilotinib in comparison with other TKIs, with resultant interest in delineating the pathophysiology and implications for rationale cardiovascular risk modification.

Epigenetic modifications as potential therapeutic targets in age-related macular degeneration and diabetic retinopathy.

Recently, aberrant epigenetic modifications have been identified in the pathogenesis of the posterior eye diseases, age-related macular degeneration (AMD) and diabetic retinopathy (DR). This has led to the development of alternative therapies that can alter aberrant chromatin-remodelling processes involved in AMD and DR. These novel therapeutic agents could help to ameliorate the challenges associated with current treatments that are limited by variable patient response and disease heterogeneity.

Investigation of the biological properties of Cinnulin PF in the context of diabetes: mechanistic insights by genome-wide mRNA-Seq analysis.

The accumulating evidence of the beneficial effects of cinnamon (Cinnamomum burmanni) in type-2 diabetes, a chronic age-associated disease, has prompted the commercialisation of various supplemental forms of the spice. One such supplement, Cinnulin PF(®), represents the water soluble fraction containing relatively high levels of the double-linked procyanidin type-A polymers of flavanoids. The overall aim of this study was to utilize genome-wide mRNA-Seq analysis to characterise the changes in gene expression caused by Cinnulin PF in immortalised human keratinocytes and microvascular endothelial cells, which are relevant with respect to diabetic complications.

Influence of natural and synthetic histone deacetylase inhibitors on chromatin.

Significance: Histone deacetylase inhibitors (HDACIs) have emerged as a new class of anticancer therapeutics. The hydroxamic acid, suberoylanilide hydroxamic acid (Vorinostat, Zolinza™), and the cyclic peptide, depsipeptide (Romidepsin, Istodax™), were approved by the U.S.

Chromatin modifying agents - the cutting edge of anticancer therapy.

Chromatin modifying compounds are emerging as the next generation of anticancer therapies. By altering gene expression they could be able to correct uncontrolled proliferation and, in certain cases, aberrant apoptotic pathways, which are hallmarks of malignant cells. The modulation of gene expression is regulated via chromatin remodelling processes that include DNA methylation and chromatin modifications.

Chlorambucil-sensitive and -resistant lymphoid cells display different responses to the histone deacetylase inhibitor, sodium butyrate.

Clinical chemoresistance is a frequent complication of alkylating agent treatment of malignant tumours. Chromatin remodelling using histone deacetylase inhibitors (e.g.