Vitamin K is a fat-soluble nutrient discovered in 1935 and its role in blood coagulation has been thoroughly explored. In recent years, studies conducted in vitro and on animals highlighted vitamin K involvement in brain cells development and survival. In particular, vitamin K seems to have an antiapoptotic and anti-inflammatory effect mediated by the activation of Growth Arrest Specific Gene 6 and Protein S. Moreover, this vitamin is involved in sphingolipids metabolism, a class of lipids that participate in the proliferation, differentiation, and survival of brain cells. An altered expression in sphingolipids profile has been related to neuroinflammation and neurodegeneration. This review stems from a growing interest in the role of vitamin K in brain functions, especially in cognition, also in view of an expected increase of prevalence of Alzheimer's disease and other forms of dementia. It collects recent researches that show interesting, even though not definitive, evidence of a direct correlation between vitamin K levels and cognitive performance. Moreover, vitamin K antagonists, used worldwide as oral anticoagulants, according to recent studies may have a negative influence on cognitive domains such as visual memory, verbal fluency and brain volume. The aim of this review is to analyze the evidence of clinical studies carried out up to date on the relationship between vitamin K intake and cognitive performances. The involvement of vitamin K antagonists (VKAs) in declining cognitive performances is also addressed separately.
Vernal keratoconjunctivitis (VKC) is a rare, recurrent and multifactorial ocular disease, which typically flares up during spring and affects especially male children and adolescents. This condition does not usually respond to common treatments with antihistamines or mast cells stabilizers, whereas corticosteroids have effective results. Corticosteroids need to be carefully administered, to avoid adverse effects, mainly the secondary development of glaucoma, cataracts, or infections. Immunosuppressive agents, such as cyclosporin (CyA) or tacrolimus are, therefore, frequently employed in VKC patients. Only the 0.1% CyA (1 mg/mL) concentration has an approved and specific clinical indication for the treatment of VKC and this drug was given the denomination of orphan drug by the European Commission (EU/3/06/360) in 2006. So far, few studies have been conducted to evaluate the efficacy and the side effects of topical 0.1% CyA. Different topical CyA concentrations, ranging from 0.05% to 2%, and various types of formulation are available at the moment. In the future, 0.1% CyA will presumably take an important part in the management of VKC. The present review focuses on eye drops containing 0.1% CyA; however, more studies will be needed to define its long-term efficacy in the natural course of this severe ocular disease.
High-mobility group box 1 (HMGB1) is a protein that is part of a larger family of non-histone nuclear proteins. HMGB1 is a ubiquitary protein with different isoforms, linked to numerous physiological and pathological pathways. HMGB1 is involved in cytokine and chemokine release, leukocyte activation and migration, tumorigenesis, neoangiogenesis, and the activation of several inflammatory pathways. HMGB1 is, in fact, responsible for the trigger, among others, of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), toll-like receptor-4 (TLR-4), and vascular endothelial growth factor (VEGF) pathways. Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM) that is rapidly growing in number. DR is an inflammatory disease caused by hyperglycemia, which determines the accumulation of oxidative stress and cell damage, which ultimately leads to hypoxia and neovascularization. Recent evidence has shown that hyperglycemia is responsible for the hyperexpression of HMGB1. This protein activates numerous pathways that cause the development of DR, and HMGB1 levels are constantly increased in diabetic retinas in both proliferative and non-proliferative stages of the disease. Several molecules, such as glycyrrhizin (GA), have proven effective in reducing diabetic damage to the retina through the inhibition of HMGB1. The main focus of this review is the growing amount of evidence linking HMGB1 and DR as well as the new therapeutic strategies involving this protein.
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