Epigallocatechin-3-Gallate, an Active Green Tea Component to Support Anti-VEGFA Therapy in Wet Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a largely incurable disease and an emerging problem in aging societies. It occurs in two forms, dry and wet (exudative, neovascular), which may cause legal blindness and sight loss. Currently, there is not any effective treatment for dry AMD. Meanwhile, repeated intravitreal injections with antibodies effective against vascular endothelial growth factor A (VEGFA) slow down wet AMD progression but are not free from complications. (-)-Epigallocatechin-3-gallate (EGCG) is an active compound of green tea, which exerts many beneficial effects in the retinal pigment epithelium and the neural retina. It has been reported to downregulate the VEGFA gene by suppressing its activators. The inhibition of mitogen-activated protein kinases 1 and 3 (MAPK1 and MAPK3) may lie behind the antiangiogenic action of EGCG mediated by VEGFA. EGCG exerts protective effects against UV-induced damage to retinal cells and improves dysfunctional autophagy. EGCG may also interact with the mechanistic target rapamycin (MTOR) and unc-51-like autophagy activating kinase (ULK1) to modulate the interplay between autophagy and apoptosis. Several other studies report beneficial effects of EGCG on the retina that may be related to wet AMD. Therefore, controlled clinical trials are needed to verify whether diet supplementation with EGCG or green tea consumption may improve the results of anti-VEGFA therapy in wet AMD.

Oral Glucosamine in the Treatment of Temporomandibular Joint Osteoarthritis: A Systematic Review.

Temporomandibular disorders (TMDs) occur frequently within the general population and are the most common non-dental cause of orofacial pain. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative joint disease (DJD). There have been several different methods of treatment of TMJ OA listed, including pharmacotherapy among others. Due to its anti-aging, antioxidative, bacteriostatic, anti-inflammatory, immuno-stimulating, pro-anabolic and anti-catabolic properties, oral glucosamine seems to be a potentially very effective agent in the treatment of TMJ OA. The aim of this review was to critically assess the efficacy of oral glucosamine in the treatment of TMJ OA on the basis of the literature. PubMed and Scopus databases were analyzed with the keywords: (temporomandibular joints) AND ((disorders) OR (osteoarthritis)) AND (treatment) AND (glucosamine). After the screening of 50 results, eight studies have been included in this review. Oral glucosamine is one of the symptomatic slow-acting drugs for osteoarthritis. There is not enough scientific evidence to unambiguously confirm the clinical effectiveness of glucosamine supplements in the treatment of TMJ OA on the basis of the literature. The most important aspect affecting the clinical efficacy of oral glucosamine in the treatment of TMJ OA was the total administration time. Administration of oral glucosamine for a longer period of time, i.e., 3 months, led to a significant reduction in TMJ pain and a significant increase in maximum mouth opening. It also resulted in long-term anti-inflammatory effects within the TMJs. Further long-term, randomized, double-blind studies, with a unified methodology, ought to be performed to draw the general recommendations for the use of oral glucosamine in the treatment of TMJ OA.

Vitamin D3 Metabolism and Its Role in Temporomandibular Joint Osteoarthritis and Autoimmune Thyroid Diseases.

The aim of this review was to present the metabolism of vitamin D3, as well as to discuss the role of vitamin D3 in bone metabolism, temporomandibular joint osteoarthritis (TMJ OA), and autoimmune thyroid diseases (AITD) on the basis of the literature. Vitamin D3 plays a significant role in human health, as it affects the calcium-phosphate balance and regulates the bone metabolism. Calcitriol impresses the pleiotropic effect on human biology and metabolism. Its modulative function upon the immune system is based on the reduction of Th1 cell activity and increased immunotolerance. Vitamin D3 deficiency may lead to an imbalance in the relationship between Th1/Th17 and Th2, Th17/Th reg, and is considered by some authors as one of the possible backgrounds of autoimmune thyroid diseases (AITD), e.g., Hashimoto's thyroiditis or Graves' disease. Moreover, vitamin D3, through its direct and indirect influence on bones and joints, may also play an important role in the development and progression of degenerative joint diseases, including temporomandibular joint osteoarthritis. Further randomized, double blind studies are needed to unequivocally confirm the relationship between vitamin D3 and abovementioned diseases and to answer the question concerning whether vitamin D3 supplementation may be used in the prevention and/or treatment of either AITD or OA diseases.

Nutrition in Cancer Therapy in the Elderly-An Epigenetic Connection?

The continuous increase in life expectancy results in a steady increase of cancer risk, which consequently increases the population of older adults with cancer. Older adults have their age-related nutritional needs and often suffer from comorbidities that may affect cancer therapy. They frequently are malnourished and present advanced-stage cancer. Therefore, this group of patients requires a special multidisciplinary approach to optimize their therapy and increase quality of life impaired by aging, cancer, and the side effects of therapy. Evaluation strategies, taking advantage of comprehensive geriatric assessment tools, including the comprehensive geriatric assessment (CGA), can help individualize treatment. As epigenetics, an emerging element of the regulation of gene expression, is involved in both aging and cancer and the epigenetic profile can be modulated by the diet, it seems to be a candidate to assist with planning a nutritional intervention in elderly populations with cancer. In this review, we present problems associated with the diet and nutrition in the elderly undergoing active cancer therapy and provide some information on epigenetic aspects of aging and cancer transformation. Nutritional interventions modulating the epigenetic profile, including caloric restriction and basal diet with modifications (elimination diet, supplementary diet) are discussed as the ways to improve the efficacy of cancer therapy and maintain the quality of life of older adults with cancer.

Zinc and Autophagy in Age-Related Macular Degeneration.

Zinc supplementation is reported to slow down the progression of age-related macular degeneration (AMD), but there is no general consensus on the beneficiary effect on zinc in AMD. As zinc can stimulate autophagy that is declined in AMD, it is rational to assume that it can slow down its progression. As melanosomes are the main reservoir of zinc in the retina, zinc may decrease the number of lipofuscin granules that are substrates for autophagy. The triad zinc-autophagy-AMD could explain some controversies associated with population studies on zinc supplementation in AMD as the effect of zinc on AMD may be modulated by genetic background. This aspect was not determined in many studies regarding zinc in AMD. Zinc deficiency induces several events associated with AMD pathogenesis, including increased oxidative stress, lipid peroxidation and the resulting lipofuscinogenesis. The latter requires autophagy, which is impaired. This is a vicious cycle-like reaction that may contribute to AMD progression. Promising results with zinc deficiency and supplementation in AMD patients and animal models, as well as emerging evidence of the importance of autophagy in AMD, are the rationale for future research on the role of autophagy in the role of zinc supplementation in AMD.

Can vitamin D protect against age-related macular degeneration or slow its progression?

Dietary vitamin D plays an important role in maintaining proper vision. Age-related macular degeneration (AMD) is a complex eye disease with unknown pathogenesis. Studies on dietary supplementation and AMD occurrence and progression have produced conflicting results. In its advanced stage, AMD may be associated with apoptosis, pyroptosis or necroptosis of retinal cells. Vitamin D has been reported to play a role in modulating each of these programmed death pathways. Vitamin D is a modulator of the immune system and it acts synergistically with two members of the regulators of complement activation family H and I, whose specific variants are the most important genetic factors for AMD pathogenesis. Angiogenesis is an essential component of the neovascular form of AMD, the most devastating type of the disease and vitamin D is reputed to possess antiangiogenic properties. Cellular DNA damage response is weakened in AMD patients and so it is another process that can be modulated by vitamin D. Finally, impaired autophagy is claimed to play a role in AMD and emerging evidence suggests that vitamin D can influence autophagy. Therefore, several pathways of vitamin D metabolism and AMD pathogenesis overlap, suggesting that vitamin D could modulate the course of AMD.

Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations.

Vitamin C is an antioxidant that may scavenge reactive oxygen species preventing DNA damage and other effects important in cancer transformation. Dietary vitamin C from natural sources is taken with other compounds affecting its bioavailability and biological effects. High pharmacological doses of vitamin C may induce prooxidant effects, detrimental for cancer cells. An oxidized form of vitamin C, dehydroascorbate, is transported through glucose transporters, and cancer cells switch from oxidative phosphorylation to glycolysis in energy production so an excess of vitamin C may limit glucose transport and ATP production resulting in energetic crisis and cell death. Vitamin C may change the metabolomic and epigenetic profiles of cancer cells, and activation of ten-eleven translocation (TET) proteins and downregulation of pluripotency factors by the vitamin may eradicate cancer stem cells. Metastasis, the main reason of cancer-related deaths, requires breakage of anatomical barriers containing collagen, whose synthesis is promoted by vitamin C. Vitamin C induces degradation of hypoxia-inducible factor, HIF-1, essential for the survival of tumor cells in hypoxic conditions. Dietary vitamin C may stimulate the immune system through activation of NK and T cells and monocytes. Pharmacological doses of vitamin C may inhibit cancer transformation in several pathways, but further studies are needed to address both mechanistic and clinical aspects of this effect.