An important link between brain aging and a class of growth/survival factors called neurotrophins has recently been demonstrated. In particular, brain-derived neurotrophic factor (BDNF) plays a fundamental role during age-related synaptic loss, preventing cerebral atrophy and cognitive decline. The aim of the present study was to investigate whether the use of low dose BDNF sequentially kinetic activated (SKA) was able to counteract some mechanisms underlying the degeneration and aging of nervous tissue by increasing endogenous protection mechanisms. Both in vitro and in vivo experiments were performed to assess the ability of BDNF SKA to protect and regenerate survival-related molecular pathways, studying intestinal absorption in vitro and brain function in vivo. Our pioneering results show that BDNF SKA is able to induce the endogenous production of BDNF, using its receptor TrkB and influencing the apolipoprotein E expression. Moreover, BDNF SKA exerted effects on β-Amyloid and Sirtuin 1 proteins, confirming the hypothesis of a fine endogenous regulatory effect exerted by BDNF SKA in maintaining the health of both neurons and astrocytes. For this reason, a change in BDNF turnover is considered as a positive factor against brain aging.

This review presents recent knowledge on the neuroprotective effects of vitamin D and their usefulness as oral supplementation when combined with other molecules, such as curcumin. A critical look at the effectiveness of vitamin D in this field is also provided. Vitamin D plays a crucial role in neuroprotection and in the cognitive decline associated with aging, where vitamin D’s levels are related to the levels of several neurotrophic factors. An important role of vitamin D has also been observed in the mechanism of neuroinflammation, which is the basis of several aging conditions, including cognitive decline and neurodegeration; furthermore, the neuroprotective effect of vitamin D in the cognitive decline of aging has recently been reported. For this reason, many food supplements created for humans contain vitamin D alone or combined with other molecules with antioxidant properties. However, recent studies also explored negative consequences of the use at a high dosage of vitamin D. Vitamin D in tissues or brain cells can also modulate calbindin-D28K, parvalbumin, and calretinin, and is involved in immune function, thanks also to the combination with curcumin. Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation and oxidative DNA damage. In particular, curcumin is a potent immune-regulatory agent and its administration has been reported to attenuate cognitive impairments. These effects could be exploited in the future to control the mechanisms that lead to the brain decay typical of neurodegenerative diseases.

Transferrins constitute the most important iron regulation system in vertebrates and some invertebrates. Soluble transferrins, such as bovine lactoferrin and hen egg white ovotransferrin, are glycoproteins with a very similar structure with lobes that complex with iron. In this in vitro study, a comparison of bovine lactoferrin and ovotransferrin was undertaken to confirm the comparability of biological effects. An in vitro gastric barrier model using gastric epithelial cells GTL-16 and an in vitro intestinal barrier model using CaCo-2 cells was employed to evaluate iron absorption and barrier integrity. An analysis of the molecular pathways involving DMT-1 (divalent metal transporter 1), ferritin and ferroportin was also carried out. These in vitro data demonstrate the activity of both 15% saturated and 100% saturated ovotransferrin on the iron regulation system. Compared with the commercial bovine lactoferrin, both 15% saturated and 100% saturated ovotransferrin were found to act in a more physiological manner. Based on these data, it is possible to hypothesise that ovotransferrin may be an excellent candidate for iron supplementation in humans; in particular, 15% saturated ovotransferrin is the overall best performing product. In vivo studies should be performed to confirm this in vitro data.

Background: Magnesium is involved in a wide variety of physiological processes including direct relaxation of smooth muscle. A magnesium imbalance can be considered the primary cause or consequence of many pathophysiological conditions. The smooth muscle tissue of the uterus, i.e., the myometrium, undergoes numerous physiological changes during life, fundamental for uterine activities, and it receives proven benefits from magnesium supplementation. However, magnesium supplements have poor absorption and bioavailability. Furthermore, no data are available on the direct interaction between intestinal absorption of magnesium and relaxation of the myometrium. Methods: Permeability in human intestinal cells (Caco-2 cells) and direct effects on myometrial cells (PHM1-41 cells) of two different forms of magnesium, i.e., sucrosomial and bisglycinate, were studied in order to verify the magnesium capacity of modulate contractility. Cell viability, reactive oxygen species (ROS) and nitric oxide (NO) production, magnesium concentration, contractility, and pathways involved were analyzed. Results: Data showed a better influence of buffered chelate bisglycinate on intestinal permeability and myometrial relaxation over time with a maximum effect at 3 h and greater availability compared to the sucrosomial form. Conclusions: Magnesium-buffered bisglycinate chelate showed better intestinal absorption and myometrial contraction, indicating a better chance of effectiveness in human applications.

Background: Glaucoma is currently the leading cause of irreversible blindness; it is a neuropathy characterized by structural alterations of the optic nerve, leading to visual impairments. The aim of this work is to develop a new oral formulation able to counteract the early changes connected to glaucomatous degeneration. The composition is based on gastrodin and vitamin D3 combined with vitamin C, blackcurrant, and lycopene. Methods: Cells and tissues of the retina were used to study biological mechanisms involved in glaucoma, to slow down the progression of the disease. Experiments mimicking the conditions of glaucoma were carried out to examine the etiology of retinal degeneration. Results: Our results show a significant ability to restore glaucoma-induced damage, by counteracting ROS production and promoting cell survival by inhibiting apoptosis. These effects were confirmed by the intracellular mechanism that was activated following administration of the compound, either before or after the glaucoma induction. In particular, the main results were obtained as a preventive action of glaucoma, showing a beneficial action on all selected markers, both on cells and on eyecup preparations. It is therefore possible to hypothesize both the preventive and therapeutic use of this formulation, in the presence of risk factors, and due to its ability to inhibit the apoptotic cycle and to stimulate cell survival mechanisms, respectively. Conclusion: This formulation has exhibited an active role in the prevention or restoration of glaucoma damage for the first time.

The authors would like to publish this addendum to their recent publication