Alopecia areata (AA) is a dermatological condition characterized by non-scarring hair loss. Exact etiopathogenesis of AA is still unknown although it is known that several factors contribute to the collapse of the hair-follicle (HF)-immune-privileged (IP) site. Oxidative stress (OS) plays an important role in skin diseases. The aim of this review was to clarify the role of OS in AA pathogenesis and diagnosis, and to discuss potential treatment options. Oxidative-stress markers are altered in serum and skin samples of patients with AA, confirming a general pro-oxidative status in patients with AA. OS induces MHC class I chain-related A (MICA) expression in HF keratinocytes that activates the receptor NKG2D, expressed in NK cells and CD8+ T cytotoxic cells leading to destabilization of the HF immune-privileged site through the production of IFN-γ that stimulates JAK1 and JAK2 pathways. OS also activates the KEAP1-NRF2 pathway, an antioxidant system that contributes to skin homeostasis. In addition, a decrease of ATG5 and LC3B in the hair matrix and an increase in p62 levels indicates a reduction of intrafollicular autophagy during the evolution of AA. Potential biomarkers of OS in AA could be: malondialdehyde (MDA), advanced glycation end-products (AGEs), and ischemic-modified albumin (IMA). JAK inhibitors are the new frontier in treatment of AA and the use of nutraceuticals that modulate the OS balance, in combination with standard treatments, represent promising therapeutic tools.
Lime (Citrus aurantiifolia) is a plant belonging to the family of Rutaceae and to the genus Citrus. The fruit is widely used in the United States, Mexico, Southeast Asia, Latin America, but is increasingly widespread all over the world. It is used as a fresh fruit, in the preparation of foods, sweets and drinks and its oils are used in the cosmetic and pharmaceutical industry. The main adverse reactions to lime seem to be represented by contact dermatitis, allergic and phototoxic type. In the context of allergic forms, several allergens have been identified in the citrus family, the main one being limonene, but no noteworthy cross-reactivity has been identified. However, a case of fruit protein contact dermatitis has been described, showing sensitization to other fruits, such as kiwi, avocado, pineapple and apple. There are several molecules responsible for phototoxic reactions and mainly belonging to the coumarin and furocoumarins families. Reactions related to ingesting the fruit or inhaling pollen from the tree appear to be rare, as there are no known cases reported in the literature. The increasing diffusion of lime in Europe must pay attention to possible adverse reactions due to contact with this fruit, which seem destined to increase in future years. Further importance must be placed on patch tests and on the possibility of using alternative extracts to classic fragrance mixes.
Skin cancer is a prevalent type of cancer worldwide and has a high growth rate compared to other diseases. Although modern targeted therapies have improved the management of cutaneous neoplasms, there is an urgent requirement for a safer, more affordable, and effective chemoprevention and treatment strategy for skin cancer. Nutraceuticals, which are natural substances derived from food, have emerged as a potential alternative or adjunctive treatment option. In this review, we explore the current evidence on the use of omega-3 fatty acids and polyphenols (curcumin, epigallocatechin gallate, apigenin, resveratrol, and genistein) for the treatment of melanoma and non-melanoma skin cancer (NMSC), as well as in their prevention. We discuss the mechanisms of action of the aforementioned nutraceuticals and their probable therapeutic benefits in skin cancer. Omega-3 fatty acids, curcumin, epigallocatechin gallate, apigenin, resveratrol, and genistein have several properties, among which are anti-inflammatory and anti-tumor, which can help to prevent and treat skin cancer. However, their effectiveness is limited due to poor bioavailability. Nanoparticles and other delivery systems can improve their absorption and targeting. More research is needed to evaluate their safety and effectiveness as a natural approach to skin cancer prevention and treatment. These compounds should not replace conventional cancer treatments, but may be used as complementary therapy under the guidance of a healthcare professional.
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