Atopic dermatitis: regenerating mitochondria, an additional contribution to protecting the epidermal barrier - Mitochon (2024)

Andrea Tognelli, Farmacista – Firenze

What’s New?
In May 2024, the journal Frontiers in Immunology published the article “Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning” (1), which adds important insights into the role of mitochondria in the onset and progression of atopic dermatitis (2, 3, 4) (Note 1).

In recent years a growing number of articles have examined alterations in the activities carried out by mitochondria (mitochondrial dysfunction) and their relationship to atopic dermatitis, for example:

• the reduced activity of nuclear factor erythroid 2-related transcription factor-2 (NRF2), which under physiological conditions regulates the genes encoding antioxidant enzymes (5);
• the high production of free radicals, such as hydrogen peroxide (6), and alteration of mitochondrial metabolism (7);
• mitochondrial DNA damage, which contributes to triggering the pathogenesis of atopic dermatitis and other allergic conditions (e.g., food) to the development of asthma and allergic rhinitis. This progression is, referred to as the “atopic march,” beginning in the skin and gastrointestinal tract and eventually affecting the upper and lower respiratory tracts (8).

In addition, experimental and clinical research has focused well on the contribution of the physiological functions of mitochondria in maintaining skin health (9).
In fact, mitochondrial integrity is critical for the control of the aging process (aging), ultraviolet (UV) ray effects, wound healing, cancer risk, etc.. These tasks of mitochondria are performed through multiple molecular and cellular mechanisms, in addition to the priority production of energy essential for cellular life (9, 10, 11).

Equally well known are the connections between mitochondrial dysfunction and diseases closely related to atopic dermatitis, both skin and systemic, such as asthma and allergic rhinitis and gastrointestinal disorders (5, 9,10).

The centrality of mitochondrial dysfunction in the aging processes of the organism, and in many noncommunicable diseases, was recently addressed in the News of Mitochon Ltd. website https://www.mitochon.it/ (12).
Indeed, the study of mitochondria and oxidative stress/inflammation are shown to be burgeoning areas of research that open up new opportunities for prevention and treatment for many chronic age-related diseases (13).

Atopic dermatitis and mitochondria: beyond the bioenergetic role

The Frontiers in Immunology article examined mitochondria-related differential gene expression (mitochondria-related differentially expressed genes, MitoDEGs) in samples taken from patients with atopic dermatitis (1).

With the help of a machine learning algorithm used by an artificial intelligence system, researchers identified biopathological variations in mitochondria in atopic dermatitis for the first time.
These variations involve gene expression implicated in many cellular mechanisms.
For example, some antioxidant genes are involved that control mitochondria activities, such as respiratory and mitochondrial dynamics (12), as well as the response to stress conditions.
If altered, these genetic mechanisms can negatively impact energy and oxidoreductive reactions, the transport of micromolecules (e.g., calcium) across the mitochondrial membrane, and the metabolism of amino acids that form the protein component of the skin.

This research also emphasizes the importance of mitochondria in the immune system. Immune cells require a large amount of energy supplied by mitochondria, which, in turn, influence immune and inflammatory responses. Dysfunctional mitochondria can no longer perform these fundamental functions necessary for the body’s defense.

In practice, the results of the study allowed linking the pathogenesis of atopic dermatitis to precise gene expression, and the critical role of mitochondrial dysfunction in this disease.

Mitochondria target
Furthermore, the Frontiers in Immunology article (1) introduces the strategy of considering mitochondria as a target for the treatment of atopic dermatitis, making use of antioxidant molecules.

Topic further explored by the International Journal Molecular Sciences in March 2024 “Dermatologic Manifestations of Mitochondrial Dysfunction: A Review of the Literature,” where significant results achieved with coenzyme Q10, for topical and systemic use, are highlighted (9, 12, 14, 15), which will be discussed in more detail below.

Additional and important acquisitions
During 2024, the mechanisms that alter the epidermal barrier in individuals with atopic dermatitis were further investigated.

August 2024 saw the publication of the Davos Global Allergy Forum – 4th Davos Declaration (16), an articulate analysis of the state of the art on atopic dermatitis, to which numerous articles have been added over the past few months.

New elements emerge on inflammatory, immunological, and those mechanisms related to oxidative stress, with their bidirectional relationships, in addition to the mentioned mitochondrial dysfunction, and genetic predisposition (2, 3, 9, 13, 16, 17), here are some essential points:

• Genetic factors involve several genes that regulate epidermal structural proteins and immune mechanisms (16, 18, 19, 20, 21, 22), resulting in alterations that have been further investigated by the study conducted with machine learning (1).
• Alterations in the epidermal barrier in subjects with atopic dermatitis are attributed to reduced expression of filaggrin, a filamentous protein bound to keratin fibers, also involved in pH regulation, which is increased in atopic dermatitis (16, 23, 24). There is a deficiency of ceramides, the sphingolipid molecules present in the cell membrane, which are indispensable constituents of the epidermal barrier (16, 25, 26, 27, 28). As well as increased activity of epidermal proteases, the keratolytic enzymes that under physiological conditions ensure skin regeneration. Their excessive action weakens skin structures (16, 29, 30).
• A damaged epidermal barrier exposes the skin more to the daily aggression of environmental agents (16, 31, 32). Therefore, conditions are created for increased production of free radicals such as reactive oxygen species (ROS), which trigger inflammatory and immune and allergic-type responses by Th2 lymphocytes. Inflammatory cytokines directly contribute to increased barrier damage by damaging proteins (16, 29, 33), such as filaggrin, with its key role in skin structures (3, 16, 23, 24).
• ROS react directly with various macromolecules, lipids, proteins, carbohydrates, nucleic acids, resulting in metabolic alterations (18) and the onset of chain reactions up to cell death. These are all events that cause the further increase of skin and systemic inflammation. In this environment, skin cells, keratinocytes, Langerhans cells, fibroblasts, increase ROS production, generating a vicious cycle. The result is the lowering of concentrations and activities of enzymatic antioxidants and those non-enzymatic antioxidants naturally present in the human body. In practice, a reduced antioxidant capacity of the body is established (29, 33).
• Keratinocytes are considered the key cells in atopic dermatitis, as they trigger interactions with immune cells and sensory neurons, producing itching and inflammation (34).
• Alterations in lipid synthesis and secretion are found in the skin surface of individuals with atopic dermatitis. This results in lowered levels of ceramides (Note 2), cholesterol and free fatty acids, which under physiological conditions stabilize the epidermal barrier (35).
• In subjects with atopic dermatitis, the increase in skin pH can alter the microbial composition with the risk of proliferation of Streptococcus Aureus, a bacterium responsible for skin and systemic infections (16, 34, 36).
• Alterations in the gut microbiota are also related to atopic dermatitis. The composition of gut bacteria is implicated in multiple mechanisms, e.g., neuroimmunological, inflammatory, oxidative; and has a specific relationship with mitochondrial dysfunction and vice versa (36, 37). Therefore, maintaining the balance of the gut microbiota has a positive impact on atopic dermatitis, through nutrition and/or (38, 39) targeted supplementation (40) with the goal of preventing gut dysbiosis and related systemic and skin complications, including atopic dermatitis (39).
• The aging process has close relationships with atopic dermatitis, which also has a high prevalence in adults and the elderly (Note 1).
  The progression of dermatitis is also facilitated by changes resulting from skin and systemic aging.
  Beyond the age of 30 years, there is progressive decline of the immune system, the presence of chronic mild inflammation (inflammaging), structural and functional changes in the skin, lowering of antioxidant defenses, and other age-dependent pathophysiological processes (41).
  Atopic dermatitis in young adults and the elderly is associated with increased risk of cardiovascular disease (42), hormonal and metabolic implications, gastrointestinal, musculoskeletal, etc. (41).
  In addition, atopic dermatitis exposes to an increased risk of cognitive decline (43, 44), anxiety and depression (45, 46), with in considerable impact on quality of life (16, 47, 48).

Antioxidants/anti-inflammatories: what contribution?
The targeted use of specific antioxidant/anti-inflammatory molecules is thought to be beneficial in patients with atopic dermatitis of an allergic nature, who account for 80% of cases. These patients have elevated serum immunoglobulin E (IgE) class levels and skin barrier damage (29).
The goal of restoring mitochondria functions with the use of antioxidant/anti-inflammatory molecules (1, 9) is proposed as a useful option to lower ROS levels and modulate inflammatory phenomena (12, 13). These interventions allow reactivation of mitochondria energy production and cellular activities, mitigating the resulting sequelae of clinical manifestations (12, 13, 14).

Topical and systemic use of certain antioxidants/anti-inflammatories also compensates for the inexorable decline in the body’s antioxidant capacity (29).

Recall that the gradual depletion of the body’s antioxidant defense systems is accentuated by various external agents, ultraviolet (UV) rays, pollutants, etc., as well as by advancing age and inherent lifestyle factors, insufficient dietary antioxidant intake, concomitant diseases, etc. (16, 29, 39, 50).

In atopic dermatitis, the burden of oxidative stress and lipid peroxidation further lowers the concentrations of antioxidant enzymes: catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase.

Low levels are also found for nonenzymatic antioxidants, such as of vitamin C and E (29, 39), and D (29 – 39), which, among its many activities, also influences the immune system and has anti-inflammatory action (29).

The progressive decline in concentrations also affects nonenzymatic antioxidants synthesized by the body.
Reduced levels of coenzyme Q10 occur in patients with asthma and other chronic inflammatory diseases (50, 51).
Glutathione deficiency is particularly pronounced in respiratory and cardiovascular diseases and during aging of the body. (33, 51, 52, 53).

The molecules in the Mitochon srl line
The following is a review of the scientific literature regarding atopic dermatitis and the molecules contained in the cosmeceutical line bit.ly/4aY7Pyy and the nutraceuticals Mitofast® bit.ly/3VUlGkS and Mitofast B12 bit.ly/4d5ll4P from the company Mitochon srl https://www.mitochon.it/.

Mitochon Ltd. research has developed its products taking as its goal the regeneration of mitochondria and cellular functions to preserve skin health and combat signs of skin and systemic aging.

In addition to high quality standards, Mitochon Ltd. products are distinguished by the stability and bioavailability of the molecules, which are used at high dosages.

Formulated with P.AS.S.® pharmaceutical technology, Mitochon srl cosmeceutical products contain:
Coenzyme Q10, glutathione, vitamins A (retinyl palmitate), C (ascorbyl palmitate), E (tocopherol), folic acid, the hyaluronic acid precursor N-acetylglucosamine, fatty acids (oleic acid) and ceramides, these sphingolipids are present in three forms AP, EOP, NP.

Mitofast®: coenzima Q10, resveratrolo, N-acetilcisteina, N-acetiglucosamina, acido folico e vitamina C.

Mitofast B12: liquid supplement of vitamin B12 (cianocobalamina).

Coenzyme Q10 is essential for the functioning of the mitochondria, to reduce oxidation and inflammation in the body (54).

Important clinical results for skin health (1, 9, 50) and significant anti-aging benefits have been documented, as illustrated by a recent article in the Journal Clinical and Aesthetic Dermatology (55) and previous research (56, 57, 58).
Coenzyme Q10 also has very promising clinical evidence in atopic dermatitis, including a specific antibacterial action (90% of patients suffer from S. aureus infections) as well as antioxidant/anti-inflammatory effects (59), which are useful in various skin diseases such as psoriasis (60, 61, 62).

Glutathione concentrations can be increased (50) by oral administration of its precursors such as
N-acetylcysteine (NAC), to avoid the gastrointestinal degradation undergone by glutathione taken directly orally.
Both oral NAC use (50, 53) and topical application of glutathione help to mitigate the manifestations of atopic dermatitis due to potent antioxidant/anti-inflammatory activity (53, 63, 64, 65, 66, 67).

To restore vitamin C (ascorbic acid) concentrations, topical application is more advantageous than the oral route. This is possible with the use of molecules that release ascorbic acid into the skin after absorption. An example of this is ascorbyl palmitate, a lipophilic molecule with high transepidermal penetration, especially when delivered by specific formulations (e.g., P.AS.S.®, Permeable AntioxidantS System). These are very innovative aspects, focused by the journal Pharmaceutics in August 2024 (68) and other previous articles (62, 69, 70, 71).
The contribution of ascorbic acid comes from stimulating collagen synthesis, regulating the presence of ceramides, and benefits for skin wound healing. By these mechanisms, ascorbic acid plays a very important role in stabilizing the epidermal barrier, including the lipid component (39). The antioxidant/anti-inflammatory and immune system actions have significant benefits in anti-aging and inflammatory skin diseases (69, 70, 71).

Vitamin E (tocopherol) for topical use allows to increase the low skin concentrations present in atopic dermatitis and perform the antioxidant/anti-inflammatory actions, and modulate the immune response (39). These are activities to protect cell membranes and thus the epidermal barrier, resulting in improved lesions and symptomatology (39, 62, 71, 72, 73, 74, 75, 76, 77).

Vitamin A is naturally present in the skin but is subject to progressive decline. It performs antioxidant, anti-inflammatory and immunomodulatory actions. It has protective effects against Staphylococcus aureus infections common in atopic dermatitis, and experimental studies also prospect antifungal activities (39, 62).
Topical application is optimized by appropriate pharmaceutical technologies (79) and the use of active vitamin A metabolites such as retinyl palmitate (71). Studies show improved elasticity and regeneration process of collagen fibers, benefits on cellular repair (73) and to counteract skin photo-aging (80), with excellent tolerability (81).

Folic acid, vitamin B12 and other B vitamins have specific anti-inflammatory and antioxidant functions, as well as regulate many skin and systemic cellular functions, and the composition of the gut microbiota. Therefore, they play a key role in skin health (82, 83, 84, 85, 86).

Fatty acids, such as oleic acid (Fig. 1), and the three forms of ceramides (Fig 2, 3, 4) (Note 2) help restore the lipid component of the skin and facilitate the delivery of fat-soluble active ingredients (87, 88, 89).
Specific formulations, such as P.AS.S.®, further optimize the penetration of the three forms of ceramides, which are subject to degradation in atopic dermatitis but are critical to the integrity of the epidermal barrier (87, 88, 89).
These lipid components have emollient properties and modulate skin hydration. Ceramides also demonstrate antimicrobial effects (87) and reduction of IgE levels (35).
These are all actions that are shown to be particularly beneficial in atopic dermatitis and inflammatory skin diseases.

Fig 1 Oleic acid
National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 445639, oleic acid. Retrieved November 23, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Oleic-Acid.

Fig 2 Ceramide AP
National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 44625889, N-(2-idrossiottadecanoil)-idrossifinganina. Retrieved November 23, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/N-2-hydroxyoctadecanoyl-hydroxysphinganine.

Fig 3 Ceramide EOP
National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 76966617, Ceramide 9. Retrieved November 23, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Ceramide-9.

Fig 4 Ceramide NP
National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 57378373, Ceramide np. Retrieved November 23, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Ceramide-np.

For allergic diseases, an important contribution also comes from polyphenols. Among these, oral resveratrol stands out for its modulatory action on the immune system and gut microbiota (90), and its known anti-inflammatory, antioxidant, neuroprotective, antiaging, etc. effects (91, 92). Resveratrol protects the epidermal barrier, promotes fibroblast proliferation, and raises collagen III concentrations (62, 93, 94). Therefore, from available research, resveratrol also seems very promising in atopic dermatitis (95, 96, 97, 98, 99).

Mitofast® in clinical studies
In studies to date (100), the orosoluble nutraceutical Mitofast® bit.ly/3VUlGkS has demonstrated significant increases in blood concentrations of coenzyme Q10 and glutathione, even in subjects who were initially deficient in them.

Blood levels of vitamin E are also significantly elevated. This vitamin is regenerated into its active form by the action of coenzyme Q10 and vitamin C contained in Mitofast.

Skin condition improves in 36 percent of cases, thanks in part to the action of N-acetylglucosamine on the increase of hyaluronic acid in the dermis (101) and the proven antiaging effects of the other components of Mitofast®: resveratrol, coenzyme Q10, N-acetylcysteine, vitamin C and folic acid.

Conclusions

• The most recent research confirms the involvement of mitochondrial dysfunction in the pathogenesis of atopic dermatitis and related problems (1, 9, 13).
• The goal of restoring mitochondrial integrity by reducing oxidative stress and inflammation also demonstrates significant clinical benefits in atopic dermatitis and its complications (1, 9, 13).
• The targeted use of cosmeceuticals and nutraceuticals containing specific antioxidant/anti-inflammatory molecules, and appropriate lipid emollients (35), can be a valuable support to pharmacological treatments of atopic dermatitis, including moderating the use of molecules that may cause adverse events in long-term treatments (29).

Note 1 (2, 3, 4, 102, 103, 104)
Atopic diseases include asthma, allergic rhinitis, and atopic dermatitis, also known as eczema.
Atopic dermatitis is one of the most prevalent chronic inflammatory diseases, and in the last 30 years it has an increasing trend.
In highly developed countries, the prevalence is 20% in pediatric and 10% in adult, including older age groups, with a prevalence of 7% to 10% over age 75.
It occurs recurrently (acute and chronic phases) and its complex pathogenesis includes genetic aspects and immunological dysfunction.
The epidermal barrier plays a major role in the development and progression of atopic dermatitis, as it is exposed to multiple external agents (air pollutants, ultraviolet rays, cigarette smoke, etc.) that exacerbate the disease.
Atopic dermatitis is characterized by itching and skin lesions.
Clinical management includes topical and systemic treatments, which have greatly developed in recent years.
Patients with atopic dermatitis should undergo appropriate clinical evaluations, appropriate pharmacological and nonpharmacological treatments, and disease monitoring.
Among the practical recommendations to be followed, the following are important:
Avoid using harsh soaps and washing with water at high temperatures; avoid excessive rubbing of the skin.
Very gentle products and hypoallergenic moisturizers are recommended for the daily routine.

Note 2 (105, 106)
Ceramides are important lipid constituents of cell membranes and play an essential role in the integrity of the epidermal barrier. They are sphingolipids, formed by a sphingosine molecule bound to a lipid structure.
There are various types of ceramides, among those most studied in the clinic for cosmeceutical use we find the following designations: AP (ceramide 6), EOP (ceramide 9), NP (ceramide 3). These ceramides have been selected for their specific structural functions in the epidermal barrier where, under physiological conditions, they account for 30-40% of the epidermis.
Ceramides AP, EOP, NP are combined with other lipid ingredients (e.g., oleic acid) to extend the benefits on the skin barrier and to maintain skin hydration, as well as effective protection against external agents, bacterial and fungal infections, and an important antiaging effect.
Ceramide NP has also been studied in the special conditions of corticosteroid-treated skin, demonstrating an important contribution to restoring the structure and functions of the epidermal barrier. This is a very important result for inflammatory skin diseases, such as atopic dermatitis, which involve prolonged drug treatments.

Bibliography

1. Yu H, Lin J, Yuan J, Sun X, Wang C, Bai B. Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning. Front Immunol. 2024 May 7;15:1367602. doi: 10.3389/fimmu.2024.1367602.

2. Carrascosa-Carrillo JM, Aterido A, Li T, Guillén Y, Martinez S, Marsal S, Julià A. Toward Precision Medicine in Atopic Dermatitis Using Molecular-Based Approaches. Actas Dermosifiliogr. 2024 Jan;115(1):T66-T75. English, Spanish. doi: 10.1016/j.ad.2023.10.032.

3. Afshari M, Kolackova M, Rosecka M, Čelakovská J, Krejsek J. Unraveling the skin; a comprehensive review of atopic dermatitis, current understanding, and approaches. Front Immunol. 2024 Mar 4;15:1361005. doi: 10.3389/fimmu.2024.1361005.

4. Manuale MSD versione per professionisti. Dermatite atopic a (eczema) Gen 2023. https://www.msdmanuals.com/it/professionale/disturbi-dermatologici/dermatite/dermatite-atopica-eczema

5. Koch M, Kockmann T, Rodriguez E, Wehkamp U, Hiebert P, Ben-Yehuda Greenwald M, Stölzl D, Beer HD, Tschachler E, Weidinger S, Werner S, Auf dem Keller U. Quantitative Proteomics Identifies Reduced NRF2 Activity and Mitochondrial Dysfunction in Atopic Dermatitis. J Invest Dermatol. 2023 Feb;143(2):220-231.e7. doi: 10.1016/j.jid.2022.08.048.

6. Minzaghi D, Pavel P, Kremslehner C, Gruber F, Oberreiter S, Hagenbuchner J, Del Frari B, Blunder S, Gruber R, Dubrac S. Excessive Production of Hydrogen Peroxide in Mitochondria Contributes to Atopic Dermatitis. J Invest Dermatol. 2023 Oct;143(10):1906-1918.e8. doi: 10.1016/j.jid.2023.03.1680.

7. Leman G, Pavel P, Hermann M, Crumrine D, Elias PM, Minzaghi D, Goudounèche D, Roshardt Prieto NM, Cavinato M, Wanner A, Blunder S, Gruber R, Jansen-Dürr P, Dubrac S. Mitochondrial Activity Is Upregulated in Nonlesional Atopic Dermatitis and Amenable to Therapeutic Intervention. J Invest Dermatol. 2022 Oct;142(10):2623-2634.e12. doi: 10.1016/j.jid.2022.01.035.

8. Wang S, Liu B, Huang J, He H, Zhou L, He Y, Yan J, Tao A. Succinate and mitochondrial DNA trigger atopic march from atopic dermatitis to intestinal inflammation. J Allergy Clin Immunol. 2023 Apr;151(4):1050-1066.e7. doi: 10.1016/j.jaci.2022.11.026.

9. Natarelli, N.; Gahoonia, N.; Aflatooni, S.; Bhatia, S.; Sivamani, R.K. Dermatologic Manifestations of Mitochondrial Dysfunction: A Review of the Literature.Int. J. Mol. Sci.2024,25, 3303. https://doi.org/10.3390/ijms25063303

10. Jang H, Kim M, Hong JY, Cho HJ, Kim CH, Kim YH, Sohn MH, Kim KW. Mitochondrial and Nuclear Mitochondrial Variants in Allergic Diseases. Allergy Asthma Immunol Res. 2020 Sep;12(5):877-884. doi: 10.4168/aair.2020.12.5.877.

11. Khosrojerdi M, Azad FJ, Yadegari Y, Ahanchian H, Azimian A. The role of microRNAs in atopic dermatitis. Noncoding RNA Res. 2024 May 28;9(4):1033-1039. doi: 10.1016/j.ncrna.2024.05.012.

12. Mini – Review Benessere e salute mitocodriale https://www.mitochon.it/obiettivo-benessere-partendo-dalla-salute-dei-mitocondri/

13. Nediani, C.; Ruzzolini, J.; Dinu, M. Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III.Antioxidants2024,13, 1404. https://doi.org/10.3390/antiox13111404

14. Mini-Review Infiammazione Cronica – Antiossidanti https://www.mitochon.it/infiammazione-cronica-attualita-sul-ruolo-di-specifici-antiossidanti-per-combatterla-a-livello-cutaneo-e-sistemico/

15. Mini-Review Coenzima Q10 https://www.mitochon.it/coenzima-q10-anti-aging-mitocondriale-per-la-pelle/

16. Traidl-Hoffmann C, Afghani J, Akdis CA, Akdis M, Aydin H, Bärenfaller K, Behrendt H, Bieber T, Bigliardi P, Bigliardi-Qi M, Bonefeld CM, Bösch S, Brüggen MC, Diemert S, Duchna HW, Fähndrich M, Fehr D, Fellmann M, Frei R, Garvey LH, Gharbo R, Gökkaya M, Grando K, Guillet C, Guler E, Gutermuth J, Herrmann N, Hijnen DJ, Hülpüsch C, Irvine AD, Jensen-Jarolim E, Kong HH, Koren H, Lang CCV, Lauener R, Maintz L, Mantel PY, Maverakis E, Möhrenschlager M, Müller S, Nadeau K, Neumann AU, O’Mahony L, Rabenja FR, Renz H, Rhyner C, Rietschel E, Ring J, Roduit C, Sasaki M, Schenk M, Schröder J, Simon D, Simon HU, Sokolowska M, Ständer S, Steinhoff M, Piccirillo DS, Taïeb A, Takaoka R, Tapparo M, Teixeira H, Thyssen JP, Traidl S, Uhlmann M, van de Veen W, van Hage M, Virchow C, Wollenberg A, Yasutaka M, Zink A, Schmid-Grendelmeier P. Navigating the evolving landscape of atopic dermatitis: Challenges and future opportunities: The 4th Davos declaration. Allergy. 2024 Oct;79(10):2605-2624. doi: 10.1111/all.16247.

17. Criado PR, Miot HA, Bueno-Filho R, Ianhez M, Criado RFJ, de Castro CCS. Update on the pathogenesis of atopic dermatitis. An Bras Dermatol. 2024 Nov-Dec;99(6):895-915. doi: 10.1016/j.abd.2024.06.001.

18. Schuler CF 4th, Tsoi LC, Billi AC, Harms PW, Weidinger S, Gudjonsson JE. Genetic and Immunological Pathogenesis of Atopic Dermatitis. J Invest Dermatol. 2024 May;144(5):954-968. doi: 10.1016/j.jid.2023.10.019.

19. Savva M, Papadopoulos NG, Gregoriou S, Katsarou S, Papapostolou N, Makris M, Xepapadaki P. Recent Advancements in the Atopic Dermatitis Mechanism. Front Biosci (Landmark Ed). 2024 Feb 22;29(2):84. doi: 10.31083/j.fbl2902084.

20. Huang Y, Zhou W, Liu S, Zeng D, Zhou W. Association between polymorphisms and atopic dermatitis susceptibility: A systematic review and meta-analysis. Gene. 2024 Jun 30;913:148397. doi: 10.1016/j.gene.2024.148397.

21. Yew YW, Loh M, Brown SJ. Understanding Atopic Dermatitis in Asian and European Population Cohorts Using Complementary Omics Techniques. J Invest Dermatol. 2024 Nov 5:S0022-202X(24)02171-7. doi: 10.1016/j.jid.2024.08.036.

22. Akhtar S, Alsayed RKME, Ahmad F, AlHammadi A, Al-Khawaga S, AlHarami SMAM, Alam MA, Al Naama KAHN, Buddenkotte J, Uddin S, Steinhoff M, Ahmad A. Epigenetic control of inflammation in Atopic Dermatitis. Semin Cell Dev Biol. 2024 Feb 15;154(Pt C):199-207. doi: 10.1016/j.semcdb.2023.04.005.

23. Stefanovic N, Irvine AD. Filaggrin and beyond: New insights into the skin barrier in atopic dermatitis and allergic diseases, from genetics to therapeutic perspectives. Ann Allergy Asthma Immunol. 2024 Feb;132(2):187-195. doi: 10.1016/j.anai.2023.09.009.

24. Khatib CM, Klein-Petersen AW, Rønnstad ATM, Egeberg A, Christensen MO, Silverberg JI, Thomsen SF, Irvine AD, Thyssen JP. Increased loss-of-function filaggrin gene mutation prevalence in atopic dermatitis patients across northern latitudes indicates genetic fitness: A systematic review and meta-analysis. Exp Dermatol. 2024 Jul;33(7):e15130. doi: 10.1111/exd.15130.

25. Schild J, Kalvodová A, Zbytovská J, Farwick M, Pyko C. The role of ceramides in skin barrier function and the importance of their correct formulation for skincare applications. Int J Cosmet Sci. 2024 Aug;46(4):526-543. doi: 10.1111/ics.12972.

26. Mijaljica D, Townley JP, Spada F, Harrison IP. The heterogeneity and complexity of skin surface lipids in human skin health and disease. Prog Lipid Res. 2024 Jan;93:101264. doi: 10.1016/j.plipres.2023.101264.

27. Berdyshev E. Skin Lipid Barrier: Structure, Function and Metabolism. Allergy Asthma Immunol Res. 2024 Sep;16(5):445-461. doi: 10.4168/aair.2024.16.5.445.

28. Chng CC. The roles of ceramides and multivesicular emulsion (MVE) technology in atopic dermatitis: a narrative review. Med J Malaysia. 2024 Jan;79(1):85-94.

28. Kondo A, Takenaka Y, Fujiwara A, Takahashi S, Kitade-Miyayama M, Morifuji M, Kawashima M, Ishiguro N. Changes in the composition of molecular species of covalently bound and free ceramides [EOS], and their correlation with disease severity in atopic dermatitis. Exp Dermatol. 2024 Mar;33(3):e15025. doi: 10.1111/exd.15025.

29. De Simoni E, Candelora M, Belleggia S, Rizzetto G, Molinelli E, Capodaglio I, Ferretti G, Bacchetti T, Offidani A, Simonetti O. Role of antioxidants supplementation in the treatment of atopic dermatitis: a critical narrative review. Front Nutr. 2024 Jun 12;11:1393673. doi: 10.3389/fnut.2024.1393673.

30. Fan M, Fan X, Lai Y, Chen J, Peng Y, Peng Y, Xiang L, Ma Y. Protease-Activated Receptor 2 in inflammatory skin disease: current evidence and future perspectives. Front Immunol. 2024 Sep 5;15:1448952. doi: 10.3389/fimmu.2024.1448952.

31. Zeldin J, Ratley G, Shobnam N, Myles IA. The clinical, mechanistic, and social impacts of air pollution on atopic dermatitis. J Allergy Clin Immunol. 2024 Oct;154(4):861-873. doi: 10.1016/j.jaci.2024.07.027.

32. Paik K, Na JI, Huh CH, Shin JW. Particulate Matter and Its Molecular Effects on Skin: Implications for Various Skin Diseases. Int J Mol Sci. 2024 Sep 13;25(18):9888. doi: 10.3390/ijms25189888.

33. Alessandrello, C.; Sanfilippo, S.; Minciullo, P.L.; Gangemi, S. An Overview on Atopic Dermatitis, Oxidative Stress, and Psychological Stress: Possible Role of Nutraceuticals as an Additional Therapeutic Strategy.Int. J. Mol. Sci.2024,25, 5020. https://doi.org/10.3390/ijms25095020

34. Ständer S, Luger T, Kim B, Lerner E, Metz M, Adiri R, Canosa JM, Cha A, Yosipovitch G. Cutaneous Components Leading to Pruritus, Pain, and Neurosensitivity in Atopic Dermatitis: A Narrative Review. Dermatol Ther (Heidelb). 2024 Jan;14(1):45-57. doi: 10.1007/s13555-023-01081-0.

35. Tang X, Li M. The role of the skin in the atopic march. Int Immunol. 2024 Oct 26;36(11):567-577. doi: 10.1093/intimm/dxae053.

36. Zhou Z, Yang J, Liu Q, Gao J, Ji W. Patho-immunological mechanisms of atopic dermatitis: The role of the three major human microbiomes. Scand J Immunol. 2024 Nov;100(5):e13403. doi: 10.1111/sji.13403.

37. Jang, J.-H.; Jang, S.-Y.; Ahn, S.; Oh, J.-Y.; Yeom, M.; Ko, S.-J.; Park, J.-W.; Kwon, S.-K.; Kim, K.; Lee, I.-S.; et al. Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression.Int. J. Mol. Sci.2024,25, 2753. https://doi.org/10.3390/ijms25052753

38. Borrego-Ruiz, A.; Borrego, J.J. Nutritional and Microbial Strategies for Treating Acne, Alopecia, and Atopic Dermatitis.Nutrients2024,16, 3559. https://doi.org/10.3390/nu16203559

39. Joshi M, Hiremath P, John J, Ranadive N, Nandakumar K, Mudgal J. Modulatory role of vitamins A, B3, C, D, and E on skin health, immunity, microbiome, and diseases. Pharmacol Rep. 2023 Oct;75(5):1096-1114. doi: 10.1007/s43440-023-00520-1.

40. Mini-Review Vitamine complesso B – microbiota https://www.mitochon.it/le-vitamine-del-gruppo-b-cosa-ce-di-nuovo-parte-2/

41. Chen PY, Shen M, Cai SQ, Tang ZW. Association Between Atopic Dermatitis and Aging: Clinical Observations and Underlying Mechanisms. J Inflamm Res. 2024 May 28;17:3433-3448. doi: 10.2147/JIR.S467099.

42. Zirpel H, Ständer S, Frączek A, Olbrich H, Ludwig RJ, Thaçi D. Atopic dermatitis is associated with an increased risk of cardiovascular diseases: a large-scale, propensity-score matched US-based retrospective study. Clin Exp Dermatol. 2024 Oct 24;49(11):1405-1412. doi: 10.1093/ced/llae164.

43. Kuryłło, M.; Mojs, E. Do Atopic Dermatitis and Psoriasis Have an Impact on Cognitive Decline—Latest Research Review.Healthcare2024,12, 1170. https://doi.org/10.3390/healthcare12121170

44.Zhou Q, Yang D, Xiong C, Li X. Atopic dermatitis and cognitive dysfunction in middle-aged and older adults: A systematic review and meta-analysis. PLoS One. 2023 Oct 25;18(10):e0292987. doi: 10.1371/journal.pone.0292987.

45. Schonmann Y, Mansfield KE, Hayes JF, Abuabara K, Roberts A, Smeeth L, Langan SM. Atopic Eczema in Adulthood and Risk of Depression and Anxiety: A Population-Based Cohort Study. J Allergy Clin Immunol Pract. 2020 Jan;8(1):248-257.e16. doi: 10.1016/j.jaip.2019.08.030.

46. Hartono, S.P., Chatrath, S., Aktas, O.et al.Interventions for anxiety and depression in patients with atopic dermatitis: a systematic review and meta-analysis.Sci Rep14, 8844 (2024). https://doi.org/10.1038/s41598-024-59162-9

47. Chu, CY., Chan, Y., Wananukul, S.et al.Quality of Life and Burden of Moderate-to-Severe Atopic Dermatitis in Adult Patients Within the Asia–Pacific Region: A Cross-sectional Survey.Dermatol Ther (Heidelb)14, 2479–2493 (2024). https://doi.org/10.1007/s13555-024-01244-7

48. Bashyam AM, Ganguli S, Mahajan P, Feldman SR. Lifelong Impact of Severe Atopic Dermatitis on Quality of Life: A Case Report. Dermatol Ther (Heidelb). 2021 Jun;11(3):1065-1070. doi: 10.1007/s13555-021-00515-x.

49. Agrawal, R.; Hu, A.; Bollag, W.B. The Skin and Inflamm-Aging.Biology2023,12, 1396. https://doi.org/10.3390/biology12111396

50. Mini-Review Motivi per l’Integrazione Mirata https://www.mitochon.it/4-motivi-1-per-utilizzare-lintegrazione-mirata-contro-linvecchiamento-cutaneo-e-sistemico/

51. Du Q, Meng W, Athari SS, Wang R. The effect of Co-Q10 on allergic rhinitis and allergic asthma. Allergy Asthma Clin Immunol. 2021 Mar 20;17(1):32. doi: 10.1186/s13223-021-00534-5.

52. Labarrere CA, Kassab GS. Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation. Front Nutr. 2022 Nov 1;9:1007816. doi: 10.3389/fnut.2022.1007816.

53. Mini-Review Glutatione / NAC https://www.mitochon.it/glutatione-perche-proteggere-le-sue-concentrazioni-cellulari-nellantiaging/

54. McRae MP. Coenzyme Q10 Supplementation in Reducing Inflammation: An Umbrella Review. J Chiropr Med. 2023 Jun;22(2):131-137. doi: 10.1016/j.jcm.2022.07.001.

55. Lain ET, Agrawal N, Ruvolo E, Weise JM, Callender VD. The Role of Coenzyme Q10 in Skin Aging and Opportunities for Topical Intervention: A Review. J Clin Aesthet Dermatol. 2024 Aug;17(8):50-55.

56. Ayunin, Q., Miatmoko, A., Soeratri, W.et al.Improving the anti-ageing activity of coenzyme Q10 through protransfersome-loaded emulgel.Sci Rep12, 906 (2022). https://doi.org/10.1038/s41598-021-04708-4

57. Žmitek K, Pogačnik T, Mervic L, Žmitek J, Pravst I. The effect of dietary intake of coenzyme Q10 on skin parameters and condition: Results of a randomised, placebo-controlled, double-blind study. Biofactors. 2017 Jan 2;43(1):132-140. doi: 10.1002/biof.1316.

58. 44265 Oral coenzyme Q10: the new authority in skin aging. Results of a randomized, double-blind, placebo-controlled trial in elderly women 2023 Poster Abstracts Journal of the American Academy of Dermatology. September 2023 Vol. 89 Issue 3SupplementAB1-AB252

59. Wu S, Pang Y, He Y, Zhang X, Peng L, Guo J, Zeng J. A comprehensive review of natural products against atopic dermatitis: Flavonoids, alkaloids, terpenes, glycosides and other compounds. Biomed Pharmacother. 2021 Aug;140:111741. doi: 10.1016/j.biopha.2021.111741.

60. Sudeep Sudesh Pukale, Deepak Kumar Sahel, Anupama Mittal, Deepak Chitkara, Coenzyme Q10 loaded lipid-polymer hybrid nanoparticles in gel for the treatment of psoriasis like skin condition, Journal of Drug Delivery Science and Technology,

Vol. 76, 2022, https://doi.org/10.1016/j.jddst.2022.103672.

61. Mantle, D.; Hargreaves, I.P. Coenzyme Q10 and Autoimmune Disorders: An Overview.Int. J. Mol. Sci.2024,25, 4576. https://doi.org/10.3390/ijms25084576

62. Gǎlbǎu, C.-Ş.; Irimie, M.; Neculau, A.E.; Dima, L.; Pogačnik da Silva, L.; Vârciu, M.; Badea, M. The Potential of Plant Extracts Used in Cosmetic Product Applications—Antioxidants Delivery and Mechanism of Actions.Antioxidants2024,13, 1425. https://doi.org/10.3390/antiox13111425

63. Mini-Review N-acetilcisteina https://www.mitochon.it/n-acetilcisteina-nac-dalla-clinica-allanti-aging/

64. CuiX,MiT,XiaoX,ZhangH,DongY,HuangN, et al.Topical glutathione amino acid precursors protect skin against environmental and oxidative stress.J Eur Acad Dermatol Venereol.2024;38(Suppl. 3):3–11.https://doi.org/10.1111/jdv.19717

65. Tieu, S.; Charchoglyan, A.; Paulsen, L.; Wagter-Lesperance, L.C.; Shandilya, U.K.; Bridle, B.W.; Mallard, B.A.; Karrow, N.A. N-Acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals.Antioxidants2023,12, 1867. https://doi.org/10.3390/antiox12101867

66. Adil M, Amin SS, Mohtashim M. N-acetylcysteine in dermatology. Indian J Dermatol Venereol Leprol 2018;84:652-659

67. Janeczek M, Moy L, Riopelle A, Vetter O, Reserva J, Tung R, Swan J. The Potential Uses of N-acetylcysteine in Dermatology: A Review. J Clin Aesthet Dermatol. 2019 May;12(5):20-26. Epub 2019 May 1. PMID: 31320973; PMCID: PMC6561714

68. Stolić Jovanović A, Tadić VM, Martinović M, Žugić A, Nešić I, Blagojević S, Jasnić N, Tosti T. Liposomal Encapsulation of Ascorbyl Palmitate: Influence on Skin Performance. Pharmaceutics. 2024 Jul 20;16(7):962. doi: 10.3390/pharmaceutics16070962.

69. Mini-Review Precursori acido ascorbico https://www.mitochon.it/precursori-dellacido-ascorbico-per-massimizzare-lattivita-antiaging-per-via-topica-e-locale-ulteriori-acquisizioni-2024/

70. Mini-Review Vitamina C https://www.mitochon.it/vitamina-c-il-contributo-per-lanti-aging-cutaneo/

71. Mini-Review Dermatite Seborroica https://www.mitochon.it/dermatite-seborroica-attualita-sul-contributo-della-dermocosmesi/

72. Mini – Review Vitamina E ruolo sistemico e dermocosmesi https://www.mitochon.it/vitamina-e-aggiornamenti-generali-e-ruolo-nei-trattamenti-antiaging-della-pelle/

73. Januszewski, J.; Forma, A.; Zembala, J.; Flieger, M.; Tyczyńska, M.; Dring, J.C.; Dudek, I.; Świątek, K.; Baj, J. Nutritional Supplements for Skin Health—A Review of What Should Be Chosen and Why.Medicina2024,60, 68. https://doi.org/10.3390/medicina60010068

74. Teo CWL, Tay SHY, Tey HL, Ung YW, Yap WN. Vitamin E in Atopic Dermatitis: From Preclinical to Clinical Studies. Dermatology. 2021;237(4):553-564. doi: 10.1159/000510653.

75. Liu X, Yang G, Luo M, Lan Q, Shi X, Deng H, Wang N, Xu X, Zhang C. Serum vitamin E levels and chronic inflammatory skin diseases: A systematic review and meta-analysis. PLoS One. 2021 Dec 14;16(12):e0261259. doi: 10.1371/journal.pone.0261259.

76. Berardesca E, Cameli N. Vitamin E supplementation in inflammatory skin diseases. Dermatol Ther. 2021 Nov;34(6):e15160. doi: 10.1111/dth.15160.

77. Harun MS, Wong TW, Fong CW. Advancing skin delivery of α-tocopherol and γ-tocotrienol for dermatitis treatment via nanotechnology and microwave technology. Int J Pharm. 2021 Jan 25;593:120099. doi: 10.1016/j.ijpharm.2020.120099.

78. Garcia-Bilbao A, Gómez-Fernández P, Larush L, et al. Preparation, characterization, and biological evaluation of retinyl palmitate and Dead Sea water loaded nanoemulsions toward topical treatment of skin diseases.Journal of Bioactive and Compatible Polymers. 2020;35(1):24-38. doi:10.1177/0883911519885970

79. Oh, H.; Lee, J.S.; Kim, S.; Lee, J.-H.; Shin, Y.C.; Choi, W.I. Super-Antioxidant Vitamin A Derivatives with Improved Stability and Efficacy Using Skin-Permeable Chitosan Nanocapsules.Antioxidants2023,12, 1913. https://doi.org/10.3390/antiox12111913

80. Shu P, Li M, Zhao N, Wang Y, Zhang L, Du Z. Efficacy and mechanism of retinyl palmitate against UVB-induced skin photoaging. Front Pharmacol. 2023 Oct 20;14:1278838. doi: 10.3389/fphar.2023.1278838.

81. Milosheska D, Roškar R. Use of Retinoids in Topical Antiaging Treatments: A Focused Review of Clinical Evidence for Conventional and Nanoformulations. Adv Ther. 2022 Dec;39(12):5351-5375. doi: 10.1007/s12325-022-02319-7.

82. Elgharably N, Al Abadie M, Al Abadie M, Ball PA, Morrissey H. Vitamin B group levels and supplementations in dermatology. Dermatol Reports. 2022 Jul 6;15(1):9511. doi: 10.4081/dr.2022.9511.

83. Mini-Review Vitamina B12 – Acido Folico https://www.mitochon.it/vitamina-b12-e-acido-folico-cosa-ce-di-nuovo-parte-1/

84. Mini-Review Vitamina B12 https://www.mitochon.it/vitamina-b12-nelle-strategie-antiaging/

85. Mini-Review Acido Folico https://www.mitochon.it/acido-folico-dalla-clinica-allantiaging-attualita-2024/

86. Song, Mengmeng1,*; Xu, Benjamin P.2.The anti-inflammatory effects of folic acid. Precision Nutrition 3(2):p e00070, June 2024. | DOI: 10.1097/PN9.0000000000000070

87. Chng CC. The roles of ceramides and multivesicular emulsion (MVE) technology in atopic dermatitis: a narrative review. Med J Malaysia. 2024 Jan;79(1):85-94. PMID: 38287763.

88. Şahin Bektay H, Sağıroğlu AA, Bozali K, Güler EM, Güngör S. The Design and Optimization of Ceramide NP-Loaded Liposomes to Restore the Skin Barrier. Pharmaceutics. 2023 Nov 27;15(12):2685. doi: 10.3390/pharmaceutics15122685.

89. Draelos ZD, Baalbaki N, Colon G, Dreno B. Ceramide-Containing Adjunctive Skin Care for Skin Barrier Restoration During Acne Vulgaris Treatment. J Drugs Dermatol. 2023 Jun 1;22(6):554-558. doi: 10.36849/JDD.7142.

90. Prakash V, Bose C, Sunilkumar D, Cherian RM, Thomas SS, Nair BG. Resveratrol as a Promising Nutraceutical: Implications in Gut Microbiota Modulation, Inflammatory Disorders, and Colorectal Cancer. Int J Mol Sci. 2024 Mar 16;25(6):3370. doi: 10.3390/ijms25063370.

91. Farhan, M.; Rizvi, A.; Aatif, M.; Muteeb, G.; Khan, K.; Siddiqui, F.A. Dietary Polyphenols, Plant Metabolites, and Allergic Disorders: A Comprehensive Review.Pharmaceuticals2024,17, 670. https://doi.org/10.3390/ph17060670

92. Alesci A, Nicosia N, Fumia A, Giorgianni F, Santini A, Cicero N. Resveratrol and Immune Cells: A Link to Improve Human Health. Molecules. 2022 Jan 10;27(2):424. doi: 10.3390/molecules27020424.

93. Mini-Review Resveratrolo Peri- Post-Menopausa https://www.mitochon.it/peri-e-post-menopausa-novita-sui-vantaggi-dellintegrazionealimentare-mirata/

94. Mini-Review Resveratrolo effetti neuroprotettivi https://www.mitochon.it/cervello-e-cognitivita-effetti-neuroprotettivi-del-resveratrolo/

95. Marko, M.; Pawliczak, R. Resveratrol and Its Derivatives in Inflammatory Skin Disorders—Atopic Dermatitis and Psoriasis: A Review.Antioxidants2023,12, 1954. https://doi.org/10.3390/antiox12111954

96. Carlucci CD, Hui Y, Chumanevich AP, Robida PA, Fuseler JW, Sajish M, Nagarkatti P, Nagarkatti M, Oskeritzian CA. Resveratrol Protects against Skin Inflammation through Inhibition of Mast Cell, Sphingosine Kinase-1, Stat3 and NF-κB p65 Signaling Activation in Mice. Int J Mol Sci. 2023 Apr 4;24(7):6707. doi: 10.3390/ijms24076707.

97. Leis K, Pisanko K, Jundziłł A, Mazur E, Mêcińska-Jundziłł K, Witmanowski H. Resveratrol as a factor preventing skin aging and affecting its regeneration. Postepy Dermatol Alergol. 2022 Jun;39(3):439-445. doi: 10.5114/ada.2022.117547.

98. He Q, Liu W, Chen Z, Wei G, Jiang J, Zhang L, Zhou L. Resveratrol modulates the Nrf2/NF-κB pathway and inhibits TSLP-mediated atopic march. Allergol Immunopathol (Madr). 2024 Jan 1;52(1):1-8. doi: 10.15586/aei.v52i1.963

99. Conte, R.; De Luca, I.; Valentino, A.; Cerruti, P.; Pedram, P.; Cabrera-Barjas, G.; Moeini, A.; Calarco, A. Hyaluronic Acid Hydrogel Containing Resveratrol-Loaded Chitosan Nanoparticles as an Adjuvant in Atopic Dermatitis Treatment.J. Funct. Biomater.2023,14, 82. https://doi.org/10.3390/jfb14020082

100. Mini-Review studio pilota Mitofast https://www.mitochon.it/mitofast-nuovi-ed-importanti-risultati-da-uno-studio-clinico-preliminare/

101. Mini-Review N-acetilglusosamina https://www.mitochon.it/n-acetilglucosamina-nag-per-il-trofismo-cutaneo/

102. Chan LN, Magyari A, Ye M, Al-Alusi NA, Langan SM, Margolis D, McCulloch CE, Abuabara K. The epidemiology of atopic dermatitis in older adults: A population-based study in the United Kingdom. PLoS One. 2021 Oct 6;16(10):e0258219. doi: 10.1371/journal.pone.0258219.

103. Maurelli, M., Chiricozzi, A., Peris, K., Gisondi, P., & Girolomoni, G. (2023). Atopic Dermatitis in the Elderly Population.Acta Dermato-Venereologica,103, adv13363. https://doi.org/10.2340/actadv.v103.13363

104. Wang X, Li L-F. Clinical features of eczema and dermatitis in the elderly: A cross-sectional study in mainland China.European Journal of Inflammation. 2022;20. doi:10.1177/20587392211069758

105. Lim SH, Kim EJ, Lee CH, Park GH, Yoo KM, Nam SJ, Shin KO, Park K, Choi EH. A Lipid Mixture Enriched by Ceramide NP with Fatty Acids of Diverse Chain Lengths Contributes to Restore the Skin Barrier Function Impaired by Topical Corticosteroid. Skin Pharmacol Physiol. 2022;35(2):112-123. doi: 10.1159/000518517. Epub 2021 Jul 19. Erratum in: Skin Pharmacol Physiol. 2022;35(2):124. doi: 10.1159/000521871.

106. Yokose U, Ishikawa J, Morokuma Y, Naoe A, Inoue Y, Yasuda Y, Tsujimura H, Fujimura T, Murase T, Hatamochi A. The ceramide [NP]/[NS] ratio in the stratum corneum is a potential marker for skin properties and epidermal differentiation. BMC Dermatol. 2020 Aug 31;20(1):6. doi: 10.1186/s12895-020-00102-1.