Molecular Mechanisms of Atopic Dermatitis Pathogenesis

Atopic dermatitis is a chronic, non-infectious inflammatory dermatosis. Acharacteristic feature is persistent itching of the skin. The chronic, relapsing course of the disease, economic burden, and the whole family’s involvement in the treatment process immensely reduce the quality of life of patients and their families. The disease emerges as a social problem by increasing indirect costs, such as visiting a doctor, absenteeism from work and school, and avoiding social interactions. Thepathophysiology of atopic dermatitis is complex and multifactorial. It includes genetic disorders, a defect in the epidermal barrier, an altered immune response, anddisruption of the skin’s microbial balance. The numerous complex changes at thegenetic level and innate and adaptive immunity provide the basis for characterizing the various phenotypes and endotypes of atopic dermatitis. Emerging therapies rely on the action of specific molecules involved in the disease’s pathogenesis. It may be the starting point for the individualization of atopic dermatitis treatment. This paper will try to present some molecular mechanisms of atopic dermatitis and their clinical implications.

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Influence of dupilumab on the economic burden of severe asthma and atopic dermatitis

Kachestvennaya klinicheskaya praktika ◽

10.37489/2588-0519-2020-3-15-26 ◽

2020 ◽

pp. 15-26

Author(s):

I. S. Krysanov ◽

V. S. Krysanova ◽

O. I. Karpov ◽

V. Yu. Ermakova

Keyword(s):

Atopic Dermatitis ◽

Severe Asthma ◽

Economic Burden ◽

Weighted Average ◽

Indirect Costs ◽

Current Treatment ◽

Severe Atopic Dermatitis ◽

Local Conditions ◽

Economic Burden Of Disease

The prevalence of comorbidity — asthma and atopic dermatitis — is not understood well yet. More severe processes decreasing quality of life and increasing a social-economic burden of disease are occurred in such kind comorbidity.Aim: an evaluation of economic burden of non-control severe asthma in combination with severe atopic dermatitis in the local conditions.Materials and methods. Analysis has been performed for adult patients; the bottom-up approach of costs evaluation was used. Direct medical and non-medical as well as indirect costs were calculated for two models: Model 1 — current practice of the treatment, Model 2 — treatment with Dupilumab. Results. Model 1 — Weighted average expenditures for one patient were 3,1 mln RUR, indirect costs were dominated (76 % from the total), severe atopic dermatitis had 15 % of total. Model 2 (with Dupilumab) — Dupilumab has decreased the total weighted average cost on 903 905 RUR. The total economic burden of comorbidity was 17,6 bln RUR in the current treatment option, and 12,4 bln RUR in Dupilumab hand (different is 5,2 bln RUR, or burden decrease is expected on 29,2 %).Conclusion. The wider introduction of Dupilumab into clinical practice, which allows achieving control in the treatment of severe asthma and severe atopic dermatitis, should reduce treatment costs and reduce the socio-economic burden of these diseases as a result.

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Melatonin as an Antioxidant and Immunomodulator in Atopic Dermatitis—A New Look on an Old Story: A Review

Antioxidants ◽

10.3390/antiox10081179 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1179

Author(s):

Andrzej Kazimierz Jaworek ◽

Jacek Cezary Szepietowski ◽

Przemysław Hałubiec ◽

Anna Wojas-Pelc ◽

Jolanta Jaworek

Keyword(s):

Atopic Dermatitis ◽

Disease Severity ◽

Sleep Disturbances ◽

Skin Inflammation ◽

Inflammatory Dermatosis ◽

Sleep Abnormalities ◽

Chronic Skin ◽

Endogenous Substances

Atopic dermatitis (AD) is common inflammatory dermatosis, typically with chronic and recurrent course, which significantly reduces the quality of life. Sleep disturbances are considered to be remarkably burdensome ailments in patients with AD, and are routinely included during assessment of disease severity. Therefore, endogenous substances engaged in the control of circadian rhythms might be important in pathogenesis of AD and, possibly, be used as biomarkers of disease severity or even in development of novel therapies. Melatonin (MT), the indoleamine produced by pineal gland (but also by multiple other tissues, including skin), plays a pivotal role in maintaining the sleep/wake homeostasis. Additionally, it possesses strong antioxidant and anti-inflammatory properties, which might directly link chronic skin inflammation and sleep abnormalities characteristic of AD. The objective of this work is to systematically present and summarize the results of studies (both experimental and clinical) that investigated the role of MT in the AD, with a focus on the antioxidant and immunomodulatory effects of MT.

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Oxidative Stress in Cancer-Prone Genetic Diseases in Pediatric Age: The Role of Mitochondrial Dysfunction

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/4782426 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Serafina Perrone ◽

Federica Lotti ◽

Ursula Geronzi ◽

Elisa Guidoni ◽

Mariangela Longini ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Molecular Mechanisms ◽

Recent Literature ◽

Genetic Disorders ◽

Genetic Diseases ◽

Progeroid Syndromes ◽

Clinical Strategy

Oxidative stress is a distinctive sign in several genetic disorders characterized by cancer predisposition, such as Ataxia-Telangiectasia, Fanconi Anemia, Down syndrome, progeroid syndromes, Beckwith-Wiedemann syndrome, and Costello syndrome. Recent literature unveiled new molecular mechanisms linking oxidative stress to the pathogenesis of these conditions, with particular regard to mitochondrial dysfunction. Since mitochondria are one of the major sites of ROS production as well as one of the major targets of their action, this dysfunction is thought to be the cause of the prooxidant status. Deeper insight of the pathogenesis of the syndromes raises the possibility to identify new possible therapeutic targets. In particular, the use of mitochondrial-targeted agents seems to be an appropriate clinical strategy in order to improve the quality of life and the life span of the patients.

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Bone Metastasis: Mechanisms, Therapies and Biomarkers

Physiological Reviews ◽

10.1152/physrev.00012.2019 ◽

2020 ◽

Author(s):

Philippe Clezardin ◽

Rob Coleman ◽

Margherita Puppo ◽

Penelope Ottewell ◽

Edith Bonnelye ◽

...

Keyword(s):

Bone Marrow ◽

Bone Metastasis ◽

Tumor Cells ◽

Molecular Mechanisms ◽

Skeletal Metastases ◽

Therapeutic Effects ◽

Pain Disability ◽

Emerging Therapies ◽

Skeletal Complications

Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability), which negatively affect the patient's quality of life. Here, we first discuss the burden of skeletal complications in cancer bone metastasis. We then describe the pathophysiology of bone metastasis. Bone metastasis is a multistage process; long before the development of clinically detectable metastases, circulating tumor cells settle and enter a dormant state in normal vascular and endosteal niches present in the bone marrow, which provide immediate attachment and shelter, and only become active years later as they proliferate and alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. The molecular mechanisms involved in mediating each of these steps are described and we also explain how tumor cells interact with a myriad of interconnected cell populations in the bone marrow, including a rich vascular network, immune cells, adipocytes and nerves. We discuss metabolic programs that tumor cells could engage with to specifically grow in bone. We also describe the progress and future directions of existing bone-targeted agents and report emerging therapies that have arisen from recent advances in our understanding of the pathophysiology of bone metastases. Finally, we discuss the value of bone turnover biomarkers in detection and monitoring of progression and therapeutic effects in patients with bone metastasis.

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Melatonin as an Antioxidant and Immunomodulator in Atopic Dermatitis–A New Look on an Old Story–A Review

10.20944/preprints202106.0581.v1 ◽

2021 ◽

Author(s):

Andrzej Kazimierz Jaworek ◽

Jacek C Szepietowski ◽

Przemysław Hałubiec ◽

Anna Wojas-Pelc ◽

Jolanta Jaworek

Keyword(s):

Atopic Dermatitis ◽

Disease Severity ◽

Sleep Disturbances ◽

Skin Inflammation ◽

Inflammatory Dermatosis ◽

Sleep Abnormalities ◽

Chronic Skin ◽

Endogenous Substances

Atopic dermatitis (AD) is common inflammatory dermatosis, typically with chronic and recurrent course, which significantly reduces the quality of life. Sleep disturbances are considered to be remarkably burdensome ailments in the patients with AD, and are routinely included during assessment of disease severity. Therefore, endogenous substances engaged in the control of circadian rhythms might be important in pathogenesis of AD and, possibly, be used as biomarkers of disease severity or even in development of novel therapies. Melatonin (MT), the indoleamine produced by pineal gland (but also by multiple other tissues, including skin), plays a pivotal role in maintaining the sleep/wake homeostasis. Additionally, it possess strong antioxidant and anti-inflammatory properties, which might directly link chronic skin inflammation and sleep abnormalities characteristic of AD. The objective of this work is to systematically present and summarize the results of studies (both experimental and clinical) that investigated the role of MT in the AD, with focus on the antioxidant and immunomodulatory effects of MT.

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Study on the Molecular Basis of Huanglian Jiedu Decoction Against Atopic Dermatitis Integrating Chemistry, Biochemistry, and Metabolomics Strategies

Frontiers in Pharmacology ◽

10.3389/fphar.2021.770524 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jing Chen ◽

Saizhen Chen ◽

Jinguang Chen ◽

Bixin Shen ◽

Zhengli Jiang ◽

...

Keyword(s):

Atopic Dermatitis ◽

Molecular Mechanisms ◽

Skin Inflammation ◽

Treated Group ◽

Chemical Components ◽

Biochemical Indices ◽

Significant Chemical ◽

Physiological And Biochemical ◽

Metabolomics Analysis

Atopic dermatitis (AD) is a common chronic relapsing skin inflammation, which severely affect the quality of life of patients. Inhibiting itching and enhancing immunity to mitigate scratching are key elements in the fight against AD. Huanglian Jiedu decoction (HLJDD) has multiple pharmacological effects in the treatment of AD. However, the effective ingredients and underlying molecular mechanisms have not yet been fully explored. Thus, this study integrates chemistry, biochemistry, and metabolomics strategies to evaluate the active substance basis of HLJDD against AD. First, HLJDD was split to five fractions (CPF, 40AEF, 90AEF, PEF and WEF) and 72 chemical components were identified. NSD (Non-similarity degree) among the different fractions showed significant chemical differences (>81%). Interleukin IL-13, IL-17A, IL-3, IL-31, IL-33, IL4, IL-5, TSLP, IgE, and histamine in the serum, and IL-4Rα, JAK1, and HRH4 levels in skin, participating in inhibiting itching and regulating immunity signaling, were found to be restored to varying degrees in AD treating with HLJDD and its fractions, especially 40AEF and CPF. Untargeted metabolomics analysis demonstrated that forty metabolites were differential metabolites in plasma between the HLJDD-treated group and the AD group, involving in histidine metabolism, arginine biosynthesis, pyrimidine metabolism, and so on. Further, targeted metabolomics analysis revealed that eleven differential metabolites, associating with physiological and biochemical indices, were significant improved in the HLJDD and its fractions groups. In conclusion, HLJDD exhibited anti-AD effects by inhibiting itching and enhancing immunity, which in turn regulating the levels of relative metabolites, and CPF and 40AEF were considered the most important components of HLJDD.

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