Dissecting the enigma of scleroderma: possible involvement of the kynurenine pathway

Noakes, Rowland

doi:10.1515/pterid-2016-0010

Cited by 3 publications

(1 citation statement)

References 79 publications

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“…Penetrating into skin, the transcription factor aryl hydrocarbon receptor (AhR) is specifically activated [6][7][8][9], resulting in the upregulation of various pharmacological processes, e.g., enzymes of the cytochrome P450 family [10], melanogenesis [11], cellular oxidant/antioxidant regulation [12], immune regulation [13][14][15] and regulation of the epidermal barrier function [16] (Figure 1). From this, the pathogenesis of various skin diseases is stimulated, such as vitiligo [17], psoriasis [18,19] scleroderma [20], neurodermatitis [21], and acne vulgaris [22]. Further, the promotion of dermal carcinogenesis is discussed in following references [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Symurban Nanocrystals for Advanced Anti-Pollution Skincare

Köpke

Pyo

2020

Cosmetics

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Several of most common dermatoses worldwide, e.g., psoriasis and atopic dermatitis, are worsened in their clinical picture when the skin is regularly exposed to an increased air pollution level, e.g., particulate matter. This is explainable by the activation of the aryl hydrocarbon receptor (AhR) in the skin, which results in an increased release of proinflammatory cytokines and matrix metalloproteinases. Symurban is a competitive AhR antagonist and thus allows the effective protection of skin. In order to improve its dermal bioavailability as a poorly soluble active agent (0.25 µg/mL), nanocrystals were prepared and evaluated. Nanocrystals are pure active crystals reduced in particle size to the submicron range of 100 to 1000 nm. They feature the properties of nanocrystals, such as increased saturation solubility and dissolution velocity, without having to be declared as nanomaterial. Production methods and parameters were systematically investigated. Wet bead milling at 2000 rpm for 30 min yielded the best results. A z-average of 280 nm was achieved for a 10% Symurban suspension with a polydispersity index of 0.20, indicating a narrow size distribution. For the long-term stabilization of the nanocrystal suspension, the performance of 15 surfactants of different categories and HLB values were investigated and evaluated. It was found that non-ionic surfactants in general were better able to stabilize the system than anionic or amphoteric surfactants. Highest stability of over 12 months at 25 °C was achieved with 2% Plantacare 810 UP, an ECOCERT surfactant with high skin tolerance. The suspension was also chemically long-term stable with >97% of remaining Symurban over 12 months. The saturation solubility of Symurban as nanocrystals was significantly increased from 0.25 to 2.9 μg/mL, which corresponds to a factor of >11. In a case study of one male volunteer with healthy skin conditions, penetration profiles of Symurban nanocrystal hydrogel and commercial anti-pollution serum containing an identical amount of Symurban were determined and compared. After 20 min of exposure, the relative Symurban concentration in the deeper skin layers (tape 19-30) was more than two times higher for nanocrystal hydrogel (16%) than the commercial serum (7%). These results suggest that nanocrystals are a promising delivery system for the poorly soluble anti-pollution agent Symurban.

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Section: Introductionmentioning

confidence: 99%

Symurban Nanocrystals for Advanced Anti-Pollution Skincare

Köpke

Pyo

2020

Cosmetics

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The role of kynurenine pathway aryl hydrocarbon receptor axis in autoimmune diseases of the skin

Noakes¹

2023

Translational Autoimmunity

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Kynurenines as a Novel Target for the Treatment of Inflammatory Disorders

Mor,

Tankiewicz-Kwedlo,

Ciwun

et al. 2024

Cells

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This review discusses the potential of targeting the kynurenine pathway (KP) in the treatment of inflammatory diseases. The KP, responsible for the catabolism of the amino acid tryptophan (TRP), produces metabolites that regulate various physiological processes, including inflammation, cell cycle, and neurotransmission. These metabolites, although necessary to maintain immune balance, may accumulate excessively during inflammation, leading to systemic disorders. Key KP enzymes such as indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), tryptophan 2,3-dioxygenase (TDO), and kynurenine 3-monooxygenase (KMO) have been considered promising therapeutic targets. It was highlighted that both inhibition and activation of these enzymes may be beneficial, depending on the specific inflammatory disorder. Several inflammatory conditions, including autoimmune diseases, for which modulation of KP activity holds therapeutic promise, have been described in detail. Preclinical studies suggest that this modulation may be an effective treatment strategy for diseases for which treatment options are currently limited. Taken together, this review highlights the importance of further research on the clinical application of KP enzyme modulation in the development of new therapeutic strategies for inflammatory diseases.

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Dissecting the enigma of scleroderma: possible involvement of the kynurenine pathway

Cited by 3 publications

References 79 publications

Symurban Nanocrystals for Advanced Anti-Pollution Skincare

Symurban Nanocrystals for Advanced Anti-Pollution Skincare

The role of kynurenine pathway aryl hydrocarbon receptor axis in autoimmune diseases of the skin

Kynurenines as a Novel Target for the Treatment of Inflammatory Disorders

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