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Understanding Solar Skin Elastosis-Cause and Treatment
Abstract
Photoageing, also called actinic ageing, is the main cause of prematurely aged skin. Our expertise in elastic fibers has led us to discover a process triggered in response to ultraviolet (UV) light and which upsets the balance of elastin fibers: there is too much elastin and insufficient lysyl oxidase (LOXL1) enzyme to form functional elastic fibers. This imbalance then leads to an accumulation of nonfunctional elastin, which forms aggregates. In addition to this imbalance, UV rays also induce elafin synthesis by fibroblasts. Known to be a marker of elastotic aggregates, elafin crystallizes the elastin fibers and stimulates the formation of aggregates that cannot be naturally eliminated by the skin. We developed a Hamamelis virginiana leaf extract that was able to restore both the balance between elastin and LOXL1 and to decrease the elafin synthesis to fight and correct the damage. This specific Hamamelis virginiana extract increased LOXL1 expression by twofold and decreased elafin synthesis. As a consequence, elastic fibers became functional and aggregates of unfunctional fibers decreased. The specific Hamamelis extract activity was confirmed in vivo with decreasing wrinkles and improving skin firmness.
... Among these proteins, the most important is type I collagen (COL I, fibrillar). Total skin collagen is made of 80 to 85% of COL I [5]. ...
... The microscope slides were evaluated by using an Olympus BX 41 microscope in magnification ×40 and ×100. The immunohistochemical report was performed by estimating with visual evaluation the percentage of COL I expression on a scale of 1 to 5, positively (weak +, weak to moderate ++, moderate +++, moderate to severe ++++, and severe +++++) [5]. ...
... It was observed that in people over the age of 75, solar elastosis was milder than in the age of 65, and we would expect the reduction to be more severe in older skin. This could be a random finding observed in our samples owing to various factors, for example, lifestyle, location, duration of sun exposure, etc. [5]. Nevertheless, the possible cause could be the relation with the ozone layer, as the stratospheric ozone is an effective UV absorber. ...
Ultraviolet radiation exposure is the dominant environmental determinant of all major forms of skin cancer, and the main cause of prematurely aged skin that is referred to as photoaging. Collagen type I (COL I) is expressed differently along with the dermis between healthy and pathological skin tissues. The aim of this study was to understand the impact of solar radiation in the dermis and assess the impact of solar radiation to COL I. The hematoxylin and eosin staining protocol was performed in tissue paraffin blocks and then they were stained immunohistochemically with the rabbit monoclonal anti-COL I antibody. A total of 270 slides were studied with an Olympus BX 41 microscope; we scored positively the expression of COL I in dermis and statistically analyzed with IBM SPSS Statistics. Based on our results, we observed that solar elastosis changes the structure of the skin’s collagen. In healthy tissues, COL I had a uniform expression along with the dermis. In tissues with aging, COL I expression was weaker and lost homogeneity. In pathological tissues (non-melanoma skin cancers, NMSCs), precancerous lesions, and benign skin lesions), the expression of COL I was observed to be almost weaker than tissues with aging in all body parts and much weaker below the lesions. The most severe solar elastosis was observed in the extremities. The degree of severity of the solar elastosis in relation to age did not appear to be completely affected. Solar radiation divides the collagen more rapidly than normal biological aging and solar elastosis was observed into the skin tissues with photoaging, which replaces the collagen fibers of the skin. These results confirm previous studies, which have shown that skin COL I decreases during aging, more in photoaging and even more in skin cancers. We conclude that skin COL I expression is reduced as a result of ultraviolet radiation and leading to negative impacts on the skin.
... This imbalance leads to the accumulation of nonfunctional elastin, which aggregates in disorganized deposits. In addition, UV rays also induce fibroblasts to produce more elafin, which crystallizes the elastin fibers helping the formation of aggregates that cannot be eliminated by natural metabolic processes [3,4]. More precisely dermal fibroblasts potentially express elafin on UV irradiation, UV-mediated elafin interacts with elastin, and the elafinelastin complex protects elastic fibers from elastolytic degradation, leading to the accumulation of elastic fibers in the actinic elastosis of sun-damaged skin [5]. ...
... Patient evaluation by means of the FACE-Q questionnaire was obtained only post-operatively and not also in the pre-operative phase. 3 Page 8 of 9 ...
Background
Actinic elastosis is a non-curable skin condition manifesting with wrinkling, reduction of elasticity, pigmentation, and roughness of the skin. Many aesthetic treatments aimed at reducing its aesthetic impact have been suggested. The aim of this study is to compare fat grafting, fractioned CO2 laser resurfacing, and hybrid filler in order to detect which one is more effective in improving actinic elastosis.
Methods
Patients meeting the following criteria were included in the study: dermatological diagnosis of elastosis, primary surgical or non-surgical treatment for elastosis, at least 1 year follow-up, pre- and post-operative photo-documentation, proficiency in Italian language, and signed consent for study participation. The study was performed with a randomized design; patients were randomly divided in three groups: group 1, fat grafting; group 2, hybrid filler; and group 3, CO2 laser resurfacing. All patients were asked to answer the FACE-Q satisfaction with the face post-operative module. Two plastic surgeons, blinded to the treatment method used, were selected to examine pre- and post-operative photographs, rating the outcomes on a 1–5 VAS scale.
Results
Seventy-five patients were enrolled, 4 males and 71 females, aged between 50 and 80 years. Both the FACE-Q and VAS scores were higher in groups 1 and 2. No major complications were reported in any of the groups.
Conclusions
Elastosis remains a genetically based skin condition, which cannot be considered curable. Hybrid filler and adipose tissue transfer can be both considered valid options to improve skin elastosis both in terms of patient satisfaction and enhancement of skin quality.
Level of evidence:Level II, Therapeutic study2229
... It appears superficially because, as it is known, UVA radiation is absorbed more by the epidermis (at a percentage of 80%) and less by the dermis (at a percentage of 20%) [17]. It was also confirmed in this study that in the dermis, UV radiation divides the collagen more rapidly than in biological aging [18]. The formation of an abnormal elastin stripe (solar elastosis) below the epidermis was observed in the skin with photoaging, which replaces (by covering) the collagen fibers of the skin [19]. ...
... Finally, previous studies emphasized the presence of COL VI in malignant cells by enhancing the production of primitive factors and causing epithelial-mesenchymal transition [16,18]. In addition, it affects the microenvironment of the tumor by increasing the mobility of macrophages and endothelial cells, thus promoting tumor inflammation and angiogenesis. ...
Both endogenous and exogenous factors cause skin aging. This study aimed to compare the differential expressions of collagen type I (COL I) and collagen type VI (COL VI) in skins with biological aging and photoaging. In order to comprehend the impact of solar radiation in the dermis and the expression of COL I and COL VI, we studied the expression and their detection in healthy skin and in skin that had been characterized by aging. The hematoxylin and eosin staining protocol was performed in tissue paraffin blocks and they were then stained immunohistochemically with rabbit monoclonal anti-COL I and anti-COL VI antibodies. A total of 201 slides were studied with an Olympus BX 41 microscope, and the expressions of COL I and COL VI in the dermis were scored on a scale of 1 to 5, and then positively and statistically analyzed with IBM SPSS Statistics software. The results show that solar elastosis changes the structure of the skin’s collagen and solar elastosis was observed in the skin tissues with photoaging without appearing to be affected by its appearance in relation to age. Solar radiation divides the collagen fibers more rapidly than normal biological aging and replaces the collagen fibers of the skin. COL I and COL VI are expressed differently along the dermis of healthy skin tissue and the skin tissue subject to photoaging.
... Post-sun elastosis is associated with a change in the organization of elastic fibers. It is further accompanied by the accumulation of tropoelastin in the reticular layer of the dermis, forming aggregates of abnormal, immature elastin fibers [41,42]. In addition, degradation of collagen fibers of the extracellular matrix can be observed in skin chronically exposed to UV. ...
Skin aging is associated with both intrinsic and extrinsic aging, with extrinsic aging caused by environmental factors and overlaying the effects of chronological aging. The main aim of this study was to evaluate the effect of preparations containing Helix aspersa snail mucus on skin regeneration with photoaging features. Before and 3 months after the series of treatments, skin biopsy specimens from the right preauricular region of the face were taken from six women. Histological, morphometric, and immunohistochemical analyses were performed. Positive changes, indicating a reduction in photoaging related to the reduction in epidermis thickness 3 months after the end of the treatments, were noted in each group. A statistically significant increase in the thickness of the collagen fiber bundles was also observed in the patients 3 months after a series of micro-needle mesotherapy treatments with snail mucus and 0.9% NaCl. There was a significant increase in the immuno-expression of Ki-67 and PCNA in the dermis. The aforementioned significance applies to patients in whom snail mucus was introduced with the use of micro-needle mesotherapy and needle-free mesotherapy. Moreover, a statistically significant increased area with the immunoexpression of MMP-2 in the dermis was observed in the above-mentioned groups of patients, who were treated with the preparation containing snail filtrate. The results of the study suggest that the use of snail mucus preparations for skincare, as well as its introduction by micro-needle and needleless mesotherapy, had a beneficial effect on the condition of the skin.
... Our team has previously applied actinic elastosis (AE), a histopathological finding also referred to as solar elastosis characterized by the accumulation of abnormal amorphous or elastotic fibers and basophilic degeneration [50,51], as a biomarker for chronic UV exposure, which we have found differs in magnitude among subtypes of melanoma, cutaneous squamous cell carcinoma, and basal cell carcinoma cases [52,53]. Given the multifarious drivers of different rare skin cancers and our relatively incomplete understanding of the relative importance of these drivers, efforts to systematically explore biomarkers that can inform the prevention and/or treatment of these cancers are indicated. ...
Simple Summary
While sun exposure and associated tissue changes stemming from ultraviolet radiation are closely associated with the most common forms of skin cancer, far less is known regarding rare types of skin cancer. In this study, for the first time, we used a light microscopy technique to evaluate connective tissue changes in samples from patients with six different types of rare skin cancers, assessing the relationship between these changes, patient age, and whether tumors arose on sun-exposed parts of the body. We found that these tissue changes were most pronounced for patients with specific cancers known to be linked to chronic sun damage and tumors arising on sun-exposed parts of the body. We also noted tumor type-specific trends in terms of sex ratios, sites of tumor presentation, and the relationship between the development of particular tumors and patient immunosuppression. Our results are important and novel as they expand the available data associated with these rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic, and/or therapeutic approaches.
Abstract
(1) Background: Rare skin cancers include epithelial, neuroendocrine, and hematopoietic neoplasias as well as cutaneous sarcomas. Ultraviolet (UV) radiation and sunburns are important drivers for the incidence of certain cutaneous sarcomas; however, the pathogenetic role of UV light is less clear in rare skin cancers compared to keratinocyte cancer and melanoma. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure among selected rare skin cancers (atypical fibroxanthoma [AFX], pleomorphic dermal sarcoma [PDS], dermatofibrosarcoma protuberans [DFSP], Kaposi sarcoma [KS], Merkel cell carcinoma [MCC], and leiomyosarcoma [LMS]) while taking into account relevant clinical variables (age, sex, and body site). (2) Methods: We newly established a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 210 rare skin cancers from 210 patients with their clinical variables. (3) Results: TEG values were correlated with age and whether tumors arose on UV-exposed body sites. TEG values were significantly higher in AFX and PDS cases compared to all other analyzed rare skin cancer types. As expected, TEG values were low in DFSP and KS, while MCC cases exhibited intermediate TEG values. (4) Conclusions: High cumulative UV exposure is more strongly associated with AFX/PDS and MCC than with other rare skin cancers. These important results expand the available data associated with rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic and/or therapeutic approaches.
... However, irregular coarse and thickened elastic fiber accumulation is seen in the upper dermis on histology. 90 Finally, Granulomatous slack skin should also be ruled out. This condition affects mainly the groin and axillae; it starts as patches and plaques that become lax and pedunculus over time. ...
Acquired cutis laxa (ACL) is a rare, nonhereditary cutaneous disorder characterized by saggy inelastic skin. It has been associated with various inflammatory, autoimmune, and neoplastic diseases, in addition to certain infections and medication. This article reviews ACL the demographical, clinical, and histological features of ACL, focusing on all associated disorders. Additionally, this review article provides an in‐depth discussion of all the mechanisms implicated in the pathogenesis of ACL and all therapeutic options available; we also present an algorithm for the workup of patients with ACL. A systematic literature review was performed on PubMed/Medline and EMBASE databases, searching for all available articles on ACL with no limits on participant age, race, sex, nationality, or publication date. Ninety‐eight articles were included. The total number of included patients was 110, with a mean age of 36.4 years at presentation (range 0.25–78) and a M:F sex ratio of 1.24. ACL was most commonly associated with inflammatory disorders (43%) followed by neoplastic disorders (27%). In 73% of the neoplastic‐associated cases, ACL occurred on average 2.4 years before malignancy onset. ACL occurs months to years after an underlying inflammatory disorder. In 10% of the cases, ACL was associated with a particular drug, and in 2%, it was associated with specific infections. Data were derived from case reports, case series, letters to editors, observational studies, and abstracts. Limitations include the accuracy of published data, potential patient selection, and reporting bias. Dermatologists should be alert to these associations to provide adequate screening and management of patients with ACL.
... The microscope slides were evaluated by using an Olympus BX 41 microscope in magnification x40 and x100. The Immunohistochemical report was performed by estimating with visual evaluation the percentage of Col VI expression on a scale of 1 to 5 positively (weak +, weak to moderate ++, moderate +++, moderate to severe ++++, and severe +++++) [10]. The study focused on Col VI's expression in three indexes. ...
... Fortunately, this condition can be stabilized or reversed with proper treatment. 35 Tobacco use kills more than 8 million people each year. 36 It is considered to be the largest preventable cause of illness and early death worldwide. ...
BACKGROUND
There is a lack of studies evaluating the oral health of traditional indigenous communities in Brazil.
OBJECTIVES
Thus, the objective of this study was to describe the oral health characteristics of the indigenous Fulni-ô ethnic group in Northeast Brazil.
DESIGN AND SETTING
A cross-sectional observational investigation was conducted within the Project on Atherosclerosis among Indigenous Populations.
METHODS
This study included participants of both sexes from the Fulni-ô ethnic group. The participants included in this investigation underwent a comprehensive oral health evaluation by a registered and experienced dentist to assess oral health and identify potentially malignant oral lesions. Participants with suspicious lesions were referred for biopsy. Shapiro-Wilk, Mann-Whitney, and Student’s t-tests were used, and measures of central tendency and dispersion were described. Statistical significance was 5%.
RESULTS
A total of 104 individuals were included in this study. The prevalence of the use of tobacco derivatives was 94.0%, with similarities between sexes. The prevalence of oral changes in this study population was 84.4%. Fifty-one individuals who underwent oral reassessment were referred for oral lesion biopsy.
CONCLUSIONS
This study demonstrated a high prevalence of oral alterations in the Fulni-ô population. Histopathological analyses indicated the presence of mild oral epithelial dysplasia in five cases.
KEY WORDS (MeSH terms):
Oral health; Tobacco use disorder; Epidemiology; Indigenous peoples; Pathology
AUTHORS’ KEY WORDS:
Health of indigenous peoples; Cross-sectional study; Health, public; Oral epithelial dysplasia; Oral cavity
... Photoageing leads to the accumulation of elastin-breakdown products in the papillary dermis. The process is called elastosis and is clinically manifested as papules, nodules, and deep furrows [26]. Subcutaneous tissue is built of adipocytes creating a protective layer against mechanical and thermal factors; its thinning with age weakens this barrier and negatively affects the appearance of the skin. ...
Although interest in aesthetic medicine is growing, the focus is often placed outside of the facial area, namely on the skin of the neck and cleavage. Exposure to the sun and muscle movements cause the prompt development of wrinkles that may appear there, even before they show up on the face. We conducted a literature review devoted to micro-needling to identify its role in anti-ageing treatments and to determine the gaps in current knowledge. A search in Medline identified 52 publications for neck and face micro-needling. Micro-needling is an anti-ageing procedure that involves making micro-punctures in the skin to induce skin remodelling by stimulating the fibroblasts responsible for collagen and elastin production. It can be applied to the skin of the face, neck, and cleavage. Two to four weeks should be allowed between repeated procedures to achieve an optimal effect. The increase in collagen and elastin in the skin can reach 400% after 6 months, with an increase in the thickness of the stratum granulosum occurring for up to 1 year. In conclusion, micro-needling can be considered an effective and safe aesthetic medicine procedure which is conducted at low costs due to its low invasiveness, low number of adverse reactions, and short recovery time. Little evidence identified in the literature suggests that this procedure requires further research.
... Fortunately, this condition can be stabilized or reversed with proper treatment. 35 Tobacco use kills more than 8 million people each year. 36 It is considered to be the largest preventable cause of illness and early death worldwide. ...
Glioblastoma multiforme (GBM) is a malignant brain tumor with one of the worst general survivorship cases among the existing neoplasia. This aggressiveness is due to its complex molecular heterogeneity, immunohistochemistry and genetics. The current therapeutic approach brings little contribution to the improvement of the survival of the patients. Due to that, new forms of treatment have been explored, one of them being immunotherapy. In this aspect, the inflammasome pathway, which induces inflammation and immunosuppressive tumor response, contributing to the progression of the tumor, seems to be a new alternative to improve the treatment efficacy and the survival of the patients.
... It has been reported that LOX expression decreases during photoaging and that this enzyme is essential for elastic fiber homeostasis and maintenance of elastogenesis [38]. Pain et al. [39] complemented that too much elastin and insufficient lysyl oxidase enzyme (LOXL1) to form functional elastic fibers may be caused by an imbalance of the elastin fibers in response to ultraviolet light. For this marker, a significant increase in gene expression was observed in the periocular region, which was not confirmed in the reconstituted skin model. ...
Introduction:
Photoaging is the process by which ultraviolet rays gradually induce clinical and histological changes in the skin through the production and organization of biological molecules, such as elastin, which is critical to skin strength and elasticity. After exposure to radiation, elastin may undergo alternative mRNA splicing, resulting in modified proteins that contribute to the formation of aging characteristics, such as solar elastosis. The present work aimed to study two different forms of elastin under these conditions: normal elastin and elastin that had been altered in exon 26A.
Methods:
These different forms of elastin were characterized for gene expression by quantitative real-time polymerase chain reaction (qPCR) and for protein expression by immunohistochemistry of ex vivo skins (from photoexposed and non-photoexposed areas) and in vitro reconstituted skin. In addition, up- and downstream molecules in the elastin signaling cascade were evaluated.
Results:
As a result, a significant increase in the gene expression of elastin 26A was observed in both ex vivo photoexposed skin tissues and the in vitro photoexposed reconstituted skins. Additionally, significant increases in the gene expression levels of matrix metalloproteinase-12 (MMP12) and lysyl oxidase (LOX) were observed in the ex vivo skin model. The evaluation of protein expression levels of some photoaging markers on the reconstituted skin revealed increased tropoelastin and fibrillin-1 expression after photoexposure.
Conclusion:
This work contributes to a better understanding of the biological mechanisms involved in photoaging, making it possible to obtain new strategies for the development of dermocosmetic active ingredients to prevent and treat skin aging.
... The balance in the composition of those proteins is essential for skin function and health and, interestingly, Mϕ play an important role in this context. For instance, Mϕ synthesize metalloelastases (e.g., metalloelastase 12) that participate in the elimination of nonfunctional elastin aggregates generated in the skin as a consequence of photoaging [64,65]. ...
The skin is our largest organ and the outermost protective barrier. Its aging reflects both intrinsic and extrinsic processes resulting from the constant insults it is exposed to. Aging in the skin is accompanied by specific epigenetic modifications, accumulation of senescent cells, reduced cellular proliferation/tissue renewal, altered extracellular matrix, and a proinflammatory environment favoring undesirable conditions, including disease onset. Macrophages (Mφ) are the most abundant immune cell type in the skin and comprise a group of heterogeneous and plastic cells that are key for skin homeostasis and host defense. However, they have also been implicated in orchestrating chronic inflammation during aging. Since Mφ are related to innate and adaptive immunity, it is possible that age-modified skin Mφ promote adaptive immunity exacerbation and exhaustion, favoring the emergence of proinflammatory pathologies, such as skin cancer. In this review, we will highlight recent findings pertaining to the effects of aging hallmarks over Mφ, supporting the recognition of such cell types as a driving force in skin inflammaging and age-related diseases. We will also present recent research targeting Mφ as potential therapeutic interventions in inflammatory skin disorders and cancer.
... These results are in agreement with the general conception that increased tropoelastin without cross-linking leads to impaired elastogenesis and results in skin disorders when in severe conditions. For example, UV damage can result in skin elastosis due to an elastin accumulation, combined with insufficient LOXL1 enzyme, resulting in dis-functional elastic fibre formation [38]. ...
Background:
The loss of structural elastin due to intrinsic and extrinsic ageing results in the skin's inability to stretch and recoil (decrease in elasticity) and manifests as loss of skin firmness and sagging. While other extracellular matrix (ECM) components such as collagen and hyaluronic acid are continually synthesized and assembled through life, elastic fibres are not. Elastic fibre assembly and functionality require fibre cross-linking, induced by the lysyl oxidase-like (LOXL) enzymes, which sharply decrease during ageing.
Objective:
To evaluate the enhanced elastogenic effect of a blackberry-dill extract combination, which was hypothesized to induce elastin fibre component synthesis, fibre cross-linking and reduce elastin fibre degradation.
Methods:
The blackberry and the dill extracts were tested separately and in combination to confirm single ingredient bioactivity and synergistic benefits. Human skin explants, dermal fibroblasts, elastase assays, ELISAs, quantitative real-time PCRs and spectrofluorometer measurements were used. Moreover, a double-blinded, placebo-controlled clinical study was carried out to assess skin elasticity using Cutometer and histologically from biopsies.
Results:
The blackberry extract induced elastin gene expression, elastin promoter activity and inhibited elastic fibre degradation by matrix metalloproteinases (MMPs) 9 and 12. The dill extract induced elastin, collagen and LOXL1 gene expression, resulting in enhanced fibre cross-linking in human skin explants. Clinically, the blackberry and dill combination treatment displayed synergistic pro-elasticity activity as compared to each ingredient alone and placebo.
Conclusion:
Taken together, these results demonstrated the two multimodal plant-based extracts complemented each other in terms of bioactivity and resulted in a synergistic elastogenesis induction.
... В естественно стареющей коже наблюдаются постепенные атрофические изменения эпидермиса, истончение дермы, уплощение дермо-эпидермального соединения. Кожа с признаками фотостарения, напротив, часто ассоциируется с увеличением толщины эпидермиса (гиперкератоз) и дегенеративным повреждением дермальной соединительной ткани, известным как солнечный эластоз [5]. ...
Skin is the organ in permanent contact with environmental factors which could accelerate the aging process. The changes occurring due to the aging process are particularly noticeable in the skin. Skin ageing is dependent on endogenous and exogenous factors determined by environmental factors, primarily the ultraviolet radiation (photoaging).The Authors reviewed the articles available at PubMed, ResearchGate and GoogleScholar on the composition and application of preparations containing snail mucus. The results of the literature analysis revealed that snail mucus contains substances such as allantoin, glycolic acid, lactic acid, collagen, elastin, extracellular matrix metalloproteinases as well as their inhibitors, and antioxidant enzymes. Also, it was demonstrated that the use of preparations containing snail mucus had beneficial effects on the condition of the skin, including improved skin hydration, normalisation of the thickness of the epidermis, improved skin structure, increased cell proliferation index, reduction of skin elastosis and decreased hyperpigmentation. Moreover, the regenerative mechanism of action of snail mucus resulted in a clinical alleviation of lesions in patients with dermatological problems of various aetiology. Therefore, it appears that snail mucus could be a good biostimulator and its use has many beneficial effects for the skin.
Background
Photodamage creates changes within the skin layers known as solar elastosis. This presents as fragmentation of collagen and elastin fibers, decreases in the extracellular matrix (ECM) ground substance, as well as hyaluronic acid decrease in the thinning epidermis. Traditional immunohistochemistry (IHC) staining has failed to differentiate degenerated elastin from new elastin fibers generated with various topical strategies.
Aims
A combination of stains that can offer a regenerative narrative distinguishing newly formed collagen and elastin from that of degenerated protein, thus distinguishing “good” vs “bad” elastin.
Methods
A series of stains were explored based on their ability to identify early regenerative changes within epidermal, dermal, and ECM areas to examine consistency of outcomes and reliability.
Results
A combination of Movat, fibrillin, elafin, and versican for elastogenesis and reversal of solar elastosis. CD44 for HA status (mainly epidermal) and Herovici stain for identifying early collagenesis in the ECM provides a comprehensive range of stains for identifying new elastin and collagen
Conclusion
This suggested stain combination appears to offer an ideal collection of stains for identifying regenerative events within the skin layers.
Exfoliation syndrome (XFS) is an age-related systemic disease that affects the extracellular matrix. It increases the risk of glaucoma (exfoliation glaucoma, XFG) and susceptibility to diseases of elastin-rich connective tissues. LOXL1 (lysyl oxidase-like 1) is still recognized as the major genetic effect locus in XFS and XFG in all populations worldwide, although its genetic architecture is incompletely understood. LOXL1 is a key cross-linking enzyme in elastic fiber formation and remodeling, which is compatible with the pathogenetic concept of XFS as a specific type of elastosis. This review provides an overview on the current knowledge about the role of LOXL1 in the etiology and pathophysiology of XFS and XFG. It covers the known genetic associations at the LOXL1 locus, potential mechanisms of gene regulation, implications of LOXL1 in XFS-associated fibrosis and connective tissue homeostasis, its role in the development of glaucoma and associated systemic diseases, and the currently available LOXL1-based in vivo and in vitro models. Finally, it also identifies gaps in knowledge and suggests potential areas for future research.
Objectives
While the effect of ultraviolet radiation (UVR) on human skin has been extensively studied, very little is known on how UVR impacts on hair follicle (HF) homeostasis. Here, we investigated how solar spectrum UVR that hits the human skin surface impacts on HF biology, and whether any detrimental effects can be mitigated by a widely used cosmetic and nutraceutical ingredient, caffeine.
Methods
Human scalp skin with terminal HFs was irradiated transepidermally ex vivo using either 10 J/cm² UVA (340‐440 nm) + 20 mJ/cm² UVB (290–320 nm) (low dose) or 50 J/cm² UVA + 50 mJ/cm² UVB (high dose) and organ‐cultured under serum‐free conditions for 1 or 3 days. 0.1% caffeine (5.15 mM) was topically applied for 3 days prior to UV exposure with 40 J/cm² UVA + 40 mJ/cm² UVB and for 3 days after UVR. The effects on various toxicity and vitality read‐out parameters were measured in defined skin and HF compartments.
Results
Consistent with previous results, transepidermally UVR exerted skin cytotoxicity and epidermal damage. Treatment with high and/or low UVA+UVB doses also induced oxidative DNA damage and cytotoxicity in human HFs. In addition, it decreased proliferation and promoted apoptosis of HF outer root sheath (ORS) and hair matrix (HM) keratinocytes, stimulated catagen development, differentially regulated the expression of HF growth factors, and induced perifollicular mast cell degranulation. UVR‐mediated HF damage is more severe after irradiation with high UVR dose and reached also deeper HF compartments. The topical application of 0.1% caffeine did not induce skin or HF cytotoxicity and stimulated the expression of IGF‐1 in the proximal HF ORS. However, it promoted keratinocyte apoptosis in selected HF compartments. Moreover, caffeine provided protection towards UVR‐mediated HF cytotoxicity and dystrophy, keratinocyte apoptosis, and negative modulation of the catagen‐promoting growth factor.
Conclusion
Our study highlights the clinical relevance of our scalp UV irradiation ex vivo assay and provides the first evidence that transepidermal UV radiation negatively affects important human HF functions, suggesting that it is a sensible prophylactic strategy to integrate agents such as caffeine that can act as HF photoprotectants into sun‐protective cosmeceutical and nutraceutical formulations.
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