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- Dexamethasone, a synthetic glucocorticoid, induces the activity of
androgen receptor in human dermal papilla cells-
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Abstract: Psychosocial stress stimulates the secretion of glucocorticoids (GCs), which are stress-related neurohormones. GCs are secreted from hair follicles and promote hair follicle regression by inducing cellular apoptosis. Moreover, the androgen receptor (AR) is abundant in the balding scalp and androgens suppress hair growth by binding to androgen receptor (AR) in androgenetic alopecia (AGA). First, by using immunofluorescence, we investigated whether the treatment of dermal papilla (DP) cells with dexamethasone (DEX), a synthetic GC, causes the translocation of the glucocorticoid receptor (GR) into the nucleus. DEX treatment causes the translocation of the GR into the nucleus. Next, we investigated whether stress-induced GCs affect the AR, a key factor in male pattern baldness. In this study, we first assessed that DEX increases the expression of AR mRNA in non-balding DP cells, which rarely express AR without androgen. RU486, a GR antagonist, attenuated DEX-inducible AR mRNA expression and AR activation in human non-balding DP cells. In addition, AR translocated into the nucleus after DEX treatment. Furthermore, we indeed showed that the expression of AR was induced in the nucleus by DEX in DP cells of human and mouse hair follicles.Our results first suggest that stress-associated hair loss may be due to increased AR expression and activity induced by DEX. These results demonstrate that hair loss occurs in non-balding scalps with low AR expression
PubDate: Fri, 13 May 2022 12:29:54 +020
- A composite of hepatocyte growth factor and
5α-dihydrotestosterone–gelatin microspheres with adipose-derived stem
cells enhances wound healing-
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Abstract: Introduction: Reconstructing sebaceous glands is one goal of functionally healing patients who have suffered severe burns, instead of the simple pursuit of wound closure. Effective regeneration of skin appendages remains a challenge in skin wound management and research. Objective: The aim of this study was to evaluate the differentiation of ADSC into sebaceous glands, and clarified the involvement of HGF and 5α-DHT in this process. Methods: This study used hepatocyte growth factor (HGF)– and 5α-dihydrotestosterone (5α-DHT)–gelatin microspheres to treat human adipose-derived stem cells (ADSCs) and investigated the reconstruction of sebaceous glands. HGF– and 5α-DHT–gelatin microspheres were constructed using microcapsule slow-release technology. Mice full-thickness skin-wound model was established to evaluate wound healing and hematoxylin-eosin staining was utilized to determine the skin structure. Results: In vitro analyses found that HGF– and 5α-DHT–gelatin microspheres promoted migration of and tube formation by ADSCs. Furthermore, AKT/ERK signaling, which is related to sebocyte and sweat gland epithelial cell growth, were activated after HGF and 5α-DHT treatment. An in vivo wound healing model demonstrated that ADSCs primed with amnion-loaded HGF– and 5α-DHT–gelatin microspheres promoted wound healing and increased sebaceous gland formation compared to the control group. Conclusions: This study confirms the efficacy of ADSCs treated with amnion and HGF– and 5α-DHT–gelatin microspheres in accelerating wound healing and effectively restoring sebaceous glands. This engineered tissue provides insight into and a novel therapeutic material for burns and full-thickness skin wounds.¬¬
PubDate: Tue, 19 Apr 2022 11:37:25 +020
- Induction of Radiodermatitis in Nude Mouse Model using Gamma Irradiator
IBL 637-
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Abstract: Introduction: Acute radiodermatitis is a common, though severe, side effect of radiotherapy against cancer that may lead to an interruption or even abortion of the radiotherapy. Mouse models provide an excellent tool to study pathomechanisms of a radiation-induced dermatitis as well as to test and develop novel innovative treatment strategies. Objective: The aim of this study is to provide an overview of different mouse models and irradiation devices that have been used so far and to describe the process of the induction of a radiation dermatitis in an immune proficient nude mouse model (SKH1-Hrhr) using a IBL 637 Cesium-137γ-ray machine. Methods: This process includes the construction of a radiation shielding chamber, restricting the radiation to the right hind leg of the mouse, a dosimetry and a dose finding study to identify the appropriate irradiation dose to induce a moderate radiation dermatitis.Results: A radiation shielding chamber was successfully constructed allowing selective irradiation of the right hind leg. A moderate radiodermatitis is induced with irradiation doses in the range of 60 – 70 Gy under the here described conditions. Symptoms peak about eight days after irradiation and decrease relatively quickly thereafter. Histological analyses confirmed typical signs of inflammation.Conclusion: This study describes for the first time a protocol to induce a moderate radiodermatitis in the nude mouse model SKH1-Hrhr using a IBL 637 gamma irradiator. This protocol will allow researchers to study novel treatment strategies to alleviate the burden of a radiodermatitis as a side effect of cancer treatment.
PubDate: Wed, 13 Apr 2022 16:12:52 +020
- Correlation of Body Mass Index with Epidermal Biophysical Properties
Varies with Gender in Chinese-
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Abstract: Background: Epidermal function is associated with diabetes and renal disease. Whether obesity can reflect the changes in epidermal function is not clear yet. Objective: We assessed here the correlation of epidermal functions with body mass index (BMI) in a large Chinese cohort. Methods and Subjects: A total of 1405 Chinese aged 21 to 96 years old were enrolled in this study. Epidermal functions, including transepidermal water loss (TEWL), stratum corneum hydration and skin surface pH, were measured on the flexor forearm and the shin. Subjects’ height and body weight were also measured. Results: Age positively correlated with both TEWL and skin surface pH, while negatively correlating with stratum corneum hydration on both the forearm and the shin of females. Similarly, age positively correlated with skin surface pH, while negatively correlating with stratum corneum hydration on both the forearm and the shin of males. In females, BMI positively correlated with skin surface pH, while negatively correlating with stratum corneum hydration on both the forearm and the shin. However, BMI correlated with neither skin surface pH on both the forearm and the shin nor with stratum corneum hydration on the shin of males. Conclusion: These results demonstrate that correlations of BMI with age and epidermal functions vary with gender.
PubDate: Mon, 04 Apr 2022 13:39:26 +020
- Percutaneous egression: What do we know'
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Abstract: Background: The process by which drugs leave the bloodstream to enter the skin compartments is important in determining appropriate routes of delivery and developing more efficacious medications. We conducted a general literature review on percutaneous egression mechanisms. Summary: Studies demonstrate that the stratum corneum (SC) is a compartment for systemically delivered drugs. Upon reviewing the available literature, it became apparent that there may be multiple mechanisms of percutaneous egression dependent upon drug physiochemical properties. These mechanisms include, but are not limited to, desquamation, sebum secretion, sweat transport and passive diffusion. While drugs often utilize one major pathway, it is possible that all mechanisms may play a role to varying extents. Key Messages: Available literature suggests that hydrophilic substances tended to travel from blood to the upper layers of the skin via sweat, whereas lipophilic substances utilized sebum secretion to reach the SC. Upon reaching the skin surface, the drugs spread laterally before penetrating back into the skin as if they were topically administered. More data are warranted to identify additional percutaneous egression mechanisms, precise drug action sites and accelerate drug development.
PubDate: Thu, 24 Mar 2022 12:57:59 +010
- LncRNA XIST engages in psoriasis via sponging miR-338-5p to regulate
keratinocyte proliferation and inflammation-
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Abstract: Introduction: Psoriasis is an immune-mediated polygenic inflammatory skin disease, keratinocyte proliferation is an important mechanism. The study investigated the role and regulatory relationship between lncRNA XIST and miR-338-5p in psoriatic patients and cell models.Methods: Serum samples were collected from 55 psoriasis patients. HaCaT was recruited for the cell experiments, and induced by M5 cytokines to mimic psoriasis in vitro. XIST and miR-338-5p levels were detected via qRT-PCR. Cell viability under different treatments was evaluated using CCK-8. ELISA was applied to measure the concentration of inflammatory cytokines. The regulatory relationship was confirmed using luciferase reporter gene assay.Results: Serum XIST was elevated in patients with psoriasis, and can distinguish the psoriasis patients from healthy controls according to the ROC curve. High level of XIST was positively correlated with with PASI score and serum TNF-α, IL-17A and IL-22 concentrations in psoriasis patients. XIST silencing suppressed M5-induced keratinocyte proliferation and restrained the discharge of inflammatory cytokines (TNF-α, IL-17A, IL-22) and chemokines (CXCL1, CXCL8, CCL20). XIST can sponge miR-338-5p, and miR-338-5p downregulation abolished the inhibitory effect of XIST silencing on cell proliferation and inflammation. miR-338-5p was at high expression in the clinical serum samples from psoriasis patients. The target relationship between miR-338-5p and IL-6 was proved.Conclusion: LncRNA XIST is highly expressed in the serum of patients with psoriasis, and was positively correlated with disease severity and inflammation. XIST may regulate keratinocyte proliferation and inflammation via regulating miR-338-5p/IL-6 axis.
PubDate: Tue, 01 Mar 2022 10:17:15 +010
- Lateral Dermal Penetration is Dependent on the Lipophilicity of Active
Ingredients-
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Abstract: Introduction:With its large surface area skin facilitates a topical administration of active ingredients, and thus percutaneous delivery to a specific target site. Due to its high barrier function and different diffusion characteristics skin governs the efficacy of these active ingredients and a bioavailability in the epidermal and dermal tissue. Objective:In order to characterize the vertical and lateral movement of molecules into and inside the skin the diffusivity of active ingredients with different physico-chemical properties and their penetration ability in different dermal skin layers was investigated. Methods:A novel lateral dermal microdialysis (MD) penetration setup was used to compare the diffusion characteristics of active ingredients into superficial and deep implanted MD membranes in porcine skin. The corresponding membrane depth was determined via ultrasound and the active ingredients concentration via high-pressure liquid chromatography (HPLC) measurement.Results:The depth depended penetration of superficial and deep implanted MD membranes and the quantitative diffusivity of two active ingredients was compared. An experimental lateral MD setup was used to determine the influence of percutaneous skin penetration characteristics of an active ingredient with different lipophilic and hydrophilic characteristics. Therefore, hydrophilic caffeine and lipophilic LIP1, which have an identical molecular weight, but different lipophilic characteristics were tested for their penetration ability inside a propylene glycol (PG) and oleic acid (OA) formulation. Conclusion:The vertical and lateral penetration movement of caffeine was found to exceed that of LIP1 through the hydrophilic dermal environment. The findings of this study show that the lipophilicity of active ingredients influence the penetration movement and that skin enables a conical increasing lateral diffusivity and transdermal delivery.
PubDate: Wed, 16 Feb 2022 15:26:30 +010
- RP-18 TLC and Computational Descriptors of Skin Permeability of Sunscreens
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Abstract: AbstractThe relationships between the reversed-phase thin layer chromatographic retention parameters obtained on octadecyl-modified silica (RP-18) sorbent for mobile phases containing water and one of six water-miscible organic modifiers (acetone, methanol, acetonitrile, tetrahydrofurane, N,N-dimethylformamide, 1,4-dioxane) and skin permeability coefficients were studied for a group of 21 cosmetic raw materials, mainly organic sunscreens and preservatives.The correlations between the skin permeability coefficients log Kd calculated in silico using EpiSuite software and the RP-18 thin layer chromatographic retention parameters are mostly linear, especially for compounds of lower-to-medium lipophilicity.. It was established that skin permeability coefficient models based on retention parameters collected for mobile phases containing acetone or dioxane (75% v/v), proposed for structurally unrelated cosmetic raw materials are also applicable to other actives, as shown using a test set of compounds whose in vivo log Kd data are available. Skin permeability models developed in this study have the benefit of being based on easily obtained, chromatographic descriptors and their applicability extends beyond cosmetic chemistry.
PubDate: Mon, 07 Feb 2022 17:04:08 +010
- Erratum
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Abstract:
Skin Pharmacol Physiol
PubDate: Mon, 07 Feb 2022 12:08:03 +010
- Common cosmetic compounds can reduce air pollution-induced oxidative
stress and pro-inflammatory response in the skin-
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Abstract: Introduction: Constantly increasing air pollution (AP) poses a concern negatively affecting our health including the skin. A typical manifestation of the skin damage induced by AP is its premature aging, irritation, skin barrier impairment, pigmentation disorders and development or exacerbation of various skin diseases. For these reasons, it is crucial to protect the skin from the negative effects of AP. In this study we evaluated the ability of some compounds commonly used in dermatological or cosmetic preparations with various biological activities to reduce AP-induced skin damage. Methods: We established a new experimental model using porcine skin explants exposed to cigarette smoke (CS) where we determined the level of reactive oxygen species (ROS) in the stratum corneum, skin barrier lipids peroxidation and gene expression of the pro-inflammatory cytokine IL-6 in the epidermis. We then tested several polysaccharides and their derivatives such as sodium hyaluronate (SH) of different molecular weights (MW, 1,6 MDa, 300 kDa, 15 kDa, 5 kDa), yeast glucomannan, schizophyllan and carboxymethyl β-glucan, a vitamin C derivative sodium ascorbyl phosphate, niacinamide and D-panthenol for their ability to prevent CS-induced skin damage. For the evaluation and comparison of their mechanism of action, film-forming effect was determined by TEWL and gloss measurements and the antioxidant properties were assessed by DPPH assay.Results: In the skin samples exposed to CS we observed significant negative changes such as the presence of large amount of ROS in the stratum corneum, a high level of skin barrier lipids peroxidation and upregulated IL6 gene expression. Pretreatment of the skin samples with all the tested substances significantly prevented CS-induced skin damage. The most effective was high MW SH probably due to its best film-forming effect and sodium ascorbyl phosphate with the best antioxidant properties.Conclusion: AP leads to a significant skin damage which can be effectively prevented by using some conventional cosmetic and dermatological ingredients with various mechanisms of action.
PubDate: Mon, 31 Jan 2022 14:47:43 +010
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