Antitumor Activity of Diallyl Sulfide in Two-StageMouse Skin Model of Carcinogenesis

It has been reported that diallyl sulfide (DAS), a sulfur-containing volatile compound in garlic (Allium sativum ), exerts anticarcinogenic activity in various rodent tumor models. In the present study, the antitumor property of DAS was tested in Swiss albino mice in the two steqe initiation-promotion mouse skin carcinogenesis. Skin cancers were initiated topically with a single subcarcinOgenic dose (52μg) of 7, 12-dimethyl benz (a) anthracene (DMBA). Promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) at a dose of 5μg/animal for 32 weeks. DAS was applied topically (250μg/animal) thrice weekly for 3 weeks for anti-initiating and 1 h prior to each promotion treatment for anti-promoting studies. The results showed that the treatment schedule of DAS can effectively delay the onset of tumorigenesis and reduce the cumulative number of tumors and the average number of tumors per mouse. In groups in which DAS applied prior to initiation or promotion, a significant population of the aniinals remained tumor-free till the termination of experiment. These findings suggest that DAS can effectively inhibit chemically induced mouse skincarcinogenesis.

Chemopreventive Effects of Black Tea Polyphenols in Mouse Skin Model of Carcinogenesis

In the present investigations, the antitumorigenic effect of black tea polyphenols (BTP) in twcrstage mouse skin model of carcinogenesis was studied. The animals were initiated with a single 'subcarcinogenic' topical dose (52 μg/200 μl acetone ) of 7, 12-dimethylbenzanthracene (DMBA). To evaluate the anti-tumour initiating activity, BTP was topically applied twice a week for three weeks prior to DMBA application, followed by topical treatment with 12-o-tetradecanoyl phorbol-13-acetate (TPA) (5 μg/200 μl acetone, 2x/wk. ) as promoter. For evaluation of antitumor promoting activity, BTP was applied prior to each treatment of TPA. BTP application showed marked inhibitory effect as antitumour initiator as well as antitumour promoter in mouse skin medel of two-stage carcinogenesis. Since initiation involves genetic pathway and tumour promotion involves epigenetic pathway, it seems that BTP exerts its antitumorigenic effect by altering both genetic and epigenetic pathways

Integrated Organ-on-a-chip with Human-induced Pluripotent Stem Cells Directional Differentiation for 3D Skin Model Generation

Keratinocytes and fibroblasts,derived from hiPSCs,were used to construct the human epidermal model by a culture patch made by monolayer poly-(lactic-co-glycolic acid)(PLGA)nanofibers and a human skin-on-a-chip device.Unlike the conventional culture dish method,two different epidermal cells are successfully adhered to the front and back sides of the patch,which produces a three-dimensional nanofibrous scaffold similar to a natural extracellular matrix before the patch was cultured in the skin-on-a-chip device to mimic the physiological conditions of human skin.As expected,the differentiated hiPSCs show the expression of keratinocyte-and fibroblast-specific proteins on the patch,and the layering is found between these two kinds of cells,indicating that this approach creates a powerful in vitro system for modeling skin development and diseases.

Overview of Recombinant Skin Models and Progress in Their Application in Vitro Assessment of Toxicity and Efficacy

A recombinant skin model is a model in which skin cells are grown in vitro on a bioactive scaffold and provided with adequate nutrition to promote cell proliferation and differentiation to produce a mock skin structure and biological features. The development of recombinant skin models allows for effective and scientifically sound in vitro evaluation tests. This review briefly summarizes the overview of recombinant skin models and the progress of their application in in vitro evaluation which focuses on three aspects: skin irritation, skin corrosivity, and anti-skin aging. Moreover, an outlook on the future development of recombinant skin models is also provided in this review.

Validation of the Suitability of Stripped Lipid as a Skin Model in Plasma Medical Investigations

In this work, the suitability of lipid stripping as an alternative model of stratum corneum for plasma medical studies was investigated. Plasma treatment experiments were performed on samples prepared by the cyanoacrylat stripping method. Therefore, two different dielectric barrier discharge-based plasma sources driven by high-voltage pulses in the microsecond and nanosecond range were applied. The lipid sample heating, change in pH-value, and the interaction with plasma-induced UV-radiation are presented and discussed with respect to existing findings on skin samples. After the plasma treatment, the lipid stripping shows similar changes compared to human skin relating to sample heating and pH-value. The investigation of the interplay with UV- radiation shows a high absorption in the wavelength range of 250 nm up to 400 nm. Further, the thickness, surface structure, and composition of lipid stripping samples were determined. The stripped sample shows a thickness of 3 ± 1 μm whereby approximately 30% of the sample surface is covered by lipids. In addition, it was shown that there are no changes in structure caused by the sample preparation. Based on the results of this work, it can be stated that lipid stripping represents an appropriate skin model for plasma medical investigations.

Reconstruction of 3D Skin Model and Its Application in Evaluation the Efficacy of Cosmetic Raw Materials and Active Intredients

Via the use of Mimedisc~? as a scaffold, the normal human dermal fibroblasts were first seeding into the scaffold to form a dermal equivalent after three weeks, and then seeding normal human epidermal keratinocytes on it, followed by immersion and air-liquid interphase culture stage, to finally form a 3 D sponge matrix skin model which has a very similar structure of normal human skin(NHS). The results of Masson staining, and immunohistochemistry(IHC), immunofluorescence(IF) staininccg show that this skin model has a very similar structure and key protein expression of NHS. Meanwhile, this model was used as a tool to investigate the effect of Himalaya cedar extract on Dermal-Epidermal Junction(DEJ) in vitro. Results show that the Himalayan cedar extract can significantly increase the thickness of the epidermis, thus increase the barrier capacity of the skin to resist external environment. Further, this Himalaya cedar extract can promote the expressions of Laminin 5 and Collagen VII of DEJ. The expressions of the Laminin 5 and Collagen VII increased 20% and 47% respectively.So the Himalaya cedar extract displays the potential to be applied in development of anti-aging cosmetics.

Apple of Sodom (<em>Calatropis procera</em>) Callus Extract, a Novel Skincare Active and Its Biological Activity in Skin Models When Combined with Dead Sea Water

Background: Calotropis procera (C. procera), is an authentic plant naturally grown in the flora of Dead Sea region. Despite its toxicity, C. procera presents healing properties. However, it has not been implemented yet in cosmetics as an active ingredient. Objective: The biological effects of C. procera callus extract on skin were elucidated solely and in combination with Dead Sea water (DSW). Methods: The capability of C. procera extract to protect against skin inflammation and irritation was tested on ex vivo human skin organ culture by LPS and SDS addition respectively. Viability and cytokine secretion were evaluated. The combination of C. procera extract with Dead Sea water was tested on full thickness skin equivalents. Gene expression and relevant biochemical markers for glycolysis, hypoxia and extracellular matrix balance were tested. Results: C. procera extract exhibits a protective biological activity against skin irritation and inflammation at the biochemical level. Furthermore, a combination of C. procera extract and DSW demonstrates a potential contribution for skin wellbeing via enhance energy production, resistance to hypoxia and extracellular matrix balance. Conclusions: Topical application of C. procera callus extract might support skin balance and wellbeing at the molecular level. Hence, it is recommended for new cosmetic formulae as standalone or in combination with Dead Sea water, in the effort to achieve anti-aging bio-activity that is working beyond skin aging symptoms, especially via skin calming effects and skin energy enhancement.

Influence of Surface Topography on the Tactile Friction of Medical Compression Textiles against a Mechanical Skin Model

Influence of surface topography on the tactile friction of medical compression textiles was studied in this paper. The friction behavior was investigated for three kinds of medical textiles with various structures and compositions by using a textile friction analyzer under dry condition. In order to simulate the contacts of textiles/human finger, a mechanical skin model with similar texture to the skin and applied normal load oflN were selected. Meanwhile, the 3D surface topography of textiles was measured using a digital microscope. The topographical data were analyzed concerning height distribution and material ratio, and the real contact area was estimated as a function of penetration depth. Results showed that the investigated textiles revealed a significant variation on the friction coefficients, which were （ 0.41 ± 0.01 ） （ polyamide, jersey 2 × 2 ）, （0.56 ± 0. 01） （cotton, jersey 2×2） and （0. 47 ± 0. 01） （polyamide, jersey 1 × 1 ）, respectively. The textile with higher friction coefficient was found to own a relative compact and homogenous surface and larger contact area, vice versa.

Fingertip skin models for analysis of the haptic perception of textiles

This paper presents finite element models of the fingertip skin which have been created to simulate the contact of textile objects with the skin to gain a better understanding of the perception of textiles through the skin, the so-called hand of textiles. Many objective and subjective techniques have already been developed for analysing the hand of textiles;however, none of them provide exact overall information concerning the sensation of textiles through the skin. As the human skin is a complex heterogeneous hyperelastic body composed of many particles, some simplifications had to be made at the early stage of building the models;however, their utilitarian value was maintained. The models relate only to mechanical loading of the skin. They predict a low deformation of the fingertip skin under the pressure of virtual heterogeneous material: acrylic, coarse wool, and steel.

3D skin models along with skin-on-a-chip systems:A critical review

Skin is the largest organ in human body,and it plays an important role in regulating physiological microenvironments and acts as a barrier to protect human body from harmful intrusions.The demand for fully functional skin models(also called skin equivalents,SE)in an in-vivo mimicking culturing microenvironment has been increased dramatically due to the fast development in skin disease treatments and skin care products.Owing to the emerging of the concept and technology of organ-on-chips along with the three-dimensional(3D)bioprinting technology,3D skin models and their applications have been fast evolving.In this paper,the advances in the development of 3D skin models along with skin-on-a-chip(SOC)are reviewed and commented.One of the findings with this paper is that the SOC together with the 3D bioprinting technology is promising to construct fully functional 3D skin models in the field of pharmaceutical and cosmetic industries.

Establishment of Mus Skin Photo-damage Model by 8-MOP plus UVA Irradiation

To establish a simple and reliable animal model of skin photo-damage, 20 mice were treated with 8-MOP and exposed to UVA （UVA 320-400 nm） for 24 h. After irradiation, the structure of the epidermis and dermis, collagen fibers, elastic fibers were observed by using HE staining and Weigert technique and compared with the normal controls. The acanthosis and epidemis proliferation with accompanying hyperkeratosis and parakeratosis were observed. Inflammatory infiltration was noted in the dermis. The elastic fibers became coarse, irregularly arranged and clustered, with their number increased. The collagen fibers showed obvious degeneration and some amorphous materials could also be observed. The blood vessels were irregularly dilated and vascular walls were thickened, with infiltration of inflammatory cells. It is concluded that murine photodamage model can be quickly, conveniently and reliably established by means of 8-MOP/UVA.

3D Numerical Simulation of Epidermal Skin Turnover Process Using a Particle Model

Skin is the largest organ of the human body. In recent years, concern regarding the cosmetics area has increased, and research studies on anti-aging therapy or cosmetics have been rapidly conducted. Skin cells are not only changing its shape but also its physical properties during the epidermal skin turnover process. Computational simulation can be useful in further understanding the mechanisms of skin formation. We propose a particle model that can handle complex biological phenomena, including cell interactions and is a suitable method for simulating skin formation. The particle model was applied to simulate three-dimensional skin formation accompanied by proliferation and cornification of skin cells. The simulation results represented and reproduced the epidermal skin turnover phenomenon.

Use of Acellular Fish Skin for Dura Repair in an Ovine Model: A Pilot Study

Recently the use of biologic materials as dura mater repair patches has been increasing. The purpose of this study is to assess the basis for efficacy and safety of using a novel fish derived acellular dermis (Kerecis Omega3 DuraTM). In an ovine model a craniotomy under general anaesthesia was performed. A defect was produced in the dural covering of approximately 1 × 2 cm and closed with an onlay technique, with Kerecis Omega3 Dura. The bone defect was covered with the bony flap and the overlying tissues closed in layers. At 2, 5, 8 and 11 weeks the sheep underwent MRI scanning followed by euthanasia, necropsy and histological assessment. MRI images taken at 2, 5, 8 and 11 weeks showed initially moderate inflammatory response, which diminished over time, and at 11 weeks no evidence of inflammation existed. There was evidence of cerebrospinal fluid leakage at no time point. Necropsy revealed some adhesions at 5 and 8 weeks, in particular at 5 weeks, but at 11 weeks there were no adhesions found. From 2 - 11 weeks, there was evidence of initially an inflammatory reaction followed by neodura formation at the defect site through cellular ingrowth and remodeling of the acellular fish skin. Histology showed a histiocytic foreign body reaction initially that subsided over time. As early as 8 weeks there was evidence of neodura formation and by 11 weeks there was a minimal inflammatory response with an intact neodura formed. In this pilot study the Kerecis Omega3 Dura patches performed in a safe and efficacious manner. This new material needs to be fully assessed and compared with other products that are currently on the market in a larger scale animal study.

Nrf2 Pathway Involvement in the Beneficial Skin Effects of Moderate Ionic Osmotic Stress—The Case of The Dead Sea Water

Objectives: Exposing skin to moderate ionic osmotic stress (MIOS) triggers several biochemical responses. The objective of this work is to reveal the mechanism triggered by MIOS on the skin surface. Furthermore, this work aims to study the involvement of the Nrf2 (nuclear factor erythroid-2-related factor 2) pathway, activated by MIOS, and its beneficial effect in protecting skin against stress via the stimulation of phase II enzymes. Methods: HaCaT cells and human skin organ culture were exposed to Dead Sea Water (DSW) as MIOS inducers and the induction of internal ROS elevation, Nrf2 translocation, mRNA gene expressions of the phase II enzymes, heme-oxygenase 1 (HO1), and Catalase (CAT) were determined. Results: Skin exposure to MIOS increases Nrf2 translocation to the nucleus, leading to increased levels of ROS, HO1, and CAT. Furthermore, exposing skin to MIOS promotes protection against UVB-related risks. This is demonstrated by attenuation of the expression of biomarkers, related to UVB-induced damage, Caspase-3, IL-8, and IL-1β. Conclusions: Skin exposure to MIOS leads to the activation of Nrf2 skin defense pathway and, therefore, could present beneficial advantages to human skin health, as demonstrated on human skin models. The beneficial effects of MIOS, induced by DSW are significantly superior to eq. NaCl brine, suggests that MIOS protection of skin against stress is partially related to specific mineral combinations.

Edible Bird’s Nest, an Asian Health Food Supplement, Possesses Skin Lightening Activities: Identification of N-Acetylneuraminic Acid as Active Ingredient

Edible bird’s nest (EBN;Yan Wo), or cubilose, is originated from the salivary secretion of Aerodramus fuciphagus. In Asia, EBN is famous for its unproven skin lightening function. Here, we aim to reveal the active ingredients of EBN responsible for skin lightening function. Three major fractions were isolated from EBN water extract by chromatography using LC-MS/MS, bioactivities of these isolated fractions were analyzed by assays of tyrosinase, melanocytes and 3D human skin model, from which, N-acetylneuraminic acid (NANA), the second isolated fraction showed an inhibition effect on tyrosinase activity in a dose-dependent manner. The IC50 of tyrosinase originated from mushroom and human was 16.93 mM and 0.10 mM respectively. Furthermore, only EBN with higher content of NANA (e.g. White and Red EBN), but not EBN with less NANA (e.g. Grass EBN), showed promising skin lightening function. This is the first report to reveal NANA being an active ingredient of EBN on skin lightening function.

体外构建新型化妆品检测用皮肤InspectskinⅠ的初步研究

目的探讨ES源表皮干细胞（ESC）与高分子材料构建人工皮肤Inspectskin Ⅰ的方法，为化妆品皮肤毒性检验替代模型奠定基础。方法采用嵌入式培养法，先将3-羟基丁酸-co-3-羟基戊酸共聚物（PHBV）支架与原代小鼠成纤维细胞共培养5d构建真皮，再于表面放置ESC细胞，气-液界面培养7—10d，形态学和β1整合素、CK10、CK19免疫组化观察。结果成纤维细胞可在真皮支架内粘附，ESC细胞可在支架表面增殖分化形成含基底层、棘层和角化层的复层表皮结构，免疫组化表明基底层以上细胞中表达CK10明显增多，基底层有些细胞仍呈β1整合素和CK19阳性。结论Inspectskin Ⅰ替代皮肤模型是由ESC细胞分化形成的角化复层表皮结构和PHBV真皮结构共同构成的全层皮肤模型。

Numerical investigation into pillar failure induced by time-dependent skin degradation

This paper focuses on the instability mechanism of an isolated pillar, caused by time-dependent skin degradation and strength heterogeneity. The time-dependent skin degradation is simulated with a non-linear rheological model capable of simulating tertiary creep, whereby two different pillar failure cases are investigated. The first case is of an isolated pillar in a deep hard rock underground mine and subjected to high stresses. The results show that pillar degradation is limited to the regions near the surface or the skin until two months after ore extraction. Afterwards degradation starts to extend deeper into the pillar, eventually leaving a highly-stressed pillar core due to stress transfer from the failed skin.Rockburst potential indices show that the risk increases exponentially at the core as time goes by. It is then demonstrated that the progressive skin degradation cannot be simulated with conventional strain-softening model assuming brittle failure. The parametric study with respect to the degree of heterogeneity reveals that heterogeneity is key to the occurrence of progressive skin degradation. The second case investigated in this study is pillar failure taking place in a very long period. Such failure becomes significantly important when assessing the risk for ground subsidence caused by pillar collapse in an abandoned mine. The analysis results demonstrate that the employed non-linear rheological model can simulate gradual skin degradation taking place over several hundred years. The percentage of damage zone volume within the pillar is merely 1% after a lapse of one days and increases to 50% after one hundred years, indicating a high risk for pillar collapse in the long term. The vertical displacements within the pillar also indicate the risk of subsidence. The proposed method is suitable for evaluating the risk of ground surface subsidence above an abandoned mine.

Determination of the neutron skin thickness from interaction cross section and charge-changing cross section for B,C,N,O,F isotopes

The effective neutron and proton root-meansquare radius of stable and unstable nuclei(^(12-15,17)B,^(12-20)C,^(14-21)N,^(16-24)O and ^(18-21,23-26)F) were deduced from the charge-changing cross section,σ_(cc),and the interaction cross sections,σ_I,by using a statistical abrasion-ablation model calculation.The extracted proton radii are in good agreement with the data from the Atomic Data and Nuclear Data Tables within the errors.Furthermore,we can observe that the neutron skin thickness increases monotonously with the increasing neutron number in these isotopes,which is consistent with the systematical trend of theoretical calculations.

EpiSkin皮肤模型应用概述

本文主要综述了EpiSkin皮肤模型在化妆品刺激和腐蚀性能的动物替代试验中发挥的作用,同时也介绍了其构成及检测原理。