Human Skin Tissue Research Articles

The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation

The transcription factor ΔNp63 regulates epithelial stem cell function and maintains the integrity of stratified epithelial tissues by acting as transcriptional repressor or activator towards a distinct subset of protein-coding genes and microRNAs. However, our knowledge of the functional link between ∆Np63 transcriptional activity and long non-coding RNAs (lncRNAs) expression is quite limited. Here, we show that in proliferating human keratinocytes ∆Np63 represses the expression of the lncRNA NEAT1 by recruiting the histone deacetylase HDAC1 to the proximal promoter of NEAT1 genomic locus. Upon induction of differentiation, ∆Np63 down-regulation is associated by a marked increase of NEAT1 RNA levels, resulting in an increased assembly of paraspeckles foci both in vitro and in human skin tissues. RNA-seq analysis associated with global DNA binding profile (ChIRP-seq) revealed that NEAT1 associates with the promoter of key epithelial transcription factors sustaining their expression during epidermal differentiation. These molecular events might explain the inability of NEAT1-depleted keratinocytes to undergo the proper formation of epidermal layers. Collectively, these data uncover the lncRNA NEAT1 as an additional player of the intricate network orchestrating epidermal morphogenesis.

Ex Vivo Human Histology Fractional Treatment with a New CO2 Scanner: A Potential Application on Deep Scarring.

Background and Objectives: For many years, fully ablative laser treatments, particularly those performed with a carbon dioxide (CO2) laser, were regarded as the gold standard for resurfacing. This study's goal is to assess the depth that can be reached by a new CO2 scanner system, through a skin model with greater dermal thickness, to use in the treatment of deep scarring. Materials and Methods: Male human skin tissue was laser-treated using a CO2 fractional laser and a new scanning system, and all samples were fixed in 10% neutral buffered formalin, dehydrated using a series of crescent alcohol, embedded in paraffin, sectioned in series (4-5 µm thick), stained with haematoxylin and eosin (H&E), and then analysed under an optical microscope. Results: From the epidermis through the underlying papillary and reticular dermis to various depths of the dermis, microablation columns of damage and coagulated microcolumns of collagen were observed. The reticular dermis was fully penetrated up to 6 mm at higher energy levels (210 mJ/DOT), resulting in deeper tissue injury. Although the laser might penetrate further, the skin stops there, leaving just the fat and muscular tissue. Conclusions: The deep layers of the dermis can be penetrated by the CO2 laser system throughout the entire dermal thickness when using the new scanning system, suggesting that this laser's potential impact, at the selected settings, covers all skin targets required to perform superficial or deep treatments on any dermatological issue. Finally, patients who have problems, such as morbid scar-deep complications, which affect their quality of life, are more likely to profit from this innovative technique.

Active iodine regulated in cow dung biochar-based hydrogel combined with PDT/PTT for MRSA infected wound therapy

Iodine has been successed in combating bacteria over a century, but its toxic effects on human skin tissues and cells have been overlooked. In this work, a cow dung biochar-based polyvinyl alcohol/polyvinylpyrrolidone hydrogel (BCPP) was designed to in situ produce iodine on-demand and regulate its release via the light triggering strategy for the infected wound therapy. Benefiting from the reactive oxygen species (ROS) generation and the photothermal conversion properties of cow dung biochar (BC), the as-prepared hydrogel in situ transformed iodide into active iodine under the visible (Vis) light irradiation and regulated the release of active iodine under the near-infrared (NIR) light irradiation. The active iodine combined with photodynamic and photothermal effects of BCPP endowed hydrogel excellent antibacterial effects on ampicillin-resistant Escherichia coli (AREC) and methicillin-resistant Staphylococcus aureus (MRSA) while showing low toxicity to the mammalian cells. The in vivo wound therapy test results demonstrated that this hydrogel resisted MRSA infection, accelerated the healing process, and promoted epithelial regeneration.

Engineered Human Tissue as A New Platform for Mosquito Bite-Site Biology Investigations.

Vector-borne diseases transmitted through the bites of hematophagous arthropods, such as mosquitoes, continue to be a significant threat to human health globally. Transmission of disease by biting arthropod vectors includes interactions between (1) saliva expectorated by a vector during blood meal acquisition from a human host, (2) the transmitted vector-borne pathogens, and (3) host cells present at the skin bite site. Currently, the investigation of bite-site biology is challenged by the lack of model 3D human skin tissues for in vitro analyses. To help fill this gap, we have used a tissue engineering approach to develop new stylized human dermal microvascular bed tissue approximates-complete with warm blood-built with 3D capillary alginate gel (Capgel) biomaterial scaffolds. These engineered tissues, termed a Biologic Interfacial Tissue-Engineered System (BITES), were cellularized with either human dermal fibroblasts (HDFs) or human umbilical vein endothelial cells (HUVECs). Both cell types formed tubular microvessel-like tissue structures of oriented cells (82% and 54% for HDFs and HUVECs, respectively) lining the unique Capgel parallel capillary microstructures. Female Aedes (Ae.) aegypti mosquitoes, a prototypic hematophagous biting vector arthropod, swarmed, bit, and probed blood-loaded HDF BITES microvessel bed tissues that were warmed (34-37 °C), acquiring blood meals in 151 ± 46 s on average, with some ingesting ≳4 µL or more of blood. Further, these tissue-engineered constructs could be cultured for at least three (3) days following blood meal acquisitions. Altogether, these studies serve as a powerful proof-of-concept demonstration of the innovative BITES platform and indicate its potential for the future investigation of arthropod bite-site cellular and molecular biology.

Analysis of optical absorption of photoaged human skin using a high-frequency illumination microscopy analysis system.

Skin is composed of different layers, including the stratum corneum, epidermal living layer and papillary and reticular dermis. Each has specific optical properties due to differences in their biological components. Alterations in the skin's cutaneous biological components resulting from photoaging caused by chronic exposure to UV light affect the deterioration of appearance associated with the skin's optical properties. Various methods for analysing cutaneous optical properties have been previously proposed, including mathematical models and computer simulations. However, these were insufficient to elucidate changes in each skin layer and comprehensively understand the skin's integrated optical properties. We focused on UV-induced yellowing of the facial skin. We evaluated site-specific optical absorption of human skin tissue sections to investigate the yellowish discoloration, which is suggested to be related to the photodamage process. The method includes our original technique of separating the transmitted and scattered light using high-frequency illumination microscopy, leading to microscopic analysis of the tissue's optical absorption in the regions of interest. In analysing the sun-exposed facial skin tissue sections, we successfully showed that dermal regions of aged skin have increased absorption at 450 nm, where yellowish colours are complemented. Furthermore, we confirmed that elastic fibres with observable histological disorder resulting from photodamage are a prominent source of high optical absorption. We detected changes in the skin's optical absorption associated with dermal degeneration resulting from photodamage using a novel optical microscopy technique. The results provide a base for the evaluation of optical property changes for both yellowing discoloration and other tissue disorders.

Amendments of weld formation in human skin laser soldering.

A computational modeling is employed for quantitative assessment of weld formation and area of tissue temperature necrosis during the human skin laser soldering. The evaluation is carried out depending on the components composition of using solders, including bovine serum albumin (BSA), indocyanine green (ICG), and carbon nanotubes (CNT), as well as the angle of incidence of laser light and its pulse duration. The influence of CNT on the change of thermodynamic characteristics of albumin denaturation and the rate of formation of the laser weld is investigated. The obtained results suggest to limit the duration of laser light pulse by temperature relaxation time to minimize transfer of thermal energy to reduce the heating of human skin tissues. The developed model has a great potential for further optimization of laser soldering of biological tissues technology with greater efficiency in minimizing the weld area. This article is protected by copyright. All rights reserved.

Distinguishing Malignant Melanoma and Benign Nevus of Human Skin by Retardance Using Mueller Matrix Imaging Polarimeter

Malignant melanoma is considered the most serious type of skin cancer. In clinical practice, the conventional technique based on subjective visual examination has a high rate of misdiagnosis for malignant melanoma and benign nevus. Polarization imaging techniques have great potential in clinical diagnosis due to the advantages of improving sensitivity to functional structures, such as microfiber. In this paper, a set of human skin tissue sections, including 853 normal, 851 benign nevus, and 874 malignant melanoma, were analyzed and differentiated using a homemade high-fidelity Mueller matrix imaging polarimeter. The quantitative result using support vector machine algorithms confirmed that, while scalar retardance yields lower accuracy rates, vectorial retardance results in greater accuracy for both the training and testing sets. In particular, the cross-validation accuracy for the training set increased from 88.33% to 98.60%, and the prediction accuracy for the testing set increased from 87.92% to 96.19%. This tackles the limitation of the examination based on clinical experience and suggests that vectorial retardance can provide more accurate diagnostic evidence than scalar retardance. Unfortunately, it is inconvenient and time-consuming to read and analyze each component of the vectorial retardance simultaneously in the qualitative assessment. To address this clinical challenge, a color-encoded vectorial retardance imaging method was implemented. This method can provide superior tissue-specific contrast and more fiber details than scalar retardance. The anisotropic microfiber variation among different skin lesions, including the orientation and distribution, can be clearly highlighted. We believe that this work will not only enable early and rapid diagnosis of skin cancer but also provide a good observation and analysis of the state of cancer progression.

Numerical study on the blocking effect of skin on Flash-Ball Impact and damage assessment

To explore the response law of non-lethal large-size kinetic energy projectiles to blunt attack on skin tissue, and to evaluate the skin injury characteristics of the attacked personnel and the use safety of kinetic energy projectiles. Based on the LS-DYNA simulation software, a three-layer skin simulation model and a Flash-Ball rubber bullet model are established, and the force-time and deformation-time biomechanical corridors of the Flash-Ball rubber bullet impacting human skin tissue are obtained. The corridor curve and the energy transfer and diffusion are analyzed and compared. The safety evaluation of the damage caused by the rubber bullet shooting a human body at different distances is carried out using the empirical formula of the penetration limit. Finally, the safe shooting distance is obtained. The results show that the model used in the simulation has a good correlation with the experimental data, its biomechanical corridor characteristics are different from those of conventional vehicle impact and small-size projectile response characteristics. The energy transfer and action time of medium and low-speed impact may cause greater damage. The fat layer is the largest energy absorption unit. The minimum safe shooting distance to ensure skin tissue from penetrating damage is 15.8 m, and the limit specific kinetic energy of skin damage is 7.88 J/cm2. This study can be extended to the study of biomechanical response law and safety evaluation under the impact of the same type of large kinetic energy projectile, which provides an important theoretical reference for the police to use large kinetic energy projectiles to conduct safe shooting in peacekeeping operations.

Innovative Rocuronium Bromide Topical Formulation for Targeted Skin Drug Delivery: Design, Comprehensive Characterization, In Vitro 2D/3D Human Cell Culture and Permeation.

Cutaneous squamous cell carcinoma (cSCC) is the second-most common type of non-melanoma skin cancer and is linked to long-term exposure to ultraviolet (UV) radiation from the sun. Rocuronium bromide (RocBr) is an FDA-approved drug that targets p53-related protein kinase (PRPK) that inhibits the development of UV-induced cSCC. This study aimed to investigate the physicochemical properties and in vitro behavior of RocBr. Techniques such as thermal analysis, electron microscopy, spectroscopy and in vitro assays were used to characterize RocBr. A topical oil/water emulsion lotion formulation of RocBr was successfully developed and evaluated. The in vitro permeation behavior of RocBr from its lotion formulation was quantified with Strat-M® synthetic biomimetic membrane and EpiDerm™ 3D human skin tissue. Significant membrane retention of RocBr drug was evident and more retention was obtained with the lotion formulation compared with the solution. This is the first systematic and comprehensive study to report these findings.

The therapeutic role of fibronectin in the re-epithelialization response following wounding in a human skin/mouse xenografting model

Abstract The atopic environment diminishes wound re-epithelialization and the defect in the wound healing process is IL-4 dependent. IL-4 represses fibronectin secretion from keratinocytes and impairs the ability of keratinocytes in culture to migrate into a scratch and to close a wound in vivo. Addition of fibronectin to culture increased closure of the scratch assay in vitro and re-epithelialization of wound tissue in vivo when fibronectin was applied topically. In this study, a human skin/mouse xenografting model was used to test the ability of IL-4 to impair re-epithelialization in human skin and to test whether fibronectin can mitigate the effects of IL-4. Human skin was grafted onto immunodeficient SCID/NOD mice. Approximately 10–12 weeks post-transplantation, human skin was fully integrated onto the mouse. A shallow punch biopsy was performed on the human skin to generate a wound that did not penetrate into mouse tissue. Human IL-4 was intravenously injected twice a week before the punch and recombinant fibronectin was spread over the wound twice daily after the wounding. Anatomic wound healing was monitored, and EDC gene expression and skin histology were assessed. Our results showed that mice injected with human IL-4 had delayed wound healing, decreased human EDC gene expression and increased MMP19 and CCL26 expression in human skin tissue. Treatment of skin with fibronectin attenuated the effect of IL-4 on human gene expression and promoted wound healing and re-epithelialization. These results suggest that fibronectin has a potential therapeutic role in the treatment of atopic lesions. Supported by grants from NIH (R01AI095282)

Effect of Mechanical Tension on the Long-Chain Noncoding RNA Expression Profile of Human Skin Regeneration.

This study investigates the potential gene regulation of long-chain noncoding RNAs (lncRNAs) during skin regeneration by analyzing the changes in the lncRNA expression profile during skin regeneration under mechanical tension. Through the effect of mechanical tension on human skin tissue, the authors observed that after the accelerated differentiation and proliferation of skin epidermal cells, the lncRNA expression profile was compared with that of normal epidermal cells, and differential expression of lncRNA in skin tissue was found. Fifty-three lncRNAs were differentially expressed between the experimental and control groups, and compared with the control group, 22 lncRNAs were upregulated and 31 lncRNAs were downregulated in the experimental group. In addition, through the annotation of the functions of gene ontology and kyoto encyclopedia of genes and genomes, it was further clarified that the main signaling pathway of lncRNAs in the process of skin tissue expansion is involved in the regulation of skin tissue regeneration, and the regulatory network of lncRNAs and microRNAs was established. The results of this study will provide a theoretical basis for the mechanism of lncRNA regulation of skin regeneration, and changes in the lncRNA expression profile can also provide clues for the study of the biological regulation mechanism of skin regeneration.

357 Bioengineered human ageing skin tissue: A new in vitro platform to investigate the biology of ageing skin and restore skin health

357 Bioengineered human ageing skin tissue: A new in vitro platform to investigate the biology of ageing skin and restore skin health

Skin wound healing effects of (+)-syringaresinol from ginseng berry

BackgroundGinseng has been used as a traditional medicine and functional cosmetic ingredients for many years. Recent studies have focused on the potential biological effects of the ginseng berry and its ingredients. (+)-Syringaresinol (SYR) is enriched in ginseng berry and its beneficial effects on the skin have been recently reported. However, little is known about the its effects on the wound healing process of skin. MethodsHere, we evaluated the skin wound healing effect of (+)-SYR using the human fibroblast Hs68 cell and ex vivo pig and human skin tissue model. Scratch wound test and hydrogen peroxide (HPO) induce chemical wound model were employed. Results(+)-SYR promoted the migration and proliferation of Hs68 cells without significant cytotoxicity at the tested concentrations. Especially, in ex vivo pig and human skin tissue, HPO-induced chemical wound was recovered almost completely by (+)-SYR. In line with the finding in Hs68, the protein expression levels of TGF-β and PCNA, a proliferation marker were increased, demonstrating the beneficial effects of (+)-SYR on skin wound repair. ConclusionCollectively, we demonstrated that (+)-SYR from ginseng berry, can enhance the wound healing effect by accelerating cell proliferation and skin regeneration, suggesting the potential utility of (+)-SYR for skin wound repair.

Optical Properties of Human Skin Phototypes and Their Correlation with Individual Angle Typology

Objective: This study aims to correlate human skin phototypes with complete optical characterization (absorption, scattering, effective attenuation, optical penetration, and albedo coefficients) based on individual typology angle (ITA) values and colorimetric parameters. Methods: A colorimeter was used to group 12, fresh, ex vivo human skin samples according to their phototype; the CIELAB color scale and ITA values were employed. An integrating sphere system and the inverse adding-doubling algorithm were applied during optical characterization, conducted from 500 to 1300 nm. Results: On the basis of ITA values and their classification, the skin samples were separated into six groups: two intermediates, two tan, and two brown. In the visible range, for lower ITA values (darker skins), the absorption and effective attenuation coefficient parameters increased, whereas the albedo and depth penetration parameters decreased. In the infrared region, all the phototypes had similar parameters. The scattering coefficient was similar for all the samples and did not change with ITA values. Conclusions: ITA analysis, a quantitative method, showed that the human skin tissue's optical properties and pigmentation colors were highly correlated.

Topical Application of Peptide Nucleic Acid Antisense Oligonucleotide for MMP-1 and Its Potential Anti-Aging Properties

Matrix metalloproteinase-1 (MMP-1) is a zinc-containing endopeptidase that degrades dermal collagen and other extracellular matrix molecules. It is recognized as one of the most important indicators of cellular senescence and age-related skin changes. Here, we introduced a novel MMP-1 peptide nucleic acid (PNA) derivative-PNA-20 carboxyethyl fluorene (CEF)-which can interact with and consequently silence the MMP-1 gene sequence. The investigation on the efficacy of PNA-20 CEF in MMP-1 silencing in human dermal fibroblasts revealed significantly decreased expression of MMP-1 at both gene and protein levels. Treatment with PNA-20 CEF showed significantly increased expression of collagen I protein, indicating its potential role in preventing the degradation of collagen I and consequently combating the skin aging process. Its topical application on 3D human skin tissue showed successful absorption into the epidermis and the upper dermis. Furthermore, the additional 4-week single-arm prospective study on 21 Asian women revealed improvements in facial wrinkles, skin moisture, elasticity, and density after the use of the topical PNA-20 CEF cosmeceutical formulation. Additional in-vitro and ex-vivo studies are needed for a comprehensive understanding of the skin anti-aging effects of MMP-1 PNA.

Lung adenocarcinoma presenting with eosinophilic erythroderma associated with anti‐KRT6B antibodies: Case report

AbstractParaneoplastic erythroderma (PE) is a rare and potentially life‐threatening inflammatory condition associated with malignancy. PE may potentially develop due to antibodies produced against tumoral antigens that cross‐react with epidermal structures. We report a patient with paraneoplastic eosinophilic erythroderma associated with lung adenocarcinoma. Erythroderma and eosinophilia subsided after wedge‐resection of the tumour. To tackle the pathogenesis of PE in this patient, we performed western blot analysis (WB) using healthy human skin tissue lysate and the patient's serum. Samples were analysed first by immunoprecipitation of autoantibody‐target protein complexes and mass spectrometry to reveal the corresponding protein. After incubating patient serum with skin proteins, in WB, we could observe a distinct band around 60 kD. Later, immunoprecipitation for mass spectrometry showed a bar in the same area which was not present in healthy controls. Mass spectrometric analysis revealed that KRT6B might be the potential target protein. In this patient with PE, which resolved after surgical removal of lung adenocarcinoma, the antibody production to tumoral antigens cross‐reacting with keratins in skin may have initiated the dermatitis.

Fiber-based quantum-dot pulse oximetry for wearable health monitoring with high wavelength selectivity and photoplethysmogram sensitivity

Increasing demand for real-time healthcare monitoring is leading to advances in thin and flexible optoelectronic device-based wearable pulse oximetry. Most previous studies have used OLEDs for this purpose, but did not consider the side effects of broad full-width half-maximum (FWHM) characteristics and single substrates. In this study, we performed SpO2 measurement using a fiber-based quantum-dot pulse oximetry (FQPO) system capable of mass production with a transferable encapsulation technique, and a narrow FWHM of about 30 nm. Based on analyses we determined that uniform angular narrow FWHM-based light sources are important for accurate SpO2 measurements through multi-layer structures and human skin tissues. The FQPO was shown to have improved photoplethysmogram (PPG) signal sensitivity with no waveguide-mode noise signal, as is typically generated when using a single substrate (30–50%). We successfully demonstrate improved SpO2 measurement accuracy as well as all-in-one clothing-type pulse oximetry with FQPO.

Simulation and analysis of heat transfer performance of electrical heating fabric at low temperature based on skin tissue

PurposeAt present, electrical heating clothing is widely used to keep ourselves warm at low temperature. The purpose of this paper is to explore the heat transfer performance of electrical heating fabric and the thermal comfort of human skin at low temperature.Design/methodology/approachThe combined model of skin-electrical heating fabric system was established to simulate human skin tissue wearing electrical heating clothing. A series of simulation experiments are designed on the basis of verifying the effectiveness of the combined model. The temperature distribution inside the combined model and on the skin surface under different heating powers is simulated and analyzed. At the same time, the influence of ambient temperature on the thermal performance of electrical heating fabric was explored.FindingsThe skin model with blood vessels reflected the temperature change of human skin wearing electrical heating clothing. The higher the heating power of the electrical heating fabric was, the greater the temperature of the skin surface changed, the faster the temperature rose and the longer the time required to reach the stable state would be. After the heating element was electrified, it had the greatest effect on the average temperature of the epidermis and dermis, had smaller effect on the average temperature of subcutaneous layer and had little effect on the temperature of blood vessels. When the heating power was the same, the higher the ambient temperature was, the more obvious the heating effect of electrical heating fabric was. Electrical heating fabrics with different heating powers were suitable for different ambient temperature ranges.Originality/valueA reasonable and effective evaluation method for the thermal comfort of electrical heating fabric was provided by establishing the skin model and combined model of the skin-electrical heating fabric system. It provides a reference for the design and application of electrical heating clothing.

A Fiber Optic Sensor for Monitoring the Spectral Alterations and Depth in Ex Vivo and In Vivo Cryosurgery

This article discusses how to monitor the freezing depth during cryotherapy using a fiber optic array sensor. The sensor was used to measure the backscattered and transmitted light from frozen and unfrozen ex vivo porcine tissue and in vivo human skin tissue (finger). The technique exploited the variations in optical diffusion properties of the frozen and unfrozen tissues to determine the extent of freezing. Ex vivo and in vivo measurements yielded comparable results, despite spectral variations attributable to the hemoglobin absorption peak in the human frozen and unfrozen tissues. However, because the spectral fingerprints of the freeze-thaw process in the ex vivo and in vivo experiments were similar, we could extrapolate the maximum depth of freezing. Therefore, this sensor has the potential to be utilized for monitoring cryosurgery in real time.

Multilayer In Vitro Human Skin Tissue Platforms for Quantitative Burn Injury Investigation.

This study presents a multilayer in vitro human skin platform to quantitatively relate predicted spatial time-temperature history with measured tissue injury response. This information is needed to elucidate high-temperature, short-duration burn injury kinetics and enables determination of relevant input parameters for computational models to facilitate treatment planning. Multilayer in vitro skin platforms were constructed using human dermal keratinocytes and fibroblasts embedded in collagen I hydrogels. After three seconds of contact with a 50-100 °C burn tip, ablation, cell death, apoptosis, and HSP70 expression were spatially measured using immunofluorescence confocal microscopy. Finite element modeling was performed using the measured thermal characteristics of skin platforms to determine the temperature distribution within platforms over time. The process coefficients for the Arrhenius thermal injury model describing tissue ablation and cell death were determined such that the predictions calculated from the time-temperature histories fit the experimental burn results. The activation energy for thermal collagen ablation and cell death was found to be significantly lower for short-duration, high-temperature burns than those found for long-duration, low-temperature burns. Analysis of results suggests that different injury mechanisms dominate at higher temperatures, necessitating burn research in the temperature ranges of interest and demonstrating the practicality of the proposed skin platform for this purpose.