Damage To Human Skin Research Articles

The fed-batch production of mannosylerythritol lipids by Ustilago maydis DSM 4500 from hydrophilic carbon sources

Glycolipids are a class of widely studied biosurfactants with excellent applicability in cosmetic and pharmaceutical formulations. This class of biosurfactants includes mannosylerythritol lipids (MELs), which have gained particular interest due to their moisturizing and healing activity for dry and damaged human skin, arising from conditions such as eczema. Traditionally, MELs have been produced by growing certain basidiomycetous yeasts on vegetable oils. However, oils are a comparatively expensive substrate, which negatively affects the economic performance of MEL production. In addition to this, vegetable oils significantly complicate the downstream processing required to produce a product with the required purity for most applications. To address these challenges, this study investigated MEL-A production exclusively from hydrophilic carbon sources by Ustilago maydis DSM 4500. By implementing a fed-batch production strategy, maximum MEL-A concentration of 0.87 g/L was achieved from glucose exclusively. Also, adding micronutrients (such as MnSO4) to MEL-A production showed a 24.1% increase in the product titer, implying other metabolites are formed, favoring MEL production.

Multiclass skin lesion classification using deep learning networks optimal information fusion

A serious, all-encompassing, and deadly cancer that affects every part of the body is skin cancer. The most prevalent causes of skin lesions are UV radiation, which can damage human skin, and moles. If skin cancer is discovered early, it may be adequately treated. In order to diagnose skin lesions with less effort, dermatologists are increasingly turning to machine learning (ML) techniques and computer-aided diagnostic (CAD) systems. This paper proposes a computerized method for multiclass lesion classification using a fusion of optimal deep-learning model features. The dataset used in this work, ISIC2018, is imbalanced; therefore, augmentation is performed based on a few mathematical operations. After that, two pre-trained deep learning models (DarkNet-19 and MobileNet-V2) have been fine-tuned and trained on the selected dataset. After training, features are extracted from the average pool layer and optimized using a hybrid firefly optimization technique. The selected features are fused in two ways: (i) original serial approach and (ii) proposed threshold approach. Machine learning classifiers are used to classify the chosen features at the end. Using the ISIC2018 dataset, the experimental procedure produced an accuracy of 89.0%. Whereas, 87.34, 87.57, and 87.45 are sensitivity, precision, and F1 score respectively. At the end, comparison is also conducted with recent techniques, and it shows the proposed method shows improved accuracy along with other performance measures.

Native human and mouse skin infection models to study Candida auris-host interactions

The World Health Organization (WHO) declared certain fungal pathogens as global health threats for the next decade. Candida auris (C. auris) is a newly emerging skin-tropic multidrug-resistant fungal pathogen that can cause life-threatening infections of high mortality in hospitals and healthcare settings. Here, we address an unmet need and present novel native ex vivo skin models, thus extending previous C. auris-host interaction studies. We exploit histology and immunofluorescence analysis of ex vivo skin biopsies of human adult and fetal, as well as mouse origin infected with C. auris via distinct routes. We demonstrate that an intact skin barrier efficiently protects from C. auris penetration and invasion. Although C. auris readily grows on native human skin, it can reach deeper layers only upon physical disruption of the barrier by needling or through otherwise damaged skin. By contrast, a barrier disruption is not necessary for C. auris penetration of native mouse skin. Importantly, we show that C. auris undergoes morphogenetic changes upon skin penetration, as it acquires pseudohyphal growth phenotypes in deeper human and mouse dermis. Taken together, this new human and mouse skin model toolset yields new insights into C. auris colonization, adhesion, growth and invasion properties of native versus damaged human skin. The results form a crucial basis for future studies on skin immune defense to colonizing pathogens, and offer new options for testing the action and efficacy of topical antimicrobial compound formulations.

Nuclear and Urinary Measurements Show the Efficacy of Sun-Protection Factor 50+ Sunscreen against DNA Photoproducts upon Real-Life Recreational Exposure

Sunscreens have been shown to protect against UVR-induced DNA damage in human skin under laboratory conditions. We presently extended these observations to real-life conditions in volunteers after their ordinary exposure habits during summer holidays. Volunteers were randomly assigned to a control group and an educated group supplied with a SPF ≥50 sunscreen and receiving instructions for use. A questionnaire was used to determine the extent of exposure. No difference in average solar UVR exposure was found between the two groups. DNA photoprotection was first assessed by, to our knowledge, a previously unreported noninvasive assay on the basis of the quantification of pyrimidine dimers released by DNA repair in urine. Damage was also quantified in the nuclear DNA extracted from the roof of suction blisters collected after recreational exposure. The urinary concentration of photoproducts was significantly higher in the control than in the educated group. The same trend was observed for the level of photoproducts in the DNA from suction blisters. The unambiguous observation of an efficient photoprotection against DNA damage afforded by sunscreen under real-life conditions provides strong support for the efficiency of the sunscreens. In addition, the results validate the use of urinary DNA photoproducts as a noninvasive assay applicable to photoprotection.

Rg3-loaded P407/CS/HA hydrogel inhibits UVB-induced oxidative stress, inflammation and apoptosis in HaCaT cells

UVB radiation can damage human skin, whereas Ginsenoside Rg3, the active ingredient in red ginseng that is processed from ginseng (Panax ginseng C.A. Meyer), could inhibit UVB induced cell damage through anti-oxidation. Meanwhile, P407/CS/HA hydrogel has significant biomedical applications as carriers of drugs. However, the beneficial effects of Rg3-loaded hydrogel (Rg3-Gel) on human HaCaT keratinocytes induced by UVB have rarely been reported. In our study, Rg3 was loaded into hydrogel and the effect of Rg3-Gel against UVB‑induced Hacat cells damages was determined by measuring its ability to alleviate UVB‑induced elevation of oxidative stress, pro-inflammatory and apoptotic response. We found that the treatment with Rg3-Gel inhibited the generation of intracellular ROS and MDA and upregulated the expression of antioxidant enzymes SOD and GSH-Px which were inhibited by UVB exposure. Increased levels of pro-inflammatory cytokines TNF‑α, COX‑2, iNOS and IL‑1β following UVB irradiation were suppressed by the introduction of Rg3-Gel. Additionally, the level of Bcl-2 was decreased and the expression of Bax and Caspase3 were enhanced by Rg3-Gel treatment. In conclusion, Rg3-Gel equipped with the synergistic effect of Rg3 and hydrogel has an effective inhibitory effect on UVB-induced oxidative stress, inflammatory and apoptosis.

Self-powered high-performance ultraviolet C photodetector based on poly(9-vinyl carbazole)/SnO2 quantum dot heterojunction

Ultraviolet C (UVC) photodetectors have attracted significant attention recently owing to the importance of UVC detection for preventing human skin damage, monitoring environmental conditions, detecting power facility aging, and military applications. The “solar-blindness” of UVC detectors ensures low noise levels, benefiting from lower interference than other environmental signals. In this study, a solution-processed PN heterojunction consisting of P-type polymer (poly(9-vinyl carbazole) (PVK)) and N-type metal oxide quantum dots (SnO2 QDs) was used to develop a self-powered high-performance UVC photodetector. Reducing the size of the SnO2 QDs significantly enhanced the selective absorption of the UVC wavelength range via quantum confinement. The device architecture and constituent film thickness were carefully controlled to enhance the performance of the PVK/SnO2 QD UVC photodetector. Under the optimized conditions, the device exhibited remarkable responsivity (49.6 mA W−1 at 254 nm and 166 mA W−1 at 220 nm), detectivity (2.16 × 1010 Jones at 254 nm), UVC/ultraviolet A (UVA) rejection ratio (R254 nm/R365 nm and R220 nm/R365 nm of ~260 and 880, respectively), and stability over long-term self-powered on/off operations. Our solar-blind UVC photodetector can be used to inexpensively, simply, and precisely monitor hazardous UVC light in various applications.

Improvement of irradiation-induced fibroblast damage by α2-macroglobulin through alleviating mitochondrial dysfunction

Context α2-Macroglobulin (α2-M) is believed to be a potential anti-irradiation agent, but related mechanisms remains unclear. Objective We investigated the irradiation protective effect of α2-M. Materials and methods A total of 10 Gy dose of irradiation was used to damage human skin fibroblasts. The influence of α2-M (100 µg/mL) on the proliferation, migration, invasion and apoptosis of fibroblasts was observed using Cell Counting Kit-8 (CCK8), wound healing, transwell, and flow cytometry. Malondialdehyde, superoxide dismutase and catalase was measured using related ELISA kits. The levels of mitochondrial membrane potential and calcium were detected using flow cytometry. The expression of transient receptor potential melastatin 2 (TRPM2) was investigated through western blotting and immunofluorescence staining. Results High purity of α2-M was isolated from Cohn fraction IV. α2-M significantly increased cell proliferation, migration, invasion, but suppressed cell apoptosis after irradiation. The promotion of cell proliferation, migration and invasion by α2-M exceeded over 50% compared group irradiation. The increased cell ratio in the S phase and decreased cell ratio in the G2 phase induced by irradiation were remarkably reversed by α2-M. α2-M markedly suppressed the increased oxidative stress level caused by irradiation. The mitochondrial damage induced by irradiation was improved by α2-M through inhibiting mitochondrial membrane potential loss, calcium and TRPM2 expression. Discussion and conclusions α2-M significantly promoted the decreased fibroblast viability and improved the mitochondria dysfunction caused by irradiation. α2-M might present anti-radiation effect through alleviating mitochondrial dysfunction caused by irradiation. This study could provide a novel understanding about the improvement of α2-M on irradiation-induced injury.

106 Luminate - a non-invasive, high-throughput genomic test for assessment of UV damage in human skin

Extensive ultraviolet (UV) exposure has been shown to damage DNA leading to genetic mutations, immune suppression and photoaging. Moreover, non-melanoma skin cancer such as basal, and squamous cell carcinoma arise from the colonization of cells bearing mutations caused by UV exposure. Luminate combines non-invasive skin sample collection using the DermTech Smart StickerTM and the high-throughput, ultrasensitive, multiplexed detection of low-frequency mutations based on MALDI-TOF mass spectrometry (MS).

Preventative effects of antioxidants on changes in sebocytes, outer root sheath cells, and Cutibacterium acnes-pretreated mice by particulate matter: No significant difference among antioxidants.

ObjectivesParticulate matter (PM) is an air pollutant that can damage human skin; antioxidants have shown some efficacy in alleviating PM-induced skin inflammation. We investigated the antioxidant effects of punicalagin, epigallocatechin-3-gallate (EGCG), and resveratrol on PM-induced changes in cultured human sebocytes, outer root sheath (ORS) cells, and Cutibacterium acnes-pretreated mice.MethodsSebocytes and ORS cells were cultured with 100 μg/mL PM10 and 5 μM punicalagin, 1 μM EGCG, or 1 μM resveratrol for 24 h. In C. acnes-pretreated mice, inflammatory nodules were treated with 100 μg/mL PM10 and 5 μM punicalagin, 1 μM EGCG, or 1 μM resveratrol. Cell viability was measured using an MTT assay. Antioxidant effects were analyzed according to RNA expression, using real-time PCR, as well as reactive oxygen species (ROS) and sebum measurements.ResultsAntioxidants inhibited the upregulation of inflammatory cytokines, matrix metalloproteinase, aryl hydrocarbon receptor, and NF-kB as well as the production of ROS induced by PM10 in cultured sebocytes and ORS cells. The preventative effects of punicalagin and EGCG on biomarker expression in cultured sebocytes and ORS cells were slightly greater than those of resveratrol, though the difference was not significant. In C. acnes-pretreated mice, the antioxidants inhibited inflammatory cytokine and matrix metalloproteinase expression as well as sebum production.ConclusionsAntioxidants effectively reduced the expression of inflammatory biomarkers and sebum production in cultured sebocytes, ORS cells, and C. acnes-pretreated mice.

UPAYA PENINGKATAN PRODUKTIVITAS GETAH PINUS (Pinus merkusii) MENGGUNAKAN STIMULANSIA EKSTRAK LENGKUAS (Alpinia galanga) DAN JAHE (Zingiber officinale)

With the increasing world demand for pine resin, one of the efforts that can be made to increase the production of pine resin is to use stimulants of sap / stimulants. So far, in the activity of tapping pine sap, inorganic stimulants are used, but the main components are sulfuric acid and nitric acid or a mixture of which is a strong oxidizing agent that can damage human skin, wood and the environment if used in the long term and excessively. Alternative use of stimulants from natural ingredients that are safe, relatively inexpensive, and easy to obtain, such as galangal (Alpinia galanga) and ginger (Zingiber officinale). This research was conducted to determine the effect of stimulant administration of galangal and ginger extracts on increasing the productivity of pine sap. The results of this study showed that the highest sap productivity was produced by pine trees using ginger organic stimulants with a 50% concentration of 11.15 g / koakan / day. The quality of pine sap that has the best quality is produced by the stimulant of ginger, while the use of the stimulant of galangal has second quality based on SNI 7837: 2016.

Effects of

BackgroundParticulate matter (PM) is one of the air pollutants that can damage human skin; the recent increase in the amount of PM may be detrimental to skin health.ObjectiveWe aimed to investigate the effects of PM on cultured human sebocytes and outer root sheath (ORS) cells and the effects of Siegesbeckia Herba extract (SHE) on PM-treated cultured cells.MethodsSebocytes and ORS cells were cultured. The cultured cells were treated with various concentrations of PM of <10 µm in size (PM10) (10 µg/ml, 25 µg/ml, 50 µg/ml, and 100 µg/ml) for 24 h. Real-time polymerase chain reaction, measurement of reactive oxygen species (ROS), small interfering (si) RNA transfection, Oil Red O and Nile red staining, and immunofluorescence staining were performed to analyze the presence of inflammatory cytokines, matrix metalloproteinases (MMPs), aryl hydrocarbon receptor (AhR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), ROS, and lipid production. In addition, PM10 (100 µg/ml)-treated cultured cells were treated with 10 mg/ml of SHE.ResultsPM10 upregulates the expression of inflammatory cytokines, MMPs, AhR, NF-κB, and ROS in cultured human sebocytes and ORS cells. The production of ROS was dramatically reduced in AhR siRNA-transfected cells. In addition, PM10 upregulates sebum production in cultured sebocytes. SHE inhibited the upregulation of inflammatory cytokines, MMPs, AhR, NF-κB, ROS, and sebum production in cultured human sebocytes and/or ORS cells by PM10.ConclusionEffects of PM10 on cultured human sebocytes and ORS cells can be regulated by SH.

Comparison of Single and Combined Use of Ergothioneine, Ferulic Acid, and Glutathione as Antioxidants for the Prevention of Ultraviolet B Radiation-Induced Photoaging Damage in Human Skin Fibroblasts

Ultraviolet B (UVB) irradiation can cause human skin damage or skin aging and wrinkle formation through photochemical reactions. Antioxidative substances may ameliorate UV damage. In this study, the anti-photoaging activity of three antioxidants—ergothioneine, ferulic acid, and glutathione—was investigated after UVB irradiation of Hs68 human skin fibroblast cells. The cells treated with these three antioxidants appeared similar to unirradiated control cells. UVB irradiation decreased cell viability by 26% compared to that of unirradiated control cells. However, the addition of either single or combined antioxidants enhanced cell viability after UVB irradiation. These three antioxidants can inhibit the production of reactive oxygen species (ROS) induced by the UVB irradiation of the Hs68 cells. Ergothioneine showed a greater inhibitory effect on matrix metalloproteinase-1 (MMP-1) performance than the other two antioxidants. IL-1 alpha was not detected in the Hs68 cells after exposure to a radiation dose of 150 mJ/cm2. Ergothioneine showed better restoration of type 1 procollagen than either ferulic acid or glutathione. Based on these results, the addition of two antioxidants was expected to restore type Ι procollagen production. In summary, these results demonstrate that the three tested antioxidants protect the skin against UVB-induced damage. The single and combined use of ergothioneine, ferulic acid, and glutathione has the potential for development as anti-photoaging materials in cosmetic applications.

Determining safety thresholds in high-powered lasers

Lasers are ubiquitous in modern applications, but as their power increases, so does their potential to damage human skin.

073 A non-invasive genomic test for early assessment of UV damage in human skin

UV-exposure leads to mutations in skin cells, which may clonally expand and ultimately turn into cancerous lesions ('field cancerization'). Early detection of low-frequency cancer-causing UV-signature mutations in still normal-appearing skin remains a challenge. We have developed a non-invasive genomic test capable of quantifiably detecting UV-signature mutations with high sensitivity to change this paradigm. This genomic test combines DermTech's non-invasive skin sample collection technology 'adhesive skin collection kits' with an ultrasensitive and multiplexed MALDI-TOF mass spectrometry-based mutation detection platform, 'the MassARRAY' from Agena Bioscience. The test includes over two dozen DNA driver mutations in genes such as TP53, CDKN2A, NOTCH1, and NOTCH2, known to be associated with the development of non-melanoma skin cancers. In a proof-of-concept study, contralaterally collected skin samples from sun-exposed body sites in subjects of varying race, age, and gender were tested. UV-signature mutations were detected in sun-exposed skin, with the numbers of mutations increasing with the subjects' age. In our reference control neonatal keratinocytes, no UV signature mutations were detected. This genomic test demonstrates reliable detection of UV-signature mutations in sun-exposed skin samples collected using DermTech's non-invasive skin sample collection technology and offers the opportunity to non-invasively assess UV-damage of skin that lacks visual elements of UV damage. Additional studies will help understand the correlation of UV-damage detected in normal-appearing skin to future non-melanoma skin cancer risk. We envision this proactive genomic approach to measure UV damage to change how photoaging is assessed and treated.

Mitochondrial DNA as a Sensitive Biomarker of UV-Induced Cellular Damage in Human Skin.

Mitochondrial DNA (mtDNA) has been demonstrated to be a reliable biomarker of UV-induced genetic damage in both animal and human skin. Properties of the mitochondrial genome which allow for its use as a biomarker of damage include its presence in multiple copies within a cell, its limited repair mechanisms, and its lack of protective histones. To measure UV-induced mtDNA damage (particularly in the form of strand breaks), real-time quantitative PCR (qPCR) is used, based on the observation that PCR amplification efficiency is decreased in the presence of high levels of damage. Here, we describe the measurement of UV-induced mtDNA damage which includes the extraction of cellular DNA, qPCR to determine the relative amount of mtDNA, qPCR to determine UV-induced damage within a long strand of mtDNA, and the verification of the amplification process using gel electrophoresis.

A new model to investigate UVB-induced cellular senescence and pigmentation in melanocytes

Ultraviolet (UV) light is known to potentially damage human skin and accelerate the skin aging process. Upon UVB exposure, melanocytes execute skin protection by increasing melanin production. Senescent cells, including senescent melanocytes, are known to accumulate in aged skin and contribute to the age-associated decline of tissue function. However, melanocyte senescence is still insufficiently explored. Here we describe a new model to investigate mechanisms of UVB-induced senescence in melanocytes and its role in photoaging. Exposure to mild and repeated doses of UVB directly influenced melanocyte proliferation, morphology and ploidy. We confirmed UVB-induced senescence with increased senescence-associated β-galactosidase positivity and changed expression of several senescence markers, including p21, p53 and Lamin B1. UVB irradiation impaired proteasome and increased autophagic activity in melanocytes, while expanding intracellular melanin content. In addition, using a co-culture system, we could confirm that senescence-associated secretory phenotype components secreted by senescent fibroblasts modulated melanogenesis. In conclusion, our new model serves as an important tool to explore UVB-induced melanocyte senescence and its involvement in photoaging and skin pigmentation.

Imaging of metabolic activity adaptations to UV stress, drugs and differentiation at cellular resolution in skin and skin equivalents – Implications for oxidative UV damage

The epidermis is a multi-layered epithelium that consists mainly of keratinocytes which proliferate in its basal layer and then differentiate to form the stratum corneum, the skin's ultimate barrier to the environment. During differentiation keratinocyte function, chemical composition, physical properties, metabolism and secretion are profoundly changed. Extrinsic or intrinsic stressors, like ultraviolet (UV) radiation thus may differently affect the epidermal keratinocytes, depending on differentiation stage. Exposure to UV elicits the DNA damage responses, activation of pathways which detoxify or repair damage or induction of programmed cell death when the damage was irreparable. Recently, rapid diversion of glucose flux into the pentose phosphate pathway (PPP) was discovered as additional mechanism by which cells rapidly generate reduction equivalents and precursors for nucleotides – both being in demand after UV damage. There is however little known about the correlation of such metabolic activity with differentiation state, cell damage and tissue localization of epidermal cells. We developed a method to correlate the activity of G6PD, the first and rate-limiting enzyme of this metabolic UV response, at cellular resolution to cell type, differentiation state, and cell damage in human skin and in organotypic reconstructed epidermis. We thereby could verify rapid activation of G6PD as an immediate UVB response not only in basal but also in differentiating epidermal keratinocytes and found increased activity in cells which initiated DNA damage responses. When keratinocytes had been UVB irradiated before organotypic culture, their distribution within the skin equivalent was abnormal and the G6PD activity was reduced compared to neighboring cells. Finally, we found that the anti-diabetic and potential anti-aging drug metformin strongly induced G6PD activity throughout reconstructed epidermis. Activation of the protective pentose phosphate pathway may be useful to enhance the skin's antioxidant defense systems and DNA damage repair capacity on demand.

Cross talk between calcium and ROS regulate the UVA-induced melanin response in human melanocytes.

Exposure to high doses of solar long wavelength ultraviolet radiation (UVA) damages human skin via reactive oxygen species (ROS). Whether physiological UVA doses also generate ROS that has an effect on the skin remains unknown. We previously showed that in human epidermal melanocytes UVA activates a G-protein coupled signaling pathway that leads to calcium mobilization and increased melanin. Here, we report that ROS generated by the UVA phototransduction pathway are critical cellular messengers required to augment melanin. Using simultaneous UVA exposure and live-cell imaging of primary human melanocytes, we found that physiological doses of UVA generate two spatiotemporally distinct sources of ROS: one upstream of the G-protein activation that potentiates calcium responses, and another source downstream of calcium, in the mitochondria (ROSmito ). UVA-evoked signaling led to mitochondrial calcium uptake via mitochondrial calcium uniporter to promote ROSmito production leading to melanin synthesis. Our findings reveal a novel mechanism in which ROS function as signaling messengers necessary for melanin production, thus having a protective role in the UVA-induced skin response.

A Single-chip Resonance-frequency Tracking Microwave-excited Plasma Driver IC for Portable Biomedical Applications

This paper presents a first-time single-chip microwave-excited plasma driver IC with resonance-frequency tracking and output-power-regulation scheme for biomedical applications. The power module includes a driver IC and a power amplifier, and is designed to provide stable microwave power that is required for generation of a plasma jet. A 2.4- GHz coaxial transmission line resonator is used to generate the plasma jet using input microwave power. The proposed system continuously monitors the resonance frequency, and controls it by adaptively changing the microwave frequency. To prevent the plasma jet from becoming high enough to damage human skin, the system monitors the power entering the resonator and keeps it constant. The proposed microwave plasma driver IC is implemented in a 0.18-μm complementary metal-oxide-semiconductor process. The system generates stable 1 W with a frequency tracking.

An approach to design a wristwatch for the protection of the human skin damage induced by ultraviolet and infrared radiations

Ultraviolet radiations (UV) absorbed by the skin can drive photochemical reactions which range from sunburn to skin cancer. The repeated exposure to Infrared radiations (IR) induces the heat into the skin, which causes dehydration and erythema as an immediate effect. This heat activates the metalloproteinase enzyme that reduces the number of procollagen and collagen fibers in the dermal skin, which results premature skin aging. This work aims to design a protective measure in order to avoid these damages. The proposed protective measure is a wristwatch with an alert alarm which can sense UV and IR radiations. Whenever UV/IR radiation levels exceed beyond the defined limits, alarm will be activated that warns the user to apply protective measures. These radiations are detected by SI1145 digital UV Index/IR/visible light sensor and assigned, using Arduino, to an appropriate UV index and IR radiation levels. The IR and UV readings were recorded several times and at four different hours through the day. The readings showed its highest value at 10am and 2pm, which are considered the highest sun intensity. The other readings were at 6am and 5pm and considered the least dangerous hours. The data collected from the sensor are used to program the alarm. To combine all components, a PCB and a prototype were designed and printed. The UV/IR wristwatch is applicable to alert the user from the continuous and accumulated harmful effects of the radiations and enable them to seek protective measures.