A comparative analysis of deferoxamine treatment modalities for dermal radiation-induced fibrosis.

The iron chelator, deferoxamine (DFO), has been shown to potentially improve dermal radiation-induced fibrosis (RIF) in mice through increased angiogenesis and reduced oxidative damage. This preclinical study evaluated the efficacy of two DFO administration modalities, transdermal delivery and direct injection, as well as temporal treatment strategies in relation to radiation therapy to address collateral soft tissue fibrosis. The dorsum of CD-1 nude mice received 30 Gy radiation, and DFO (3 mg) was administered daily via patch or injection. Treatment regimens were prophylactic, during acute recovery, post-recovery, or continuously throughout the experiment (n = 5 per condition). Measures included ROS-detection, histology, biomechanics and vascularity changes. Compared with irradiated control skin, DFO treatment decreased oxidative damage, dermal thickness and collagen content, and increased skin elasticity and vascularity. Metrics of improvement in irradiated skin were most pronounced with continuous transdermal delivery of DFO. In summary, DFO administration reduces dermal fibrosis induced by radiation. Although both treatment modalities were efficacious, the transdermal delivery showed greater effect than injection for each temporal treatment strategy. Interestingly, the continuous patch group was more similar to normal skin than to irradiated control skin by most measures, highlighting a promising approach to address detrimental collateral soft tissue injury following radiation therapy.

Peroxisome proliferator-activated receptor-δ-mediated upregulation of catalase helps to reduce ultraviolet B-induced cellular injury in dermal fibroblasts.

BACKGROUND: Previous studies suggested that the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-δ plays an essential role in cellular responses against oxidative stress. OBJECTIVE: To investigate how PPAR-δ elicits cellular responses against oxidative stress in primary human dermal fibroblasts (HDFs) exposed to ultraviolet B (UVB). METHODS: The present study was undertaken in HDFs by performing real-time polymerase chain reaction, gene silencing, cytotoxicity and reporter gene assay, analyses for catalase and reactive oxygen species, and immunoblot analyses. RESULTS: The PPAR-δ activator GW501516 upregulated expression of catalase and this upregulation was attenuated by PPAR-δ-targeting siRNA. GW501516-activated PPAR-δ induced catalase promoter activity through a direct repeat 1 response element. Mutation of this response element completely abrogated transcriptional activation, indicating that this site is a novel type of PPAR-δ response element. In addition, GW501516-activated PPAR-δ counteracted the reductions in activity and expression of catalase induced by UVB irradiation. These recovery effects were significantly attenuated in the presence of PPAR-δ-targeting siRNA or the specific PPAR-δ antagonist GSK0660. GW501516-activated PPAR-δ also protected HDFs from cellular damage triggered by UVB irradiation, and this PPAR-δ-mediated reduction of cellular damage was reversed by the catalase inhibitor or catalase-targeting siRNA. These effects of catalase blockade were positively correlated with accumulation of reactive oxygen species in HDFs exposed to UVB. Furthermore, GW501516-activated PPAR-δ targeted peroxisomal hydrogen peroxide through catalase in UVB-irradiated HDFs. CONCLUSION: The gene encoding catalase is a target of PPAR-δ, and this novel catalase-mediated pathway plays a critical role in the cellular response elicited by PPAR-δ against oxidative stress.

Anti-Inflammatory Effects Induced by Near-Infrared Light Irradiation through M2 Macrophage Polarization.

Near-infrared (NIR) can penetrate the dermis. NIR is able to regulate cutaneous component cells and immune cells and shows significant anti-inflammatory therapeutic effects. However, the mechanisms of these effects are largely unknown. The purpose of this study is to elucidate NIR-induced molecular mechanisms on macrophages because macrophages play initial roles in directing immune responses by their M1 or M2 polarizations. Proteomic analysis revealed that NIR radiation enhanced the expression of mitochondrial respiratory gene citrate synthase. This increased citrate synthase expression was triggered by NIR-induced H3K4 hypermethylation on the citrate synthase gene promoter but not by heat, which led to macrophage M2 polarization and finally resulted in TGFß1 release from CD4+ cells. These cellular effects were validated in human primary macrophages and abdominal NIR-irradiated mouse experiments. In a phorbol 12-myristate 13-acetate‒induced inflammatory model on mouse ear, we confirmed that NIR irradiation induced significant anti-inflammatory effects through decreased M1 counts, reduced TNF-α, and increased CCL22 and/or TGFß1 levels.

A novel role for bone marrow-derived cells to recover damaged keratinocytes from radiation-induced injury.

Exposure to moderate doses of ionizing radiation (IR), which is sufficient for causing skin injury, can occur during radiation therapy as well as in radiation accidents. Radiation-induced skin injury occasionally recovers, although its underlying mechanism remains unclear. Moderate-dose IR is frequently utilized for bone marrow transplantation in mice; therefore, this mouse model can help understand the mechanism. We had previously reported that bone marrow-derived cells (BMDCs) migrate to the epidermis-dermis junction in response to IR, although their role remains unknown. Here, we investigated the role of BMDCs in radiation-induced skin injury in BMT mice and observed that BMDCs contributed to skin recovery after IR-induced barrier dysfunction. One of the important mechanisms involved the action of CCL17 secreted by BMDCs on irradiated basal cells, leading to accelerated proliferation and recovery of apoptosis caused by IR. Our findings suggest that BMDCs are key players in IR-induced skin injury recovery.

Environmentally-Induced (Extrinsic) Skin Aging: Exposomal Factors and Underlying Mechanisms.

As a barrier organ, the skin is an ideal model to study environmentally-induced (extrinsic) aging. In this review, we explain the development of extrinsic skin aging as a consequence of skin exposure to specific exposomal factors, their interaction with each other, and the modification of their effects on the skin by genetic factors. We also review the evidence that exposure to these exposomal factors causes extrinsic skin aging by mechanisms that critically involve the accumulation of macromolecular damage and the subsequent development of functionally altered and/or senescent fibroblasts in the dermal compartment of the skin.

Human Fibroblasts In Vitro Exposed to 2.45 GHz Continuous and Pulsed Wave Signals: Evaluation of Biological Effects with a Multimethodological Approach.

The increasing exposure to radiofrequency electromagnetic fields (RF-EMF), especially from wireless communication devices, raises questions about their possible adverse health effects. So far, several in vitro studies evaluating RF-EMF genotoxic and cytotoxic non-thermal effects have reported contradictory results that could be mainly due to inadequate experimental design and lack of well-characterized exposure systems and conditions. Moreover, a topic poorly investigated is related to signal modulation induced by electromagnetic fields. The aim of this study was to perform an analysis of the potential non-thermal biological effects induced by 2.45 GHz exposures through a characterized exposure system and a multimethodological approach. Human fibroblasts were exposed to continuous (CW) and pulsed (PW) signals for 2 h in a wire patch cell-based exposure system at the specific absorption rate (SAR) of 0.7 W/kg. The evaluation of the potential biological effects was carried out through a multimethodological approach, including classical biological markers (genotoxic, cell cycle, and ultrastructural) and the evaluation of gene expression profile through the powerful high-throughput next generation sequencing (NGS) RNA sequencing (RNA-seq) approach. Our results suggest that 2.45 GHz radiofrequency fields did not induce significant biological effects at a cellular or molecular level for the evaluated exposure parameters and conditions.

5-(N-Trifluoromethylcarboxy)aminouracil as a Potential DNA Radiosensitizer and Its Radiochemical Conversion into N-Uracil-5-yloxamic Acid.

Hypoxia-a hallmark of solid tumors-dramatically impairs radiotherapy, one of the most common anticancer modalities. The adverse effect of the low-oxygen state can be eliminated by the concomitant use of a hypoxic cell radiosensitizer. In the present paper, we show that 5-(N-trifluoromethylcarboxy) aminouracil (CF3CONHU) can be considered as an effective radiosensitizer of DNA damage, working under hypoxia. The title compound was synthesized in the reaction of 5-aminouracil and trifluoroacetic anhydride in trifluoroacetic acid. Then, an aqueous and deoxygenated solution of the HPLC purified compound containing tert-butanol as a hydroxyl radical scavenger was irradiated with X-rays. Radiodegradation in a 26.67 ± 0.31% yield resulted in only one major product-N-uracil-5-yloxamic acid. The mechanism that is possibly responsible for the formation of the observed radioproduct has been elucidated with the use of DFT calculations. The cytotoxic test against the PC3 prostate cancer cell line and HDFa human dermal fibroblasts confirmed the low cytotoxicity of CF3CONHU. Finally, a clonogenic assay and flow cytometric analysis of histone H2A.X phosphorylation proved the radiosensitization in vitro.

A Prospective, Split-Face, Randomized Study Comparing Picosecond to Q-Switched Nd: YAG Laser for Treatment of Epidermal and Dermal Pigmented Lesions in Asians.

BACKGROUND: Whether picosecond lasers outperform Q-switched lasers in treating pigmented lesions has not been clearly evaluated. OBJECTIVE: To compare the efficacy and safety of picosecond and Q-switched lasers in treating epidermal and dermal pigmented lesions in Asians. METHODS: Eight subjects with lentigines and 6 subjects with acquired bilateral nevus of Ota-like macules were enrolled. Subjects was randomly treated with a picosecond laser on one side of the face and a Q-switched laser on the other side. Subjective assessments on pigment clearance, and adverse effect were obtained at Weeks 0, 4, 12, and 24 after the final treatment. RESULTS: Clinical improvement differed between the 2 laser systems at Week 4 (p = .034), Week 12 (p = .039), and Week 24 (p = .027), with 85.7% of picosecond and 57.2% of Q-switched laser sites showing >50% improvement at 6 months. There was no significant difference in the incidence of side effect and healing time, but picosecond laser was significantly associated with a lower treatment discomfort (p = .05). CONCLUSION: The picosecond laser seems to be more effective and better tolerated than Q-switched laser for the treatment of pigmented lesions in Asians.

Alpha-neoendorphin can reduce UVB-induced skin photoaging by activating cellular autophagy.

Skin aging is influenced by several genetic, physiological, and environmental factors. In particular, ultraviolet (UV) exposure is an important factor involved in inducing skin photoaging. Autophagy controlling homeostatic balance between the synthesis, degradation, and recycling of cellular organelles and proteins plays important regulatory roles in several biological processes, including aging. The opioid neuropeptide α-neoendorphin (named NEP) is an endogenous decapeptide (N-YGGFLRKYPK-C) that activates the kappa opioid receptor and exhibits certain anti-aging and anti-wrinkling effects on skin cells; however, its action mechanism has not yet been elucidated. Therefore, the aim of this study was to determine the effects of NEP on anti-skin aging and autophagy activation in human dermal fibroblast cells. Western blot results showed that NEP down-regulates the production of phospho-mammalian target of rapamycin (p-mTOR), whereas increases the expression of key autophagy-related molecules such as Beclin-1, Atg5-Atg12, and LC3-II. The immunocytochemical analysis performed with anti-LC3-II antibody also showed that the autophagic indicators, autophagosomes are formed by NEP. These results suggest that NEP can activate cellular autophagy through mTOR-Beclin-1-mediated signaling pathway. It was also revealed by CM-H2DCF-DA assay and Western blottings that NEP can reduce the production of ultraviolet B (UVB)-induced reactive oxygen species (ROS) like with N-acetylcysteine (NAC), resulting in decreasing the expression levels of skin aging-related proteins, such as phospho-ERK (p-ERK), phospho-p38 (p-p38), and phospho-JNK (p-JNK). Furthermore, NEP could increase the type I procollagen production, while decreasing MMP-1, MMP-2, and MMP-9 activities. Taken together, the results demonstrate that NEP can reduce UVB-induced photoaging by activating autophagy.

Effects of ultra-weak fractal electromagnetic signals on the aqueous phase in living systems: a test-case analysis of molecular rejuvenation markers in fibroblasts.

Skin aging is primarily associated with the alterations in dermal extracellular matrix, in particular a decrease in collagen type-1 content. Recent studies have shown that collagen-degrading matrix metalloproteinase (MMP-1) is produced by fibroblasts in response to chronoaging, which in human dermal fibroblasts leads to the release of proinflammatory cytokines. Past studies showed that anti-inflammatory capabilities could be induced via non-chemical means. One of these methods makes use of ultra-weak fractal electromagnetic (uwf-EM) signals. Such ultra-/very-low frequency (U/VLF) signals (few nT in intensity and within 0.5-30 kHz) interact with aqueous solutions in living systems. The fractal nature of such EM-signals relates to the self-similar property by which a "cut-out" and magnified piece of this signal reveals again the original. Thus, the aim of this study is twofold, to i) investigate the extent of this modulating effect using Human Dermal Fibroblasts (HDF)-cells, and ii) analyse molecular rejuvenation markers therein. We could demonstrate that a 10 min uwf-EM exposure (prior to incubation) increases type-1 collagen and modulates elastin in human fibroblasts cultured up to 96 h, while at the same time reduces IL-6, TNF-α and MMP-1 (the later three being statistically significant). Such up- respectively down-regulation of corresponding genes are strong indicators of an EM-induced hormetic effect that influences the epigenomic landscape of HDFs. In the Appendix, we present, in the framework of Quantum Field Theory (QFT), water as a biphasic liquid and how its coherent fraction can be affected by uwf-EM signals while at the same time resolving the "kT paradox".

Skin Biomechanics and miRNA Expression Following Chronic UVB Irradiation.

Objective: Exposure to ultraviolet (UV) light from the sun is known to accelerate the skin aging process and leads to significant alterations in skin biomechanics; however, the molecular mechanisms by which chronic UVB affects biomechanical properties of the skin have not been well described. Approach: A murine model for chronic UVB exposure was used to examine changes in epidermal barrier function, skin biomechanics, and miRNA expression as a result of UVB. Results: UVB irradiation caused skin to be weaker, less elastic, stiffer, and less pliable. Notably, these changes were not reversed after a 5-week period of recovery. Following UVB exposure, dermal collagen fibrils were significantly smaller in diameter and expression of the miR-34 family was significantly increased. Innovation: To our knowledge, this is the first study to concurrently examine alterations in skin function, miRNA expression, and tissue biomechanics in response to chronic UVB exposure. Conclusion: The data suggest that UVB alters miR-34 family expression in skin, in addition to dysregulating collagen structure with subsequent reductions in strength and elasticity. miRNAs may play a pivotal role in regulating extracellular matrix deposition and skin biomechanics following chronic UVB exposure, and thus may be a possible target for therapeutic development. However, additional studies are needed to directly probe the link between UVB exposure, miRNA production, and skin biomechanics.

Efficacy and safety of the picosecond 755-nm alexandrite laser for treatment of dermal pigmentation in Asians-a retrospective study.

Q-Switched laser devices have been a standard treatment modality for dermal pigmentary disorders since the 1990s. However, the adverse events are sometimes intolerable even if the efficacy has been well accepted. These adverse events stop the patient from continuing the treatment and cause other cosmetic issues. Since 2012, the first picosecond laser for cosmetic applications was approved; it seems promising for treating pigmentary disorders in a new way, but lack strong evidence. We evaluated the efficacy and safety of a 755-nm picosecond laser for treatment of dermal pigmentary disorders in Asians. This is a 2-year retrospective study. We reviewed 36 female cases, including 8 cases of nevus of Ota and 28 cases of acquired bilateral nevus of Ota-like macules. Institutional Review Board (IRB) approval was granted by the Chang Gung Memorial Hospital medical research ethics committee (IRB 201900833B0). The epidemiologic data was collected. These patients have been treated with the 755-nm picosecond laser for 1 to 4 sessions at variable treatment interval. Our parameter settings were fluence of 2.73-3.98 J/cm2, with a spot size of 2.9 to 2.4 mm under the 650-ps mode. The pulse duration is 650 ps and fluence range is from 2.73 to 3.98 J/cm. Photographs were taken prior to every treatment and 1 month following the treatment. Two dermatologists conducted the clinical evaluation independently. Clinical improvement was observed in all with a minimal side effect. A total of 88.89% of patients had moderate to marked improvement in following 1 to 4 sessions. Transient swelling and erythema were observed in all patients but resolved within 24 h. Only one patient (2.78%) developed hypopigmentation and two patients (5.56%) had hyperpigmentation temporarily. Faster clearance could be achieved by the picosecond 755-nm laser for treating dermal pigmentary disorders in Asians. The treatment course is well tolerable and has minimal side effects.

Radiofrequency therapy in esthetic dermatology: A review of clinical evidences.

BACKGROUND: Chronological skin aging causes the modification of genetic material through enzymes and proteins changes. The process reduces cellular proliferation, along with loss of tissue elasticity, reduced ability to regulate aqueous exchanges, and inefficient tissue replication. Appearance is negatively affected by cumulative changes in coloration, texture, and elasticity over time. The increase in the population's average life expectancy boosts the search for cosmetic therapies that can delay aging, mostly for the noninvasive modalities. Among the various options, radiofrequency therapy is a technique that can help reduce the effects of skin aging. AIM: Therefore, this study aims to review clinical evidence provided by scientific literature on the benefits of using radiofrequency therapy in reducing skin aging effects. METHODS: A review of the literature concerning skin aging, characteristics of radiofrequency therapy, and radiofrequency therapy in the treatment of skin laxity and mechanism of action was conducted using PubMed. RESULTS: The included studies have suggested that the mechanism of radiofrequency action is heating the dermis while preserving the epidermis. This heating causes immediate collagen denaturation, which is followed by the formation of new collagen, naturally providing skin tightening and greater elasticity. CONCLUSION: Even when used as single therapeutic modality, radiofrequency seems to meet the expectations in reducing the effects of skin aging.

Optical coherence tomographic (OCT) evaluation of intraoral non-ablative erbium: YAG laser (SMOOTH mode) in rejuvenation of nasolabial folds; A prospective randomized split face comparative pilot study.

BACKGROUND: There are both few non-comparative studies investigating the efficacy of intraoral Er: YAG laser (SMOOTH mode) in rejuvenating nasolabial folds (NLFs) and lack of valid and objective wrinkles scales. In this prospective randomized split face comparative pilot study, we investigated the safety and efficacy of intraoral Er: YAG laser (SMOOTH MODE) compared with extraoral approach in rejuvenating NLFs using OCT as an objective evaluating tool. MATERIALS AND METHODS: Twenty adult women with notable NLFs were randomized in this study. The patients received 5 monthly sessions of Er: YAG laser (SMOOTH mode) using intraoral approach on one side and extraoral approach on the other side. Outcome was evaluated 2 weeks and 4 months post-treatment by Global Aesthetic Improvement Scale (GAIS), OCT, and patients' satisfaction. Side effects were also evaluated. RESULTS: Intraoral sides had significant increase in OCT evaluated dermal thickness at 4 months post-treatment (P = .03) without side effects compared with extraoral sides. Extraoral approach had significantly higher patients' satisfaction compared with intraoral approach at 2 weeks and 4 months post-treatment (P = .03, .02, respectively). Insignificant differences between both approaches were found regarding GAIS scoring, OCT evaluated epidermal thickness at 2 weeks and 4 months post-treatment, and OCT evaluated dermal thickness at 2 weeks post-treatment (P < .05). CONCLUSION: Intraoral Er: YAG laser (SMOOTH mode) is safer and more effective than extraoral approach in rejuvenating NLFs. OCT is a promising objective tool for evaluating facial wrinkles. Further studies are still needed.

Histological examination of skin tissue in the porcine animal model after simultaneous and consecutive application of monopolar radiofrequency and targeted pressure energy.

BACKGROUND: The cosmetic appearance of skin is substantially influenced by the organization of connective fibers and underlying subcutaneous tissue. It has been previously documented that radiofrequency and pressure energies alone are able to improve skin appearance; however, detailed histological evaluation should be done to determine their synergistic effect. AIMS: This histological study investigates the difference between simultaneous and consecutive application of monopolar radiofrequency with targeted pressure energy on porcine skin. METHODS: In a total of four weekly abdominal treatments, simultaneous emission of the energies was applied to two pigs (12 minutes per session); additionally, two pigs were treated consecutively (12 + 12 minutes per session). The 5th pig served as a control subject. Biopsies were obtained at baseline, after the 4th treatment, and at 1-month follow-up. Primary outcomes were to document changes of dermal and hypodermal tissues. RESULTS: In the treated subjects, the amount of collagen and elastin fibers increased significantly (P < .001). At follow-up, simultaneous application showed a significantly higher increase in collagen and elastin fibers (by 59% and 64%, respectively), when compared to consecutive. Thickness of the dermis increased more in the pigs treated simultaneously (+848.8 µm/50.17%; P < .001). Treated tissue also showed the upper part of dermis to be rich in blood vessels and better organized interlobular septa in hypodermis. No significant change was observed in the control subject. CONCLUSION: Simultaneous application produces significantly more profound changes, when compared to consecutive treatment. Further research is needed but our findings represent a new potential treatment of various skin conditions like cellulite or laxity.

Red light-promoted skin barrier recovery: Spatiotemporal evaluation by transepidermal potential.

The light-promoted recovery of epidermal barrier of skin was evaluated by the associated recovery of transepidermal potential (TEP), the potential difference between the surface and dermis of skin, by using porcine skin samples. An accelerated recovery of TEP was observed by irradiation of red light with the irradiance of 40 mW/cm2 and a duration of > 10 min. The influence of the light stimulation to the surroundings (~ 20 mm) was also observed. The irradiations of blue and purple lights were ineffective in accelerating the barrier recovery. These characteristics of the light stimulation would be useful for the design of effective and safe phototherapy devices for skin. The present study proves that the TEP can serve as a spatiotemporal indicator of the epidermal barrier function.

Baicalein inhibits matrix metalloproteinase 1 expression via activation of TRPV1-Ca-ERK pathway in ultraviolet B-irradiated human dermal fibroblasts.

Increased matrix metalloproteinase 1 (MMP-1) expression is a feature of photo-aged skin. We investigated the effects of baicalein and sulphoraphane on ultraviolet B (UVB) irradiation-induced MMP-1 expression and apoptosis using human dermal fibroblasts. UVB irradiation not only increased MMP-1 expression, but also caused apoptosis. Both baicalein and sulphoraphane protected cells from UVB irradiation-induced apoptosis, but only baicalein inhibited MMP-1 expression. UVB irradiation activated 12-lipoxygenase, and its product, 12-hydroxyeicosatetraenoic acid, activated TRPV1 channels. The resulting UVB irradiation-induced Ca2+ increase was blocked by the 12-lipoxygenase inhibitor baicalein and the TRPV1 blocker capsazepine, but not by the Nrf2 inducer sulphoraphane. UVB irradiation also increased ROS generation and decreased Nrf2 protein levels. UVB irradiation-induced MMP-1 expression was blocked by the Ca2+ chelator BAPTA, by capsazepine and by TRPV1 silencing. However, induction was unaffected by the antioxidant N-acetylcysteine. ERK phosphorylation and JNK phosphorylation were induced by UVB irradiation, but only ERK phosphorylation was Ca2+ sensitive. Increased MMP-1 expression was blocked by PD98059, but not by SP600125. Thus, increased MMP-1 expression is mediated by increased cytosolic Ca2+ and ERK phosphorylation. UVB irradiation-induced ROS generation is also Ca2+ sensitive, and UVB irradiation-induced apoptosis is caused by increased ROS. Thus, baicalein, by blocking the UVB irradiation-induced cytosolic Ca2+ increase, protects cells from UVB irradiation-induced MMP-1 expression and apoptosis. In contrast, sulphoraphane, by decreasing cellular ROS, protects cells from only UVB-induced apoptosis. Thus, targeting 12-lipoxygenase may provide a therapeutic approach to improving the health of photo-aged human skin.

Extract of Deschampsia antarctica (EDA) Prevents Dermal Cell Damage Induced by UV Radiation and 2,3,7,8-Tetrachlorodibenzo-p-dioxin.

Exposure to natural and artificial light and environmental pollutants are the main factors that challenge skin homeostasis, promoting aging or even different forms of skin cancer through a variety of mechanisms that include accumulation of reactive oxygen species (ROS), engagement of DNA damage responses, and extracellular matrix (ECM) remodeling upon release of metalloproteases (MMPs). Ultraviolet A radiation is the predominant component of sunlight causative of photoaging, while ultraviolet B light is considered a potentiator of photoaging. In addition, different chemicals contribute to skin aging upon penetration through skin barrier disruption or hair follicles, aryl hydrocarbon receptors (AhR) being a major effector mechanism through which toxicity is exerted. Deschampsia antarctica is a polyextremophile Gramineae capable of thriving under extreme environmental conditions. Its aqueous extract (EDA) exhibits anti- photoaging in human skin cells, such as inhibition of MMPs, directly associated with extrinsic aging. EDA prevents cellular damage, attenuating stress responses such as autophagy and reducing cellular death induced by UV. We demonstrate that EDA also protects from dioxin-induced nuclear translocation of AhR and increases the production of loricrin, a marker of homeostasis in differentiated keratinocytes. Thus, our observations suggest a potential use exploiting EDA's protective properties in skin health supplements.

Interactive thermal tissue reactions of 7-MHz intense focused ultrasound and 1-MHz and 6-MHz radiofrequency on cadaveric skin.

BACKGROUND: Intense focused ultrasound (IFU) and radiofrequency (RF) systems generate thermal tissue reactions in multiple zones in the skin, with the microscopic features thereof varying according to energy sources and treatment parameters. OBJECTIVE: To evaluate interactive thermal tissue reactions of IFU and RF in cadaveric skin. METHODS: Thermal reaction patterns generated by IFU, invasive bipolar RF, and non-invasive monopolar RF treatments were analyzed in cadaveric skin of the inner thigh. Additionally, combination treatment, including IFU and invasive bipolar RF, IFU and non-invasive monopolar RF, invasive bipolar RF and IFU, and non-invasive monopolar RF and IFU, was delivered to cadaveric skin and microscopically evaluated. RESULTS: Combination treatment with 1.5-mm IFU followed by 1.5-mm invasive RF elicited multiple thermal injury zones of coagulation and ablation in the mid to lower dermis. Therein, IFU-induced thermal reactions were indistinguishable from RF-induced thermal reactions. Non-invasive RF treatment on IFU-pretreated cadaveric tissue specimens exhibited greater degrees of thermal injury, with wider and deeper penetration, compared to non-invasive RF treatment alone. Furthermore, RF-pretreated tissues showed marked differences in the patterns of IFU-induced thermal tissue reactions. CONCLUSION: Our data suggest that combination treatments with IFU and RF elicit various patterns of interactive thermal tissue reactions.

Induction of angiogenic and inflammation-associated dermal biomarkers following acute UVB exposure on bio-engineered pigmented dermo-epidermal skin substitutes in vivo.

PURPOSE: Ultraviolet (UV) radiation adversely affects skin health at cellular and molecular levels. Hence, UV radiation can directly induce inflammatory responses in the dermis by inducing erythema, edema, inflammation, dermal fibroblasts alterations, and extracellular matrix modifications. METHODS: Human keratinocytes, melanocytes, and fibroblasts were isolated from skin biopsies, cultured, and expanded in vitro. Fibroblasts were seeded into collagen type I hydrogels that were subsequently covered by keratinocytes and melanocytes. These pigmented dermo-epidermal skin substitutes (pigmDESS) were transplanted for 5 weeks onto full-thickness skin wounds on the back of immuno-incompetent rats, exposed to a single UVB dose of 250 mJ/cm2 or unexposed and excised after 1 week. The effects onto the dermis were assessed regarding cell number, cell phenotype, and cell proliferation. Local inflammation by granulocytes (HIS48) or macrophages (CD11b, iNOS) was analyzed by immunohistochemistry staining. RESULTS: We observed a significantly enhanced ingrowth rate of blood capillaries, but not of lymphatic capillaries at 1 week post-irradiation. Moreover, the enhanced vascularization of pigmDESS after UVB exposure was concomitant with a high infiltration of granulocytes and monocytes/macrophages to the dermal part of grafts. In addition, a heterogeneous expression of HIF-1α and TNFα was detected at this early phase after UVB exposure. In local cellular response examination, results only show a moderate cell proliferation in the dermis. CONCLUSIONS: We were able to define early markers of UVB-induced effects in the dermis of pigmDESS. Overall, a single UVB dose induces temporary acute angiogenic and immune responses during the early post-irradiation phase in vivo.