Increase In Epidermal Thickness Research Articles

Carboxytherapy for striae distensae: A promising modality.

Striae distensae (SD) is a very common skin problem. Although a lot of treatment modalities have been proposed, few of them are effective. Recently, carbon dioxide therapy (CDT) or carboxytherapy was used in many indications of cosmetic dermatology such as SD. To objectively evaluate the use and effectiveness of CDT for treatment of SD. Twenty patients were subjected to 8 sessions of CDT injection at 2-week intervals using carboxy-gun. Patients were photographed, and skin specimens were obtained from the treated area before and after 4months of treatment. Using a computerized 3D camera, skin topography was objectively analyzed before and after treatment. Evaluation of collagen and elastic fibers by special histopathological staining, in addition to histometric analysis, was also done to evaluate treatment efficacy. Clinically, SD was statistically significantly improved after CDT injection compared with baseline (mean percentage of improvement of length and width, 59.8±15.9; P<.05). Meanwhile, the improvement observed by the 3D camera correlated with the clinical improvement. Histometric analysis showed an increase in epidermal thickness (P<.0001) in association with re-appearance of rete ridges following treatment. Histochemical evaluation of changes in elastic and collagen fibers after treatment showed better organization of curled and fragmented elastic fibers, which was accompanied by an increase in collagen content that became denser, arranged in bundles and parallel to the epidermis. CDTis an effective, promising, and simple minimally invasive procedure for improving SD with few side effects and low downtime.

Cellulose nanocrystal preparation from Gelidium amansii and analysis of its anti-inflammatory effect on the skin in vitro and in vivo

Treated Gelidium amansii cellulose nanocrystal (TGa CNC) was prepared from treated Gelidium amansii (TGa) and evaluated for its anti-inflammatory effect on human keratinocytes and mice skin. Using three independent cell lines, TGa CNC showed no cytotoxicity in HaCaT, Beas-2B, and Raw 264.7 cells. A non-toxic dose of TGa CNC suppressed ultraviolet (UV) B-induced AP (activated protein)-1, and subsequent cyclooxygenase (COX)-2 gene and protein expression in HaCaT cells. TGa CNC suppressed translocation of c-Jun from the cytosol to the nucleus responds to UVB irradiation. Additionally, TGa CNC suppressed UVB-induced extracellular signal-regulated kinases (ERKs)1/2/MEK/2/B-Raf, c-Jun N-terminal kinase (JNK)1/2/MKK4/7, Akt, and epidermal growth factor receptor (EGFR) phosphorylation in HaCaT cells. Dorsal treatment of TGa CNC significantly suppressed acute UVB-induced increase in epidermal thickness and COX-2 expression in mice skin. Overall, these results indicate that TGa CNC exerts potent anti-inflammatory activity through the inhibition of abnormal COX-2 expression and mitogen-activated protein kinases (MAPK)s signaling pathways.

Optical Coherence Tomography-Assisted Evaluation of Fractional Er:YAG Laser Versus Fractional Microneedling Radiofrequency in Treating Striae Alba.

Striae distensae (SD) is a challenging skin condition. Striae alba (SA) represents the chronic late atrophic stage of SD. Fractional laser technology is among the modalities used for treating SD. Lately, fractional microneedling radiofrequency (FMR) is gaining increased popularity in treating SD. The aim of our study was to assess and compare the efficacy of FMR and fractional Er:YAG laser in the treatment of SA. Twenty female patients were enrolled in the study fulfilling all inclusion and exclusion criteria. On a randomly selected half side of the body, the patients were treated with 2940 nm fractional Er:YAG laser while the other half side was treated with the FMR. Both modalities showed a significant reduction in the width of the widest striae (P < 0.005); however, there was no significant difference between them. Using optical coherence tomography, all patients demonstrated a mean significant increase in epidermal thickness; however, the FMR-treated sites showed significantly better results when compared with the ER:YAG-treated sides (P = 0.029). Scar improvements in both modalities did not correlate to skin type, duration, or site of the striae. Er:YAG and FMR represent two safe, effective, tolerable modalities for treating SA and are associated with minimal side effects. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Effect of defensins-containing eye cream on periocular rhytids and skin quality.

Defensins are peptides shown to activate LGR6 stem cells to stimulate the production of new basal stem cells in the epidermis. Use of topical definsin-containing products has been shown to address signs of global skin aging including decrease of wrinkles and increase of epidermal thickness. To investigate the ability of a topical defensin-containing skincare product in improving the structure and function of aging periocular skin using objective and subjective outcome measures. A prospective pilot trial of a defensin-containing eye cream was performed in patients with periocular rhytids over 6weeks. Subjective changes in skin quality and aging characteristics were compared using a patient survey tool. Objective changes in periocular skin quality were analyzed using the QuantifiCare imaging system and the DermLab ultrasound scanner by blinded reviewers. A total of eight patients completed treatment; two were male, and six were female. The average age was 51years (range 37-63). Compliance with product application as reported on the participant application log was over 90%. Overall, there was an average 2.1 point improvement in subjective measures of skin quality on the consumer questionnaire (P=.002). QuantifiCare imaging of pores, wrinkles, and oiliness showed 370% improvement, 55% improvement, and 12% improvement, respectively. DermaLab noninvasive measurements of elasticity, skin thickness, and hydration showed improvement of 120%, 28%, and 6%, respectively. The use of topical formulations of definsin-containing eye cream statically improves patient-reported outcomes of skin quality, especially redness, sensitivity to weather, age spots, and crow's feet.

The use of Carboxytherapy alone or in combination with fractional CO2 laser for facial rejuvenation: A split-face comparative study.

A wide variety of minimally invasive treatments are available for skin aging. Recently, carbon dioxide therapy (CDT) or carboxytherapy was used in many cosmetic indications including facial rejuvenation. To compare the efficacy of CDT alone versus combined CDT and fractional CO2 laser in management of facial aging. Twenty-Five female patients with bilateral and symmetrical facial aging were included in the study. The right (Rt) hemiface received 8 sessions of CDT whereas the left (Lt) side was treated with combined technique (6 sessions of CDT and 2 sessions of fractional CO2 in between. Clinical and objective evaluation using 3D skin analysis, histological, and morphometric analysis were performed. Clinical evaluation demonstrated that all patients (100%) were satisfied with no significant difference between both sides of the face (P>.05). Regarding texture and pigmentation improvement, the Lt side (combined) showed significant improvement compared to the Rt side (P<.05). Using Antera 3D camera, there was a significant difference (P<.05) in 3D improvement percent in textural changes while there was no significant difference (P>.05) in the 3D percent of wrinkles improvement between both sides. The Lt side showed more significant increase in epidermal thickness after treatment when compared to the Rt side (P<.05) with evident neocollagen formation. Carboxytherapy is an easy, safe, simple, and a relatively effective method for facial rejuvenation with minimal downtime. Better results were achieved when used in combination with fractional CO2 laser.

Therapeutic Effects of Cold-Pressed Perilla Oil Mainly Consisting of Linolenic acid, Oleic Acid and Linoleic Acid on UV-Induced Photoaging in NHDF Cells and SKH-1 Hairless Mice.

Positive physiological benefits of several plant oils on the UV-induced photoaging have been reported in some cell lines and model mice, but perilla oil collected from the seeds of Perilla frutescens L. has not been investigated in this context. To study the therapeutic effects of cold-pressed perilla oil (CPO) on UV-induced photoaging in vitro and in vivo, UV-induced cellular damage and cutaneous photoaging were assessed in normal human dermal fibroblasts (NHDFs) and HR-1 hairless mice. CPO contained five major fatty acids including linolenic acid (64.11%), oleic acid (16.34%), linoleic acid (11.87%), palmitic acid (5.06%), and stearic acid (2.48%). UV-induced reductions in NHDF cell viability, ROS production, SOD activity, and G2/M cell cycle arrest were remarkably improved in UV + CPO treated NHDF cells as compared with UV + Vehicle treated controls. Also, UV-induced increases in MMP-1 protein and galactosidase levels were remarkably suppressed by CPO. In UV-radiated hairless mice, topical application of CPO inhibited an increase in wrinkle formation, transepidermal water loss (TEWL), erythema value, hydration and melanin index on dorsal skin of UVB-irradiated hairless mice. CPO was observed to similarly suppress UV-induced increases in epidermal thickness, mast cell numbers, and galactosidase and MMP-3 mRNA levels. These results suggest CPO has therapeutic potential in terms of protecting against skin photoaging by regulating skin morphology, histopathology and oxidative status.

Anti-Atopic Effect of Acorn Shell Extract on Atopic Dermatitis-Like Lesions in Mice and Its Active Phytochemicals.

To investigate the potential effects of acorn shells on atopic dermatitis (AD), we utilized oxazolone (OX)- or 2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesion mouse models. Our research demonstrates that Acorn shell extract (ASE) improved the progression of AD-like lesions, including swelling, which were induced by oxazolone on Balb/c mouse ears. Additionally, ASE significantly decreased the ear thickness (OX: 0.42 ± 0.01 mm, OX-ASE: 0.32 ± 0.02 mm) and epidermal thickness (OX: 75.3 ± 32.6 µm, OX-ASE: 46.1 ± 13.4 µm). The continuous DNCB-induced AD mouse model in SKH-1 hairless mice demonstrated that ASE improved AD-like symptoms, including the recovery of skin barrier dysfunction, Immunoglobulin E hyperproduction (DNCB: 340.1 ± 66.8 ng/mL, DNCB-ASE: 234.8 ± 32.9 ng/mL) and an increase in epidermal thickness (DNCB: 96.4 ± 21.9 µm, DNCB-ASE: 52.4 ± 16.3 µm). In addition, we found that ASE suppressed the levels of AD-involved cytokines, such as Tumor Necrosis Factor α, IL-1β, IL-25 and IL-33 in both animal models. Furthermore, gallic acid and ellagic acid isolated from ASE suppressed β-hexosaminidase release and IL-4 expression in RBL-2H3 cells. The acorn shell and its active phytochemicals have potential as a new remedy for the improvement of atopic dermatitis and other inflammatory diseases.

Non-thermal plasma inhibits mast cell activation and ameliorates allergic skin inflammatory diseases in NC/Nga mice

Non-thermal plasma (NTP) has many functional activities such as, sterilization, wound healing and anti-cancer activity. Despite of its wide spread biomedical application, the effect of NTP on immune cells and allergic response has not been well studied. In this study, we determined whether NTP suppresses mast cell activation, which is important for allergic response, and ameliorates an atopic dermatitis (AD)-like skin inflammatory disease in mice. Exposure to NTP-treated medium during mast cell activation inhibited the expression and production of IL-6, TNF-α and suppressed NF-κB activation. We also investigated whether NTP treatment ameliorates house dust mite (HDM)-induced AD-like skin inflammation in mice. NTP treatment inhibited increases in epidermal thickness and recruitment of mast cells and eosinophils, which are important cell types in AD pathogenesis. In addition, Th2 cell differentiation was induced by application of HDM and the differentiation was also inhibited in the draining lymph node of NTP-treated mice. Finally, the expression of AD-related cytokines and chemokines was also decreased in NTP-treated mice. Taken together, these results suggest that NTP might be useful in the treatment of allergic skin diseases, such as AD.

Influence of Buffers of Different pH and Composition on the Murine Skin Barrier, Epidermal Proliferation, Differentiation, and Inflammation

The pH of the skin is tightly regulated by endogenous buffering systems. We examined the influence of buffers of different pH and composition on skin barrier repair, pH, inflammation, and epidermal thickness/proliferation/differentiation. After tape-stripping in hairless mice buffers with pH 4–7 were applied in patch test chambers. After removal of the chambers, skin pH and transepidermal water loss (TEWL) were monitored for 24 h, and biopsies were taken for histology/immunohistology. Hairless mice showed a basal skin pH of about 5.8. Following barrier disruption and application of water, the pH increased by 0.6 units; increase in pH was reduced by the pH 4 glycolate buffer, unchanged by pH 4 citrate and pH 5.5 buffers, and even increased by the pH 7 buffer. pH 5.5, pH 4 citrate, and pH 4 glycolate buffers led to a slight, while the pH 7 buffer led to a significant increase in TEWL after barrier disruption compared to water. The pH 7 buffers led to a significant increase in epidermal thickness/proliferation/differentiation and inflammation after barrier disruption, whereas buffers with pH 4 and 5.5 caused a slight increase. In conclusion, only the pH 4 glycolate buffer significantly reduced the skin barrier disruption-related increase in skin pH. This was accompanied by only slight increase in epidermal thickness and inflammation compared to water. Application of the pH 7 buffer led to a significant increase in the skin pH, TEWL, epidermal thickness, and inflammation. The results are important for the formulation of topical products for effective acidification in pathological skin conditions.

Effects of Commercially Available Whitening Creams on the Epidermal Thickness of Guinea Pig Skin.

To determine the effects of commonly used commercial skin lightening creams on the thickness of epidermis of guinea pig skin. Animal experimental study. Department of Anatomy, King Edward Medical University, Lahore, from March to May 2015. Forty-eight adult, colored guinea pigs were used in this study. The animals were randomly divided into four groups. Group I was control group (no cream application). The animals of group II, III and IV were treated with skin whitening creams A, B and C respectively once daily, 6 days/week for eight weeks duration. The observations of skin specimens were made after 4 and 8 weeks for epidermal thickness at histological level. Microscopic examination showed variable degrees of epidermal thickening with the three creams applied for 4 weeks. The increase in thickness of epidermis ranged from 49.1 μm in control group to maximum of 106.4 μm in group ll. These effects were further intensified after 8 weeks application. The use of whitening creams caused skin damage by increasing the epidermal thickness of varying extent.

Commentary to ‘Topical estradiol increases epidermal thickness and dermal collagen of foreskin prior to hypospadia surgery – randomized double blinded controlled trial’

Summary Introduction The use of preoperative topical testosterone stimulation prior to hypospadias correction aims to increase penile size and achieve better surgical results. Topical estradiol has been shown to improve the quality of skin in other sites, but its use in boys with hypospadia has not yet been elucidated. Objective This study aims to evaluate the primary effects in epidermal thickness and collagen distribution of estradiol compared to testosterone and placebo in skin of prepuce before hypospadia surgery. Matherials and methods Patients were randomized into three groups according to the topical hormone used: TG: Testosterone ointment; EG: Estradiol ointment; CG: Neutral base ointment. Fragments of foreskin were excised, fixed and then sectioned for histology. For each sample, epidermal thickness and dermal collagen expression was measured by specific computer analysis, P-values of Results Thirty-three patients with a mean age of 4.01 ± 2.92 years were included. Hypospadia classification was similar in all three groups. Mean epidermal thickness and collagen type I expression in EG were greater than those of the other groups. Collagen type III expression was similar in all groups. Discussion Foreskin has a fundamental role in many techniques of hypospadias surgery and can be used either as a graft or a flap in the correction of the penile defect. Increase of epidermal thickness and dermal collagen observed in the present study has already been related to use of estradiol in other skin sites, but not yet in foreskin. Further studies are needed to evaluate the real significance of these findings in boys with hypospadias. Conclusion Use of topical estradiol before hypospadias surgery lead to greater epidermal thickness and increases dermal collagen expression in foreskin. Download : Download high-res image (376KB) Download : Download full-size image

Amniotic fluid-derived mesenchymal stem cell products combined with microneedling for acne scars: A split-face clinical, histological, and histometric study.

Postacne scars are still a challenge in its management. Microneedling is a popular minimally invasive technique in treatment of such scars. However, the addition of topical stem cell products after microneedling is considered a new treatment regimen for these scars. To compare efficacy of amniotic fluid-derived mesenchymal stem cell-conditioned media (AF-MSC-CM) and microneedling vs microneedling alone in management of atrophic acne scars. Ten cases with atrophic postacne scars received five sessions of microneedling, with 2-week interval on both sides of the face. Then, AF-MSC-CM was topically applied to right side of the face after microneedling. Clinical examination with histopathological and computerized histometric analysis was done 1month after the sessions. There was significant increase in the improvement percentage of acne scars on right side (dermaroller and AF-MSC-CM) vs left side of face (dermaroller; P<0.001). Histologically, improvement of character of collagen and elastic fibers was noticed, especially on right side. Meanwhile, significant increase in epidermal thickness on both sides of face was detected. Amniotic fluid-derived mesenchymal stem cell-conditioned media combined with microneedling is more effective in management of atrophic postacne scars than microneedling alone.

Topical estradiol increases epidermal thickness and dermal collagen of foreskin prior to hypospadia surgery – Randomized double blinded controlled trial

The use of preoperative topical testosterone stimulation prior to hypospadias correction aims to increase penile size and achieve better surgical results. Topical estradiol has been shown to improve the quality of skin in other sites, but its use in boys with hypospadia has not yet been elucidated. This study aims to evaluate the primary effects in epidermal thickness and collagen distribution of estradiol compared to testosterone and placebo in skin of prepuce before hypospadia surgery. Patients were randomized into three groups according to the topical hormone used: TG: Testosterone ointment; EG: Estradiol ointment; CG: Neutral base ointment. Fragments of foreskin were excised, fixed and then sectioned for histology. For each sample, epidermal thickness and dermal collagen expression was measured by specific computer analysis, P-values of <0.05. Thirty-three patients with a mean age of 4.01±2.92 years were included. Hypospadia classification was similar in all three groups. Mean epidermal thickness and collagen type I expression in EG were greater than those of the other groups. Collagen type III expression was similar in all groups. Foreskin has a fundamental role in many techniques of hypospadias surgery and can be used either as a graft or a flap in the correction of the penile defect. Increase of epidermal thickness and dermal collagen observed in the present study has already been related to use of estradiol in other skin sites, but not yet in foreskin. Further studies are needed to evaluate the real significance of these findings in boys with hypospadias. Use of topical estradiol before hypospadias surgery lead to greater epidermal thickness and increases dermal collagen expression in foreskin.

Does climate-related in situ variability of Scots pine (Pinus sylvestris L.) needles have a genetic basis? Evidence from common garden experiments.

The correlations of phenotypic traits with environmental drivers suggest that variability of these traits is a result of natural selection, especially if such trait correlations are based on genetic variability. We hypothesized that in situ correlations of structural needle traits of Scots pine (Pinus sylvestris L) with minimal winter temperature (Tmin) reported previously from a temperate/boreal transect would be conserved when plants are cultivated under common conditions. We tested this hypothesis by analyzing needles from two common gardens located in the temperate zone, one including adult trees and the other juvenile seedlings. The majority of adult needle traits for which correlations with Tmin were found in the field turned out to be under environmental influence. In contrast, the majority of traits studied in juvenile needles were correlated with the original Tmin suggesting the role of past natural selection in shaping their variability. Juvenile needles thus appeared to be inherently less plastic than adult needles, perhaps reflecting the stronger selective pressure acting during juvenile, as compared with adult, ontogenetic stage. Genetically based cold-climate adaptation in either juvenile or adult needles, or both, involved an increase in leaf mass per area and leaf density, decrease in needle length, reduction in the amount of xylem and phloem, increase in thickness of epidermis, decrease in tracheid diameter and increase in tracheid density, and increase in diameter and volume fraction of resin ducts. We also show that at least some traits, such as transverse xylem and phloem areas and number of fibers, scale with needle length, suggesting that climate-related trait variation may also be mediated by changes in needle length. Moreover, slopes of these allometric relationships may themselves be plastically modified. The phenotypic syndrome typical of needles from cold environments may thus be under environmental, genetic and allometric control.

Different Root Anatomical Changes in Salt-tolerant and Salt-sensitive Foxtail Millet Genotypes

Foxtail millet is relatively tolerant to salinity stress and thus can be grown in salinity affected areas. This study was conducted to identify anatomical changes in the roots of foxtail millet genotypes with different tolerance level to salt stress. Four foxtail millet genotypes, namely ICERI-5 and ICERI-6 (salt tolerant) and ICERI-4 and ICERI-10 (salt sensitive), were grown hydroponically for 1 week prior to 60 and 120 mM salt stress treatments. Root anatomical changes were observed on the fifth day after treatments. The results showed that salt stress significantly induced some anatomical changes in the roots of foxtail millet, i.e. increased epidermis and cortex thickness, increased root diameter, and increased the number of root hairs. The increase in epidermis thickness, root diameter and the number of root hairs due to the salt application were more pronounced in the sensitive genotypes. Number of protoxylem in the tolerant genotypes were significantly increased due to salt stress, however salinity significantly decreased the number of protoxylem in the sensitive genotypes. The different anatomical changes under salt stress between the tolerant- and sensitive genotypes indicated that some anatomical attributes of the roots might determine the salt tolerance level of foxtail millet.

Crocin Ameliorates Atopic Dermatitis Symptoms by down Regulation of Th2 Response via Blocking of NF-κB/STAT6 Signaling Pathways in Mice

Crocin, a major constituent of Gardenia jasminoides, is a natural colorant carotenoid compound that has been reported to have anti-inflammatory effects. This study investigated the therapeutic effects of crocin on mice with atopic dermatitis induced by Dermatophagoides farinae crude extract, which is a common environmental allergen in house dust that causes atopic dermatitis in humans. Crocin application ameliorated Dermatophagoides farinae crude extract-induced atopic dermatitis symptoms by inhibiting the dermatitis severity score, ear thickness, and serum immunoglobulin E levels in NC/Nga mice. The increases in epidermal thickness and dermal inflammatory cells (eosinophil and mast cells) infiltrations observed on the dorsal back skin of atopic dermatitis control mice were inhibited in a dose-dependent manner by topical application of crocin in atopic dermatitis treatment mice. Crocin inhibited the Dermatophagoides farinae crude extract-induced increase of thymus and activation-regulated chemokines, interleukin (IL)-4, and IL-13 on the dorsal skin of mice. Crocin also inhibited Dermatophagoides farinae crude extract-induced activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription (STAT) 6. These results show that crocin ameliorates atopic dermatitis symptoms by down regulation of the Th2 cells-mediated immune response via blocking of NF-κB/STAT6 signaling pathways.

Therapeutic effects of topically-administered guar gum nanoparticles in oxazolone-induced atopic dermatitis in mice

Introduction: Atopic dermatitis (AD) is a chronic disease of the skin, involving itchy, reddish and scaly lesions. It mainly affects children and has a high prevalence in developing countries. AD may occur due to environmental or genetic factors. Currently, all therapeutic strategies involve methods to simply alleviate the symptoms, and include lotions and corticosteroids, which have adverse effects. Use of phytochemicals and natural products has not yet been exploited fully. The particle used in this study is derived from Cyamopsis tetragonoloba, an edible polysaccharide with a galactomannan component. The mannose component mainly increases its specificity towards cellular uptake by mannose receptors, highly expressed by macrophages. The aim of this study was to determine the therapeutic effect of guar gum nanoparticles (GN) in vitro and in vivo in AD.&#x0D; Methods: To assess the wound healing capacity of GN, we first treated adherent fibroblast cells, with a scratch injury, with GN. GN successfully healed the wound caused by the scratch. In the in vivo experiments, Balb/c mice ears were treated topically with oxazolone (Oxa) to induce AD, and then were topically treated with GN. The ear thickness increased significantly until day 28 upon treatment with Oxa.&#x0D; Results: Application of GN showed a significant decrease in ear thickness as assessed on day 28. The total cell count of skin cells that showed a fold increase, when treated with Oxa, was again decreased after topical application of GN on the affected skin. The eosinophil count, as assessed by Giemsa staining, was also increased when treated with Oxa, while GN application led to a significant decrease. Serum IgE levels were restored by GN. T helper cell and macrophage populations, when examined by flow cytometry, showed an increase in percentage when treated with Oxa; the percentage was reduced after application of GN. Hematoxylin &amp; Eosin (H&amp;E) staining of the ear tissue showed an increase in epidermal thickness in Oxa-treated mice, while GN application showed reduced cellular infiltration and epidermal thickness.&#x0D; Conclusion: Overall, our results showed that GN, when administered topically, was successful in alleviating dermatitis caused by Oxa.

Wound healing effects of a Curcuma zedoaria polysaccharide with platelet-rich plasma exosomes assembled on chitosan/silk hydrogel sponge in a diabetic rat model

One homogeneous polysaccharide (ZWP) was successfully isolated and purified from the rhizomes of Curcuma zedoaria and the aim of present study was to determine the potential of chitosan/silk hydrogel sponge loaded with platelet-rich plasma exosomes (PRP-Exos), ZWP or PRP-Exos/ZWP on wound-healing in diabetic rats. An in vivo diabetic wound healing study showed that separate or combined treatments all resulted in a wound contraction in diabetic rats, as evidenced by a decrease of ulcer and an increase of epidermal thickness, but PRP-Exos/ZWP combination therapy was more successful in wound closing than either PRP-Exos or ZWP single administration. This could be due to the upregulation of collagen synthesis and deposition, as well as angiogenesis at the wound site. In addition to this, no side effects was observed in all treated groups during healing process. These findings provide a mechanistic basis for PRP-Exos/ZWP as a potential therapeutic strategy to accelerate skin repair in diabetes.

198 The JAK1/2 inhibitor ruxolitinib induces cell cycle arrest and apoptosis through inhibiting STAT3 phosphorylation in squamous cell carcinoma

Ruxolitinib is an FDA approved JAK1/2 inhibitor that has shown efficacy in human head and neck squamous cell carcinoma, lung, and breast carcinoma, however, its therapeutic effect has not been elucidated in cutaneous squamous cell carcinoma (cSCC). cSCC is the second most common form of skin cancer, which causes significant morbidity due to local recurrence and metastasis. Therefore, there is an unmet need for novel therapeutic approaches for this malignancy. Here, we investigated whether inhibition of the JAK/STAT pathway has antitumor effects in cSCC. We found that JAK1/2 inhibition with ruxolitinib in the human SCC39 cell line in vitro resulted in STAT3 signaling-dependent decreased proliferation and cell cycle arrest at G2/M. This response was accompanied by decreased levels of cyclin D1 and increased levels p27Kip1. Moreover, ruxolitinib induced apoptosis in SCC cells as demonstrated by increased levels of cleaved caspase-3. Furthermore, we found that in vivo, topical application of ruxolitinib inhibited a TPA-induced increase in keratinocyte proliferation and a subsequent increase in epidermal thickness in Balb/c mice. In this model of cSCC tumor promotion, we also found that topical JAK inhibition resulted in a marked inflammatory infiltrate in TPA-treated animals. Taken together, we demonstrated the therapeutic potential of JAK1/2/STAT3 inhibition in cSCC, making ruxolitinib a promising anti-cancer drug against SCC development and progression. Moreover, this treatment option will be beneficial for high-risk groups such as solid organ transplant recipients or patients with recessive dystrophic epidermolysis bullosa where aggressive cSCC is a major complication resulting in considerable morbidity and mortality.

The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways

BackgroundHesperidin is a flavonoid with antioxidant, anti-inflammatory, and immune modulatory activities. Photoaging is a consequence of chronic exposure to the sun and ultraviolet (UV) radiation. This study was designed to evaluate the efficacy of hesperidin against photoaging of dorsal skin in hairless mice.MethodsHairless male mice (6-week-old) were divided into three groups (n = 7): control, UVB-treated vehicle, and UVB-treated hesperidin groups. UVB-irradiated mice from hesperidin group were orally administered 0.1 mL of water containing 100 mg/kg body weight per day hesperidin.ResultsThe mean length and depth of wrinkles in the UVB-treated hesperidin group significantly improved after the oral administration of hesperidin, which significantly inhibited the increase in epidermal thickness and epidermal hypertrophy (P < 0.05). UVB irradiation of mice induced epidermal barrier dysfunction including an increase in the transepidermal water loss (TEWL); however, hesperidin decreased the TEWL. UVB irradiation increased the expression of MMP-9 and pro-inflammatory cytokines whereas UVB-treated hesperidin group showed reduced expression. These results indicate that hesperidin showed anti-photoaging activity in the UVB-irradiated hairless mice. In conclusion, hesperidin inhibited the UVB-induced increase in skin thickness, wrinkle formation, and collagen fiber loss in male hairless mice.ConclusionsThese results suggest that hesperidin shows potent anti-photoaging activity by regulating MMP-9 expression through the suppression of MAPK-dependent signaling pathways.