Increase In Epidermal Thickness Research Articles

Increment of growth factors in mouse skin treated with non-thermal plasma.

Non-thermal plasma (NTP) has several beneficial effects, and can be applied as a novel instrument for skin treatment. Recently, many types of NTP have been developed for potential medical or clinical applications, but their direct effects on skin activation remain unclear. In this study, the effect of NTP on the alteration of mouse skin tissue was analyzed. After NTP treatment, there were no signs of tissue damage in mouse skin, whereas significant increases in epidermal thickness and dermal collagen density were detected. Furthermore, treatment with NTP increased the expression of various growth factors, including TGF-α, TGF-β, VEGF, GM-CSF, and EGF, in skin tissue. Therefore, NTP treatment on skin induces the expression of growth factors without causing damage, a phenomenon that might be directly linked to epidermal expansion and dermal tissue remodeling.

Morpho-physiological Tolerance Mechanisms of Talinum patens to Lead

The objective of this study was to evaluate lead phytotoxicity on Talinum patens and the morpho-physiological tolerance mechanisms. The following parameters were considered: germination percentage, germination speed index, root and shoot length, fresh and dry matter, lead content in tissues, enzymatic antioxidant system, proline content, lipid peroxidation, root anatomy, cytogenetic analysis, and chlorophyll fluorescence. The experimental design was completely randomized, with five concentrations: 0, 50, 100, 250, and 500 μM Pb(NO3)2 and five replicates. Exposure to Pb(NO3)2 solutions did not influence germination, shoot length, or fresh and dry matter. However, a Pb(NO3)2-dependent concentration effect was observed, which reduced cell division in the root meristematic zone (mitotic index), reducing their length. Superoxide dismutase, catalase, and ascorbate peroxidase showed increased activity when exposed to lead, and the same effect was detected for proline content and lipid peroxidation. There was an increase in the dissipation of excess energy in photosystems, as well as an increase in epidermal thickness. Therefore, Talinum patens plants had morpho-physiological characteristics that favor their germination, development, and metal tolerance.

Potential inhibitory effects of the traditional herbal prescription Hyangso-san against skin inflammation via inhibition of chemokine production and inactivation of STAT1 in HaCaT keratinocytes.

Inflammatory skin disease are caused by multiple factors, including susceptibility genes, and immunologic and environmental factors, and are characterized by an increase in epidermal thickness and the infiltration of macrophages, keratinocytes, mast cells, eosinophils and other inflammatory cells. Keratinocytes may serve an important role in the pathogenesis of inflammatory skin diseases. The traditional herbal decoction Hyangso‑san (HSS) has been used to treat symptoms of the common cold, including headache, pantalgia, fever and chills. However, to the best of our knowledge, there is no evidence regarding whether HSS has an effect on inflammatory skin diseases. The present study investigated the anti‑skin inflammation activity of HSS using the HaCaT human keratinocyte cell line. The mRNA expression and production of inflammatory chemokines, including C‑C motif chemokine ligand22 (CCL22), CCL5, CCL17, and interleukin(IL)‑8, was measured using reverse transcription polymerase chain reaction and ELISA analyses. Moreover, we evaluated the effect of HSS on signal transducer and activator of transcription1 (STAT1) pathway in HaCaT cells. The cells were stimulated with tumor necrosis factor‑α (TNF‑α) and interferon‑γ (IFN‑γ) to induce an inflammatory reaction. In the TNF‑α‑and IFN‑γ‑stimulated cells, the production and expression of inflammatory chemokines were observed, including CCL22, CCL5, CCL17 andIL‑8. In addition, stimulation with TNF‑α and IFN‑γ increased the phosphorylation and nuclear translocation of STAT1 in HaCaT cells. By contrast, HSS extract treatment inhibited TNF‑α‑andIFN‑γ‑induced STAT1 activation. Results from the present study indicated that HSS exhibited inhibitory effects on TNF‑α‑and IFN‑γ‑mediated chemokine production and expression by targeting STAT1 in keratinocytes. Overall, the results indicated that HSS may be a potential candidate therapeutic drug for inflammatory skin diseases such as atopic dermatitis.

Evaluation of the Response of Fractional Carbon Dioxide (CO2) Laser and Punch Elevation Technique in Treatment of Acne Scars : A Split-Face Comparative Clinical, Histopathological and Immune Histochemical Study

Background: Acne is the most common skin disease affecting adolescents and young adults, with associated scarring and its sequelae. Treatment options are either lifting procedures raising scar base closer to normal skin surface, or resurfacing ones injuring epidermis and superficial dermis with neocollagenesis and epidermal repair. Punch elevation (PE) method is better for improving deep atrophic acne scars, that can be combined with depth resurfacing. CO2 laser stimulates new collagen formation, tightens skin and raises scar to surface. Aim of the Work: to assess efficacy and safety of combination of PE technique and fractional co2 laser (Fr co2 L) compared to fr co2 L alone. Subjects and Methods: 20 atrophic post acne scars patients were subjected to history taking, general and dermatological examinations, identifying scars types and grades. Treatment response at start, before each fr. co2 L session and 4 weeks after last laser session was clinically evaluated by Goodman and Baron scale, and recording patients’ photographs, satisfaction, and complications. Histopathological examination of scar skin biopsies before and 4 weeks after the last fr. co2 L session was done using H&E, Mallory trichome, sliver stain and immunohistochemical VEGF. Results: combined treatment with fr co2 L and PE was more effective in improving post acne scars than fr. co2 L resurfacing alone. Histopathological examination before combined fr. co2 L and PE treatment and 1 month after the last fr. co2 L session showed high significant increase in epidermal thickness (H&E), increase in collagen fiber type III (Mallory trichrome stain), decrease in collagen fiber type I (sliver stain) and increase in fibroblasts’ activity (VEGF). Conclusion: both PE technique and fr. co2 L resurfacing show promising efficacy and safety in treating atrophic post acne scars, complementing each other to improve skin texture and appearance, with excellent cosmetic outcomes.

Combination of a 2940 nm Er:YAG laser with recombinant bovine basic fibroblast growth factor (rb-bFGF) and light-emitting diode-red light (LED-RL) for the treatment of striae alba: A pilot study.

Striae distensae (SD) are a common dermatologic problem that plagues many people. Although there are many therapeutic modalities have been used to treat SD, effective method has been disappointing for striae Alba. To evaluate the clinical and histopathologic efficacy and safety of the 2940-nm erbium yttrium aluminum garnet (Er:YAG) ablative fractional laser (AFL) with recombinant bovine basic fibroblast growth factor (rb-bFGF) and light-emitting diode-red light (LED-RL) for the treatment of striae alba. Thirty volunteers with striae distensae alba were enrolled. The subjects completed treatments with the 2940-nm Er:YAG AFL 6 times at 4-week intervals. Following this treatment, the subjects were required to spray rb-BFGF for 1week at home. They then received LED-RL once every 7days for three sessions between the two laser treatments. Two independent investigators evaluated clinical improvement at pretreatment and 1, 3, 6, and 12months post-treatment, patients also provided self-assessments of clinical improvement. Two biopsies were obtained from two subjects, both of the same sites of striae alba, one before the first treatment and one 6months after the last session. All 30 subjects demonstrated clinical improvement after treatment. Skin biopsies after treatment showed an increase in epidermal thickness, dermal thickness, and collagen and elastin density when compared to that at the baseline. The combination of the 2940-nm Er:YAG laser with rb-bFGF and LED-RL for the treatment of striae alba was a safe and effective approach for improving the appearance of striae alba.

NOD2 deficiency exacerbates imiquimod-induced, psoriasis-like dermatitis

Abstract Nucleotide-binding oligomerization domain containing protein 2 (NOD2) is a CARD domain-containing pattern recognition protein in which inactivating mutations can cause Crohn’s disease. Mechanisms that have been suggested to explain the inflammation in Crohn’s disease associated with loss of NOD2 function include inadequate intestinal antibacterial defense or, on the other hand, diminished inhibition of toll-like receptor (TLR) signaling. Psoriasis is a common autoimmune skin disease for which recent data show significant up-regulation of NOD2 in keratinocytes of the lesional skin. We investigated a role for NOD2 in a TLR-driven mouse model of psoriasis-like dermatitis in which IL-17A and IL-22 are critical contributors. Following topical application of the TLR7/8 agonist, imiquimod, as compared with wild-type controls, Nod2−/− mice showed increases in epidermal thickness, epidermal neutrophils, and numbers of α/β and γ/δ T cells capable of producing IL-17A and IL-22 as well as expression of mRNAs for IL-17 and IL-22 in the treated skin. In addition, we found increased levels of mRNAs for IL-1β, and for several IL-1-inducible proteins, including COX2 and the neutrophil chemoattractants CCL3, CXCL2, and CXCL3, and decreased levels of mRNA for IL-1RA in the imiquimod-treated skin of the Nod2−/− mice. Taken together, these data suggest that NOD2 may be limiting skin inflammation in psoriasis by regulating IL-1/TLR signaling, supporting an important immunomodulatory role for NOD2 in inflammatory disease.

Targeted disruption of TC-PTP in the proliferative compartment augments STAT3 and AKT signaling and skin tumor development

Tyrosine phosphorylation is a vital mechanism that contributes to skin carcinogenesis. It is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here, we report the critical role of T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, in chemically-induced skin carcinogenesis via the negative regulation of STAT3 and AKT signaling. Using epidermal specific TC-PTP knockout (K14Cre.Ptpn2fl/fl) mice, we demonstrate loss of TC-PTP led to a desensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes. TC-PTP deficiency also resulted in a significant increase in epidermal thickness and hyperproliferation following exposure to the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Western blot analysis showed that both phosphorylated STAT3 and phosphorylated AKT expressions were significantly increased in epidermis of TC-PTP-deficient mice compared to control mice following TPA treatment. Inhibition of STAT3 or AKT reversed the effects of TC-PTP deficiency on apoptosis and proliferation. Finally, TC-PTP knockout mice showed a shortened latency of tumorigenesis and significantly increased numbers of tumors during two-stage skin carcinogenesis. Our findings reveal that TC-PTP has potential as a novel target for the prevention of skin cancer through its role in the regulation of STAT3 and AKT signaling.

Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems.

Platelet rich plasma (PRP) was tested as a potential therapy for androgenetic alopecia (AGA) through two different clinical protocols in which one population (18 participants) received half-head treatment with autologous non-activated PRP (A-PRP) produced by CPunT Preparation System (Biomed Device, Modena, Italy) and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group) received treatment with calcium-activated PRP (AA-PRP) produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System). For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs) and in total hair density (65 ± 5 hair cm2), whereas negligible improvements in hair count (1.1 ± 1.4 hairs) and density (1.9 ± 10.2 hair cm2) were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus −73 ± 30 hair cm2 hair densities, Regen versus Arthrex). Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.

Anti-wrinkle effects of Sargassum muticum ethyl acetate fraction on ultraviolet B-irradiated hairless mouse skin and mechanistic evaluation in the human HaCaT keratinocyte cell line.

The present study investigated the photoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME) against ultraviolet B (UVB)-induced skin damage and photoaging in a mouse model. HR-1 strain hairless male mice were divided into three groups: An untreated control group, a UVB-irradiated vehicle group and a UVB-irradiated SME group. The UVB-irradiated mice in the SME group were orally administered with SME (100 mg/kg body weight in 0.1 ml water per day) and then exposed to radiation at a dose of 60–120 mJ/cm2. Wrinkle formation and skin damage were evaluated by analysis of skin replicas, epidermal thickness and collagen fiber integrity in the dermal connective tissue. The mechanism underlying the action of SME was also investigated in the human HaCaT keratinocyte cell line following exposure of the cells to UVB at a dose of 30 mJ/cm2. The protein expression levels and activity of matrix metalloproteinase-1 (MMP-1), and the binding of activator protein-1 (AP-1) to the MMP-1 promoter were assessed in the HaCaT cells using western blot analysis, an MMP-1 fluorescent assay and a chromatin immune-precipitation assay, respectively. The results showed that the mean length and depth of the wrinkles in the UVB-exposed hairless mice were significantly improved by oral administration of SME, which also prevented the increase in epidermal thickness triggered by UVB irradiation. Furthermore, a marked increase in collagen bundle formation was observed in the UVB-treated mice with SME administration. SME pretreatment also significantly inhibited the UVB-induced upregulation in the expression and activity of MMP-1 in the cultured HaCaT keratinocytes, and the UVB-enhanced association of AP-1 with the MMP-1 promoter. These results suggested that SME may be useful as an anti-photoaging resource for the skin.

Abstract 4071: Targeted disruption of T-cell protein tyrosine phosphatase in mouse epidermis reveals its critical role in chemically-induced skin carcinogenesis

Abstract Environmental factors such as chemical toxicants contribute to the development of skin cancer by creating mutations in housekeeping genes and proto-oncogenes which disrupt intracellular signaling mechanisms. One vital signaling mechanism is tyrosine phosphorylation signaling. Phosphotyrosine signaling is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Recently we reported TC-PTP (PTPN2) is critical regulator of STAT3 signaling in mouse keratinocytes. To assess the role of TC-PTP in skin carcinogenesis, we generated epidermal-specific TC-PTP-deficient (K14Cre.PTPN2fl/fl) transgenic mice. Loss of TC-PTP led to a desensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes. TC-PTP deficiency in epidermis resulted in a significant increase in epidermal thickness and hyperproliferation (assessed by bromodeoxyuridine (BrdU) labeling index) compared to control mice following treatment with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Consistently, primary keratinocytes derived from TC-PTP-deficient mice showed a faster growth rate. To further investigate the role of TC-PTP in skin carcinogenesis, TC-PTP-deficient mice were subjected to two-stage skin carcinogenesis analysis. TC-PTP-deficient mice showed a shortened latency of tumor development and significantly increased numbers of tumors compared to control mice, demonstrating TC-PTP deficiency predisposes mice to skin carcinogenesis. The data reveals TC-PTP may be a novel potential target for the prevention of skin cancer due to its role in the regulation of proliferation and apoptosis in epidermis. Citation Format: Hyunseung Lee, Mihwa Kim, Liza D. Morales, Thomas J. Slaga, John DiGiovanni, Dae J. Kim. Targeted disruption of T-cell protein tyrosine phosphatase in mouse epidermis reveals its critical role in chemically-induced skin carcinogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4071.

Physiological, Anatomical and Metabolic Implications of Salt Tolerance in the Halophyte Salvadora persica under Hydroponic Culture Condition.

Salt tolerance mechanism of an extreme halophyte Salvadora persica was assessed by analyzing growth, nutrient uptake, anatomical modifications and alterations in levels of some organic metabolites in seedlings imposed to various levels of salinity (0, 250, 500, and 750 mM NaCl) under hydroponic culture condition. After 21 days of salt treatment, plant height, leaf area, and shoot biomass decreased with increase in salinity whereas the leaf succulence increased significantly with increasing salinity in S. persica. The RWC% of leaf increased progressively in salt-treated seedlings as compared to control. Na+ contents of leaf, stem and root increased in dose-dependent manner whereas there was no significant changes in K+ content. There was significant alterations in leaf, stem, and root anatomy by salinity. The thickness of epidermis and spongy parenchyma of leaf increased in salt treated seedlings as compared to control, whereas palisade parenchyma decreased dramatically in extreme salinity (750 mM NaCl). There was a significant reduction in stomatal density and stomatal pore area of leaf with increasing salinity. Anatomical observations of stem showed that the epidermal cells diameter and thickness of cortex decreased by salinity whereas thickness of hypodermal layer, diameter of hypodermal cell, pith area and pith cell diameter increased by high salinity. The root anatomy showed an increase in epidermal thickness by salinity whereas diameters of epidermal cells and xylem vessels decreased. Total soluble sugar content remained unchanged at all levels of salinity whereas reducing sugar content increased by twofold at high salinity (750 mM NaCl). The starch content of leaf decreased progressively in NaCl treated seedlings as compared to control. Total free amino acid content did not change at low salinity (250 mM), whereas it increased significantly at higher salinity (500 and 750 mM NaCl). The proline content increased in NaCl treated seedlings as compared to control. There was no significant changes in polyphenols level of leaf at all levels of salinity. The results from the present study reveal that seedlings imposed with various levels of salinity experience physiological, biochemical and anatomical modifications in order to circumvent under extreme saline environment. The vital mechanisms of salt tolerance in S. persica are higher accumulation of organic metabolites, increase in leaf succulency, efficient Na+ sequestration in the vacuole, K+ retention in the photosynthetic tissue and increase in WUE by reducing stomatal density. Therefore, S. persica is a potential halophytic species to be cultivated in saline lands to eliminate excess salt and make it favorable for agriculture.

Abnormalities in the basement membrane structure promote basal keratinocytes in the epidermis of hypertrophic scars to adopt a proliferative phenotype.

The majority of studies on scar formation have mainly focused on the dermis and little is known of the involvement of the epidermis. Previous research has demonstrated that the scar tissue-derived keratinocytes are different from normal cells at both the genetic and cell biological levels; however, the mechanisms responsible for the fundamental abnormalities in keratinocytes during scar development remain elusive. For this purpose, in this study, we used normal, wound edge and hypertrophic scar tissue to examine the morphological changes which occur during epidermal regeneration as part of the wound healing process and found that the histological structure of hypertrophic scar tissues differed from that of normal skin, with a significant increase in epidermal thickness. Notably, staining of the basement membrane (BM) appeared to be absent in the scar tissues. Moreover, immunofluorescence staining for cytokeratin (CK)10, CK14, CK5, CK19 and integrin-β1 indicated the differential expression of cell markers in the epidermal keratinocytes among the normal, wound edge and hypertrophic scar tissues, which corresponded with the altered BM structures. By using a panel of proteins associated with BM components, we validated our hypothesis that the BM plays a significant role in regulating the cell fate decision of epidermal keratinocytes during skin wound healing. Alterations in the structure of the BM promote basal keratinocytes to adopt a proliferative phenotype both in vivo and in vitro.

Transgenic expression of human amphiregulin in mouse skin: inflammatory epidermal hyperplasia and enlarged sebaceous glands.

To explore the role of amphiregulin in inflammatory epidermal hyperplasia, we overexpressed human AREG (hAREG) in FVB/N mice using a bovine K5 promoter. A construct containing AREG coding sequences flanked by 5' and 3' untranslated region sequences (AREG-UTR) led to a >10-fold increase in hAREG expression compared to an otherwise-identical construct containing only the coding region (AREG-CDR). AREG-UTR mice developed tousled, greasy fur as well as elongated nails and thickened, erythematous tail skin. No such phenotype was evident in AREG-CDR mice. Histologically, AREG-UTR mice presented with marked epidermal hyperplasia of tail skin (2.1-fold increase in epidermal thickness with a 9.5-fold increase in Ki-67(+) cells) accompanied by significantly increased CD4+ T-cell infiltration. Dorsal skin of AREG-UTR mice manifested lesser but still significant increases in epidermal thickness and keratinocyte hyperplasia. AREG-UTR mice also developed marked and significant sebaceous gland enlargement, with corresponding increases in Ki-67(+) cells. To determine the response of AREG-UTR animals to a pro-inflammatory skin challenge, topical imiquimod (IMQ) or vehicle cream was applied to dorsal and tail skin. IMQ increased dorsal skin thickness similarly in both AREG-UTR and wild type mice (1.7- and 2.2-fold vs vehicle, P < 0.001 each), but had no such effect on tail skin. These results confirm that keratinocyte expression of hAREG elicits inflammatory epidermal hyperplasia, and are consistent with prior reports of tail epidermal hyperplasia and increased sebaceous gland size in mice expressing human epigen.

Gold nanoparticles protect against skin photoaging through photothermal effects in ICR mice: a preliminary study

Objective To investigate the protective effect of gold nanoparticles against skin photoaging through photothermal effects in female ICR mice, and to explore its possible mechanisms. Methods A total of 32 healthy female ICR mice were randomly and equally divided into four groups: normal control group receiving no treatment, model group receiving ultraviolet radiation alone, red laser group irradiated with red laser followed by ultraviolet radiation, gold nanoparticle group pretreated with gold nanoparticle solution under occlusion with a black plastic film for 30 minutes followed by red laser and ultraviolet radiation. Ultraviolet radiation was conducted thrice a week for 14 weeks, and the hairs in an area sized about 16 cm2 on the back of mice were shaved before each radiation in the model group, red laser group and gold nanoparticle group. At the end of experiment, the skin appearance of mice was observed by naked eyes and dermoscopy. Then, all the mice were sacrificed and skin samples were resected from the tested areas on the back. Haematoxylin-eosin (HE) and Masson's staining was performed to observe the changes of skin structure and collagen fibers, and the image analysis software ImageJ was used to calculate the area fraction (AA%) occupied by collagen fibers. The DCFH-DA probe was utilized to determine the level of reactive oxygen species (ROS) , and enzyme-linked immunosorbent assay (ELISA) was performed to measure the expression of matrix metalloproteinase-13 (MMP-13) in skin samples. Statistical analysis was carried out by one-way analysis of variance (ANOVA) for intergroup comparisons followed by the least significant difference (LSD) -t test for multiple pair-wise comparisons. The simple linear regression analysis was performed to assess the relationship between ROS levels and MMP-13 expression. Results After ultraviolet radiation, a series of characteristic photoaging changes were observed in the skin of mice in the model group, such as squamation, brown-yellowish discoloration, coarsening, thickening, appearance of deep wrinkles and lack of flexibility. Dermoscopy also showed skin coarseness, crusting and brown spots with breakage of and hemorrhage from capillaries in the model group. Compared with the normal control group, the model group showed significant increases in epidermal thickness (81.32 ± 7.09 vs. 38.42 ± 13.64 μm, P 0.05). The simple linear regression analysis showed that ROS levels were positively correlated with MMP-13 expression (r= 0.864, P= 0.018) . Conclusion The photothermal effects of gold nanoparticles can protect ICR mice from skin photoaging to a certain degree, likely by down-regulating the generation of ROS and expression of the downstream factor MMP-13. Key words: Skin aging; Ultraviolet rays; Reactive oxygen species; Matrix metalloproteinase 13; Animal experimentation; Metal nanoparticles; Gold nanoparticle

Adenosine A2A receptor plays an important role in radiation-induced dermal injury.

Ionizing radiation is a common therapeutic modality and following irradiation dermal changes, including fibrosis and atrophy, may lead to permanent changes. We have previously demonstrated that occupancy of A2A receptor (A2AR) stimulates collagen production, so we determined whether blockade or deletion of A2AR could prevent radiation-induced fibrosis. After targeted irradiation (40 Gy) of the skin of wild-type (WT) or A2AR knockout (A2ARKO) mice, the A2AR antagonist ZM241385 was applied daily for 28 d. In irradiated WT mice treated with the A2AR antagonist, there was a marked reduction in collagen content and skin thickness, and ZM241385 treatment reduced the number of myofibroblasts and angiogenesis. After irradiation, there is an increase in loosely packed collagen fibrils, which is significantly diminished by ZM241385. Irradiation also induced an increase in epidermal thickness, prevented by ZM241385, by increasing the number of proliferating keratinocytes. Similarly, in A2ARKO mice, the changes in collagen alignment, skin thickness, myofibroblast content, angiogenesis, and epidermal hyperplasia were markedly reduced following irradiation. Radiation-induced changes in the dermis and epidermis were accompanied by an infiltrate of T cells, which was prevented in both ZM241385-treated and A2ARKO mice. Radiation therapy is administered to a significant number of patients with cancer, and radiation reactions may limit this therapeutic modality. Our findings suggest that topical application of an A2AR antagonist prevents radiation dermatitis and may be useful in the prevention or amelioration of radiation changes in the skin.

Histological effects of the smoke of Verbascum speciosum leaves on the healing of rats wounds

The aim of this study was to assess the effect of the smoke of Verbascum speciocum leaves grown in 'Bouein Zahra' region, on the healing of skin lesions in Wistar rats. In this study in vivo conditions, 36 adult male Wistar rats were randomly divided into 3 groups. The operation day was considered as day zero and the procedure took 10 days. After the end of the treatment, i.e., on the 14 day, rats were killed by choloroform and samples were collected for histological analysis Masson trichrome and Vangason staining for collogen and hydroxyprolline amino acid OD assessment was applied. Studies in experimental groups exposed to the smoke of the leaves revealed that there was no increase in epidermis thickness, hair follicles diameter, skin, nor in the number and diameter of blood vessels as compared with control and sham groups. However, the amount of hair follicles was decreased. There was an increase in collogen diameter but this increase was not significant. But a significant increase was observed in OD of hydroxyl proline amino acid assessment (p<0.001) in experimental groups compared with sham and control groups. The results indicated that the use of smoke of V.speciocum leaves on the skin lesion had absolutely no increase on the wound healing ratios and its closure; it maximally could had very little effect on the proliferation as one step in the repair process, which needs further investigation.

Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2mg) 30min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants.

Erlotinib-Induced Skin Inflammation Is IL-1 Mediated in KC-Tie2 Mice and Human Skin Organ Culture

Epidermal growth factor receptor (EGFR) is the prototypical member of the ErbB network comprised of four transmembrane receptor tyrosine kinases (EGFR/ErbB1, ErbB2, ErbB3, and ErbB4). These receptors bind EGF and heregulin family ligands in a dynamic, feedback-regulated fashion, activating multiple signal transduction pathways and ultimately affecting many cellular functions (Avraham and Yarden, 2011; Wilson et al., 2009). ErbB receptors and their ligands are overexpressed in a wide spectrum of hyperplastic epithelial disorders including psoriasis and cancers. Numerous monoclonal antibodies and receptor tyrosine kinase inhibitors have been designed to block their activation (Yarden and Pines, 2012), and are highly effective for treating colorectal and non-small cell lung cancers. However, skin toxicity is frequently observed in patients undergoing therapy with EGFR inhibitors (EGFRIs) (Lacouture, 2006), including papular and pustular eruptions of the face and trunk, nail changes, dry skin, itch, and hair loss (Lacouture and Lai, 2006). These side-effects are the major dose-limiting toxicity of EGFRI therapy (Boone et al., 2007) and emphasize the importance of understanding the mechanisms involved.

Artocarpin-enriched extract reverses collagen metabolism in UV-exposed fibroblasts

In previous studies, the Artocarpus incisus extract containing 45% w/w artocarpin showed activities of antioxidation, antimelanogenesis and restoration of wrinkled-skin fibroblasts. Here, extract containing 90% w/w artocarpin was tested for its antioxidant activity and in ultraviolet (UV) A-irradiated fibroblasts, its ability to restore type I collagen and inhibit matrix metalloproteinase-1 (MMP-1) elevation. This extract was a less effective antioxidant of EC50 of 116.0 ± 5.1 μg/mL than L-ascorbic acid (9.7 ± 0.01 μg/mL). The extract (0.625–50 μg/mL) showed no cytotoxicity toward primary human skin fibroblasts. MMP-1 was markedly elevated at 72 h after UVA irradiation compared to non-irradiation cells (p < 0.01). This UVA-induced elevation was inhibited by 50 μg/mL extract or 50 ng/mL all-trans retinoic acid. In an aged and sun-exposed skin tissue culture model, the increase of epidermal thickness in the 250 μg/mL artocarpin-enriched extract or 75 μg/mL all-trans retinoic acid-treated group when compared to the non-treated group was markedly observed since day 1 of treatment. Moreover, the extract or all-trans retinoic acid-treated groups exhibited higher density of immunofluorescence staining of type I collagen than non-treated group. This coincides with significantly higher (p < 0.05) collagen content, as indicated by measuring hydroxyproline. Our results firstly revealed that the artocarpin-enriched extract reversed the activities of UVA-irradiated fibroblasts and improved the type I collagen deposition in aged/photoaged skin.

Morphological Studies on the Inhibitory Effects of Photoaging Skin of Fermented Red Ginseng in Hairless Mice

To investigate the anti-photoaging effect of fermented Red Ginseng(RG) in SKH-1 mice. We examined the effects of extracts of non-fermented RG(NRG group), fermented RG(FRG group) and fortified fermented RG(FFRG group) on skin wrinkles formation, histological changes related to the number of epidermal cell layers, epidermal thickness, neutrophil infiltration into dermis, degradation of collagen fibers, and the number of mast cells, and immunohistochemical changes related to cytokines and enzymes in photoaging skin caused by UVB irradiation of SKH-1 mice. The oral administration(300 ㎎/㎏ B.W./day) and topical application(100 ㎕/mouse/day) of extracts of NRG, FRG and FFRG inhibited increases in epidermal thickness and wrinkle formation compared to control group in dorsal skin induced by UVB irradiation. We observed more increased stainability of acid fuschin and aniline blue in dermis of FFRG group than those of other groups. Furthermore, NRG, FRG and FFRG prevented the disruption of collagen fibers within papillary layer of dermis, and decreased number of mast cells in the dorsal skins induced by UVB irradiation. We observed fine wrinkle formation in FFRG group. Treatment with NRG, FRG and FFRG decreased immunohistochemical density of myeloperoxidase related to inflammation in the photoaging skin. We observed more decreased immunohistochemical density of myeloperoxidase in FFRG group than those of other groups. Immunohistochemical density of PCNA and Ki-67 in FFRG group was more decreased than those of other groups. Our study suggests that fermented red ginseng extracts participates in inhibitory effects in the morphological processes related to photoaging skin on UVB irradiated SKH-1 mice.