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Experimental Dermatology

QingXiang Gao, GuiXuan Zhou, Sung-Jan Lin, Ralf Paus, ZhiCao Yue
Chemotherapy and radiotherapy are common modalities for cancer treatment. While targeting rapidly growing cancer cells, they also damage normal tissues and cause adverse effects. From the initial insult such as DNA double strand break, production of reactive oxygen species (ROS), and a general stress response, there are complex regulatory mechanisms that control the actual tissue damage process. Besides apoptosis, a range of outcomes for the damaged cells are possible including cell cycle arrest, senescence, mitotic catastrophe, and inflammatory responses and fibrosis at the tissue level...
November 20, 2018: Experimental Dermatology
Malcolm Maden, Jason O Brant
Members of the Acomys genus, known as spiny mice, are unique among mammals in being perfectly capable of regenerating large areas of skin that have been removed. During this regenerative process hairs, sebaceous glands, erector pili muscles, adipocytes and the panniculus carnosus all regenerate and the dermis does not scar. We review here the processes that the epidermis and the individual components of the dermis undergo in the regeneration process of the spiny mouse, the molecules that have been identified as potentially being important in regeneration and relate this to what has been proposed as playing a role in studies from the lab mouse, Mus musculus...
November 20, 2018: Experimental Dermatology
Elina Zuelgaray, David Boccara, Sophie Ly Ka So, Françoise Boismal, Maurice Mimoun, Martine Bagot, Armand Bensussan, Jean-David Bouaziz, Laurence Michel
Normal aging is associated with an impaired systemic immune response contributing to an increased susceptibility to infectious diseases. The aim of this study was to compare the lymphocyte phenotype in human skin from old and young healthy subjects. Skin samples from donors were used for explant cultures before flow cytometry analysis. Our results depicted a higher proportion of CD4+ and a lower proportion of CD8+ among CD3+ T-cells, a decreased proportion of CD45RA+ naive T-cells (3.5 ± 1.9% vs 22.9 ± 11...
November 15, 2018: Experimental Dermatology
Soon-Hyo Kwon, Jung-Im Na, Ji-Young Choi, Kyoung-Chan Park
Management of melasma is highly challenging due to inconsistent treatment results and frequent relapses. However, recent studies revealed that melasma may not only be a disease of melanocytes, but also a photoaging skin disorder. Herein, we attempt to validate that melasma is indeed a photoaging disorder by presenting the histopathologic findings of melasma: solar elastosis, altered basement membrane, increased vascularization, and increased mast cell count. We also provide some therapeutic implications based on these findings and a discussion on the latest updates and perspectives regarding treatment...
November 13, 2018: Experimental Dermatology
Jong Il Park, Ji Eun Lee, Cheol Hwan Myung, Chan Song Jo, Hye Sung Jang, Jae Sung Hwang
Melanophilin (Mlph) forms an interaction with Rab27a and the actin-based motor protein MyosinVa (MyoVa) on mature melanosome membranes and the tripartite complex regulates melanosome transport in melanocytes. In this study, we found that Rab27a siRNA decreased Mlph and Rab27a protein levels, but Mlph mRNA levels were not changed. Other Rab27a siRNA sequences also showed the same results. When Rab27a siRNA was treated with melan-a melanocytes, Rab27a protein was decreased within 6 h and Mlph protein was decreased within 24 h...
November 12, 2018: Experimental Dermatology
Rebecca Duit, Tim J Hawkins, Arto Määttä
Thioglycolate is a potent depilatory agent. In addition, it has been proposed to be useful as a penetration enhancer for transepidermal drug delivery. However, the effects on hair structure and stress responses it elicits in epidermal keratinocytes have not been fully characterized. We have used label-free confocal and fluorescence lifetime imaging supported by electron microscopy to demonstrate how thioglycolate damages hair cuticle cells by generating breakages along the endocuticle and leading to swelling of cortex cells...
November 11, 2018: Experimental Dermatology
Zhi Su, Stephanie Paulsboe, Joseph Wetter, Katherine Salte, Arun Kannan, Sheeba Mathew, Amanda Horowitz, Clare Gerstein, Marian Namovic, Viktor Todorović, Jane Seagal, Rebecca M Edelmayer, Michelle Viner, Lisa Rinaldi, Li Zhou, Laura Leys, Susan Huang, Leyu Wang, Ramkrishna Sadhukhan, Prisca Honore, Steve McGaraughty, Victoria E Scott
Psoriasis vulgaris (PV) results from activation of IL-23/Th17 immune pathway and is further amplified by cytokines/chemokines from skin cells. Among skin derived pro-inflammatory cytokines, IL-36 family members are highly upregulated in PV patients and play a critical role in general pustular psoriasis. However, there is limited data showing crosstalk between the IL-23 and IL-36 pathways in PV. Herein, potential attenuation of skin inflammation in the IL-23-induced mouse model of psoriasiform dermatitis by functional inhibition of IL-36 receptor (IL-36R) was interrogated...
November 11, 2018: Experimental Dermatology
Xiao Jiang, Fan Wu, Yuan Xu, Jian-Xin Yan, Yin-Di Wu, Sheng-Hong Li, Xuan Liao, Jun-Xian Liang, Ze-Hua Li, Hong-Wei Liu
BACKGROUND: Recent evidence suggests that angiotensin II (Ang II) plays a role in cutaneous wound healing. Mesenchymal stem cells (MSCs) are known as a rich source of cells that re-establish healed skin. However, the potential impact of Ang II on MSC differentiation into keratinocytes is still unknown. OBJECTIVE: The present study was conducted to explore the effect of Ang II on differentiation of bone marrow-derived MSCs (BM-MSCs) into keratinocytes. METHODS: BM-MSCs were isolated from rat bone marrow and cultured...
November 9, 2018: Experimental Dermatology
Isabella Doche, George L Wilcox, Marna Ericson, Neusa S Valente, Ricardo Romiti, Brian D McAdams, Maria K Hordinsky
Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocytic scarring alopecias affecting primarily the scalp. Although both diseases may share some clinical and histopathological features, in the last decade, FFA has become an "epidemic" particularly in Europe, North and South America with unique clinical manifestations compared to LPP, thus, raising the idea that this disease may have a different pathogenesis. Symptoms such as scalp burning, pruritus, or pain are usually present in both diseases, suggesting a possible role for nerves and neuropeptides in the pathogenesis of both diseases...
November 8, 2018: Experimental Dermatology
Il-Hong Bae, Eun Soo Lee, Jae Won Yoo, Sung Hoon Lee, Jae Young Ko, Yong Jin Kim, Tae Ryong Lee, Dae-Yong Kim, Chang Seok Lee
Hyperpigmentation is caused by excessive production of melanin in melanocytes. Mannosylerythritol lipids (MELs) are glycolipid biosurfactants that are abundantly produced by yeasts and used commercially in cosmetics. However, the potential depigmenting efficacy of MELs has not been evaluated. In this study, the depigmentary effect of MELs was tested in primary normal human melanocytes (NHMs), α-melanocyte-stimulating hormone (MSH)-stimulated B16 cells (murine melanoma cells) and a human skin equivalent (MelanoDerm) using photography, Fontana-Masson (F&M) staining, and two-photon microscopy...
November 8, 2018: Experimental Dermatology
Isabella Doche, Ricardo Romiti, Maria K Hordinsky, Neusa S Valente
Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocyte-mediated scarring alopecias which clinically affect primarily the anterior and mid scalp. However, unaffected scalp areas have not yet been investigated in a systemic manner. In this study we assessed histopathologic changes in affected and unaffected scalp in both diseases and healthy control subjects and compared these findings with clinical signs and scalp symptoms. We have demonstrated that "normal-appearing" scalp that is devoid of clinical lesions of LPP and FFA showed lymphocytic perifollicular inflammation around the isthmus/infundibulum areas in 65% of biopsy specimens, perifollicular fibrosis in 15% and mucin deposits in 7...
November 7, 2018: Experimental Dermatology
Eleni Zingkou, Georgios Pampalakis, Dimitra Kiritsi, Manthoula Valari, Nathalie Jonca, Georgia Sotiropoulou
The role of epidermal proteolysis in overdesquamation was revealed in Netherton syndrome, a rare ichthyosis due to genetic deficiency of the LEKTI inhibitor of serine proteases. Recently, we developed activography, a new histochemical method, to spatially localize and semi-quantitatively assess proteolytic activities using activity-based probes. Activography provides specificity and versatility compared to in situ zymography, the only available method to determine enzymatic activities in tissue biopsies. Here, activography was validated in skin biopsies obtained from an array of distinct disorders and compared with in situ zymography...
November 3, 2018: Experimental Dermatology
Anastasia Therianou, Magdalini Vasiadi, Danae A Delivanis, Theodora Petrakopoulou, Alexandra Katsarou-Katsari, Christina Antoniou, Alexandros Stratigos, Irene Tsilioni, Andreas Katsambas, Dimitris Rigopoulos, Theoharis C Theoharides
Psoriasis is characterized by keratinocyte proliferation and chronic inflammation, but the pathogenesis is still unclear. Dysregulated mitochondria (mt) could lead to reduced apoptosis and extracellular secretion of mtDNA, acting as "innate pathogen" triggering inflammation. Serum was obtained from healthy volunteers and psoriatic patients. Mitochondrial DNA was extracted from the serum and amplified with quantitative PCR (qPCR). Punch biopsies were obtained from lesional and non-lesional psoriatic skin (10 cm apart) and from healthy volunteers, were placed in RNA later and were stored at -80°C until RNA was extracted and cDNA was synthesized; gene expression of uncoupling protein 2 (UCP2), Dynamin-related protein 1 (Drp1) and calcineurin, involved in the regulation of mitochondria function, was detected with qPCR...
November 3, 2018: Experimental Dermatology
Haihong Li, Liyun Chen, Mingjun Zhang, Sitian Xie, Cuiping Zhang
We previously showed three-dimensional (3D) reconstructed eccrine sweat glands have similar structures as native eccrine sweat glands, but whether the 3D reconstructed sweat glands appropriately secrete fluid is still unknown. In this study, Matrigel-embedded human eccrine sweat gland cells or Matrigel alone were implanted into the groin subcutis of the nude mice. Ten weeks post-implantation, images of the subcutaneously formed plugs, as well as footpads of rats, pre- and post-pilocarpine/normal saline (NS) injection were acquired using a fat-suppressed proton density-weighted magnetic resonance imaging (MRI) sequence at 7...
November 3, 2018: Experimental Dermatology
Ayako Hobo, Kazutoshi Harada, Tatsuo Maeda, Masaki Uchiyama, Ryokichi Irisawa, Masashi Yamazaki, Ryoji Tsuboi
Lichen planopilaris (LPP) is a primary cicatricial alopecia characterized by the infiltration of lymphocytes in the upper portion of hair follicles. Inflammation around the bulge region of hair follicles induces destruction of hair follicle stem cells and tissue fibrosis, resulting in permanent hair loss. Treatment is still challenging, and the precise pathophysiology of this disorder is unknown. To clarify the pathogenesis of LPP, we performed histological and immunohistochemical analysis on specimens obtained from LPP patients...
October 31, 2018: Experimental Dermatology
Jung Eun Kim, Jee Hye Oh, Young Jun Woo, Ji Hee Jung, Kwan Ho Jeong, Hoon Kang
Mesenchymal stem cell therapy (MSCT) has been suggested as a new therapeutic strategy for immunologic disorders. There have been only a few attempts to treat alopecia areata (AA) with MSCT. MSCT efficacy and mechanism of action in treating AA is not known. We sought to investigate the effect of human hematopoietic mesenchymal stem cells (hHMSCs) on an in vitro model of AA and to explore relevant mechanisms that regulate efficacy. An AA-like environment was induced by pretreatment of human dermal papilla cells (hDPCs) with interferon gamma (IFN-γ)...
October 29, 2018: Experimental Dermatology
Xiaojiao Zhang, Fuling Luo, Jing Li, Jingyuan Wan, Li Zhang, Hongzhong Li, Aijun Chen, Jin Chen, Tao Cai, Xian He, Thomas S Lisse, Hengguang Zhao
Cutaneous squamous cell carcinoma (SCC) is one of the most common non-melanoma skin cancers worldwide. While its exact tumorgenesis mechanisms is far from well-established and less satisfied therapeutic strategy can be clinically used nowadays. In this study we intended to investigate the role of DNA damage-inducible transcript 4 (DDIT4) in human SCC. Firstly, we identified DDIT4 is significantly suppressed in human SCC tissue and cultured A431 cell line, and reduced DDIT4 accelerates keratinocytes proliferation but impedes the autophagy flux through mTORC1 pathway by affecting the downstream S6 Kinase1, 4E-BP1, Beclin1 and LC3 II/I...
October 29, 2018: Experimental Dermatology
Hanqian Zhang, Maja Ericsson, Simone Weström, Anders Vahlquist, Marie Virtanen, Hans Törmä
Autosomal recessive congenital ichthyosis (ARCI) is a group of monogenic skin disorders caused by mutations in any of at least 12 different genes, many of which are involved in the epidermal synthesis of ω-O-acylceramides (acylCer). AcylCer are essential precursors of the corneocyte lipid envelope crosslinked by transglutaminase-1 (TGm-1), or a yet unidentified enzyme, for normal skin barrier formation. We hypothesized that inactivating TGM1 mutations will lead to a compensatory overexpression of the transcripts involved in skin barrier repair, including many other ARCI-causing genes...
October 29, 2018: Experimental Dermatology
Tingyan Mi, Yiying Dong, Uma Santhanam, Nan Huang
Skin surface is constantly exposed to environmental and secreted stressors such as UV, air pollution, and peroxidized sebum. The current study aims to use reconstructed human skin equivalents to demonstrate topical stressor induced hyperpigmentation and evaluate bioactives' potential protective effect. Given that polycyclic aromatic hydrocarbons are representative airborne particle-bound organic compounds with known relevance to pigmentation pathways, benzo(a)pyrene was selected as surrogate environmental toxin...
October 19, 2018: Experimental Dermatology
Roland Hubaux, Coralie Bastin, Michel Salmon
Recent advances in the development of human-based in vitro models offer new tools for drug screening and mechanistic investigations of new therapeutic agents. However, there is a lack of evidence that disease models respond favorably to potential drug candidates. Atopic dermatitis (AD) is a very common disease associated with an altered skin barrier and chronic inflammation. Here, we demonstrate that the AD-like features of a reconstructed human epidermis (RHE) model treated with Th2 cytokines are reversed in the presence of molecules known to have a beneficial effect on damaged skin as a result of modulating various signaling cascades including the Liver X Receptors (LXR) and JAK/STAT pathways...
October 19, 2018: Experimental Dermatology
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