Subjects -> MEDICAL SCIENCES (Total: 8679 journals)
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DERMATOLOGY AND VENEREOLOGY (163 journals)                     

Showing 1 - 163 of 163 Journals sorted alphabetically
Acta Dermato-Venereologica     Open Access   (Followers: 12)
Acta Dermatovenerologica Croatica     Open Access   (Followers: 1)
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Advances in Dermatology     Full-text available via subscription   (Followers: 15)
Advances in Skin & Wound Care     Hybrid Journal   (Followers: 30)
African Journal of AIDS Research     Hybrid Journal   (Followers: 8)
AIDS     Hybrid Journal   (Followers: 24)
AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV     Hybrid Journal   (Followers: 10)
AIDS Patient Care and STDs     Hybrid Journal   (Followers: 3)
AIDS Research and Human Retroviruses     Hybrid Journal   (Followers: 9)
AIDS Research and Therapy     Open Access   (Followers: 15)
AIDS Research and Treatment     Open Access   (Followers: 2)
Aktuelle Dermatologie     Hybrid Journal   (Followers: 7)
Allergo Journal     Full-text available via subscription   (Followers: 2)
American Journal of Clinical Dermatology     Full-text available via subscription   (Followers: 26)
American Journal of Dermatopathology     Hybrid Journal   (Followers: 18)
Anais Brasileiros de Dermatologia     Open Access   (Followers: 2)
Anaplastology     Open Access  
Annales de Dermatologie et de Vénéréologie     Full-text available via subscription  
Archives de Pédiatrie     Full-text available via subscription  
Archives de sciences sociales des religions     Open Access   (Followers: 1)
Archives des Maladies du Coeur et des Vaisseaux - Pratique     Hybrid Journal  
Archives of Dermatological Research     Hybrid Journal   (Followers: 7)
Archives of Gerontology and Geriatrics     Hybrid Journal   (Followers: 13)
Archives of Industrial Hygiene and Toxicology     Open Access   (Followers: 8)
Archives of Medical Research     Hybrid Journal   (Followers: 3)
Archives of Physical Medicine and Rehabilitation     Hybrid Journal   (Followers: 58)
Archivio di Ortopedia e Reumatologia     Hybrid Journal  
Asian Journal of Dermatology     Open Access   (Followers: 2)
ästhetische dermatologie & kosmetologie     Full-text available via subscription  
Australasian Journal of Dermatology     Hybrid Journal   (Followers: 8)
Berkala Ilmu Kesehatan Kulit dan Kelamin / Periodical of Dermatology and Venereology     Open Access  
Biomedical Dermatology     Open Access  
BMC Dermatology     Open Access   (Followers: 13)
BMJ Sexual & Reproductive Health     Hybrid Journal   (Followers: 2)
British Journal of Dermatology     Hybrid Journal   (Followers: 54)
Case Reports in Dermatological Medicine     Open Access   (Followers: 2)
Case Reports in Dermatology     Open Access   (Followers: 9)
Clinical and Experimental Dermatology     Hybrid Journal   (Followers: 13)
Clinical Dermatology Review     Open Access   (Followers: 5)
Clinical Skin Cancer     Full-text available via subscription  
Clinical, Cosmetic and Investigational Dermatology     Open Access   (Followers: 10)
Clinics in Dermatology     Hybrid Journal   (Followers: 14)
Contact Dermatitis     Hybrid Journal   (Followers: 8)
Cosmetics     Open Access   (Followers: 5)
Current Dermatology Reports     Hybrid Journal   (Followers: 7)
Current Fungal Infection Reports     Hybrid Journal   (Followers: 5)
Current HIV Research     Hybrid Journal   (Followers: 7)
Current HIV/AIDS Reports     Hybrid Journal   (Followers: 6)
Current Sexual Health Reports     Hybrid Journal   (Followers: 3)
Cutaneous and Ocular Toxicology     Hybrid Journal   (Followers: 10)
Der Hautarzt     Hybrid Journal   (Followers: 2)
Dermatitis     Hybrid Journal   (Followers: 1)
Dermato-Endocrinology     Open Access   (Followers: 2)
Dermatología Venezolana     Open Access  
Dermatologic Clinics     Full-text available via subscription   (Followers: 4)
Dermatologic Reviews     Hybrid Journal  
Dermatologic Surgery     Hybrid Journal   (Followers: 9)
Dermatologic Therapy     Hybrid Journal   (Followers: 2)
Dermatologica Sinica     Open Access  
Dermatological Nursing     Full-text available via subscription   (Followers: 2)
Dermatology     Full-text available via subscription   (Followers: 20)
Dermatology and Cosmetic     Open Access   (Followers: 8)
Dermatology and Therapy     Open Access   (Followers: 4)
Dermatology Online Journal     Open Access   (Followers: 1)
Dermatology Reports     Open Access   (Followers: 3)
Dermatology Research and Practice     Open Access   (Followers: 4)
Dermatopathology     Open Access   (Followers: 3)
Egyptian Journal of Dermatology and Venerology     Open Access   (Followers: 1)
EMC - Cosmetologia Medica e Medicina degli Inestetismi Cutanei     Full-text available via subscription  
EMC - Dermatología     Full-text available via subscription   (Followers: 1)
European Journal of Dermatology     Hybrid Journal   (Followers: 15)
Experimental Dermatology     Hybrid Journal   (Followers: 10)
Expert Review of Dermatology     Hybrid Journal   (Followers: 15)
Forum Dermatologicum     Hybrid Journal  
Graefe's Archive for Clinical and Experimental Ophthalmology     Hybrid Journal   (Followers: 9)
Güncel Dermatoloji Dergisi     Open Access  
HautinForm     Full-text available via subscription  
hautnah     Hybrid Journal  
hautnah dermatologie     Hybrid Journal  
HIV & AIDS Review     Full-text available via subscription   (Followers: 13)
HIV Clinical Trials     Hybrid Journal   (Followers: 5)
HIV Medicine     Hybrid Journal   (Followers: 3)
Indian Dermatology Online Journal     Open Access   (Followers: 3)
Indian Journal of Dermatology     Open Access   (Followers: 2)
Indian Journal of Dermatology, Venereology and Leprology     Open Access   (Followers: 4)
Indian Journal of Dermatopathology and Diagnostic Dermatology     Open Access  
Indian Journal of Drugs in Dermatology     Open Access   (Followers: 1)
Indian Journal of Paediatric Dermatology     Open Access   (Followers: 2)
Indian Journal of Sexually Transmitted Diseases and AIDS     Open Access   (Followers: 2)
International Archives of Medicine     Open Access   (Followers: 3)
International Journal of Dermatology     Hybrid Journal   (Followers: 14)
International Journal of Dermatology and Clinical Research     Open Access   (Followers: 2)
International Journal of Research in Dermatology     Open Access   (Followers: 1)
International Journal of STD & AIDS     Hybrid Journal   (Followers: 7)
International Journal of Women's Dermatology     Open Access   (Followers: 1)
International STD Research & Reviews     Open Access   (Followers: 1)
JAAD Case Reports     Open Access   (Followers: 1)
JAIDS : Journal of Acquired Immune Deficiency Syndromes     Hybrid Journal   (Followers: 4)
JAMA Dermatology     Full-text available via subscription   (Followers: 49)
JAMA Facial Plastic Surgery     Full-text available via subscription   (Followers: 13)
JMIR Dermatology     Open Access   (Followers: 1)
Journal of AIDS & Clinical Research     Open Access   (Followers: 3)
Journal of Clinical & Experimental Dermatology Research     Open Access   (Followers: 6)
Journal of Clinical and Investigative Dermatology     Open Access   (Followers: 2)
Journal of Cosmetic Dermatology     Hybrid Journal   (Followers: 11)
Journal of Cosmetics, Dermatological Sciences and Applications     Open Access   (Followers: 7)
Journal of Cutaneous Immunology and Allergy     Open Access  
Journal of Cutaneous Medicine and Surgery     Full-text available via subscription  
Journal of Dermatological Research     Open Access  
Journal of Dermatological Science     Hybrid Journal   (Followers: 2)
Journal of Dermatological Science Supplement     Full-text available via subscription   (Followers: 1)
Journal of Dermatological Treatment     Hybrid Journal   (Followers: 2)
Journal of Dermatology & Dermatologic Surgery     Open Access   (Followers: 1)
Journal of General-Procedural Dermatology & Venereology Indonesia     Open Access  
Journal of HIV/AIDS & Social Services     Hybrid Journal   (Followers: 9)
Journal of Investigative Dermatology     Hybrid Journal   (Followers: 28)
Journal of Investigative Dermatology Symposium Proceedings     Full-text available via subscription  
Journal of Sexual Medicine     Hybrid Journal   (Followers: 6)
Journal of Sexually Transmitted Diseases     Open Access   (Followers: 3)
Journal of Skin and Stem Cell     Open Access   (Followers: 3)
Journal of Skin Cancer     Open Access   (Followers: 3)
Journal of Surgical Dermatology     Open Access   (Followers: 1)
Journal of the American Academy of Dermatology     Full-text available via subscription   (Followers: 37)
Journal of the Dermatology Nurses' Association     Hybrid Journal   (Followers: 3)
Journal of the Egyptian Women’s Dermatologic Society     Partially Free  
Journal of the European Academy of Dermatology and Venereology     Hybrid Journal   (Followers: 15)
Journal of the International AIDS Society     Open Access   (Followers: 10)
Journal of the Saudi Society of Dermatology & Dermatologic Surgery     Open Access   (Followers: 1)
Karger Kompass Dermatologie     Full-text available via subscription  
Karger Kompass Pneumologie     Full-text available via subscription   (Followers: 1)
Langenbeck's Archives of Surgery     Hybrid Journal   (Followers: 4)
Medical and Surgical Dermatology     Hybrid Journal   (Followers: 1)
Medical Mycology     Open Access   (Followers: 4)
Nepal Journal of Dermatology, Venereology & Leprology     Open Access   (Followers: 1)
Neurobehavioral HIV Medicine     Open Access   (Followers: 2)
OA Dermatology     Open Access   (Followers: 1)
Open AIDS Journal     Open Access  
Open Dermatology Journal     Open Access  
Perspectives On Sexual and Reproductive Health     Hybrid Journal   (Followers: 7)
Pigment International     Open Access   (Followers: 1)
Psoriasis : Targets and Therapy     Open Access   (Followers: 4)
Revista Internacional de Ciencias Podológicas     Open Access  
SAHARA : Journal of Social Aspects of HIV / AIDS Research Alliance     Open Access   (Followers: 5)
Scars, Burns & Healing     Open Access  
Serbian Journal of Dermatology and Venereology     Open Access   (Followers: 1)
Sex Education: Sexuality, Society and Learning     Hybrid Journal   (Followers: 5)
Sexual & Reproductive Healthcare     Hybrid Journal   (Followers: 2)
Sexual Health     Hybrid Journal   (Followers: 4)
Sexually Transmitted Diseases     Hybrid Journal   (Followers: 7)
Sexually Transmitted Infections     Hybrid Journal   (Followers: 6)
Skin Appendage Disorders     Full-text available via subscription   (Followers: 1)
Skin Pharmacology and Physiology     Full-text available via subscription   (Followers: 7)
Skin Research and Technology     Hybrid Journal   (Followers: 6)
Southern African Journal of HIV Medicine     Open Access   (Followers: 3)
Sri Lanka Journal of Sexual Health and HIV Medicine     Open Access  
Studies in Gender and Sexuality     Hybrid Journal   (Followers: 21)
Surgical & Cosmetic Dermatology     Open Access   (Followers: 3)
The Journal of Dermatology     Hybrid Journal   (Followers: 4)
The Rose Sheet     Full-text available via subscription   (Followers: 2)
Vestnik dermatologii i venerologii     Open Access  
Veterinary Dermatology     Hybrid Journal   (Followers: 8)


Similar Journals
Journal Cover
Journal of Dermatological Science
Journal Prestige (SJR): 1.359
Citation Impact (citeScore): 2
Number of Followers: 2  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0923-1811
Published by Elsevier Homepage  [3200 journals]
  • Emerging evidence for the essential role of hyaluronan in cutaneous
    • Abstract: Publication date: Available online 19 March 2019Source: Journal of Dermatological ScienceAuthor(s): Jun Muto, Koji Sayama, Richard L. Gallo, Koji KimataAbstractHyaluronan (HA), a linear non-sulfated glycosaminoglycan, participates in a variety of biological processes in the skin, such as cell-matrix interactions and activation of chemokines/cytokines, enzymes, and growth factors. In these activation events, HA acts as a damage-associated molecular pattern (DAMP). This review discusses the progress in functional research on HA, and its associated factors, in several aspects of cutaneous biology; e.g., immunity, cancer biology, and wound repair.
  • Efficacy and safety of dupilumab monotherapy in adults with
           moderate-to-severe atopic dermatitis: A pooled analysis of two phase 3
           randomized trials (LIBERTY AD SOLO 1 and SOLO 2)
    • Abstract: Publication date: Available online 12 March 2019Source: Journal of Dermatological ScienceAuthor(s): Diamant Thaçi, Eric Simpson, Mette Deleuran, Yoko Kataoka, Zhen Chen, Abhijit Gadkari, Laurent Eckert, Bolanle Akinlade, Neil M.H. Graham, Gianluca Pirozzi, Marius ArdeleanuAbstractBackgroundTwo phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in adults with moderate-to-severe atopic dermatitis (AD).ObjectivesTo report a pooled analysis of these trials to further explore dupilumab’s effects on AD clinical parameters, patient-reported outcomes (PROs), symptoms of anxiety/depression, health-related quality of life (HRQoL), and safety.MethodsA pooled analysis of two 16-week phase 3 studies in adults with moderate-to-severe AD (N = 1,379) inadequately controlled with/inadvisable for topical medications, randomized to dupilumab 300 mg once weekly (qw), every 2 weeks (q2w), or placebo.ResultsDupilumab significantly improved all pre-specified efficacy endpoints versus placebo (P 
  • COA-Cl prevented TGF-β1-induced CTGF expression by Akt dephosphorylation
           in normal human dermal fibroblasts, and it attenuated skin fibrosis in
           mice models of systemic sclerosis
    • Abstract: Publication date: Available online 12 March 2019Source: Journal of Dermatological ScienceAuthor(s): Kozo Nakai, Sakiko Karita, Junske Igarashi, Ikuko Tsukamoto, Katsuya Hirano, Yasuo KubotaAbstractBackgroundSystemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs. Although transforming growth factor (TGF)-β1-induced connective tissue growth factor (CTGF/CCN2) expression has been presented in SSc fibrosis, the therapeutic potential of targeting CTGF in SSc has not been fully explored. COA-Cl is a novel nucleic acid analog, which is reported to have pleiotropic beneficial biologic effects.ObjectiveWe examine the effects of COA-Cl on TGF-β1-induced CTGF expression in normal human dermal fibroblast (NHDF). We also examined the effects of COA-Cl on CTGF expression in a mouse SSc model of angiotensin II (Ang II)-induced skin fibrosis.MethodsNHDF was cultured for in vitro experiments. For in vivo experiments, C57BL/6 J mice were treated with Ang II for 14 days by subcutaneous osmotic pump. Quantitative real-time polymerase chain reaction, western blot analysis, immunohistochemical staining and immunofluorescence staining were performed to examine the expression levels of CTGF and phosphorylation levels of Smad2/3, ERK1/2 and Akt.ResultsCOA-Cl attenuated the TGF-β1-induced expression of both CTGF mRNA and protein in NHDF. Although COA-Cl did not alter the TGF-β1-induced phosphorylation of Smad2/3 or ERK1/2, it reduced the TGF-β1-induced phosphorylation levels of Akt in NHDF. Notably, COA-Cl dephosphorylated the Akt of lysates of TGF-β1-treated NHDF. COA-Cl reduced the levels of CTGF mRNA, CTGF protein, dermal thickness, collagen content and Akt phosphorylation in the skin of mice SSc model.ConclusionThese results imply that the inhibition of TGF-β1-induced CTGF expression by COA-Cl may be a therapeutic approach for SSc.
  • Evaluating hair growth promoting effects of candidate substance: A review
           of research methods
    • Abstract: Publication date: Available online 12 March 2019Source: Journal of Dermatological ScienceAuthor(s): Jungyoon Ohn, Kyu Han Kim, Ohsang KwonAbstractAndrogenetic alopecia (AGA) is the most common form of hair loss disorder. As the prevalence of AGA rises, the demand for AGA treatments is rising accordingly, prompting research to identify therapeutic candidates to treat AGA. Because AGA is caused by crosstalk among multiple hair follicle (HF) cell components, understanding the effects of candidate molecules on HF cells is essential to determining therapeutic candidates for treatment. To date, research has centered on HF dermal papilla and outer root sheath cells and has indicated that the hair growth effects of candidate substances may be mediated via alterations in several signaling pathways and signature genes in these HF cells. In more integrative evaluations, the HF unit is used as an ex vivo organ culture model to verify the effects of therapeutic candidates. Animal models have also been used to evaluate the effects of candidate substances. The main outcomes used to evaluate the effects of candidate substances are 1) changes in HF growth rates in vitro, 2) anagen induction capabilities, and 3) the effects of androgen modulation. This article reviews a series of methods used to evaluate the hair growth-promoting effects of candidate substances, providing an overview of cell assays, organs, and animal models used in AGA research in order to facilitate AGA research moving forward.
  • GPR15 is not critically involved in the regulation of murine psoriasiform
    • Abstract: Publication date: Available online 12 March 2019Source: Journal of Dermatological ScienceAuthor(s): Tanya Sezin, Linda Kempen, Lisa-Maria Meyne, Sadegh Mousavi, Detlef Zillikens, Christian D. SadikAbstractBackgroundGPR15 has been implicated in the pathogenesis of T cell-driven inflammation of the skin and the gut. Expression levels of the GPR15 ligand GPR15 L are increased in psoriatic skin and considered as potential biomarker for the treatment response to anti-IL-17 antibody therapies. However, the significance of the GPR15 L/GPR15 for the pathogenesis of psoriasis and the mechanisms regulating GPR15 L expression are still elusive.ObjectiveTo determine the significance of GPR15 signaling in mouse models of psoriasis.MethodsWe addressed the role of the GPR15 L/GPR15 in the Aldara™-induced psoriasiform dermatitis (AIPD) and the IL-23-induced dermatitis model. In both models, we charted the expression levels of GPR15 L in the skin and assessed the significance of GPR15 L/GPR15 by examining Gpr15-/- mice.ResultsGPR15 L levels were increased in the AIPD, but not in the IL-23-induced dermatitis model. Deficiency in Gpr15 did not alter the course of disease neither in the AIPD, nor in the IL-23-induced dermatitis model. In neither model, deficiency in Gpr15 modulated disease on the histopathological or the molecular level. Despite the induction of GPR15 L in the AIPD model, GPR15+ cells did not accumulate in the skin.ConclusionGPR15 L expression is induced in psoriasiform dermatitis, but the activation of the IL-23/IL-17 axis alone is not sufficient for its induction. This restricts the potential use of GPR15 L levels as biomarker for the treatment response to anti-IL-17 antibody therapy. Our results leave a significant role of GPR15 in the pathogenesis of psoriasiform dermatitis rather unlikely. Hence, GPR15 L probably modulates psoriasiform dermatitis via GPR15-independent pathways.
  • Exosomal miRNA derived from keratinocytes regulates pigmentation in
    • Abstract: Publication date: Available online 12 March 2019Source: Journal of Dermatological ScienceAuthor(s): Ying Liu, Linli Xue, Hang Gao, Lucheng Chang, Xiuju Yu, Zhiwei Zhu, Xiaoyan He, Jianjun Geng, Yanjun Dong, Hongquan Li, Liping Zhang, Haidong WangAbstractBackgroundPigmentation is controlled by complex mechanisms. Evidence suggests that miRNAs can regulate pigmentation. However, the mechanism has not been fully elucidated. Objective In this study, we revealed a novel mechanism that regulates pigmentation involving exosomes, miRNAs and the crosstalk between keratinocytes and melanocytes.MethodsThe expression and localization of exosome specific marker TSG101 in keratinocytes and melanocytes; Changes of melanin content in melanocytes after co-culture of exosome and melanocytes; Expression changes of target gene TYR and its related genes and inhibitory effect of miR-330-5p on pigmentation were studied by using various molecular biological techniques.ResultsIn this experiment, we used miR-330-5p in keratinocytes to verify the effect of keratinocyte derived exosome on melanocyte pigmentation. First, we found that keratinocytes secrete exosomes carrying miR-330-5p; moreover, greater miR-330-5p expression was found in exosomes derived from keratinocytes that overexpressed miR-330-5p. Second, we found that exosomes derived from keratinocytes with overexpression of miR-330-5p caused a significant increase in miR-330-5p in melanocytes. Finally, exosomes derived from keratinocytes that overexpressed miR-330-5p induced a significant decrease in the production of melanin and expression of TYR in melanocytes. Meanwhile, we overexpressed miR-330-5p in melanocytes, which also proved the inhibitory effect of miR-330-5p on pigmentation.ConclusionThese findings suggest that keratinocytes crosstalk with melanocytes in the epidermal melanin unit via exosomal miRNAs. These studies reveal an important role of exosomes in melanocyte pigmentation, which opens a new pathway of melanogenesis.
  • A novel RORγt inhibitor is a potential therapeutic agent for the topical
           treatment of psoriasis with low risk of thymic aberrations
    • Abstract: Publication date: Available online 8 March 2019Source: Journal of Dermatological ScienceAuthor(s): Chihiro Imura, Azumi Ueyama, Yoshikazu Sasaki, Masaya Shimizu, Yoko Furue, Nobuyuki Tai, Kenichiro Tsujii, Kazufumi Katayama, Takayuki Okuno, Michitaka Shichijo, Kiyoshi Yasui, Mina YamamotoAbstractBackgroundRetinoic acid receptor-related orphan receptor gamma t (RORγt) has critical roles in the development, maintenance and function of interleukin (IL)-17-producing cells and is a highly attractive target for the treatment of IL-17-mediated autoimmune disease, particularly psoriasis. On the other hand, RORγt is also critical for controlling apoptosis during thymopoiesis, and genetic RORγt ablation or systematic RORγt inhibition cause progressive thymic aberrations leading to T cell lymphomas.ObjectiveWe investigated whether topical administration of our novel RORγt inhibitor, S18-000003 has therapeutic potential for psoriasis with low risk of thymic aberrations.MethodsWe evaluated the effect of topical S18-000003 on psoriasis-like skin inflammation and influence on the thymus in a 12-O-tetradecanoylphorbol-13-acetate-induced K14.Stat3C mouse psoriasis model.ResultsS18-000003 markedly inhibited the development of psoriatic skin inflammation via suppression of the IL-17 pathway. In the skin, S18-000003 suppressed all subsets of IL-17-producing cells that we previously identified in this psoriasis model: Th17 cells, Tc17 cells, dermal γδ T cells, TCR− cells that probably included innate lymphoid cells, and CD4−CD8− double-negative αβ T cells. Notably, neither reduction of CD4+CD8+ double-positive thymocytes nor dysregulation of cell cycling was observed in S18-000003-treated mice, even at a high dose.ConclusionOur topically administered RORγt inhibitor is a potential therapeutic agent for psoriasis with low risk of thymic lymphoma.
  • Extracellular vesicles derived from Malassezia furfur stimulate IL-6
           production in keratinocytes as demonstrated in in vitro and in vivo models
    • Abstract: Publication date: Available online 7 March 2019Source: Journal of Dermatological ScienceAuthor(s): Yu-Jing Zhang, Yang Han, Yu-Zhe Sun, Hang-Hang Jiang, Min Liu, Rui-Qun Qi, Xing-Hua GaoAbstractBackgroundMalassezia is one of the commensal microorganisms colonized on human skin and has been shown to be related to several inflammatory cutaneous disorders. Previous studies indicated that Malassezia. sympodialis (M. sympodialis) can produce extracellular vesicles, however, the immunoregulatory function of Malassezia extracellular vesicles on keratinocytes has not been studied.ObjectiveTo investigate the extracellular vesicular production capability of Malassezia. furfur (M. furfur) and examine their immunoregulatory effects both in vitro and in vivo.MethodsExtracellular vesicles derived from M. furfur were isolated by sequential ultracentrifugation procedure. Their structure and diameter were determined by negative stain TEM and NTA, respectively. Confocal microscopy was used to visualize the internalization of these nanoparticles into HaCaT cells and mice epidermal keratinocytes. The expressions of inflammatory cytokines were screened using PCR Array assay and validated in vitro by qPCR and ELISA assays. In vivo cytokine production was measured by the IHC method. The role of NF-κB in such process was evaluated in HaCaT cells by western blot assay.ResultsOur results showed that M. furfur produced ovoid-shaped nanoparticles, which could be then internalized into HaCaT cells, as well as mice epidermal keratinocytes. IL-6 expression was significantly enhanced in response to extracellular vesicular stimulation both in vitro and in vivo, in which process the activation of NF-κB was involved.ConclusionM. furfur has the ability to release extracellular vesicles, which can be internalized into keratinocytes and promote the production of IL-6 with the involvement of NF-κB dependent pathway. Such findings reveal some important new insights into Malassezia pathogenesis and therapy.
  • Stat3 activation in epidermal keratinocytes induces Langerhans cell
           activation to form an essential circuit for psoriasis via IL-23 production
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s): Kimiko Nakajima, Sayo Kataoka, Kenji Sato, Mikiro Takaishi, Mayuko Yamamoto, Hideki Nakajima, Shigetoshi SanoAbstractBackgroundPsoriasis is an inflammatory disease associated with aberrant crosstalk between the epidermis and immune system. However, the role of Langerhans cells (LCs) in psoriasis remains controversial.ObjectivesTo elucidate whether LCs are functionally involved in the development of psoriasis using a mouse model.MethodsTwo lines of transgenic mice were used and crossed. They included K5.Stat3C, the psoriasis-model mouse and langerin DTR knock-in (KI) mouse. We performed immunofluorescence staining for LCs in psoriatic lesion of human and model mice. Flow cytometric analyses were performed to compare between dendritic cells (DCs) and LCs in the epidermis and skin-draining lymph nodes (sDLNs). To assess cytokine/chemokine expression in the skin lesion or primary cultured keratinocytes, we performed RT-PCR, microarray analysis or intracellular staining on the flow cytometer.ResultsLCs were activated in psoriatic lesion of patients with psoriasis and K5.Stat3C mice. Compared with non-transgenic mice, K5.Stat3C mice constitutively showed an increased number of LCs in the sDLNs before psoriasis-like lesion developed. Stat3C transgenic keratinocytes expressed an elevated level of IL-1α. Psoriasis-like lesion in K5.Stat3C mice were attenuated in the absence of LCs, indicating that LCs were essential to the development of psoriasis-like lesion. Furthermore, we also recognized that epidermal LCs in psoriatic lesion of not only K5.Stat3C mice but also psoriasis patients produced IL-23.ConclusionsOur study suggests that Stat3 activation in keratinocytes may impact on LC activation in situ via IL-1α stimulation, at least in part, and that their presence may be essential for the pathogenesis of psoriasis through producing IL-23.
  • Dyschromatosis symmetrica hereditaria and reticulate acropigmentation of
           Kitamura: An update
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s): Michihiro Kono, Masashi AkiyamaAbstractDyschromatosis symmetrica hereditaria (DSH) and reticulate acropigmentation of Kitamura (RAK) are rare, inherited pigmentary diseases. DSH shows a mixture of pigmented and depigmented macules on the extremities. RAK shows reticulated, slightly depressed pigmented macules on the extremities. The causative gene of DSH was clarified as ADAR1 by positional cloning including linkage analysis and haplotype analysis in 2003. Ten years later, the causative gene of RAK was identified as ADAM10 by whole-exome sequencing, in 2013. ADAR1 is an RNA-editing enzyme which catalyzes the deamination of adenosine to inosine (A-to-I) in double-stranded RNA substrates during post-transcription processing. Inosine acts as guanine during translation, resulting in codon alterations or alternative splice sites that lead to functional changes in proteins when they occur in coding regions. In 2012, it was clarified that ADAR1 mutations cause Aicardi-Goutières syndrome 6, which is a severe genetic inflammatory disease that affects the brain and the skin. A zinc metalloprotease, a disintegrin and metalloprotease domain-containing protein 10 (ADAM10), is involved in the ectodomain shedding of various membrane proteins and shows various functions in vivo. ADAM10 is known to be involved in the ectodomain shedding of Notch proteins as substrates in the skin. We speculate that the pathogenesis of RAK and Dowling-Degos disease (DDD, a pigmentary disease similar to RAK) is associated with the Notch signaling pathway. In addition, ADAM10 mutations proved to be associated with late-onset Alzheimer disease. This review comprehensively discusses the updated pathophysiology of those genetic pigmentary disorders.
  • Obituary: Stephen I. Katz, MD, PhD (1941–2018)
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s):
  • Simple cell culture media expansion of primary mouse keratinocytes
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s): Sooah Kim, Byung Woo Kim, Vicky P. Prizmic, Eugene Oh, Victoria Yu, Benjamin Evans, Dongwon Kim, Luis A. Garza
  • JSID Fellowship Shiseido Research Grant
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s):
  • Association of glucose 6-phosphate dehydrogenase (G6PD) 3’UTR
           polymorphism with vitiligo and in vitro studies on G6PD inhibition in
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s): Mohmmad Shoab Mansuri, Mala Singh, Shahnawaz D. Jadeja, Rasheedunnisa Begum
  • Hypoxia accelerates the progression of angiosarcoma through the regulation
           of angiosarcoma cells and tumor microenvironment
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s): Saki Maeda-Otsuka, Ikko Kajihara, Yukino Tasaki, Saori Yamada-Kanazawa, Ryoko Sakamoto, Soichiro Sawamura, Mamiko Masuzawa, Mikio Masuzawa, Yasuyuki Amoh, Daichi Hoshina, Riichiro Abe, Yoshihiro Komohara, Hironobu IhnAbstractBackgroundAngiosarcoma is a rare malignant tumor with a poor prognosis. It is known that hypoxic condition activates tumor progression in several cancers. Additionally, hypoxic tumor microenvironment accelerates immune escape. However, the presence and significance of hypoxia in angiosarcoma has not been adequately investigated.ObjectiveTo study the role of hypoxia in the progression of angiosarcoma.MethodsThe protein level of hypoxia inducible factor-1α (HIF-1α) in angiosarcoma was examined using immunohistochemistry and immunoblotting. To study the effect of hypoxia on tumor progression, cell proliferation, migration, invasion, and tube formation assays were performed in angiosarcoma cells. The influence of tumor cell supernatant in hypoxia from angiosarcoma cells on immune escape and angiogenesis was analysed to investigate the modulatory effect of hypoxia on tumor microenvironment of angiosarcoma. The molecular mechanism related to these results was investigated using immunoblotting and real time RT-PCR.ResultsHIF-1α protein was over-expressed in angiosarcoma tissues and cell lines under hypoxic conditions, and there was heterogeneity of oxygen supply in angiosarcoma. Hypoxia enhanced the proliferation, migration, and invasion abilities and inhibited tube formation in angiosarcoma cells. Tumor cell supernatant in hypoxia from angiosarcoma cells activated the monocyte invasion ability, facilitated its differentiation into M2-like macrophages, and suppressed cell-adhesion. These in vitro results were compatible to the pathological findings of angiosarcoma patients.ConclusionHypoxia plays a major role in progression of angiosarcoma cells by enhancing cell proliferation, migration, and invasion and by modulating the tumor microenvironment.
  • The impact of irradiance on UVB-induced cutaneous immunosuppression:
           Implications on administering most efficient phototherapy
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s): Hsiao-Chi Lai, Chang-Shen Lin, Ching-Shuang Wu, Cheng-Che E. LanAbstractBackgroundUltraviolet B (UVB) is commonly used for treating dermatologic conditions. Recently, high irradiance UVB (HIUVB) has been suggested to be more effective for treating skin conditions as compared to its low irradiance (LI) counterpart. The biological impact of UVB radiation emitted at different irradiance on cutaneous immunity remains obscure.ObjectiveThis study aimed to explore the impacts of UVB radiation administered at equivalent fluence (mJ/cm2) but different irradiance (mW/cm2) on cutaneous immune response.MethodsCultured bone marrow derived dendritic cell (BMDC) were treated with equivalent fluence of UVB radiation with HIUVB or LIUVB. The phenotypic and functional alterations of BMDCs were documented. Animal models were used to validate the in vitro results in vivo and explore the mechanisms involved.ResultsAfter equivalent fluence of UVB radiation, the HIUVB treated BMDC showed significantly lower MHCII and CD86 expressions, reduced capacity to stimulate T cell proliferation, and enhanced activation of aryl hydrocarbon receptor (AhR)-activated genes as compared to control while their LIUVB treated counterpart showed no significant change. Using animal model, the HIUVB induced significantly higher immune suppressive effect in mice as compared to their LIUVB counterpart after equivalent fluence of UVB treatment. The superior immune suppressive effect of HIUVB over LIUVB radiation was not observed when similar experiments were performed using AhR-deficient mice.ConclusionWe propose irradiance played an important role modulating UVB-induced cutaneous immune suppression. Future works on UVB phototherapy, both clinical and research, should incorporate this important parameter into consideration.
  • Possible contribution of PDGF-BB-induced autophagy in dermatofibrosarcoma
           protuberans: Autophagy marker Atg5 could be a differential marker between
           dermatofibrosarcoma protuberans and dermatofibroma
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s): Sei-ichiro Motegi, Chisako Fujiwara, Akiko Sekiguchi, Sahori Yamazaki, Yoko Yokoyama, Masahito Yasuda, Osamu Ishikawa
  • Dual wavelength 5-aminolevulinic acid photodynamic therapy using a novel
           flexible light-emitting diode unit
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s): Hideyuki Masuda, Makoto Kimura, Akiko Nishioka, Hiroshi Kato, Akimichi MoritaAbstractBackgroundPhotosensitizers used for photodynamic therapy (PDT) to treat dermatologic disease are metabolized into mainly protoporphyrin IX (PpIX), which has five absorption wavelength peaks: 410 nm, 510 nm, 545 nm, 580 nm, and 630 nm. Although only red light around 635 nm and blue light around 400 nm are used as light sources for PDT, the efficiency of PDT might be improved by using multiple wavelengths, including those that correspond to the other absorption peaks of PpIX. Furthermore, because the target disease often occurs on the face, a flexible-type light-source unit that can be fitted to the lesion without unnecessarily exposing the mucous membranes, e.g., the eyes, nostrils, and mouth, is preferred.ObjectiveWe investigated the efficacy of a flexible light-emitting diode (LED) unit that emits multiple wavelengths to improve PDT effects.MethodsHaCaT cells were incubated with 5-ALA and subsequently irradiated with either a single wavelength or sequentially with two wavelengths. Cell viability and reactive oxygen species were analyzed. Nude mice were implanted with COLO679 cells by subcutaneous injection into the flank. 5-ALA was subcutaneously injected into the tumor. The tumor was irradiated with 50 J/cm2 (day 0) and assessed daily until day 21.ResultsThe synergistic PDT effects of dual-wavelength irradiation and reactive oxygen species production were highest with the 405-nm and 505-nm wavelength combination. This dual wavelength combination was also the most effective in vivo.ConclusionWe could therefore conclude that dual-wavelength PDT is an efficient strategy for improving the therapeutic effects of PDT. Using a flexible LED unit is expected to achieve more uniform irradiation of uneven areas.
  • Atypical protein kinase C isoforms differentially regulate directional
           keratinocyte migration during wound healing
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s): Natsuko Noguchi, Tomonori Hirose, Tomoko Suzuki, Masami Kagaya, Kazuhiro Chida, Shigeo Ohno, Motomu Manabe, Shin-Ichi OsadaAbstractBackgroundThe epidermis possesses regenerative properties that become apparent only after wounding. Atypical protein kinase C (aPKC) isoforms aPKCζ and aPKCλ form a ternary complex with Par3 and Par6, and play crucial roles in establishing and maintaining epithelial cell polarity. The epidermal loss of aPKCλ results in progressive depletion of hair follicle stem cells. However, it is unclear whether aPKCs have equivalent activities in epidermal regeneration.ObjectivesTo clarify functional differences between aPKCζ and aPKCλ in cutaneous wound healing.MethodsWe compared cutaneous wound healing processes in vivo using mutant mice with genetic deletion of each aPKC isoform. We also analyzed functional differences between aPKCζ and aPKCλ in cell proliferation, directional cell migration, and formation of microtubules in vitro using primary keratinocytes established from each mutant mouse.ResultsWound healing was significantly retarded in epidermis-specific aPKCλ knockout mice. In aPKCλ-deleted keratinocytes, the correct orientation of cell protrusions toward the wound was disrupted through the destabilization of Par6β. The elongation of stabilized β-tubulin was also deteriorated in aPKCλ-deleted keratinocytes, leading to defects in cell spreading. Conversely, wound healing and directional cell migration in aPKCζ-deleted mice were comparable to those in their control littermates.ConclusionsaPKCs are not functionally equivalent; aPKCλ, but not aPKCζ, plays a primary role in cutaneous wound healing.
  • Circulating CCL20: A potential biomarker for active vitiligo together with
           the number of Th1/17 cells
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s): Li Zhang, Yuli Kang, Shujun Chen, Li Wang, Min Jiang, Leihong XiangAbstractBackgroundVitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear.ObjectiveTo investigate the potential role of CCL20 and the involvement of Th1/17 and Tc1/17 cells in the mechanism in vitiligo.MethodsOne hundred patients with vitiligo, and 20 healthy controls were included. The serum and blister fluid IL-17, IFN-γ, CCL20, and CXCL10 were studied using enzyme-linked immunosorbent assays. The numbers of Th1/17 cells and Tc1/17 cells in circulation were quantified using flow cytometry. CCR6 mRNA in peripheral blood mononuclear cells (PBMCs) was analyzed by real-time polymerase chain reaction and the protein level was confirmed by western blotting. CCR6 and CCL20 expression in lesions was analyzed by immunohistochemistry.ResultsThe serum CCL20 level was significantly elevated in patients with vitiligo. The level of serum CCL20 was higher in active than in the stable stage, which correlated positively with the Vitiligo European Task Force spreading score and the Vitiligo Area Scoring Index score. Patients with active vitiligo had elevated numbers of circulating Th1/17 cells and Tc1/17 cells, and upregulated expression of CCR6 in PBMCs and lesions. After effective treatment, the level of CCL20 in sera and blister fluid was significantly decreased, as were the numbers of circulating Th1/17 cells and Tc1/17 cells.ConclusionCCL20 might be a vital biomarker of active vitiligo, and circulating Th1/17 and Tc1/17 cells are involved in the pathogenesis of vitiligo.
  • Editors Choice
    • Abstract: Publication date: February 2019Source: Journal of Dermatological Science, Volume 93, Issue 2Author(s):
  • Optimum wavelength characteristics for phototherapy utilizing deep
           ultraviolet light-emitting diodes
    • Abstract: Publication date: Available online 29 January 2019Source: Journal of Dermatological ScienceAuthor(s): Hideyuki Masuda, Makoto Kimura, Akimichi Morita
  • Androgens modulate keratinocyte differentiation indirectly through
           enhancing growth factor production from dermal fibroblasts
    • Abstract: Publication date: Available online 26 January 2019Source: Journal of Dermatological ScienceAuthor(s): Chanat Kumtornrut, Takeshi Yamauchi, Saaya Koike, Setsuya Aiba, Kenshi YamasakiAbstractBackgroundThe main pathogenesis of acne vulgaris is increase in sebum production and abnormal keratinization of the hair infundibulum. The androgens are involved in acne pathogenesis by modulating sebaceous glands to enhance sebum production. However, the molecular mechanisms of abnormal keratinization of the hair infundibulum are not fully elucidated.ObjectiveWe hypothesized that the androgens affect the dermal fibroblasts, another androgen receptor-positive cells in the skin, resulting in abnormal keratinization through keratinocyte-fibroblast interaction.MethodsWe investigated effects of androgens and estrogens on growth factors expressions by RT-PCR and western blot analysis in human fibroblast (hFB), human keratinocyte (hKC), and fibroblast-keratinocyte co-culture. In vivo, we examined the growth factor expression in acne lesions compared to normal hair follicles by laser-assisted confocal microscope.ResultsIn vitro, androgens but not estrogens significantly increased amphiregulin (AREG), epiregulin (EREG), fibroblast growth factor (FGF) 10, and insulin-like growth factor binding protein (IGFBP) 5 mRNA and protein expressions in human fibroblasts but not in keratinocytes. In vivo, AREG, EREG, FGF10, and IGFBP5 were more abundant in acne lesion compared to normal facial skin. FGF10 suppressed cytokeratin 1 and cytokeratin 10 expression in hKC, which was along with the decreased ratio of cytokeratin 10 against cytokeratin 14 in acne lesions compared to normal facial skin. Also, DHT suppressed cytokeratin 1 and cytokeratin 10, in fibroblast-keratinocyte co-culture similarly to the effect of FGF10 to hKC.ConclusionThese observations suggested that androgens enhance growth factors production from dermal fibroblasts, and growth factors from fibroblasts alter keratinocyte differentiation in acne lesion.
  • Serum concentrations of HGF are correlated with response to anti-PD-1
           antibody therapy in patients with metastatic melanoma
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s): Yosuke Kubo, Satoshi Fukushima, Yukiko Inamori, Mina Tsuruta, Sho Egashira, Saori Yamada-Kanazawa, Satoshi Nakahara, Aki Tokuzumi, Azusa Miyashita, Jun Aoi, Ikko Kajihara, Yusuke Tomita, Kazumasa Wakamatsu, Masatoshi Jinnin, Hironobu IhnAbstractBackgroundAnti-programmed cell death protein (PD)-1 antibody treatment is associated with a notable improvement in only 30%–40% of patients. Thus, a predictive and easily measured marker of the clinical benefit of anti-PD-1 antibody treatment is necessary; therefore, in this study, we focused on the serum concentration of hepatocyte growth factor (HGF).ObjectivesTo evaluate whether the serum concentration of HGF can be used as a biomarker for the clinical response to anti-PD-1 antibody therapy.MethodsThis study included 29 metastatic melanoma patients receiving nivolumab or pembrolizumab. Nine patients responded to anti-PD-1 antibody treatment, whereas the other 20 patients did not. The serum concentrations of HGF were analyzed by using ELISA. In 28 patients, immunohistochemical analysis of the HGF protein in patients’ cancer tissues was also performed. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with an anti-CD3 antibody in the presence or absence of HGF and c-MET inhibitor. The expression of perforin in CD8+ T cells were evaluated by using flow cytometry.ResultsAmong the 29 recruited patients, the non-responders displayed higher serum concentrations of HGF than the responders (P =  0.00124). Patients with low serum concentrations of HGF showed longer overall survival (N = 28, P =  0.039; HR 0.3125, 95% CI 0.1036–0.9427) and progression-free survival (N = 24, P =  0.0068; HR 0.2087, 95% CI 0.06525–0.6676) than those with high concentrations of HGF. We observed a significant correlation between the serum concentration of HGF and immunohistochemical-positive staining (P =  0.000663). In a flow cytometry analysis of PBMCs from healthy donors, HGF was found to downregulate perforin secretion. Furthermore, the addition of capmatinib, a specific inhibitor of c-MET, increased the expression of perforin in CD8+ T cells.ConclusionsHGF concentration represents a valid biomarker that can be further developed for the evaluation of anti-PD-1 therapy. Our results suggested that c-MET inhibition promotes perforin expression in CD8+ T cells. Therefore, c-MET inhibitors can activate the immune system and may play an important role in combined immunotherapy.
  • Regulatory and effector B cells: Friends or foes'
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s): Takashi MatsushitaAbstractB cells have moved to the center stage in many autoimmune diseases including autoantibody-mediated diseases and T cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. B cells play an important role for immune response beyond antibody production through mechanisms like antigen presentation and cytokine production. However, not all B cells positively regulate immune responses. Regulatory B cells negatively regulate immune responses by production of anti-inflammatory cytokines such as IL-10, IL-35, and TGF-β. Regulatory B cells have been found to be decreased and/or functionally impaired in various autoimmune diseases. In contrast, B cells also produce pro-inflammatory cytokines, such as IL-6, IFN-γ and GM ­ CSF. These effector B cells contribute to the pathogenesis of autoimmune diseases. Regulatory and effector B cell balance regulates immune response through the release of cytokines. Furthermore, a protocol that selectively depletes effector B cells while sparing regulatory B cells would represent a potent therapy for autoimmune diseases rather than pan-B cell depletion using anti-CD20 mAb.
  • Genetic polymorphism predicting Methotrexate efficacy in Chinese patients
           with psoriasis vulgaris
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s): Ye hong Kuang, Yan Lu, Ke xiang Yan, Pan pan Liu, Wang qing Chen, Min xue Shen, Yi jing He, Li sha Wu, Qun Shi Qin, Xing chen Zhou, Jie Li, Juan Su, Cheng zhiLv, Wu Zhu, Xiang ChenAbstractBackgroundMethotrexate is the first systemic therapeutics of psoriasis. It is reported that 40% of the patients achieved a PASI75 after 12 weeks with a small dose of methotrexate (15 mg / w) treatment. So far there is not any large-scale exome sequencing been used to predict the efficacy of methotrexate in the treatment of psoriasis vulgaris.ObjectiveTo analyze the genetic polymorphism to predict methotrexate efficacy in Chinese patients with psoriasis vulgaris.MethodsIn this study, we used the whole exon high-throughput sequencing technology to detect the DNA sequence of 22 psoriasis vulgaris patients (11 responders, 11 non-responders) treated with methotrexate and captured approximately 236 variants with statistically significant in the whole exon sequencing, then in accordance with statistical differences and clinical relevance, we further selected 36 SNPs and 14 SNPs that have been reported in articles associated with the response of methotrexate. We used MassARRAY method to verify the 50 SNPs in 100 psoriatic patients treated with methotrexate.ResultsWe found 3 SNPs, rs216195T > C in SMG6, rs1050301G > A in IMMT, rs2285421T > C in UPK1A which might associate with the drug response of methotrexate.ConclusionWe have searched 3 new SNPs that could predict the efficacy of methotrexate in psoriasis vulgaris to some extent, providing a theoretical basis for precision medicine of methotrexate in future.
  • Cell-to-cell transmission of HSV-1 in differentiated keratinocytes
           promotes multinucleated giant cell formation
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s): Yoshiko Yamamoto, Takenobu Yamamoto, Yumi Aoyama, Wataru FujimotoAbstractBackgroundHerpes simplex virus (HSV) infection in the skin causes small grouped vesicles characterized by acantholytic cells and multinucleated giant cells (MGCs). Although viral factors have been studied as fusion proteins, little is known how the differentiation status of keratinocytes is involved in the formation of MGCs by HSV-1 infection.ObjectiveAs the human epidermis is composed of several layers of keratinocytes that undergo terminal differentiation, we aimed to elucidate whether the differentiation status of keratinocytes affects viral entry, propagation, cell-to-cell transmission of HSV-1, and MGC formation.MethodsHaCaT cells and normal human epidermal keratinocytes were cultured in either low- or high-Ca2+ medium. After HSV-1 infection, cellular morphology, viral propagation, and expression of cytoskeletal and intercellular adhesion molecules were examined sequentially. Viral entry, replication, and expression of HSV receptors were analyzed. Cell-to-cell transmission and fusion after HSV-1 infection was evaluated using the Cell Tracker™ Red CMTPX dye system.ResultsKeratinocytes in high-Ca2+ medium formed MGCs, but those in low-Ca2+ medium formed single nuclear round cells in response to HSV-1 infection. HSV-1 entered the keratinocytes more effectively in low-Ca2+ than in high-Ca2+ medium, although transcripts of HSV receptors were comparable in both conditions. HSV-1 could replicate more efficiently in high-Ca2+ than in low-Ca2+ medium. A cell-to-cell fusion assay showed that HSV-1-infected and adjacent-uninfected keratinocytes were involved in MGCs in high-Ca2+ but not in low-Ca2+ medium.ConclusionDifferentiated keratinocytes promote MGC formation by cell-to-cell fusion with resolution of cell membrane and cell-to-cell transmission of HSV-1 from infected keratinocytes to neighboring uninfected keratinocytes.
  • Increased expression of aquaporin-1 in dermal fibroblasts and dermal
           microvascular endothelial cells possibly contributes to skin fibrosis and
           edema in patients with systemic sclerosis
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s): Takashi Yamashita, Yoshihide Asano, Ryosuke Saigusa, Takashi Taniguchi, Kouki Nakamura, Shunsuke Miura, Tetsuo Toyama, Takehiro Takahashi, Yohei Ichimura, Megumi Hirabayashi, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi SatoAbstractBackgroundAquaporin-1 (AQP1), a water channel protein controlling the water contents of cells and tissues, exerts pleiotropic effects on various biological activities, including inflammation, angiogenesis, and extracellular matrix remodeling, by regulating cell behaviors and tissue water balance.ObjectiveTo investigate AQP1 roles in systemic sclerosis (SSc) which is characterized by autoimmune inflammation, vasculopathy, and tissue fibrosis.MethodsAQP1 expression was evaluated by immunohistochemistry and quantitative reverse transcription PCR in skin samples from human and animal models and by immunoblotting in cultured cells. Fli1 binding to the AQP1 promoter was evaluated by chromatin immunoprecipitation. Cell migration was assessed by scratch assay.ResultsDermal fibroblasts and endothelial cells highly expressed AQP1 in SSc lesional skin, and AQP1 expression in dermal fibroblasts and endothelial cells positively correlated with the degrees of tissue fibrosis and edema, respectively. Consistently, SSc dermal fibroblasts up-regulated AQP1 compared with normal dermal fibroblasts in vitro. Furthermore, TGF-β stimulation induced AQP1 expression in normal dermal fibroblasts, while TGF-β1 antisense oligonucleotide suppressed AQP1 expression in SSc dermal fibroblasts. In endothelial cells, Fli1 deficiency resulted in AQP1 up-regulation in vivo and in vitro and Fli1 bound to the AQP1 promoter. Importantly, SSc dermal fibroblasts and FLI1 siRNA-treated endothelial cells had a pro-migratory property, which was remarkably diminished by gene silencing of AQP1.ConclusionAQP1 is up-regulated in SSc dermal fibroblasts and SSc endothelial cells at least partially due to autocrine TGF-β stimulation and Fli1 deficiency, respectively, possibly contributing to inflammation, vasculopathy, and tissue fibrosis by regulating tissue edema and cell migration.
  • Editors Choice
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s):
  • Nanoparticle-mediated local delivery of pioglitazone attenuates
           bleomycin-induced skin fibrosis
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s): Mai Kanemaru, Jun Asai, Jun-ichiro Jo, Takahiro Arita, Minako Kawai-Ohnishi, Miho Tsutsumi, Makoto Wada, Yasuhiko Tabata, Norito KatohAbstractBackgroundNanoparticle-loaded delivery systems have attracted much attention recently. Poly(lactic-co-glycolic acid) (PLGA) is one of the most successful biodegradable polymers for biomedical applications. There are only a few studies on the treatment of dermal fibrosis with sustained-release drugs. Peroxisome proliferator-activated receptor-γ (PPAR-γ) plays an important role in endogenous anti-fibrotic defense mechanisms. Recent studies have suggested that pioglitazone, a synthetic PPAR-γ activator, has effects beyond reducing blood sugar and it can reduce fibrosis and inflammation when used systemically.ObjectiveWe aimed to assess the effects of local injections of pioglitazone-loaded PLGA nanoparticles (PGN-NP) on an experimental sclerosis and to demonstrate the in vivo pharmacokinetics of subcutaneously administered PLGA nanoparticles.MethodsLocally injectable PGN-NP were prepared and subcutaneously administered to bleomycin (BLM)-induced scleroderma model mice. The effect of pioglitazone was also evaluated with cultured fibroblasts. Coumarin-6-loaded fluorescent PLGA nanoparticles (FL-NP) and silicon naphthalocyanine-loaded near-infrared PLGA nanoparticles (NIR-NP) were used to demonstrate in vitro cellular uptake by cultured fibroblasts and the in vivo pharmacokinetics of subcutaneously administered nanoparticles.ResultsWeekly subcutaneous injections of PGN-NP attenuated skin fibrosis in BLM-induced scleroderma model mice. Pioglitazone significantly suppressed migration ability and TGF-β-mediated myofibroblast differentiation in cultured fibroblasts. FL-NP were internalized into cultured fibroblasts within 60 min, and PGN-NP-primed fibroblasts expressed anti-fibrotic phenotypes. Subcutaneously injected NIR-NP remained in the vicinity of the injection site more than non-particulate silicon naphthalocyanine.ConclusionThese results provide a basis for the development of new treatments for dermal fibrosis and a better understanding of the potential of PLGA nanoparticles in dermatology.
  • Botulinum toxin blocks mast cells and prevents rosacea like inflammation
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s): Jae Eun Choi, Tyler Werbel, Zhenping Wang, Chia Chi Wu, Tony L. Yaksh, Anna Di NardoAbstractBackgroundRosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.ObjectivesTo investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.MethodsPrimary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.ResultsOnabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.ConclusionsThese findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.
  • The first Japanese case of familial porphyria cutanea tarda diagnosed by a
           UROD mutation
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s): Akinobu Matsui, Eijiro Akasaka, Daiki Rokunohe, Yasushi Matsuzaki, Daisuke Sawamura, Hajime Nakano
  • Dysbiosis of oral microbiota in palmoplantar pustulosis patients
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s): Michiyoshi Kouno, Yurie Akiyama, Masaki Minabe, Naohiko Iguchi, Takeshi Nomura, Kazuyuki Ishihara, Shinichi Takahashi
  • The key question of irradiance when it comes to the effects of visible
           light in the skin
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s): Thierry Passeron
  • Impairment of lipophagy by PNPLA1 mutations causes lipid droplet
           accumulation in primary fibroblasts of Autosomal Recessive Congenital
           Ichthyosis patients
    • Abstract: Publication date: January 2019Source: Journal of Dermatological Science, Volume 93, Issue 1Author(s): Gizem Onal, Ozlem Kutlu, Ebru Ozer, Devrim Gozuacik, Aysen Karaduman, Serap Dokmeci EmreAbstractBackgroundAutosomal Recessive Congenital Ichthyosis (ARCI) is a group of epidermal keratinization disorders. One of the disease-associated proteins, patatin-like phospholipase domain-containing protein-1 (PNPLA1), plays a key role in the epidermal omega-O-acylceramide synthesis and localizes on the surface of lipid droplets (LDs).ObjectivePreviously, routine clinical test results showed abnormal LD accumulation in blood smear samples of our ARCI patients with PNPLA1 mutations. To investigate the abnormal accumulation of LDs, we analyzed primary fibroblast cells of ARCI patients with PNPLA1 mutations (p.Y245del and p.D172N). We hypothesized that PNPLA1 mutations might affect lipophagy-mediated regulation of LDs and cause intracellular lipid accumulation in ARCI patients.MethodsLD accumulation was analyzed by fluorescence staining with BODIPY®493/503 in the fibroblasts of patient cells and PNPLA1 siRNA transfected control fibroblast cells. The expression of PNPLA1 and its effects on the lipophagy-mediated degradation of LDs were analyzed by immunocytochemistry and immunoblotting.ResultsOur results showed that mutant or downregulated PNPLA1 protein causes abnormal intracellular LD accumulation. We found that PNPLA1 mutations affect neither the cellular localization nor the expression levels of the protein in fibroblast cells. When we analyzed lipophagic degradation process, LC3 expression and the number of autophagosomes were significantly decreased in fibroblast cells of the patients. In addition, co-localization of LDs with autophagosomes and lysosomes were markedly less than that of the control group.ConclusionPNPLA1 mutations caused disturbances in both autophagosome formation and fusion of autophagosomes with lysosomes. Our results indicate a possible role for PNPLA1 protein in LD regulation via lipophagy-mediated degradation.
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