David W C Hunt, Iordanka A Ivanova, Lina Dagnino
Chronic inflammatory skin disorders are frequently associated with impaired skin barrier function. Selective phosphodiesterase-4 (PDE4) inhibition constitutes an effective therapeutic strategy for the treatment of inflammatory skin diseases. We now report the pharmacological anti-inflammatory profile of DRM02, a novel pyrazolylbenzothiazole derivative with selective in vitro inhibitory activity toward PDE4 isoforms A, B and D. DRM02 treatment of cultured primary human and mouse epidermal keratinocytes interfered with pro-inflammatory cytokine production elicited by interleukin-1α and tumor necrosis factor-α...
June 1, 2020: Tissue Barriers
Yuqin Zhu, Yuxiang Ma, Weidong Zu, Jianing Song, Hua Wang, You Zhong, Hongmei Li, Yanmin Zhang, Qianqian Gao, Bo Kong, Junyu Xu, Fei Jiang, Xinren Wang, Shuwen Li, Chenhe Liu, Haichun Liu, Tao Lu, Yadong Chen
A series of N-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives with NF-κB inducing kinase (NIK) inhibitory activity were obtained through structure-based drug design and synthetic chemistry. Among them, 4-(3-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-4-morpholinophenyl)-2-(thiazol-2-yl)but-3-yn-2-ol (12f) was identified as a highly potent NIK inhibitor, along with satisfactory selectivity. The pharmacokinetics of 12f and its ability to inhibit interleukin 6 secretion in BEAS-2B cells were better than compound 1 developed by Amgen...
June 1, 2020: Journal of Medicinal Chemistry
Renu George, Anju George, T Sathish Kumar
Juvenile localized scleroderma (morphea) is the predominant scleroderma in childhood which affects the skin and may extend to the underlying fascia, muscle, joints and bone. The assessment of activity and damage can be done with a validated instrument like LoSCAT. Disease classified as "low severity" which includes superficial plaque morphea can be treated with topical mid potent- potent steroids, tacrolimus, calcipotriol or imiquimod in combination with phototherapy. Methotrexate is recommended for linear, deep and generalized morphea...
March 2020: Indian Dermatology Online Journal
Padmini Iriventi, N Vishal Gupta, Riyaz Ali M Osmani, V Balamuralidhara
BACKGROUND: Combination of curcumin with anti-inflammatory drug like caffeine shows augmented antipsoriatic action compared to curcumin alone and reduce the time taken for treatment of Psoriasis. OBJECTIVE: The objective of the present study was to develop nanosponge (NS) based topical gel of curcumin (CUR) and caffeine (CFN) combination that acts as a potential system for the treatment of psoriasis. METHODS: NS composed of dimethyl carbonate (DMC) as crosslinker and beta-cyclodextrin (β-CD) as polymer were prepared by hot melt method and incorporated in topical gels...
May 29, 2020: Daru: Journal of Faculty of Pharmacy, Tehran University of Medical Sciences
Shiguang Peng, Mei Cao, Xiaoying Sun, Yaqiong Zhou, Chu-Yen Chen, Tian Ma, Hongjin Li, Bin Li, Bo Zhu, Xin Li
Psoriasis is a common chronic inflammatory skin disease. Programmed cell death ligand 1 (PD‑L1) and programmed cell death 1 (PD‑1) are expressed on immune cells in a number of chronic inflammatory diseases. However, a limited number of studies have investigated the expression and function of the PD‑L1 and PD‑1 pathway in psoriatic inflammation. The present study used human psoriasis samples and imiquimod‑induced murine psoriasis models to investigate the potential role of PD‑1 in the modulation of psoriatic inflammation...
May 21, 2020: International Journal of Molecular Medicine
Xue Mei Li, Kyung Eun Jung, Su Hyuk Yim, Dong Kyun Hong, Chang Deok Kim, Jeong Yeon Hong, Ho Jung Lee, Sung Yul Lee, Jung Eun Kim, Chang Wook Park
Autophagy, one mechanism of programmed cell death, is fundamental to cellular homeostasis. Previous studies have identified autophagy as a novel mechanism by which cytokines control the immune response. However, its precise role in immune-related inflammatory skin diseases such as psoriasis remains unclear. Thus, this study explored the functional role of autophagy in psoriatic inflammation of epidermal keratinocytes. Strong light chain 3 immunoreactivity was observed in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model, and it was readily induced by polycytidylic acid (poly (I:C)), which stimulates Toll-like receptor 3 (TLR3), in human epidermal keratinocytes in vitro...
2020: BioMed Research International
Momoko Nakao, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato
Interferon regulatory factors (IRFs) play diverse roles in the regulation of the innate and adaptive immune responses in various diseases. In psoriasis, IRF2 is known to be involved in pathogenesis, while studies on other IRFs are limited. In this study, we investigated the role of IRF5 in psoriasis using imiquimod-induced psoriasis-like dermatitis. Although IRF5 is known to play a critical role in the induction of proinflammatory cytokines by immune cells, such as dendritic cells (DCs), macrophages, and monocytes, IRF5 deficiency unexpectedly exacerbated psoriasiform skin inflammation...
May 23, 2020: International Journal of Molecular Sciences
Yanqin Wang, Xinxin Li, Xiaoyun Xing, Haibo Xue, Ruiqun Qi, Hong Ji, Lei Ma
Purpose: To evaluate the regulating effect of Notch-Hes1 signaling on IL-17A+ γδ + T cell expression and IL-17A secretion in mouse psoriasis-like skin inflammation. Materials and Methods: Experimental mice were randomly divided into control group, model group (5% imiquimod- (IMQ-) treated mice), and intervention group (IMQ and γ -secretase inhibitor DAPT cotreated mice). The severity of psoriasis-like skin inflammation was evaluated by target lesion score based on the clinical psoriasis area and severity index (PASI)...
2020: Mediators of Inflammation
Kuntal DAS, Someswar Deb, Tejaswini Karanth
Objectives: The aim of this study was to evaluate the influence of metal ions present in soil as well as in leaf samples of Calendula officinalis and Phlebodium decumanum for the treatment of psoriasis. Materials and Methods: To meet the objective, soil and leaf samples were estimated for metal ions by atomic absorption spectrophotometer to determine the influence in antipsoriatic activity. Thereafter imiquimod-induced dermatitis lesions were created in grouped mice...
September 2019: Turkish journal of pharmaceutical sciences
Andrea Rodríguez-Tejero, Ahinoa Bueno-Rodríguez, Trinidad Montero-Vílchez, Salvador Arias-Santiago, Alejandro Molina-Leyva
No abstract text is available yet for this article.
May 23, 2020: Dermatologic Therapy
Christopher Hoyle, Elena Redondo-Castro, James Cook, Te-Chen Tzeng, Stuart M Allan, David Brough, Eloise Lemarchand
Microglial inflammation driven by the NLRP3 inflammasome contributes to brain disease and is a therapeutic target. Most mechanistic studies on NLRP3 activation utilise two-dimensional pure microglial cell culture systems. Here we studied the activation of the NLRP3 inflammasome in organotypic hippocampal slices, which allowed us to investigate microglial NLRP3 activation in a three-dimensional, complex tissue architecture. Toll-like receptor 2 and 4 activation primed microglial inflammasome responses in hippocampal slices by increasing NLRP3 and IL-1β expression...
May 23, 2020: Immunology
Jiajing Lu, Xin Xu, Ying Li, Ning Yu, Yangfeng Ding, Yuling Shi
Psoriasis is a common chronic skin disease characterized by epidermal proliferation and inflammation. Pustular psoriasis (PP) is one of the most serious and refractory. The number, differentiation, and function of B10 cells in patients with PP were analyzed, and the relationship between B10 cells and PP, an autoimmune disease, was explored. We established an Imiquimod psoriasis mouse model and subcutaneously injected B10 cells as treatment. We found that the proportion of B10 cells in the peripheral blood of patients with PP was lower than that of the normal controls...
May 22, 2020: Dermatologic Therapy
Ignasi Marti-Marti, Mercè Alsina, Priscila Giavedoni, Irene Fuertes
No abstract text is available yet for this article.
May 18, 2020: Enfermedades Infecciosas y Microbiología Clínica
Giancristoforo Simona, Diociaiuti Andrea, K Tchidjou Hyppolite, Lucchetti Maria Chiara, Carnevale Claudia, Rotunno Roberta, D'Argenio Patrizia, El Hachem Maya
BACKGROUND/OBJECTIVES: Anogenital condylomata acuminata are induced by human papillomavirus (HPV) and they rarely manifest in immunocompetent children. Therapeutic options depend on patient's age and general conditions and extension of the lesions. However, management is still a challenge and recurrences are frequent. Cryotherapy, laser and surgical treatments in children are painful and frequently require general anesthesia. Imiquimod is a topical immune response modifier and constitutes a non-invasive alternative for the treatment of anogenital condylomata acuminata...
May 19, 2020: Dermatologic Therapy
Jiun-Wen Guo, Yu-Pin Cheng, Chih-Yi Liu, Haw-Yueh Thong, Chi-Jung Huang, Yang Lo, Chen-Yu Wu, Shiou-Hwa Jee
Psoriasis is a chronic inflammatory skin disorder with a pathogenesis involving the interleukin-23/interleukin-17 axis. Salvianolic acid B exerts several pharmacological effects, such as antioxidation, anti-inflammation, and antitumor effects. The anti-psoriatic effects of salvianolic acid B have not been reported. In this study, we aimed to determine the optimum vehicle for salvianolic acid B, investigate its therapeutic effect on psoriatic-like skin conditions, and explore its underlying mechanisms of action...
May 17, 2020: Pharmaceutics
Victoria Psomiadou, Christos Iavazzo, Athanasios Douligeris, Alexandros Fotiou, Anastasia Prodromidou, Nikolaos Mplontzos, Evgenia Karavioti, George Vorgias
Human papillomavirus (HPV) has been directly related to acuminate warts and cervical cancer, the second most common neoplasia among women. Given the lack of treatment against the virus itself, many medications have been utilised, mainly aiming in modifying the host's immunological response. We present the case of a 54 years old postmenopausal patient with a history of vaginal cuff wart and HPV persistence that we managed in our clinic for 6 months with a mix of curcumin, aloe vera, amla and other natural ingredients...
2020: Acta Medica (Hradec Králové)
Yan Wang, Ping Li, Lu Zhang, Jing Fu, Tingting Di, Ningfei Li, Yujiao Meng, Jianning Guo, Jingxia Zhao
Psoriasis is a common, chronic multifactorial inflammatory skin disease with both genetic and environmental components. A number of studies have suggested that psoriasis episodes are often preceded by stressful life events. Nevertheless, the underline mechanisms of stress in psoriasis remain unexplored. To address this question, we established an emotional stress mouse model induced by empty bottle stimulation, and applied imiquimod (IMQ), a ligand of TLR7/8 and effective potent immune activator, on the dorsal skin to induce psoriasis-like lesions...
May 18, 2020: Journal of Leukocyte Biology
Kai Chen, Yuhao Liu, Jianbo He, Nathan Pavlos, Chao Wang, Jacob Kenny, Jinbo Yuan, Qingwen Zhang, Jiake Xu, Wei He
Steroid-induced osteonecrosis of the femoral head (ONFH) is a progressive bone disorder which typically results in femoral head collapse and hip joint dysfunction. It is well-accepted that abnormal osteoclast activity contributes to loss of bone structural integrity and subchondral fracture in ONFH. However, the pathophysiologic mechanisms underlying the recruitment and hyperactivation of osteoclasts in ONFH remain incompletely understood. We assessed the changes of reactive oxygen species (ROS) level and subsequent osteoclast alterations in steroid-induced osteonecrotic femoral heads from both patients and rat ONFH models...
2020: International Journal of Biological Sciences
Gabriela V Pinget, Jian Tan, Paula Niewold, Eugenia Mazur, Alexandra S Angelatos, Nicholas J C King, Laurence Macia
Psoriasis is a chronic inflammatory condition of the skin, autoimmune in nature, that affects millions of people worldwide. It is driven by IL-17-producing CD4 and γδ-T cells and targeted by current anti-IL-17 or anti-IL-23 monoclonal antibody therapies. These treatments are expensive, increase the risk of opportunistic infections and do not specifically target the inflammatory cascade. Other cells, including inflammatory monocytes have been shown to migrate to psoriatic plaques in both human disease and the imiquimod (IMQ)-induced mouse model and could thus constitute potential alternative therapeutic targets...
May 7, 2020: Journal of Investigative Dermatology
Timothy S Wang, Caitlin C Griffiths, Elise M Roman
No abstract text is available yet for this article.
May 6, 2020: Journal of the American Academy of Dermatology
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