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Psoriasis and gene therapy

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https://www.readbyqxmd.com/read/29143979/analysis-of-anti-tnf-induced-skin-lesions-reveals-strong-th1-activation-with-some-distinct-immunological-characteristics
#1
E Stoffel, H Maier, E Riedl, M-C Brüggen, B Reininger, M Schaschinger, C Bangert, E Guenova, G Stingl, P M Brunner
BACKGROUND: Psoriasiform and eczematous eruptions are the most common dermatological adverse reaction linked to anti-TNF-α therapy. Yet, a detailed characterization of their immune phenotype is lacking. OBJECTIVES: We sought to characterize anti-TNF-α induced inflammatory skin lesions on a histopathologic, cellular and molecular level, compared to psoriasis, eczema (atopic dermatitis), and healthy control skin. METHODS: Histopathologic evaluation, gene expression (quantitative RT-PCR) and computer-assisted immunohistologic studies (TissueFAXS) were performed on 19 skin biopsies from IBD (n=17) and rheumatoid arthritis (n=2) patients with new-onset inflammatory skin lesions during anti-TNF-α-therapy...
November 16, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29131243/photodynamic-therapy-with-5-aminolevulinic-acid-suppresses-ifn-%C3%AE-induced-k17-expression-in-hacat-cells-via-mapk-pathway
#2
X-L Wang, Q Sun
OBJECTIVE: Psoriasis is a chronic inflammatory skin disorder that greatly affects the patient's quality of life. Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has recently been applied for inflammatory dermatoses including psoriasis. However, the therapeutic effect of ALA-PDT is yet to be validated, and the underlying mechanisms remain unclear. MATERIALS AND METHODS: In this study, a psoriatic model was established by treating HaCaT cells with 250 U/ml IFN-γ for 48 h...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29094282/tofacitinib-a-new-oral-therapy-for-psoriasis
#3
REVIEW
Alexandra Azevedo, Tiago Torres
Psoriasis is a common, chronic, immune-mediated disease associated with several comorbidities. Biologic therapy revolutionized the treatment of moderate-to-severe psoriasis, improving physical and emotional burden of the disease. Still, there are unmet needs in the treatment of psoriasis regarding long-term efficacy, tolerability, safety, route of administration, and cost. The increased knowledge of the pathogenesis of the intracellular metabolic pathways allowed the development of new compounds that inhibit certain intracellular proteins involved in the immune response...
November 1, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29031638/dbgaps-a-comprehensive-database-of-genes-and-genetic-markers-associated-with-psoriasis-and-its-subtypes
#4
Shweta Aggarwal, Arnab Nayek, Dibyabhaba Pradhan, Rashi Verma, Monika Yadav, Kalaiarasan Ponnusamy, Arun Kumar Jain
Psoriasis is a systemic hyperproliferative inflammatory skin disorder, although rarely fatal but significantly reduces quality of life. Understanding the full genetic component of the disease association may provide insight into biological pathways as well as targets and biomarkers for diagnosis, prognosis and therapy. Studies related to psoriasis associated genes and genetic markers are scattered and not easily amendable to data-mining. To alleviate difficulties, we have developed dbGAPs an integrated knowledgebase representing a gateway to psoriasis associated genomic data...
October 12, 2017: Genomics
https://www.readbyqxmd.com/read/28921458/pharmacogenetics-and-pharmacogenomics-in-moderate-to-severe-psoriasis
#5
REVIEW
María C Ovejero-Benito, Ester Muñoz-Aceituno, Alejandra Reolid, Miriam Saiz-Rodríguez, Francisco Abad-Santos, Esteban Daudén
Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis...
September 18, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28887914/curcumin-attenuates-the-scurfy-induced-immune-disorder-a-model-of-ipex-syndrome-with-inhibiting-th1-th2-th17-responses-in-mice
#6
Gihyun Lee, Hwan-Suck Chung, Kyeseok Lee, Hyeonhoon Lee, Minhwan Kim, Hyunsu Bae
BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is a lethal autoimmune disease caused by mutations in the Foxp3 gene scurfin (scurfy). Immunosuppressive therapy for IPEX patients has been generally ineffective and has caused severe side effects, however curcumin has shown immune regulation properties for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel diseases without side effects. OBJECTIVE: The aim of this study was to investigate whether curcumin would attenuate symptoms of IPEX in mouse model and would prolong its survival period...
September 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28865459/clinical-efficacy-and-il-17-targeting-mechanism-of-indigo-naturalis-as-a-topical-agent-in-moderate-psoriasis
#7
RANDOMIZED CONTROLLED TRIAL
Hui-Man Cheng, Yang-Chang Wu, Qingmin Wang, Michael Song, Jackson Wu, Dion Chen, Katherine Li, Eric Wadman, Shung-Te Kao, Tsai-Chung Li, Francisco Leon, Karen Hayden, Carrie Brodmerkel, C Chris Huang
BACKGROUND: Indigo naturalis is a Traditional Chinese Medicine (TCM) ingredient long-recognized as a therapy for several inflammatory conditions, including psoriasis. However, its mechanism is unknown due to lack of knowledge about the responsible chemical entity. We took a different approach to this challenge by investigating the molecular profile of Indigo naturalis treatment and impacted pathways. METHODS: A randomized, double-blind, placebo-controlled clinical study was conducted using Indigo naturalis as topical monotherapy to treat moderate plaque psoriasis in a Chinese cohort (n = 24)...
September 2, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28833576/towards-the-development-of-a-rnai-based-topical-treatment-for-psoriasis-proof-of-concept-in-a-3d-psoriasis-skin-model
#8
Desmet Eline, Mireille Van Gele, Lynda Grine, Katrien Remaut, Jo Lambert
RNA interference has emerged as a powerful tool for therapeutic gene silencing, as it offers the possibility to silence virtually any known pathology-causing gene. However, in vivo delivery of RNAi molecules is hampered by their unfavorable physicochemical characteristics and susceptibility to degradation by endogenous enzymes. To overcome these limitations, we recently developed an elastic liposomal formulation, called DDC642, as topical delivery system of therapeutic RNAi molecules for skin disorders. In this study, we validated the therapeutic efficacy of DDC642-encapsulated RNAi molecules in the treatment of psoriasis using three different in vitro models: a standardized keratinocyte monolayer culture, psoriasis-induced keratinocytes and a psoriasis reconstructed skin model...
August 20, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28747603/autoinflammatory-diseases-in-dermatology-ditra-and-camps
#9
REVIEW
Kazumitsu Sugiura
Deficiency of interleukin thirty-six receptor antagonist (DITRA) and CARD14 mediated psoriasis (CAMPS) are autoinflammatory diseases in dermatology. The causative genes of DITRA and CMAPS have been identified recently. In this paper, IL36RN and CARD14, the causative gene for DITRA and CAMPS, respectively were explained. In addition, clinical features and therapies for generalized pustular psoriasis not associated with psoriasis vulgaris (GPP without PsV), and pityriasis rubra pilaris type V (PRP type V) were described...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28745729/highlights-of-skin-disease-education-foundation-s-41st-annual-hawaii-dermatology-seminar%C3%A2
#10
Kenneth B Gordon, Craig L Leonardi, Daniel E Furst, Neal Bhatia, Lawrence F Eichenfield, Katie Beleznay
New therapies, recent pathophysiological findings, and updated guidelines combined to create compelling presentations at the Skin Disease Education Foundation's 41st Annual Hawaii Dermatology Seminar™. This educational supplement summarizes the highlights of clinical sessions presented during this CME/CE conference. A growing understanding of the biology of psoriasis has facilitated the development of increasingly efficacious medications. Skin clearance used to be regarded as an impractical goal for psoriasis therapy...
June 2017: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28705779/autoimmune-aspects-of-psoriasis-heritability-and-autoantigens
#11
REVIEW
Jörg Christoph Prinz
Chronic immune-mediated disorders (IMDs) constitute a major health burden. Understanding IMD pathogenesis is facing two major constraints: Missing heritability explaining familial clustering, and missing autoantigens. Pinpointing IMD risk genes and autoimmune targets, however, is of fundamental importance for developing novel causal therapies. The strongest association of all IMDs is seen with human leukocyte antigen (HLA) alleles. Using psoriasis as an IMD model this article reviews the pathogenic role HLA molecules may have within the polygenic predisposition of IMDs...
July 10, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28698171/natural-compounds-for-the-treatment-of-psoriatic-arthritis-a-proposal-based-on-multi-targeted-osteoclastic-regulation-and-on-a-preclinical-study
#12
Shiqiang Deng, Jianwen Cheng, Jinmin Zhao, Felix Yao, Jiake Xu
BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting approximately 2% to 3% of the population globally, and is characterized by both peripheral articular manifestations and axial skeletal involvement. Conventional therapies for PsA have not been fully satisfactory, though natural products (NPs) have been shown to be highly effective and represent important treatment options for psoriasis. PsA is a multigenic autoimmune disease with both environmental and genetic factors contributing to its pathogenesis...
July 11, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28617319/pde4-inhibition-and-inflammatory-bowel-disease-a-novel-therapeutic-avenue
#13
REVIEW
Marco Spadaccini, Silvia D'Alessio, Laurent Peyrin-Biroulet, Silvio Danese
BACKGROUND: In the last few decades, a better knowledge of the inflammatory pathways involved in the pathogenesis of Inflammatory Bowel Disease (IBD) has promoted biological therapy as an important tool to treat IBD patients. However, in spite of a wider spectrum of biological drugs, a significant proportion of patients is unaffected by or lose their response to these compounds, along with increased risks of infections and malignancies. For these reasons there is an urgent need to look for new pharmacological targets...
June 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28602842/immune-responses-and-parasitological-observations-induced-during-probiotic-treatment-with-medicinal-trichuris-suis-ova-in-a-healthy-volunteer
#14
Andrew R Williams, Anders Dige, Tue Kruse Rasmussen, Christian L Hvas, Jens F Dahlerup, Lars Iversen, C Rune Stensvold, Jørgen Agnholt, Peter Nejsum
Ingestion of eggs (ova) of the porcine nematode parasite Trichuris suis (TSO) may reduce the severity of autoimmune disorders, however the development of TSO treatment as a useful therapy for autoimmune diseases is hampered by a lack of knowledge on the development of the parasite and the nature of the local immune responses in humans. Here, we used colonoscopy to investigate the development of T. suis and related mucosal and systemic immune responses during TSO treatment in an intestinally healthy male volunteer...
August 2017: Immunology Letters
https://www.readbyqxmd.com/read/28597172/the-p2x7-receptor-is-not-essential-for-development-of-imiquimod-induced-psoriasis-like-inflammation-in-mice
#15
Nicholas J Geraghty, Kylie J Mansfield, Stephen J Fuller, Debbie Watson, Ronald Sluyter
Psoriasis is a chronic inflammatory skin disorder, characterised by epidermal hyperplasia (acanthosis) and leukocyte infiltration of the skin. Current therapies are inadequate, highlighting the need for new therapeutic targets. The P2X7 receptor is implicated in the pathogenesis of psoriasis. This study investigated the role of P2X7 in imiquimod (IMQ)-induced psoriasis-like inflammation. Topically applied IMQ caused twofold greater ear swelling in BALB/c mice compared to C57BL/6 mice, which encode a partial loss-of-function missense mutation in the P2RX7 gene...
June 8, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28585891/in%C3%A2-vitro-psoriasis-models-with-focus-on-reconstructed-skin-models-as-promising-tools-in-psoriasis-research
#16
Eline Desmet, Anesh Ramadhas, Jo Lambert, Mireille Van Gele
Psoriasis is a complex chronic immune-mediated inflammatory cutaneous disease associated with the development of inflammatory plaques on the skin. Studies proved that the disease results from a deregulated interplay between skin keratinocytes, immune cells and the environment leading to a persisting inflammatory process modulated by pro-inflammatory cytokines and activation of T cells. However, a major hindrance to study the pathogenesis of psoriasis more in depth and subsequent development of novel therapies is the lack of suitable pre-clinical models mimicking the complex phenotype of this skin disorder...
June 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28557155/tumour-stage-mycosis-fungoides-regressing-with-milia-and-pustules-after-total-skin-electron-beam-therapy
#17
LETTER
T Puiu, D A Porto, F Siddiqui, H W Lim
No abstract text is available yet for this article.
October 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28505128/a-proposal-for-a-study-on-treatment-selection-and-lifestyle-recommendations-in-chronic-inflammatory-diseases-a-danish-multidisciplinary-collaboration-on-prognostic-factors-and-personalised-medicine
#18
Vibeke Andersen, Uffe Holmskov, Signe Bek Sørensen, Mohamad Jawhara, Karina W Andersen, Anette Bygum, Lone Hvid, Jakob Grauslund, Jimmi Wied, Henning Glerup, Ulrich Fredberg, Jan Alexander Villadsen, Søren Geill Kjær, Jan Fallingborg, Seyed A G R Moghadd, Torben Knudsen, Jacob Brodersen, Jesper Frøjk, Jens F Dahlerup, Ole Haagen Nielsen, Robin Christensen, Anders Bo Bojesen, Grith Lykke Sorensen, Steffen Thiel, Nils J Færgeman, Ivan Brandslund, Allan Stensballe, Erik Berg Schmidt, Andre Franke, David Ellinghaus, Philip Rosenstiel, Jeroen Raes, Berit Heitmann, Mette Boye, Charlotte Lindgaard Nielsen, Lars Werner, Jens Kjeldsen, Torkell Ellingsen
Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome...
May 15, 2017: Nutrients
https://www.readbyqxmd.com/read/28489810/a-case-report-of-hereditary-neuropathy-with-liability-to-pressure-palsies-accompanied-by-type-2-diabetes-mellitus-and-psoriasis
#19
Jing Li, Bing Niu, Xiaoling Wang, Huaiqiang Hu, Bingzhen Cao
RATIONALE: Hereditary neuropathy with liability to pressure palsy (HNPP) is an episodic, multifocal neuropathy, with a typical clinical presentation of recurrent transient pressure palsies, which is induced by a PMP22 deletion. Another neuropathy caused by a PMP22 duplication is Charcot-Marie-Tooth disease type 1A (CMT1A). PMP22 is a gene coding a protein called peripheral myelin protein 22 (PMP22), which plays an essential role in the formation and maintenance of compact myelin. Coexistence of type 2 diabetes mellitus (T2DM) and CMT1A has been reported in many work, however HNPP patients with T2DM are rare, and comorbidity of HNPP and psoriasis has not been reported previously...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28444425/pharmacogenetic-markers-to-predict-the-clinical-response-to-methotrexate-in-south-indian-tamil-patients-with-psoriasis
#20
S Indhumathi, Medha Rajappa, Laxmisha Chandrashekar, P H Ananthanarayanan, D M Thappa, V S Negi
INTRODUCTION: Despite the advent of several new systemic therapies, methotrexate remains the gold standard for the treatment of moderate to severe psoriasis. However, there exists a significant heterogeneity in individual response to methotrexate. There are no consistently reliable markers to predict methotrexate treatment response till date. OBJECTIVES: We aimed to demonstrate the association of certain genetic variants in the HLA (HLA-A2, HLA-B17, and HLA-Cw6) and the non-HLA genes including T-helper (Th)-1, Th-2, Th-17 cytokine genes (IFN-γ, IL-2, IL-4, IL-10, IL-12B, and IL-23R), and T-regulatory gene (FOXP3) with the methotrexate treatment response in South Indian Tamil patients with psoriasis...
August 2017: European Journal of Clinical Pharmacology
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