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Psoriasis and gene therapy

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https://www.readbyqxmd.com/read/29730187/identification-of-proresolving-and-inflammatory-lipid-mediators-in-human-psoriasis
#1
Alexander V Sorokin, Paul C Norris, Justin T English, Amit K Dey, Abhishek Chaturvedi, Yvonne Baumer, Joanna Silverman, Martin P Playford, Charles N Serhan, Nehal N Mehta
BACKGROUND: Psoriasis (PSO) is an immune-mediated inflammatory disease associated with metabolic and cardiovascular comorbidities. It is now known that resolution of inflammation is an active process locally controlled by specialized proresolving mediators (SPMs), named resolvins (Rvs), protectins, and maresins. OBJECTIVE: It is unknown whether these potent lipid mediators (LMs) are involved in PSO pathophysiology and if the skin and blood have disease-specific SPMs phenotype profiles...
April 6, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29726727/epigenetic-therapy-and-dermatologic-disease-moving-beyond-ctcl
#2
Joshua S Mervis, Jean S McGee
The epigenetic regulation of gene expression is accomplished primarily through DNA methylation, histone modification, and gene silencing via the action of microRNAs. While previously very difficult to study, the field of epigenetics has been greatly facilitated by recent technological innovations. Alterations in the epigenome and epigenetic machinery are now known to be present in a variety of diseases, most notably cancers. Moreover, evidence has emerged that epigenetic dysregulation plays a causative role in disease pathogenesis...
May 4, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29619998/association-of-il36rn-mutation-with-clinical-features-therapeutic-response-to-acitretin-and-frequency-of-recurrence-in-patients-with-generalized-pustular-psoriasis
#3
Teng Zhu, Hongzhong Jin, Dan Shu, Feng Li, Chao Wu
Previous studies have revealed that IL36RN mutations play a pivotal role in the pathogenesis of generalized pustular psoriasis (GPP), however, the clinical relevance is unclear. To investigate the correlation between IL36RN mutations and clinical features, recurrence frequency, and therapeutic response to acitretin in GPP patients with long-term follow-up. This retrospective cohort study, lasting 2-4 years, included 61 GPP and 48 psoriasis vulgaris (PV) patients. Sequence analysis of all five exons of the IL36RN gene revealed two genetic variants (c...
April 5, 2018: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/29565192/pharmacotherapeutic-approaches-for-treating-psoriasis-in-difficult-to-treat-areas
#4
Dario Kivelevitch, Jillian Frieder, Ian Watson, So Yeon Paek, M Alan Menter
Despite great therapeutic advancements in psoriasis, four notable difficult-to-treat areas including the scalp, nails, intertriginous (including genitals), and palmoplantar regions, pose a challenge to both physicians and patients. Localized disease of these specific body regions inflicts a significant burden on patients' quality of life and requires an adequate selection of treatments. Areas covered: This manuscript discusses appropriate therapies and important treatment considerations for these difficult-to-treat areas based on the available clinical data from the literature...
March 22, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29559344/longitudinal-study-of-the-psoriasis-associated-skin-microbiome-during-therapy-with-ustekinumab-in-a-randomized-phase-3b-clinical-trial
#5
Michael Loesche, Kamyar Farahi, Kimberly Capone, Steven Fakharzadeh, Andrew Blauvelt, Kristina Callis Duffin, Samuel E DePrimo, Ernesto J Muñoz-Elías, Carrie Brodmerkel, Bidisha Dasgupta, Marc Chevrier, Kevin Smith, Joseph Horwinski, Amanda Tyldsley, Elizabeth A Grice
BACKGROUND: Plaque psoriasis, a chronic inflammatory disease primarily affecting the skin, is thought to have a multifactorial etiology, including innate immune system dysregulation, environmental triggers, and genetic susceptibility. PURPOSE: We sought to further understand the role of skin microbiota in psoriasis pathogenesis, as well as their response to therapy. We systematically analyzed dynamic microbiota colonizing psoriasis lesions and adjacent nonlesional skin in 114 patients prior to and during ustekinumab treatment in a Phase 3b clinical trial...
March 17, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29551126/role-of-mda-7-il-24-a-multifunction-protein-in-human-diseases
#6
Mitchell E Menezes, Praveen Bhoopathi, Anjan K Pradhan, Luni Emdad, Swadesh K Das, Chunqing Guo, Xiang-Yang Wang, Devanand Sarkar, Paul B Fisher
Subtraction hybridization identified genes displaying differential expression as metastatic human melanoma cells terminally differentiated and lost tumorigenic properties by treatment with recombinant fibroblast interferon and mezerein. This approach permitted cloning of multiple genes displaying enhanced expression when melanoma cells terminally differentiated, called melanoma differentiation associated (mda) genes. One mda gene, mda-7, has risen to the top of the list based on its relevance to cancer and now inflammation and other pathological states, which based on presence of a secretory sequence, chromosomal location, and an IL-10 signature motif has been named interleukin-24 (MDA-7/IL-24)...
2018: Advances in Cancer Research
https://www.readbyqxmd.com/read/29544684/anti-il-12-il-23p40-antibody-ameliorates-dermatitis-and-skin-barrier-dysfunction-in-mice-with-imiquimod-induced-psoriasis-like-dermatitis
#7
Takehiro Takahashi, Yoko Koga, Mie Kainoh
Psoriasis is a chronic inflammatory skin disease characterized by erythema, skin hyperplasia, scales, and keratinocyte hyperproliferation. While the cause of psoriasis is not clearly understood, a dysregulated immune system, especially activation of IL-23/IL-17 axis, has been strongly implicated in the pathogenesis of psoriasis. For example, anti-IL-23 therapy is effective in psoriasis patients, and thus IL-23 is considered as a potential therapeutic target for the treatment of psoriasis. The skin barrier provides protection of the human body against infection from external pathogens...
March 12, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29454820/il12b-il23a-il23r-and-hla-c-06-genetic-variants-in-psoriasis-susceptibility-and-response-to-treatment
#8
Adriana Bojko, Roksana Ostasz, Monika Białecka, Adam Klimowicz, Damian Malinowski, Robert Budawski, Piotr Bojko, Marek Droździk, Mateusz Kurzawski
The role of interleukin-23 is crucial in the pathogenesis of psoriasis, and IL23A, IL12B and IL23R genetic variants have been associated with the disease in genome-wide association studies. In the current paper we have conducted a confirmation study of the abovementioned genetic factors in a case-control analysis of 507 psoriatic patients and 396 controls from a Polish population, and subsequently analyzed the impact of genetic variants on response to topical and NB-UVB therapy in a subset of 306 patients. Case-control analysis revealed an association of IL12B rs3212227 and IL23R rs11209026 minor allele carrier status with reduced odds for psoriasis (OR = 0...
April 2018: Human Immunology
https://www.readbyqxmd.com/read/29356172/therapy-response-was-not-altered-by-hla-cw6-status-in-psoriasis-patients-treated-with-secukinumab-a-retrospective-case-series
#9
LETTER
F Anzengruber, M Drach, J-T Maul, A G Kolios, B Meier, A A Navarini
No abstract text is available yet for this article.
January 22, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29328507/genetics-of-immune-mediated-inflammatory-diseases
#10
REVIEW
T David, S F Ling, A Barton
Immune-mediated inflammatory diseases (IMIDs) are characterized by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co-morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome-wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged...
January 12, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29318966/chronic-inflammatory-diseases-and-atherosclerotic-cardiovascular-disease-innocent-bystanders-or-partners-in-crime
#11
Peter Riis Hansen
Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research...
January 9, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29158815/tethering-interleukin-22-to-apolipoprotein-a-i-ameliorates-mice-from-acetaminophen-induced-liver-injury
#12
Wei Chen, Xuyao Zhang, Jiajun Fan, Wenjing Zai, Jingyun Luan, Yubin Li, Shaofei Wang, Qicheng Chen, Yichen Wang, Yanxu Liang, Dianwen Ju
Increasing evidence indicates that interleukin-22 (IL-22) holds tremendous potential as a protective agent in preventing liver injury, but its pleiotropic effects and pathogenic role in carcinogenesis, rheumatoid arthritis and psoriasis restrict its systemic application. Here, we first developed a nanoparticle (liposIA) as a liver-targeted agent through IL-22 tethered to apolipoprotein A-I (ApoA-I) in a gene therapy vector. LiposIA was prepared using thin film dispersion method and the complexes exhibited desirable nanoparticle size, fine polydisperse index, highly efficient transfection, and excellent serum and storage stability...
2017: Theranostics
https://www.readbyqxmd.com/read/29143979/analysis-of-anti-tumour-necrosis-factor-induced-skin-lesions-reveals-strong-t-helper-1-activation-with-some-distinct-immunological-characteristics
#13
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 reactions linked to anti-tumour necrosis factor (TNF)-α therapy. Yet, a detailed characterization of their immune phenotype is lacking. OBJECTIVES: To characterize anti-TNF-α-induced inflammatory skin lesions at a histopathological, cellular and molecular level, compared with psoriasis, eczema (atopic dermatitis) and healthy control skin. METHODS: Histopathological evaluation, gene expression (quantitative real-time polymerase chain reaction) and computer-assisted immunohistological studies (TissueFAXS) were performed on 19 skin biopsies from patients with inflammatory bowel disease (n = 17) and rheumatoid arthritis (n = 2) 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
#14
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
#15
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...
February 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29031638/dbgaps-a-comprehensive-database-of-genes-and-genetic-markers-associated-with-psoriasis-and-its-subtypes
#16
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
#17
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
#18
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
#19
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
#20
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
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