Psoriasis and gene therapy

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Developing protein drugs that can target intracellular sites remains a challenge due to their inadequate membrane permeability. Efficient carriers for cytosolic protein delivery are required for protein-based drugs, cancer vaccines, and CRISPR-Cas9 gene therapies. Here, we report a screening process to identify highly efficient materials for cytosolic protein delivery from a library of dual-functionalized polymers bearing both boronate and lipoic acid moieties. Both ligands were found to be crucial for protein binding, endosomal escape, and intracellular protein release...

BACKGROUND: Psoriasis is an immune-mediated disorder influenced by environmental factors on a genetic basis. Despite advancements, challenges persist, including the diminishing efficacy of biologics and small-molecule targeted agents, alongside managing recurrence and psoriasis-related comorbidities. Unraveling the underlying pathogenesis and identifying valuable biomarkers remain pivotal for diagnosing and treating psoriasis. METHODS: We employed a series of bioinformatics (including single-cell sequencing data analysis and machine learning techniques) and statistical methods to integrate and analyze multi-level data...

Psoriasis is a common chronic inflammatory skin disease characterized by abnormal activation and infiltration of T-cells and excessive proliferation of keratinocytes (KCs). Its pathogenesis is complex and frequently accompanied by the imbalance of T-cell subpopulations, contributing to its development and further exacerbation. Therefore, the immune system, especially T-cells, is mainly involved in the pathogenesis of psoriasis. While T-cell activation not only requires the first recognition of T-cell receptor and major histocompatibility complex peptide, co-stimulatory and co-inhibitory pathways are reported to promote or dampen T-cell responses through a variety of mechanisms...

Despite the abundance of epidemiological evidence for the high comorbid rate between psoriasis and obesity, systematic approaches to common inflammatory mechanisms have not been adequately explored. We performed a meta-analysis of publicly available RNA-sequencing datasets to unveil putative mechanisms that are postulated to exacerbate both diseases, utilizing both late-stage, disease-specific meta-analyses and consensus gene co-expression network (cWGCNA). Single-gene meta-analyses reported several common inflammatory mechanisms fostered by the perturbed expression profile of inflammatory cells...

BACKGROUND: Generalised pustular psoriasis (GPP) is a rare and chronic skin disease historically treated with therapies that were originally intended to treat plaque psoriasis (PsO). However, GPP and plaque PsO have distinct pathogeneses and clinical courses. OBJECTIVES: This study aimed to further characterise the unique genetic background of GPP by summarising evidence on the frequency and type of IL3 6RN gene mutation, a gene that normally suppresses proinflammatory responses, in patients with GPP compared to patients with GPP and plaque PsO, and patients with plaque PsO only...

Moderate-to-severe psoriasis (Ps) treatment includes systemic drugs and biological agents. Apremilast, a small molecule primarily metabolized by cytochrome CYP3A4, modulates the immune system by specifically inhibiting phosphodiesterase type 4 (PDE4) isoforms and is currently used for the treatment of Ps and psoriatic arthritis (PsA). Clinical trials and real-world data showed variable efficacy in response among Ps patients underlying the need for personalized therapy. This study implements a candidate-gene and a network-based approach to identify genetic markers associated with apremilast response in forty-nine Greek Ps patients...

BACKGROUND AND PURPOSE: The interleukin (IL)-36 pathway is a critical player in the pathogenesis of pustular psoriasis. However, therapies targeting this pathway are limited or unaffordable (e.g. the anti-IL-36 receptor antibody). AMP-activated protein kinase (AMPK), a regulator of cellular energy and metabolism, is known to participate in inflammatory diseases. However, its role in IL-36-induced skin inflammation remains unclear. Therefore, we sought to investigate the role of AMPK signals in regulating IL-36-induced responses in the skin...

Psoriasis is a common chronic inflammatory skin disease with a complex pathogenesis involving immune system dysregulation and inflammation. Previous studies have indicated that metabolic abnormalities are closely related to the development and occurrence of psoriasis. However, the specific involvement of amino acid metabolism in the pathogenesis of psoriasis remains unclear. In this study, we conducted a comprehensive analysis of amino acid metabolism pathway changes in psoriasis patients using transcriptome data, genome-wide association studies (GWASs) data, and single-cell data...

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is characterized by hyperkeratosis that produces the classic silvery scales, and the pathogenesis of psoriasis involves abnormal proliferation of keratinocytes. Emerging evidence supports that apoptosis regulates keratinocyte proliferation and formation of stratum corneum, which maintains the homeostasis of the skin. Qinzhuliangxue mixture (QZLX) is a representative formula for the treatment of psoriasis which earliest recorded in the classic Chinese medicine book Xia's Surgery...

A persistent long-standing, inflammatory skin condition that is brought on by a variety of factors is psoriasis. It is distinguished by itchy, scaly, reddish plaques, particularly on areas of the body that are frequently chafed, including the extensor sites of the limbs. Recent developments in molecular-targeted therapy that use biologics or small-molecule inhibitors can effectively cure even the worst psoriatic indications. The outstanding clinical outcomes of treatment help to clarify the disease's detrimental consequences on quality of life...

BACKGROUND: Psoriasis is a highly heterogeneous autoinflammatory disease. At present, heterogeneity in disease has not been adequately translated into concrete treatment options. Our aim was to develop and verify a new stratification scheme that identifies the heterogeneity of psoriasis by the integration of large-scale transcriptomic profiles, thereby identifying patient subtypes and providing personalized treatment options whenever possible. METHODS: We performed functional enrichment and network analysis of upregulated differentially expressed genes using microarray datasets of lesional and non-lesional skin samples from 250 psoriatic patients...

INTRODUCTION: Immunotherapy with biologics targeting programmed cell death protein-1 (PD-1) is highly effective in the treatment of various malignancies. Nevertheless, it is frequently responsible for unexpected cutaneous manifestations, including psoriasis-like dermatitis. The pathogenesis of anti-PD-1-induced psoriasis has yet to be clarified, even though it is plausible that some innate and adaptive immunity processes are in common with canonical psoriasis. The genetic predisposition to psoriasis of patients could also be a contributing factor...

BACKGROUND: Disturbed gut microbiota and associated metabolic dysfunction exist in Psoriasis. Despite the growing use of interleukin-17 inhibitor (anti-IL17) therapy, the effect of anti-IL17 on gut/skin microbiota function is not fully understood in patients with Psoriasis. OBJECTIVE: Therefore, we explored whether Psoriasis is associated with alterations in selected gut/skin microbiota in a study cohort, and a longitudinal cohort study to reveal the effects of IL-17A inhibitor treatment on gut microbiota in Psoriasis...

Calcium/calmodulin-dependent protein kinase IV (CaMK4) serves as a pivotal mediator in the regulation of gene expression, influencing the activity of transcription factors within a variety of immune cells, including T cells. Altered CaMK4 signaling is implicated in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, which are characterized by dysregulated immune responses and clinical complexity. These conditions share common disturbances in immune cell functionality, cytokine production, and autoantibody generation, all of which are associated with disrupted calcium-calmodulin signaling...

Inflammation resolution is an essential process for preventing the development of chronic inflammatory diseases. However, the mechanisms that regulate inflammation resolution in psoriasis are not well understood. Here, we report that ANKRD22 is an endogenous negative orchestrator of psoriasiform inflammation, as ANKRD22-deficient mice are more susceptible to IMQ-induced psoriasiform inflammation. Mechanistically, ANKRD22 deficiency leads to excessive activation of TNFRII-NIK-mediated noncanonical NF-κB signaling pathway, resulting in hyperproduction of IL-23 in DCs...

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease. N6-methyladenosine (m6A) is involved in numerous biological processes in both normal and diseased states. Herein, we aimed to explore the potential role of m6A regulators in the diagnosis of psoriasis and predict molecular mechanisms by which m6A regulators impact psoriasis. METHODS: GSE30999 (170 human skin tissue samples) and GSE13355 (180 human skin tissue samples) were downloaded as the training analysis dataset and validation dataset respectively...

Psoriasis is accepted as a chronic, inflammatory, immune-mediated skin disease triggered by complex environmental and genetic factors. For a long time, disease recurrence, drug rejection, and high treatment costs have remained enormous challenges and burdens to patients and clinicians. Natural products with effective immunomodulatory and anti-inflammatory activities from medicinal plants have the potential to combat psoriasis and complications. Herein, an imiquimod (IMQ)-induced psoriasis-like dermatitis model is established in mice...

Topical ROCEN (Roc), liposomal arthrocen hydrogel, is a robust anti-inflammatory formulation which has been developed for skin diseases such as eczema. Therefore, we aimed to evaluate the efficacy of Roc 2% on the healing of imiquimod (Imiq)-induced psoriasis in a mouse model. Psoriasis was induced by applying Imiq topically to the mice's back skin once daily for five consecutive days. Moreover, a group of animal experiments was treated with Cyclosporine A (CsA), as a standard drug, for comparison with Roc treated group...

PURPOSE: Guselkumab is a highly effective biologic agent for treating psoriasis. This study aimed to explore potential transcription factors involved in psoriasis pathogenesis and response to guselkumab treatment, aiming to provide new therapeutic strategies for psoriasis. PATIENTS AND METHODS: We analyzed gene expression and single-cell RNA-seq data from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) that upregulated in psoriasis and downregulated after guselkumab treatment were subjected to enrichment analyses...