Weighted Gene Co-Expression Network Analysis of Oxymatrine in Psoriasis Treatment

Xue, Xiaoxiao; Guo, Yatao; Zhao, Qianying; Li, Yongwen; Rao, Mi; Qi, Wenjing; Shi, Huijuan

doi:10.2147/jir.s402535

Cited by 4 publications

(4 citation statements)

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“…Cluster 0 was characterized by the expression of SPRR2D, SPRR2F, and SPRR2A, whereas cluster 1 exhibited high expression of KRT23, CCL20, and SPINK5 ( Supplementary Figure S3E ). Interestingly, the association of SPRR2A and SPRR2D with psoriasis has been previously confirmed ( 12 ), supporting the relevance of our findings. We further performed KEGG enrichment analysis to explore the functional implications of these keratinocyte subclusters.…”

Section: Resultssupporting

confidence: 90%

Single-cell sequencing analysis and multiple machine-learning models revealed the cellular crosstalk of dendritic cells and identified FABP5 and KLRB1 as novel biomarkers for psoriasis

Ma,

An,

Hao

et al. 2024

Front. Immunol.

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BackgroundPsoriasis 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.MethodsWe 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. We observed the cellular changes in psoriatic skin tissues, screened the key genes Fatty acid binding protein 5 (FABP5) and The killer cell lectin-like receptor B1 (KLRB1), evaluated the efficacy of six widely prescribed drugs on psoriasis treatment in modulating the dendritic cell-associated pathway, and assessed their overall efficacy. Finally, RT-qPCR, immunohistochemistry, and immunofluorescence assays were used to validate.ResultsThe regulatory influence of dendritic cells (DCs) on T cells through the CD70/CD27 signaling pathway may emerge as a significant facet of the inflammatory response in psoriasis. Notably, FABP5 and KLRB1 exhibited up-regulation and co-localization in psoriatic skin tissues and M5-induced HaCaT cells, serving as potential biomarkers influencing psoriasis development.ConclusionOur study analyzed the impact of DC-T cell crosstalk in psoriasis, elucidated the characterization of two biomarkers, FABP5 and KLRB1, in psoriasis, and highlighted the promise and value of tofacitinib in psoriasis therapy targeting DCs.

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Section: Resultssupporting

confidence: 90%

Single-cell sequencing analysis and multiple machine-learning models revealed the cellular crosstalk of dendritic cells and identified FABP5 and KLRB1 as novel biomarkers for psoriasis

Ma,

An,

Hao

et al. 2024

Front. Immunol.

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“…The mechanism by which oxymatrine exerts its therapeutic effect for psoriasis has been investigated, but it remains unclear [ 19 , 20 , 30 ]. Psoriasis is often triggered by infections and other various factors, resulting in metabolic abnormality and an imbalance in immune modulation [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Psoriasis is indeed a cytokine-driven inflammatory skin disease in which interferon (IFN)-γ, TNFα, IL-17, and IL-22 cytokines have a pathogenic action [ 35 – 38 ]. Oxymatrine not only changes the STAT pathway (i.e., IL-17 pathway) in the pathogenesis of psoriasis, but also affects the inflammatory, infection, and metabolic pathways, and consequently achieves multiple therapeutic effects [ 19 , 20 ]. In the present study, TNFa, IL-12, IL-23, IL-17A, and IL-36γ levels were significantly elevated in the patients with EP, compared with that of the healthy volunteers, and the abnormally high levels declined with oxymatrine treatment.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Oxymatrine in the Treatment of Patients with Erythrodermic Psoriasis

Shi,

Chen,

et al. 2024

Dermatol Ther (Heidelb)

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Introduction The management of erythrodermic psoriasis (EP), a rare but severe type of psoriasis, is challenging, especially in patients with concomitant chronic hepatitis B (CHB). We previously demonstrated that oxymatrine treatment alleviated severe plaque psoriasis, but its therapeutic potential in treating EP remains unexplored. This study was to assess the efficacy and safety of oxymatrine for the treatment of EP, with attention to concomitant CHB. Methods In this investigator-initiated clinical trial, four consecutive patients with EP, including two (A and B) with concomitant CHB, were treated with intravenous administration of oxymatrine as monotherapy for 8 weeks, and scheduled to be followed up for a minimum of 24 weeks. The primary outcome was at least 75% improvement in the psoriasis area and severity index (PASI 75) at week 32. Secondary outcomes included the body surface area (BSA) score, dermatology life quality index (DLQI)], and safety. Results Patients A, B, and C achieved PASI 75 at treatment completion and week 32, demonstrating improvements of 77.4%, 97.2%, and 100% in PASI, respectively. Their BSA and DLQI were also improved significantly at week 32 and throughout follow-up of 37, 57, and 105 weeks, respectively. The viral loads in patients A and B with CHB decreased modestly. Patient D discontinued after follow-up for 19 weeks, and the primary outcome could not be analyzed. No adverse events were reported during treatment and follow-up. Conclusion Oxymatrine appears to be efficacious and safe for the treatment of patients with EP, including those with concomitant CHB. Trial Registration This study was registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; Registration number ChiCTR-TRC-14004301). Supplementary Information The online version contains supplementary material available at 10.1007/s13555-024-01181-5.

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“…At 12, 24, 36, and 48 h post-infection, proteins were extracted by washing cells with chilled PBS and lysing in cold RIPA:PMSF buffer (100:1) for 20-30 min. After centrifugation at 12,000 rpm for 20 min at 4 • C, supernatants were preserved for subsequent analysis [44].…”

Section: Western Blot Analysis Of Protein Expression In Pmvecsmentioning

confidence: 99%

Oxymatrine Modulation of TLR3 Signaling: A Dual-Action Mechanism for H9N2 Avian Influenza Virus Defense and Immune Regulation

Zhi,

Zhao,

Liu

et al. 2024

Molecules

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In our research, we explored a natural substance called Oxymatrine, found in a traditional Chinese medicinal plant, to fight against a common bird flu virus known as H9N2. This virus not only affects birds but can also pose a threat to human health. We focused on how this natural compound can help in stopping the virus from spreading in cells that line the lungs of birds and potentially humans. Our findings show that Oxymatrine can both directly block the virus and boost the body’s immune response against it. This dual-action mechanism is particularly interesting because it indicates that Oxymatrine might be a useful tool in developing new ways to prevent and treat this type of bird flu. Understanding how Oxymatrine works against the H9N2 virus could lead to safer and more natural ways to combat viral infections in animals and humans, contributing to the health and well-being of society. The H9N2 Avian Influenza Virus (AIV) is a persistent health threat because of its rapid mutation rate and the limited efficacy of vaccines, underscoring the urgent need for innovative therapies. This study investigated the H9N2 AIV antiviral properties of Oxymatrine (OMT), a compound derived from traditional Chinese medicine, particularly focusing on its interaction with pulmonary microvascular endothelial cells (PMVECs). Employing an array of in vitro assays, including 50% tissue culture infectious dose, Cell Counting Kit-8, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot, we systematically elucidated the multifaceted effects of OMT. OMT dose-dependently inhibited critical antiviral proteins (PKR and Mx1) and modulated the expression of type I interferons and key cytokines (IFN-α, IFN-β, IL-6, and TNF-α), thereby affecting TLR3 signaling and its downstream elements (NF-κB and IRF-3). OMT’s antiviral efficacy extended beyond TLR3-mediated responses, suggesting its potential as a versatile antiviral agent. This study not only contributes to the growing body of research on the use of natural compounds as antiviral agents but also underscores the importance of further investigating the broader application of OMT for combating viral infections.

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Weighted Gene Co-Expression Network Analysis of Oxymatrine in Psoriasis Treatment

Cited by 4 publications

References 54 publications

Single-cell sequencing analysis and multiple machine-learning models revealed the cellular crosstalk of dendritic cells and identified FABP5 and KLRB1 as novel biomarkers for psoriasis

Single-cell sequencing analysis and multiple machine-learning models revealed the cellular crosstalk of dendritic cells and identified FABP5 and KLRB1 as novel biomarkers for psoriasis

Efficacy and Safety of Oxymatrine in the Treatment of Patients with Erythrodermic Psoriasis

Oxymatrine Modulation of TLR3 Signaling: A Dual-Action Mechanism for H9N2 Avian Influenza Virus Defense and Immune Regulation

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