FASEB JOURNAL
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2025
·Vol. 39
·期 7
·e70539
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IF 4.2
Yingjie Shen,Yitong Zhou,Kuziwakwashe Alice Chiwa,Junxin Wang,Shihong Ren,Mingxuan Wang,Hongru Ren,Yeyi Zheng,Ying Yu,Lutao Jiang,Jingmou Yu,Yuchun Qiao,Litai Jin,Jianlin Lou,Xiangkuo Zheng
Psoriasis is an immune-mediated inflammatory dermatological disorder characterized by the interaction between immune cells and keratinocytes, which perpetuates cutaneous inflammation and cellular hyperproliferation. In this study, we identified a strong δ-catenin signature in psoriatic skin; however, the precise role of δ-catenin remains to be elucidated. Additionally, we observed that Interleukin (IL)-17A, a pivotal cytokine involved in the development of psoriatic lesions, induces δ-catenin expression in HEKn and HACAT cells. From a mechanistic perspective, δ-catenin initiated NF-κB signaling, subsequently leading to the activation of IL-6 and IL-8 production. Furthermore, silencing δ-catenin expression mitigated IL-17A-induced hyperproliferation of keratinocytes through the NF-κB pathway. Our study further identified miR-101 and miR-122 as upstream regulators of δ-catenin, exerting their effects by downregulating δ-catenin protein levels. We demonstrated that miR-101 and miR-122 can inhibit the hyperproliferation of keratinocytes induced by δ-catenin. These findings validate the role of δ-catenin in the pathogenesis of psoriasis, particularly in keratinocyte-mediated inflammatory responses and cellular hyperproliferation. Consequently, miR-101 and miR-122 hold potential as therapeutic agents in the treatment of psoriasis. Graphical The schematic diagram delineates the signaling pathway associated with IL-17A-induced psoriasis, highlighting the upregulation of delta-catenin, which initiates NF-κB signaling. This activation subsequently leads to the production of IL-6 and IL-8, as well as the hyperproliferation of keratinocytes. Furthermore, miR-101 and miR-122 function as inhibitors of delta-catenin, effectively obstructing this signaling cascade.
研究领域:
皮肤病学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Hongyao Du,Pei Liu,Jinjin Zhu,Jiajia Lan,Yan Li,Lianbin Zhang,Jintao Zhu,Juan Tao
Methotrexate (MTX) is one of the first-line treatments for moderate to severe psoriasis, while the side effects caused by injection and oral administration of MTX greatly restrict its clinical application. Transdermal drug delivery offers a desirable alternative to the conventional approaches, but the performances of the currently available skin penetration enhancement techniques are not so satisfactory. To address these limitations, we developed a dissolving microneedle (MN) patch made of hyaluronic acid (HA) with excellent water solubility, biocompatibility, biodegradability, and mechanical properties. The amount of MTX encapsulated in the needles of the patch could be controlled during the fabrication process for precise dosage. Interestingly, the MTX-loaded MNs successfully penetrated imiquimod (IMQ)-induced thickened epidermis in mice and delivered the drug intralesionally. Meanwhile, fast dissolution of HA endowed the MNs with operability for patients. We found that the MTX-loaded MNs not only showed well-maintained inhibitory effect in vitro but also alleviated the psoriasis-like skin inflammation in mice. Moreover, the MTX-loaded MNs were significantly more efficacious than taking the same dose of drug orally. Consequently, a higher oral dose of MTX was required for a comparable amelioration, which in turn increased its systemic toxicity. Taken together, the proposed MTX-loaded dissolving MN patch strategy provides a new opportunity for efficient and safe treatment of psoriasis.
研究领域:
药剂学
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皮肤病学
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生物医学工程
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DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 19
·6328
·
IF 4.927
Huanan Yu,Yuanqi Liu,Fang Zheng,Wenyu Chen,Kun Wei
Psoriasis is a chronic inflammatory skin disorder accompanied by excessive keratinocyte proliferation. Erianin (Eri) is an ideal drug candidate for inhibiting proliferation and inducing apoptosis in the treatment of psoriasis. However, Eri’s poor water solubility and low penetration activity across the skin hinder its application in local medicine. In this study, we developed a novel photo-responsive dendritic mesoporous silica nanoparticle-based carrier to deliver erianin, improved its bioavailability, and achieved sustained-release effects. Spiropyran (SP), 3-aminopropyltriethoxysilane (APTES), and perfluorodecyltriethoxysilane (PFDTES) were conjugated to the outer surface, which allowed Eri to be released in response to UV radiation. The physicochemical properties of photo-responsive dendritic mesoporous silica nanoparticles ([email protected]) were characterized via multiple techniques, such as using a Fourier-transform infrared spectrometer, a high-resolution transmission electron microscope, and nuclear magnetic resonance (NMR) spectroscopy. The anti-proliferative properties and light-triggered release of erianin-loaded photo-responsive dendritic mesoporous silica nanoparticles were assessed via the MTT assay and a drug release study in vitro. Erianin-loaded photo-responsive dendritic mesoporous silica nanoparticles (UV) exhibit a significantly enhanced HaCat cell-inhibiting efficacy compared to other formulations, as demonstrated by their extremely low cell viability of 10.0% (concentration: 500 mg/mL), indicating their capability to release a drug that responds to UV radiation. The cellular uptake of photo-responsive dendritic mesoporous silica nanoparticles ([email protected]) was observed via confocal laser scanning microscopy (CLSM). These experimental results show that[email protected]could be effectively endocytosed into cells and respond to ultraviolet light to release Eri, achieving a more effective psoriasis treatment. Therefore, this drug delivery system may be a promising strategy for addressing the question of Eri’s delivery and psoriasis therapy.Keywords:erianin;mesoporous silica nanoparticles;photo-responsive;psoriasis;drug delivery
研究领域:
药学
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纳米技术
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皮肤病学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Hua Wang,Yangxue Fu,Pei Liu,Fei Qu,Shuo Du,Yan Li,Hongyao Du,Lianbin Zhang,Juan Tao,Jintao Zhu
Glucocorticoid-based creams are commonly used for treatments of psoriatic skin lesions while showing poor permeation because the thickened stratum corneum severely limits drug absorption. Although dissolving microneedle (DMN) patches have been employed in treating skin disease by virtue of their direct target to the lesion site, conventional DMN patches are generally fabricated from the water-soluble matrix, making them difficult to efficiently encapsulate hydrophobic glucocorticoids. Here, we develop a mechanically robust supramolecular DMN composed of hydroxypropyl β-cyclodextrin (HPCD) to effectively and uniformly load triamcinolone acetonide (TA). The TA-loaded HPCD DMN (TAMN) exhibits excellent mechanical performance that can easily pierce the thickened psoriasis lesions and deliver TA efficiently. Owing to the increased water solubility and bioavailability of TA after inclusion into HPCD, TAMN shows a superior in vitro inhibitory effect on immortalized human keratinocyte (HaCaT) cells. Importantly, the administration of TAMN twice a week effectively alleviates psoriatic signs and reduces the expression of Ki67, IL-23, and IL-17 in the ear lesions of imiquimod-induced psoriasis-like mice. This supramolecular DMN provides a promising strategy for the efficient treatment of psoriasis and other skin diseases, greatly broadens the applications of supramolecular materials in transdermal drug delivery, and widens the range of drugs in DMNs.
研究领域:
药剂学
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皮肤病学
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生物医学工程
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DOI
PubMed
高影响因子
EXPERIMENTAL DERMATOLOGY
·
2020
·Vol. 30
·期 7
·932-942
·
IF 3.368
Aimin Liu,Buxin Zhang,Wei Zhao,Yuanhui Tu,Qingxing Wang,Jing Li
Psoriasis is a chronic inflammatory disease characterized by abnormal hyperproliferation and differentiation. The object of this study is to explore the role of microRNA-215-5p in psoriasis-like inflammation. The expression of miR-215-5p was found to be down-regulated in pro-inflammatory factor-stimulated HaCaT cells and imiquimod (IMQ)-treated skin tissues. Overexpression of miR-215-5p suppressed the proliferation and cell cycle progression of HaCaT cells. Further, miR-215-5p agomir alleviated the disease severity, pathological features and Ki67 positive cells in IMQ-treated mice. Luciferase assay confirmed that miR-215-5p could bind to the 3′UTR of DYRK1A. The in vitro and in vivo results showed that miR-215-5p negatively regulates DYRK1A, which further inhibited EGFR and its downstream signalling pathways, AKT and ERK. Collectively, our results provide evidence that overexpression of miR-215-5p inhibits the proliferation of HaCaT cells and alleviates psoriasis-like inflammation partly by DYRK1A mediated inhibition of the EGFR signalling pathway. miR-215-5p may serve as a novel small molecule for therapeutic intervention in psoriasis.
研究领域:
分子生物学
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皮肤科
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炎症性疾病
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微小RNA研究
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DOI
PubMed
高影响因子
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
·
2024
·
IF 2.7
Yu-Hang Dai,Fang-Li Sun,Rui-Miao Wei,Jia-Ji Guo,De-Li Dong,Zhi-Jie Sun
Psoriasis is a chronic inflammatory skin disease. Topical medicines are the preferred treatment for mild to moderate psoriasis, but the effect of excipients used in semi-solid preparations on psoriasis-like skin inflammation is not fully understood. In the present study, we investigated the effect of stearyl alcohol, a commonly used excipient, on imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. Psoriasis-like skin inflammation was induced by topical IMQ treatment on the back of mice. Skin lesion severity was evaluated by using psoriasis area and severity index (PASI) scores. The skin sections were stained by haematoxylin–eosin and immunohistochemistry. Stearyl alcohol (20% in vaseline) treatment significantly reduced the IMQ-induced increase of PASI scores and epidermal thickness in mice. IMQ treatment increased the number of Ki67- and proliferating cell nuclear antigen (PCNA)-positive cells in the skin, and the increases were inhibited by stearyl alcohol (20% in vaseline) treatment. Stearyl alcohol treatment (1%, 5%, 10% in vaseline) dose-dependently ameliorated IMQ-induced increase of PASI scores and epidermal thickness in mice. Hexadecanol (20% in vaseline), stearic acid (20% in vaseline) and vaseline treatment had no significant effect on IMQ-induced psoriasis-like skin inflammation in mice. In conclusion, stearyl alcohol has the effect of improving IMQ-induced psoriasis-like skin inflammation in mice.
研究领域:
药理学
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皮肤病学
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炎症
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2021
·
IF 3.935
Xinying He,Han Cao,Xia Li,Yan Li,Yunqiu Yu
Lysophosphatidylcholine (LPC) was commonly known as a class of significant differential metabolites of high relevance with many diseases including psoriasis, of which the accurate determination is of great importance to diagnosis or prediction to many diseases. However, it is challenging and complicated because of the enormous biological sample complexity and impurities interference. In this study, we synthesized a magnetic nanocomposite MG@PD@TiO 2 and took advantage of the interactions of Lewis acid−base between the phosphate groups in LPCs and Ti ions on MG@PD@TiO 2 nanomaterials for selective separation and enrichment of LPCs from complex biological matrix. The solid-phase extraction sample pretreatment process by means of MG@PD@TiO 2 nanomaterials coupled with LC–MS/MS method was then applied to actual determination of six typical LPCs (LPC 10:0, 14:0, 16:0, 18:0, 18:1, 22:0) in human plasma. The extraction conditions were scientifically optimized by single-factor test (adsorbent amount, adsorption and desorption time, elution solvent type, eluant volume). Under the optimal conditions, the detection limits (LOD, S/N = 3) and quantification limits (LOQ, S/N = 10) were 1 and 5 ng/mL for LPC 10:0 and LPC 14:0, 0.02 and 0.1 ng/mL for LPC 16:0 and LPC 18:1, 0.05 and 0.2 ng/mL LPC 18:0 and LPC 22:0, respectively. The intra- and inter-day precisions were 3.82–12.60 % (n = 6) and 3.29–13.50 % (n = 6) respectively, the recoveries were in the range of 91.92–113.69 % and the stability of the analytes in the matrix performed well with RSDs≤15.51 %. Finally, the developed method was successfully applied to the accurate determination of six LPCs biomarkers of plasma in patients with psoriasis (n = 10) and control groups (n = 10).
研究领域:
分析化学
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医学
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生物标志物研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2019
·
IF 3.414
Xiao Qiang Li,Yong Chen,Hong Mei Zhou,Hui Li Shi,Xiao Ning Yan,Li Ping Lin,Ren Xiang Tan
Ethnopharmacological relevance Rosin, an exudate of conifer trees such as Pinus masscnlana (Pinaceae), has been used to treat psoriasis for nearly two thousand years in China despite its so far undefined pharmacology. Unfortunately, the rosin intoxication is noted from time to time, but the water-boiled rosin (WBR) has been documented to be safer. This study was performed to evaluate the in vivo anti-psoriasis efficacy of WBR. Materials and methods The main phytochemicals in WBR were quantified by high performance liquid chromatography (HPLC). WBR was evaluated in the imiquimod-induced psoriasis-like inflammation mouse model for its anti-psoriasis effect at 130, 260, and 390 mg/kg, which were set according to the dose used for patients. Through a combination of q-PCR, flow cytometry, and histopathological and immunohistochemical (IHC) analysis, the in vivo efficacy was assessed in terms of the psoriasis area severity index (PASI), epidermal keratinocyte proliferation, Th1 and Th17 cell numbers in spleen, and mRNA expressions of inflammatory cytokines. Result Oral administration of WBR ameliorates the psoriasis-like dermatitis in the imiquimod-generated mouse model. In particular, WBR given at 260 or 390 mg/kg significantly restores the normal keratinization of dorsal lesion if compared with the untreated psoriatic mice. Such an effect was addressed to correlate to the Th1/Th17 cell reduction in spleen and the suppressed expression of IL-17A, IL-17F, IL-22, IL-23, TNF- α , K17, and proliferating cell nuclear antigen (PCNA) after the WBR administration. Conclusion WBR is effective in the imiquimod-induced psoriasis-like inflammation mouse model with the efficacy arising from its proliferation inhibition of Th1/Th17 cells and epidermal keratinocytes via the down-regulation of the relevant inflammatory cytokines such as IL-23, IL-17A, and IL-17F. Collectively, WBR harvested and processed in the traditional manner is an efficacious psoriasis-treating agent.
研究领域:
药理学
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免疫学
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民族药理学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Wei Zhou,Mengmeng Hu,Xiaohao Zang,Qifa Liu,Jiantang Du,Jingrong Hu,Lanyue Zhang,Zhiyun Du,Zhangmin Xiang
Psoriasis is considered as a common chronic immune-mediated skin disorder characterized by abnormal keratinocyte proliferation. Luteolin, an anti-inflammatory natural flavonoid with well-accepted inhibition effect against keratinocyte proliferation, was hypothesized to have a potential therapeutic effect for psoriasis. In this paper, we investigated the relieving effect of luteolin against imiquimod-induced psoriasis-like lesions on BALB/c mice and its possible anti-inflammatory mechanisms in lipopolysaccharide-stimulated macrophages (RAW264.7 cells). We found that luteolin ameliorated psoriasis-like skin lesions, suppressed the cutaneous infiltration of macrophages, T cells and neutrophils, and downregulated the expression of cytokines like IL-6, IL-1β, TNF-α, IL-17A and IL-23 in both skin lesions and eyeball blood of model mice. In vitro, we observed luteolin significantly suppressed the levels of psoriasis-related pro-inflammatory cytokines, such as IL-17A, IL-6, TNF-α and IL-23, and inflammatory mediators like nitric oxide NO, inducible NOS, COX-2 in RAW264.7 cells. The anti-inflammatory activity was accomplished by inhibiting NF-κB expression and activation. This study demonstrates luteolin is effective in alleviating psoriasis-like skin lesions and downregulating inflammatory response via NF-κB pathway, suggesting luteolin as a potential molecule for further therapeutic research of inflammation-related skin diseases like psoriasis.
研究领域:
免疫学
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药理学
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皮肤病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
·
2020
·
IF 2.09
Jiaxing Fan,Jianglu Zhou,Shenmin Su,Yunqiu Yu,Lihong Chen,Yunchen Le,Xiaopan Wang,Li Zhang,Jie Zheng,Xia Li
Psoriasis is a common chronic inflammatory skin disease which may exhibit a variety of skin clinical manifestations associated with multiple comorbidities. However, its pathogenesis associated with metabolism has not yet been understood. The metabolites of tricarboxylic acid (TCA) cycle and amino acids are interlinked with each other and involve many physiological processes. This study determined 32 metabolites of TCA cycle and amino acids in psoriasis using an improved GC-MS method. This one-pot derivatization applied silanization and oximation simultaneously for easy, quick and sensitive quantitative detection of 32 metabolites in serum of patients with psoriasis. Through the established GC-MS method, 32 metabolites in serum were detected in a single run. The result of this preliminary study showed that there were significant alterations of the metabolites in tricarboxylic acid (TCA) cycle and amino acids before and after treatment. A shift towards healthy controls of these metabolites after treatment was observed using principal component analysis (PCA) as well. Receiver operating-characteristic curve (ROC) analysis of the analyzed 32 metabolites filtered 5 potential biomarkers of the clinical efficacy of the treatment. This result suggested the importance of these metabolites in the pathogenesis of psoriasis. To our best know, this is the first targeted metabolomics work to study the changes of TCA cycle metabolites and amino acids in the background of treatment of psoriasis.
研究领域:
医学
·
代谢组学
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产品关联
DOI
高影响因子
Clinical Cosmetic and Investigational Dermatology
·
2023
·
IF 2.3
Zijun Wu,Qin Yang,Kai Xu,Juanjuan Wu,Bin Yang
Background IL-27 involves psoriasis pathogenesis potentially by promoting excessive keratinocyte proliferation. However, the underlying mechanisms remain unclear. This study aims to explore the key genes and molecular mechanisms of IL-27-induced keratinocyte proliferation.Methods Primary keratinocytes and immortalized human keratinocyte HaCaT cells were treated with different concentrations of IL-27 for 24 h and 48 h respectively. CCK-8 assay was used to detect cell viability and Western blot was used to detect the expression of CyclinE and CyclinB1. Primary keratinocytes and HaCaT cells were treated with IL-27, and their differentially expressed (DE) genes were obtained by transcriptome sequencing. Then Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed to predict related pathways, and the long non-coding RNA-microRNA-messenger RNA network and protein-protein interaction network were constructed to screen key genes. Biochemical experiments were performed to assess the content of glucose (Glu), lactic acid (LA), and ATP. Flow cytometry and Mito-Tracker Green staining were used to detect mitochondrial membrane potential and the number of mitochondria respectively. Western blot was performed to assess the expression of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), phosphoglycerate kinase 1 (PGK1), phosphorylated dynamin-related protein 1 (p-DRP1) (s637) and mitofusin 2 (MFN2).Results IL-27 concentration-dependently increased keratinocyte viability and the expression of CyclinE and CyclinB1. Bioinformatics analysis showed that the enriched pathways of DE genes were closely associated with cellular metabolism. miR-7-5p, EGFR, PRKCB, PLCB1 and CALM3 were key genes. IL-27 increased the content of LA, mitochondrial membrane potential, and the expression of GLUT1, HK2, LDHA, PGK1, p-DRP1 (s637), and MFN2, accompanied by decreased contents of Glu and ATP (P<0.001).Conclusion IL-27 potentially promotes keratinocyte proliferation by enhancing glycolysis, mitochondrial function, and mitochondrial fusion. The findings of this study may be conducive to revealing the role of IL-27 in the pathogenesis of psoriasis.
研究领域:
免疫学
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细胞生物学
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分子生物学
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皮肤科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOTECHNOLOGY
·
2024
·
IF 2.4
Chen Ya,Zhu Congcong,Tai Zongguang,Lian Tianyan,Zhu Quangang,Chen Zhongjian
Apoptosis is a natural physiological process of programmed cell death. It is essential for maintaining the homeostasis of the body and the immune system. The dysfunction of apoptosis can lead to the development of autoimmune diseases. In psoriasis, the dysfunction of keratinocyte proliferation manifests as an impairment of apoptosis. Cordycepin is the major active component in cordyceps militaris and has pharmacological effects, including regulation of apoptosis. The pharmacological mechanism of Cordycepin in psoriasis remains unclear. In this study, bioinformatics analysis revealed that the mechanism may be associated with the p53 apoptotic pathway. Further, we confirmed in the experiments that cordycepin inhibited the interleukin (IL)-17A-induced proliferation of HaCaT cells and down-regulated the expression of proliferating cell nuclear antigen (PCNA) and Ki-67. Regulating the expression of apoptotic proteins BAX, Bcl-2, and p53 promote apoptosis. Further investigation of the upstream pathway of apoptosis revealed that cordycepin could normalize the abnormal p53-mouse double minute 2 (MDM2) feedback loop. In vivo results showed that the cordycepin gel could effectively improve imiquimod (IMQ)-induced psoriasis-like skin lesions in mice, and the p53-MDM2 pathway was verified at the protein level. In conclusion, the anti-psoriasis effect of Cordycepin and its potential mechanism have not been discussed in detail. However, our work supports the idea that Cordycepin can be further developed as an Active Pharmaceutical Ingredient (API) for the treatment of psoriasis.
研究领域:
药理学
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皮肤科
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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