Scope: Imiquimod (IMQ)-induced psoriasis-like mouse models are widely used for psoriasis research, but existing methods fail to sustain disease manifestation over time. This study explores the effect of different IMQ dosing frequencies on maintaining psoriasis symptoms in mice. Methods and Results: We compared a general IMQ model (General Model) with models that used spaced dosing (D-D Model) or 5-6 doses per week (3D-D Model) over a 28-day duration. Each experimental group consisted of eight mice (n=8) to ensure statistical significance. Both the D-D and 3D-D models maintained classic pathological features of psoriasis, including immune cell accumulation in skin and sustained levels of psoriasis-related inflammatory factors in the blood, compared to the control and General Model groups. Transcriptomic analysis revealed that D-D Model and 3D-D models mice exhibited more severe psoriasis-like lesions and significantly increased expression of IL-17 and IL-23 signaling genes (IL-17A, IL-17F, S100A9) compared to the General Model. Furthermore, adjusted dosing frequencies influenced the metabolic profile, with higher regulation of TRP channels and 2-oxocarboxylic acid metabolism in the skin of D-D mice. Subsequent, Identification and validation of a conserved psoriasis biomarker signature via machine learning and cross-species analysis. Conclusion: Adjusting the dosing frequency of conventional imiquimod-induced psoriasis-like mouse models to alternate-day administration (D-D) or three days on followed by one day off (3D-D) maintained long-term psoriasis symptoms. enhancing IL-17/ IL-23 signaling pathways. This modification resulted in a model exhibiting biological characteristics more closely resembling those in humans, thereby providing a more clinically relevant model for chronic psoriasis. Despite these advantages, the current model has not yet fully recapitulated the complex seasonal and cyclical nature of clinical psoriasis.

Background:This meta-analysis investigates the association between maternal anxiety/depression during pregnancy and the development of eczema/atopic dermatitis (AD) in offspring. Methods:A literature search was conducted across four electronic databases (PubMed, Web of Science, Embase, and the Cochrane Library) for studies published from database inception until July 2025. In this study, maternal depression and anxiety were defined as conditions physician-diagnosed or assessed with standardized scales during pregnancy. The primary outcome was the incidence of eczema/AD in the offspring. Result:A total of 12 cohort studies were included in this meta-analysis. Pooled results indicated that maternal depression [odds ratio (OR) = 1.06, 95% confidence interval (95% CI) = 1.01-1.11, p = 0.015] or anxiety (OR = 1.11, 95% CI = 1.03-1.19, p = 0.005) during pregnancy was potentially associated with a higher incidence of offspring eczema and AD. Subgroup analysis revealed that there was a higher incidence of AD in offspring with maternal anxiety during pregnancy (OR = 1.24, p = 0.028), while no significant difference was observed in the incidence of eczema (p = 0.286). A higher incidence of offspring eczema/AD was observed in offspring of both Eastern (OR = 1.13, p = 0.043) and Western (OR = 1.34, p = 0.049) countries. Moreover, the incidence was higher in offspring when maternal anxiety was identified in the first (OR = 1.13, p = 0.036) or second (OR = 1.25, p = 0.010) trimester, whereas no significant difference was found for exposure in the third trimester (p = 0.152). For maternal depression during pregnancy, offspring had a higher incidence of AD (OR = 1.17, p < 0.001), while no significant difference was observed for eczema (p = 0.145). Furthermore, the incidence of offspring eczema/AD was higher in Eastern countries (OR = 1.14, p = 0.035), while Western countries group showed no significant difference (p = 0.111). Additionally, when analyzed by timing of exposure, the incidence was higher when depression was identified in the second trimester (OR = 1.30, p = 0.027), with no significant difference found in the third trimester (p = 0.163). Conclusion:This study suggests that maternal depression/anxiety during pregnancy is potentially associated with the development of eczema/AD in offspring.

Background:Nasal Streptococcus pyogenes (SP) infection triggers psoriasis relapse, with the systemic-to-cutaneous immune relay poorly understood. This study aims to elucidate role of dendritic cell (DC) metabolic reprogramming and trafficking in driving SP-induced psoriasis relapse. Methods:A murine psoriasis model was established using imiquimod (IMQ) and intranasal SP challenge, with disease severity evaluated via PASI scoring and histology, epidermal proliferation (Ki67) and T cell (CD3) via immunofluorescence, immunohistochemistry, and IL-23, IL-17A, and IL-1β levels via enzyme-linked immunosorbent assay (ELISA) in skin. Immune cell infiltration (DCs, γδ T cells) was analyzed by flow cytometry, RNA-seq identified affected genes and pathways, and real-time polymerase chain reaction (qPCR) /Western blot (WB) detected transcription and protein levels of target genes in SP lipoteichoic acid (LTA)-activated BMDCs in vitro. Oxygen consumption rate (OCR), extracellular acidification rate (ECAR), wound healing, Transwell migration, and co-culture assays assessed metabolic reprogramming and migration function of BMDCs in response to LTA in vitro. CD11c-Luc reporter mice were monitored via bioluminescence imaging (BLI) to dynamically track DC migration in vivo, and confocal immunofluorescence co-localization was used to visualize DC-γδT cell interactions in skin. Results:Nasal SP infection exacerbated psoriasis-like lesions by increasing PASI scores (10.3 ± 0.2 in Re-SP vs 8.2 ± 0.4 in Re, P < 0.01), epidermal thickness, pro-inflammatory cytokines (IL-17A levels increased by approximately 2.1-fold in Re-SP compared to Re), and promoting DC maturation, γδT cell infiltration, and IL-17A production via TLR2/NF-κB/nitric oxide synthase 2(NOS2) signaling. RNA-seq and in vitro assays demonstrated SP induces DC aerobic glycolysis (as evidenced by significantly increased ECAR and suppressed OCR) and hyper-mobility through TLR2 activation, upregulating TLR2, NF-κB markers (p-IKBα, p-p65), NOS2, and myosin-related proteins (p-myosin phosphatase target subunit 1, MYPT1 and p-myosin light chain, MLC), with inhibited TLR2 reducing these effects. In vivo, SP triggered rapid DC activation and trafficking to skin, forming immunological synapse with γδT cells to induce IL-17A. Conclusion:These findings suggest that nasal SP infection may exacerbate psoriasis relapse through TLR2-dependent DC metabolic reprogramming and trafficking, which in turn promote γδ T cell IL-17A production. However, as these findings are derived from preclinical mouse models and in vitro experiments, validation in human psoriasis cohorts and chronic disease models is required before clinical translation can be considered.

Inspection is the first of the four diagnoses.Skin inspection is not only an important part of the four diagnoses of Chinese medicine,but also the characteristic and essence of Chinese dermatology.The development of artificial intelligence(AI)technology provides an opportunity for the intelligent research of skin inspection in traditional Chinese medicine(TCM).This study aims to review the application status of artificial intelligence in TCM skin inspection,and summarize the research progress of various artificial intelligence technologies in skin lesion differentiation,syndrome differentiation and location differentiation,and propose future directions for AI empowerment in TCM dermatology.Based on the basic theory of Chinese medicine and skin clinical thinking of Chinese medicine,this article puts forward the prospect of AI empowerment from the aspects of macro and micro combination,point and surface combination,mind-body combination and time-space combination.This study discusses the existing problems and challenges in the intersection of AI and TCM dermatology.The intersection of AI and TCM dermatological inspection is at the developmental stage.AI has broad application prospects within TCM dermatology,but it also faces numerous challenges.While AI offers opportunities to modernize TCM dermatology,challenges such as aligning AI with TCM's holistic principles and ensuring clinical relevance remain.Further research integrates AI with TCM skin inspection methods,the intricate connotations and applications of TCM dermatological Inspection will be fully realized,thereby providing reference for the development of artificial intelligence to help TCM dermatology diagnosis and treatment technology.

Scope: The global prevalence of obesity has significantly increased, presenting a major health challenge. High-fat diet (HFD)-induced obesity is closely related to the disease severity of psoriasis, but the mechanism is not fully understood. Methods and results: The study utilizes the HFD-induced obesity model along with an imiquimod (IMQ)-induced psoriasis-like mouse model (HFD-IMQ) to conduct transcriptomics and metabolomic analyses. HFD-induced obese mice exhibits more severe psoriasis-like lesions compared to normal diet (ND)-IMQ mice. The expression of genes of the IL-17 signaling pathway ( IL-17A, IL-17F, S100A9, CCL20, CXCL1 ) is significantly upregulated, leading to an accumulation of T cells and neutrophils in the skin. Moreover, the study finds that there is an inhibition of the branched-chain amino acids (BCAAs) catabolism pathway, and the key gene branched-chain amino transferase 2 (Bcat2) is significantly downregulated, and the levels of leucine, isoleucine, and valine are elevated in the HFD-IMQ mice. Furthermore, the study finds that the peroxisome proliferator-activated receptor gamma (PPAR γ) is inhibited, while STAT3 activity is promoted in HFD-IMQ mice. Conclusion: HFD-induced obesity significantly amplifies IL-17 signaling and exacerbates psoriasis, with a potential role played by Bcat2-mediated BCAAs metabolism. The study suggests that BCAA catabolism and PPAR γ-STAT3 exacerbate inflammation in psoriasis with obesity.

Ethnopharmacological relevance Cooling Blood and Detoxicating Formular (CBDF) based on the theory of cooling blood and dosing detoxification, is a useful traditional Chinese medicine (TCM) medication for psoriasis with blood-heat syndrome. Aim of the study Investigate the active constituents and mechanisms of the CBDF for the treatment of psoriasis. Materials and methods UPLC-Q-Orbitrap-HRMS technique was used to analyse the ingredients of CBDF absorbed into plasma and skin tissue. The therapeutic efficacy of CBDF was evaluated in treating an imiquimod (IMQ)-induced mouse model was assessed. Transcriptome analysis and gene enrichment analysis were used to explore the changes in gene expression and pathways following treatment with the CBDF. Validation was performed using western blotting, quantitative RT-PCR, flow cytometry, gene knockout and molecular docking in vitro and in vivo. Results 26 compounds were identified in the plasma of IMQ-induced psoriasis-like mouse with CBDF treatment, and higher levels of cimifugin in the lesion. CBDF improved the pathological changes of psoriasis, with inhibition of TNF-α, IL-23, and IL-17A and upregulation of IL-10. Gene enrichment analysis showed that the therapeutic effect of CBDF was related to AMPK pathway. In psoriasis lesions, the AMPK and fatty acid oxidation were suppressed, and glycolysis was enhanced. The Prkaa2, encoding AMPKα2 was down-regulated in psoriasis patients. CBDF inhibited glycolysis while stimulating fatty acid oxidation by the activating AMPK, thereby exerting an inhibitory effect on inflammation. CBDF inhibited MHCII, CD80, and CD86 on dendritic cells of skin drainage lymph node. In vitro, CBDF inhibited bone marrow-derived DCs secrete IL-23, TNF-α, and lactate, while enhanced fatty acid oxidation and AMPK activity. However, the therapeutic effect was weakened in AMPKα2 deletion. Additionally, psoriasis lesions and dendritic cells activation were significantly aggravated after AMPKα2 knockout. The key ingredients of the CBDF, cimifugin, rutin, astilbin, quercetin, and prim-O-glucosylcimifugin, all exhibit a notable affinity towards AMPKα2 binding. Conclusions CBDF ameliorates psoriasis symptoms and inhibit dendritic cells maturation by regulating metabolic reprogramming in an AMPK-dependent mechanism.

Ethnopharmacological relevance: The inflammatory skin condition psoriasis is immune-related. The decoction of Jianpi-Yangxue-Jiiedu (JPYX) is a useful medication for psoriasis. However, the underlying mechanics of JPYX have not yet been clarified. Aim of the study: The objective of this study was to investigate the mechanism underlying the efficacy of JPYX in the treatment of psoriasis in the context of a high-fat diet. Materials and methods: This work generated a high-fat feeding model of imiquimod (IMQ)-induced psoriasis-like lesion mice. The blood composition of JPYX was examined using ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS). The mechanism of JPYX decoction for treating psoriasis was predicted using methods of network pharmacology, metabolomics, and transcriptomics. Results: JPYX prevented the release of inflammatory cytokines, decreased keratinocyte proliferation, enhanced the percentage of Treg cells in the skin, lymph nodes, and thymus, and greatly alleviated psoriatic lesions. Network pharmacology predicted that IL-1 beta, TNF, STAT3, and EGFR may be potential targets, and KEGG results showed that PI3K-AKT-mTOR may be a potential mechanism of action. Verification of experimental data demonstrated that the JPYX decoction dramatically decreased mTOR and AKT phosphorylation. According to metabolomics analysis, amino acids and their metabolites, benzene and its substitutes, aldehyde ketone esters, heterocyclic compounds, etc. were the primary metabolites regulated by JPYX. KEGG enrichment analysis of differential metabolites was performed. Fatty acid biosynthesis, Type I polyketide structures, Steroid hormone biosynthesis, Biosynthesis of unsaturated fatty acid, etc. Transcriptomic results showed that JPYX significantly regulated skin development, keratinocyte differentiation, and oxidative phosphorylation. Further experimental data verification showed that JPYX decoction significantly reduced the mRNA levels of mt-Nd4, mt-Nd5, mt-Nd1, Ifi205, Ifi211, and mt-Atp8. Conclusions: JPYX may improve psoriasis by regulating the metabolic pathways of fatty acids and electron transport of oxidative phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE:Qing-Re-Chu-Shi Decoction (QRCSD), a traditional Chinese herbal formula, has been employed as a complementary and alternative therapy for inflammatory skin diseases. However, its active constituents and the mechanistic basis of its action on atopic dermatitis remain in adequately understood.AIM OF THE STUDY:Atopic dermatitis (AD) is an allergic dermatitis marked by eczematous lesions and pruritus. The study aimed to elucidate the underlying effects of QRCSD on AD and to identify the components responsible for its therapeutic efficacy in a mouse model.MATERIALS AND METHODS:Network pharmacology and UPLC-mass analysis were used to anticipate the pharmacological mechanisms and to identify active components of QRCSD, respectively. A DNCB-induced AD-like model was established in NC/Nga mice. QRCSD or prednisolone (as a positive control) was administered via gavage every other day from day14 to day 21. Dermatitis severity score, scratching behavior, skin barrier function, spleen index, Th1/Th2 lymphocyte ratio, and serum IgE levels were evaluated. Protein arrays, including 40 inflammatory cytokines, were performed on skin lesions, followed by confirmation experiments of Western blotting in dorsal skin lesions.RESULTS:The construction of a QRCSD-AD-Network and topological analysis firstly proposed potential targets of QRCSD acting on AD. Animal experiments demonstrated that oral administration of QRCSD ameliorated AD-like lesions, reduced epidermal thickness and mast cell count, decreased serum IgE levels, augmented tight junction protein (Claudin 1, Occludin) levels, and regulated the Th1/Th2 balance in the spleen, as well as spleen index. Elevated levels of interleukin (IL)-4, IL-5, IL-6, IL-17, and Eotaxin were revealed in AD-like skin lesions by protein arrays. Western blotting confirmed that the phosphorylation levels of ERK, P38, JNK, STAT3 and P65 were downregulated, and IL-6 expression was also reduced following QRCSD treatment.CONCLUSIONS:The study enhances the understanding of the anti-inflammatory and immunomodulatory effects of QRCSD, showcasing its significant protective role against atopic dermatitis. Treatment with QRCSD may be considered as a viable candidate for complementary and alternative therapy in managing atopic dermatitis.

Purpose:Resveratrol (Res) is a natural polyphenol with anti-inflammatory and immunomodulatory effects. Alterations in metabolic pathways have been studied in psoriasis. This study is aimed to further explore the potential molecular mechanism of psoriasis improvement by Res.Patients and Methods:Imiquimod (IMQ)-induced psoriasis-like mouse model was established to observe the effects of Res. NanoString nCounter Metabolic Pathways Panel was used to analyze the changed mRNA and qRT-PCR was used for validation. Flow cytometry was used to analyze immune cell subsets in skin lesions. In vitro, we observed the effects of Res on R848-stimulated macrophages glycolysis and inflammation.Results:Res reduced the proliferation of keratinocytes and the secretion of inflammatory cytokines in IMQ-induced psoriasis-like mouse model. Psoriasis model skin lesions were in a state of hypoxia, with upregulated glycolysis and downregulated AMPK activity. Res inhibited the levels of hypoxia-related genes (hif1α, hif3α) and glycolysis-related genes (hk1, ldha), meanwhile increased the levels of AMPK genes (prkaa1, prkaa2). Flow cytometry analysis revealed that Res decreased the infiltration of macrophages in psoriasis-like lesions. In addition, Res decreased the secretion of macrophage-associated pro-inflammatory cytokines (IL-23, TNF-α, IL-1β). In vitro, Res diminished the secretion of IL-23, TNF-α, IL-1β, and lactate by R848-stimulated macrophages and activated AMPK.Conclusion:This study suggested that Res diminished psoriasis symptoms by inhibiting macrophages infiltration and inhibiting glycolysis, which providing novel insights into the underlying mechanisms of therapeutic action of Res in the treatment of psoriasis.

Background: At present, acupuncture-related practices have been widely used to treat psoriasis. In our study, we investigated the effect and explored the mechanism of electroacupuncture (EA) on acupoints Baihui (DU20) and Xuehai (SP10) for the treatment of psoriasis. Methods: Imiquimod-induced psoriasis-like mouse model was used in this study. Mice were treated with electroacupuncture at DU20 and SP10 (depth of 2-3 mm, frequency of 2/15 Hz, intensity of 0.5-1.0 mA, 10 min/day). The severity of psoriasis-like lesions for each group was assessed. In addition, histological analysis of the lesions were performed. The levels of inflammatory cytokines were determined using Elisa. The expression levels of Substance P (SP) and NK1R were measured using Western blotting. In addition, NK1R inhibitor was administrated to evaluate the target of electroacupuncture in our mouse model. Results: Electroacupuncture significantly alleviated IMQ-induced skin lesions and epidermal thickness, accompanied with reduced keratinocyte proliferation, CD3+, CD4+, and CD8+ T cells infiltration. The reduced levels of inflammatory cytokines was observed after electroacupuncture treatment. In addition, electroacupuncture inhibited the expression levels of SP and NK1R. NK1R inhibitor could ameliorate lesional symptoms and suppress epidermal thickening and CD3+, CD4+, and CD8 + T cell infiltration. Conclusions: Electroacupuncture relieved psoriasis-like inflammation and T cell infiltration. This therapeutic action was likely mediated by the modulation of Substance P and its receptor NK1R. (c) 2023 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Despite advances in transdermal drug delivery for treating psoriasis, there are still unmet medical needs, hyaluronic acid (HA)-based topical formulations as nanocarriers, which can increase drug concentration in psoriatic skin through CD44-assisted targeting. Here, HA was utilized as a matrix for nanocrystal-based hydrogel (NC-gel) to deliver indirubin topically for psoriasis treatments. Indirubin nanocrystals (NCs) were prepared through wet media milling and were then mixed with HA to create indirubin NC/HA gels. A mouse model of imiquimod (IMQ)-induced psoriasis and M5-induced keratinocyte proliferation were established. Then, the efficacy of indirubin delivery targeted at CD44, and anti-psoriatic efficacy using indirubin NC/HA gels (HA-NC-IR group) were evaluated. The HA hydrogel network embedding indirubin NCs enhanced cutaneous absorption of poorly water-soluble indirubin. The co-localization of CD44 and HA in psoriasis-like inflamed skin was highly elevated, suggesting that indirubin NC/HA gels specifically adhered to CD44, leading to an increase in indirubin accumulation in the skin. Additionally, indirubin NC/HA gels enhanced the anti-psoriatic effect of indirubin in both a mouse model and HaCaT cells stimulated with M5. The results indicate that NC/HA gels targeting overexpressed CD44 protein can improve the delivery of topical indirubin to psoriatic inflamed tissues. This suggests that a topical drug delivery system could be a viable approach for formulating multiple insoluble natural products to treat psoriasis.

Background: Diabetic wounds represent a severe clinical challenge in which impaired M2 macrophage polarization and continuous macrophage glycolysis play crucial roles. Calycosin-7-glucoside (CG) is an isoflavone component in Astragali Radix (AR), which has become a research focus for treating diabetic wounds following reports indicating that it has anti-inflammatory effects. However, the mechanism through which CG can treat diabetic wounds is yet to be deciphered. Purpose: This study aimed to evaluate the therapeutic effect of CG on diabetic wounds and its underlying mechanism. Methods: The potential mechanism underlying the treatment of diabetic wounds by CG was screened using bioinformatics. The therapeutic effects of CG were then investigated using a db/db diabetic wound model. Moreover, an LPS- and IFN-gamma-induced RAW264.7 cell inflammation model was used to elucidate the mechanism underlying the therapeutic effects of CG against diabetic wounds. Results: Network pharmacology predicted that the AMPK pathway could be the main target through which CG treats diabetic wounds. In db/db diabetic mice, CG could accelerate wound healing and promote granulation tissue regeneration. Protein chip technology revealed that CG increased the production of M-CSF, G-CSF, GM-CSF, IL-10, IL-13, and IL-4 but not that of MCP-1, IL-1 beta, IL-1 alpha, TNF-alpha, and TNF-RII. Moreover, CG elevated the proportion of Ly6C(Lo/-) anti-inflammatory monocytes in peripheral blood and M2 macrophages in the wound. The ELISA and flow cytometry analyses revealed that CG enhanced the levels of IL-10, VEGF, CD206, and Arg-1 expression whereas it considerably reduced the levels of IL-1, IL-6, IL-12, TNF-alpha, CD86, and iNOS expression. Meanwhile, CG increased the macrophage mitochondrial membrane potential and decreased the mitochondrial ADP/ATP ratio and glycolysis rate of M1 macrophages through the ROS/AMPK/STAT6 pathway. Conclusions: The network pharmacology and molecular dockin identified the AMPK pathway as a critical pathway for treating diabetic wounds using topical CG application. CG was found to promote anti-inflammatory monocyte recruitment and decrease the mitochondrial glycolysis rate to induce M2 macrophage polarization via the ROS/AMPK/STAT6 pathway. These results suggest that CG might be a promising therapeutic agent for diabetic wounds.

Background: Psoriasis is a prevalent chronic inflammatory skin condition marked by immune cell infiltration and keratinocyte abnormal proliferation. Cimicifugae Rhizoma - Smilax glabra Roxb (CS) herb pair, the main component of Shengma Detoxification Decoction, has been proven effective for the treatment of psoriasis. However, the mechanism is yet to be deciphered. Purpose: To explore the mechanism of CS for the treatment of psoriasis. Methods: The imiquimod-induced psoriasis-like lesion mouse model was used to identify the targets and the molecular mechanisms of CS. Network pharmacology combined with RNA-seq strategy was employed to predict the targets and mechanisms of CS for psoriasis. Metabolomics approaches were used to demonstrate the complexity of CS for the treatment of psoriasis. Finally, a compound-response-enzyme-gene network was constructed based on the multi-omics results to elucidate potential connections. Results: The CS herb pair could significantly improve psoriatic lesions and reduce the inflammatory cell infiltration and proliferation of keratinocytes in skin lesions. Network pharmacology predicted that TNF, JNK, IL-6, and IL-1 beta could be potential targets. RNA-seq data revealed that CS could significantly regulate genes and signaling pathways associated with Th17 responses, such as IL-36, IL-1 beta, CCl2, CXCL16, keratin 14, keratin 5, and antimicrobial peptides S100A8 and S100A9 well as MAPK, mTOR, and other signaling pathways. Further experimental data validated that CS treatment remarkably reduced the expression of inflammatory cytokines and factors, such as CCL2, CCL7, IL1F6, IL-17, IL-23, IL-1 beta, TNF-alpha, and IL-6, and inhibited the phosphorylation of p38 and ERK1/2. This indicated that CS exerts its therapeutic effect by inhibiting the MAPK signaling pathways. In addition, metabolomic analyses demonstrated that CS treatment improved seven metabolic pathways, these included phenylalanine, tyrosine, pyruvate metabolism, carnitine metabolism, etc. Four key metabolites (L-Arginine, L-Phenylalanine, L-Carnitine, O-Acetylcarnitine) and nine differential genes (CMA1, PCBD2, TPSAB1, TPSB2, etc.) were identified that affected amino acid metabolism, carnitine metabolism, and other pathways contributing to the infiltration of Th17 cells in psoriatic lesions. Conclusion: CS could alleviate IMQ-induced psoriasis-like dermatitis by reducing the expression of cytokines and chemokines mediated by the MAPK pathway, and improved amino acid and carnitine metabolism in vivo. Our study is the first to demonstrate the complex mechanism of CS for the treatment of psoriasis and provides a new paradigm to elucidate the pharmacological effects of Traditional Chinese Medicine (TCM) drugs for psoriasis from multiple perspectives.

OBJECTIVE:To observe the effect of moxibustion on skin lesions and immune inflammatory response in psoriasis mice, and to explore the possible mechanism of moxibustion for psoriasis.METHODS:A total of 32 male BALB/c mice were randomly divided into a normal group, a model group, a moxibustion group and a medication group, 8 mice in each group. Psoriasis model was induced by applying 5% imiquimod cream on the back for 7 days in the model group, the moxibustion group and the medication group. At the same time of model establishment, the moxibustion group was treated with suspension moxibustion on skin lesions on the back, 20 min each time, once a day; the medication group was treated with 1 mg/kg methotrexate tablet solution by gavage, once a day. Both groups were intervened for 7 days. The daily changes of skin lesions were observed, and the psoriasis area and severity index (PASI) score was evaluated; the histopathological changes of skin lesions were observed by HE staining; the positive expression of proliferating cell nuclear antigen (PCNA) and T lymphocyte surface marker CD3 were detected by immunohistochemistry; the expression level of serum interleukin (IL) -17A was detected by ELISA, and the relative expressions of tumor necrosis factor-α (TNF-α), IL-1β and IL-6 mRNA in skin lesions were detected by real-time PCR.RESULTS:The increased and hypertrophy scale, dry skin, red and swollen epidermis and obvious infiltration were observed in the model group, and each score and total score of PASI were higher than those in the normal group (P<0.01). The scale score, infiltration score, and total score of PASI in the moxibustion group were lower than those in the model group (P<0.01); the infiltration score and total score of PASI in the medication group were lower than those in the model group (P<0.01, P<0.05). The inflammatory cell infiltration in the model group was obvious, and the thickness of epidermal layer was increased compared with that in the normal group (P<0.01); the inflammatory cell infiltration and Munro micro abscess were decreased in the moxibustion group and the medication group, and the thickness of epidermal layer was decreased compared with that in the model group (P<0.01). Compared with the normal group, the positive cell number of PCNA and T was increased (P<0.01), and the body mass was decreased, and the spleen index was increased (P<0.01), and the expression of serum IL-17A and the relative expression of TNF-α, IL-1β and IL-6 mRNA in the skin lesions was increased in the model group (P<0.01). Compared with the model group, the positive cell number of PCNA and T was reduced (P<0.01), and the spleen index and the relative expression of TNF-α, IL-1β and IL-6 mRNA were reduced (P<0.01) in the moxibustion group and the medication group; the body mass of mice in the moxibustion group was higher than that in the model group (P<0.01); the content of serum IL-17A in the medication group was lower than that in the model group (P<0.01); the relative expression of TNF-α, IL-1β mRNA in the moxibustion group was higher than that in the medication group (P<0.01).CONCLUSION:Moxibustion could effectively improve the scale and infiltration of skin lesions in psoriasis mice. Its mechanism may be related to inhibiting inflammatory response and regulating immunity.

目的:观察齐墩果酸对咪喹莫特诱导的银屑病样小鼠的皮损及STAT3通路的干预作用.方法:72只BALB/c雄性小鼠,按随机数字表法随机分为空白组、模型组、甲氨蝶吟组、齐墩果酸低、中、高剂量组,每组12只,于背部备皮.除空白组外,其余各组小鼠每日于背部备皮区域涂抹5％咪喹莫特乳膏诱导银屑病样皮损;甲氨蝶呤组及齐墩果酸各浓度组每日灌胃对应药物0.2 mL/只;每日观察皮损状态并拍照记录,每日对小鼠皮损面积及严重程度(Psoriasis Area and Severity Index,PASI)进行评分;造模第4、7天取小鼠皮损区域皮肤,免疫印迹法检测皮损中STAT3信号通路中STAT3磷酸化表达情况;第7天称量小鼠体重及脾重,计算脾指数,同时取小鼠皮损区域皮肤;苏木素-伊红(HE)染色观察皮损组织病理学改变,并测量表皮厚度;免疫组织化学法及免疫组织荧光法检测皮损中CD3+、CD4+、CD8+T细胞浸润情况及Ki67表达情况;实时荧光定量PCR法检测皮损中白介素-17(Interleukin-17,IL-17)mRNA相对表达情况.结果:与空白组相比,造模后模型组小鼠背部皮肤出现红斑、鳞屑、浸润性皮损,第4天及第7天PASI评分升高(P＜0.01);第7天模型组表皮厚度明显增加,体重下降,脾指数上升,皮损中Ki67、CD3+、CD4+、CD8+T细胞表达量升高,皮损中IL-17的mRNA相对表达量升高(均P＜0.01);第4及第7天,模型组小鼠皮损中p-STAT3的表达量均明显升高(P＜0.05,P＜0.01);与模型组相比,第4天各治疗组在PASI评分略降低(P＞0.05),第7天各治疗组PASI评分明显降低(均P＜0.01);第7天齐墩果酸各剂量组小鼠体重略有上升(P＞0.05);甲氨蝶吟组小鼠脾指数明显下降(P＜0.01),齐墩果酸低、中剂量组小鼠脾指数略下降(P＞0.05);各治疗组小鼠表皮厚度较模型组明显下降(P＜0.01或P＜0.05),小鼠皮肤中Ki-67表达量、CD4+、CD8+T细胞表达量均明显降低(均P＜0.01);甲氨蝶呤组、齐墩果酸低、中、高剂量组小鼠皮损中CD3+T细胞表达量均下降(P＜0.05,P＞0.05,P＜0.01,P＜0.01),其中在齐墩果酸各剂量组中,中剂量组在脾指数下降、表皮厚度变薄、CD3+、CD4+、CD8+T细胞减少方面均略优于低、高剂量组(P＞0.05);甲氨蝶呤组及齐墩果酸中剂量组小鼠皮损中IL-17的mRNA水平较模型组明显下降(P＜0.01,P＜0.05);造模给药第4天,甲氨蝶呤组小鼠皮损中p-STAT3水平较模型组明显下降(P＜0.05),齐墩果酸中剂量组略下降(P＞0.05);造模给药第7天,两个治疗组小鼠皮损中p-STAT3水平较模型组均明显下降(均P＜0.01).结论:齐墩果酸低、中、高剂量均可以改善咪喹莫特诱导的小鼠银屑病样皮损的严重程度,减轻炎性细胞浸润,中剂量组疗效较好,其机制可能通过抑制STAT3通路中p-STAT3的表达从而降低了 IL-17的含量,且药效随作用时间的延长而逐渐增加.

OBJECTIVE:To observe the effect of fire needling on psoriasis-like lesion and the signal transducer and activator of transcription 3 (STAT3) pathway in mice and compare the therapeutic effect between different interventions of fire needling therapy (surrounding technique of fire needling, fire needling at "Dazhui" [GV 14] and "Zusanli" [ST 36]).METHODS:Thirty male BALB/c mice were randomized into a blank group, a model group, a dexamthasone group, a surrounding technique group and an acupoint group, 6 mice in each one. Except the blank group, the mice in the rest groups were established as psoriasis-like lesion model by topical application with imiquimod cream, once daily, consecutively for 8 days. From day 4 to day 8, in the dexamthasone group, gastric infusion with 0.2 mL dexamthasone was administered, once daily. On day 4, 6 and 8, in the surrounding technique group, fire needling was exerted around the skin lesion; and fire needling was applied to "Dazhui" (GV 14) and "Zusanli" (ST 36) in the acupoint group, once a day. The changes in skin lesion on the dorsal parts of mice were observed in each group to score the psoriasis area and severity index (PASI). Using HE staining, the dermal morphological changes and epidermal thickness were observed in the mice of each group. The positive expression of proliferating cell-associated antigen Ki-67 was determined by immunofluorescence. Immunohistochemistry method was used to determine the expressions of , and T cells of skin tissue in each group. Using real-time PCR, the expressions of interleukin (IL)-17, IL-22, tumor necrosis factor α(TNF-α) mRNA were determined. Western blot method was adopted to determine the protein expressions of STAT3 and p-STAT3 in skin tissue in each group.RESULTS:Compared with the blank group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all increased in the mice of the model group (P<0.01). Except for the erythema scores of the dexamethasone group and the surrounding technique group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all decreased in each intervention group as compared with the model group (P<0.01). The infiltration scores and the total scores in the dexamethasone group and the acupoint group were lower than those in the surrounding technique group respectively (P<0.01, P<0.05). In comparison with the blank group, Ki-67 positive cell numbers and the numbers of , and T cells in skin tissue were increased in the mice of the model group (P<0.01). Ki-67 positive cell numbers and the numbers of , and T cells were reduced in each intervention group as compared with the model group (P<0.01), and the numbers of and T cells in the acupoint group were less than the surrounding technique group (P<0.01). Compared with the blank group, the mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all increased in the model group (P<0.01). The mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all decreased in each intervention group as compared with the model group (P<0.01, P<0.05). The mRNA expressions of IL-17, IL-22 and TNF-α in the acupoint group, as well as mRNA expression of IL-17 in the surrounding technique group were all lower than the dexamethasone group (P<0.01), while, the mRNA expression of IL-22 in the acupoint group was lower than the surrounding technique group (P<0.01).CONCLUSION:Fire needling therapy improves skin lesion severity in imiquimod induced psoriasis-like lesion of the mice, which is probably related to the inhibition of STAT3 pathway activation and the decrease of Th17 inflammatory factors expression. The systemic regulation of fire needling at "Dazhui" (GV 14) and "Zusanli" (ST 36) is superior to the local treatment.

银屑病是一种复杂的慢性复发性炎症性疾病,不仅存在组织不可逆的损伤和免疫异常,还存在干细胞的严重异常.干细胞异常表达了表皮增生、血管生成和炎性反应等相关基因,还分泌了细胞生长因子(EGF)、血管内皮生长因子(VEGF)、炎性因子、免疫细胞趋化因子等,在银屑病的发病中有着重要的作用.本文对间充质干细胞(MSC)、表皮干细胞(ESC)、造血干细胞(HSC)在银屑病发病中的作用机制进行综述.

目的:通过对比凉血解毒方,观察活血解毒方对咪喹莫特诱导的银屑病样小鼠皮损紧密连接蛋白表达以及皮损复发的干预作用,为中医药通过调节皮肤屏障治疗及延缓银屑病复发提供生物学证据.方法:选用C57BL/6J小鼠,随机分为空白对照组、模型组、阳性药(氨甲蝶呤)组、活血解毒方组和凉血解毒方组,小鼠背部剃毛后给予咪喹莫特涂抹诱导银屑病样皮损模型.初次干预7 d后,间隔30 d,除空白对照组外各组仅涂抹咪喹莫特诱导银屑病复发皮损模型.期间对皮损拍照并进行银屑病面积和严重程度指数(PASI)评分;水油笔检测皮损表皮含水量;HE染色观察其病理改变并测量表皮厚度;免疫荧光法检测小鼠表皮Ki67表达;免疫组化法检测表皮兜甲蛋白(loricrin),真皮中紧密连接蛋白claduin-1、claudin-7和occludin的表达及CD3+T淋巴细胞浸润.Western blot法检测皮损occludin的表达.结果:活血解毒方可缓解咪喹莫特诱导的小鼠银屑病样皮损,降低PASI评分及表皮厚度(P<0.05);与模型组比较,活血解毒方可增加皮损区表皮水分含量(P<0.05),减少表皮Ki67和loricrin的异常表达和真皮CD3+T细胞浸润(P<0.01),增加claudin-1、claudin-7和occludin的表达(P<0.05),增强紧密连接的结构完整性.活血解毒方亦可减轻二次诱导的小鼠银屑病样皮损表现,降低PASI评分及表皮厚度(P<0.05).结论:活血解毒方可能通过调节紧密连接蛋白表达,恢复受损的表皮屏障功能,从而减轻银屑病复发皮损表现.

Background: Psoriasis is a psychosomatic immune skin disease with psychological factors contributing to the disease. Substance P (SP) is highly expressed in the psoriatic lesions of patients and is involved in pathological disease progression. Tribulus terrestris L. has been used as a Chinese herbal medicine for disease prevention for thousands of years. Terrestrosin D (TED) has been identified as the effective monomeric component of Tribulus terrestris L..Purpose: We investigated whether TED could reverse imiquimod-induced psoriatic lesions, and then, investigated its potential mechanism of action both in vivo and in vitro.Methods: 5% imiquimod cream was applied onto the backs of mice for 6 days to induce psoriasis-like skin lesions. The psoriatic area and severity index (PASI) was then used for scoring disease severity. Pathological changes and Ki-67 expression levels in skin lesions were measured using hematoxylin and eosin (H & E) and immunofluorescence staining after TED administration. The in vivo and in vitro expression levels of inflammatory cytokines, the ratio of DCs, and SP were measured using ProcartaPlex Mouse Cytokine panels, flow cytometry, and western blotting. Behavioral assessments were determined using the open field and elevated plus-maze (EPM) test.Results: TED decreased PASI scores, epidermal thickness, Ki-67 expression levels, the ratio of DCs in the spleen, and secretion of IL-12p70, IL-18, and TNF-alpha in imiquimod-induced psoriasis-like murine models. Furthermore, TED increased IL-10 secretion levels, improved behavior, and down-regulated the expression levels of SP. Additionally, TED inhibited the in vitro maturation and activation of SP-induced CD11c(+) DCs and the release of IL-12p70 and IL-23.Conclusion: TED reduced DCs maturation, down-regulated the expression levels of inflammatory factors, and improved skin lesions and behavior of psoriasis-like murine models by inhibiting the interaction between Substance P and Dendritic cells.

目的:通过建立脾虚-银屑病样复合小鼠模型探讨脾虚对银屑病皮损及分子机制的影响.方法:苦寒泻下结合营养限制法建立脾虚证模型后,咪喹莫特乳膏局部涂抹诱导银屑病样模型.观察小鼠皮损面积和疾病严重程度(PASI)及其组织形态学变化;免疫组织化学法检测皮损中增殖细胞核抗原(PCNA)和CD3的表达;RT-PCR技术检测皮损中FOXP3、ROR-γt、白细胞介素2(IL-2)基因表达水平.结果:与对照-IMQ组比较,脾虚-IMQ组小鼠皮损鳞屑和表皮厚度明显升高(P＜0.05),炎性细胞浸润显著,皮损中ROR-γtmRNA表达的升高趋势有所减缓,但Foxp3 mRNA显著降低(P＜0.05).结论:脾虚可加重银屑病皮损的严重程度,尤其鳞屑增多、皮损肥厚,与脾虚血燥的临床表现较一致,探索其机制可能与Treg/Th 17平衡偏移有关.