Apigenin ameliorates imiquimod-induced psoriasis in C57BL/6J mice by inactivating STAT3 and NF-κB

Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.

Coleus forskohlii shows anti-psoriatic activity in imiquimod-induced psoriasis rats

Objective:To evaluate anti-psoriatic activity of Coleus forskohlii in rats with imiquimod-induced psoriasis.Methods:Imiquimod was used to induce psoriasis in rats.Body weight,skin thickness,erythema,scaling,spleen weight,and histological alternations were measured to assess the effect of Coleus forskohlii.Furthermore,an emulgel formulation containing Coleus forskohlii 10%was prepared and characterized along with its ex vivo permeation studies.Results:The emulgel formulation containing Coleus forskohlii 10%had a pH of 5.40±0.36,with optimum spreadability of(31.67±2.08)g/(cm·s)and viscosity of(15966.67±1274.10)cps,and enhanced both the rate and the extent of drug permeation through psoriatic skin.In an ex vivo study,the quantity of drug permeated(19.18%),deposited(52.38%),and drug remaining in the donor compartments(28.31%)was satisfactory.Coleus forskohlii significantly alleviated imiquimod-induced psoriasis by increasing glutathione and superoxide dismutase activity,decreasing malondialdehyde and nitric oxide levels,and alleviating histological alternations in rat skin.Conclusions:Coleus forskohlii can alleviate imiquimod-induced psoriasis,which may be used as a therapeutic candidate for the treatment of psoriasis.

Secoemestrin C Ameliorates Psoriasis-like Skin Inflammation in Mice by Suppressing the TNF-α/NF-κB Signaling Pathway

Objective Secoemestrin C(SC),an epitetrathiodioxopiperazine isolated from Aspergillus nidulans,has been previously reported to have immunomodulatory and hepatoprotective effects against acute autoimmune hepatitis.However,the effect of SC on regulating the inflammation and its underlying mechanisms in the pathogenesis of psoriasis remain unclear.This study aimed to evaluate the effects of SC on inflammatory dermatosis both in vitro and in vivo.Methods In vitro,HaCaT cells were induced with tumor necrosis factor-alpha(TNF-α,10 ng/mL)to establish an inflammatory injury model,and the expression of nuclear transcription factor-κB(NF-κB)pathway components was measured using qRT-PCR and Western blotting.An in vivo mouse model of imiquimod(IMQ)-induced psoriasis-like skin inflammation was used to evaluate the effectiveness of SC in alleviating psoriasis.Results SC significantly blocked the activation of NF-κB signaling in TNF-α-stimulated HaCaT cells.In addition,systemic and local administration of SC improved psoriatic dermatitis in the IMQ-induced mouse model.SC reduced skin scale and significantly inhibited the secretion of inflammatory factors in skin lesions.Conclusion The protective effect of SC against psoriatic-associated inflammation reveals its potential therapeutic value for treating psoriasis.

Moyamoya syndrome may result from psoriasis: Four case reports

BACKGROUND Moyamoya syndrome(MMS)is a group of diseases that involves more than one underlying disease and is accompanied by moyamoya vascular phenomena.Psoriasis is a chronic immune skin disease closely linked to high blood pressure and heart disease.However,psoriasis-related MMS has not been reported.CASE SUMMARY We collected data on patients with stroke due to MMS between January 2017 and December 2019 and identified four cases of psoriasis.Case histories,imaging,and hematological data were collected.The average age of the initial stroke onset was 58.25±11.52 years;three cases of hemorrhagic and one case of ischemic stroke were included.The average duration from psoriasis confirmation to the initial MMS-mediated stroke onset was 17±3.56 years.All MMS-related stenoses involved the bilateral cerebral arteries:Suzuki grade III in one case,grade IV in two cases,and grade V in one case.Abnormally elevated plasma interleukin-6 levels were observed in four patients.Two patients had abnormally elevated immunoglobulin E levels,and two had thrombocytosis.All four patients received medication instead of surgery.With an average follow-up time of 2 years,two causing transient ischemic attacks occurred in two patients,and no hemorrhagic events occurred.CONCLUSION Psoriasis may be a potential risk factor for MMS.Patients with psoriasis should be screened for MMS when they present with neurological symptoms.

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Medical dilemma:Programmed death 1 blockade(sintilimab)therapy in patients suffering from tumours combined with psoriasis

Tumour immunotherapy represented by immune checkpoint inhibitors(ICIs)has greatly improved the overall prognosis of patients with malignant tumours,and is regarded as an important breakthrough in the field of medicine in recent years.ICIs have gradually become the core of tumour therapy and are increasingly used in the clinic.In order to achieve early clinical prediction and management of immune-related adverse events(irAEs),it is still necessary to perform further research on the mechanisms,risk factors,and predictors of irAE occurrence in the future.Zhou et al describe the consultation of a patient with advanced gastric cancer combined with chronic plaque psoriasis.This case provides an important reference for the use of programmed cell death protein-1(PD-1)inhibitors in patients of tumours combined with chronic plaque psoriasis.This case also highlights that screening of high-risk groups for irAEs is critical before applying PD-1 inhibitors to patients with chronic psoriasis combined with tumours.PD-1 inhibitors are new and potent antineoplastic agents that can cause serious immunerelated adverse events such as toxic epidermal necrolysis release and psoriasis.Glucocorticosteroids are the first-line agents for irAEs.The incidence of rheumatic irAEs may be higher in reality,which will inevitably become a new challenge for rheumatologists and dermatologists.

Mechanism of traditional Chinese medicine in the treatment of psoriasis with depression:A review

Psoriasis is a kind of immune-mediated, chronic, inflammatory skin disease, which is often associated with different degrees of psychological disorders. Specifically, there is a significant correlation between psoriasis and depression, and they show the relationships of reciprocal causation and mutual promotion. Psoriasis with depression is more harmful than simple psoriasis, and its prognosis is worse, which brings a huge burden to the family and society and is worthy of clinical attention. Based on the pathogenic factors of western medicine and pathogenesis of traditional Chinese medicine in psoriasis with depression, the paper summarized and elaborated the research progress on the mechanism of traditional Chinese medicine in the treatment of psoriasis with depression, in order to provide new ideas for clinical treatment.

Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population

Background:Psoriasis is a disease caused by genetics and immune system dysfunction,affecting the skin and joints.Toll-like receptors(TLRs)play an important role in triggering the innate immune response and controlling adaptive immunity.The role of TLR2 in the progression of psoriasis is not well understood.Methods:A case-control study was conducted on a northern Chinese Han population,consisting of psoriasis patients and healthy control subjects.Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction(ARMS-PCR),and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls.Results:Four TLR2 SNPs(rs11938228,rs4696480,rs3804099,rs5743699)were genotyped and found to be in linkage disequilibrium.The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model.The haplotypes ATTC and ATCC were found to be protective against psoriasis.Conclusion:Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.

The Application Progress of Skin Imaging Technology in Psoriasis

Skin imaging technologies such as dermoscopy, high-frequency ultrasound, reflective confocal microscopy and optical coherence tomography are developing rapidly in clinical application. Skin imaging technology can improve clinical diagnosis rate, and its non-invasiveness and repeatability make it occupy an irreplaceable position in clinical diagnosis. With the “booming development” of medical technology, skin imaging technology can improve clinical diagnosis rate. Researchers have made significant advances in assisting clinical diagnosis, prediction, and treatment of disease. This article reviews the application and progress of skin imaging in the diagnosis of psoriasis.

Systemic Amyloidosis Secondary to Psoriasis: A Rare, Autoimmune and Genetically-Determined Disorder That Is Amenable to Treatment with Cyclosporin A—Cyclosporin A for Psoriasis-Induced Amyloidosis

Background: Systemic secondary amyloidosis (SSA) is associated with chronic inflammatory disorders and/or chronic infections. Patients and Methods: Over the past 10 years;a total of 21 patients, with long-term (17 months) and extensive psoriasis (P) with psoriasis area severity index (PASI) >29, were evaluated. Results: Two patients had nephrotic syndrome (proteinuria 3.9 and 3.6 g/day) and decrease creatinine clearance (46 and 62 ml/minute). Their renal biopsy revealed Congo-red (+) nodular glomerulosclerosis that lacked immune-deposits and resisted wash with K-permanganate wash indicating SSA. Three months subsequent to Cyclosporin A (CyA) therapy with 100 mg twice daily;psoriasis improved in all patients with decrease in (PASI) from 29.5 to 3.5 1. In the 2 patients with SSA;proteinuria decreased to 2.1 and 1.8 g/day and creatinine clearance improved to 51 and 69 ml/minute. Such improvement persisted up to 2 years of follow up and up to 78 months in patients with SSA. Conclusion: psoriasis-induced SSA is an autoimmune disease, with genetic predisposition that is amenable to CyA therapy.

Chemerin Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production

Objective Psoriasis is often combined with metabolic abnormalities,such as obesity and diabetes.The upregulation of chemerin,which is an essential protein produced primarily from white fat,is strongly correlated to the development of psoriasis.However,there is no clarification on its exact function and mechanism in disease pathogenesis.The present study aims to determine its function and mechanism in disease pathogenesis.Methods The present study used a psoriasislike inflammatory cell model and imiquimod(IMQ)-induced mouse model to confirm whether chemerin is upregulated in psoriasis patients.Results Chemerin enhanced the keratinocyte proliferation,inflammatory cytokine secretion,and activation of the MAPK signaling pathway.Crucially,the intraperitoneal injection of neutralizing anti-chemerin antibody(ChAb)diminished the epidermal proliferation and inflammation in the IMQ-induced mouse model.Conclusion The present results indicate that chemerin promotes keratinocyte proliferation,and enhances the production of inflammatory cytokines,thereby aggravating the psoriasis.Thus,chemerin can be a prospective target for the treatment of psoriasis.

Water-responsive gel extends drug retention and facilitates skin penetration for curcumin topical delivery against psoriasis

Psoriasis is a chronic inflammatory skin disease characterized by erythema,scaling,and skin thickening.Topical drug application is recommended as the first-line treatment.Many formulation strategies have been developed and explored for enhanced topical psoriasis treatment.However,these preparations usually have low viscosity and limited retention on the skin surface,resulting in low drug delivery efficiency and poor patient satisfaction.In this study,we developed the first water-responsive gel(WRG),which has a distinct water-triggered liquid-to-gel phase transition property.Specifically,WRG was kept in a solution state in the absence of water,and the addition of water induced an immediate phase transition and resulted in a high viscosity gel.Curcumin was used as a model drug to investigate the potential of WRG in topical drug delivery against psoriasis.In vitro and in vivo data showed that WRG formulation could not only extend skin retention but also facilitate the drug permeating across the skin.In a mouse model of psoriasis,curcumin loaded WRG(CUR-WRG)effectively ameliorated the symptoms of psoriasis and exerted a potent anti-psoriasis effect by extending drug retention and facilitating drug penetration.Further mechanism study demonstrated that the anti-hyperplasia,anti-inflammation,anti-angiogenesis,anti-oxidation,and immunomodulation properties of curcumin were amplified by enhanced topical drug delivery efficiency.Notably,neglectable local or systemic toxicity was observed for CUR-WRG application.This study suggests that WRG is a promising formulation for topically psoriasis treatment.

Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis

Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress.Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis.Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved.Herein,we reported a nanotransdermal delivery system composed of all-trans retinoic acid(TRA),triphenylphosphine(TPP)-modified cerium oxide(CeO2)nanoparticles,flexible nanoliposomes and gels(TCeO_(2)-TRA-FNL-Gel).The results revealed that TCeO_(2)synthesized by the anti-micelle method,with a size of approximately 5 nm,possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species(ROS).TCeO_(2)-TRA-FNL prepared by the film dispersion method,with a size of approximately 70 nm,showed high drug encapsulation efficiency(>96%).TCeO_(2)-TRA-FNL-Gel further showed sustained drug release behaviors,great transdermal permeation ability,and greater skin retention than the free TRA.The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO_(2)-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells.The results of in vivo imiquimod(IMQ)-induced model indicated that TCeO_(2)-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms.In summary,the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.

Correlation analysis of anxiety with psoriasis severity, oxidative stress and inflammatory factors in patients with psoriasis vulgaris

Objective:To investigate the anxiety status of patients with psoriasis vulgaris,and analyze the correlation between anxiety and severity of the disease,oxidative stress factors and inflammatory factors.Methods:From August 2021 to February 2022,84 patients with psoriasis in the Dermatology Department of Dongzhimen Hospital of Traditional Chinese Medicine were recruited.Hamilton anxiety scale(HAMA),psoriasis lesion area and severity index(PASI),VAS pruritus scale(VAS)were collected to detect serum malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH px),interleukin-6(IL-6),interleukin-17A(IL-17A),and tumor necrosis factor-α(TNF-α).Based on the HAMA score,a group controlled study and correlation analysis were conducted.In addition,the HAMA scores of 84 healthy people were collected for a controlled study.Results:HAMA score of patients with psoriasis vulgaris was higher than that of healthy people(Z=-7.730,P<0.05).There were differences in PASI,VAS scores,MDA,SOD,GSH px,IL-6,IL-17A secretion levels between psoriasis vulgaris patients with anxiety and psoriasis vulgaris patients without anxiety.HAMA score was positively correlated with PASI and VAS scores in patients with psoriasis vulgaris(r=0.564,0.513,P<0.05).It was positively correlated with MDA,IL-6,IL-17A in serum(r=0.390,0.355,0.248,P<0.05).It was negatively correlated with SOD and GSH px(r=-0.313,-0.502,P<0.05);and TNF-αnot relevant.Conclusion:The anxiety risk of psoriasis patients was higher than that of healthy people;anxiety is closely related to psoriasis,and is reflected in the skin lesions,itching,oxidative stress and inflammatory factor levels of psoriasis patients.The comorbidity mechanism of anxiety and psoriasis may be related to oxidative stress and up regulation of inflammatory factors.

Mepolizumab induced palmoplantar psoriasis:A case report

BACKGROUND Atopic dermatitis and asthma are two diseases whose pathogenesis is largely attributable to the activation,at least in the initial stages,of T helper(Th)-2 Lymphocytes,the related cytokine axis,and B lymphocytes with antibody production.Psoriasis is conversely a pathology resulting from a recruitment of Th-17 and Th-1 lymphocytes,after an initial role of innate immunity.Mepolizumab is a humanized monoclonal antibody directed against interleukin(IL)-5,a central cytokine in the Th-2 axis,therefore involved in the pathogenesis of asthma.Several authors have described the appearance of psoriatic lesions in patients with asthma or atopic dermatitis following the therapy with dupilumab,a monoclonal antibody that blocks the interleukin(IL)-4,another Th-2 cytokine.CASE SUMMARY We present the case of a 59-year-old patient who developed psoriasiform lesions on the palms after mepolizumab therapy for asthma,for the activation of the parallel cytokine cascade after the blockade of IL-5.We successfully treated the patient with a topical calcipotriol and betamethasone ointment.CONCLUSION We should investigate with further attention the possible impact on the human immunological ecosystem put in place by the inhibition of the activity of individual inflammatory mediators,so as to be able to recognize the initial adverse effects early.

Chemical components and mechanism of Jiuwei Huaban pill in treating psoriasis

Objective:To systematically study the key active ingredients of Jiuwei Huaban pill in the treatment of psoriasis and explore its mechanism of action.Methods:The chemical components of Jiuwei Huaban pill were systematically identified by UPLC-QTOF/MSE,and network pharmacology method was used to study the main pharmacodynamic substances of Jiuwei Huaban pill and discuss the mechanism of action.Molecular docking technology was used to verify the binding activity of key components and target proteins.Results:A total of 75 components of Jiuwei Huaban pill were identified,35 of which were key components for psoriasis treatment,including luteolin,baicalin,baicalin,paeoniflorin and geniposide.Enrichment analysis of 30 core target pathways showed that Jiuwei Huaban pill played its role in the treatment of psoriasis from the IL-17 signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,Th17 signaling pathway,and MAPK signaling pathway.The key active components in Jiuwei Huaban pill and targets with the highest DGREE value in the"component target disease"network have strong binding activity.Conclusion:The active ingredients and mechanism of action of Jiuwei Huaban pill in the treatment of psoriasis were preliminarily clarified,which provids reference for quality control.

Advancements in Psoriasis Research: Skin Microcirculation and Its Prognostic Significance

Psoriasis, a chronic and recurring inflammatory skin disorder, is distinguished by the excessive proliferation of keratinocytes, immune cell infiltration, and angiogenesis. Ever since the observation of microvascular hyperplasia in psoriatic lesions, there has been a growing focus on exploring the intricate relationship between microcirculation and psoriasis. Furthermore, the potential utility of microcirculatory changes as prognostic indicators for psoriasis has garnered significant attention. This paper provides a comprehensive review of the role of skin microcirculation in psoriasis pathogenesis and its potential application as a clinical prognostic indicator.

Systematic review of the therapeutic effect of fire acupuncture on psoriasis vulgaris based on"releasing stagnated fire"theory

Background:To systematically evaluate the clinical efficacy of fire acupuncture(or needle)in the treatment of psoriasis vulgaris.Methods:The following electronic databases were retrieved by calculator:PubMed,Embase,Cochrane Library,CNKI,Wanfang Academic Journal Database,VIP Chinese Journal Database,etc.All the randomized controlled trials using fire needles in the treatment of psoriasis vulgaris from the self-established database to August 2021 were included,and the qualified literatures were included.Review manager 5.3 software was used for the combined analysis of the included literatures,TSA v0.9 Beta for sequential analysis,and GRADE pro V3.6 for evidence quality evaluation.Results:A total of 14 studies with 1,440 patients were included in this study.Meta analysis results showed:effective rate[RR=1.15,95%CI(1.10,1.19),P<0.00001,very low quality evidence];Psoriasis Area and Severity Index[PASI score,WMD=-2.15,95%CI(-2.40,-1.90),P<0.00001,evidence of low quality],Dermatology Life Quality Index scale[DLQI score,WMD=-3.56,95%CI(-4.86,-2.26),P<0.00001,very low quality evidence],the experimental group was better than the control group(P<0.05).Sequential analysis further showed that the use of fire needle as the primary treatment could significantly reduce PASI score.The adverse reactions rate of the experimental group was 6%,and that of the control group was 11%,P<0.05.Conclusion:Fire acupuncture as the main treatment can reduce PASI and QLDI scores of patients with psoriasis vulgaris,improve the treatment efficiency,and fewer adverse reactions.

A Systematic Review of Patient-Reported Outcome Measurement for Psoriasis in Chinese Population

Objective To review the development of patient-reported outcome measurement(PROM)for patients with psoriasis in China,and to analyze the main results and methodology.Methods The systematic review method of COSMIN(consensus-based standards for the selection of health measurement instruments)was adopted,and the domestic and foreign databases were searched to find the patient-reported outcome scales based on Chinese psoriasis patients.Then,the included studies were evaluated by using COSMIN risk of bias checklist.Results and Conclusion A total of 3 studies were included,involving 3 scales.We found that the quality evaluation of the development process of the 3 scales was not high,and there were large methodological loopholes in the whole cycle of scale development and verification.The included studies have many problems such as low extrapolation,poor quality,and lack of validation,which can provide more insights for the quality control requirements of the whole cycle of scale development in the future.

Molecular mechanism of Compound Qingdai Capsule in the treatment of psoriasis based on network pharmacology and molecular docking

Objective:Although Compound Qingdai Capsule(CQC)successfully treats psoriasis,the exact mechanism remains unclear.Our research used network pharmacology to investigate the molecular mechanism of CQC in treating psoriasis.Methods:The Traditional Chinese Medicine Systems Pharmacology platform was used to screen the bioactive chemical elements and identify gene targets,and the ingredient-target network was visualized by Cytoscape software.Genes associated with psoriasis were found in the Gene Expression Omnibus database.The protein-protein interaction network was created using STRING and Cytoscape,and the hub genes were identified using MCODE and topological analysis.Gene ontology and Kyoto encyclopedia of genes and genomes analyses were applied to obtain hub genes’biological processes and signaling pathways.Subsequently,the ingredient-target-pathway-disease network was visualized by Cytoscape.Results:Finally,an active ingredient-target network of CQC containing 130 active ingredients and 213 targets was built.Conclusion:The top 3 bioactive components were identified as quercetin,luteolin,and kaempferol,and the top 5 hub genes were identified as IL1B,CXCL8,STAT3,MMP9,and HMOX1.The critical pathways of CQC treatment in psoriasis were AGE-RAGE signaling,IL-17 signaling,TNF signaling,Fluid shear stress and atherosclerosis,and Toll-like receptor signaling pathway.Molecular docking confirmed a robust binding affinity between the main active ingredients of CQC with the hub target proteins.On this basis,additional animal or cellular research might be undertaken to investigate the targets and mechanisms of CQC treatment in psoriasis.