Objective To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization(MR)study.Methods A two-sample MR study was performed using summarized statistics from the g...Objective To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization(MR)study.Methods A two-sample MR study was performed using summarized statistics from the genome-wide association studies(GWAS)conducted in reproductive traits,as well as GWAS data on overall psoriasis,psoriatic arthritis(PsA),and psoriasis vulgaris(PV).Besides univariable MR(UVMR),multivariable MR and two-step MR was used to calculate the independent effects and quantify the proportion mediated by education or body mass index(BMI).Results Genetically predicted early age at first sexual intercourse(AFS)led to an increased risk of overall psoriasis[odds ratio(OR)UVMR:0.54];36.13%of this effect was mediated through BMI and 47.79%through educational attainment.The direct negative casual association between age at first birth(AFB)-PsA was dominant(ORUVMR:0.76),with 49.61%proportion of the mediation due to BMI.The mediating effect was found for BMI on the AFS-PV relationship,which accounted for 26.27%of the proportion.AFS was inversely associated with the risk of overall psoriasis and PV,with considerable mediation by BMI and educational attainment.Conclusion Early AFB may cause a higher risk of PsA,while the AFS-PsA association was fully mediated by BMI.展开更多
Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in...Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.展开更多
BACKGROUND Erythrodermic psoriasis(EP)is a rare and life-threatening form of psoriasis associated with significant morbidity and mortality.Systemic immunosuppre-ssive therapies are often required but may predispose to...BACKGROUND Erythrodermic psoriasis(EP)is a rare and life-threatening form of psoriasis associated with significant morbidity and mortality.Systemic immunosuppre-ssive therapies are often required but may predispose to opportunistic infections.Disseminated herpes simplex virus type-1(HSV-1)is an unusual complication in otherwise immunocompetent patients and has not been reported in association with ixekizumab therapy for EP.CASE SUMMARY We describe a 49-year-old man with longstanding severe plaque psoriasis,liver cirrhosis,and bipolar disorder who developed EP involving>90%of body surface area[Psoriasis Area and Severity Index(PASI)45].Following initial stabil-ization,he was admitted to the intensive care unit(ICU)with hemodynamic instability,leukocytosis with eosinophilia,and diffuse desquamation.Ixekizumab was initiated with high-dose topical clobetasol.During his ICU stay,he developed recurrent bacteremias and neurologic decline(Glasgow Coma Scale 7/15),fo-llowed by the appearance of widespread vesicles and hemorrhagic crusts.HSV-1 infection was confirmed by polymerase chain reaction(PCR).Immunosuppressive therapy was withheld,and intravenous acyclovir was started,leading to progre-ssive improvement.After ten days,ixekizumab was reintroduced with careful monitoring,resulting in marked clinical improvement(PASI 9.7 at six weeks).The patient remained stable on long-term follow-up with oral acyclovir prophylaxis.CONCLUSION This case highlights the diagnostic and therapeutic challenges of managing EP in the setting of biologic therapy.Disseminated cutaneous HSV-1 should be considered in immunosuppressed patients presenting with new vesicular eruptions,and prompt PCR testing with early antiviral therapy is essential.A multidisciplinary approach is critical to balance immunosuppression for disease control with infection risk.展开更多
OBJECTIVE:To explore the therapeutic mechanisms of Xiaoyin Anshen Yin( 消银安神饮, XYAS) in treating psoriasis associated with sleep focusing on melatonin and the regulation of the nuclear factor kappa-B(NF-κB) pathw...OBJECTIVE:To explore the therapeutic mechanisms of Xiaoyin Anshen Yin( 消银安神饮, XYAS) in treating psoriasis associated with sleep focusing on melatonin and the regulation of the nuclear factor kappa-B(NF-κB) pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups, and administered distilled water, XYAS and its two different disassembly prescriptions by gavage respectively. Four types of drug-containing serums corresponding to the four groups were then prepared. Tumor necrosis factor(TNF)-α stimulated Ha Ca T was used to establish a psoriasis cell model, and the serums and the retinoid related orphan receptor alpha(RORα) inverse agonist were used respectively to intervene in the model. Enzyme-linked immunosorbent assay was used to detect the levels of interleukin(IL)-6 and melatonin in each group;flow cytometry was used to detect the levels of reactive oxygen species(ROS), mitochondrial membrane potential, and apoptosis;Western blot was used to evaluate the levels of superoxide dismutase 2(SOD2), cytochrome-c(Cyt-c), inhibitor of kappa-B alpha(IκBα), p65 and phosphorylated p65. RESULTS:XYAS and its disassembly prescriptions inhibited the secretion of inflammatory factors such as IL-6, reduced the ROS content and Cyt-c expression, increased the mitochondrial membrane potential and SOD2 content, promoted the apoptosis in Ha Ca T cells and inhibited the activation of the NF-κB pathway. XYAS was also found increase the melatonin content. The above effects are beneficial in the treatment of psoriasis combined with sleep disorders. Meanwhile, XYAS no longer had a significant ameliorative effect after applying the RORα inverse agonist, suggesting that the therapeutic effect of XYAS is related to RORα. CONCLUSIONS:The results of this study confirm that XYAS can be utilized for the treatment of psoriasis combined with sleep disorders via inhibiting the NF-κB pathway, anti-inflammatory, antioxidant and proapoptotic, which is in part related to the regulatory role of melatonin and its receptor RORα.展开更多
BACKGROUND Psoriasis is a chronic inflammatory condition related to an increased athero-sclerotic cardiovascular disease(ASCVD)risk.AIM To investigate whether lipoprotein(a)[Lp(a)]levels are increased in patients with...BACKGROUND Psoriasis is a chronic inflammatory condition related to an increased athero-sclerotic cardiovascular disease(ASCVD)risk.AIM To investigate whether lipoprotein(a)[Lp(a)]levels are increased in patients with psoriasis.METHODS A comprehensive literature search up to January 30,2025 was conducted utilizing PubMed and Cochrane Library databases.A qualitative synthesis and a meta-analysis on Lp(a)mean differences(MD)between psoriasis cases and healthy controls(HC)was performed.The protocol of this meta-analysis has been re-gistered to PROSPERO(No.CRD420250652465).RESULTS Eighteen studies with 1650 psoriasis patients and 1621 HC were eligible for qua-litative synthesis.Pooled analysis from 16 studies(1401 psoriasis patients and 1320 HC)demonstrated that psoriasis patients had significantly higher Lp(a)levels compared with the HC group(MD:6.72 mg/dL,95%CI:4.32-9.12,P<0.00001,I2=71%).Sensitivity analyses according to the region of origin was also performed.The pooled analysis of the European sub-population showed a pronounced increase in Lp(a)levels in 189 patients with psoriasis vs 178 HC(MD:15.86 mg/dL,95%CI:5.79-25.92,P<0.002,I2=79%),while the pooled analysis on the Asian sub-population demonstrated a smaller but still significant difference in Lp(a)levels between 1177 psoriasis patients and 1127 HC(MD:4.95 mg/dL,95%CI:2.99-6.92,P<0.00001,I2=58%).CONCLUSION Our findings suggest that Lp(a)levels are significantly elevated in psoriasis patients,further adding to their ASCVD risk.展开更多
Psoriasis is a prevalent inflammatory disease that shares chronic inflammation pathways with the pathophysiology of metabolic syndrome(MetS),type-2 diabetes mellitus and atherosclerosis.A high prevalence of steatosis ...Psoriasis is a prevalent inflammatory disease that shares chronic inflammation pathways with the pathophysiology of metabolic syndrome(MetS),type-2 diabetes mellitus and atherosclerosis.A high prevalence of steatosis and advanced liver fibrosis has been described in psoriasis.The influence of MetS and its compounds,patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 gene polymorphisms and the cumulative dose of methotrexate(MTX)in the progression of steatotic disease are still under debate.A suitable new classification for psoriasis-related liver disease,under the umbrella of steatotic liver disease(SLD),might be evaluated due to the potential impact of MTX on liver steatosis.Considering the interplay between the MetS,steatosis and MTX,a new definition for this complex disease might be discussed since it is not entirely addressed under the umbrella of SLD and metabolic-dysfunction associated SLD.Hence,shortly,a discussion could be raised on the feasible term“Met-Drug SLD”,metabolic and drug-induced SLD,which comprises both metabolic dysfunction and drug-related SLD.This review aims to report the best evidence to accurately classify liver disease in psoriasis,considering the new definition of SLD,allowing appropriate management once it is carefully defined.展开更多
Background: Erythrodermic psoriasis (EP) is a rare, severe variant of psoriasis characterized by widespread erythema, scaling, and systemic complications. Despite advances in systemic treatments, the management of EP ...Background: Erythrodermic psoriasis (EP) is a rare, severe variant of psoriasis characterized by widespread erythema, scaling, and systemic complications. Despite advances in systemic treatments, the management of EP remains challenging, particularly in patients with comorbidities or contraindications to standard therapies. Objectives: To evaluate the effectiveness of ozonated water as an adjunctive treatment for EP, delivered using a patented robotic therapy system designed for hygiene and infection prevention in non-self-sufficient patients. Methods: We report the case of a 90-year-old male patient with acute EP who received daily skin treatments with ozonated water in conjunction with supportive care, including rehydration and antibiotics. The intervention was facilitated by the robotic system “COPERNICO Surveillance & Prevention,” which ensured standardized hygiene practices and clinical documentation. Results: Within one week of treatment, the patient showed complete desquamation of necrotic skin, resolution of erythema, and significant metabolic recovery. Fever subsided, renal function improved, and the patient was discharged in stable condition. Follow-up confirmed sustained clinical improvement, and no adverse events were reported. Conclusions: Ozonated water demonstrated efficacy in alleviating the dermatological and systemic manifestations of EP in a high-risk elderly patient. This case highlights the potential of ozone therapy as a safe, cost-effective adjunctive treatment for EP and underscores the utility of robotic systems in managing complex dermatological conditions. Further research is warranted to validate these findings in larger cohorts.展开更多
Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold ...Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold molding process with 20%w/v poly-vinylpyrrolidone and 15%w/v polyvinyl alcohol.The SFA-MNs were assessed for morphology,mechanical properties,in vitro dissolution,identification of components,and skin lesion improvement in imiquimod-induced psoriasis mice.Results:The SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis,facilitating efficient drug delivery.Furthermore,they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differ-entiation 3 and tumor necrosis factor-a.In addition,this system alleviated skin inflammation,splenic swelling,and thymic atrophy in the psoriasis-like mouse model.Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios(m/z)of the secondary fragments N-methylcytisine,5a,9a-dihydroxymatrine,sophoramine,matrine,oxysophocarpine,oxymatrine,and kushenol O.Conclusion:The drug delivery strategy combining traditional herbal S.flavescens with soluble micro-needle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models,enabling enhanced therapeutic effects compared with the control group.展开更多
Objective: To explore the effect of Health Action Process Approach (HAPA) theory in patients with type D personality psoriasis. Methods: A total of 66 patients with type D personality psoriasis admitted to the dermato...Objective: To explore the effect of Health Action Process Approach (HAPA) theory in patients with type D personality psoriasis. Methods: A total of 66 patients with type D personality psoriasis admitted to the dermatology department of a top-three hospital in Jingzhou City from November 2022 to July 2023 were selected and divided into control group and test group with 33 cases in each group by random number table method. The control group received routine health education, and the experimental group received health education based on the HAPA theory. Chronic disease self-efficacy scale, hospital anxiety and depression scale and skin disease quality of life scale were used to evaluate the effect of intervention. Results: After 3 months of intervention, the scores of self-efficacy in experimental group were higher than those in control group (P P Conclusion: Health education based on the theory of HAPA can enhance the self-efficacy of patients with type D personality psoriasis, relieve negative emotions and improve their quality of life.展开更多
Psoriasis is a common and chronic immune-mediated disorder that severely impacts the life quality of patients.Phosphodiesterase-4(PDE4)inhibitors have attracted significant interests in the psoriasis treatment due to ...Psoriasis is a common and chronic immune-mediated disorder that severely impacts the life quality of patients.Phosphodiesterase-4(PDE4)inhibitors have attracted significant interests in the psoriasis treatment due to their ability to suppress the inflammatory cascades.In this study,extensive screening of an in-house library of 1200 Chinese medicinal plant extracts identified Platycladus orientalis(L.)Franco(P.orientalis)as a potent PDE4 inhibitor,exhibiting 42.7%inhibition at 0.2μg/m L.Subsequent bioassayguided isolation revealed flavonoids,particularly amentoflavone(AMF),as the principal component responsible for PDE4 inhibition.To enrich the effective ingredients,a purification protocol using microporous resin was developed,yielding a flavonoid-rich extract(FLDs)that efficiently increased AMF content from 6.2%to 72.3%and improved PDE4 inhibitory activity to 74.2%at 0.2μg/mL.Notably,P.orientalis with favorable safety profiles demonstrated superior in vitro and in vivo anti-psoriasis effects to both AMF and the approved PDE4 inhibitor apremilast.These findings highlight the potential of P.orientalis as a novel therapeutic agent for psoriasis and provide valuable insights for its development in psoriasis treatment.展开更多
This research aimed to identify and validate ferroptosis-related signature genes associated with psoriasis through a comprehensive bioinformatics approach,while also predicting potential traditional Chinese medicines(...This research aimed to identify and validate ferroptosis-related signature genes associated with psoriasis through a comprehensive bioinformatics approach,while also predicting potential traditional Chinese medicines(TCMs)targeting these genes.The findings might offer a foundation for understanding ferroptosis mechanisms in psoriasis and exploring TCM-based therapeutic strategies.To begin,we retrieved gene expression profile data from psoriasis patients and healthy controls from the Gene Expression Omnibus(GEO)database,followed by data normalization.Ferroptosis-associated differentially expressed genes(Fer-DEGs)were identified using the FerrDb database.Subsequent GO and KEGG enrichment analyses provided insights into the biological functions and signaling pathways of these Fer-DEGs.Core Fer-DEGs were identified using machine learning algorithms,and their expression levels were further validated with an external dataset to evaluate diagnostic potential.Additionally,the symMap database facilitated the reverse prediction of TCMs targeting these key signature genes.The analysis identified 265 significant Fer-DEGs.GO enrichment indicated their involvement in diverse biological processes,while KEGG analysis highlighted their roles in various pathways,including ferroptosis,autophagy,cancer,infection,and metabolism,as well as PI3K-Akt,FoxO,mTOR,and HIF-1 signaling pathways.Machine learning pinpointed nine core psoriasis-related Fer-DEGs:PRKAA2,ANO6,POR,PTEN,MAPK8,ZFAS1,ADAM23,TMBIM4,and PARP14,all demonstrating strong diagnostic performance.Predicted TCMs primarily included those with heat-clearing,detoxifying,blood-activating,stasis-resolving,and phlegm-resolving properties.In conclusion,our study suggested that PRKAA2,ANO6,POR,PTEN,MAPK8,ZFAS1,ADAM23,TMBIM4,and PARP14 were key players in the ferroptosis pathway in psoriasis.TCMs with properties such as heat-clearing,blood activation,and phlegm resolution might hold promise for anti-ferroptosis interventions in psoriasis treatment.展开更多
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 ...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.展开更多
Psoriasis,a prevalent inherited skin condition,involves an inflammatory response as a key pathogenic mechanism.The Optimized Yinxieling Formula(OYF),rooted in traditional Chinese medicine,is extensively utilized in cl...Psoriasis,a prevalent inherited skin condition,involves an inflammatory response as a key pathogenic mechanism.The Optimized Yinxieling Formula(OYF),rooted in traditional Chinese medicine,is extensively utilized in clinical settings to treat psoriasis.Although previous studies have demonstrated OYF’s significant anti-inflammatory effects in psoriasis,its potential molecular targets and active components remain unexplored.This study aimed to unveil the anti-psoriasis molecular targets and active components of OYF.Our findings indicated that OYF extract markedly reduced the production of several inflammatory mediators,including IL-23,nitric oxide,TNF-α,and IL-1β,in LPS-induced RAW264.7 cells.We synthesized OYF extract-crosslinked beads to isolate pharmacological targets from RAW264.7 lysates using an affinity purification strategy,known as Target Fishing.The enriched target proteins were subsequently identified via LC-MS/MS,followed by bioinformatics analysis to map the psoriasis-associated pathway-gene network.We identified a total of 76 potential target proteins,which were highly associated with mRNA transcription mechanisms.In particular,pathway-gene network analysis revealed that the IL-23 inflammatory pathway was involved in the anti-psoriasis effect of OYF extract.We further utilized a target protein-based affinity capture strategy,combined with LC-MS and SPR analysis,to globally screen OYF’s active components,focusing on the mRNA transcription regulator,fused in sarcoma(FUS).This process led to the identification of umbelliferone,vanillic acid,protocatechuic acid,gentisic acid,and echinacoside as key compounds targeting FUS to inhibit IL-23 expression.Additionally,we formulated a compound cocktail(CpdC),which significantly reduced psoriasis area and severity index(PASI)scores and the expressions of IL-23 and Ki67 in an imiquimod(IMQ)-induced psoriasis mouse model.Collectively,our study elucidates the primary molecular targets and active components of OYF,offering novel insights for psoriasis treatment.展开更多
Objective Secoemestrin C(SC),an epitetrathiodioxopiperazine isolated from Aspergillus nidulans,has been previously reported to have immunomodulatory and hepatoprotective effects against acute autoimmune hepatitis.Howe...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.展开更多
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)blocka...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.展开更多
As a global public health issue that can cause systemic diseases,COVID-19 inflicts various harms on patients and impacts those with comorbidities.Psoriasis is primarily driven by a subset of T helper cells and the cyt...As a global public health issue that can cause systemic diseases,COVID-19 inflicts various harms on patients and impacts those with comorbidities.Psoriasis is primarily driven by a subset of T helper cells and the cytokines[1],and microbial infection is a predisposing factor in up to 45%of patients[2].Infection with SARS-CoV-2 may trigger the aggravation of psoriasis.Thus,we conducted a survey to explore the proportion of psoriasis patients who experienced exacerbation and relapse after SARS-CoV-2 infection and also performed a preliminary investigation into the mechanisms involved.One hundred and twenty-four psoriasis patients(79 males and 45 females)who contracted COVID-19 were followed up and provided detailed information.展开更多
Background Epidemiological studies have suggested a potential connection between psoriasis and an increased risk of aortic valve stenosis(AS),though the impact of psoriasis on AS progression remains uncertain.The stud...Background Epidemiological studies have suggested a potential connection between psoriasis and an increased risk of aortic valve stenosis(AS),though the impact of psoriasis on AS progression remains uncertain.The study aims to investigate the causal relationship between psoriasis and AS using Mendelian randomization(MR)analysis,as well as to uncover potential mechanisms underlying this association.Methods A two-sample MR analysis was conducted using publicly available summary statistics from genome-wide association studies(GWAS)of psoriasis and AS.Cis-eQTL and significant genes were identified for each causal single-nucleotide polymorphisms(SNPs),followed by pathway enrichment and protein-protein interaction(PPI)analysis for functional evaluation.Hub genes were pinpointed by Cytospace.The transcriptional profile of AS population was acquired,and interconnected genes networks were clustered using Molecular Complex Detection(MCODE).Results Our results demonstrate a significant causal relationship between psoriasis and AS,with a genetic predisposition to psoriasis associated with a higher AS risk(odds ratio:1.46).Pathway and PPI analyses unveiled 15 hub genes,including HLA-C,HLA-B,ISG15,IFIT3,and MX2,along with immune-related pathways linking psoriasis and AS.Moreover,the transcriptional profiling of the AS database highlighted the significant involvement of adaptive immune cells in AS development.Notably,among the 15 hub genes,ISG15,MX2,OAS3,OASL,IFI6,and EPSTI1 exhibited higher expression in the AS population.Conclusion Our study provides compelling evidence supporting a causal relationship between psoriasis and AS.Furthermore,the identified hub genes and immune-related pathways may play an important role in the development of both diseases.展开更多
This study aimed to evaluate the effects of Bifi dobacterium breve CCFM683 on psoriasis and to investigate the underlying mechanisms.B.breve CCFM683 significantly ameliorated psoriasis in mice as well as elevated the ...This study aimed to evaluate the effects of Bifi dobacterium breve CCFM683 on psoriasis and to investigate the underlying mechanisms.B.breve CCFM683 significantly ameliorated psoriasis in mice as well as elevated the deoxycholic acid(DCA)and lithocholic acid(LCA)in the colon compared with those of the imiquimod(IMQ)-treated mice.Meanwhile,B.breve CCFM683 increased the relative abundance of DCA-producing Lachnoclostridium and diminished the harmful Desulfovibrio and Prevotellaceae UCG001.Additionally,the farnesoid X receptor(FXR)in the skin was activated and the expression of the Toll-like receptor 4(TLR4)/nuclear factor kappa-B(NF-κB)pathway was inhibited,and the downstream interleukin(IL)-17 and tumor necrosis factor(TNF)-αwere downregulated whereas IL-10 was up-regulated.Moreover,the subsequent hyperproliferation of keratinocytes and the dysfunction of the epidermal barrier were improved.In conclusion,CCFM683 administration ameliorated IMQ-induced psoriasis via modulating gut microbiota,promoting the DCA production,regulating the FXR-TLR4/NF-κB pathway,diminishing proinflammatory cytokines,and regulating keratinocytes and epidermal barrier.These findings may be conducive to elucidating the mechanism for probiotics to ameliorate psoriasis and to promote its clinical trials in skin disease.展开更多
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 hig...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.展开更多
In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expresse...In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expressed in T cells that regulates the immune system’s activity to prevent over-activation and tissue damage caused by inflammation.However,PD-1 is also expressed in tumor cells and functions as an immune evasion mechanism,making it a therapeutic target to enhance the immune response and eliminate tumor cells.Consequently,immune checkpoint inhibitors(ICIs)have emerged as an option for certain tumor types.Nevertheless,blocking immune checkpoints can lead to immune-related adverse events(irAEs),such as psoriasis and cytokine release syndrome(CRS),as exemp-lified in the clinical case presented by Zhou et al involving a patient with adva-nced gastric cancer who received sintilimab,a monoclonal antibody targeting PD-1.Subsequently,the patient experienced exacerbation of psoriasis and CRS.The objective of this editorial article is to elucidate potential immunologic mechanisms that may contribute to the development of CRS and psoriasis in patients receiving ICIs.It is crucial to acknowledge that while ICIs offer superior safety and efficacy compared to conventional therapies,they can also manifest irAEs affecting the skin,gastrointestinal tract,or respiratory system.In severe cases,these irAEs can lead to life-threatening complications such as circulatory shock or multiorgan failure.Consequently,it is recommended that patients receiving ICIs undergo regular monitoring to identify and manage these adverse events effectively.展开更多
基金supported by the National Key R&D Program of China(No,2019YFA0112100)the National Natural Science Foundation of China(No.81472073)the Fundamental Research Funds for the Central Universities of Central South University(Grant Number:2022ZZTS0824).
文摘Objective To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization(MR)study.Methods A two-sample MR study was performed using summarized statistics from the genome-wide association studies(GWAS)conducted in reproductive traits,as well as GWAS data on overall psoriasis,psoriatic arthritis(PsA),and psoriasis vulgaris(PV).Besides univariable MR(UVMR),multivariable MR and two-step MR was used to calculate the independent effects and quantify the proportion mediated by education or body mass index(BMI).Results Genetically predicted early age at first sexual intercourse(AFS)led to an increased risk of overall psoriasis[odds ratio(OR)UVMR:0.54];36.13%of this effect was mediated through BMI and 47.79%through educational attainment.The direct negative casual association between age at first birth(AFB)-PsA was dominant(ORUVMR:0.76),with 49.61%proportion of the mediation due to BMI.The mediating effect was found for BMI on the AFS-PV relationship,which accounted for 26.27%of the proportion.AFS was inversely associated with the risk of overall psoriasis and PV,with considerable mediation by BMI and educational attainment.Conclusion Early AFB may cause a higher risk of PsA,while the AFS-PsA association was fully mediated by BMI.
基金supported by the National Natural Science Foundation(82173426)the Natural Science Foundation of Hunan Province(2023JJ30984),China。
文摘Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
文摘BACKGROUND Erythrodermic psoriasis(EP)is a rare and life-threatening form of psoriasis associated with significant morbidity and mortality.Systemic immunosuppre-ssive therapies are often required but may predispose to opportunistic infections.Disseminated herpes simplex virus type-1(HSV-1)is an unusual complication in otherwise immunocompetent patients and has not been reported in association with ixekizumab therapy for EP.CASE SUMMARY We describe a 49-year-old man with longstanding severe plaque psoriasis,liver cirrhosis,and bipolar disorder who developed EP involving>90%of body surface area[Psoriasis Area and Severity Index(PASI)45].Following initial stabil-ization,he was admitted to the intensive care unit(ICU)with hemodynamic instability,leukocytosis with eosinophilia,and diffuse desquamation.Ixekizumab was initiated with high-dose topical clobetasol.During his ICU stay,he developed recurrent bacteremias and neurologic decline(Glasgow Coma Scale 7/15),fo-llowed by the appearance of widespread vesicles and hemorrhagic crusts.HSV-1 infection was confirmed by polymerase chain reaction(PCR).Immunosuppressive therapy was withheld,and intravenous acyclovir was started,leading to progre-ssive improvement.After ten days,ixekizumab was reintroduced with careful monitoring,resulting in marked clinical improvement(PASI 9.7 at six weeks).The patient remained stable on long-term follow-up with oral acyclovir prophylaxis.CONCLUSION This case highlights the diagnostic and therapeutic challenges of managing EP in the setting of biologic therapy.Disseminated cutaneous HSV-1 should be considered in immunosuppressed patients presenting with new vesicular eruptions,and prompt PCR testing with early antiviral therapy is essential.A multidisciplinary approach is critical to balance immunosuppression for disease control with infection risk.
基金National Natural Science Foundation of China:Study on the Mechanism of Cooling Blood and Tranquilizing Mind in the Treatment of Psoriasis with Sleep Disorder based on the Regulation of Oxidative Stress by Melatonin (No. 82074436)。
文摘OBJECTIVE:To explore the therapeutic mechanisms of Xiaoyin Anshen Yin( 消银安神饮, XYAS) in treating psoriasis associated with sleep focusing on melatonin and the regulation of the nuclear factor kappa-B(NF-κB) pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups, and administered distilled water, XYAS and its two different disassembly prescriptions by gavage respectively. Four types of drug-containing serums corresponding to the four groups were then prepared. Tumor necrosis factor(TNF)-α stimulated Ha Ca T was used to establish a psoriasis cell model, and the serums and the retinoid related orphan receptor alpha(RORα) inverse agonist were used respectively to intervene in the model. Enzyme-linked immunosorbent assay was used to detect the levels of interleukin(IL)-6 and melatonin in each group;flow cytometry was used to detect the levels of reactive oxygen species(ROS), mitochondrial membrane potential, and apoptosis;Western blot was used to evaluate the levels of superoxide dismutase 2(SOD2), cytochrome-c(Cyt-c), inhibitor of kappa-B alpha(IκBα), p65 and phosphorylated p65. RESULTS:XYAS and its disassembly prescriptions inhibited the secretion of inflammatory factors such as IL-6, reduced the ROS content and Cyt-c expression, increased the mitochondrial membrane potential and SOD2 content, promoted the apoptosis in Ha Ca T cells and inhibited the activation of the NF-κB pathway. XYAS was also found increase the melatonin content. The above effects are beneficial in the treatment of psoriasis combined with sleep disorders. Meanwhile, XYAS no longer had a significant ameliorative effect after applying the RORα inverse agonist, suggesting that the therapeutic effect of XYAS is related to RORα. CONCLUSIONS:The results of this study confirm that XYAS can be utilized for the treatment of psoriasis combined with sleep disorders via inhibiting the NF-κB pathway, anti-inflammatory, antioxidant and proapoptotic, which is in part related to the regulatory role of melatonin and its receptor RORα.
文摘BACKGROUND Psoriasis is a chronic inflammatory condition related to an increased athero-sclerotic cardiovascular disease(ASCVD)risk.AIM To investigate whether lipoprotein(a)[Lp(a)]levels are increased in patients with psoriasis.METHODS A comprehensive literature search up to January 30,2025 was conducted utilizing PubMed and Cochrane Library databases.A qualitative synthesis and a meta-analysis on Lp(a)mean differences(MD)between psoriasis cases and healthy controls(HC)was performed.The protocol of this meta-analysis has been re-gistered to PROSPERO(No.CRD420250652465).RESULTS Eighteen studies with 1650 psoriasis patients and 1621 HC were eligible for qua-litative synthesis.Pooled analysis from 16 studies(1401 psoriasis patients and 1320 HC)demonstrated that psoriasis patients had significantly higher Lp(a)levels compared with the HC group(MD:6.72 mg/dL,95%CI:4.32-9.12,P<0.00001,I2=71%).Sensitivity analyses according to the region of origin was also performed.The pooled analysis of the European sub-population showed a pronounced increase in Lp(a)levels in 189 patients with psoriasis vs 178 HC(MD:15.86 mg/dL,95%CI:5.79-25.92,P<0.002,I2=79%),while the pooled analysis on the Asian sub-population demonstrated a smaller but still significant difference in Lp(a)levels between 1177 psoriasis patients and 1127 HC(MD:4.95 mg/dL,95%CI:2.99-6.92,P<0.00001,I2=58%).CONCLUSION Our findings suggest that Lp(a)levels are significantly elevated in psoriasis patients,further adding to their ASCVD risk.
文摘Psoriasis is a prevalent inflammatory disease that shares chronic inflammation pathways with the pathophysiology of metabolic syndrome(MetS),type-2 diabetes mellitus and atherosclerosis.A high prevalence of steatosis and advanced liver fibrosis has been described in psoriasis.The influence of MetS and its compounds,patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 gene polymorphisms and the cumulative dose of methotrexate(MTX)in the progression of steatotic disease are still under debate.A suitable new classification for psoriasis-related liver disease,under the umbrella of steatotic liver disease(SLD),might be evaluated due to the potential impact of MTX on liver steatosis.Considering the interplay between the MetS,steatosis and MTX,a new definition for this complex disease might be discussed since it is not entirely addressed under the umbrella of SLD and metabolic-dysfunction associated SLD.Hence,shortly,a discussion could be raised on the feasible term“Met-Drug SLD”,metabolic and drug-induced SLD,which comprises both metabolic dysfunction and drug-related SLD.This review aims to report the best evidence to accurately classify liver disease in psoriasis,considering the new definition of SLD,allowing appropriate management once it is carefully defined.
文摘Background: Erythrodermic psoriasis (EP) is a rare, severe variant of psoriasis characterized by widespread erythema, scaling, and systemic complications. Despite advances in systemic treatments, the management of EP remains challenging, particularly in patients with comorbidities or contraindications to standard therapies. Objectives: To evaluate the effectiveness of ozonated water as an adjunctive treatment for EP, delivered using a patented robotic therapy system designed for hygiene and infection prevention in non-self-sufficient patients. Methods: We report the case of a 90-year-old male patient with acute EP who received daily skin treatments with ozonated water in conjunction with supportive care, including rehydration and antibiotics. The intervention was facilitated by the robotic system “COPERNICO Surveillance & Prevention,” which ensured standardized hygiene practices and clinical documentation. Results: Within one week of treatment, the patient showed complete desquamation of necrotic skin, resolution of erythema, and significant metabolic recovery. Fever subsided, renal function improved, and the patient was discharged in stable condition. Follow-up confirmed sustained clinical improvement, and no adverse events were reported. Conclusions: Ozonated water demonstrated efficacy in alleviating the dermatological and systemic manifestations of EP in a high-risk elderly patient. This case highlights the potential of ozone therapy as a safe, cost-effective adjunctive treatment for EP and underscores the utility of robotic systems in managing complex dermatological conditions. Further research is warranted to validate these findings in larger cohorts.
基金supported by the National Natural Science Foundation of China(82274225)NATCM's Project of High-level Construction of Key TCM Disciplines-Beijing University of Chinese Medicine-Life Science from the Perspective of Chinese Medicine(zyyzdxk-2023263).
文摘Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold molding process with 20%w/v poly-vinylpyrrolidone and 15%w/v polyvinyl alcohol.The SFA-MNs were assessed for morphology,mechanical properties,in vitro dissolution,identification of components,and skin lesion improvement in imiquimod-induced psoriasis mice.Results:The SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis,facilitating efficient drug delivery.Furthermore,they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differ-entiation 3 and tumor necrosis factor-a.In addition,this system alleviated skin inflammation,splenic swelling,and thymic atrophy in the psoriasis-like mouse model.Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios(m/z)of the secondary fragments N-methylcytisine,5a,9a-dihydroxymatrine,sophoramine,matrine,oxysophocarpine,oxymatrine,and kushenol O.Conclusion:The drug delivery strategy combining traditional herbal S.flavescens with soluble micro-needle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models,enabling enhanced therapeutic effects compared with the control group.
文摘Objective: To explore the effect of Health Action Process Approach (HAPA) theory in patients with type D personality psoriasis. Methods: A total of 66 patients with type D personality psoriasis admitted to the dermatology department of a top-three hospital in Jingzhou City from November 2022 to July 2023 were selected and divided into control group and test group with 33 cases in each group by random number table method. The control group received routine health education, and the experimental group received health education based on the HAPA theory. Chronic disease self-efficacy scale, hospital anxiety and depression scale and skin disease quality of life scale were used to evaluate the effect of intervention. Results: After 3 months of intervention, the scores of self-efficacy in experimental group were higher than those in control group (P P Conclusion: Health education based on the theory of HAPA can enhance the self-efficacy of patients with type D personality psoriasis, relieve negative emotions and improve their quality of life.
基金supported by the National Key R&D Program of China(No.2023YFF1205102)National Natural Science Foundation of China(Nos.22277019,22307031,22377023 and 22077143)+2 种基金the Fundamental Research Funds for Hainan University(Nos.RZ2200001094,KYQD(ZR)-21031,and KYQD(ZR)-21108)Collaborative Innovation Center Funds for Hainan University(No.XTCX2022JKA01)the Science Foundation of Hainan Province(Nos.KJRC2023B10 and 824YXQN420)。
文摘Psoriasis is a common and chronic immune-mediated disorder that severely impacts the life quality of patients.Phosphodiesterase-4(PDE4)inhibitors have attracted significant interests in the psoriasis treatment due to their ability to suppress the inflammatory cascades.In this study,extensive screening of an in-house library of 1200 Chinese medicinal plant extracts identified Platycladus orientalis(L.)Franco(P.orientalis)as a potent PDE4 inhibitor,exhibiting 42.7%inhibition at 0.2μg/m L.Subsequent bioassayguided isolation revealed flavonoids,particularly amentoflavone(AMF),as the principal component responsible for PDE4 inhibition.To enrich the effective ingredients,a purification protocol using microporous resin was developed,yielding a flavonoid-rich extract(FLDs)that efficiently increased AMF content from 6.2%to 72.3%and improved PDE4 inhibitory activity to 74.2%at 0.2μg/mL.Notably,P.orientalis with favorable safety profiles demonstrated superior in vitro and in vivo anti-psoriasis effects to both AMF and the approved PDE4 inhibitor apremilast.These findings highlight the potential of P.orientalis as a novel therapeutic agent for psoriasis and provide valuable insights for its development in psoriasis treatment.
基金Yunnan Provincial Excellent Clinical Talents Training Project(the First Batch)(Yunnan Financial Society(2024)No.103).
文摘This research aimed to identify and validate ferroptosis-related signature genes associated with psoriasis through a comprehensive bioinformatics approach,while also predicting potential traditional Chinese medicines(TCMs)targeting these genes.The findings might offer a foundation for understanding ferroptosis mechanisms in psoriasis and exploring TCM-based therapeutic strategies.To begin,we retrieved gene expression profile data from psoriasis patients and healthy controls from the Gene Expression Omnibus(GEO)database,followed by data normalization.Ferroptosis-associated differentially expressed genes(Fer-DEGs)were identified using the FerrDb database.Subsequent GO and KEGG enrichment analyses provided insights into the biological functions and signaling pathways of these Fer-DEGs.Core Fer-DEGs were identified using machine learning algorithms,and their expression levels were further validated with an external dataset to evaluate diagnostic potential.Additionally,the symMap database facilitated the reverse prediction of TCMs targeting these key signature genes.The analysis identified 265 significant Fer-DEGs.GO enrichment indicated their involvement in diverse biological processes,while KEGG analysis highlighted their roles in various pathways,including ferroptosis,autophagy,cancer,infection,and metabolism,as well as PI3K-Akt,FoxO,mTOR,and HIF-1 signaling pathways.Machine learning pinpointed nine core psoriasis-related Fer-DEGs:PRKAA2,ANO6,POR,PTEN,MAPK8,ZFAS1,ADAM23,TMBIM4,and PARP14,all demonstrating strong diagnostic performance.Predicted TCMs primarily included those with heat-clearing,detoxifying,blood-activating,stasis-resolving,and phlegm-resolving properties.In conclusion,our study suggested that PRKAA2,ANO6,POR,PTEN,MAPK8,ZFAS1,ADAM23,TMBIM4,and PARP14 were key players in the ferroptosis pathway in psoriasis.TCMs with properties such as heat-clearing,blood activation,and phlegm resolution might hold promise for anti-ferroptosis interventions in psoriasis treatment.
基金supported by the National Natural Science Foundation of China(NSFC)(81973316,82173807)the China Postdoctoral Science Foundation(2020M681914)+1 种基金the Fund from Tianjin Municipal Health Commission(ZC200093)the Open Fund of Tianjin Central Hospital of Obstetrics and Gynecology/Tianjin Key Laboratory of human development and reproductive regulation(2021XHY01)。
文摘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.
基金supported by the State Key Laboratory of Dampness Syndrome of Chinese Medicine,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine(No.SZ2021ZZ51)the National Key R&D Program of China(No.2022YFC3501601)+1 种基金the National Natural Sciences Foundation of China(Nos.82174008,81973505)Jinan New 20 Policies for Higher Education Funding(No.202228048)and the Fundamental Research Funds for the Central Universities.
文摘Psoriasis,a prevalent inherited skin condition,involves an inflammatory response as a key pathogenic mechanism.The Optimized Yinxieling Formula(OYF),rooted in traditional Chinese medicine,is extensively utilized in clinical settings to treat psoriasis.Although previous studies have demonstrated OYF’s significant anti-inflammatory effects in psoriasis,its potential molecular targets and active components remain unexplored.This study aimed to unveil the anti-psoriasis molecular targets and active components of OYF.Our findings indicated that OYF extract markedly reduced the production of several inflammatory mediators,including IL-23,nitric oxide,TNF-α,and IL-1β,in LPS-induced RAW264.7 cells.We synthesized OYF extract-crosslinked beads to isolate pharmacological targets from RAW264.7 lysates using an affinity purification strategy,known as Target Fishing.The enriched target proteins were subsequently identified via LC-MS/MS,followed by bioinformatics analysis to map the psoriasis-associated pathway-gene network.We identified a total of 76 potential target proteins,which were highly associated with mRNA transcription mechanisms.In particular,pathway-gene network analysis revealed that the IL-23 inflammatory pathway was involved in the anti-psoriasis effect of OYF extract.We further utilized a target protein-based affinity capture strategy,combined with LC-MS and SPR analysis,to globally screen OYF’s active components,focusing on the mRNA transcription regulator,fused in sarcoma(FUS).This process led to the identification of umbelliferone,vanillic acid,protocatechuic acid,gentisic acid,and echinacoside as key compounds targeting FUS to inhibit IL-23 expression.Additionally,we formulated a compound cocktail(CpdC),which significantly reduced psoriasis area and severity index(PASI)scores and the expressions of IL-23 and Ki67 in an imiquimod(IMQ)-induced psoriasis mouse model.Collectively,our study elucidates the primary molecular targets and active components of OYF,offering novel insights for psoriasis treatment.
文摘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.
基金Supported by Shaoxing Health Science and Technology Program,No.2022SY016,No.2022KY010.
文摘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.
基金supported by academic promotion programme of Shandong First Medical University(2019LJ002)the key research and development program of Shandong Province(2021LCZX07).
文摘As a global public health issue that can cause systemic diseases,COVID-19 inflicts various harms on patients and impacts those with comorbidities.Psoriasis is primarily driven by a subset of T helper cells and the cytokines[1],and microbial infection is a predisposing factor in up to 45%of patients[2].Infection with SARS-CoV-2 may trigger the aggravation of psoriasis.Thus,we conducted a survey to explore the proportion of psoriasis patients who experienced exacerbation and relapse after SARS-CoV-2 infection and also performed a preliminary investigation into the mechanisms involved.One hundred and twenty-four psoriasis patients(79 males and 45 females)who contracted COVID-19 were followed up and provided detailed information.
基金supported by the National Natural Science Foundation of China(81970325,and82170375)Sichuan Science and Technology Program(2023YFS0296)+3 种基金Key Research and Development Project of Science&Technology Department of Sichuan Province(2022ZDZX0020 and 2023YFS-0296)Key Research and Development Support Project of Science&Technology Department of Chengdu(2021-YF08-00121-GX)Chinese Medical Association Cardiovascular Branch(CSC)Clinical Research Special Fund Project(CSCF2020B04)West China Hospital“1·3·5”Discipline of Excellence Project-“Percutaneous transcatheter aortic valve implantation”and“Mechanisms of aortic stenosis a nd the clinical applications”。
文摘Background Epidemiological studies have suggested a potential connection between psoriasis and an increased risk of aortic valve stenosis(AS),though the impact of psoriasis on AS progression remains uncertain.The study aims to investigate the causal relationship between psoriasis and AS using Mendelian randomization(MR)analysis,as well as to uncover potential mechanisms underlying this association.Methods A two-sample MR analysis was conducted using publicly available summary statistics from genome-wide association studies(GWAS)of psoriasis and AS.Cis-eQTL and significant genes were identified for each causal single-nucleotide polymorphisms(SNPs),followed by pathway enrichment and protein-protein interaction(PPI)analysis for functional evaluation.Hub genes were pinpointed by Cytospace.The transcriptional profile of AS population was acquired,and interconnected genes networks were clustered using Molecular Complex Detection(MCODE).Results Our results demonstrate a significant causal relationship between psoriasis and AS,with a genetic predisposition to psoriasis associated with a higher AS risk(odds ratio:1.46).Pathway and PPI analyses unveiled 15 hub genes,including HLA-C,HLA-B,ISG15,IFIT3,and MX2,along with immune-related pathways linking psoriasis and AS.Moreover,the transcriptional profiling of the AS database highlighted the significant involvement of adaptive immune cells in AS development.Notably,among the 15 hub genes,ISG15,MX2,OAS3,OASL,IFI6,and EPSTI1 exhibited higher expression in the AS population.Conclusion Our study provides compelling evidence supporting a causal relationship between psoriasis and AS.Furthermore,the identified hub genes and immune-related pathways may play an important role in the development of both diseases.
基金supported by the National Natural Science Foundation of China(32072227,32021005)111 Project(BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province.
文摘This study aimed to evaluate the effects of Bifi dobacterium breve CCFM683 on psoriasis and to investigate the underlying mechanisms.B.breve CCFM683 significantly ameliorated psoriasis in mice as well as elevated the deoxycholic acid(DCA)and lithocholic acid(LCA)in the colon compared with those of the imiquimod(IMQ)-treated mice.Meanwhile,B.breve CCFM683 increased the relative abundance of DCA-producing Lachnoclostridium and diminished the harmful Desulfovibrio and Prevotellaceae UCG001.Additionally,the farnesoid X receptor(FXR)in the skin was activated and the expression of the Toll-like receptor 4(TLR4)/nuclear factor kappa-B(NF-κB)pathway was inhibited,and the downstream interleukin(IL)-17 and tumor necrosis factor(TNF)-αwere downregulated whereas IL-10 was up-regulated.Moreover,the subsequent hyperproliferation of keratinocytes and the dysfunction of the epidermal barrier were improved.In conclusion,CCFM683 administration ameliorated IMQ-induced psoriasis via modulating gut microbiota,promoting the DCA production,regulating the FXR-TLR4/NF-κB pathway,diminishing proinflammatory cytokines,and regulating keratinocytes and epidermal barrier.These findings may be conducive to elucidating the mechanism for probiotics to ameliorate psoriasis and to promote its clinical trials in skin disease.
文摘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.
基金Supported by Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz,No.NC23189.0.
文摘In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expressed in T cells that regulates the immune system’s activity to prevent over-activation and tissue damage caused by inflammation.However,PD-1 is also expressed in tumor cells and functions as an immune evasion mechanism,making it a therapeutic target to enhance the immune response and eliminate tumor cells.Consequently,immune checkpoint inhibitors(ICIs)have emerged as an option for certain tumor types.Nevertheless,blocking immune checkpoints can lead to immune-related adverse events(irAEs),such as psoriasis and cytokine release syndrome(CRS),as exemp-lified in the clinical case presented by Zhou et al involving a patient with adva-nced gastric cancer who received sintilimab,a monoclonal antibody targeting PD-1.Subsequently,the patient experienced exacerbation of psoriasis and CRS.The objective of this editorial article is to elucidate potential immunologic mechanisms that may contribute to the development of CRS and psoriasis in patients receiving ICIs.It is crucial to acknowledge that while ICIs offer superior safety and efficacy compared to conventional therapies,they can also manifest irAEs affecting the skin,gastrointestinal tract,or respiratory system.In severe cases,these irAEs can lead to life-threatening complications such as circulatory shock or multiorgan failure.Consequently,it is recommended that patients receiving ICIs undergo regular monitoring to identify and manage these adverse events effectively.
