Objective:To observe the effect of Sanshi decoction on BRD4/NF-κB/NLRP3 pathwaymediated macrophage pyroptosis,so as to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthritis.Methods...Objective:To observe the effect of Sanshi decoction on BRD4/NF-κB/NLRP3 pathwaymediated macrophage pyroptosis,so as to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthritis.Methods:THP-1 was induced into macrophages with foboside and the divided into the control group,model group,low-dose,medium-dose,high-dose group of Sanshi decoction,and BRD4 inhibitor group.Except for the control group,the remaining groups were induced with monosodium urate crystals to construct a gouty arthritis cell model.The activity of macrophages was detected by CCK8,the level of macrophage pyroptosis was detected by flow cytometry,the activity of LDH,the content of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay,and the expression of related proteins in the BRD4/NF-κB/NLRP3 pathway was detected by Western blot.Results:Compared with the control group,macrophage activity was decreased in the model group,and the level of pyroptosis,LDH activity,contents of IL-1β and IL-18,expression levels of BRD4,p-NF-kB p65,NLRP3,Caspase-1 p20,and IL-1β protein were significantly up-regulated,the differences were statistically significant(P<0.05 and P<0.01).Compared with the model group,macrophage activity was up-regulated in the Sanshi Decoction,and the level of pyroptosis,LDH activity,IL-1β and IL-18 contents,expression levels of BRD4,p-NF-kB p65,NLRP3,Caspase-1 p20,and IL-1β protein were significantly decreased with statistically significant differences(P<0.05 and P<0.01).Conclusion:Sanshi decoction inhibits macrophage pyroptosis by inhibiting BRD4/NF-κB/NLRP3 pathway activation,thus improving the inflammation level of gouty arthritis.展开更多
Objective:To observe the effect of Sanshi decoction on P2X7R/PKR pathway-mediated activation of macrophage NLRP3 inflammasome to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthriti...Objective:To observe the effect of Sanshi decoction on P2X7R/PKR pathway-mediated activation of macrophage NLRP3 inflammasome to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthritis.Methods:THP-1 macrophages were divided into control group,model group,low dose group,medium dose group,high dose group of Sanshi decoction and inhibitor group.The remaining groups were induced with monosodium urate crystals to establish a gouty arthritis cell model except the control group.Flow cytometry was used to detect macrophage ROS levels in each group,ELISA to detect MDA levels and SOD and GSH-PX activities in each group,and Western blot to detect P2X7R/PKR pathway and NLRP3 inflammasome-associated protein expression.We also used CCK-8 and flow cytometry to measure MH7A activity and apoptotic levels.Results:Compared with the control group,the ROS level,the content of MDA,the activities of SOD and GSH-PX were significantly increased,and the expression levels of NLRP3,full-length IL-1β,pro-IL-1β,full-length IL-18,pro-IL-18,full-length caspase-1,GSDMD-NT,P2X7R and p-PKR protein expression levels were significantly upregulated,and GSDMD-FL protein expression was significantly downregulated in the model group,and that the differences between them were statistically significant(P<0.05 and P<0.01).Compared with the model group,Sanshi decoction could reduce macrophage ROS levels,MDA content,SOD and GSHPX activities,and downregulate macrophage NLRP3,mature IL-1β,pro IL-1β,mature IL-18,pro IL-18,mature caspase-1,GSDMD-NT,P2X7R and p-PKR protein expression,and upregulate GSDMD-FL protein expression,with statistically significant differences(P<0.05 and P<0.01).In addition,MH7A activity was downregulated,and apoptosis level was upregulated in the model group in comparison with the control group,and differences were all significantly different(P<0.05).As compared to the model group,Sanshi decoction could significantly increase the activity of MH7A and inhibit the level of apoptosis,and that the differences between them were statistically significant(P<0.05 and P<0.01).Conclusion:Sanshi decoction can achieve the therapeutic effect of gouty arthritis by inhibiting P2X7R/PKR pathway activation,thus reducing the activation level of NLRP3.展开更多
Objective:To systematically evaluate the efficacy of traditional Chinese medicine decoction combined with arthroscopy in the treatment of gouty arthritis.Methods:A systematic search of CNKI,CBM,WanFang,VIP,PubMed,Coch...Objective:To systematically evaluate the efficacy of traditional Chinese medicine decoction combined with arthroscopy in the treatment of gouty arthritis.Methods:A systematic search of CNKI,CBM,WanFang,VIP,PubMed,Cochrane Library,and EMBASE databases,and the receipt of the database until February 2021.Randomized controlled trials(RCTs)of traditional Chinese medicine(TCM)decoction combined with arthroscopy in the treatment of gouty arthritis.Two researchers independently read the title and abstract to screen and them read the full text to clarify whether it should be included.The method of Cochrane systematic review was used to evaluate the quality of the literature,and the RevMan 5.3 software was used to conduct meta-analysis of the data.Results:Nineteen RCTs were finally included.A total of 1383 patients,697 cases in the treatment group were treated with traditional Chinese medicine decoction combined with arthroscopy,and 686 cases in the control group were treated with arthroscopy alone or combined with western medicine.Meta-analysis results showed that the total clinical effective rate(P<0.00001)of the treatment group was better than that of the control group.Visual analogue scoring(VAS)score(P=0.0005,P<0.00001,P=0.03)and erythrocyte sedimentation rate(ESR)level(P<0.00001,P<0.00001,P<0.00001)reduction in each subgroup was better than that of the control group.The Lysholm score of the treatment group increased(P<0.00001,P<0.00001,P=0.19),while for blood uric acid(UA)level(P<0.00001,P=0.18,P<0.0001)and C-reactive protein(CRP)levels(P<0.0001,P<0.00001,P=0.23)two subgroups were better than the control group,but there was no significant difference in one subgroup.Conclusion:Traditional Chinese medicine decoction combined with arthroscopy is effective in treating gouty arthritis,which can relieve pain,improve joint function,and reduce body inflammation and uric acid levels.However,in the future,clinical studies with larger sample sizes,more reasonable designs,and higher quality are still needed to demonstrate this conclusion.展开更多
Objective:To explore the effect of imbalance of tumor necrosis factor receptor related factor-6(TRAF-6),interleukin 1 receptor associated kinase-1(IRAK-1)and neutrophil alkaline phosphatase-3(NALP3)in patients with go...Objective:To explore the effect of imbalance of tumor necrosis factor receptor related factor-6(TRAF-6),interleukin 1 receptor associated kinase-1(IRAK-1)and neutrophil alkaline phosphatase-3(NALP3)in patients with gouty arthritis.Methods:The retrospective experiment was conducted on 105 patients with gouty arthritis admitted to our hospital(47 patients with acute onset and 58 patients with remission,namely group A and group B);meanwhile,another 61 healthy volunteers were selected for control,namely group C.The enrolling of the three groups was dated from May 2017 to May 2018,and TRAF-6,IRAK-1 and NALP3 of all subjects were tested through real-time fluorescence quantification(RT-PCR),and the correlation between the three inflammatory factors and gouty arthritis was compared.Results:1)Through treatment,ESR,BUA and total addiment in group A and B were higher than those in group C,among which the three indicators in group A were higher than those in group B(P<0.05),while CRP was lower than that of group C,and the two indicators in group A were lower than those in group B(P<0.05).2)There was no significant difference in the relative expression of TRAF-6 mRNA between group A and group B before treatment(P>0.05),significantly lower than group C(P<0.05);the above indicators of group A and group B were improved to some extent after treatment,but group A was still lower than group B(P<0.05),and the degree of improvement of group A was also lower than that of group C(P<0.05),while the degree of improvement of group B was not significantly different from that of group C(P>0.05).3)The relative expression level of IRAK-1mRNA in group A and group B before treatment showed no significant difference(P>0.05),but was also lower than that in group C(P<0.05).The relative expression level of IRAK-1mRNA in group A and group B increased to some extent after treatment,with group A significantly lower than group C(P<0.05),and group B showed no significant difference compared with group C(P>0.05).4)The relative expression level of NALP-3 mRNA in group A and group B showed no significant difference(P>0.05)before treatment,significantly higher than that in group C(P<0.05);the relative expression of NALP-3 mRNA in group A was not significantly decreased(P>0.05)after treatment,while that in group B was significantly decreased after treatment(P<0.05),indicating significant different compared with group A and group C.5)There was no correlation between)TRAF-6,ESR,CRP and total addiment(P>0.05);IRAK-1 was negatively correlated with CRP,BUA and total addiment(P<0.05);NALP-3 was negatively correlated with ESR and CRP(P<0.05).Conclusion:TRAF-6,IRAK-1 and NALP-3 are all under abnormal expression in the developing of new gouty arthritis,acting as important participants in promoting the occurrence,development and outcome of illness states,so the intervening measures should be taken.展开更多
Objective:The mechanism of Chinese herbal medicine"Bi xie and Tu fuling"on the treatment of gouty arthritis was explored through network pharmacological methods.Methods:First,the TCMSP Chinese medicine syste...Objective:The mechanism of Chinese herbal medicine"Bi xie and Tu fuling"on the treatment of gouty arthritis was explored through network pharmacological methods.Methods:First,the TCMSP Chinese medicine system pharmacology database and analysis platform were used to define the bioavailability(OB)30%and drug-likeness(DL)0.18.Database to mine genetic targets related to gouty arthritis disease.Finally,the two genes are intersected to construct a Chinese medicine regulatory network of Chinese medicine-components-target genes-disease.The genes in the network are used to construct a protein interaction network to find core genes for analysis of GO and KEGG.Results:There were a total of 84 active ingredients in Chinese medicine Poria and Poria cocos,and 17 effective ingredients and 180 genetic targets were obtained after screening.600 disease targets for gouty arthritis were identified,and 58 were common target genes for both.PPI network analysis revealed that IL1β,VEGFA,MAPK1,IL10,and PTGS2 may be drugs for treating gouty arthritis.Key targets.GO enrichment analysis identified 1,399 entries(P<0.05),of which biological processes mainly include biological stimulation,biological regulation,cell metabolism,etc;KEGG pathway enrichment analysis identified 152 signal pathways,of which signal pathways involved inflammation,metabolism,In terms of aging,mainly including the IL-4,IL-10,IL-13,IL-17signal pathway,etc.Conclusion:"Bi xie and Tu fuling"drugs have anti-inflammatory and immunological effects on gouty arthritis through multiple targets and multiple pathways.The mechanism of lowering uric acid and protecting liver and kidney is not clear.It needs molecular biology research to improve it.The mechanism of the action of the"Bi xie and Tu fuling"medicine pair provides new ideas for the clinical prescriptions.展开更多
[Objectives]To study the anti-inflammatory effect of Simiao Liangxue granule on the rats with acute gouty arthritis(AGA).[Methods]A total of 60 male SD rats were randomly divided into 6 groups with 10 rats in each gro...[Objectives]To study the anti-inflammatory effect of Simiao Liangxue granule on the rats with acute gouty arthritis(AGA).[Methods]A total of 60 male SD rats were randomly divided into 6 groups with 10 rats in each group.The rats in the colchicine group were intragastrically administered with 0.65 mg/kg colchicine,and the rats in low,medium and high dose groups of Simiao Liangxue granule were intragastrically administered with Simiao Liangxue granule with mass concentration of 0.4,0.8 and 1.6 g/kg,respectively.The rats in the normal control group and the model group were given the same amount of normal saline for 7 d,and the acute gouty arthritis model was prepared 1 h after administration on the 5th d.At the end of the experiment,the degree of joint swelling and joint inflammation index,the content of interleukin-1β,tumor necrosis factor-a and cyclooxygenase-2 in articular cartilage,and the content of interleukin-8,NO and UA in serum of rats were measured,and the histomorphological observation was performed.[Results]Compared with the normal control group,the joints of rats were swollen to different degrees,the inflammation score was significantly increased,and the content of IL-1β,TNF-αand COX-2 in the soft tissue of the joints was significantly increased in each group(P<0.05);compared with the model group,the joint swelling degree and inflammation score of rats in the colchicine group and Simiao Liangxue granule group were significantly decreased,the content of IL-1β,TNF-αand COX-2 in the joint soft tissue was also significantly decreased(P<0.05),and the indexes of each dose group of Simiao Liangxue granule were similar to those of the colchicine group;compared with the normal control group,the content of IL-8,NO and UA in the joint soft tissue of rats was significantly increased in each group(P<0.05);compared with the model group,the content of all indexes in joint soft tissue of rats in normal control group,colchicine group and Simiao Liangxue granule group were significantly decreased(P<0.05);the content of various indexes in the joint soft tissue of rats in the low and medium dose groups of Simiao Liangxue granule was higher than that in the colchicine group,and decreased significantly with the increase of the dose of Simiao Liangxue granule(P<0.05);the inflammatory index decreased significantly with the increase of the dose of Simiao Liangxue granule(P<0.05);the inflammation and degeneration in each dose group of Simiao Liangxue granule were milder than those in the model group,and the symptoms were relieved to some extent with the increase of dose(P<0.05).[Conclusions]Simiao Liangxue granule has the effect of anti-inflammation and detumescence,and its mechanism may be related to the content of factors that reduce inflammation including IL-1β,TNF-α,C0X-2,IL-8,NO and UA.展开更多
Objective:To Find the core targets and drug action mechanism of Si Miao decoction for the treatment of acute gouty arthritis.Methods:Through the TCMSP database,the chemical composition of all the drugs in Si Miao deco...Objective:To Find the core targets and drug action mechanism of Si Miao decoction for the treatment of acute gouty arthritis.Methods:Through the TCMSP database,the chemical composition of all the drugs in Si Miao decoction was obtained.The Perl script was compiled and the UniProt database was searched to determine the corresponding target of the chemical composition.Then,the disease databases such as OMIM,DisGeNET,and GeneCards were searched in order to determine acute gouty arthritis Related targets.Finally,screen common targets for drugs and diseases,use the STRING database and Cytoscape software to build a network control map of drugs-chemical components-targets-disease.Use R language software to screen common targets and find the four best The core targets of San for the treatment of acute gouty arthritis.The GO and KEGG analysis of the core targets were performed to clarify the core targets and mechanism of Si Miao decoction for the treatment of gout.Results:There are 64 effective chemical components in Si Miao decoction,197 genetic targets,600 disease targets,and 58 common targets.It is predicted that IL6,VEGFA,IL1B,JUN,PTGS2,and CCL2 may be treated by Si Miao decoction for gout The core target of arthritis.GO enrichment analysis identified 85 entries,of which biological processes mainly included the regulation of cytokine activity,protease activation,nucleic acid expression,etc.;KEGG pathway enrichment analysis identified 135 signaling pathways,of which signaling pathways involved the IL-17 signaling pathway,TNF signaling pathway,Th17 cell differentiation and other pathways.Conclusion:Si Miao decoction acts on acute gouty arthritis by regulating the occurrence of inflammation,and has significant anti-inflammatory and immune effects.The formula is rigorous and scientific,and it is worthy of clinical application.展开更多
Objective:To investigate the effect and anti-inflammatory mechanism the effect of Flemingia Roxb.exAit extract on acute gouty arthritis.Methods:Sixty SD rats were randomly divided into 6 groups by weight,control and m...Objective:To investigate the effect and anti-inflammatory mechanism the effect of Flemingia Roxb.exAit extract on acute gouty arthritis.Methods:Sixty SD rats were randomly divided into 6 groups by weight,control and model group,(100、150、200 mg/kg)of Flemingia Roxb.exAit extract group and colchicine group.The rats of each group were given by intragastric for 7 days of continuous administration,meanwhile,there were given 0.9%NaCl solution instead as control and model group.The acute gouty arthritis model was constructed through right ankle joint cavity injection of sodium urate crystal solutionon day 5 after 1 h,but rats in the negative control group were injected with 0.9%NaCl solution into the articular cavity of the right foot.The general condition of rats and the degree of joint swelling,and the gait was observed after constructed model.To detected the joint fluid IL-1β、TNF-α、IL-6 indicators,and the expression of NLRP3,Caspase-1 protein in ankle joint tissue for 2 hours after the last administration.Results:Groups of Flemingia Roxb.exAit extract could markedly reduce the joint swelling on acute gouty arthritis rat model,improve gait in a dose-dependent manner,high dose group of Flemingia Roxb.exAit extract did particularly well(Pjoint swelling<0.01;Pgait<0.05),close to the therapeutic effect colchicine group.Further mechanism studies show that the joint fluid IL-1β、TNF-α、IL-6 level was reduced by Flemingia Roxb.exAit extract group,the expressions of NLRP3、Caspase-1 protein of Flemingia Roxb.exAit extract group was decreased observbly than model group,but the most obvious is that high dose group as well as colchicine group(PNALP3<0.01;PCaspase-1<0.01).Conclusion:Flemingia Roxb.exAit extract has the effect of treating acute gouty arthritis and its mechanism may be related toinhibiting NLRP3 inflammasome activation and inhibiting inflammatory response.展开更多
Transcriptional coactivators regulate the rate of gene expression in the nucleus.Nuclear receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but ...Transcriptional coactivators regulate the rate of gene expression in the nucleus.Nuclear receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains unclear.Here,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory conditions.Unexpectedly,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic specks.Mechanistically,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active caspase-1.Of note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in macrophages.Genetic ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in mice.Consistent with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling results.Conclusively,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.展开更多
Gouty arthritis is a very familiar inflammatory arthritis.Controlling inflammation is the key to preventing gouty arthritis.However,colchicine,the most highly represented drug used in clinical practice,has strict cont...Gouty arthritis is a very familiar inflammatory arthritis.Controlling inflammation is the key to preventing gouty arthritis.However,colchicine,the most highly represented drug used in clinical practice,has strict contraindications owing to some severe side effects.Curcumin(Cur),a natural anti-inflammatory drug,has demonstrated good safety and efficacy.However,the rapid degradation,poor aqueous solubility,and low bioavailability of Cur limit its therapeutic effect.To strengthen the effectiveness and bioavailability of Cur.Cur loaded tetrahedral framework nucleic acids(Cur-TFNAs)were synthesized to deliver Cur.Compared with free Cur,Cur-TFNAs exhibit a preferable drug stability,good biocompatibility(CCK-8 assay),ease of uptake(immunofluorescence),and higher tissue utilization(in vivo biodistribution).Most importantly,Cur-TFNAs present better anti-inflammatory effect than free Cur both in vivo and in vitro experiments through the determination of inflammation-related cytokines expression.Therefore,we believe that Cur-TFNAs have great prospects for the prevention of gout and similar inflammatory diseases.展开更多
Objective: To study the therapeutic effect of treatment of acute gouty arthritis (AGA) respectively by electroacupuncture (EA) with different frequency and oral intake of Western medicine. Methods: Seventy-two patient...Objective: To study the therapeutic effect of treatment of acute gouty arthritis (AGA) respectively by electroacupuncture (EA) with different frequency and oral intake of Western medicine. Methods: Seventy-two patients of AGA were randomly assigned into three groups, 24 in each group. Group A was treated with EA 100 Hz; Group B with EA 2 Hz; and Group C with Western medicine. The analgesic effect, initiating time and sustaining time of analgesia were observed and the level of serum uric acid was measured before and after treatment. Results:The initiating time of analgesia was shorter while the sustaining time of analgesia was longer in Group A and B than those in Group C (all P<0. 01). The efficacy of analgesia was higher in Group B than that in Group A , and a better effect was shown in Group B in reducing serum uric acid level than that in Group A (P<0.01), which was near that in Group C (P>0.05). Conclusion: EA is an effective treatment for AGA, and low frequency (2 Hz) EA showed a better efficacy.展开更多
OBJECTIVE:To evaluate the clinical efficacy and safety of external application of Traditional Chinese Medicine (EATCM) on acute gouty arthritis (AGA).METHODS:Six electronic data bases were retrieved from their incepti...OBJECTIVE:To evaluate the clinical efficacy and safety of external application of Traditional Chinese Medicine (EATCM) on acute gouty arthritis (AGA).METHODS:Six electronic data bases were retrieved from their inception to march 2017.15 randomized controlled clinical trials (RCTs) were included.The quality of the literatures was assessed according to Cochrane review criteria by using RevMan5.3 software;and related data was counted using Stata14.0 software.RESULTS:There was no significant difference in C-reactiveprotein (CRP) between experimental intervention group and control group [(WMD =1.093,95% C/(-2.514,4.701);P =0.553)].In terms of overall efficacy,the EATCM's treatment group was significantly superior to control group [(OR =3.692;95% CI (2.408,5.661);P <0.001)].The EATCM was better than western medicine treatments or other interventions in reducing the adverse reactions [(OR =0.135;95% CI (0.067,0.274);P < 0.001)].All these funnel plots showed unlikelihood of publishing bias.But due to excessive heterogeneity,the statistical results of serum uric acid and visual analogue scale and CRP between the two groups became uncertain.CONCLUSION:The results indicate that EATCM may have greater overall efficacy with fewer adverse drug reactions,although the evidence is weak owing to the low methodological quality and the small number of the included trials.展开更多
The NLRP3 inflammasome’s core and most specific protein,NLRP3,has a variety of functions in inflammation-driven diseases.Costunolide(COS)is the major active ingredient of the traditional Chinese medicinal herb Saussu...The NLRP3 inflammasome’s core and most specific protein,NLRP3,has a variety of functions in inflammation-driven diseases.Costunolide(COS)is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity,but the principal mechanism and molecular target of COS remain unclear.Here,we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3,altering the ATPase activity and assembly of NLRP3 inflammasome.We declare COS’s great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation.We also reveal that theα-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation.Taken together,NLRP3 is identified as a direct target of COS for its anti-inflammasome activity.COS,especially theα-methylene-γ-butyrolactone motif in COS structure,might be used to design and produce novel NLRP3 inhibitors as a lead compound.展开更多
Objective To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino(TSDN)on the arachidonic acid pathway in monosodium urate(MSU)crystal-induced M1-polarized m...Objective To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino(TSDN)on the arachidonic acid pathway in monosodium urate(MSU)crystal-induced M1-polarized macrophages.Methods M1 polarization of RAW264.7 cells were induced by 1µg/mL lipopolysaccharide(LPS).The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of TSDN.MSU(500µg/mL)was used to induce the gouty arthritis model.Afterwards,10µg/L TSDN and 8µmol/L celecoxib,which was used as a positive control,were added to the above LPS and MSU-induced cells for 24 h.The mRNA and protein expressions of cyclooxygenase(COX)2,5-lipoxygenase(5-LOX),microsomal prostaglandin E synthase derived eicosanoids(mPGES)-1,leukotriene B(LTB)4,cytochrome P450(CYP)4A,and prostaglandin E_(2)(PGE_(2))were tested by real-time polymerase chain reaction and Western blotting,respectively.The enzyme-linked immunosorbent assay was used to test the contents of M1 markers,including inducible nitric oxid synthase(NOS)2,CD80,and CD86.Results TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2,5-LOX,CYP4A,LTB4,and PGE_(2)(P<0.01)while increased the mRNA and protein expression of mPGES-1(P<0.05 or P<0.01).TSDN could also significantly decrease the contents of NOS2,CD80,and CD86(P<0.01).Conclusion TSDN has an anti-inflammation effect on gouty arthritis in an in vitro model by regulating arachidonic acid signaling pathway.展开更多
Objective:To conduct the meta-analysis and trial sequential analysis(TSA) on clinical trials of fire needling therapy in treatment of gouty arthritis and review systematically the clinical therapeutic effect of fire n...Objective:To conduct the meta-analysis and trial sequential analysis(TSA) on clinical trials of fire needling therapy in treatment of gouty arthritis and review systematically the clinical therapeutic effect of fire needling therapy on gouty arthritis so as to provide the medical evidences of the extensive application of this therapy in treatment of gouty arthritis.Methods:The relevant clinical trials of fire needling therapy for treatment of gouty arthritis were searched from China National knowledge Infrastructure,Wanfang Data Knowledge Service Platform,Chinese Science and Technology Journal Database,American Medical Online,Dutch Medical Literature Database and International Evidence-Based Medical library.Using Review Manager 5.3 software,the quality of the included trials was assessed and meta-analysis was performed.With TSA v0.9 software,the trial sequential analysis was conduced on the appropriate outcomes.Results:A total of 10 trials were included with 775 patients involved.The analysis results showed that compared with the western medication,the total effective rate(RR=1.14’95%CI [1.09,1.20]),the curative rate(RR=1.59’95%CI [1.33,1.89]),the reduced VAS score(MD=-1.44’ 95%CI [-1.93,-0.951]) and the reduced incidence of adverse reaction(RR=0.27’ 95% CI [0.09,0.76]) of the fire needling therapy were different significantly(all P <0.05).Regarding the reduction of blood uric acid(MD=-40.47’ 95%CI [-80.21,-0.72]) and the score of symptoms and physical signs(MD=-1.38’95% CI [-3.71,0.95]),the effect of fire needling therapy was similar to that of western medication group(both P≥0.05).The trial sequential analysis suggested that the result was reliable,in which,the total effective rate of fire needling therapy was much higher than the western medication.But,it was potentially a false-positive finding,in which,fire needling therapy was much more advantageous at reducing blood uric acid as compared with the western medication.Conclusion:Based on the analytic results,it can be determined that fire needling therapy,as an effective approach to the treatment of gouty arthritis,has a certain advantage as compared with western medication.Given the low overall quality of trials,it still needs high-quality clinical trial to verify the findings of this study results.展开更多
Aberrant inflammasome activation contributes to the pathogenesis of various human diseases,including atherosclerosis,gout,and metabolic disorders.Elucidation of the underlying mechanism involved in the negative regula...Aberrant inflammasome activation contributes to the pathogenesis of various human diseases,including atherosclerosis,gout,and metabolic disorders.Elucidation of the underlying mechanism involved in the negative regulation of the inflammasome is important for developing new therapeutic targets for these diseases.Here,we showed that Raf kinase inhibitor protein(RKIP)negatively regulates the activation of the NLRP1,NLRP3,and NLRC4 inflammasomes.RKIP deficiency enhanced caspase-1 activation and IL-1P secretion via NLRP1,NLRP3,and NLRC4 Inflammasome activation In primary macrophages.The overexpression of RKIP in THP-1 cells inhibited NLRP1,NLRP3,and NLRC4 inflammasome activation.RKIP-deficient mice showed increased sensitivity to Aluminduced peritonitis and Salmonella typhimurium-induced inflammation,indicating that RKIP inhibits NLRP3 and NLRC4 inflammasome activation in vivo.Mechanistically,RKIP directly binds to apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC)and competes with NLRP1,NLRP3,or NLRC4 to interact with ASC thus interrupting inflammasome assembly and activation.The depletion of RKIP aggravated inflammasome-related diseases such as monosodium urate(MSU)-induced gouty arthritis and high-fat diet(HFD)-induced metabolic disorders.Furthermore,the expression of RKIP was substantially downregulated in patients with gouty arthritis or type 2 diabetes(T2D)compared to healthy controls.Collectively,our findings suggest that RKIP negatively regulates NLRP1,NLRP3,and NLRC4 inflammasome activation and is a potential therapeutic target for the treatment of inflammasome-related diseases.展开更多
OBJECTIVE:To investigate the interaction between nuclear factor kappa-B(NF-κB)and inflammatory cytokines in synovial cell inflammatory responses induced by sodium urate,and to evaluate the efficacy of Xixiancao(Herba...OBJECTIVE:To investigate the interaction between nuclear factor kappa-B(NF-κB)and inflammatory cytokines in synovial cell inflammatory responses induced by sodium urate,and to evaluate the efficacy of Xixiancao(Herba Siegesbeckiae Orientalis)on these interactions.METHODS:The interactions between NF-κB and inflammatory cytokines/mediators in synovial cells in acute gouty arthritis were investigated.We observed the expressions of NF-κB,interleukin(IL)-1β,IL-8,and tumor necrosis factor alpha(TNF-α)in synovial cells at different timepoints in an in vitro model of synovial cell inflammatory responses induced by sodium urate and in an in vivo model of gouty arthritis.Changes in the expressions of NF-κB,IL-1β,IL-8,and TNF-αin synovial cells of all experimental groups were compared and observed after treatment with different doses of Xixiancao(Herba Siegesbeckiae Orientalis)and colchicine.The interactions between NF-κB and IL-1β,IL-8,and TNF-αwere analyzed.Pathological changes in synovial tissues were observed in rats with acute gouty arthritis.RESULTS:Compared with the blank group,the expression levels of NF-κB,IL-1β,IL-8,and TNF-αwere increased significantly at different timepoints in the in vitro model of synovial cell inflammatory responses induced by sodium urate,and in the in vivo model of gouty arthritis.Compared with the model group,the expressions of NF-κB,IL-1β,IL-8,and TNF-αin synovial cells induced by sodium urate were decreased in the different Xixiancao(Herba Siegesbeckiae Orientalis)dose groups and the colchicine group.The effect was more obvious in the high dose Xixiancao(Herba Siegesbeckiae Orientalis)group.The expression of NF-κB in synovial cells was positively correlated with the expressions of IL-1β,IL-8,and TNF-α.Histopathological examination of synovial tissues in the high dose Xixiancao(Herba Siegesbeckiae Orientalis)group and Colchicine group showed that the characteristics of acute gouty arthritis were reduced,and there was a trend towards a positive correlation between NF-κB and inflammatory cytokine expressions.CONCLUSION:The activation of NF-κB is associated with the activation of IL-1β,IL-8,and TNF-αduring the pathogenesis of acute gouty arthritis,leading to the continuation and enhancement of the inflammatory response.Expressions of IL-1β,IL-8,and TNF-αin synoviocytes during acute gouty arthritis effectively inhibit local inflammation.展开更多
基金Heilongjiang Province Tradit Chin Med Research Projec(No.ZHY19-006)。
文摘Objective:To observe the effect of Sanshi decoction on BRD4/NF-κB/NLRP3 pathwaymediated macrophage pyroptosis,so as to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthritis.Methods:THP-1 was induced into macrophages with foboside and the divided into the control group,model group,low-dose,medium-dose,high-dose group of Sanshi decoction,and BRD4 inhibitor group.Except for the control group,the remaining groups were induced with monosodium urate crystals to construct a gouty arthritis cell model.The activity of macrophages was detected by CCK8,the level of macrophage pyroptosis was detected by flow cytometry,the activity of LDH,the content of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay,and the expression of related proteins in the BRD4/NF-κB/NLRP3 pathway was detected by Western blot.Results:Compared with the control group,macrophage activity was decreased in the model group,and the level of pyroptosis,LDH activity,contents of IL-1β and IL-18,expression levels of BRD4,p-NF-kB p65,NLRP3,Caspase-1 p20,and IL-1β protein were significantly up-regulated,the differences were statistically significant(P<0.05 and P<0.01).Compared with the model group,macrophage activity was up-regulated in the Sanshi Decoction,and the level of pyroptosis,LDH activity,IL-1β and IL-18 contents,expression levels of BRD4,p-NF-kB p65,NLRP3,Caspase-1 p20,and IL-1β protein were significantly decreased with statistically significant differences(P<0.05 and P<0.01).Conclusion:Sanshi decoction inhibits macrophage pyroptosis by inhibiting BRD4/NF-κB/NLRP3 pathway activation,thus improving the inflammation level of gouty arthritis.
基金Heilongjiang Province Traditional Chinese Medicine Research Project(No.ZHY19-006)。
文摘Objective:To observe the effect of Sanshi decoction on P2X7R/PKR pathway-mediated activation of macrophage NLRP3 inflammasome to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthritis.Methods:THP-1 macrophages were divided into control group,model group,low dose group,medium dose group,high dose group of Sanshi decoction and inhibitor group.The remaining groups were induced with monosodium urate crystals to establish a gouty arthritis cell model except the control group.Flow cytometry was used to detect macrophage ROS levels in each group,ELISA to detect MDA levels and SOD and GSH-PX activities in each group,and Western blot to detect P2X7R/PKR pathway and NLRP3 inflammasome-associated protein expression.We also used CCK-8 and flow cytometry to measure MH7A activity and apoptotic levels.Results:Compared with the control group,the ROS level,the content of MDA,the activities of SOD and GSH-PX were significantly increased,and the expression levels of NLRP3,full-length IL-1β,pro-IL-1β,full-length IL-18,pro-IL-18,full-length caspase-1,GSDMD-NT,P2X7R and p-PKR protein expression levels were significantly upregulated,and GSDMD-FL protein expression was significantly downregulated in the model group,and that the differences between them were statistically significant(P<0.05 and P<0.01).Compared with the model group,Sanshi decoction could reduce macrophage ROS levels,MDA content,SOD and GSHPX activities,and downregulate macrophage NLRP3,mature IL-1β,pro IL-1β,mature IL-18,pro IL-18,mature caspase-1,GSDMD-NT,P2X7R and p-PKR protein expression,and upregulate GSDMD-FL protein expression,with statistically significant differences(P<0.05 and P<0.01).In addition,MH7A activity was downregulated,and apoptosis level was upregulated in the model group in comparison with the control group,and differences were all significantly different(P<0.05).As compared to the model group,Sanshi decoction could significantly increase the activity of MH7A and inhibit the level of apoptosis,and that the differences between them were statistically significant(P<0.05 and P<0.01).Conclusion:Sanshi decoction can achieve the therapeutic effect of gouty arthritis by inhibiting P2X7R/PKR pathway activation,thus reducing the activation level of NLRP3.
基金National Natural Science Foundation of China(No.82060871,81860857)。
文摘Objective:To systematically evaluate the efficacy of traditional Chinese medicine decoction combined with arthroscopy in the treatment of gouty arthritis.Methods:A systematic search of CNKI,CBM,WanFang,VIP,PubMed,Cochrane Library,and EMBASE databases,and the receipt of the database until February 2021.Randomized controlled trials(RCTs)of traditional Chinese medicine(TCM)decoction combined with arthroscopy in the treatment of gouty arthritis.Two researchers independently read the title and abstract to screen and them read the full text to clarify whether it should be included.The method of Cochrane systematic review was used to evaluate the quality of the literature,and the RevMan 5.3 software was used to conduct meta-analysis of the data.Results:Nineteen RCTs were finally included.A total of 1383 patients,697 cases in the treatment group were treated with traditional Chinese medicine decoction combined with arthroscopy,and 686 cases in the control group were treated with arthroscopy alone or combined with western medicine.Meta-analysis results showed that the total clinical effective rate(P<0.00001)of the treatment group was better than that of the control group.Visual analogue scoring(VAS)score(P=0.0005,P<0.00001,P=0.03)and erythrocyte sedimentation rate(ESR)level(P<0.00001,P<0.00001,P<0.00001)reduction in each subgroup was better than that of the control group.The Lysholm score of the treatment group increased(P<0.00001,P<0.00001,P=0.19),while for blood uric acid(UA)level(P<0.00001,P=0.18,P<0.0001)and C-reactive protein(CRP)levels(P<0.0001,P<0.00001,P=0.23)two subgroups were better than the control group,but there was no significant difference in one subgroup.Conclusion:Traditional Chinese medicine decoction combined with arthroscopy is effective in treating gouty arthritis,which can relieve pain,improve joint function,and reduce body inflammation and uric acid levels.However,in the future,clinical studies with larger sample sizes,more reasonable designs,and higher quality are still needed to demonstrate this conclusion.
基金General project of science and technology development fund of Nanjing medical university (NMUB2018163)
文摘Objective:To explore the effect of imbalance of tumor necrosis factor receptor related factor-6(TRAF-6),interleukin 1 receptor associated kinase-1(IRAK-1)and neutrophil alkaline phosphatase-3(NALP3)in patients with gouty arthritis.Methods:The retrospective experiment was conducted on 105 patients with gouty arthritis admitted to our hospital(47 patients with acute onset and 58 patients with remission,namely group A and group B);meanwhile,another 61 healthy volunteers were selected for control,namely group C.The enrolling of the three groups was dated from May 2017 to May 2018,and TRAF-6,IRAK-1 and NALP3 of all subjects were tested through real-time fluorescence quantification(RT-PCR),and the correlation between the three inflammatory factors and gouty arthritis was compared.Results:1)Through treatment,ESR,BUA and total addiment in group A and B were higher than those in group C,among which the three indicators in group A were higher than those in group B(P<0.05),while CRP was lower than that of group C,and the two indicators in group A were lower than those in group B(P<0.05).2)There was no significant difference in the relative expression of TRAF-6 mRNA between group A and group B before treatment(P>0.05),significantly lower than group C(P<0.05);the above indicators of group A and group B were improved to some extent after treatment,but group A was still lower than group B(P<0.05),and the degree of improvement of group A was also lower than that of group C(P<0.05),while the degree of improvement of group B was not significantly different from that of group C(P>0.05).3)The relative expression level of IRAK-1mRNA in group A and group B before treatment showed no significant difference(P>0.05),but was also lower than that in group C(P<0.05).The relative expression level of IRAK-1mRNA in group A and group B increased to some extent after treatment,with group A significantly lower than group C(P<0.05),and group B showed no significant difference compared with group C(P>0.05).4)The relative expression level of NALP-3 mRNA in group A and group B showed no significant difference(P>0.05)before treatment,significantly higher than that in group C(P<0.05);the relative expression of NALP-3 mRNA in group A was not significantly decreased(P>0.05)after treatment,while that in group B was significantly decreased after treatment(P<0.05),indicating significant different compared with group A and group C.5)There was no correlation between)TRAF-6,ESR,CRP and total addiment(P>0.05);IRAK-1 was negatively correlated with CRP,BUA and total addiment(P<0.05);NALP-3 was negatively correlated with ESR and CRP(P<0.05).Conclusion:TRAF-6,IRAK-1 and NALP-3 are all under abnormal expression in the developing of new gouty arthritis,acting as important participants in promoting the occurrence,development and outcome of illness states,so the intervening measures should be taken.
基金National administration of TCM base special fund(No.JDZX2015277)Beijing municipal science and technology commission science and technology star project(No.Z191100001119025)
文摘Objective:The mechanism of Chinese herbal medicine"Bi xie and Tu fuling"on the treatment of gouty arthritis was explored through network pharmacological methods.Methods:First,the TCMSP Chinese medicine system pharmacology database and analysis platform were used to define the bioavailability(OB)30%and drug-likeness(DL)0.18.Database to mine genetic targets related to gouty arthritis disease.Finally,the two genes are intersected to construct a Chinese medicine regulatory network of Chinese medicine-components-target genes-disease.The genes in the network are used to construct a protein interaction network to find core genes for analysis of GO and KEGG.Results:There were a total of 84 active ingredients in Chinese medicine Poria and Poria cocos,and 17 effective ingredients and 180 genetic targets were obtained after screening.600 disease targets for gouty arthritis were identified,and 58 were common target genes for both.PPI network analysis revealed that IL1β,VEGFA,MAPK1,IL10,and PTGS2 may be drugs for treating gouty arthritis.Key targets.GO enrichment analysis identified 1,399 entries(P<0.05),of which biological processes mainly include biological stimulation,biological regulation,cell metabolism,etc;KEGG pathway enrichment analysis identified 152 signal pathways,of which signal pathways involved inflammation,metabolism,In terms of aging,mainly including the IL-4,IL-10,IL-13,IL-17signal pathway,etc.Conclusion:"Bi xie and Tu fuling"drugs have anti-inflammatory and immunological effects on gouty arthritis through multiple targets and multiple pathways.The mechanism of lowering uric acid and protecting liver and kidney is not clear.It needs molecular biology research to improve it.The mechanism of the action of the"Bi xie and Tu fuling"medicine pair provides new ideas for the clinical prescriptions.
基金Guangxi Natural Science Foundation(2020GXNSFAA259059)National Training Program for Characteristic Technology Inheritance of Traditional Chinese Medicine(20184828005)In-hospital Preparation Development Project of the First Affiliated Hospital of Guangxi University of Chinese Medicine in 2017(2017ZJ001).
文摘[Objectives]To study the anti-inflammatory effect of Simiao Liangxue granule on the rats with acute gouty arthritis(AGA).[Methods]A total of 60 male SD rats were randomly divided into 6 groups with 10 rats in each group.The rats in the colchicine group were intragastrically administered with 0.65 mg/kg colchicine,and the rats in low,medium and high dose groups of Simiao Liangxue granule were intragastrically administered with Simiao Liangxue granule with mass concentration of 0.4,0.8 and 1.6 g/kg,respectively.The rats in the normal control group and the model group were given the same amount of normal saline for 7 d,and the acute gouty arthritis model was prepared 1 h after administration on the 5th d.At the end of the experiment,the degree of joint swelling and joint inflammation index,the content of interleukin-1β,tumor necrosis factor-a and cyclooxygenase-2 in articular cartilage,and the content of interleukin-8,NO and UA in serum of rats were measured,and the histomorphological observation was performed.[Results]Compared with the normal control group,the joints of rats were swollen to different degrees,the inflammation score was significantly increased,and the content of IL-1β,TNF-αand COX-2 in the soft tissue of the joints was significantly increased in each group(P<0.05);compared with the model group,the joint swelling degree and inflammation score of rats in the colchicine group and Simiao Liangxue granule group were significantly decreased,the content of IL-1β,TNF-αand COX-2 in the joint soft tissue was also significantly decreased(P<0.05),and the indexes of each dose group of Simiao Liangxue granule were similar to those of the colchicine group;compared with the normal control group,the content of IL-8,NO and UA in the joint soft tissue of rats was significantly increased in each group(P<0.05);compared with the model group,the content of all indexes in joint soft tissue of rats in normal control group,colchicine group and Simiao Liangxue granule group were significantly decreased(P<0.05);the content of various indexes in the joint soft tissue of rats in the low and medium dose groups of Simiao Liangxue granule was higher than that in the colchicine group,and decreased significantly with the increase of the dose of Simiao Liangxue granule(P<0.05);the inflammatory index decreased significantly with the increase of the dose of Simiao Liangxue granule(P<0.05);the inflammation and degeneration in each dose group of Simiao Liangxue granule were milder than those in the model group,and the symptoms were relieved to some extent with the increase of dose(P<0.05).[Conclusions]Simiao Liangxue granule has the effect of anti-inflammation and detumescence,and its mechanism may be related to the content of factors that reduce inflammation including IL-1β,TNF-α,C0X-2,IL-8,NO and UA.
基金National Natural Resources Foundation program(No.81373802)Beijing Natural Science Foundation(No.7172244)Beijing Science and Technology Project(No.Z191100006619024)
文摘Objective:To Find the core targets and drug action mechanism of Si Miao decoction for the treatment of acute gouty arthritis.Methods:Through the TCMSP database,the chemical composition of all the drugs in Si Miao decoction was obtained.The Perl script was compiled and the UniProt database was searched to determine the corresponding target of the chemical composition.Then,the disease databases such as OMIM,DisGeNET,and GeneCards were searched in order to determine acute gouty arthritis Related targets.Finally,screen common targets for drugs and diseases,use the STRING database and Cytoscape software to build a network control map of drugs-chemical components-targets-disease.Use R language software to screen common targets and find the four best The core targets of San for the treatment of acute gouty arthritis.The GO and KEGG analysis of the core targets were performed to clarify the core targets and mechanism of Si Miao decoction for the treatment of gout.Results:There are 64 effective chemical components in Si Miao decoction,197 genetic targets,600 disease targets,and 58 common targets.It is predicted that IL6,VEGFA,IL1B,JUN,PTGS2,and CCL2 may be treated by Si Miao decoction for gout The core target of arthritis.GO enrichment analysis identified 85 entries,of which biological processes mainly included the regulation of cytokine activity,protease activation,nucleic acid expression,etc.;KEGG pathway enrichment analysis identified 135 signaling pathways,of which signaling pathways involved the IL-17 signaling pathway,TNF signaling pathway,Th17 cell differentiation and other pathways.Conclusion:Si Miao decoction acts on acute gouty arthritis by regulating the occurrence of inflammation,and has significant anti-inflammatory and immune effects.The formula is rigorous and scientific,and it is worthy of clinical application.
基金2016 Hainan Medical College Students Innovation and Entrepreneurship Training Program(No.HYCX2016055)2017 Hainan College Students Innovation and Entrepreneurship Training Program Project(No.2017098)。
文摘Objective:To investigate the effect and anti-inflammatory mechanism the effect of Flemingia Roxb.exAit extract on acute gouty arthritis.Methods:Sixty SD rats were randomly divided into 6 groups by weight,control and model group,(100、150、200 mg/kg)of Flemingia Roxb.exAit extract group and colchicine group.The rats of each group were given by intragastric for 7 days of continuous administration,meanwhile,there were given 0.9%NaCl solution instead as control and model group.The acute gouty arthritis model was constructed through right ankle joint cavity injection of sodium urate crystal solutionon day 5 after 1 h,but rats in the negative control group were injected with 0.9%NaCl solution into the articular cavity of the right foot.The general condition of rats and the degree of joint swelling,and the gait was observed after constructed model.To detected the joint fluid IL-1β、TNF-α、IL-6 indicators,and the expression of NLRP3,Caspase-1 protein in ankle joint tissue for 2 hours after the last administration.Results:Groups of Flemingia Roxb.exAit extract could markedly reduce the joint swelling on acute gouty arthritis rat model,improve gait in a dose-dependent manner,high dose group of Flemingia Roxb.exAit extract did particularly well(Pjoint swelling<0.01;Pgait<0.05),close to the therapeutic effect colchicine group.Further mechanism studies show that the joint fluid IL-1β、TNF-α、IL-6 level was reduced by Flemingia Roxb.exAit extract group,the expressions of NLRP3、Caspase-1 protein of Flemingia Roxb.exAit extract group was decreased observbly than model group,but the most obvious is that high dose group as well as colchicine group(PNALP3<0.01;PCaspase-1<0.01).Conclusion:Flemingia Roxb.exAit extract has the effect of treating acute gouty arthritis and its mechanism may be related toinhibiting NLRP3 inflammasome activation and inhibiting inflammatory response.
基金supported by grants from the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(2015R1A3A2032927 and 2021R1A2C1008130).
文摘Transcriptional coactivators regulate the rate of gene expression in the nucleus.Nuclear receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains unclear.Here,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory conditions.Unexpectedly,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic specks.Mechanistically,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active caspase-1.Of note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in macrophages.Genetic ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in mice.Consistent with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling results.Conclusively,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.
基金funded by the National Key R&D Program of China[2019YFA0110600]National Natural Science Foundation of China[81970916,81671031].
文摘Gouty arthritis is a very familiar inflammatory arthritis.Controlling inflammation is the key to preventing gouty arthritis.However,colchicine,the most highly represented drug used in clinical practice,has strict contraindications owing to some severe side effects.Curcumin(Cur),a natural anti-inflammatory drug,has demonstrated good safety and efficacy.However,the rapid degradation,poor aqueous solubility,and low bioavailability of Cur limit its therapeutic effect.To strengthen the effectiveness and bioavailability of Cur.Cur loaded tetrahedral framework nucleic acids(Cur-TFNAs)were synthesized to deliver Cur.Compared with free Cur,Cur-TFNAs exhibit a preferable drug stability,good biocompatibility(CCK-8 assay),ease of uptake(immunofluorescence),and higher tissue utilization(in vivo biodistribution).Most importantly,Cur-TFNAs present better anti-inflammatory effect than free Cur both in vivo and in vitro experiments through the determination of inflammation-related cytokines expression.Therefore,we believe that Cur-TFNAs have great prospects for the prevention of gout and similar inflammatory diseases.
文摘Objective: To study the therapeutic effect of treatment of acute gouty arthritis (AGA) respectively by electroacupuncture (EA) with different frequency and oral intake of Western medicine. Methods: Seventy-two patients of AGA were randomly assigned into three groups, 24 in each group. Group A was treated with EA 100 Hz; Group B with EA 2 Hz; and Group C with Western medicine. The analgesic effect, initiating time and sustaining time of analgesia were observed and the level of serum uric acid was measured before and after treatment. Results:The initiating time of analgesia was shorter while the sustaining time of analgesia was longer in Group A and B than those in Group C (all P<0. 01). The efficacy of analgesia was higher in Group B than that in Group A , and a better effect was shown in Group B in reducing serum uric acid level than that in Group A (P<0.01), which was near that in Group C (P>0.05). Conclusion: EA is an effective treatment for AGA, and low frequency (2 Hz) EA showed a better efficacy.
基金Supported by National Natural Science Foundation of China Youth Science Foundation(No.81503598)
文摘OBJECTIVE:To evaluate the clinical efficacy and safety of external application of Traditional Chinese Medicine (EATCM) on acute gouty arthritis (AGA).METHODS:Six electronic data bases were retrieved from their inception to march 2017.15 randomized controlled clinical trials (RCTs) were included.The quality of the literatures was assessed according to Cochrane review criteria by using RevMan5.3 software;and related data was counted using Stata14.0 software.RESULTS:There was no significant difference in C-reactiveprotein (CRP) between experimental intervention group and control group [(WMD =1.093,95% C/(-2.514,4.701);P =0.553)].In terms of overall efficacy,the EATCM's treatment group was significantly superior to control group [(OR =3.692;95% CI (2.408,5.661);P <0.001)].The EATCM was better than western medicine treatments or other interventions in reducing the adverse reactions [(OR =0.135;95% CI (0.067,0.274);P < 0.001)].All these funnel plots showed unlikelihood of publishing bias.But due to excessive heterogeneity,the statistical results of serum uric acid and visual analogue scale and CRP between the two groups became uncertain.CONCLUSION:The results indicate that EATCM may have greater overall efficacy with fewer adverse drug reactions,although the evidence is weak owing to the low methodological quality and the small number of the included trials.
基金supported by the National Natural Science Foundation of China(81930108 to Guang Liang,82000793 to Wu Luo,and 82170373 to Yi Wang)Natural Science Foundation of Zhejiang Province(LY22H070004 to Wu Luo,China)+1 种基金Zhejiang Provincial Key Scientific Project(2021C03041 to Guang Liang,China)Wenzhou Scientific Project in China(Y20210213 to Wu Luo)。
文摘The NLRP3 inflammasome’s core and most specific protein,NLRP3,has a variety of functions in inflammation-driven diseases.Costunolide(COS)is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity,but the principal mechanism and molecular target of COS remain unclear.Here,we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3,altering the ATPase activity and assembly of NLRP3 inflammasome.We declare COS’s great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation.We also reveal that theα-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation.Taken together,NLRP3 is identified as a direct target of COS for its anti-inflammasome activity.COS,especially theα-methylene-γ-butyrolactone motif in COS structure,might be used to design and produce novel NLRP3 inhibitors as a lead compound.
基金Supported by Joint Guidance Project of Heilongjiang Natural Science Foundation(No.LH2021H099)Start Fund of Postdoctoral Research in Heilongjiang Province(No.LBH-Q19188)+3 种基金Outstanding Youth Development Fund of Heilongjiang University of Chinese Medicine(No.2019JC06)Project of Heilongjiang Administration of Traditional Chinese Medicine(No.ZHY202094)Graduate Innovative Scientific Research Project of Heilongjiang University of Chinese Medicine(No.2020yjscx057)Natural Science Foundation of Heilongjiang Province(Key project,No.ZD2020H006)。
文摘Objective To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino(TSDN)on the arachidonic acid pathway in monosodium urate(MSU)crystal-induced M1-polarized macrophages.Methods M1 polarization of RAW264.7 cells were induced by 1µg/mL lipopolysaccharide(LPS).The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of TSDN.MSU(500µg/mL)was used to induce the gouty arthritis model.Afterwards,10µg/L TSDN and 8µmol/L celecoxib,which was used as a positive control,were added to the above LPS and MSU-induced cells for 24 h.The mRNA and protein expressions of cyclooxygenase(COX)2,5-lipoxygenase(5-LOX),microsomal prostaglandin E synthase derived eicosanoids(mPGES)-1,leukotriene B(LTB)4,cytochrome P450(CYP)4A,and prostaglandin E_(2)(PGE_(2))were tested by real-time polymerase chain reaction and Western blotting,respectively.The enzyme-linked immunosorbent assay was used to test the contents of M1 markers,including inducible nitric oxid synthase(NOS)2,CD80,and CD86.Results TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2,5-LOX,CYP4A,LTB4,and PGE_(2)(P<0.01)while increased the mRNA and protein expression of mPGES-1(P<0.05 or P<0.01).TSDN could also significantly decrease the contents of NOS2,CD80,and CD86(P<0.01).Conclusion TSDN has an anti-inflammation effect on gouty arthritis in an in vitro model by regulating arachidonic acid signaling pathway.
基金Supported by National Natural Science Foundation of China:81460763,81960908.
文摘Objective:To conduct the meta-analysis and trial sequential analysis(TSA) on clinical trials of fire needling therapy in treatment of gouty arthritis and review systematically the clinical therapeutic effect of fire needling therapy on gouty arthritis so as to provide the medical evidences of the extensive application of this therapy in treatment of gouty arthritis.Methods:The relevant clinical trials of fire needling therapy for treatment of gouty arthritis were searched from China National knowledge Infrastructure,Wanfang Data Knowledge Service Platform,Chinese Science and Technology Journal Database,American Medical Online,Dutch Medical Literature Database and International Evidence-Based Medical library.Using Review Manager 5.3 software,the quality of the included trials was assessed and meta-analysis was performed.With TSA v0.9 software,the trial sequential analysis was conduced on the appropriate outcomes.Results:A total of 10 trials were included with 775 patients involved.The analysis results showed that compared with the western medication,the total effective rate(RR=1.14’95%CI [1.09,1.20]),the curative rate(RR=1.59’95%CI [1.33,1.89]),the reduced VAS score(MD=-1.44’ 95%CI [-1.93,-0.951]) and the reduced incidence of adverse reaction(RR=0.27’ 95% CI [0.09,0.76]) of the fire needling therapy were different significantly(all P <0.05).Regarding the reduction of blood uric acid(MD=-40.47’ 95%CI [-80.21,-0.72]) and the score of symptoms and physical signs(MD=-1.38’95% CI [-3.71,0.95]),the effect of fire needling therapy was similar to that of western medication group(both P≥0.05).The trial sequential analysis suggested that the result was reliable,in which,the total effective rate of fire needling therapy was much higher than the western medication.But,it was potentially a false-positive finding,in which,fire needling therapy was much more advantageous at reducing blood uric acid as compared with the western medication.Conclusion:Based on the analytic results,it can be determined that fire needling therapy,as an effective approach to the treatment of gouty arthritis,has a certain advantage as compared with western medication.Given the low overall quality of trials,it still needs high-quality clinical trial to verify the findings of this study results.
基金supported by the National Natural Science Foundation of China(81972733)the Natural Science Foundation of Zhejiang Province(LY19H160048).
文摘Aberrant inflammasome activation contributes to the pathogenesis of various human diseases,including atherosclerosis,gout,and metabolic disorders.Elucidation of the underlying mechanism involved in the negative regulation of the inflammasome is important for developing new therapeutic targets for these diseases.Here,we showed that Raf kinase inhibitor protein(RKIP)negatively regulates the activation of the NLRP1,NLRP3,and NLRC4 inflammasomes.RKIP deficiency enhanced caspase-1 activation and IL-1P secretion via NLRP1,NLRP3,and NLRC4 Inflammasome activation In primary macrophages.The overexpression of RKIP in THP-1 cells inhibited NLRP1,NLRP3,and NLRC4 inflammasome activation.RKIP-deficient mice showed increased sensitivity to Aluminduced peritonitis and Salmonella typhimurium-induced inflammation,indicating that RKIP inhibits NLRP3 and NLRC4 inflammasome activation in vivo.Mechanistically,RKIP directly binds to apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC)and competes with NLRP1,NLRP3,or NLRC4 to interact with ASC thus interrupting inflammasome assembly and activation.The depletion of RKIP aggravated inflammasome-related diseases such as monosodium urate(MSU)-induced gouty arthritis and high-fat diet(HFD)-induced metabolic disorders.Furthermore,the expression of RKIP was substantially downregulated in patients with gouty arthritis or type 2 diabetes(T2D)compared to healthy controls.Collectively,our findings suggest that RKIP negatively regulates NLRP1,NLRP3,and NLRC4 inflammasome activation and is a potential therapeutic target for the treatment of inflammasome-related diseases.
基金Supported by the National Natural Science Foundation of China Expression of c-jun Amino-Terminal Kinase Signaling Pathway in the Acute Stage of Gout Arthritis and the Mechanism of TCM Intervention(No.81360553)Interaction of Nuclear factor-B and Cytokines in Gout Arthritis and the Intervention of Traditional Chinese Medicine(No.30271629)
文摘OBJECTIVE:To investigate the interaction between nuclear factor kappa-B(NF-κB)and inflammatory cytokines in synovial cell inflammatory responses induced by sodium urate,and to evaluate the efficacy of Xixiancao(Herba Siegesbeckiae Orientalis)on these interactions.METHODS:The interactions between NF-κB and inflammatory cytokines/mediators in synovial cells in acute gouty arthritis were investigated.We observed the expressions of NF-κB,interleukin(IL)-1β,IL-8,and tumor necrosis factor alpha(TNF-α)in synovial cells at different timepoints in an in vitro model of synovial cell inflammatory responses induced by sodium urate and in an in vivo model of gouty arthritis.Changes in the expressions of NF-κB,IL-1β,IL-8,and TNF-αin synovial cells of all experimental groups were compared and observed after treatment with different doses of Xixiancao(Herba Siegesbeckiae Orientalis)and colchicine.The interactions between NF-κB and IL-1β,IL-8,and TNF-αwere analyzed.Pathological changes in synovial tissues were observed in rats with acute gouty arthritis.RESULTS:Compared with the blank group,the expression levels of NF-κB,IL-1β,IL-8,and TNF-αwere increased significantly at different timepoints in the in vitro model of synovial cell inflammatory responses induced by sodium urate,and in the in vivo model of gouty arthritis.Compared with the model group,the expressions of NF-κB,IL-1β,IL-8,and TNF-αin synovial cells induced by sodium urate were decreased in the different Xixiancao(Herba Siegesbeckiae Orientalis)dose groups and the colchicine group.The effect was more obvious in the high dose Xixiancao(Herba Siegesbeckiae Orientalis)group.The expression of NF-κB in synovial cells was positively correlated with the expressions of IL-1β,IL-8,and TNF-α.Histopathological examination of synovial tissues in the high dose Xixiancao(Herba Siegesbeckiae Orientalis)group and Colchicine group showed that the characteristics of acute gouty arthritis were reduced,and there was a trend towards a positive correlation between NF-κB and inflammatory cytokine expressions.CONCLUSION:The activation of NF-κB is associated with the activation of IL-1β,IL-8,and TNF-αduring the pathogenesis of acute gouty arthritis,leading to the continuation and enhancement of the inflammatory response.Expressions of IL-1β,IL-8,and TNF-αin synoviocytes during acute gouty arthritis effectively inhibit local inflammation.
