Purpose:To investigate the pathological changes of the synovium in mice with post-traumatic osteoarthritis(PTOA)treated with 4-octyl itaconate(4-OI)and evaluate the therapeutic effects of 4-OI.Methods:In the phenotypi...Purpose:To investigate the pathological changes of the synovium in mice with post-traumatic osteoarthritis(PTOA)treated with 4-octyl itaconate(4-OI)and evaluate the therapeutic effects of 4-OI.Methods:In the phenotypic validation experiment,the mice were randomly divided into 3 groups:wildtype(WT)group,sham group,and destabilization of the medial meniscus(DMM)group.Through MRI,micro-CT,and histological analysis,it was determined that the DMM surgery induced a mouse PTOA model with significant signs of synovitis.At 12 weeks post-DMM surgery,synovial tissues from the DMM group and WT group mice were collected for ribonucleic acid sequencing analysis.In the 4-OI treatment experiment,mice were randomly divided into the sham group,DMM group,DMM+4-OI(50 mg/kg)group,and DMM+4-OI(100 mg/kg)group.Von Frey tests and open field tests were conducted at intervals during the 12 weeks following the DMM surgery.After 12 weeks of surgery,the efficacy of 4-OI treatment on PTOA in mice was evaluated using MRI,micro-CT,histological analysis,and quantitative real-time polymerase chain reaction.Finally,we utilized network pharmacology analysis to predict the mechanism of 4-OI in treating PTOA synovitis and conducted preliminary validation.Statistical analysis was performed using one-way ANOVA and the Kruskal-Wallis test.Difference was considered statistically significant at p<0.05.Results:The DMM surgery effectively induced a PTOA mouse model,which displayed significant symptoms of synovitis.These symptoms included a notable increase in both the number of calcified tissues and osteophytes(p<0.001),an enlargement of the calcified meniscus and synovial tissue volume(p<0.001),and thickening of the synovial lining layer attributable to M1 macrophage accumulation(p=0.035).Additionally,we observed elevated histological scores for synovitis(p<0.001).Treatment with 4-OI inhibited the thickening of M1 macrophages in the synovial lining layer of PTOA mice(p<0.001)and reduced fibrosis in the synovial stroma(p=0.004).Furthermore,it reduced the histological scores of knee synovitis in PTOA mice(p=0.006)and improved the inflammatory microenvironment associated with synovitis.Consequently,this treatment alleviated pain in PTOA mice(p<0.001)and reduced spontaneous activity(p=0.003).Bioinformatics and network pharmacology analyses indicated that 4-OI may exert its therapeutic effects by inhibiting the differentiation of synovial Th17 cells.Specifically,compared to the lipopolysaccharide stimulation group,4-OI reduced the levels of positive regulatory factors of Th17 cell differentiation(IL-1:p<0.001,IL-6:p<0.001),key effector molecules(IL-17A:p<0.001,IL-17F:p=0.004),and downstream effector molecules in the IL-17 signaling pathway(CCL2:p<0.001,MMP13:p<0.001).Conclusion:4-OI is effective in inhibiting synovitis in PTOA,thereby alleviating the associated painful symptoms.展开更多
Polyaspartic acid(PASP)composite,a scale inhibitor,was prepared from PASP,itaconic acid—acrylic acid—acrylic ester(IA-AA-AE)terpolymer and 2-phosphonobutane-1,2,4-tricarboxylic acid(PBTCA).The scale inhibition of PA...Polyaspartic acid(PASP)composite,a scale inhibitor,was prepared from PASP,itaconic acid—acrylic acid—acrylic ester(IA-AA-AE)terpolymer and 2-phosphonobutane-1,2,4-tricarboxylic acid(PBTCA).The scale inhibition of PASP composite and the effect of its synergism with a magnetic field on scale inhibition were investigated.Calcium carbonate crystals in scale samples were characterized by means of SEM and XRD.The static and dynamic experiments show that the chelating function of PASP composite for Ca2+can be enhanced by synergism with a magnetic field.Under Ca2+650 mg/L,HCO3-1,300 mg/L and PASPcomposite 4 mg/L,the scale inhibition rate of PASP composite in magnetic water can increase by 10%in static state and by 20%in dynamic experiments.Scanning electron microscope(SEM)and X-ray diffraction(XRD)results show that calcite and aragonite can be completely transformed into vaterite by using PASP composite.展开更多
基金supported by the Foundation of Chongqing Talents(grant no.CQYC2021059825).
文摘Purpose:To investigate the pathological changes of the synovium in mice with post-traumatic osteoarthritis(PTOA)treated with 4-octyl itaconate(4-OI)and evaluate the therapeutic effects of 4-OI.Methods:In the phenotypic validation experiment,the mice were randomly divided into 3 groups:wildtype(WT)group,sham group,and destabilization of the medial meniscus(DMM)group.Through MRI,micro-CT,and histological analysis,it was determined that the DMM surgery induced a mouse PTOA model with significant signs of synovitis.At 12 weeks post-DMM surgery,synovial tissues from the DMM group and WT group mice were collected for ribonucleic acid sequencing analysis.In the 4-OI treatment experiment,mice were randomly divided into the sham group,DMM group,DMM+4-OI(50 mg/kg)group,and DMM+4-OI(100 mg/kg)group.Von Frey tests and open field tests were conducted at intervals during the 12 weeks following the DMM surgery.After 12 weeks of surgery,the efficacy of 4-OI treatment on PTOA in mice was evaluated using MRI,micro-CT,histological analysis,and quantitative real-time polymerase chain reaction.Finally,we utilized network pharmacology analysis to predict the mechanism of 4-OI in treating PTOA synovitis and conducted preliminary validation.Statistical analysis was performed using one-way ANOVA and the Kruskal-Wallis test.Difference was considered statistically significant at p<0.05.Results:The DMM surgery effectively induced a PTOA mouse model,which displayed significant symptoms of synovitis.These symptoms included a notable increase in both the number of calcified tissues and osteophytes(p<0.001),an enlargement of the calcified meniscus and synovial tissue volume(p<0.001),and thickening of the synovial lining layer attributable to M1 macrophage accumulation(p=0.035).Additionally,we observed elevated histological scores for synovitis(p<0.001).Treatment with 4-OI inhibited the thickening of M1 macrophages in the synovial lining layer of PTOA mice(p<0.001)and reduced fibrosis in the synovial stroma(p=0.004).Furthermore,it reduced the histological scores of knee synovitis in PTOA mice(p=0.006)and improved the inflammatory microenvironment associated with synovitis.Consequently,this treatment alleviated pain in PTOA mice(p<0.001)and reduced spontaneous activity(p=0.003).Bioinformatics and network pharmacology analyses indicated that 4-OI may exert its therapeutic effects by inhibiting the differentiation of synovial Th17 cells.Specifically,compared to the lipopolysaccharide stimulation group,4-OI reduced the levels of positive regulatory factors of Th17 cell differentiation(IL-1:p<0.001,IL-6:p<0.001),key effector molecules(IL-17A:p<0.001,IL-17F:p=0.004),and downstream effector molecules in the IL-17 signaling pathway(CCL2:p<0.001,MMP13:p<0.001).Conclusion:4-OI is effective in inhibiting synovitis in PTOA,thereby alleviating the associated painful symptoms.
基金supported by the Natural Science Foundation of Hebei Province of China(B2004000749).
文摘Polyaspartic acid(PASP)composite,a scale inhibitor,was prepared from PASP,itaconic acid—acrylic acid—acrylic ester(IA-AA-AE)terpolymer and 2-phosphonobutane-1,2,4-tricarboxylic acid(PBTCA).The scale inhibition of PASP composite and the effect of its synergism with a magnetic field on scale inhibition were investigated.Calcium carbonate crystals in scale samples were characterized by means of SEM and XRD.The static and dynamic experiments show that the chelating function of PASP composite for Ca2+can be enhanced by synergism with a magnetic field.Under Ca2+650 mg/L,HCO3-1,300 mg/L and PASPcomposite 4 mg/L,the scale inhibition rate of PASP composite in magnetic water can increase by 10%in static state and by 20%in dynamic experiments.Scanning electron microscope(SEM)and X-ray diffraction(XRD)results show that calcite and aragonite can be completely transformed into vaterite by using PASP composite.
