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
Solvent extraction of palladium （Ⅱ） from hydrochloric acid solution with 2-n-octyl-4-isothiazolin-3-one （OIT）/cyclohexane was studied. Effects of different parameters on extraction efficiency were evaluated. 99.9...Solvent extraction of palladium （Ⅱ） from hydrochloric acid solution with 2-n-octyl-4-isothiazolin-3-one （OIT）/cyclohexane was studied. Effects of different parameters on extraction efficiency were evaluated. 99.96 % and 98.26 % palladium （Ⅱ） could be effectively extracted with 0.018 mol·L^-1 OIT/cyclohexane of 0.1 and 4.0 mol·L^-1 HCl medium, respectively. Nonpolar solvent and low acidity could improve the extracting efficiency, and successfully strip palladium （Ⅱ） from the loaded organic phase was achieved with 0.5 mol·L^-1 （NH2）2CS solution. It was proposed that the extraction of Pd com-plexes from HCl medium proceeded through the ion-association mechanism by slope method, NMR and FF-IR spectra.展开更多
The building block of N-alkyl derivative of allosamidin（chitinase inhibitor）,4,6-O-benzylidene-N-octyl-D-allosamine hydrochloride was stereoselectively synthesized in two steps under mild conditions.Nucleophilic add...The building block of N-alkyl derivative of allosamidin（chitinase inhibitor）,4,6-O-benzylidene-N-octyl-D-allosamine hydrochloride was stereoselectively synthesized in two steps under mild conditions.Nucleophilic addition of octylamine to 2- oxoglucopyranoside gave a‘carbonyl group transfer＇ product in 62%yield.Subsequent stereoselective reduction of newly formed C=O with NaBH_4 produced title compound in 75%yield.X-ray diffraction analysis indicates the title compound adopts syn 1,2,3 stereochemistry and chair-chair conformation.The crystal structure is stabilized by hydrogen bonds.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financially supported by the National Natural Science Foundation of China(No.21271073)
文摘Solvent extraction of palladium （Ⅱ） from hydrochloric acid solution with 2-n-octyl-4-isothiazolin-3-one （OIT）/cyclohexane was studied. Effects of different parameters on extraction efficiency were evaluated. 99.96 % and 98.26 % palladium （Ⅱ） could be effectively extracted with 0.018 mol·L^-1 OIT/cyclohexane of 0.1 and 4.0 mol·L^-1 HCl medium, respectively. Nonpolar solvent and low acidity could improve the extracting efficiency, and successfully strip palladium （Ⅱ） from the loaded organic phase was achieved with 0.5 mol·L^-1 （NH2）2CS solution. It was proposed that the extraction of Pd com-plexes from HCl medium proceeded through the ion-association mechanism by slope method, NMR and FF-IR spectra.
基金the financial supports from the National Natural Science Foundation of China(No. 20972142)the State Key Laboratory of Bio-organic and Natural Products Chemistry,CAS(No.08417).
文摘The building block of N-alkyl derivative of allosamidin（chitinase inhibitor）,4,6-O-benzylidene-N-octyl-D-allosamine hydrochloride was stereoselectively synthesized in two steps under mild conditions.Nucleophilic addition of octylamine to 2- oxoglucopyranoside gave a‘carbonyl group transfer＇ product in 62%yield.Subsequent stereoselective reduction of newly formed C=O with NaBH_4 produced title compound in 75%yield.X-ray diffraction analysis indicates the title compound adopts syn 1,2,3 stereochemistry and chair-chair conformation.The crystal structure is stabilized by hydrogen bonds.
