Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a promine...Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.展开更多
目的探索死亡受体3(DR3)受体激动剂(αDR3)抗体活化DR3信号通路干预抗体-介导输血相关急性肺损伤(TRALI)的有效性及可能机制。方法1)8~10周龄Balb/c小鼠40只随机均分为正常组、同型对照组、模型组、干预组;正常组不做任何处理;小鼠腹腔...目的探索死亡受体3(DR3)受体激动剂(αDR3)抗体活化DR3信号通路干预抗体-介导输血相关急性肺损伤(TRALI)的有效性及可能机制。方法1)8~10周龄Balb/c小鼠40只随机均分为正常组、同型对照组、模型组、干预组;正常组不做任何处理;小鼠腹腔注射脂多糖(LPS)0.1 mg/kg及尾静脉注射4.5 mg/kg IgG2a同型对照抗体或抗-MHC-Ⅰ分别构建同型对照组与抗体介导TRALI模型组;小鼠腹腔单剂量注射αDR3抗体1 mg/kg 3 d后,再注射LPS 0.1 mg/kg及4.5 mg/kg抗-MHC-Ⅰ构建TRALI干预组。2)注射抗-MHC-Ⅰ后小鼠死亡或观察2 h处死小鼠取肺脏和脾脏,通过免疫病理评估肺损伤、流式细胞术检测脾脏调节性T细胞(Treg)、分别使用免疫组织化学(IHC)结合光密度定量分析分别检测小鼠肺组织Treg、M1巨噬细胞、M2巨噬细胞特异性标记物Foxp3、iNOS、CD206表达,CBA定量分析IL-6、IL-1β、TNF-α、IL-10,评估αDR3抗体对小鼠TRALI模型的干预效果。结果TRALI干预组与模型组比较,1)小鼠肺组织损伤明显减轻;2)Treg比例(%)脾脏为9.295±1.349 vs 2.257±0.610;肺脏Foxp3平均光密度0.3026±0.0526 vs 0.2302±0.0163(P<0.05);Treg来源细胞因子IL-10浓度(pg/mL)为29.52±8.885 vs 8.045±1.911(P<0.05);3)肺脏iNOS平均光密度为0.2096±0.0139 vs 0.2796±0.0452,其来源的细胞因子浓度(pg/mL)IL-6为23.22±19.35 vs 301.1±157.7、IL-1β为46.76±25.34 vs 307.6±183.8、TNF-α为45.99±14.16 vs 143.9±44.43(P<0.05);肺脏CD206平均光密度为0.2912±0.0321 vs 0.2215±0.0127,其来源的细胞因子IL-10(pg/mL)为29.52±8.885 vs 8.045±1.911(P<0.05)。结论αDR3抗体可能通过活化DR3信号通路扩增小鼠的Treg,进而Treg分泌IL-10调节M1巨噬细胞极化为M2巨噬细胞起到预防小鼠发生TRALI的作用。展开更多
AIN To study the relationship of Imp2 and DR3genes with type Ⅰ diabetes mellitus.NETHODS Imp2 genotypes and DR3 wereidentified in 68 patients with type Ⅰ diabetesmellitus(Ⅰ-DM)and 71 healthy controls.Then,Ⅰ-DM pat...AIN To study the relationship of Imp2 and DR3genes with type Ⅰ diabetes mellitus.NETHODS Imp2 genotypes and DR3 wereidentified in 68 patients with type Ⅰ diabetesmellitus(Ⅰ-DM)and 71 healthy controls.Then,Ⅰ-DM patients and controls were respectivelyallocated into DR3-positive and DR3-negativegroups.The frequencies of Imp2 and DR3 genein random subjects,and Imp2 genotypes in DR3-matched subjects were compared between Ⅰ-DMpatients and controls.At the same time,Ⅰ-DMpatients were divided into 3 groups based on theonset age of diabetics:group A≤14 years,group B 15-30 years and group C≥31 years.RESULTS The frequency of DR3 in Ⅰ-DMpatients was significantly higher than that incontrols(47% vs 21%,P【0.005),and it wassignificantly higher in group A than that in groupB+C(70% vs 36%,x^2=7.07,P【0.01).Therewas a significant difference among groups withdifferent onset age of diabetics(x^2=8.19,rp=0.33,P【0.05).In random subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(43% vs 61%,P【0.05)and Imp2.R/Hhigher(53% vs 28%,P【0.05)than that incontrols,and there was no significant differenceamong groups with different onset age ofdiabetics.In DR3-positive subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(47% vs 87%,P【0.05)and Imp2-R/H higher(47% vs 13%,P【0.05)than that incontrols.In DR3-negative subjects,thefrequency of Imp2.R/H in Ⅰ-DM patients washigher than that in controls(58% vs 32%,P【0.01),but the frequency of Imp2-R/R and Imp2H/H was not significantly different betweenthese two groups.CONCLUSION DR3 gene may be one of thesusceptible genes of Ⅰ-DM,and significantlyrelated to the onset age of diabetics,and thepersons with DR3 may have an younger onsetage of diabeteS.The Imp2-R/R may be theprotective genotype of Ⅰ-DM,and Imp2-R/H thesusceptible genotype.These were not affectedby DR3 gene.Imp-2 genotypes were not relatedwith the onset age of diabetics.展开更多
As a bar-spiral galaxy,our Milky Way(MW)is quite active chemically and dynamically.Among our MW stars,is it possible to know the evolution of each star,in order to accurately study the MW formation and evolution?Recen...As a bar-spiral galaxy,our Milky Way(MW)is quite active chemically and dynamically.Among our MW stars,is it possible to know the evolution of each star,in order to accurately study the MW formation and evolution?Recently,chemodynamics scholars try to understand the stellar and MW evolution history using both chemical and dynamic information.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:82074092),Natural Science Foundation of Guangdong Province,China(Grant No.:2021A1515012219)Guangzhou University of Chinese Medicine“Double First-Class”and High-level University Discipline Collaborative Innovation Team Project,China(Grant No.:2021xk81) and Graduate Research Innovation Project of Guangzhou University of Chinese Medicine,China.
文摘Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.
文摘目的探索死亡受体3(DR3)受体激动剂(αDR3)抗体活化DR3信号通路干预抗体-介导输血相关急性肺损伤(TRALI)的有效性及可能机制。方法1)8~10周龄Balb/c小鼠40只随机均分为正常组、同型对照组、模型组、干预组;正常组不做任何处理;小鼠腹腔注射脂多糖(LPS)0.1 mg/kg及尾静脉注射4.5 mg/kg IgG2a同型对照抗体或抗-MHC-Ⅰ分别构建同型对照组与抗体介导TRALI模型组;小鼠腹腔单剂量注射αDR3抗体1 mg/kg 3 d后,再注射LPS 0.1 mg/kg及4.5 mg/kg抗-MHC-Ⅰ构建TRALI干预组。2)注射抗-MHC-Ⅰ后小鼠死亡或观察2 h处死小鼠取肺脏和脾脏,通过免疫病理评估肺损伤、流式细胞术检测脾脏调节性T细胞(Treg)、分别使用免疫组织化学(IHC)结合光密度定量分析分别检测小鼠肺组织Treg、M1巨噬细胞、M2巨噬细胞特异性标记物Foxp3、iNOS、CD206表达,CBA定量分析IL-6、IL-1β、TNF-α、IL-10,评估αDR3抗体对小鼠TRALI模型的干预效果。结果TRALI干预组与模型组比较,1)小鼠肺组织损伤明显减轻;2)Treg比例(%)脾脏为9.295±1.349 vs 2.257±0.610;肺脏Foxp3平均光密度0.3026±0.0526 vs 0.2302±0.0163(P<0.05);Treg来源细胞因子IL-10浓度(pg/mL)为29.52±8.885 vs 8.045±1.911(P<0.05);3)肺脏iNOS平均光密度为0.2096±0.0139 vs 0.2796±0.0452,其来源的细胞因子浓度(pg/mL)IL-6为23.22±19.35 vs 301.1±157.7、IL-1β为46.76±25.34 vs 307.6±183.8、TNF-α为45.99±14.16 vs 143.9±44.43(P<0.05);肺脏CD206平均光密度为0.2912±0.0321 vs 0.2215±0.0127,其来源的细胞因子IL-10(pg/mL)为29.52±8.885 vs 8.045±1.911(P<0.05)。结论αDR3抗体可能通过活化DR3信号通路扩增小鼠的Treg,进而Treg分泌IL-10调节M1巨噬细胞极化为M2巨噬细胞起到预防小鼠发生TRALI的作用。
文摘AIN To study the relationship of Imp2 and DR3genes with type Ⅰ diabetes mellitus.NETHODS Imp2 genotypes and DR3 wereidentified in 68 patients with type Ⅰ diabetesmellitus(Ⅰ-DM)and 71 healthy controls.Then,Ⅰ-DM patients and controls were respectivelyallocated into DR3-positive and DR3-negativegroups.The frequencies of Imp2 and DR3 genein random subjects,and Imp2 genotypes in DR3-matched subjects were compared between Ⅰ-DMpatients and controls.At the same time,Ⅰ-DMpatients were divided into 3 groups based on theonset age of diabetics:group A≤14 years,group B 15-30 years and group C≥31 years.RESULTS The frequency of DR3 in Ⅰ-DMpatients was significantly higher than that incontrols(47% vs 21%,P【0.005),and it wassignificantly higher in group A than that in groupB+C(70% vs 36%,x^2=7.07,P【0.01).Therewas a significant difference among groups withdifferent onset age of diabetics(x^2=8.19,rp=0.33,P【0.05).In random subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(43% vs 61%,P【0.05)and Imp2.R/Hhigher(53% vs 28%,P【0.05)than that incontrols,and there was no significant differenceamong groups with different onset age ofdiabetics.In DR3-positive subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(47% vs 87%,P【0.05)and Imp2-R/H higher(47% vs 13%,P【0.05)than that incontrols.In DR3-negative subjects,thefrequency of Imp2.R/H in Ⅰ-DM patients washigher than that in controls(58% vs 32%,P【0.01),but the frequency of Imp2-R/R and Imp2H/H was not significantly different betweenthese two groups.CONCLUSION DR3 gene may be one of thesusceptible genes of Ⅰ-DM,and significantlyrelated to the onset age of diabetics,and thepersons with DR3 may have an younger onsetage of diabeteS.The Imp2-R/R may be theprotective genotype of Ⅰ-DM,and Imp2-R/H thesusceptible genotype.These were not affectedby DR3 gene.Imp-2 genotypes were not relatedwith the onset age of diabetics.
文摘As a bar-spiral galaxy,our Milky Way(MW)is quite active chemically and dynamically.Among our MW stars,is it possible to know the evolution of each star,in order to accurately study the MW formation and evolution?Recently,chemodynamics scholars try to understand the stellar and MW evolution history using both chemical and dynamic information.
