ZnO nanorods with different morphologies were fabricated through a simple reaction method. They were characterized by means of powder x-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and e...ZnO nanorods with different morphologies were fabricated through a simple reaction method. They were characterized by means of powder x-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and ener-gy-dispersive x-ray (EDX) spectroscopy. FE-SEM images have shown that the shapes of the ZnO nanorods included straight nanorods, spear-like nanorods with sawtooth-shaped surfaces and lotus root-like nanorods. XRD and EDX indicated that all the nanorods are composed of hexagonal ZnO.展开更多
Tetrandrine(Tet), the main active constituent of Stephania tetrandra root, has been demonstrated to alleviate adjuvant-induced arthritis in rats. The present study was designed to investigate the effects of Tet on the...Tetrandrine(Tet), the main active constituent of Stephania tetrandra root, has been demonstrated to alleviate adjuvant-induced arthritis in rats. The present study was designed to investigate the effects of Tet on the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes(RA-FLS) and explore the underlying mechanisms. By using cultures of primary FLS isolated from synoviums of RA patients and cell line MH7 A, Tet(0.3, 1 μmol·L-1) was proven to significantly impede migration and invasion of RA-FLS, but not cell proliferation. Tet also greatly reduced the activation and expressions of matrix degrading enzymes MMP-2/9, the expression of F-actin and the activation of FAK, which controlled the morphologic changes in migration process of FLS. To identify the key signaling pathways by which Tet exerts anti-migration effect, the specific inhibitors of multiple signaling pathways LY294002, Triciribine, SP600125, U0126, SB203580, and PDTC(against PI3 K, Akt, JNK, ERK, p38 MAPK and NF-κB-p65, respectively) were used. Among them, LY294002, Triciribine, and SP600125 were shown to obviously inhibit the migration of MH7 A cells. Consistently, Tet was able to down-regulate the activation of Akt and JNK as demonstrated by Western blotting assay. Moreover, Tet could reduce the expressions of migration-related proteins Rho GTPases Rac1, Cdc42, and Rho A in MH7 A cells. In conclusion, Tet can impede the migration and invasion of RA-FLS, which provides a plausible explanation for its protective effect on RA. The underlying mechanisms involve the reduction of the expressions of Rac1, Cdc42, and Rho A, inhibition of the activation of Akt and JNK, and subsequent down-regulation of activation and/or expressions of MMP-2/9, F-actin, and FAK.展开更多
Although the etiology of inflammatory bowel disease is still uncertain, increasing evidence indicates that the excessive activation of NLRP3 inflammasome plays a major role. Norisoboldine(NOR), an alkaloid isolated fr...Although the etiology of inflammatory bowel disease is still uncertain, increasing evidence indicates that the excessive activation of NLRP3 inflammasome plays a major role. Norisoboldine(NOR), an alkaloid isolated from Radix Linderae, has previously been demonstrated to inhibit inflammation and IL-1β production. The present study was to examine the effect of NOR on colitis and the underlying mechanism related to NLRP3 inflammasome activation. Our results showed that NOR alleviated colitis symptom in mice induced by 2, 4, 6-trinitrobenzene sulfonic acid(TNBS). Moreover, it significantly reduced expressions of cleaved IL-1β, NLRP3 and cleaved Caspase-1 but not ASC in colons of mice. In THP-1 cells, NOR suppressed the expressions of NLRP3, cleaved Caspase-1 and cleaved IL-1β but not ASC induced by lipopolysaccharide(LPS) and adenosine triphosphate(ATP). Furthermore, NOR could activate aryl hydrocarbon receptor(AhR) in THP-1 cells, inducing CYP1 A1 mR NA expression, and promoting dissociation of Ah R/HSP90 complexes, association of AhR and ARNT, Ah R nuclear translocation, XRE reporter activity and binding activity of Ah R/ARNT/XRE. Both siA hR and α-naphthoflavone(α-NF) markedly diminished the inhibition of NOR on NLRP3 inflammasome activation. In addition, NOR elevated Nrf2 level and reduced ROS level in LPS-and ATP-stimulated THP-1 cells, which was reversed by either si AhR or α-NF treatment. Finally, correlations between activation of AhR and attenuation of colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 level in colons were validated in mice with TNBS-induced colitis. Taken together, NOR ameliorated TNBS-induced colitis in mice through inhibiting NLRP3 inflammasome activation via regulating AhR/Nrf2/ROS signaling pathway.展开更多
基金Supported by the National Natural Science Foundation of China under Grant Nos.59925206,10044001 and 59972040the Foundation of the Chinese Academy of Sciences under Grant No.KY951-AI-205-05.
文摘ZnO nanorods with different morphologies were fabricated through a simple reaction method. They were characterized by means of powder x-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and ener-gy-dispersive x-ray (EDX) spectroscopy. FE-SEM images have shown that the shapes of the ZnO nanorods included straight nanorods, spear-like nanorods with sawtooth-shaped surfaces and lotus root-like nanorods. XRD and EDX indicated that all the nanorods are composed of hexagonal ZnO.
基金supported by the National Natural Science Foundation of China(No.81373426)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Tetrandrine(Tet), the main active constituent of Stephania tetrandra root, has been demonstrated to alleviate adjuvant-induced arthritis in rats. The present study was designed to investigate the effects of Tet on the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes(RA-FLS) and explore the underlying mechanisms. By using cultures of primary FLS isolated from synoviums of RA patients and cell line MH7 A, Tet(0.3, 1 μmol·L-1) was proven to significantly impede migration and invasion of RA-FLS, but not cell proliferation. Tet also greatly reduced the activation and expressions of matrix degrading enzymes MMP-2/9, the expression of F-actin and the activation of FAK, which controlled the morphologic changes in migration process of FLS. To identify the key signaling pathways by which Tet exerts anti-migration effect, the specific inhibitors of multiple signaling pathways LY294002, Triciribine, SP600125, U0126, SB203580, and PDTC(against PI3 K, Akt, JNK, ERK, p38 MAPK and NF-κB-p65, respectively) were used. Among them, LY294002, Triciribine, and SP600125 were shown to obviously inhibit the migration of MH7 A cells. Consistently, Tet was able to down-regulate the activation of Akt and JNK as demonstrated by Western blotting assay. Moreover, Tet could reduce the expressions of migration-related proteins Rho GTPases Rac1, Cdc42, and Rho A in MH7 A cells. In conclusion, Tet can impede the migration and invasion of RA-FLS, which provides a plausible explanation for its protective effect on RA. The underlying mechanisms involve the reduction of the expressions of Rac1, Cdc42, and Rho A, inhibition of the activation of Akt and JNK, and subsequent down-regulation of activation and/or expressions of MMP-2/9, F-actin, and FAK.
基金supported by the Natural Science Foundation of Jiangsu Province of China(No.BK20140662)partially supported by the National Natural Science Foundation of China(No.81503319)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Although the etiology of inflammatory bowel disease is still uncertain, increasing evidence indicates that the excessive activation of NLRP3 inflammasome plays a major role. Norisoboldine(NOR), an alkaloid isolated from Radix Linderae, has previously been demonstrated to inhibit inflammation and IL-1β production. The present study was to examine the effect of NOR on colitis and the underlying mechanism related to NLRP3 inflammasome activation. Our results showed that NOR alleviated colitis symptom in mice induced by 2, 4, 6-trinitrobenzene sulfonic acid(TNBS). Moreover, it significantly reduced expressions of cleaved IL-1β, NLRP3 and cleaved Caspase-1 but not ASC in colons of mice. In THP-1 cells, NOR suppressed the expressions of NLRP3, cleaved Caspase-1 and cleaved IL-1β but not ASC induced by lipopolysaccharide(LPS) and adenosine triphosphate(ATP). Furthermore, NOR could activate aryl hydrocarbon receptor(AhR) in THP-1 cells, inducing CYP1 A1 mR NA expression, and promoting dissociation of Ah R/HSP90 complexes, association of AhR and ARNT, Ah R nuclear translocation, XRE reporter activity and binding activity of Ah R/ARNT/XRE. Both siA hR and α-naphthoflavone(α-NF) markedly diminished the inhibition of NOR on NLRP3 inflammasome activation. In addition, NOR elevated Nrf2 level and reduced ROS level in LPS-and ATP-stimulated THP-1 cells, which was reversed by either si AhR or α-NF treatment. Finally, correlations between activation of AhR and attenuation of colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 level in colons were validated in mice with TNBS-induced colitis. Taken together, NOR ameliorated TNBS-induced colitis in mice through inhibiting NLRP3 inflammasome activation via regulating AhR/Nrf2/ROS signaling pathway.
