Curcumfa phaeocaulis Valeton is used in traditional Chinese medicines for the treatment of blood-related disorders such as blood stasis and inflammation.Our previous studies have found that sesquiterpenes were mainly ...Curcumfa phaeocaulis Valeton is used in traditional Chinese medicines for the treatment of blood-related disorders such as blood stasis and inflammation.Our previous studies have found that sesquiterpenes were mainly isolated from C.wenyujin and C.phaeocaulis,while diarylheptanoids were the major compounds from C.kwangsiensis.And most of the isolated compounds exhibited remarkable展开更多
The effects of hypoxic endothelial cell conditioned medium (HECCM) on proliferation and collagen synthesis of cultured porcine pulmonary arterial smooth muscle cells (PASMCs) were studied by 3H-thymidine (3H-TdR) and ...The effects of hypoxic endothelial cell conditioned medium (HECCM) on proliferation and collagen synthesis of cultured porcine pulmonary arterial smooth muscle cells (PASMCs) were studied by 3H-thymidine (3H-TdR) and 3H-proline incorporations, image analysis for determination of DNA content and colorimetric assay using MTT, and the inhibitory effects of radix salviae miltiorrhizae (RSM) on them were also investigated. The results showed that HECCM could induce enhancement of the enzymatic activity of mitochondria, increase of the nucleic DNA content and increases of the 3H-TdR and 3H-proline incorporations in PASMCs. The 3H-proline incorporation in PASMCs cultured in HECCM was 1.83 times as much as that cultured in normoxic endothelial cell conditioned medium (NECCM). Compared with the control, Chinese herb medicine RSM could inhibit the proliferation of PASMCs cultured in HECCM and decrease the 3H-prolinc incorporation in PASMCs cultured in both HECCM and NECCM (P< 0.001). However, RSM had no ef fects on the nucleic DNA content and 3H-TdR incorporation into DNA of PASMCs cultured in NECCM. It suggests that hypoxia may stimulate the endothelia to synthesize and secrete some cytokines which can stimulate the proliferation and the synthesis of collagen of PASMCs and RSM can inhibit this process.展开更多
In this paper, quaternary 8-(1-acylethene-l-yl)-13-methylcoptisine chlorides targeting thioredoxin reductases (TrxRs) were designed to test the growth inhibitory activity against human cancer cell lines and the ef...In this paper, quaternary 8-(1-acylethene-l-yl)-13-methylcoptisine chlorides targeting thioredoxin reductases (TrxRs) were designed to test the growth inhibitory activity against human cancer cell lines and the effect on viability of the normal intestinal epithelial cell-6 (IEC-6) in vitro and to evaluate structure-activity relationship (SAR). The introduced α, β-unsaturated ketone groups at C-8 consisting of n-alkanoyls possessing five to ten carbons or aroyls or cyclohexylcarbonyl increased the tested activity against the target cancer cell lines. By and large, this type of improvement was increasingly graced by the elongation of the aliphatic chain of the n-alkanoyls in the range of less than ten carbon atoms. The relatively more polar l-acylethene-l-yls displayed no effect on improving the activity. All the explored aroyls showed significant effect on improving the activity of the target compounds against the tested cancer cell lines with no SAR being observed, The findings of this study suggested that oil]water partition coefficient of the test compounds was one of the key factors impacting the target activity against the tested cancer cell lines. At the concentration of 10 μmol/L, except for the compounds with n-all(anoyls possessing seven or more carbons or with α-naphthoyl, none of the other compounds displayed obvious cytotoxicity on normal IEC-6 cell when co-incubated. The survival rate of IEC-6 cell ranged from 75% to 100% for the noncytotoxic compounds.展开更多
T cell activation and tolerance are tightly regulated by costimulatory and coinhibitory molecules.B7 family members play a crucial role in regulating immune responses.In this study,we identified erythroid membrane-ass...T cell activation and tolerance are tightly regulated by costimulatory and coinhibitory molecules.B7 family members play a crucial role in regulating immune responses.In this study,we identified erythroid membrane-associated protein(ERMAP)as a novel T cell inhibitory molecule.ERMAP shares significant sequence and structural homology with existing B7 family members in its extracellular domain.The ERMAP protein is expressed on the cell surface of resting and activated antigen-presenting cells(APCs)and in some tumor tissues.The putative ERMAP receptor is expressed on activated CD4 and CD8 T cells and macrophages.Both mouse and human ERMAP-IgG2a Fc(ERMAP-Ig)fusion proteins inhibit T cell functions in vitro.Administration of ERMAP-Ig protein ameliorates autoimmune diseases,including experimental autoimmune encephalomyelitis and type 1 diabetes,in mice.Anti-ERMAP antibody enhances macrophage phagocytosis of cancer cells in vitro.Furthermore,administration of an anti-ERMAP antibody inhibits tumor growth in mice likely by blocking the inhibitory effects of ERMAP on T cells and macrophages.Our results suggest that therapeutic interaction with the ERMAP inhibitory pathway may represent a novel strategy for treating patients with autoimmune disease or cancer.展开更多
文摘Curcumfa phaeocaulis Valeton is used in traditional Chinese medicines for the treatment of blood-related disorders such as blood stasis and inflammation.Our previous studies have found that sesquiterpenes were mainly isolated from C.wenyujin and C.phaeocaulis,while diarylheptanoids were the major compounds from C.kwangsiensis.And most of the isolated compounds exhibited remarkable
文摘The effects of hypoxic endothelial cell conditioned medium (HECCM) on proliferation and collagen synthesis of cultured porcine pulmonary arterial smooth muscle cells (PASMCs) were studied by 3H-thymidine (3H-TdR) and 3H-proline incorporations, image analysis for determination of DNA content and colorimetric assay using MTT, and the inhibitory effects of radix salviae miltiorrhizae (RSM) on them were also investigated. The results showed that HECCM could induce enhancement of the enzymatic activity of mitochondria, increase of the nucleic DNA content and increases of the 3H-TdR and 3H-proline incorporations in PASMCs. The 3H-proline incorporation in PASMCs cultured in HECCM was 1.83 times as much as that cultured in normoxic endothelial cell conditioned medium (NECCM). Compared with the control, Chinese herb medicine RSM could inhibit the proliferation of PASMCs cultured in HECCM and decrease the 3H-prolinc incorporation in PASMCs cultured in both HECCM and NECCM (P< 0.001). However, RSM had no ef fects on the nucleic DNA content and 3H-TdR incorporation into DNA of PASMCs cultured in NECCM. It suggests that hypoxia may stimulate the endothelia to synthesize and secrete some cytokines which can stimulate the proliferation and the synthesis of collagen of PASMCs and RSM can inhibit this process.
基金supported by grants from the National Natural Science Foundation of China(No. 81373269)CAMS Innovation Fund for Medical Sciences(No. 2016-12M-1-010)National Science and Technology Project of China(No.2017ZX09305008002)
文摘In this paper, quaternary 8-(1-acylethene-l-yl)-13-methylcoptisine chlorides targeting thioredoxin reductases (TrxRs) were designed to test the growth inhibitory activity against human cancer cell lines and the effect on viability of the normal intestinal epithelial cell-6 (IEC-6) in vitro and to evaluate structure-activity relationship (SAR). The introduced α, β-unsaturated ketone groups at C-8 consisting of n-alkanoyls possessing five to ten carbons or aroyls or cyclohexylcarbonyl increased the tested activity against the target cancer cell lines. By and large, this type of improvement was increasingly graced by the elongation of the aliphatic chain of the n-alkanoyls in the range of less than ten carbon atoms. The relatively more polar l-acylethene-l-yls displayed no effect on improving the activity. All the explored aroyls showed significant effect on improving the activity of the target compounds against the tested cancer cell lines with no SAR being observed, The findings of this study suggested that oil]water partition coefficient of the test compounds was one of the key factors impacting the target activity against the tested cancer cell lines. At the concentration of 10 μmol/L, except for the compounds with n-all(anoyls possessing seven or more carbons or with α-naphthoyl, none of the other compounds displayed obvious cytotoxicity on normal IEC-6 cell when co-incubated. The survival rate of IEC-6 cell ranged from 75% to 100% for the noncytotoxic compounds.
基金This work was supported by grants from the NIH(1R01AI123131–01)the Connecticut Regenerative Medicine Research Fund(16-RMB-UCONN-02).
文摘T cell activation and tolerance are tightly regulated by costimulatory and coinhibitory molecules.B7 family members play a crucial role in regulating immune responses.In this study,we identified erythroid membrane-associated protein(ERMAP)as a novel T cell inhibitory molecule.ERMAP shares significant sequence and structural homology with existing B7 family members in its extracellular domain.The ERMAP protein is expressed on the cell surface of resting and activated antigen-presenting cells(APCs)and in some tumor tissues.The putative ERMAP receptor is expressed on activated CD4 and CD8 T cells and macrophages.Both mouse and human ERMAP-IgG2a Fc(ERMAP-Ig)fusion proteins inhibit T cell functions in vitro.Administration of ERMAP-Ig protein ameliorates autoimmune diseases,including experimental autoimmune encephalomyelitis and type 1 diabetes,in mice.Anti-ERMAP antibody enhances macrophage phagocytosis of cancer cells in vitro.Furthermore,administration of an anti-ERMAP antibody inhibits tumor growth in mice likely by blocking the inhibitory effects of ERMAP on T cells and macrophages.Our results suggest that therapeutic interaction with the ERMAP inhibitory pathway may represent a novel strategy for treating patients with autoimmune disease or cancer.