人们对稀土药用的兴趣普遍增加。最近Chemical Society Reviews在2006年第6期刊登了镧系元素药用研究专刊,专门介绍稀土药用研究的现状。针对该专刊和稀土药用研究的现状,作者讨论了稀土化合物药用研究的发展动向,特别讨论了需要解决的...人们对稀土药用的兴趣普遍增加。最近Chemical Society Reviews在2006年第6期刊登了镧系元素药用研究专刊,专门介绍稀土药用研究的现状。针对该专刊和稀土药用研究的现状,作者讨论了稀土化合物药用研究的发展动向,特别讨论了需要解决的关键基础问题。从新药研究模式的转变得到启发,提出如何把负面生物效应转化为药理作用,如何从干预细胞信号网络入手进行研究,如何处理活性与毒副作用的关系,以及药物合理设计的策略等。展开更多
In order to prepare calcium phosphate-based material with nano-structure and bioactivity,cationic hexadecyltrimethy1-ammonium bromide and amionic dodecyl sulfonate were used as the amphiphipile to form a liquid crysta...In order to prepare calcium phosphate-based material with nano-structure and bioactivity,cationic hexadecyltrimethy1-ammonium bromide and amionic dodecyl sulfonate were used as the amphiphipile to form a liquid crystal templete.Phosphate mineralization was induced and controlled by liquid crystal.The products,characterized by SEM,IR and X-ray diffraction analysis,are composed of liquid crystal.and HAP.These results show that the liquid crystal can be used to control calcium phosphate minerialization for the biomimetic minerials materials with various nano-structure.Product showed biological affinity to the osteogensis cell.展开更多
稀土在工业、医药领域、基础研究以及在我国的广泛农用引起了人们对其生物效应机理以及可能毒性的关注.在稀土生物学效应机理及毒性的研究中,无论是在动物水平还是细胞层次,引起生物学效应的稀土物种都是一个关键问题,一直存在争议.本...稀土在工业、医药领域、基础研究以及在我国的广泛农用引起了人们对其生物效应机理以及可能毒性的关注.在稀土生物学效应机理及毒性的研究中,无论是在动物水平还是细胞层次,引起生物学效应的稀土物种都是一个关键问题,一直存在争议.本文对以动物、细胞为模型的生物效应研究中的实验条件进行分析,对生理条件下引起稀土生物学效应的可能物种提出"稀土离子池"(rare earth ion pool)模型,并对其引起生物学效应的活性物种以及与细胞膜相互作用的方式进行了探讨,以期为阐明复杂生物学体系中稀土化合物的作用机制提供思路.展开更多
Chemotherapy and chemoprevention have been two of the most important means to control cancer incidence and mortality, and the cellular defensive machinery against oxidative/electrophilic stresses plays significant rol...Chemotherapy and chemoprevention have been two of the most important means to control cancer incidence and mortality, and the cellular defensive machinery against oxidative/electrophilic stresses plays significant roles in both means. This defensive system is composed of cytoprotective enzymes that metabolize and eliminate oxidative/electrophitic species. The transcription factor nuclear factor erythroid 2-related factor 2 （Nrf2） controls the basal and inducible expression of many cytoprotective genes, and plays a pivotal role in coordinating cellular defensive responses. Under basal conditions, the activity of Nrf2 is inhibited by binding to Kelch-like ECH-associated protein 1 （Keap 1）, which is capable of sensing oxidative/electrophilic signals. Upon oxidative/electrophilic stresses, the binding of Nrf2 to Keapl is disrupted, leading to activation of Nrf2 and induction of cytoprotective enzymes. Thus, Nrf2 has emerged as an important target of chemopreventive drugs. However, activation of Nrf2 could lead to very different outcomes depending on the cellular context. The indiscriminative protective effects of Nrf2 lead to its undesired functions in carcinogenesis and chemoresistance of cancer cells. Activation of Nrf2 provides neoplastic cells with growth advantages and protects cancer cells from chemotherapeutic drugs, resulting in poor clinical outcomes. In this means, inhibitors of Nrf2 signaling can enhance the efficacy of chemotherapeutic drugs and deserve further development. A better understanding of the regulation and functions of Nrf2 would be helpful for researches in both chemoprevention and chemotherapy of cancer.展开更多
The aim of this study was to evaluate the protective effect of thalidomide derivative ZSN-12 on acute lung injury induced by oleic acid in mice, and to investigate the possible mechanisms. The results showed that ZSN-...The aim of this study was to evaluate the protective effect of thalidomide derivative ZSN-12 on acute lung injury induced by oleic acid in mice, and to investigate the possible mechanisms. The results showed that ZSN-12 （200 mg/kg） markedly improved the pathological changes of acute lung injury. The proportion of polymorphonuclear neutrophils （PMN） was reduced by 48% （P〈0.01） and the content of nitric oxide （NO） in bronchoalveolar lavage fluid （BALF） was decreased by 33% （P〈0.05）. ZSN-12 produced significant anti-inflammatory effects in the models of xylene induced ear edema and carrageenan induced paw edema, in which ZSN-12 inhibited ear edema and paw swelling in a dose-dependent manner. The inhibition rates by ZSN-12 dosed at 200, 100, 50 mg/kg were 62%, 43%, and 30% in ear edema, respectively and 60%, 47%, and 33% in paw edema, respectively, at 3 h. Meanwhile, ZSN-12 （10, 5, 1 μmol/L） significantly restrained the ConA-induced T lymphocyte proliferation, with the inhibition rates of 33%, 30% and 22%, respectively （P〈0.01）. In conclusion, the present study showed that administration of thalidomide derivative ZSN-12 exerted significant protective effect in acute lung injury induced by oleic acid in mice, which may be related to its anti-inflammation effect. ZSN-12 inhibited the effusion of PMN, reduced the release of NO, and suppressed the proliferation of T lymphocyte.展开更多
Compound YSY-01A, a recently synthesized proteasome inhibitor, has shown potent growth-inhibitory effect on tumor cells in previous researches. However, the mechanism of its inhibitory effects, especially on cell cycl...Compound YSY-01A, a recently synthesized proteasome inhibitor, has shown potent growth-inhibitory effect on tumor cells in previous researches. However, the mechanism of its inhibitory effects, especially on cell cycle, remains largely unclear. This study aimed to evaluate the correlation between cell cycle arrest effect of YSY-01A and its anti-cancer effect, and to probe the possible molecular mechanisms for its effects on human ovarian cancer SK-OV-3 cells. The results suggested that YSY-01A significantly （P〈0.05） inhibited cellular proliferation of SK-OV-3 cells in a concentration-dependent and time-dependent manner. Furthermore, YSY-01A induced a G2/M cell cycle arrest of SK-OV-3 cells. Further investigation revealed that YSY-01A significantly （P〈0.05） changed the expression levels of a series of cell cycle related protein, such as cyclin B1, cdc2, and p-cdc2 （T14）. Meanwhile, YSY-01A could inhibit the TNF-a-induced NF-kB nuclear translocation and lead to the increase of 1kBa as well as the decrease of IKK and Gadd45a In conclusion, YSY-01A showed remarkable anti-cancer activity on SK-OV-3 cells, and its molecular mechanisms were related to G2/M cell cycle arrest.展开更多
Caffeic acid phenethyl ester （CAPE）, the main biologically active component of propolis, has been successfully synthesized from caffeic acid and β-bromoethylbenzene catalyzed by Na2CO3 in a mixed solvent of HMPA-CH...Caffeic acid phenethyl ester （CAPE）, the main biologically active component of propolis, has been successfully synthesized from caffeic acid and β-bromoethylbenzene catalyzed by Na2CO3 in a mixed solvent of HMPA-CH3CN. To better understand the struc^re-activity relationship of CAPE, phenylethyl-monobenzoylcinnamate and phenylethyl-dibenzoylcinnamate were prepared. Meanwhile, the structure of phenylethyl-monobenzoylcinnamate was confirmed by single-crystal X-ray diffiaction.展开更多
Hematological toxicity （bone marrow suppression） is the most common dose-limiting adverse effect of chemotherapies. The nuclear factor erythroid 2-related factor 2 （Nrf2） is a pivotal coordinator of cellular defen...Hematological toxicity （bone marrow suppression） is the most common dose-limiting adverse effect of chemotherapies. The nuclear factor erythroid 2-related factor 2 （Nrf2） is a pivotal coordinator of cellular defensive responses against chemical insults in many tissues including bone marrow. In the present study, the effects of tert-butylhydroquinone （tBHQ） on the expression of Nrf2-regulated genes in peripheral blood cells and cyclophosphamide （CTX）-induced hematotoxicity in mice were investigated. CTX induced apoptosis of peripheral blood nucleated cells and leukopenia in mice, accompanied by mobilization of bone marrow hematopoietic cells, tBHQ treatment induced the expression of Nrf2-regulated genes such as heine oxygenase 1 （HO1） and glutamate-cysteine ligase catalytic subtmit （GCLC） in RAW264.7 mouse macrophage cells and peripheral blood cells both in vitro and in vivo. Interestingly, pretreatment with tBHQ alleviated CTX-induced mouse peripheral blood cell apoptosis and leukopenia in vivo, indicating possible involvement of Nrf2 in the protection against CTX-induced hematotoxicity. This study provides new information on the chemotherapy-induced hematotoxicity, and suggests Nrf2 could serve as a target for the development of chemoprotectants against hematotoxicity.展开更多
Compound SLXM-2, a derivative of cyclophosphamide （CTX）, has shown potent growth-inhibitory effect on tumor cells with low toxicity in previous studies. However, the mechanism of its anti-tumor effect, especially on...Compound SLXM-2, a derivative of cyclophosphamide （CTX）, has shown potent growth-inhibitory effect on tumor cells with low toxicity in previous studies. However, the mechanism of its anti-tumor effect, especially on DNA damage, remains largely unclear. This study investigated the effect of SLXM-2 on the survival time of mice transplanted with the ascitie fluid-type hepatocarcinoma 22 （H22）. We also evaluated the correlation between DNA damaging effect of SLXM-2 and its anti-tumor effect, and to probe the possible molecular mechanism for its effect on H22 cells. The results suggested that SLXM-2 significantly （P〈0.05） prolonged the survival time of mice bearing the ascitic fluid-type H22. Furthermore, SLXM-2 induced DNA damage in a dose-dependent manner in H22 cells. Further investigation revealed that SLXM-2 significantly （P〈0.05） up-regulated the expression levels of a series of DNA damage-related proteins, such as γH2AX （Ser139）, p-Chkl （Ser296）, p-Chk2 （Thr68）, p-p53 （Ser15）, p-p53 （Ser20） and p21, and down-regulated the expression of p-ATR （Ser428） and p-ATM （Ser1981）. In conclusion, SLXM-2 showed a remarkable anti-tumor activity on ascitic fluid-type H22 cells, and its molecular mechanism is related to its DNA damaging effect.展开更多
As a novel proteasome inhibitor, remarkable proliferation inhibitory effect of compound YSY-01A was shown on tumor cells in previous studies. However, few studies has reported its effect on gastric cancer and related ...As a novel proteasome inhibitor, remarkable proliferation inhibitory effect of compound YSY-01A was shown on tumor cells in previous studies. However, few studies has reported its effect on gastric cancer and related mechanism. We evaluated the anti-proliferative effect of compound YSY-01A using MGC-803 cells and its anti-tumor effect using xenograft nu-BALB/c mouse model. Cell proliferation inhibition was assessed by SRB assay. Related protein expression levels were determined by Western blot assay. We observed that the compound YSY-01A had a significant proliferation inhibitory effect on MGC-803 cells in vitro. Experiment in vivo showed that the compound YSY-01A had a remarkable growth inhibitory effect on MGC-803 cells xenograft tumor when it was used either alone or in combination with the conventional chemotherapeutic agent 5-fluorouracil （5-FU）. Furthermore, YSY-01A and 5-FU had a synergistic effect on xenograft tumor. Results of molecular experiment showed that the compound YSY-01A had a remarkable inhibitory effect on TNF-c~ and IFN induced NF-KB nuclear translocation. At the same time, the compound YSY-01A could reduce the expression of IKK-~, IL-I~ and iNOS, while it significantly enhanced the expression of COX-2 in MGC-803 ceils. Taken together, compound YSY-01A had an impressive tumor inhibitory effect, and it worked in NF-KB-related pathway, suggesting that the compound YSY-01A was an effective therapeutic drug for patients with gastric cancer. Higher tumor cell growth inhibition after the treatment in a combination with 5-FU indicated that combining YSY-01A with 5-FU might be more effective for displaying tumor cell growth inhibitory effects on gastric cancer cells.展开更多
文摘人们对稀土药用的兴趣普遍增加。最近Chemical Society Reviews在2006年第6期刊登了镧系元素药用研究专刊,专门介绍稀土药用研究的现状。针对该专刊和稀土药用研究的现状,作者讨论了稀土化合物药用研究的发展动向,特别讨论了需要解决的关键基础问题。从新药研究模式的转变得到启发,提出如何把负面生物效应转化为药理作用,如何从干预细胞信号网络入手进行研究,如何处理活性与毒副作用的关系,以及药物合理设计的策略等。
文摘In order to prepare calcium phosphate-based material with nano-structure and bioactivity,cationic hexadecyltrimethy1-ammonium bromide and amionic dodecyl sulfonate were used as the amphiphipile to form a liquid crystal templete.Phosphate mineralization was induced and controlled by liquid crystal.The products,characterized by SEM,IR and X-ray diffraction analysis,are composed of liquid crystal.and HAP.These results show that the liquid crystal can be used to control calcium phosphate minerialization for the biomimetic minerials materials with various nano-structure.Product showed biological affinity to the osteogensis cell.
文摘稀土在工业、医药领域、基础研究以及在我国的广泛农用引起了人们对其生物效应机理以及可能毒性的关注.在稀土生物学效应机理及毒性的研究中,无论是在动物水平还是细胞层次,引起生物学效应的稀土物种都是一个关键问题,一直存在争议.本文对以动物、细胞为模型的生物效应研究中的实验条件进行分析,对生理条件下引起稀土生物学效应的可能物种提出"稀土离子池"(rare earth ion pool)模型,并对其引起生物学效应的活性物种以及与细胞膜相互作用的方式进行了探讨,以期为阐明复杂生物学体系中稀土化合物的作用机制提供思路.
基金Ministry of Science and Technology of China (The National Basic research Program of China, Grant No. 2009CB526509)supported by Peking University Health Science Center (bmu2009138-121)
文摘Chemotherapy and chemoprevention have been two of the most important means to control cancer incidence and mortality, and the cellular defensive machinery against oxidative/electrophilic stresses plays significant roles in both means. This defensive system is composed of cytoprotective enzymes that metabolize and eliminate oxidative/electrophitic species. The transcription factor nuclear factor erythroid 2-related factor 2 （Nrf2） controls the basal and inducible expression of many cytoprotective genes, and plays a pivotal role in coordinating cellular defensive responses. Under basal conditions, the activity of Nrf2 is inhibited by binding to Kelch-like ECH-associated protein 1 （Keap 1）, which is capable of sensing oxidative/electrophilic signals. Upon oxidative/electrophilic stresses, the binding of Nrf2 to Keapl is disrupted, leading to activation of Nrf2 and induction of cytoprotective enzymes. Thus, Nrf2 has emerged as an important target of chemopreventive drugs. However, activation of Nrf2 could lead to very different outcomes depending on the cellular context. The indiscriminative protective effects of Nrf2 lead to its undesired functions in carcinogenesis and chemoresistance of cancer cells. Activation of Nrf2 provides neoplastic cells with growth advantages and protects cancer cells from chemotherapeutic drugs, resulting in poor clinical outcomes. In this means, inhibitors of Nrf2 signaling can enhance the efficacy of chemotherapeutic drugs and deserve further development. A better understanding of the regulation and functions of Nrf2 would be helpful for researches in both chemoprevention and chemotherapy of cancer.
文摘The aim of this study was to evaluate the protective effect of thalidomide derivative ZSN-12 on acute lung injury induced by oleic acid in mice, and to investigate the possible mechanisms. The results showed that ZSN-12 （200 mg/kg） markedly improved the pathological changes of acute lung injury. The proportion of polymorphonuclear neutrophils （PMN） was reduced by 48% （P〈0.01） and the content of nitric oxide （NO） in bronchoalveolar lavage fluid （BALF） was decreased by 33% （P〈0.05）. ZSN-12 produced significant anti-inflammatory effects in the models of xylene induced ear edema and carrageenan induced paw edema, in which ZSN-12 inhibited ear edema and paw swelling in a dose-dependent manner. The inhibition rates by ZSN-12 dosed at 200, 100, 50 mg/kg were 62%, 43%, and 30% in ear edema, respectively and 60%, 47%, and 33% in paw edema, respectively, at 3 h. Meanwhile, ZSN-12 （10, 5, 1 μmol/L） significantly restrained the ConA-induced T lymphocyte proliferation, with the inhibition rates of 33%, 30% and 22%, respectively （P〈0.01）. In conclusion, the present study showed that administration of thalidomide derivative ZSN-12 exerted significant protective effect in acute lung injury induced by oleic acid in mice, which may be related to its anti-inflammation effect. ZSN-12 inhibited the effusion of PMN, reduced the release of NO, and suppressed the proliferation of T lymphocyte.
基金Eleventh Five-Year Plan for National Science and Technology Major Project(Grant No.2009ZX0930-010)National Science Foundation of China(Grant No.81172915)a grant from Major New Drugs Research and Development Platform of Peking University(Grant No.2009ZX09301-010)
文摘Compound YSY-01A, a recently synthesized proteasome inhibitor, has shown potent growth-inhibitory effect on tumor cells in previous researches. However, the mechanism of its inhibitory effects, especially on cell cycle, remains largely unclear. This study aimed to evaluate the correlation between cell cycle arrest effect of YSY-01A and its anti-cancer effect, and to probe the possible molecular mechanisms for its effects on human ovarian cancer SK-OV-3 cells. The results suggested that YSY-01A significantly （P〈0.05） inhibited cellular proliferation of SK-OV-3 cells in a concentration-dependent and time-dependent manner. Furthermore, YSY-01A induced a G2/M cell cycle arrest of SK-OV-3 cells. Further investigation revealed that YSY-01A significantly （P〈0.05） changed the expression levels of a series of cell cycle related protein, such as cyclin B1, cdc2, and p-cdc2 （T14）. Meanwhile, YSY-01A could inhibit the TNF-a-induced NF-kB nuclear translocation and lead to the increase of 1kBa as well as the decrease of IKK and Gadd45a In conclusion, YSY-01A showed remarkable anti-cancer activity on SK-OV-3 cells, and its molecular mechanisms were related to G2/M cell cycle arrest.
基金National Natural Science Foundation of China (Grant No. 20672008, 20972011)
文摘Caffeic acid phenethyl ester （CAPE）, the main biologically active component of propolis, has been successfully synthesized from caffeic acid and β-bromoethylbenzene catalyzed by Na2CO3 in a mixed solvent of HMPA-CH3CN. To better understand the struc^re-activity relationship of CAPE, phenylethyl-monobenzoylcinnamate and phenylethyl-dibenzoylcinnamate were prepared. Meanwhile, the structure of phenylethyl-monobenzoylcinnamate was confirmed by single-crystal X-ray diffiaction.
基金National Natural Science Foundation(Grant No.81272468 and 21001011)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,Ministry of Education
文摘Hematological toxicity （bone marrow suppression） is the most common dose-limiting adverse effect of chemotherapies. The nuclear factor erythroid 2-related factor 2 （Nrf2） is a pivotal coordinator of cellular defensive responses against chemical insults in many tissues including bone marrow. In the present study, the effects of tert-butylhydroquinone （tBHQ） on the expression of Nrf2-regulated genes in peripheral blood cells and cyclophosphamide （CTX）-induced hematotoxicity in mice were investigated. CTX induced apoptosis of peripheral blood nucleated cells and leukopenia in mice, accompanied by mobilization of bone marrow hematopoietic cells, tBHQ treatment induced the expression of Nrf2-regulated genes such as heine oxygenase 1 （HO1） and glutamate-cysteine ligase catalytic subtmit （GCLC） in RAW264.7 mouse macrophage cells and peripheral blood cells both in vitro and in vivo. Interestingly, pretreatment with tBHQ alleviated CTX-induced mouse peripheral blood cell apoptosis and leukopenia in vivo, indicating possible involvement of Nrf2 in the protection against CTX-induced hematotoxicity. This study provides new information on the chemotherapy-induced hematotoxicity, and suggests Nrf2 could serve as a target for the development of chemoprotectants against hematotoxicity.
基金Eleventh Five Year Plan for National Science and Technology Major Project(Grant No.2009ZX0930010)
文摘Compound SLXM-2, a derivative of cyclophosphamide （CTX）, has shown potent growth-inhibitory effect on tumor cells with low toxicity in previous studies. However, the mechanism of its anti-tumor effect, especially on DNA damage, remains largely unclear. This study investigated the effect of SLXM-2 on the survival time of mice transplanted with the ascitie fluid-type hepatocarcinoma 22 （H22）. We also evaluated the correlation between DNA damaging effect of SLXM-2 and its anti-tumor effect, and to probe the possible molecular mechanism for its effect on H22 cells. The results suggested that SLXM-2 significantly （P〈0.05） prolonged the survival time of mice bearing the ascitic fluid-type H22. Furthermore, SLXM-2 induced DNA damage in a dose-dependent manner in H22 cells. Further investigation revealed that SLXM-2 significantly （P〈0.05） up-regulated the expression levels of a series of DNA damage-related proteins, such as γH2AX （Ser139）, p-Chkl （Ser296）, p-Chk2 （Thr68）, p-p53 （Ser15）, p-p53 （Ser20） and p21, and down-regulated the expression of p-ATR （Ser428） and p-ATM （Ser1981）. In conclusion, SLXM-2 showed a remarkable anti-tumor activity on ascitic fluid-type H22 cells, and its molecular mechanism is related to its DNA damaging effect.
基金Eleventh Five-Year Plan for National Science and Technology Major Project(Grant No.2009ZX0930-010)National Science Foundation of China(Grant No.81172915)a grant from Major New Drug Research and Development Platform of PekingUniversity(Grant No.2009ZX09301-010)
文摘As a novel proteasome inhibitor, remarkable proliferation inhibitory effect of compound YSY-01A was shown on tumor cells in previous studies. However, few studies has reported its effect on gastric cancer and related mechanism. We evaluated the anti-proliferative effect of compound YSY-01A using MGC-803 cells and its anti-tumor effect using xenograft nu-BALB/c mouse model. Cell proliferation inhibition was assessed by SRB assay. Related protein expression levels were determined by Western blot assay. We observed that the compound YSY-01A had a significant proliferation inhibitory effect on MGC-803 cells in vitro. Experiment in vivo showed that the compound YSY-01A had a remarkable growth inhibitory effect on MGC-803 cells xenograft tumor when it was used either alone or in combination with the conventional chemotherapeutic agent 5-fluorouracil （5-FU）. Furthermore, YSY-01A and 5-FU had a synergistic effect on xenograft tumor. Results of molecular experiment showed that the compound YSY-01A had a remarkable inhibitory effect on TNF-c~ and IFN induced NF-KB nuclear translocation. At the same time, the compound YSY-01A could reduce the expression of IKK-~, IL-I~ and iNOS, while it significantly enhanced the expression of COX-2 in MGC-803 ceils. Taken together, compound YSY-01A had an impressive tumor inhibitory effect, and it worked in NF-KB-related pathway, suggesting that the compound YSY-01A was an effective therapeutic drug for patients with gastric cancer. Higher tumor cell growth inhibition after the treatment in a combination with 5-FU indicated that combining YSY-01A with 5-FU might be more effective for displaying tumor cell growth inhibitory effects on gastric cancer cells.
