BACKGROUND Regarding when to treat gastric cancer and ovarian metastasis(GCOM)and whether to have metastatic resection surgery,there is presently debate on a global scale.The purpose of this research is to examine,in ...BACKGROUND Regarding when to treat gastric cancer and ovarian metastasis(GCOM)and whether to have metastatic resection surgery,there is presently debate on a global scale.The purpose of this research is to examine,in real-world patients with GCOM,the survival rates and efficacy of metastatic vs non-metastasized resection.AIM To investigate the survival time and efficacy of metastatic surgery and neoadjuvant therapy in patients with GCOM.METHODS This study retrospectively analyzed the data of 41 GCOM patients admitted to Zhejiang Provincial People’s Hospital from June 2009 to July 2023.The diagnosis of all patients was confirmed by pathology.The primary study endpoints included overall survival(OS),ovarian survival,OS after surgery(OSAS),disease-free survival(DFS),differences in efficacy.RESULTS This study had 41 patients in total.The surgical group(n=27)exhibited significantly longer median OS(mOS)and median overall months(mOM)compared to the nonoperative group(n=14)(mOS:23.0 vs 6.9 months,P=0.015;mOM:18.3 vs 3.8 months,P=0.001).However,there were no significant differences observed in mOS,mOM,median OSAS(mOSAS),and median DFS(mDFS)between patients in the surgical resection plus neoadjuvant therapy group(n=11)and those who surgical resection without neoadjuvant therapy group(n=16)(mOS:26.1 months vs 21.8 months,P=0.189;mOM:19.8 vs 15.2 months,P=0.424;mOSAS:13.9 vs 8.7 months,P=0.661,mDFS:5.1 vs 8.2 months,P=0.589).CONCLUSION Compared to the non-surgical group,the surgical group’s survival duration and efficacy are noticeably longer.The efficacy and survival time of the direct surgery group and the neoadjuvant therapy group did not differ significantly.展开更多
Nagilactone E(NLE),a natural product with anticancer activities,is isolated from Podocarpus nagi.In this study,we reported that NLE increased programmed death ligand 1(PD-L1)expressions at both protein and mRNA levels...Nagilactone E(NLE),a natural product with anticancer activities,is isolated from Podocarpus nagi.In this study,we reported that NLE increased programmed death ligand 1(PD-L1)expressions at both protein and mRNA levels in human lung cancer cells,and enhanced its localization on the cell membrane.Mechanistically,NLE increased the phosphorylation and expression of cJun,and promoted the localization of c-Jun in the nucleus,while silencing of c-Jun by small interfering RNA(siRNA)reduced NLEinduced PD-L1.Further study showed that NLE activated the c-Jun N-terminal kinases(JNK),the upstream of c-Jun,and its inhibitor SP600125 reversed the NLE-increased PD-L1.Moreover,NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface.In summary,NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis,which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.展开更多
Pharmaceutical research has focused on the discovery and development of anticancer drugs. Clinical application of chemotherapy drugs is limited due to their severe side effects. In this regard, new naturally occurring...Pharmaceutical research has focused on the discovery and development of anticancer drugs. Clinical application of chemotherapy drugs is limited due to their severe side effects. In this regard, new naturally occurring anticancer drugs have gained increasing attention because of their potential effectiveness and safety. Fruits and vegetables are promising sources of anticancer remedy. Clausena(family Rutaceae) is a genus of flowering plants and includes several kinds of edible fruits and vegetables. Phytochemical and pharmacological studies show that carbazole alkaloids and coumarins from Clausena plants exhibit anticancer activity. This review summarizes research progresses made in the anticancer properties of plants belonging to Clausena; in particular, compounds with direct cytotoxicity, cell cycle arrest, apoptosis induction, and immune potentiation effects are discussed. This review reveals the potential use of plants from Clausena in preventing and treating cancer and provides a basis for development of relevant therapeutic agents.展开更多
Background:High proliferative rate of cancer cells requires autophagy to maintain nutrient supply and intracellular homeostasis.As a result,impairing autophagic flux could be a novel strategy of cancer therapy.Aims an...Background:High proliferative rate of cancer cells requires autophagy to maintain nutrient supply and intracellular homeostasis.As a result,impairing autophagic flux could be a novel strategy of cancer therapy.Aims and Objectives:In this study,the mechanism of a xanthone derivative isolated from Garcinia mangostana,garcinone E(GE),was investigated.Materials and Methods:Fluorescence assay was used to observe the accumulation and location of autophagosome and lysosome.Flow cytometry with Lyso-tracker red,MDC,and AO staining were applied to evaluate the lysosome accumulation and cellular acidity.Western blot and RT-qPCR were performed to evaluate the protein and mRNA levels,respectively.Results:GE could cause enhancement of LC3 II and p62 and the accumulation of autophagosome and lysosome.Meanwhile,it limited the protein level of Rab7,increased lysosomal pH,and inhibited the maturation of lysosomal hydrolases such as Cathepsin L,therefore blockaded the fusion of autophagosome and lysosome.Moreover,GE acted as a TFEB modulator by downregulating its protein level,which might contribute to autophagy dysfunction in ovarian cancer cells.Conclusions:GE interfered autophagosome–lysosome fusion in cancer cells,which demonstrated its application as an autophagy regulator and a potential therapeutic agent.展开更多
肥胖或超重已经成为现代社会严重的流行性健康问题,是导致糖尿病、脂代谢紊乱等多种代谢疾病的危险因素之一,动物实验是临床前实验研究的重要组成部分,是研究疾病、药理作用的重要方法。本研究目的是研究中链甘油三酯(Medium-Chain Trig...肥胖或超重已经成为现代社会严重的流行性健康问题,是导致糖尿病、脂代谢紊乱等多种代谢疾病的危险因素之一,动物实验是临床前实验研究的重要组成部分,是研究疾病、药理作用的重要方法。本研究目的是研究中链甘油三酯(Medium-Chain Triglycerides,MCT)对大鼠和小鼠体重影响。检索了PUBMED,EMBASE和WEB of SCIENCE三个数据库相关文献,比较分析了含中链甘油三酯或椰子油饮食干预与长链甘油三酯饮食对大鼠和小鼠体重的影响,数据以标准化平均差(SMD)或加权平均差(MD)和95%置信区间(CI)表示。结果发现,中链甘油三酯的干预可以减轻大鼠[SMD,-0.76(95%CI:-1.16,-0.37)]或小鼠[MD,-1.39(95%CI:-2.23,-0.54)]的体重。因此,中链甘油三酯的干预对大鼠和小鼠有一定的改善体重的作用。展开更多
OBJECTIVE Interleukin(IL)-1β,one of the principal inflammatory cytokines mainly secreted by monocytes and macrophages,is produced by cleavage of the inactive pro-IL^(-1)βprecursor by caspase-1 via the NLRP3 inflamma...OBJECTIVE Interleukin(IL)-1β,one of the principal inflammatory cytokines mainly secreted by monocytes and macrophages,is produced by cleavage of the inactive pro-IL^(-1)βprecursor by caspase-1 via the NLRP3 inflammasome complex.The fruits of Garcinia cambogia(Clusiaceae)are widely developed as health products for anti-obese purpose.14-deoxygarcinol(DOG)is a polyisoprenylated benzophenone from the fruits of G.cambogia,which showed potent anti-inflammatory effect in our previous study.The objective of this study was to explore the anti-inflammatory mechanism of DOG and its roles in alleviating adipose tissue inflammation and insulin resistance.METHODS The anti-inflammatory effect of DOG was evaluated on LPS plus nigericin-induced THP-1 macrophages.The expression of NLRP3 inflammasome complex proteins was analyzed by Western blotting,immunofluorescence staining and co-immunoprecipitation.The pro-inflammatory cytokines levels were determined by ELISA kits.RESULTS DOG increased the expression of Sirtuin 2(SIRT2)deacetylase and enhanced its deacetylating activity to suppress the NLRP3 inflammasome activation and IL^(-1)βsecretion in THP-1 macrophages.Moreover,DOG attenuated macrophage conditioned medium-induced inflammatory responses in adipocytes and blocked THP-1 macrophages migration towards 3T3-L1 adipocytes.CONCLUSION DOG attenuated the inflammatory crosstalk between macrophages and adipocytes through SIRT2-mediated NLRP3 inflammasome inhibition,which might be used for the treatment of adipose tissue inflammation-related metabolic disorders.展开更多
文摘BACKGROUND Regarding when to treat gastric cancer and ovarian metastasis(GCOM)and whether to have metastatic resection surgery,there is presently debate on a global scale.The purpose of this research is to examine,in real-world patients with GCOM,the survival rates and efficacy of metastatic vs non-metastasized resection.AIM To investigate the survival time and efficacy of metastatic surgery and neoadjuvant therapy in patients with GCOM.METHODS This study retrospectively analyzed the data of 41 GCOM patients admitted to Zhejiang Provincial People’s Hospital from June 2009 to July 2023.The diagnosis of all patients was confirmed by pathology.The primary study endpoints included overall survival(OS),ovarian survival,OS after surgery(OSAS),disease-free survival(DFS),differences in efficacy.RESULTS This study had 41 patients in total.The surgical group(n=27)exhibited significantly longer median OS(mOS)and median overall months(mOM)compared to the nonoperative group(n=14)(mOS:23.0 vs 6.9 months,P=0.015;mOM:18.3 vs 3.8 months,P=0.001).However,there were no significant differences observed in mOS,mOM,median OSAS(mOSAS),and median DFS(mDFS)between patients in the surgical resection plus neoadjuvant therapy group(n=11)and those who surgical resection without neoadjuvant therapy group(n=16)(mOS:26.1 months vs 21.8 months,P=0.189;mOM:19.8 vs 15.2 months,P=0.424;mOSAS:13.9 vs 8.7 months,P=0.661,mDFS:5.1 vs 8.2 months,P=0.589).CONCLUSION Compared to the non-surgical group,the surgical group’s survival duration and efficacy are noticeably longer.The efficacy and survival time of the direct surgery group and the neoadjuvant therapy group did not differ significantly.
基金supported by the Science and Technology Development Fund,Macao SAR(No.176/2017/A3)University of Macao(No.MYRG2018-00165-ICMS/CPG.020-00016-ICMS/MYRG2017-00109-ICMS)。
文摘Nagilactone E(NLE),a natural product with anticancer activities,is isolated from Podocarpus nagi.In this study,we reported that NLE increased programmed death ligand 1(PD-L1)expressions at both protein and mRNA levels in human lung cancer cells,and enhanced its localization on the cell membrane.Mechanistically,NLE increased the phosphorylation and expression of cJun,and promoted the localization of c-Jun in the nucleus,while silencing of c-Jun by small interfering RNA(siRNA)reduced NLEinduced PD-L1.Further study showed that NLE activated the c-Jun N-terminal kinases(JNK),the upstream of c-Jun,and its inhibitor SP600125 reversed the NLE-increased PD-L1.Moreover,NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface.In summary,NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis,which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.
基金supported by the Macao Science and Technology Development Fund(No.120/2013/A3)the Research Fund of University of Macao(Nos.MYRG2015-00153-ICMS-QRCM and MYRG2017-00109-ICMS)
文摘Pharmaceutical research has focused on the discovery and development of anticancer drugs. Clinical application of chemotherapy drugs is limited due to their severe side effects. In this regard, new naturally occurring anticancer drugs have gained increasing attention because of their potential effectiveness and safety. Fruits and vegetables are promising sources of anticancer remedy. Clausena(family Rutaceae) is a genus of flowering plants and includes several kinds of edible fruits and vegetables. Phytochemical and pharmacological studies show that carbazole alkaloids and coumarins from Clausena plants exhibit anticancer activity. This review summarizes research progresses made in the anticancer properties of plants belonging to Clausena; in particular, compounds with direct cytotoxicity, cell cycle arrest, apoptosis induction, and immune potentiation effects are discussed. This review reveals the potential use of plants from Clausena in preventing and treating cancer and provides a basis for development of relevant therapeutic agents.
基金supported by the Science and Technology Development Fund,Macao SAR(File no.176/2017/A3)
文摘Background:High proliferative rate of cancer cells requires autophagy to maintain nutrient supply and intracellular homeostasis.As a result,impairing autophagic flux could be a novel strategy of cancer therapy.Aims and Objectives:In this study,the mechanism of a xanthone derivative isolated from Garcinia mangostana,garcinone E(GE),was investigated.Materials and Methods:Fluorescence assay was used to observe the accumulation and location of autophagosome and lysosome.Flow cytometry with Lyso-tracker red,MDC,and AO staining were applied to evaluate the lysosome accumulation and cellular acidity.Western blot and RT-qPCR were performed to evaluate the protein and mRNA levels,respectively.Results:GE could cause enhancement of LC3 II and p62 and the accumulation of autophagosome and lysosome.Meanwhile,it limited the protein level of Rab7,increased lysosomal pH,and inhibited the maturation of lysosomal hydrolases such as Cathepsin L,therefore blockaded the fusion of autophagosome and lysosome.Moreover,GE acted as a TFEB modulator by downregulating its protein level,which might contribute to autophagy dysfunction in ovarian cancer cells.Conclusions:GE interfered autophagosome–lysosome fusion in cancer cells,which demonstrated its application as an autophagy regulator and a potential therapeutic agent.
文摘本研究以水培油菜为研究对象,考察了盐胁迫条件下壳寡糖对油菜生长的影响。结果显示,Na Cl显著抑制了油菜苗的生长,但施用了壳寡糖后,油菜苗的全植株干重、地上部分干重、地下部分干重分别提高了37.4%、38.8%和34.1%,说明壳寡糖确实能缓解盐胁迫对植物的伤害。研究还发现,100 mmol/L Na Cl胁迫环境下,壳寡糖在一定程度上抑制了油菜苗细胞内K+/Na+值的降低和丙二醛(MDA)含量的增加;壳寡糖增加了脯氨酸的积累,增强了抗氧化酶(SOD、CAT、POD)的活力;上述结果说明壳寡糖提高了油菜苗在盐胁迫下的渗透调节能力和ROS清除能力。
文摘肥胖或超重已经成为现代社会严重的流行性健康问题,是导致糖尿病、脂代谢紊乱等多种代谢疾病的危险因素之一,动物实验是临床前实验研究的重要组成部分,是研究疾病、药理作用的重要方法。本研究目的是研究中链甘油三酯(Medium-Chain Triglycerides,MCT)对大鼠和小鼠体重影响。检索了PUBMED,EMBASE和WEB of SCIENCE三个数据库相关文献,比较分析了含中链甘油三酯或椰子油饮食干预与长链甘油三酯饮食对大鼠和小鼠体重的影响,数据以标准化平均差(SMD)或加权平均差(MD)和95%置信区间(CI)表示。结果发现,中链甘油三酯的干预可以减轻大鼠[SMD,-0.76(95%CI:-1.16,-0.37)]或小鼠[MD,-1.39(95%CI:-2.23,-0.54)]的体重。因此,中链甘油三酯的干预对大鼠和小鼠有一定的改善体重的作用。
基金National Natural Science Foundation of China(81872754)Research Fund of University of Macao(MYRG2018-00037-ICMS)and Science and Technology Development Fund,Macao SAR(FDCT 0031/2019/A1)。
文摘OBJECTIVE Interleukin(IL)-1β,one of the principal inflammatory cytokines mainly secreted by monocytes and macrophages,is produced by cleavage of the inactive pro-IL^(-1)βprecursor by caspase-1 via the NLRP3 inflammasome complex.The fruits of Garcinia cambogia(Clusiaceae)are widely developed as health products for anti-obese purpose.14-deoxygarcinol(DOG)is a polyisoprenylated benzophenone from the fruits of G.cambogia,which showed potent anti-inflammatory effect in our previous study.The objective of this study was to explore the anti-inflammatory mechanism of DOG and its roles in alleviating adipose tissue inflammation and insulin resistance.METHODS The anti-inflammatory effect of DOG was evaluated on LPS plus nigericin-induced THP-1 macrophages.The expression of NLRP3 inflammasome complex proteins was analyzed by Western blotting,immunofluorescence staining and co-immunoprecipitation.The pro-inflammatory cytokines levels were determined by ELISA kits.RESULTS DOG increased the expression of Sirtuin 2(SIRT2)deacetylase and enhanced its deacetylating activity to suppress the NLRP3 inflammasome activation and IL^(-1)βsecretion in THP-1 macrophages.Moreover,DOG attenuated macrophage conditioned medium-induced inflammatory responses in adipocytes and blocked THP-1 macrophages migration towards 3T3-L1 adipocytes.CONCLUSION DOG attenuated the inflammatory crosstalk between macrophages and adipocytes through SIRT2-mediated NLRP3 inflammasome inhibition,which might be used for the treatment of adipose tissue inflammation-related metabolic disorders.
