BACKGROUND Atractylodes japonica Koidz.ex Kitam.(A.japonica,Chinese name:Guan-Cangzhu,Japanese name:Byaku-jutsu),a perennial herb,which is mainly distributed in northeast area of China,it’s often used to treat digest...BACKGROUND Atractylodes japonica Koidz.ex Kitam.(A.japonica,Chinese name:Guan-Cangzhu,Japanese name:Byaku-jutsu),a perennial herb,which is mainly distributed in northeast area of China,it’s often used to treat digestive system diseases such as gastric ulcer(GU).However,the mechanism of its potential protective effects against GU remains unclear.AIM To investigate the protective effects of A.japonica on acetic acid-induced GU rats.METHODS The chemical constituents of A.japonica were determined by ultra performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)analysis.The rat model of GU was simulated by acetic acid method.The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain,the levels of epidermal growth factor(EGF),EGF receptor(EGFR),nuclear factor kappa-B(NF-κB),interleukin-1β(IL-1β),IL-10,Na^(+)-K^(+)-ATPase(NKA)in serum and gastric tissues were determined by enzyme-linked immunosorbent assay,and the mRNA expressions of EGFR,NF-κBp65,IkappaBalpha(IκBα)and Zonula Occludens-1(ZO-1)in gastric tissues were determined by real-time reverse transcription polymerase chain reaction,and the efficacy was observed.Then,plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers,metabolic pathways and to explore the possible mechani-sms.RESULTS 48 chemical constituents were identified.Many of them have strong pharmacological activity,the results also revealed that A.japonica significantly improved the pathological damage of gastric tissues,increased the expression levels of IL-10,IκBαrelated to anti-inflammatory factors,decreased the expression levels of IL-1β,NF-κB,NF-κBp65,related to proinflammatory factors,restored the levels of factors about EGF,EGFR,ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism.Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways.CONCLUSION These findings contribute to the understanding of the potential mechanism of A.japonica to improve acetic acidinduced GU,and will be of great importance for the development and clinical application of natural drugs related to A.japonica.展开更多
In order to investigate the effect of different C4 linkage moieties on the cytotoxicity of podophyllotoxin derivatives,novel 4-Nand 4-C-substituted 4'-O-demethylepipodophyllotoxin derivatives were designed and syn...In order to investigate the effect of different C4 linkage moieties on the cytotoxicity of podophyllotoxin derivatives,novel 4-Nand 4-C-substituted 4'-O-demethylepipodophyllotoxin derivatives were designed and synthesized.All the compounds were tested against A549 and MCF-7 tumor cells in vitro,and six compounds showed significant cytotoxicity.The most active compound 9f was superior to GL-331,and exhibited potent cytotoxicity with IC_(50) value at 10^(-7) mol/L level.展开更多
Objective:Yiqi Huoxue Decoction (YQHX) has been widely used for clinical treatment of ischemic heart disease.While oxidative stress plays a key role in the pathogenesis of ischemic heart disease,the function and molec...Objective:Yiqi Huoxue Decoction (YQHX) has been widely used for clinical treatment of ischemic heart disease.While oxidative stress plays a key role in the pathogenesis of ischemic heart disease,the function and molecular mechanism underlying antioxidative protective effects of YQHX on H9c2 cardiomyocytes against ischemia/hypoxia (I/H) have yet to be well clarified.Methods:H9c2 cells were subjected to 12 h of hypoxia with serum-free conditions and then treated with or without YQHX (100-400 μg/mL).Cell viability was examined using a CCK-8 assay.Maleic dialdehyde (MDA) and superoxide dismutase (SOD) activity were detected using commercial kits.Intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential were measured using fluorescence microscopy and confocal laser-scanning microscopy,respectively.Ultrastructural details of mitochondria in H9c2 cells were observed using transmission electron microscopy.The antioxidative protective pathway was assessed by measuring mRNA and protein expression of Nrf2 and HO-1,as well as AMPK activation.Results:I/H injury gradually induced oxidative stress.Treatment with YQHX significantly increased cell viability and reversed I/H-induced oxidative stress,including reducing the production of oxidative stress products (ROS and MDA),increasing SOD levels,improving mitochondrial morphology,and increasing mitochondrial membrane potential.YQHX was also observed to increase I/H-induced expression of Nrf2 and HO-1,and the activation effects of YQHX were blocked by an AMPK inhibitor.In addition,HPLC analysis showed that YQHX contained two active antioxidative constituents (calycosin and ferulic acid).Conclusion:The results suggest that anti-oxidative effects exerted by YQHX in H9c2 cardiomyocytes may be linked to upregulation of the AMPK-mediated Nrf2/HO-1 pathway.展开更多
Flower-like Cu2SnS3 nanostructures composed of nano-flakes were successfully synthesized by solvothermal technique at 180℃for 16 h.In the preparation process,CuCI2·2H2O,SnCl2·2H2O and thiourea were used as ...Flower-like Cu2SnS3 nanostructures composed of nano-flakes were successfully synthesized by solvothermal technique at 180℃for 16 h.In the preparation process,CuCI2·2H2O,SnCl2·2H2O and thiourea were used as raw materials,and ethylene glycol were used as solvent.The results showed that the obtained product was pure phase Cu2SnS3.The average diameter of Cu2SnS3 flowers and the thickness of the nano-flakes were about 1—1.5μm and 10 nm,respectively.The influence of reaction time and solvents on the morphology,size and structure of the products was investigated by powder X-ray diffraction and fieldemission scan electron microscopy（FESEM）.The ultraviolet-visible absorption spectrum measurement indicated that the band gap of the sample was about 1.26 eV and could be applied to the absorbing layer of thin solar cell.The possible formation mechanism of flower-like Cu2SnS3 was also proposed and discussed.展开更多
Copper-catalyzed cross-couplings of aryl halides and nucleophiles,traditionally called Ullmann-type coupling reactions,were initially reported by Ullmann et al.from 1901-1929.A seminal report in 1998 by Ma et al.from ...Copper-catalyzed cross-couplings of aryl halides and nucleophiles,traditionally called Ullmann-type coupling reactions,were initially reported by Ullmann et al.from 1901-1929.A seminal report in 1998 by Ma et al.from Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences revealed an accelerating effect caused by amino acids,which brought Ullmann-type coupling reactions into a ligand-accelerating era.From 1999 to the first 10 years of 2000s,the first-generation ligands were developed by many researchers and promoted Ullmann-type coupling reactions of aryl iodides and bromides under relatively mild conditions.Amino acid ligands,developed by Ma and coworkers,are one class of the most important first-generation ligands.In the second 10 years of 2000s,Ma et al.led the discovery of second-generation ligands for copper-catalyzed cross-coupling reactions.Two great breakthroughs have been realized by using second-generation oxalic diamide and related amide ligands,with aryl chlorides as general coupling partner and with low catalyst loadings.Now copper-catalyzed cross coupling reactions of aryl halides and nucleophiles with amino acids or oxalic diamides and related amides as ligands are recognized as Ullmann-Ma reactions and have found extensive applications in organic synthesis.展开更多
Acute kidney injury(AKI)is a common clinical complication associated with high mortality in patients.Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis.Plasmacytoid den...Acute kidney injury(AKI)is a common clinical complication associated with high mortality in patients.Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis.Plasmacytoid dendritic cells(pDCs)are a unique DC subset that specializes in type Ⅰ interferon(IFN)production.Here,we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α.Deletion of pDCs using DTR^(BDCA2) transgenic(Tg)mice suppressed cisplatin-induced AKI,accompanied by marked reductions in proinflammatory cytokine production,immune cell infiltration and apoptosis in the kidney.In contrast,adoptive transfer of pDCs during AKI exacerbated kidney damage.We further identified IFN-α as the key factor that mediated the functions of pDCs during AKI,as IFN-α neutralization significantly attenuated kidney injury.Furthermore,IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells(TECs)in vitro.In addition,our data demonstrated that apoptotic TECs induced the activation of pDCs,which was inhibited in the presence of an apoptosis inhibitor.Furthermore,similar deleterious effects of pDCs were observed in an ischemia reperfusion(IR)-induced AKI model.Clinically,increased expression of IFN-α in kidney biopsies was observed in kidney transplants with AKI.Taken together,the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.展开更多
Exosomes are a class of membranous vesicles,which are approximately 50 to 100 nm in diameter;they are released into the extracellular matrix from various cells.[1]Exosomes are rich in proteins,lipids,and nucleic acids...Exosomes are a class of membranous vesicles,which are approximately 50 to 100 nm in diameter;they are released into the extracellular matrix from various cells.[1]Exosomes are rich in proteins,lipids,and nucleic acids.They have been reported to be involved in various physiological processes and are important tools for intercellular material and information communication.[2,3]Increasing evidence has indicated that exosomes can be extracted from human saliva,urine,blood,and other body fluids.[4]However,whether exosomes exist in nipple discharge remains unknown.In this study,exosomes from nipple discharge of breast cancer patients and colostrum of postpartum women were isolated using ultracentrifugation.The exosomes were identified by transmission electron microscopy(TEM),Western blot,and nanoparticle tracking analysis(NTA).The detailed methods are shown in Supplementary File 1,http://links.lww.com/CM9/A286.The study was approved by the Ethics Committee of Qilu Hospital of Shandong University(No.KYLL-2018-096),and all patients provided written informed consent.展开更多
基金Supported by National Natural Science Foundation of China,No.81973478Liaoning Revitalization Talents Program,China,No.XLYC2002004Natural Science Foundation of Liaoning Province,China,No.2019-ZD-0443.
文摘BACKGROUND Atractylodes japonica Koidz.ex Kitam.(A.japonica,Chinese name:Guan-Cangzhu,Japanese name:Byaku-jutsu),a perennial herb,which is mainly distributed in northeast area of China,it’s often used to treat digestive system diseases such as gastric ulcer(GU).However,the mechanism of its potential protective effects against GU remains unclear.AIM To investigate the protective effects of A.japonica on acetic acid-induced GU rats.METHODS The chemical constituents of A.japonica were determined by ultra performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)analysis.The rat model of GU was simulated by acetic acid method.The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain,the levels of epidermal growth factor(EGF),EGF receptor(EGFR),nuclear factor kappa-B(NF-κB),interleukin-1β(IL-1β),IL-10,Na^(+)-K^(+)-ATPase(NKA)in serum and gastric tissues were determined by enzyme-linked immunosorbent assay,and the mRNA expressions of EGFR,NF-κBp65,IkappaBalpha(IκBα)and Zonula Occludens-1(ZO-1)in gastric tissues were determined by real-time reverse transcription polymerase chain reaction,and the efficacy was observed.Then,plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers,metabolic pathways and to explore the possible mechani-sms.RESULTS 48 chemical constituents were identified.Many of them have strong pharmacological activity,the results also revealed that A.japonica significantly improved the pathological damage of gastric tissues,increased the expression levels of IL-10,IκBαrelated to anti-inflammatory factors,decreased the expression levels of IL-1β,NF-κB,NF-κBp65,related to proinflammatory factors,restored the levels of factors about EGF,EGFR,ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism.Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways.CONCLUSION These findings contribute to the understanding of the potential mechanism of A.japonica to improve acetic acidinduced GU,and will be of great importance for the development and clinical application of natural drugs related to A.japonica.
文摘In order to investigate the effect of different C4 linkage moieties on the cytotoxicity of podophyllotoxin derivatives,novel 4-Nand 4-C-substituted 4'-O-demethylepipodophyllotoxin derivatives were designed and synthesized.All the compounds were tested against A549 and MCF-7 tumor cells in vitro,and six compounds showed significant cytotoxicity.The most active compound 9f was superior to GL-331,and exhibited potent cytotoxicity with IC_(50) value at 10^(-7) mol/L level.
基金the National Natural Science Foundation of China:Study of Influence of Supplementing Qi and Activating Blood Circulation Herbs on Mitochondrial Energy Metabolism and Signal Transduction of Myocardial Ischemia Rats(No.81473552).
文摘Objective:Yiqi Huoxue Decoction (YQHX) has been widely used for clinical treatment of ischemic heart disease.While oxidative stress plays a key role in the pathogenesis of ischemic heart disease,the function and molecular mechanism underlying antioxidative protective effects of YQHX on H9c2 cardiomyocytes against ischemia/hypoxia (I/H) have yet to be well clarified.Methods:H9c2 cells were subjected to 12 h of hypoxia with serum-free conditions and then treated with or without YQHX (100-400 μg/mL).Cell viability was examined using a CCK-8 assay.Maleic dialdehyde (MDA) and superoxide dismutase (SOD) activity were detected using commercial kits.Intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential were measured using fluorescence microscopy and confocal laser-scanning microscopy,respectively.Ultrastructural details of mitochondria in H9c2 cells were observed using transmission electron microscopy.The antioxidative protective pathway was assessed by measuring mRNA and protein expression of Nrf2 and HO-1,as well as AMPK activation.Results:I/H injury gradually induced oxidative stress.Treatment with YQHX significantly increased cell viability and reversed I/H-induced oxidative stress,including reducing the production of oxidative stress products (ROS and MDA),increasing SOD levels,improving mitochondrial morphology,and increasing mitochondrial membrane potential.YQHX was also observed to increase I/H-induced expression of Nrf2 and HO-1,and the activation effects of YQHX were blocked by an AMPK inhibitor.In addition,HPLC analysis showed that YQHX contained two active antioxidative constituents (calycosin and ferulic acid).Conclusion:The results suggest that anti-oxidative effects exerted by YQHX in H9c2 cardiomyocytes may be linked to upregulation of the AMPK-mediated Nrf2/HO-1 pathway.
基金support from the National Natural Science Foundation of China(Grant Nos.50972107 and 51272059)the Key Scientific and Technological Innovation Teams of Zhejiang Province,China(No. 2009R50010)+1 种基金the Natural Science Foundation of Liaoning Province,China(No.201202087)Program of Science and Technology Project of Wenzhou,China(No.G20110012)
文摘Flower-like Cu2SnS3 nanostructures composed of nano-flakes were successfully synthesized by solvothermal technique at 180℃for 16 h.In the preparation process,CuCI2·2H2O,SnCl2·2H2O and thiourea were used as raw materials,and ethylene glycol were used as solvent.The results showed that the obtained product was pure phase Cu2SnS3.The average diameter of Cu2SnS3 flowers and the thickness of the nano-flakes were about 1—1.5μm and 10 nm,respectively.The influence of reaction time and solvents on the morphology,size and structure of the products was investigated by powder X-ray diffraction and fieldemission scan electron microscopy（FESEM）.The ultraviolet-visible absorption spectrum measurement indicated that the band gap of the sample was about 1.26 eV and could be applied to the absorbing layer of thin solar cell.The possible formation mechanism of flower-like Cu2SnS3 was also proposed and discussed.
基金The authors are grateful to the Guangdong Special SupportProgram(No.2017TX04RO59)the National Natural ScienceFoundation of China(No.21772066)for the financial support.
文摘Copper-catalyzed cross-couplings of aryl halides and nucleophiles,traditionally called Ullmann-type coupling reactions,were initially reported by Ullmann et al.from 1901-1929.A seminal report in 1998 by Ma et al.from Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences revealed an accelerating effect caused by amino acids,which brought Ullmann-type coupling reactions into a ligand-accelerating era.From 1999 to the first 10 years of 2000s,the first-generation ligands were developed by many researchers and promoted Ullmann-type coupling reactions of aryl iodides and bromides under relatively mild conditions.Amino acid ligands,developed by Ma and coworkers,are one class of the most important first-generation ligands.In the second 10 years of 2000s,Ma et al.led the discovery of second-generation ligands for copper-catalyzed cross-coupling reactions.Two great breakthroughs have been realized by using second-generation oxalic diamide and related amide ligands,with aryl chlorides as general coupling partner and with low catalyst loadings.Now copper-catalyzed cross coupling reactions of aryl halides and nucleophiles with amino acids or oxalic diamides and related amides as ligands are recognized as Ullmann-Ma reactions and have found extensive applications in organic synthesis.
基金supported by grants from the National Natural Science Foundation of China(No:81870462 and 81470990 to F.Ding,No:91642112 to R.H.,and No:31600715 to Y.L.L.)The Science and Technology Commission of Shanghai Municipality(No:18140903300 to R.H.,No:17441904200 and 19441909300 to F.D.)+5 种基金Shanghai Ninth People’s Hospital Clinical Research Program(No:JYU007 to F.D.)Shanghai Ninth People's Hospital MDT Program(2017-1-019 to F.D.)Major Special Projects of the Ministry of Science and Technology(2018ZX10302207 to Y.L.L.)Development Project of Shanghai Peak Disciplines-Integrative Medicine(20180101 to Y.L.L.)Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine(BXJ201730 to B.D.)Fundamental Research Program Funding of Ninth People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine(JYZZ082B to B.D.).
文摘Acute kidney injury(AKI)is a common clinical complication associated with high mortality in patients.Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis.Plasmacytoid dendritic cells(pDCs)are a unique DC subset that specializes in type Ⅰ interferon(IFN)production.Here,we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α.Deletion of pDCs using DTR^(BDCA2) transgenic(Tg)mice suppressed cisplatin-induced AKI,accompanied by marked reductions in proinflammatory cytokine production,immune cell infiltration and apoptosis in the kidney.In contrast,adoptive transfer of pDCs during AKI exacerbated kidney damage.We further identified IFN-α as the key factor that mediated the functions of pDCs during AKI,as IFN-α neutralization significantly attenuated kidney injury.Furthermore,IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells(TECs)in vitro.In addition,our data demonstrated that apoptotic TECs induced the activation of pDCs,which was inhibited in the presence of an apoptosis inhibitor.Furthermore,similar deleterious effects of pDCs were observed in an ischemia reperfusion(IR)-induced AKI model.Clinically,increased expression of IFN-α in kidney biopsies was observed in kidney transplants with AKI.Taken together,the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.
基金grants from the National Natural Science Foundation of China(Nos.81402192 and 81802406)Shandong Provincial Natural Science Foundation,China(Nos.ZR2019BH061 and ZR2018MH029)+3 种基金the Shandong Key Research and Development Plan(No.2019GSF108058)the Funding for New Clinical and Practical Techniques of Qilu Hospital of Shandong University(No.2019-1)the Science and Technology Development Plan of Jinan(the Medical and Health Science and Technology Innovation Plan,No.201704091)Shandong Co-innovation center of classic TCM formula.
文摘Exosomes are a class of membranous vesicles,which are approximately 50 to 100 nm in diameter;they are released into the extracellular matrix from various cells.[1]Exosomes are rich in proteins,lipids,and nucleic acids.They have been reported to be involved in various physiological processes and are important tools for intercellular material and information communication.[2,3]Increasing evidence has indicated that exosomes can be extracted from human saliva,urine,blood,and other body fluids.[4]However,whether exosomes exist in nipple discharge remains unknown.In this study,exosomes from nipple discharge of breast cancer patients and colostrum of postpartum women were isolated using ultracentrifugation.The exosomes were identified by transmission electron microscopy(TEM),Western blot,and nanoparticle tracking analysis(NTA).The detailed methods are shown in Supplementary File 1,http://links.lww.com/CM9/A286.The study was approved by the Ethics Committee of Qilu Hospital of Shandong University(No.KYLL-2018-096),and all patients provided written informed consent.
