Natural products have long been a crucial source of,or provided inspiration for new agrochemical discovery.Naturally occurring 18β-glycyrrhetinic acid shows broad-spectrum bioactivities and is a potential skeleton fo...Natural products have long been a crucial source of,or provided inspiration for new agrochemical discovery.Naturally occurring 18β-glycyrrhetinic acid shows broad-spectrum bioactivities and is a potential skeleton for novel drug discovery.To extend the utility of 18β-glycyrrhetinic acid for agricultural uses,a series of novel 18β-glycyrrhetinic acid amide derivatives were prepared and evaluated for their antibacterial potency.Notably,compound 5k showed good antibacterial activity in vitro against Xanthomonas oryzae pv.oryzae(Xoo,EC50=3.64 mg L–1),and excellent protective activity(54.68%)against Xoo in vivo.Compound 5k induced excessive production and accumulation of reactive oxygen species in the tested pathogens,resulting in damaging the bacterial cell envelope.More interestingly,compound 5k could increase the activities of plant defense enzymes including catalase,superoxide dismutase,peroxidase,and phenylalanine ammonia lyase.Taken together,these enjoyable results suggested that designed compounds derived from 18β-glycyrrhetinic acid showed potential for controlling intractable plant bacterial diseases by disturbing the balance of the phytopathogen’s redox system and activating the plant defense system.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common cancer types worldwide,and its prevention and treatment methods have garnered much attention.As the active ingredient of licorice,18β-glycyrrhetinic acid(18β-GR...BACKGROUND Gastric cancer(GC)is one of the most common cancer types worldwide,and its prevention and treatment methods have garnered much attention.As the active ingredient of licorice,18β-glycyrrhetinic acid(18β-GRA)has a variety of pharmacological effects.The aim of this study was to explore the effective target of 18β-GRA in the treatment of GC,in order to provide effective ideas for the clinical prevention and treatment of GC.AIM To investigate the mechanism of 18β-GRA in inhibiting cell proliferation and promoting autophagy flux in GC cells.METHODS Whole transcriptomic analyses were used to analyze and screen differentially expressed microRNAs(miRNAs)in GC cells after 18β-GRA intervention.Lentivirus-transfected GC cells and the Cell Counting Kit-8 were used to detect cell proliferation ability,cell colony formation ability was detected by the clone formation assay,and flow cytometry was used to detect the cell cycle and apoptosis.A nude mouse transplantation tumor model of GC cells was constructed to verify the effect of miR-328-3p overexpression on the tumorigenicity of GC cells.Tumor tissue morphology was observed by hematoxylin and eosin staining,and microtubule-associated protein light chain 3(LC3)expression was detected by immunohistochemistry.TransmiR,STRING,and miRWalk databases were used to predict the relationship between miR-328-3p and signal transducer and activator of transcription 3(STAT3)-related information.Expression of STAT3 mRNA and miR-328-3p was detected by quantitative polymerase chain reaction(qPCR)and the expression levels of STAT3,phosphorylated STAT3(p-STAT3),and LC3 were detected by western blot analysis.The targeted relationship between miR-328-3p and STAT3 was detected using the dual-luciferase reporter gene system.AGS cells were infected with monomeric red fluorescent protein-green fluorescent protein-LC3 adenovirus double label.LC3 was labeled and autophagy flow was observed under a confocal laser microscope.RESULTS The expression of miR-328-3p was significantly upregulated after 18β-GRA intervention in AGS cells(P=4.51E-06).Overexpression of miR-328-3p inhibited GC cell proliferation and colony formation ability,arrested the cell cycle in the G0/G1 phase,promoted cell apoptosis,and inhibited the growth of subcutaneous tumors in BALB/c nude mice(P<0.01).No obvious necrosis was observed in the tumor tissue in the negative control group(no drug intervention or lentivirus transfection)and vector group(the blank vector for lentivirus transfection),and more cells were loose and necrotic in the miR-328-3p group.Bioinformatics tools predicted that miR-328-3p has a targeting relationship with STAT3,and STAT3 was closely related to autophagy markers such as p62.After overexpressing miR-328-3p,the expression level of STAT3 mRNA was significantly decreased(P<0.01)and p-STAT3 was downregulated(P<0.05).The dual-luciferase reporter gene assay showed that the luciferase activity of miR-328-3p and STAT33’untranslated regions of the wild-type reporter vector group was significantly decreased(P<0.001).Overexpressed miR-328-3p combined with bafilomycin A1(Baf A1)was used to detect the expression of LC3 II.Compared with the vector group,the expression level of LC3 II in the overexpressed miR-328-3p group was downregulated(P<0.05),and compared with the Baf A1 group,the expression level of LC3 II in the overexpressed miR-328-3p+Baf A1 group was upregulated(P<0.01).The expression of LC3 II was detected after intervention of 18β-GRA in GC cells,and the results were consistent with the results of miR-328-3p overexpression(P<0.05).Additional studies showed that 18β-GRA promoted autophagy flow by promoting autophagosome synthesis(P<0.001).qPCR showed that the expression of STAT3 mRNA was downregulated after drug intervention(P<0.05).Western blot analysis showed that the expression levels of STAT3 and p-STAT3 were significantly downregulated after drug intervention(P<0.05).CONCLUSION 18β-GRA promotes the synthesis of autophagosomes and inhibits GC cell proliferation by regulating the miR-328-3p/STAT3 signaling pathway.展开更多
The electrochemical conversion is closely correlated with the electrocatalytic activities of the electrocatalyst.Herein,the urchin-like Ni-doped W_(18)O_(49)/NF with enriched active sites was prepared by solvothermal ...The electrochemical conversion is closely correlated with the electrocatalytic activities of the electrocatalyst.Herein,the urchin-like Ni-doped W_(18)O_(49)/NF with enriched active sites was prepared by solvothermal method followed by a low-temperature pyrolysis treatment was reported.Results demonstrate that the incorporation of Ni-doping triggers the lattice distortion of W_(18)O_(49) for the increasement of oxygen defects.Further,high-valent W^(6+)are partially reduced to low-valent W^(4+),wherein the electrons originate from the oxidation process of Ni^(2+)to Ni^(3+).The Ni^(3+)ions show an enhanced orbital overlap with the OER reaction intermediates.The generated W^(4+)ions contribute to release oxygen vacancies,eventually reorganizing Ni-doped W_(18)O_(49)/NF to unique electrochemical active species with a special amorphous-crystalline interface(AM/NiWO_x/NiOOH/NF).Simultaneously,the reconstruction results in an optimized valence band and conduction band.Eventually,the resultant AM/NiWO_x/NiOOH/NF with abundant active sites and improved oxidation/reduction capability exhibits more superior catalytic performance compared with the Ni-doped W_(18)O_(49)/NF counterpart.This study gives more insights in the electrochemical evolution of the tungsten-based oxide and provides effective strategies for optimizing the catalytic activity of materials with inherent hydrogen evolution reaction limitations.展开更多
Objective:To investigate the effects of 20 methanolic extracts from Malaysian selected plants on CD18/11 a expression and phagocytosis activity of leukocytes using flow cytometry analysis.Methods:The effects of methan...Objective:To investigate the effects of 20 methanolic extracts from Malaysian selected plants on CD18/11 a expression and phagocytosis activity of leukocytes using flow cytometry analysis.Methods:The effects of methanolic extracts on CD18/11 a expression and phagocytosis of leukocytes were measured by labelling the cells with CD18-fluorescein isolhiocyanaie and ingestion labelled with Escherichia coli-fluorescein isothiocyanate and then analyzed using flow cytometer.Results:About 12 out of 20 methanolic extracts of selected Malaysian medicinal plants significantly(P≤0.05) inhibited the CD18/1 la expression of leukocytes at both concentrations of 6.25 μg/mL and 100 μg/mL in dose dependent manner.The most active inhibitory was shown in Citrus aurantifolia(Christm.) Swingle and Alpinia galangal(L.) Willd.at dosage 100ug/mL.Moreover,the Orthosiphon aristatus(Blume) Miq(O.aristatus).showed the highest stimulatory activity at the concentration of 100 μg/mL.Other than that,four plant extracts significantly(P<0.05) rose the phagocytosis activities of leukocytes in dose dependent manner.However,Annona muricata L.and O.aristatus showed the highest stimulated activities at the 100 pg/mL concentration.Conclusions:The results suggest that methanolic extracts of Cirrus aurantifolia.Alpinia gaiangal,O.aristatus and Annona muricata are able to modulate innate immune system and can potentially be recognized as therapeutic agents for modulating immune system.展开更多
Some poxvirus genome of vaccinia subgenus encoded IL-18 binding prolein gene,which could block IL-18 activity but no sequence similarity to membrane IL-18 receptors.The sheep poxvirus genome subgenus also had this gen...Some poxvirus genome of vaccinia subgenus encoded IL-18 binding prolein gene,which could block IL-18 activity but no sequence similarity to membrane IL-18 receptors.The sheep poxvirus genome subgenus also had this gene.A pair of primers spanning the ORF of goat IL-18 binding protein gene in sheep poxvirus genome were designed.This gene was cloned and expressed in E.coliwith pGEX-5X-3 plasmid.After being purified,the recombinant fusion protein could inhibit goat PBMC IFN- production induced by IL-18 in goat PBMC.展开更多
基金fundings provided by the National Natural Science Foundation of China(21877021 and 32160661)the Guizhou Provincial S&T Program[(2018)4007]the Program of Introducing Talents of Discipline to Universities of China(D20023,111 Program).
文摘Natural products have long been a crucial source of,or provided inspiration for new agrochemical discovery.Naturally occurring 18β-glycyrrhetinic acid shows broad-spectrum bioactivities and is a potential skeleton for novel drug discovery.To extend the utility of 18β-glycyrrhetinic acid for agricultural uses,a series of novel 18β-glycyrrhetinic acid amide derivatives were prepared and evaluated for their antibacterial potency.Notably,compound 5k showed good antibacterial activity in vitro against Xanthomonas oryzae pv.oryzae(Xoo,EC50=3.64 mg L–1),and excellent protective activity(54.68%)against Xoo in vivo.Compound 5k induced excessive production and accumulation of reactive oxygen species in the tested pathogens,resulting in damaging the bacterial cell envelope.More interestingly,compound 5k could increase the activities of plant defense enzymes including catalase,superoxide dismutase,peroxidase,and phenylalanine ammonia lyase.Taken together,these enjoyable results suggested that designed compounds derived from 18β-glycyrrhetinic acid showed potential for controlling intractable plant bacterial diseases by disturbing the balance of the phytopathogen’s redox system and activating the plant defense system.
基金Ningxia Medical University Project,No. XZ2021005Ningxia Natural Science Foundation,Nos. 2022AAC03144 and 2022AAC02039National Natural Science Foundation of China,No. 82260879
文摘BACKGROUND Gastric cancer(GC)is one of the most common cancer types worldwide,and its prevention and treatment methods have garnered much attention.As the active ingredient of licorice,18β-glycyrrhetinic acid(18β-GRA)has a variety of pharmacological effects.The aim of this study was to explore the effective target of 18β-GRA in the treatment of GC,in order to provide effective ideas for the clinical prevention and treatment of GC.AIM To investigate the mechanism of 18β-GRA in inhibiting cell proliferation and promoting autophagy flux in GC cells.METHODS Whole transcriptomic analyses were used to analyze and screen differentially expressed microRNAs(miRNAs)in GC cells after 18β-GRA intervention.Lentivirus-transfected GC cells and the Cell Counting Kit-8 were used to detect cell proliferation ability,cell colony formation ability was detected by the clone formation assay,and flow cytometry was used to detect the cell cycle and apoptosis.A nude mouse transplantation tumor model of GC cells was constructed to verify the effect of miR-328-3p overexpression on the tumorigenicity of GC cells.Tumor tissue morphology was observed by hematoxylin and eosin staining,and microtubule-associated protein light chain 3(LC3)expression was detected by immunohistochemistry.TransmiR,STRING,and miRWalk databases were used to predict the relationship between miR-328-3p and signal transducer and activator of transcription 3(STAT3)-related information.Expression of STAT3 mRNA and miR-328-3p was detected by quantitative polymerase chain reaction(qPCR)and the expression levels of STAT3,phosphorylated STAT3(p-STAT3),and LC3 were detected by western blot analysis.The targeted relationship between miR-328-3p and STAT3 was detected using the dual-luciferase reporter gene system.AGS cells were infected with monomeric red fluorescent protein-green fluorescent protein-LC3 adenovirus double label.LC3 was labeled and autophagy flow was observed under a confocal laser microscope.RESULTS The expression of miR-328-3p was significantly upregulated after 18β-GRA intervention in AGS cells(P=4.51E-06).Overexpression of miR-328-3p inhibited GC cell proliferation and colony formation ability,arrested the cell cycle in the G0/G1 phase,promoted cell apoptosis,and inhibited the growth of subcutaneous tumors in BALB/c nude mice(P<0.01).No obvious necrosis was observed in the tumor tissue in the negative control group(no drug intervention or lentivirus transfection)and vector group(the blank vector for lentivirus transfection),and more cells were loose and necrotic in the miR-328-3p group.Bioinformatics tools predicted that miR-328-3p has a targeting relationship with STAT3,and STAT3 was closely related to autophagy markers such as p62.After overexpressing miR-328-3p,the expression level of STAT3 mRNA was significantly decreased(P<0.01)and p-STAT3 was downregulated(P<0.05).The dual-luciferase reporter gene assay showed that the luciferase activity of miR-328-3p and STAT33’untranslated regions of the wild-type reporter vector group was significantly decreased(P<0.001).Overexpressed miR-328-3p combined with bafilomycin A1(Baf A1)was used to detect the expression of LC3 II.Compared with the vector group,the expression level of LC3 II in the overexpressed miR-328-3p group was downregulated(P<0.05),and compared with the Baf A1 group,the expression level of LC3 II in the overexpressed miR-328-3p+Baf A1 group was upregulated(P<0.01).The expression of LC3 II was detected after intervention of 18β-GRA in GC cells,and the results were consistent with the results of miR-328-3p overexpression(P<0.05).Additional studies showed that 18β-GRA promoted autophagy flow by promoting autophagosome synthesis(P<0.001).qPCR showed that the expression of STAT3 mRNA was downregulated after drug intervention(P<0.05).Western blot analysis showed that the expression levels of STAT3 and p-STAT3 were significantly downregulated after drug intervention(P<0.05).CONCLUSION 18β-GRA promotes the synthesis of autophagosomes and inhibits GC cell proliferation by regulating the miR-328-3p/STAT3 signaling pathway.
基金supported by the National Natural Science Foundation of China (52073166)the China Scholarship Council (CSC) for the Research Training Program of Guojuan Hai to study at University of Wollongong(201908610223)+5 种基金the Xi’an Key Laboratory of Green Manufacture of Ceramic Materials Foundation (2019220214SYS017CG039)the Key Program for International S&T Cooperation Projects of Shaanxi Province(2020KW-038, 2020GHJD-04)the Science and Technology Program of Xi’an,China (2020KJRC0009)the Scientific Research Program Funded by Shaanxi Provincial Education Department(No. 20JY001)Science and Technology Resource Sharing Platform of Shaanxi Province (2020PT-022)Science and Technology Plan of Weiyang District,Xi’an (202009)。
文摘The electrochemical conversion is closely correlated with the electrocatalytic activities of the electrocatalyst.Herein,the urchin-like Ni-doped W_(18)O_(49)/NF with enriched active sites was prepared by solvothermal method followed by a low-temperature pyrolysis treatment was reported.Results demonstrate that the incorporation of Ni-doping triggers the lattice distortion of W_(18)O_(49) for the increasement of oxygen defects.Further,high-valent W^(6+)are partially reduced to low-valent W^(4+),wherein the electrons originate from the oxidation process of Ni^(2+)to Ni^(3+).The Ni^(3+)ions show an enhanced orbital overlap with the OER reaction intermediates.The generated W^(4+)ions contribute to release oxygen vacancies,eventually reorganizing Ni-doped W_(18)O_(49)/NF to unique electrochemical active species with a special amorphous-crystalline interface(AM/NiWO_x/NiOOH/NF).Simultaneously,the reconstruction results in an optimized valence band and conduction band.Eventually,the resultant AM/NiWO_x/NiOOH/NF with abundant active sites and improved oxidation/reduction capability exhibits more superior catalytic performance compared with the Ni-doped W_(18)O_(49)/NF counterpart.This study gives more insights in the electrochemical evolution of the tungsten-based oxide and provides effective strategies for optimizing the catalytic activity of materials with inherent hydrogen evolution reaction limitations.
基金Supported by Ministry of Higher Education.Malaysia(Grant No.GUP-SK-07-23-042)
文摘Objective:To investigate the effects of 20 methanolic extracts from Malaysian selected plants on CD18/11 a expression and phagocytosis activity of leukocytes using flow cytometry analysis.Methods:The effects of methanolic extracts on CD18/11 a expression and phagocytosis of leukocytes were measured by labelling the cells with CD18-fluorescein isolhiocyanaie and ingestion labelled with Escherichia coli-fluorescein isothiocyanate and then analyzed using flow cytometer.Results:About 12 out of 20 methanolic extracts of selected Malaysian medicinal plants significantly(P≤0.05) inhibited the CD18/1 la expression of leukocytes at both concentrations of 6.25 μg/mL and 100 μg/mL in dose dependent manner.The most active inhibitory was shown in Citrus aurantifolia(Christm.) Swingle and Alpinia galangal(L.) Willd.at dosage 100ug/mL.Moreover,the Orthosiphon aristatus(Blume) Miq(O.aristatus).showed the highest stimulatory activity at the concentration of 100 μg/mL.Other than that,four plant extracts significantly(P<0.05) rose the phagocytosis activities of leukocytes in dose dependent manner.However,Annona muricata L.and O.aristatus showed the highest stimulated activities at the 100 pg/mL concentration.Conclusions:The results suggest that methanolic extracts of Cirrus aurantifolia.Alpinia gaiangal,O.aristatus and Annona muricata are able to modulate innate immune system and can potentially be recognized as therapeutic agents for modulating immune system.
文摘Some poxvirus genome of vaccinia subgenus encoded IL-18 binding prolein gene,which could block IL-18 activity but no sequence similarity to membrane IL-18 receptors.The sheep poxvirus genome subgenus also had this gene.A pair of primers spanning the ORF of goat IL-18 binding protein gene in sheep poxvirus genome were designed.This gene was cloned and expressed in E.coliwith pGEX-5X-3 plasmid.After being purified,the recombinant fusion protein could inhibit goat PBMC IFN- production induced by IL-18 in goat PBMC.
