Introduction There is currently no standard treatment for relapsed and arsenic trioxide(ATO)-resistant acute promyelocytic leukemia(APL).Here,we report a case series of realgar-indigo naturalis formula(RIF)for the suc...Introduction There is currently no standard treatment for relapsed and arsenic trioxide(ATO)-resistant acute promyelocytic leukemia(APL).Here,we report a case series of realgar-indigo naturalis formula(RIF)for the successful treatment of patients with relapsed and ATO-resistant APL.Case presentation Two patients in the first relapse and one in the second relapse failed to achieve hematologic complete remission(HCR)when reinduced by ATO;the other five patients progressed to relapse during ATO-based regimens for post-remission therapy.These eight patients received RIF in three doses per day totaling 130 mg/kg(≤30 pills)as induction therapy and achieved HCR at a median time of 46.5 days.They received 5 years of post-remission therapy,which consisted of combined chemotherapy followed by RIF.During this period,the patients did not experience renal dysfunction or QT interval prolongation.At the last follow-up,three patients survived without relapse,two patients survived with a second or third relapse and third or fourth remission,and the other three patients relapsed for a third or fourth time and died.The 5-year overall survival and event-free survival rates were 75.0%(95%confidence interval[CI]:31.5–93.1)and 37.5%(95%CI:5.6–71.7),respectively.Conclusion RIF for induction therapy and RIF combined with chemotherapy for post-remission therapy may represent an effective and safe protocol for the treatment of patients with relapsed and ATO-resistant APL.展开更多
OBJECTIVE:To elucidate the protective effect of Qingdai(Indigo Naturalis,QD)on ulcerative colitis(UC)by means of in silico and in vivo approaches.METHODS:A systems pharmacology analysis was performed to predict the ac...OBJECTIVE:To elucidate the protective effect of Qingdai(Indigo Naturalis,QD)on ulcerative colitis(UC)by means of in silico and in vivo approaches.METHODS:A systems pharmacology analysis was performed to predict the active components of QD whereas the putative biological targets of QD against UC were obtained through target fishing,network cons-truction and enrichment analyses.Meanwhile,we examined the ameliorative effect of QD in a mouse model of dextran sulfate sodium(DSS)-induced colitis.During the 10-day experiment,the control and diseased mice were given with oral gavages of QD(1.3 g raw herbs·kg^(-1)·d^(-1))or 5-aminosalicylic acid(5-ASA,100 mg·kg^(-1)·d^(-1))every day.The underlying pharma-cological mechanisms of QD in UC were determined using polymerase chain reaction tests,histological staining,enzyme-linked immunoassays,and Western blotting analysis.RESULTS:Searching from various network pharmacology databases,29 compounds were identified in QD.According to the screening criteria suggested by TCMSP(i.e.OB≥30%and DL≥0.18),nine of them were considered the active ingredients that contribute to the ameliorative effects of QD on different mouse models of colitis.Most importantly,the protective effect of QD on DSS-induced colitis was significantly associated with modulations of the expression levels of glycogen synthase kinase 3-β(Gsk3-β)and forkhead box p3(Foxp3),which are widely considered as important regulators of excessive inflammatory responses.CONCLUSIONS:The results of this study provide solid scientific evidence for the use of QD or its core active components in the clinical management of UC.展开更多
Indigo naturalis(青黛)is also called“indigo flower,”“bright cyan,”and“cyan clam powder.”The alias“indigo flower”shows its complex progress about producing dyes.The alias“bright cyan”vividly displays the visu...Indigo naturalis(青黛)is also called“indigo flower,”“bright cyan,”and“cyan clam powder.”The alias“indigo flower”shows its complex progress about producing dyes.The alias“bright cyan”vividly displays the visual characteristics of indigo naturalis.Its another alias“cyan clam powder”implies its properties,flavors,and particular morphologic characteristics.The name of“indigo naturalis”emphasizes its wide use in ancient times to paint their eyebrows.Indigo naturalis,which comes from the Persian Kingdom,wins the favor and praise of customers in the respects of dye and cosmetics in both Eastern and Western Regions.It not only shows the infinite charm of dye culture in the Western Regions and provides a visual sensation for people,but also adds new color for Chinese medicine culture.展开更多
Objective:This article systematically analyses the effects of adverse drug events/adverse drug reactions(ADEs/ADRs)of oral Indigo Naturalis(Qingdai)preparations in order to provide references for its rational clinical...Objective:This article systematically analyses the effects of adverse drug events/adverse drug reactions(ADEs/ADRs)of oral Indigo Naturalis(Qingdai)preparations in order to provide references for its rational clinical application.Methods:All clinical studies reporting ADE/ADR related to the oral administration of Qingdai preparations were searched through electronic databases,including PubMed,the Cochrane Library,Embase,China National Knowledge Infrastructure(CNKI),China Biology Medicine disc(CBM),VIP Information Chinese Journal Service Platform(VIP),and Wanfang database,from inception to September 27,2020.Information were extracted from these literatures,including primary disease,type of adverse reactions,dose,treatment,outcomes and so on.Incidence of ADE/ADR was estimated,as well as distribution of primary diseases and victim organs and systems were analyzed.Results:A total of 682 articles were included,with 651 clinical population studies and 31 case reports.Among them,604 detailed ADR/AE involving 33459 patients using oral Qingdai preparations,and a total of 5061 cases were found to present adverse events,including 2827 cases of digestive system(abdominal pain,diarrhea,etc.),469 cases of blood system damage(thrombocytopenia,leukopenia,anemia,etc.),313 cases of liver damage(abnormal liver function,liver toxicity,elevated liver enzymes,etc.),327 cases of nervous system reactions(headache,dizziness,poor sleep,etc.)and 1186 cases of other systems and organs.Severe adverse events(SAEs)mainly were liver damage,and could be relived after symptomatic treatment.Conclusion:From the systematic information retrieval and analysis,it is found that oral Qingdai preparations application may clinically cause ADEs/ADRs in terms of gastrointestinal tract and liver damage.Therefore,when using oral Qingdai preparations,liver and stomach protection should be done.At the same time,pay close attention to various biochemical indicators and the patient's drug response during the treatment process,and,if necessary,deal with it in time so as not to deteriorate the condition.Moreover,active surveillance system should be conducted to monitor ADE/ADR,so as to establish a clearer causal relationship between the drug and the adverse event.展开更多
To explore the molecular mechanism of Ind-igo Naturalis in intervening chronic myelocytic leukemia （CML） under the guidance of protein-protein interaction network, the molecular docking technique and in vitro c...To explore the molecular mechanism of Ind-igo Naturalis in intervening chronic myelocytic leukemia （CML） under the guidance of protein-protein interaction network, the molecular docking technique and in vitro cell experiment were chosen. CML-related genes were obtained from the online mendelian inheritance in man database （OMIM）, then String 10. 0 was used for text mining and constructing the CML protein-protein interaction network. The interaction data were input in Cytoscape 3. 4. 0 software. Plug-in CentiScaPe 2. 1 was used for implement topology analysis. Small active substances of Indigo Naturalis were obtained from a third-party database, which were optimized by Chemoffice 8. 0 and Sybyl 8. 1, then small molecular ligand library was obtained. The molecular docking was carried out by Surflex-Dock module, the key target was received after scoring. Protein-protein interaction network of CML was constructed, which was consisted of 425 nodes （ proteins） and 2 799 sides （ interactions）. The key gene J.AK2 was got. CML is a polygenic disease and JAK2 is likely to be a key node.展开更多
Background:Oral administration of indigo naturalis(IN)is used as a complementary and alternative medicine(CAM)regimen for the treatment of myelodysplastic syndromes(MDS).However,its mechanism of action has not been fu...Background:Oral administration of indigo naturalis(IN)is used as a complementary and alternative medicine(CAM)regimen for the treatment of myelodysplastic syndromes(MDS).However,its mechanism of action has not been fully elucidated and needs to be further explored.Methods:By searching the traditional Chinese medicine system and analyzing platforms(TCMSP),bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine(BATMAN-TCM),and Swiss Target Prediction network database,the main active components and potential targets of IN were obtained.Based on this,a component-target network was established by Cytoscape 3.6.1 software.Differentially expressed genes(DGEs)in MDS were obtained from three GEO(Gene Expression Omnibus)gene chips.Then,the protein-protein interaction(PPI)network of DGEs was constructed and analyzed by STRING database and Cytoscape 3.6.1 software.In addition,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)biological enrichment analysis were carried out using REVIGO and KEGG Orthology Based Annotation System(KOBAS)on DGEs,respectively.Identification of IN-MDS compound targets was performed by matching potential targets of active components with disease-related targets.The results of KEGG pathway enrichment analysis were combined with compound targets to screen key targets.In the end,molecular docking was performed by SYBYL-X2.1 to verify the key targets.Results:Nine active components of IN and 439 potential targets of IN were identified by analyzing TCMSP,BATMAN-TCM,and Swiss Target Prediction network databases.Three MDS disease-related gene microarray chips were obtained from the GEO databases:GSE4619,GSE19429,and GSE58831.Through this analysis,87 DEGs were finally obtained using the Venn diagram.A PPI network of DEGs was then constructed,in which 18 genes were upregulated and 69 genes were downregulated.After the GO enrichment results were de-redundant,the representative GO terms were obtained by using REVIGO semantic similarity measuremen.The KEGG biological pathway analysis using the KOBAS indicated that the Hippo signaling pathway is important in MDS.The Hippo signaling pathway involves four genes:AREG,LEF1,SMAD7,and TCF4.By matching and mapping DEGs with potential targets,six IN-MDS compound targets were obtained:PDE4B,PLAUR,ELANE,NR3C1,AREG,and LEF1.We found that AREG and LEF1 are consistent with the genes involved in the Hippo signaling pathway.Through molecular docking simulation,we found that the indican binds best to AREG and LEF1.Conclusion:Based on the integrated pharmacology model,the material basis of the efficacy and biological molecular mechanism of IN in the treatment of MDS was systematically studied,which provided a novel indication of the CAM regimen for the improvement of MDS management.展开更多
目的:通过网络药理学和分子对接初步揭示了青黛抗2型糖尿病的作用机制。方法:从中药系统药理学数据库与分析平台(TCMSP)中根据吸收和代谢情况选出青黛的有效成分及成分所对应的靶点,将靶点转换成对应的基因,取青黛和2型糖尿病的交集基因...目的:通过网络药理学和分子对接初步揭示了青黛抗2型糖尿病的作用机制。方法:从中药系统药理学数据库与分析平台(TCMSP)中根据吸收和代谢情况选出青黛的有效成分及成分所对应的靶点,将靶点转换成对应的基因,取青黛和2型糖尿病的交集基因做PPI蛋白互作网络图,通过David数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)分析,最后采用分子对接验证。结果:筛选得到青黛的活性成分9个、交集基因204个,通过蛋白互作分析发现“STAT3、JUN、MAPK3”可能有治疗2型糖尿病的作用,KEGG富集发现,且可能通过positive regulation of transcription from RNA polymerase II promotor、response to drug、positive regulation of gene expression等信号通路进行调控。分子对接结果表明青黛中的Bisindigotin、Indican、Isovitexin等活性成分与“STAT3、JUN、MAPK3”有比较强的结合能力。结论:青黛可能是通过Bisindigotin、Indican、Isovitexin等成分调控positive regulation of transcription from RNA polymerase II promotor等相关信号通路上的STAT3、JUN、MAPK3等基因发挥治疗2型糖尿病的作用。展开更多
文摘Introduction There is currently no standard treatment for relapsed and arsenic trioxide(ATO)-resistant acute promyelocytic leukemia(APL).Here,we report a case series of realgar-indigo naturalis formula(RIF)for the successful treatment of patients with relapsed and ATO-resistant APL.Case presentation Two patients in the first relapse and one in the second relapse failed to achieve hematologic complete remission(HCR)when reinduced by ATO;the other five patients progressed to relapse during ATO-based regimens for post-remission therapy.These eight patients received RIF in three doses per day totaling 130 mg/kg(≤30 pills)as induction therapy and achieved HCR at a median time of 46.5 days.They received 5 years of post-remission therapy,which consisted of combined chemotherapy followed by RIF.During this period,the patients did not experience renal dysfunction or QT interval prolongation.At the last follow-up,three patients survived without relapse,two patients survived with a second or third relapse and third or fourth remission,and the other three patients relapsed for a third or fourth time and died.The 5-year overall survival and event-free survival rates were 75.0%(95%confidence interval[CI]:31.5–93.1)and 37.5%(95%CI:5.6–71.7),respectively.Conclusion RIF for induction therapy and RIF combined with chemotherapy for post-remission therapy may represent an effective and safe protocol for the treatment of patients with relapsed and ATO-resistant APL.
基金Supported by Natural Science Foundation of Guangdong Province:Mechanism of Chang-An Decotion in Neuropeptide Spexin related GSK-3βRegulating Intestinal Nerve Immune Network in Ulcerative Colitis(No.2018A030310614)National Natural Science Foundation of China:Mchanism of Chang-An Decotion in Intestinal Mucosal Immunity of Ulcerative Colitis on Exocrine Mediated Rab27(No.81903963)Department of Education of Guangdong Province Project:Mchanism of Chang-An decotion of Ulcerative Colitis on Exocrine Mediated GSK-3βRegulating Th17/Treg in Ulcerative Colitis(No.2017KQNCX045)。
文摘OBJECTIVE:To elucidate the protective effect of Qingdai(Indigo Naturalis,QD)on ulcerative colitis(UC)by means of in silico and in vivo approaches.METHODS:A systems pharmacology analysis was performed to predict the active components of QD whereas the putative biological targets of QD against UC were obtained through target fishing,network cons-truction and enrichment analyses.Meanwhile,we examined the ameliorative effect of QD in a mouse model of dextran sulfate sodium(DSS)-induced colitis.During the 10-day experiment,the control and diseased mice were given with oral gavages of QD(1.3 g raw herbs·kg^(-1)·d^(-1))or 5-aminosalicylic acid(5-ASA,100 mg·kg^(-1)·d^(-1))every day.The underlying pharma-cological mechanisms of QD in UC were determined using polymerase chain reaction tests,histological staining,enzyme-linked immunoassays,and Western blotting analysis.RESULTS:Searching from various network pharmacology databases,29 compounds were identified in QD.According to the screening criteria suggested by TCMSP(i.e.OB≥30%and DL≥0.18),nine of them were considered the active ingredients that contribute to the ameliorative effects of QD on different mouse models of colitis.Most importantly,the protective effect of QD on DSS-induced colitis was significantly associated with modulations of the expression levels of glycogen synthase kinase 3-β(Gsk3-β)and forkhead box p3(Foxp3),which are widely considered as important regulators of excessive inflammatory responses.CONCLUSIONS:The results of this study provide solid scientific evidence for the use of QD or its core active components in the clinical management of UC.
文摘Indigo naturalis(青黛)is also called“indigo flower,”“bright cyan,”and“cyan clam powder.”The alias“indigo flower”shows its complex progress about producing dyes.The alias“bright cyan”vividly displays the visual characteristics of indigo naturalis.Its another alias“cyan clam powder”implies its properties,flavors,and particular morphologic characteristics.The name of“indigo naturalis”emphasizes its wide use in ancient times to paint their eyebrows.Indigo naturalis,which comes from the Persian Kingdom,wins the favor and praise of customers in the respects of dye and cosmetics in both Eastern and Western Regions.It not only shows the infinite charm of dye culture in the Western Regions and provides a visual sensation for people,but also adds new color for Chinese medicine culture.
基金This research was financially supported by The National Key R&D Program of China(Grant No.2019YFC1709802).
文摘Objective:This article systematically analyses the effects of adverse drug events/adverse drug reactions(ADEs/ADRs)of oral Indigo Naturalis(Qingdai)preparations in order to provide references for its rational clinical application.Methods:All clinical studies reporting ADE/ADR related to the oral administration of Qingdai preparations were searched through electronic databases,including PubMed,the Cochrane Library,Embase,China National Knowledge Infrastructure(CNKI),China Biology Medicine disc(CBM),VIP Information Chinese Journal Service Platform(VIP),and Wanfang database,from inception to September 27,2020.Information were extracted from these literatures,including primary disease,type of adverse reactions,dose,treatment,outcomes and so on.Incidence of ADE/ADR was estimated,as well as distribution of primary diseases and victim organs and systems were analyzed.Results:A total of 682 articles were included,with 651 clinical population studies and 31 case reports.Among them,604 detailed ADR/AE involving 33459 patients using oral Qingdai preparations,and a total of 5061 cases were found to present adverse events,including 2827 cases of digestive system(abdominal pain,diarrhea,etc.),469 cases of blood system damage(thrombocytopenia,leukopenia,anemia,etc.),313 cases of liver damage(abnormal liver function,liver toxicity,elevated liver enzymes,etc.),327 cases of nervous system reactions(headache,dizziness,poor sleep,etc.)and 1186 cases of other systems and organs.Severe adverse events(SAEs)mainly were liver damage,and could be relived after symptomatic treatment.Conclusion:From the systematic information retrieval and analysis,it is found that oral Qingdai preparations application may clinically cause ADEs/ADRs in terms of gastrointestinal tract and liver damage.Therefore,when using oral Qingdai preparations,liver and stomach protection should be done.At the same time,pay close attention to various biochemical indicators and the patient's drug response during the treatment process,and,if necessary,deal with it in time so as not to deteriorate the condition.Moreover,active surveillance system should be conducted to monitor ADE/ADR,so as to establish a clearer causal relationship between the drug and the adverse event.
文摘To explore the molecular mechanism of Ind-igo Naturalis in intervening chronic myelocytic leukemia （CML） under the guidance of protein-protein interaction network, the molecular docking technique and in vitro cell experiment were chosen. CML-related genes were obtained from the online mendelian inheritance in man database （OMIM）, then String 10. 0 was used for text mining and constructing the CML protein-protein interaction network. The interaction data were input in Cytoscape 3. 4. 0 software. Plug-in CentiScaPe 2. 1 was used for implement topology analysis. Small active substances of Indigo Naturalis were obtained from a third-party database, which were optimized by Chemoffice 8. 0 and Sybyl 8. 1, then small molecular ligand library was obtained. The molecular docking was carried out by Surflex-Dock module, the key target was received after scoring. Protein-protein interaction network of CML was constructed, which was consisted of 425 nodes （ proteins） and 2 799 sides （ interactions）. The key gene J.AK2 was got. CML is a polygenic disease and JAK2 is likely to be a key node.
文摘Background:Oral administration of indigo naturalis(IN)is used as a complementary and alternative medicine(CAM)regimen for the treatment of myelodysplastic syndromes(MDS).However,its mechanism of action has not been fully elucidated and needs to be further explored.Methods:By searching the traditional Chinese medicine system and analyzing platforms(TCMSP),bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine(BATMAN-TCM),and Swiss Target Prediction network database,the main active components and potential targets of IN were obtained.Based on this,a component-target network was established by Cytoscape 3.6.1 software.Differentially expressed genes(DGEs)in MDS were obtained from three GEO(Gene Expression Omnibus)gene chips.Then,the protein-protein interaction(PPI)network of DGEs was constructed and analyzed by STRING database and Cytoscape 3.6.1 software.In addition,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)biological enrichment analysis were carried out using REVIGO and KEGG Orthology Based Annotation System(KOBAS)on DGEs,respectively.Identification of IN-MDS compound targets was performed by matching potential targets of active components with disease-related targets.The results of KEGG pathway enrichment analysis were combined with compound targets to screen key targets.In the end,molecular docking was performed by SYBYL-X2.1 to verify the key targets.Results:Nine active components of IN and 439 potential targets of IN were identified by analyzing TCMSP,BATMAN-TCM,and Swiss Target Prediction network databases.Three MDS disease-related gene microarray chips were obtained from the GEO databases:GSE4619,GSE19429,and GSE58831.Through this analysis,87 DEGs were finally obtained using the Venn diagram.A PPI network of DEGs was then constructed,in which 18 genes were upregulated and 69 genes were downregulated.After the GO enrichment results were de-redundant,the representative GO terms were obtained by using REVIGO semantic similarity measuremen.The KEGG biological pathway analysis using the KOBAS indicated that the Hippo signaling pathway is important in MDS.The Hippo signaling pathway involves four genes:AREG,LEF1,SMAD7,and TCF4.By matching and mapping DEGs with potential targets,six IN-MDS compound targets were obtained:PDE4B,PLAUR,ELANE,NR3C1,AREG,and LEF1.We found that AREG and LEF1 are consistent with the genes involved in the Hippo signaling pathway.Through molecular docking simulation,we found that the indican binds best to AREG and LEF1.Conclusion:Based on the integrated pharmacology model,the material basis of the efficacy and biological molecular mechanism of IN in the treatment of MDS was systematically studied,which provided a novel indication of the CAM regimen for the improvement of MDS management.
文摘目的:通过网络药理学和分子对接初步揭示了青黛抗2型糖尿病的作用机制。方法:从中药系统药理学数据库与分析平台(TCMSP)中根据吸收和代谢情况选出青黛的有效成分及成分所对应的靶点,将靶点转换成对应的基因,取青黛和2型糖尿病的交集基因做PPI蛋白互作网络图,通过David数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)分析,最后采用分子对接验证。结果:筛选得到青黛的活性成分9个、交集基因204个,通过蛋白互作分析发现“STAT3、JUN、MAPK3”可能有治疗2型糖尿病的作用,KEGG富集发现,且可能通过positive regulation of transcription from RNA polymerase II promotor、response to drug、positive regulation of gene expression等信号通路进行调控。分子对接结果表明青黛中的Bisindigotin、Indican、Isovitexin等活性成分与“STAT3、JUN、MAPK3”有比较强的结合能力。结论:青黛可能是通过Bisindigotin、Indican、Isovitexin等成分调控positive regulation of transcription from RNA polymerase II promotor等相关信号通路上的STAT3、JUN、MAPK3等基因发挥治疗2型糖尿病的作用。
