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
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
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
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
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
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
Background:To preliminary the feasibility and the potential mechanism of classic ancient prescription of Chinese medicine Danggui Longhui pill in the treatment of COVID-19 based on network pharmacology.Methods:The act...Background:To preliminary the feasibility and the potential mechanism of classic ancient prescription of Chinese medicine Danggui Longhui pill in the treatment of COVID-19 based on network pharmacology.Methods:The active constituents and acting targets of classic ancient prescription of Chinese medicine Danggui Longhui pill were collected and screen out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platformand Genecard databases.Cytoscape-v3.7.2 software and Search Tool for the Retrieval of Interacting Genes databases were used to construct and analyze networks and protein-protein interaction network.The R programming language software combined with Bioconductor were used to analyze gene function(the gene oncology)and gene pathway(Kyoto Encyclopedia of Genes and Genomes)enrichment of the targets.Results:Seventy-three active constituents of classic ancient prescription of Chinese medicine classic ancient prescription of Chinese medicine Danggui Longhui pill played its effect on 48 targets through 83 signal pathway were effected,including advanced glycation end products/receptor for advanced glycation end products,interleukin-17,tumorecrosis factor,NOD-like receptor and cytokine-cytokine receptor interaction.Conclusion:Classic ancient prescription of Chinese medicine Danggui Longhui pill has certain feasibility in the treatment of COVID-19.To predict the potential mechanism of classic ancient prescription of Chinese medicine Danggui Longhui pill in the treatment of COVID-19 may be related to the regulate inflammation and immune system.展开更多
Indirubin(IND),a bisindole alkaloid with remarkable pharmacological activities,has attracted significant attention in the pharmaceutical field due to its antileukemic,anti-inflammatory,and immunomodulatory properties....Indirubin(IND),a bisindole alkaloid with remarkable pharmacological activities,has attracted significant attention in the pharmaceutical field due to its antileukemic,anti-inflammatory,and immunomodulatory properties.Currently,indirubin primarily relies on plant extraction and chemical synthesis,which are hindered by complex processes,low yields,and poor environmental compatibility.These challenges pose serious obstacles to clinical supply and sustainable industrial development.In recent years,microbial synthesis technology,which is based on synthetic biology and metabolic engineering,has provided a novel approach for the efficient production of indirubin.This method offers several advantages,including high efficiency,environmental sustainability,and eco-friendliness.Hence,this manuscript systematically summarizes the biosynthesis mechanisms of indirubin,the catalytic characteristics of key enzymes,the construction strategies of engineered bacteria,and the progress in fermentation condition.To address challenges such as the difficult separation of indirubin isomers,by-product inhibition,and industrialization bottlenecks,potential solutions are proposed,aiming to promote the green biomanufacturing of indirubin.展开更多
0bjective To investigate frsty Chinese patent medicine Realgar-Indigo Naturalis Formula(RIF),which mainly contains tetra-arsenic tetra-sufide formula for the maintenance therapy of ovarian cancer.Methods We recruited ...0bjective To investigate frsty Chinese patent medicine Realgar-Indigo Naturalis Formula(RIF),which mainly contains tetra-arsenic tetra-sufide formula for the maintenance therapy of ovarian cancer.Methods We recruited all patients with ovarian epithelial cancer who were diagnosed at Peking University People's Hospital between January 2018 and January 2021.All these patients received standard chemotherapy and achieved complete remission.The patients took RIF(60 mg/kg daily in an oral divided dose)in a 4-week-on and 4-week-off regimen.The main fficacy indicators,including progresson-free interval(PFI)and overall survival(0S),were measured and evaluated regularly.Additionally,the safety and side effects were closely monitored.Results A total of 20 patients were included in this study.Regarding the treatment,patients received oral arsenic for 3--18 courses(the longest treatment interval was equivalent to 3 years).The median follow-up time was 43 months.Subsequently,data analysis was conducted,revealing that the median PFI was 23 months.P53 mutations were worse than P53 wild-type PFI,and the median PFI was 19.2 months(p=0.03).Regarding P53 wt status,the HR for disease progression or death was 0.25(95%CI 0.07 to 0.91).The 3-year OS was 89%,and the 5-year OS was 77%.The common side effects were abdominal pain and diarrhoea.Conclusions RIF compound proved to be an efctive Chinese patent medicine maintenance therapy for ovarian cancer,thus prolonging the PFI of patients and controllable side effects,in particular simple and convenient for the method of administration and better potency ratio.These findings need to be validated in multicentre research studies with large sample sizes.Trial registration number ChiCTR2400090349.展开更多
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.
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.
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.
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.
基金supported by Scientific Research Youth Fund of Health Department of Fujian Province(2018-1-90)Educational and Scientific Research Fund for Young and Middle-aged Teachers of Fujian Province(JAT191299)Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology,Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety(FS1809).
文摘Background:To preliminary the feasibility and the potential mechanism of classic ancient prescription of Chinese medicine Danggui Longhui pill in the treatment of COVID-19 based on network pharmacology.Methods:The active constituents and acting targets of classic ancient prescription of Chinese medicine Danggui Longhui pill were collected and screen out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platformand Genecard databases.Cytoscape-v3.7.2 software and Search Tool for the Retrieval of Interacting Genes databases were used to construct and analyze networks and protein-protein interaction network.The R programming language software combined with Bioconductor were used to analyze gene function(the gene oncology)and gene pathway(Kyoto Encyclopedia of Genes and Genomes)enrichment of the targets.Results:Seventy-three active constituents of classic ancient prescription of Chinese medicine classic ancient prescription of Chinese medicine Danggui Longhui pill played its effect on 48 targets through 83 signal pathway were effected,including advanced glycation end products/receptor for advanced glycation end products,interleukin-17,tumorecrosis factor,NOD-like receptor and cytokine-cytokine receptor interaction.Conclusion:Classic ancient prescription of Chinese medicine Danggui Longhui pill has certain feasibility in the treatment of COVID-19.To predict the potential mechanism of classic ancient prescription of Chinese medicine Danggui Longhui pill in the treatment of COVID-19 may be related to the regulate inflammation and immune system.
基金financially supported by the General Program of the National Natural Science Foundation of China,China(No.82173976)the National Key Research and Development Program of China,China(No.2018YFC1707205)the College Students'Innovation and Entrepreneurship Training Program(No.S202410633063).
文摘Indirubin(IND),a bisindole alkaloid with remarkable pharmacological activities,has attracted significant attention in the pharmaceutical field due to its antileukemic,anti-inflammatory,and immunomodulatory properties.Currently,indirubin primarily relies on plant extraction and chemical synthesis,which are hindered by complex processes,low yields,and poor environmental compatibility.These challenges pose serious obstacles to clinical supply and sustainable industrial development.In recent years,microbial synthesis technology,which is based on synthetic biology and metabolic engineering,has provided a novel approach for the efficient production of indirubin.This method offers several advantages,including high efficiency,environmental sustainability,and eco-friendliness.Hence,this manuscript systematically summarizes the biosynthesis mechanisms of indirubin,the catalytic characteristics of key enzymes,the construction strategies of engineered bacteria,and the progress in fermentation condition.To address challenges such as the difficult separation of indirubin isomers,by-product inhibition,and industrialization bottlenecks,potential solutions are proposed,aiming to promote the green biomanufacturing of indirubin.
基金supported by the thehorizontal project:Antitumor effects of Realgar-Indigo naturalis formula(RIF)combined with Apatinib on platinumresistant ovarian cancer Research(Project No.2022-Z-23).
文摘0bjective To investigate frsty Chinese patent medicine Realgar-Indigo Naturalis Formula(RIF),which mainly contains tetra-arsenic tetra-sufide formula for the maintenance therapy of ovarian cancer.Methods We recruited all patients with ovarian epithelial cancer who were diagnosed at Peking University People's Hospital between January 2018 and January 2021.All these patients received standard chemotherapy and achieved complete remission.The patients took RIF(60 mg/kg daily in an oral divided dose)in a 4-week-on and 4-week-off regimen.The main fficacy indicators,including progresson-free interval(PFI)and overall survival(0S),were measured and evaluated regularly.Additionally,the safety and side effects were closely monitored.Results A total of 20 patients were included in this study.Regarding the treatment,patients received oral arsenic for 3--18 courses(the longest treatment interval was equivalent to 3 years).The median follow-up time was 43 months.Subsequently,data analysis was conducted,revealing that the median PFI was 23 months.P53 mutations were worse than P53 wild-type PFI,and the median PFI was 19.2 months(p=0.03).Regarding P53 wt status,the HR for disease progression or death was 0.25(95%CI 0.07 to 0.91).The 3-year OS was 89%,and the 5-year OS was 77%.The common side effects were abdominal pain and diarrhoea.Conclusions RIF compound proved to be an efctive Chinese patent medicine maintenance therapy for ovarian cancer,thus prolonging the PFI of patients and controllable side effects,in particular simple and convenient for the method of administration and better potency ratio.These findings need to be validated in multicentre research studies with large sample sizes.Trial registration number ChiCTR2400090349.
