Cachexia represents a chronic,multiorgan,integrative wasting disease.Patients with advanced cancer often develop cachexia,denoted as"cancer-associated cachexia".Cancer-associated cachexia remains a formidabl...Cachexia represents a chronic,multiorgan,integrative wasting disease.Patients with advanced cancer often develop cachexia,denoted as"cancer-associated cachexia".Cancer-associated cachexia remains a formidable challenge that plagues mankind,prompting ongoing efforts in both Western and Chinese medicine to find viable solutions;however,as of yet,no effective treatment that can reverse cancer-associated cachexia has been identified.Integrating Chinese and Western medicine approaches has shown promise in mitigating the symptoms of wasting and anorexia associated with cancer-associated cachexia,potentially heralding a novel paradigm in its treatment and management.In this article,we summarize existing mechanistic studies and treatment modalities through a comprehensive review of relevant literature and research findings,elucidating potential challenges and future avenues for development in the treatment of"cancer-associated cachexia"using an integrated Chinese and Western medicine approach.展开更多
Objective:To investigate the effects of compound Danshen dripping pills(CDDP)on diffuse intravascular coagulation(DIC)and explore the possible mechanism of CDDP based on transcriptomic analysis.Materials and Methods:W...Objective:To investigate the effects of compound Danshen dripping pills(CDDP)on diffuse intravascular coagulation(DIC)and explore the possible mechanism of CDDP based on transcriptomic analysis.Materials and Methods:We replicated animal models of DIC using different inducers and observed the effects of CDDP on the survival rate of the model animals,hepatic and gastric fundus blood flow,abnormal prothrombin time(PT),fibrinogen(FIB)content and inflammatory factors,liver and kidney injury index.Thereafter,whole-blood transcriptome sequencing was performed,and the main target genes were selected for verification.Results:CDDP improved the survival rate of model animals,increased blood flow in the liver and stomach,improved PT and FIB values,inhibited the elevated serum levels of tumor necrosis factor-alpha and interleukin-10,increased the activity of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase,and enhanced the levels of blood urea nitrogen and creatinine.Whole-blood transcriptome sequencing analysis showed that CDDP may regulate immune inflammatory response,oxidative stress,platelet activation and aggregation,and cell apoptosis in DIC.Quantitative polymerase chain reaction(qPCR)further confirmed that CDDP improved the abnormal expression of Sqstml,Ctsd,Mylk2,and Nfkbib in the model animals.Conclusions:CDDP exerts a protective effect on the primary organs of animal models of DIC by improving organ blood flow and coagulation abnormalities and inhibiting the expression of inflammatory factors.In addition,CDDP improved the prognosis of animal models of DIC by increasing the expression of key disease-related genes,such as Sqstml and Nfkbib.展开更多
Objective:This study aimed to explore the mechanism of action of ShaoMaZhiJing granules(SMZJ)in the treatment of Tourette syndrome(TS)using metabolomic and proteomic methods.Materials and Methods:Sprague-Dawley rats w...Objective:This study aimed to explore the mechanism of action of ShaoMaZhiJing granules(SMZJ)in the treatment of Tourette syndrome(TS)using metabolomic and proteomic methods.Materials and Methods:Sprague-Dawley rats were divided into five groups:control,model,haloperidol,low-dose SMZJ(SML),and high-dose SMZJ(SMH).The TS model was established by intraperitoneally injecting 3,3'of iminodipropionitrile(IDPN).After 21 d of administration,stereotypical behaviors were observed,and brain samples were collected.Gas chromatography-time-of-flight mass spectrometry(MS)analysis was performed to analyze the brain metabolites.Furthermore,the differential proteins in the brain were analyzed using isotope-labeled relative and absolute quantitative(iTRAQ?)techniques combined with liquid chromatography-tandem mass spectrometry(LC-MS/MS).Validation experiments used enzyme-linked immunosorbent assay to measure protein phosphatase 2A(PP2A)levels.Results:Behavioral assessments revealed that the frequency of head raising and circumgyration was significantly lower in the SML group than that in the model group(P<0.05),and the frequency of head raising was significantly lower in the SMH group than that in the model group(P<0.01).The metabolomic analysis revealed that L-cysteine and uridine levels were downregulated after SMZJ treatment,and these molecules were associated with arginine,proline,taurine,hypotaurine,glutathione,cysteine,and methionine metabolism.Furthermore,iTRAQ analysis revealed that PP2A,proteasomeβsubunit-3,and thymosinβ-4 levels were significantly decreased,whereas transmembrane protein 33 level was significantly upregulated after SMZJ treatment.Validation experiments revealed that PP2A levels returned to normal after SMZJ treatment.Conclusions:Our study suggests that SMZJ improves the symptoms of IDPN-induced TS in rats.SMZJ may regulate the dopaminergic synapses,glutamatergic synapses,glutathione metabolism,and energy metabolism in rats.展开更多
BACKGROUND Previously,we have successfully constructed replication-competent hepatitis B virus(HBV)vectors by uncoupling the P open reading frame(ORF)from the preC/C ORF to carefully design the transgene insertion sit...BACKGROUND Previously,we have successfully constructed replication-competent hepatitis B virus(HBV)vectors by uncoupling the P open reading frame(ORF)from the preC/C ORF to carefully design the transgene insertion site to overcome the compact organization of the HBV genome and maintain HBV replication competence.Consequently,the replication-competent HBV vectors carrying foreign genes,including pCH-BsdR,carrying blasticidin resistance gene(399 bp),and pCH-hrGFP,carrying humanized renilla green fluorescent protein gene(720 bp),were successfully obtained.However,the replication efficiency of the former is higher but it is tedious to use,while that of the latter is poor and cannot be quantified.Hence,we need to search for a new reporter gene that is convenient and quantifiable for further research.AIM To establish a helpful tool for intracellular HBV replication and anti-viral drugs screening studies.METHODS We utilized the replication-competent HBV viral vectors constructed by our laboratory,combined with the secreted luciferase reporter gene,to construct replication-competent HBV vectors expressing the reporter gene secretory Nanoluc Luciferase(SecNluc).HepG2.TA2-7 cells were transfected with this vector to obtain cell lines with stably secreted HBV particles carrying secNluc reporter gene.RESULTS The replication-competent HBV vector carrying the SecNluc reporter gene pCHsNLuc could produce all major viral RNAs and a full set of envelope proteins and achieve high-level secreted luciferase expression.HBV replication intermediates could be produced from this vector.Via transfection with pTRE-sNLuc and selection by hygromycin,we obtained isolated cell clones,named HBV-NLuc-35 cells,which could secrete secNLuc recombinant viruses,and were sensitive to existing anti-HBV drugs.Using differentiated HepaRG cells,it was verified that recombinant HBV possessed infectivity.CONCLUSION Our research demonstrated that a replication-competent HBV vector carrying a secreted luciferase transgene possesses replication and expression ability,and the established HBV replication and expression cell lines could stably secrete viral particles carrying secNluc reporter gene.More importantly,the cell line and the secreted recombinant viral particles could be used to trace HBV replication or infection.展开更多
基金supported by China Center for the Development of Traditional Chinese Medicine Science and Technology Joint research project(CXZH202307)Shaanxi Province Traditional Chinese Medicine“Double Chain Integration”Young and Middle-aged Scientific Research and Innovation Team Project(2022-SLRH-LJ-006).
文摘Cachexia represents a chronic,multiorgan,integrative wasting disease.Patients with advanced cancer often develop cachexia,denoted as"cancer-associated cachexia".Cancer-associated cachexia remains a formidable challenge that plagues mankind,prompting ongoing efforts in both Western and Chinese medicine to find viable solutions;however,as of yet,no effective treatment that can reverse cancer-associated cachexia has been identified.Integrating Chinese and Western medicine approaches has shown promise in mitigating the symptoms of wasting and anorexia associated with cancer-associated cachexia,potentially heralding a novel paradigm in its treatment and management.In this article,we summarize existing mechanistic studies and treatment modalities through a comprehensive review of relevant literature and research findings,elucidating potential challenges and future avenues for development in the treatment of"cancer-associated cachexia"using an integrated Chinese and Western medicine approach.
文摘Objective:To investigate the effects of compound Danshen dripping pills(CDDP)on diffuse intravascular coagulation(DIC)and explore the possible mechanism of CDDP based on transcriptomic analysis.Materials and Methods:We replicated animal models of DIC using different inducers and observed the effects of CDDP on the survival rate of the model animals,hepatic and gastric fundus blood flow,abnormal prothrombin time(PT),fibrinogen(FIB)content and inflammatory factors,liver and kidney injury index.Thereafter,whole-blood transcriptome sequencing was performed,and the main target genes were selected for verification.Results:CDDP improved the survival rate of model animals,increased blood flow in the liver and stomach,improved PT and FIB values,inhibited the elevated serum levels of tumor necrosis factor-alpha and interleukin-10,increased the activity of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase,and enhanced the levels of blood urea nitrogen and creatinine.Whole-blood transcriptome sequencing analysis showed that CDDP may regulate immune inflammatory response,oxidative stress,platelet activation and aggregation,and cell apoptosis in DIC.Quantitative polymerase chain reaction(qPCR)further confirmed that CDDP improved the abnormal expression of Sqstml,Ctsd,Mylk2,and Nfkbib in the model animals.Conclusions:CDDP exerts a protective effect on the primary organs of animal models of DIC by improving organ blood flow and coagulation abnormalities and inhibiting the expression of inflammatory factors.In addition,CDDP improved the prognosis of animal models of DIC by increasing the expression of key disease-related genes,such as Sqstml and Nfkbib.
基金supported by the Tianjin Science and Technology Program Projects Science and Technology Major Special Projects and Engineering and the original Chinese medicine SMZJ secondary development,No.21ZXZYSY00010。
文摘Objective:This study aimed to explore the mechanism of action of ShaoMaZhiJing granules(SMZJ)in the treatment of Tourette syndrome(TS)using metabolomic and proteomic methods.Materials and Methods:Sprague-Dawley rats were divided into five groups:control,model,haloperidol,low-dose SMZJ(SML),and high-dose SMZJ(SMH).The TS model was established by intraperitoneally injecting 3,3'of iminodipropionitrile(IDPN).After 21 d of administration,stereotypical behaviors were observed,and brain samples were collected.Gas chromatography-time-of-flight mass spectrometry(MS)analysis was performed to analyze the brain metabolites.Furthermore,the differential proteins in the brain were analyzed using isotope-labeled relative and absolute quantitative(iTRAQ?)techniques combined with liquid chromatography-tandem mass spectrometry(LC-MS/MS).Validation experiments used enzyme-linked immunosorbent assay to measure protein phosphatase 2A(PP2A)levels.Results:Behavioral assessments revealed that the frequency of head raising and circumgyration was significantly lower in the SML group than that in the model group(P<0.05),and the frequency of head raising was significantly lower in the SMH group than that in the model group(P<0.01).The metabolomic analysis revealed that L-cysteine and uridine levels were downregulated after SMZJ treatment,and these molecules were associated with arginine,proline,taurine,hypotaurine,glutathione,cysteine,and methionine metabolism.Furthermore,iTRAQ analysis revealed that PP2A,proteasomeβsubunit-3,and thymosinβ-4 levels were significantly decreased,whereas transmembrane protein 33 level was significantly upregulated after SMZJ treatment.Validation experiments revealed that PP2A levels returned to normal after SMZJ treatment.Conclusions:Our study suggests that SMZJ improves the symptoms of IDPN-induced TS in rats.SMZJ may regulate the dopaminergic synapses,glutamatergic synapses,glutathione metabolism,and energy metabolism in rats.
基金Supported by the National Natural Science Foundation of China,No.81672041the National Major Science and Technology Special Project for Infectious Diseases of China,No.2012ZX10004503-012
文摘BACKGROUND Previously,we have successfully constructed replication-competent hepatitis B virus(HBV)vectors by uncoupling the P open reading frame(ORF)from the preC/C ORF to carefully design the transgene insertion site to overcome the compact organization of the HBV genome and maintain HBV replication competence.Consequently,the replication-competent HBV vectors carrying foreign genes,including pCH-BsdR,carrying blasticidin resistance gene(399 bp),and pCH-hrGFP,carrying humanized renilla green fluorescent protein gene(720 bp),were successfully obtained.However,the replication efficiency of the former is higher but it is tedious to use,while that of the latter is poor and cannot be quantified.Hence,we need to search for a new reporter gene that is convenient and quantifiable for further research.AIM To establish a helpful tool for intracellular HBV replication and anti-viral drugs screening studies.METHODS We utilized the replication-competent HBV viral vectors constructed by our laboratory,combined with the secreted luciferase reporter gene,to construct replication-competent HBV vectors expressing the reporter gene secretory Nanoluc Luciferase(SecNluc).HepG2.TA2-7 cells were transfected with this vector to obtain cell lines with stably secreted HBV particles carrying secNluc reporter gene.RESULTS The replication-competent HBV vector carrying the SecNluc reporter gene pCHsNLuc could produce all major viral RNAs and a full set of envelope proteins and achieve high-level secreted luciferase expression.HBV replication intermediates could be produced from this vector.Via transfection with pTRE-sNLuc and selection by hygromycin,we obtained isolated cell clones,named HBV-NLuc-35 cells,which could secrete secNLuc recombinant viruses,and were sensitive to existing anti-HBV drugs.Using differentiated HepaRG cells,it was verified that recombinant HBV possessed infectivity.CONCLUSION Our research demonstrated that a replication-competent HBV vector carrying a secreted luciferase transgene possesses replication and expression ability,and the established HBV replication and expression cell lines could stably secrete viral particles carrying secNluc reporter gene.More importantly,the cell line and the secreted recombinant viral particles could be used to trace HBV replication or infection.
