Colorectal cancer(CRC)is one of the most common malignancies of the digestive tract,with the annual incidence and mortality increasing consistently.Oxaliplatinbased chemotherapy is a preferred therapeutic regimen for ...Colorectal cancer(CRC)is one of the most common malignancies of the digestive tract,with the annual incidence and mortality increasing consistently.Oxaliplatinbased chemotherapy is a preferred therapeutic regimen for patients with advanced CRC.However,most patients will inevitably develop resistance to oxaliplatin.Many studies have reported that non-coding RNAs(ncRNAs),such as microRNAs,long non-coding RNAs,and circular RNAs,are extensively involved in cancer progression.Moreover,emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation,and by epigenetic modification.In this review,we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin.Furthermore,we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy.This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.展开更多
Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the...Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic receptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.展开更多
Background:Shengmai Yin(SMY)formula,a traditional Chinese medicine,shows a definite therapeutic effect on chronic heart failure(CHF)in clinical practice,but the molecular mechanism remains largely unknown.The PI3K/Akt...Background:Shengmai Yin(SMY)formula,a traditional Chinese medicine,shows a definite therapeutic effect on chronic heart failure(CHF)in clinical practice,but the molecular mechanism remains largely unknown.The PI3K/Akt/mTOR pathway is a classic pathway of autophagy and plays a pivotal role in the occurrence and development of CHF.Here,we aimed to investigate whether SMY formula treat CHF rats by inhibiting excessive autophagy.Methods:Echocardiography was conducted to evaluate cardiac function.Transmission electron microscopy was used to observe the arrangement of myocardial cells.Enzyme linked immunosorbent assay analysis was performed to quantitative detecting the content of N-terminal pro-B-type natriuretic peptide,stromelysin-2,TNF-α in rat serum.Western blotting was used to detect the expression of AKT,p-AKT,mTOR,p-mTOR,light chain 3(LC3),and p62.In vitro,myocardial cells were treated with hypoxia reoxygenation and then intervened with SMY.Cell counting kit-8 method was used to measure the cell viability.The immunofluorescence expression of LC3 protein were also examined.Results:In vivo,SMY intervention assisted in the ventricular remodeling,reduced the levels of N-terminal pro-B-type natriuretic peptide,stromelysin-2,TNF-αin serum,and recovered myocardial cell structure in CHF rats.Treatment with SMY significantly promoted the ratio of p-AKT/AKT,p-mTOR/mTOR,and down-regulated the expression level of p62 and the ratio of LC3-Ⅱ/LC3-Ⅰ.In vitro,when the concentration of SMY containing serum reached 40% in the medium,the activity of myocardial cells reached the highest at 135.14%.SMY inhibited the expression of LC3 in hypoxic-reoxygenation embryonic ventricular myocytes cells.When the hypoxic reoxygenation cells treated with p-mTOR inhibitor,rapamycin,or p-AKT inhibitor,API-1,SMY could also down-regulated the LC3 expression level.Conclusions:SMY formula functions in restoring cardiac function and promoting myocardial ultrastructural recovery by reducing autophagy activity through up-regulating the ratio of p-AKT/AKT,p-mTOR/mTOR,and down-regulating the expression level of p62 and the ratio of LC3-Ⅱ/LC3-Ⅰ in CHF rats.展开更多
With the incessant propulsion of the Open Door Policy,which is related to the consolidation of international collaborative partnerships,an increasing number of Chinese companies are moving toward cooperating countries...With the incessant propulsion of the Open Door Policy,which is related to the consolidation of international collaborative partnerships,an increasing number of Chinese companies are moving toward cooperating countries to participate in infrastructure construction,employing a win-win strategy in favor of the people and governments of both countries.Among the cooperation domains,our country’s electrical companies have achieved a series of remarkable results in the international Engineering,Procurement,and Construction(EPC)project market with their outstanding business capabilities and technical advantages.Nevertheless,some shortcomings cannot be overlooked,the most notable of which appears to be the impediment associated with engineering translation,which has always been an obsession among translators of Chinese companies.Taking the transmission line project in the Republic of Madagascar as an example,an analysis of French-Chinese translation methods of electrical engineering terminology in the field of the transmission line is carried out.展开更多
Pyrethroids can be ingested by humans through eating contaminated oysters,which is potentially harmful to health.This study aimed to investigate the effects of raw,steaming,and roasting on cypermethrin(CP)and fenpropa...Pyrethroids can be ingested by humans through eating contaminated oysters,which is potentially harmful to health.This study aimed to investigate the effects of raw,steaming,and roasting on cypermethrin(CP)and fenpropathrin(FP)in oysters during simulated digestion.Results showed that the amount of released CP and FP was different from raw(CP:0.617μg·g−1,FP:0.266μg·g−1),steaming(CP:0.498μg·g−1,FP:0.660μg·g−1),and roasting(CP:1.186μg·g−1,FP:0.588μg·g−1)at the end of simulated digestion.The share of cis-CP and low-efficiency CP increased significantly(p<0.05),and the share of high-efficiency trans-CP did not maintain a high level for a long time during simulated digestion.The fluorimetric titration and isothermal titration calorimetry confirmed that CP and FP could spontaneously interact with oyster actin,and CP could bind with oyster actin more tightly than FP.This study reveals that cooking methods affect the binding capacity of CP and FP to oyster tissues and influence the changes of CP and FP in oysters during digestion.Furthermore,the current study provides a reference for assessing the potential harm of pyrethroids in oysters to consumers.展开更多
基金The Natural Science Foundation of Shandong Province,No.ZR2020MH238.
文摘Colorectal cancer(CRC)is one of the most common malignancies of the digestive tract,with the annual incidence and mortality increasing consistently.Oxaliplatinbased chemotherapy is a preferred therapeutic regimen for patients with advanced CRC.However,most patients will inevitably develop resistance to oxaliplatin.Many studies have reported that non-coding RNAs(ncRNAs),such as microRNAs,long non-coding RNAs,and circular RNAs,are extensively involved in cancer progression.Moreover,emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation,and by epigenetic modification.In this review,we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin.Furthermore,we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy.This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.
基金This work was financially supported by the National Natural Science Foundation of China(Grant Nos.:82074323 and 81673572)Key Research and Development Program of Shanxi Province(Grant No.:202102130501010)+2 种基金Innovation Project for Graduate Students in Shanxi Province(Grant No.:2022Y162)the Major Science and Technology Project for“Significant New Drugs Creation”(Grant No.:2017ZX09301047)Research Project Supported by Shanxi Scholarship Council of China(Grant No.:2020019).
文摘Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic receptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.
基金financially supported by Foundation of Tianjin Municipal Education Commission(2019KJ058).
文摘Background:Shengmai Yin(SMY)formula,a traditional Chinese medicine,shows a definite therapeutic effect on chronic heart failure(CHF)in clinical practice,but the molecular mechanism remains largely unknown.The PI3K/Akt/mTOR pathway is a classic pathway of autophagy and plays a pivotal role in the occurrence and development of CHF.Here,we aimed to investigate whether SMY formula treat CHF rats by inhibiting excessive autophagy.Methods:Echocardiography was conducted to evaluate cardiac function.Transmission electron microscopy was used to observe the arrangement of myocardial cells.Enzyme linked immunosorbent assay analysis was performed to quantitative detecting the content of N-terminal pro-B-type natriuretic peptide,stromelysin-2,TNF-α in rat serum.Western blotting was used to detect the expression of AKT,p-AKT,mTOR,p-mTOR,light chain 3(LC3),and p62.In vitro,myocardial cells were treated with hypoxia reoxygenation and then intervened with SMY.Cell counting kit-8 method was used to measure the cell viability.The immunofluorescence expression of LC3 protein were also examined.Results:In vivo,SMY intervention assisted in the ventricular remodeling,reduced the levels of N-terminal pro-B-type natriuretic peptide,stromelysin-2,TNF-αin serum,and recovered myocardial cell structure in CHF rats.Treatment with SMY significantly promoted the ratio of p-AKT/AKT,p-mTOR/mTOR,and down-regulated the expression level of p62 and the ratio of LC3-Ⅱ/LC3-Ⅰ.In vitro,when the concentration of SMY containing serum reached 40% in the medium,the activity of myocardial cells reached the highest at 135.14%.SMY inhibited the expression of LC3 in hypoxic-reoxygenation embryonic ventricular myocytes cells.When the hypoxic reoxygenation cells treated with p-mTOR inhibitor,rapamycin,or p-AKT inhibitor,API-1,SMY could also down-regulated the LC3 expression level.Conclusions:SMY formula functions in restoring cardiac function and promoting myocardial ultrastructural recovery by reducing autophagy activity through up-regulating the ratio of p-AKT/AKT,p-mTOR/mTOR,and down-regulating the expression level of p62 and the ratio of LC3-Ⅱ/LC3-Ⅰ in CHF rats.
文摘With the incessant propulsion of the Open Door Policy,which is related to the consolidation of international collaborative partnerships,an increasing number of Chinese companies are moving toward cooperating countries to participate in infrastructure construction,employing a win-win strategy in favor of the people and governments of both countries.Among the cooperation domains,our country’s electrical companies have achieved a series of remarkable results in the international Engineering,Procurement,and Construction(EPC)project market with their outstanding business capabilities and technical advantages.Nevertheless,some shortcomings cannot be overlooked,the most notable of which appears to be the impediment associated with engineering translation,which has always been an obsession among translators of Chinese companies.Taking the transmission line project in the Republic of Madagascar as an example,an analysis of French-Chinese translation methods of electrical engineering terminology in the field of the transmission line is carried out.
基金supported by the National Key R&D Program of China(2019YFD0901704).
文摘Pyrethroids can be ingested by humans through eating contaminated oysters,which is potentially harmful to health.This study aimed to investigate the effects of raw,steaming,and roasting on cypermethrin(CP)and fenpropathrin(FP)in oysters during simulated digestion.Results showed that the amount of released CP and FP was different from raw(CP:0.617μg·g−1,FP:0.266μg·g−1),steaming(CP:0.498μg·g−1,FP:0.660μg·g−1),and roasting(CP:1.186μg·g−1,FP:0.588μg·g−1)at the end of simulated digestion.The share of cis-CP and low-efficiency CP increased significantly(p<0.05),and the share of high-efficiency trans-CP did not maintain a high level for a long time during simulated digestion.The fluorimetric titration and isothermal titration calorimetry confirmed that CP and FP could spontaneously interact with oyster actin,and CP could bind with oyster actin more tightly than FP.This study reveals that cooking methods affect the binding capacity of CP and FP to oyster tissues and influence the changes of CP and FP in oysters during digestion.Furthermore,the current study provides a reference for assessing the potential harm of pyrethroids in oysters to consumers.
