Background： Hypotension induced by combined spinal epidural anesthesia in parturient with hypertensive disorders of pregnancy （HDP） can easily compromise blood supply to vital organs including uteroplacental perfus...Background： Hypotension induced by combined spinal epidural anesthesia in parturient with hypertensive disorders of pregnancy （HDP） can easily compromise blood supply to vital organs including uteroplacental perfusion and result in fetal distress. The aim of this study was to investigate whether the goal-directed fluid therapy （GDFT） with LiDCOrapid system can improve well-being of both HDP parturient and their babies. Methods： Fifty-two stable HDP parturient scheduled for elective cesarean delivery were recruited. After loading with 10 ml/kg lactated Ringer＇s solution （LR）, parturient were randomized to the GDFT and control group. In the GDFT group, individualized fluid therapy was guided by increase in stroke volume （ASV） provided via LiDCO rapid system. The control group received the routine fluid therapy. The primary endpoints included maternal hypotension and the doses of vasopressors administered prior to fetal delivery. The secondary endpoints included umbilical blood gas abnormalities and neonatal adverse events. Results： The severity of HDP was similar between two groups. The total LR infusion （P 〈 0.01） and urine output （P 〈 0.05） were higher in the GDFT group than in the control group. Following twice fluid challenge tests, the systolic blood pressure, mean blood pressure, cardiac output and SV in the GDFT group were significantly higher, and the heart rate was lower than in the control group. The incidence of maternal hypotension and doses of phenylephrine used prior to fetal delivery were significantly higher in the control group than in the GDFT group （P 〈 0.01）. There were no differences in the Apgar scores between two groups. In the control group, the mean values of pH in umbilical artery/vein were remarkably decreased （P 〈 0.05）, and the incidences of neonatal hypercapnia and hypoxemia were statistically increased （P 〈 0.05） than in the GDFT group. Conclusions： Dynamic responsiveness guided fluid therapy with the LiDCOrapid system may provid展开更多
Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine a...Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-β-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) andhuman malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with theGene delivery system targeting VEGF receptors relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.展开更多
The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still lo...The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer(CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment(TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death(ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3(Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin(QTN) that elicited reactive oxygen species(ROS). To amelioratein vivo delivery barriers associated with chemotherapeutic drugs, a folate(FA)-targeted polyethylene glycol(PEG)-modified amphiphilic cyclodextrin nanoparticle(NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation(CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.展开更多
Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immu...Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immunotherapeutic drugs,has emerged as a promising approach for cancer treatment,with the advantages of cooperating two kinds of treatment mechanism,reducing the dosage of the drug and enhancing therapeutic effect.Moreover,nano-based drug delivery system(NDDS)was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery,tumor microenvironment response and site-specific release.Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations,such as liposomes(Doxil R,Lipusu R),nanoparticles(Abraxane R)and micelles(Genexol-PM R).The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment,which could greatly enhance the therapeutic efficacy,reduce the side effects and optimize the clinical outcomes of cancer patients.Herein,the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed,and recent advances of NDDS applied for chemoimmunotherapy were further reviewed.展开更多
Cancer is a deadly disease that is globally and consistently one of the leading causes of mortality every year.Despite the availability of chemotherapy,radiotherapy,immunotherapy,and surgery,a cure for cancer has not ...Cancer is a deadly disease that is globally and consistently one of the leading causes of mortality every year.Despite the availability of chemotherapy,radiotherapy,immunotherapy,and surgery,a cure for cancer has not been attained.Recently,exosomes have gained significant attention due to the therapeutic potential of their various components including proteins,lipids,nucleic acids,miRNAs,and lncRNAs.Exosomes constitute a set of tiny extracellular vesicles with an approximate diameter of 30-100 nm.They are released from different cells and are present in biofluids including blood,cerebrospinal fluid(CSF),and urine.They perform crucial multifaceted functions in the malignant progression of cancer via autocrine,paracrine,and endocrine communications.The ability of exosomes to carry different cargoes including drug and molecular information to recipient cells make them a novel tool for cancer therapeutics.In this review,we discuss the major components of exosomes and their role in cancer progression.We also review important literature about the potential role of exosomes as vaccines and delivery carriers in the context of cancer therapeutics.展开更多
The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells,which is usually caused by abnormal gene expression.RNA interference mediated by si RNA and mi RNA can sele...The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells,which is usually caused by abnormal gene expression.RNA interference mediated by si RNA and mi RNA can selectively knock down the carcinogenic genes by targeting specific m RNAs.Therefore,combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy.Due to poor stability and solubility associated with gene agents and drugs,suitable protective carriers are needed and have been widely researched for the co-delivery.In this review,we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents,as well as the advances in co-delivery systems.展开更多
In the present study,we prepared nattokinase-loaded self-double-emulsifying drug delivery system(SDEDDS)and investigated its preliminary pharmacodynamics.The type and concentration of oil phase,inner aqueous phase and...In the present study,we prepared nattokinase-loaded self-double-emulsifying drug delivery system(SDEDDS)and investigated its preliminary pharmacodynamics.The type and concentration of oil phase,inner aqueous phase and emulsifier were screened to prepare optimum nattokinase-loaded SDEDDS.Next,the optimum formulations were characterized based on microstructure,volume-weighted mean droplet size,self-emulsifying rate,yield,storage stability,in vitro release and in vivo pharmacodynamics studies.The water/oil/watermultiple emulsions exhibited typicalmultiple structure,with relatively small volumeweighted mean droplet size 6.0±0.7μm and high self-emulsifying ability(self-emulsifying time<2 min).Encapsulation of nattokinase was up to 86.8±8.2%.The cumulative release of nattokinase within 8 h was about 30%,exhibiting a sustained release effect.The pharmacodynamics study indicated that nattokinase-loaded SDEDDS could significantly prolong the whole blood clotting time in mouse and effectively improve the carrageenan-induced tail thrombosis compared with nattokinase solution.Moreover,we showed that SDEDDS could successfully self-emulsify into water/oil/water multiple emulsions upon dilution in dispersion medium with gentle stirring and effectively protect nattokinase activity in gastric environment.Our findings suggested that SDEDDS could be a promising strategy for peptide and protein drugs by oral administration.展开更多
文摘Background： Hypotension induced by combined spinal epidural anesthesia in parturient with hypertensive disorders of pregnancy （HDP） can easily compromise blood supply to vital organs including uteroplacental perfusion and result in fetal distress. The aim of this study was to investigate whether the goal-directed fluid therapy （GDFT） with LiDCOrapid system can improve well-being of both HDP parturient and their babies. Methods： Fifty-two stable HDP parturient scheduled for elective cesarean delivery were recruited. After loading with 10 ml/kg lactated Ringer＇s solution （LR）, parturient were randomized to the GDFT and control group. In the GDFT group, individualized fluid therapy was guided by increase in stroke volume （ASV） provided via LiDCO rapid system. The control group received the routine fluid therapy. The primary endpoints included maternal hypotension and the doses of vasopressors administered prior to fetal delivery. The secondary endpoints included umbilical blood gas abnormalities and neonatal adverse events. Results： The severity of HDP was similar between two groups. The total LR infusion （P 〈 0.01） and urine output （P 〈 0.05） were higher in the GDFT group than in the control group. Following twice fluid challenge tests, the systolic blood pressure, mean blood pressure, cardiac output and SV in the GDFT group were significantly higher, and the heart rate was lower than in the control group. The incidence of maternal hypotension and doses of phenylephrine used prior to fetal delivery were significantly higher in the control group than in the GDFT group （P 〈 0.01）. There were no differences in the Apgar scores between two groups. In the control group, the mean values of pH in umbilical artery/vein were remarkably decreased （P 〈 0.05）, and the incidences of neonatal hypercapnia and hypoxemia were statistically increased （P 〈 0.05） than in the GDFT group. Conclusions： Dynamic responsiveness guided fluid therapy with the LiDCOrapid system may provid
文摘Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-β-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) andhuman malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with theGene delivery system targeting VEGF receptors relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.
基金financial support from the Department of Education of Jilin Province,China(JJKH20190099KJ)the Outstanding Youth Foundation from the Department of Science and Technology of Jilin Province,China(20170520046JH)+6 种基金Health Commission of Jilin Province,China(2020Q012)Fundamental Research Funds for the Central Universities(China)Talents Cultivation Program of Jilin Universityfinancial support from National Natural Science Foundation of China(81774240,82074154)Siming Scholar from Shanghai Shuguang Hospital(SGXZ-201904,China)financial support from Science Foundation Ireland co-funded under the European Regional Development:Centre for Research in Medical Devices,CURAM(13/RC/2073,Ireland)Synthesis and Solid State Cluster,SSPC(12/RC/2275,Ireland),and Centre for Advanced Materials and Bio Engineering Research,AMBER(12/RC/2275,Ireland)。
文摘The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer(CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment(TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death(ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3(Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin(QTN) that elicited reactive oxygen species(ROS). To amelioratein vivo delivery barriers associated with chemotherapeutic drugs, a folate(FA)-targeted polyethylene glycol(PEG)-modified amphiphilic cyclodextrin nanoparticle(NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation(CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.
基金supported by the National Natural Science Foundation of China(No.81974498,No.81773652)。
文摘Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immunotherapeutic drugs,has emerged as a promising approach for cancer treatment,with the advantages of cooperating two kinds of treatment mechanism,reducing the dosage of the drug and enhancing therapeutic effect.Moreover,nano-based drug delivery system(NDDS)was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery,tumor microenvironment response and site-specific release.Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations,such as liposomes(Doxil R,Lipusu R),nanoparticles(Abraxane R)and micelles(Genexol-PM R).The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment,which could greatly enhance the therapeutic efficacy,reduce the side effects and optimize the clinical outcomes of cancer patients.Herein,the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed,and recent advances of NDDS applied for chemoimmunotherapy were further reviewed.
基金supported by National Cancer Institute(NCI)R00 CA226353-01A1Cancer Research Foundation Young Investigator Award to HJC+2 种基金Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq)grant(309380/2019-7)Fundacao de Amparoa Pesquisa do Estado de Sao Paulo(FAPESP)(2017/10051-2)to MBa fellowship supported by CNPq grant(133306/2019-4)during the development of this work.
文摘Cancer is a deadly disease that is globally and consistently one of the leading causes of mortality every year.Despite the availability of chemotherapy,radiotherapy,immunotherapy,and surgery,a cure for cancer has not been attained.Recently,exosomes have gained significant attention due to the therapeutic potential of their various components including proteins,lipids,nucleic acids,miRNAs,and lncRNAs.Exosomes constitute a set of tiny extracellular vesicles with an approximate diameter of 30-100 nm.They are released from different cells and are present in biofluids including blood,cerebrospinal fluid(CSF),and urine.They perform crucial multifaceted functions in the malignant progression of cancer via autocrine,paracrine,and endocrine communications.The ability of exosomes to carry different cargoes including drug and molecular information to recipient cells make them a novel tool for cancer therapeutics.In this review,we discuss the major components of exosomes and their role in cancer progression.We also review important literature about the potential role of exosomes as vaccines and delivery carriers in the context of cancer therapeutics.
基金supported by the National Natural Science Foundation of China (No.81373342)Beijing Natural Science Foundation (Nos.2141004 and 7142114)
文摘The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells,which is usually caused by abnormal gene expression.RNA interference mediated by si RNA and mi RNA can selectively knock down the carcinogenic genes by targeting specific m RNAs.Therefore,combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy.Due to poor stability and solubility associated with gene agents and drugs,suitable protective carriers are needed and have been widely researched for the co-delivery.In this review,we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents,as well as the advances in co-delivery systems.
基金supported by National Natural Science Foundation of China(No.81373338).
文摘In the present study,we prepared nattokinase-loaded self-double-emulsifying drug delivery system(SDEDDS)and investigated its preliminary pharmacodynamics.The type and concentration of oil phase,inner aqueous phase and emulsifier were screened to prepare optimum nattokinase-loaded SDEDDS.Next,the optimum formulations were characterized based on microstructure,volume-weighted mean droplet size,self-emulsifying rate,yield,storage stability,in vitro release and in vivo pharmacodynamics studies.The water/oil/watermultiple emulsions exhibited typicalmultiple structure,with relatively small volumeweighted mean droplet size 6.0±0.7μm and high self-emulsifying ability(self-emulsifying time<2 min).Encapsulation of nattokinase was up to 86.8±8.2%.The cumulative release of nattokinase within 8 h was about 30%,exhibiting a sustained release effect.The pharmacodynamics study indicated that nattokinase-loaded SDEDDS could significantly prolong the whole blood clotting time in mouse and effectively improve the carrageenan-induced tail thrombosis compared with nattokinase solution.Moreover,we showed that SDEDDS could successfully self-emulsify into water/oil/water multiple emulsions upon dilution in dispersion medium with gentle stirring and effectively protect nattokinase activity in gastric environment.Our findings suggested that SDEDDS could be a promising strategy for peptide and protein drugs by oral administration.
