To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we establishe...To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound expression of HO-1 protein as well as HO activity was 1.8- and 2.0-fold increased respectively in the transfected cells compared to the non-transfected ones. The treatment of VSMC with different concentrations of H2O2 led to the remarkable cell damage as indicated by survival rate and LDH leakage. However, the resistance of the HO-1 transfected VSMC against H2O2 was significantly raised. This protective effect was dramatically diminished when the transfected VSMC were pretreated with ZnPP-IX, a specific inhibitor of HO, for 24 h. In addition, we found that the growth potential of the transfected cells was significantly inhibited directly by increased activity of HO-1, and this effect might be related to decreased phosphorylation of MAPK. These results suggest that the overexpression of introduced hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation.展开更多
目的为解决中药药性描述的抽象、模糊导致难以准确把握其本质特性的问题,提出一种基于多层前馈神经网络(BP神经网络)的药向量训练(quantitative model of traditional Chinese medicine’s properties based on BP neural network,QM-BP...目的为解决中药药性描述的抽象、模糊导致难以准确把握其本质特性的问题,提出一种基于多层前馈神经网络(BP神经网络)的药向量训练(quantitative model of traditional Chinese medicine’s properties based on BP neural network,QM-BP)模型,实现中药药性的量化表示。方法首先对中药及其对应的功效进行整理,获得"中药-功效"样本对;其次,构建"中药-药向量-功效"3层结构的QM-BP模型,并利用中药的药性数据对模型进行初始化;最后,基于QM-BP模型使用"中药-功效"样本进行训练,得到BP药向量。结果将《中药学》教材所涉及的474味中药及其528个功效基于QM-BP模型训练并结合临床分析,发现训练后得到的BP药向量比药性的初始量化值更能反映中药的属性特征。此外,由于BP药向量与词向量具有相似的性质,发现功效相似的药物对应的BP药向量在欧几里得距离中距离较近,而功效差异较大的中药药向量在欧几里得距离中距离较远。结论利用BP神经网络构建药向量训练模型,在中药药性与功效具有关联性的基础上,对药性量化值进行修正,以期使药性量化值更精确。今后可优化QM-BP模型并开展药对、复方分析,以期探明中药药性及组方配伍中蕴藏的内在规律。展开更多
Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic ...Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.展开更多
Liver fibrosis results from chronic damages together with an accumulation of extracellular matrix,and no specific medical therapy is approved for that until now.Due to liver metabolic capacity for drugs,the fragility ...Liver fibrosis results from chronic damages together with an accumulation of extracellular matrix,and no specific medical therapy is approved for that until now.Due to liver metabolic capacity for drugs,the fragility of drugs,and the presence of insurmountable physiological obstacles in the way of targeting,the development of efficient drug delivery systems for anti-fibrotics seems vital.We have explored articles with a different perspective on liver fibrosis over the two decades,then collected and summarized the information by providing corresponding in vitro and in vivo cases.We have discussed the mechanism of hepatic fibrogenesis with different ways of fibrosis induction in animals.Furthermore,the critical chemical and herbal anti-fibrotics,biological molecules such as micro-RNAs,siRNAs,and growth factors,which can affect cell division and differentiation,are mentioned.Likewise,drug and gene delivery and therapeutic systems on in vitro and in vivo models are summarized in the data tables.This review article enlightens recent advances in emerging drugs and nanocarriers and represents perspectives on targeting strategies employed in liver fibrosis treatment.展开更多
Tuberculosis remains a public health threat of global proportions.Iron is a scarce resource indispensable to both host and pathogen during infection with Mycobacterium tuberculosis,the causative agent of tuberculosis....Tuberculosis remains a public health threat of global proportions.Iron is a scarce resource indispensable to both host and pathogen during infection with Mycobacterium tuberculosis,the causative agent of tuberculosis.Siderophores are critical molecules for iron acquisition under iron-limiting conditions and,as a very efficient pathogen,M.tuberculosis has evolved elaborate siderophores knowledge of which is being intensively translated into clinical practice.This paper summarizes the structures,types and physiological functions of Mycobacterium siderophores with emphasis on siderophore-inspired design of drugs and drug delivery vehicles.展开更多
Background:Mass drug administration(MDA)programmes for the control of lymphatic filariasis in Ghana,have been ongoing in some endemic districts for 16 years.The current study aimed to assess factors that govern the su...Background:Mass drug administration(MDA)programmes for the control of lymphatic filariasis in Ghana,have been ongoing in some endemic districts for 16 years.The current study aimed to assess factors that govern the success of MDA programmes for breaking transmission of lymphatic filariasis in Ghana.Methods:The study was undertaken in two"hotspot"districts(Ahanta West and Kassena Nankana West)and two control districts(Mpohor and Bongo)in Ghana.Mosquitoes were collected and identified using morphological and molecular tools.A proportion of the cibarial armatures of each species was examined.Dissections were performed onAnopheles gambiae for filarial worm detection.A questionnaire was administered to obtain information on MDA compliance and vector control activities.Data were compared between districts to determine factors that might explain persistent transmission of lymphatic filariasis.Results:High numbers of mosquitoes were sampled in Ahanta West district compared to Mpohor district(F=16.09,P=0.002).There was no significant difference between the numbers of mosquitoes collected in Kassena Nankana West and Bongo districts(F=2.16,P=0.185).Mansonia species were predominant in Ahanta West district.An.coluzzii mosquitoes were prevalent in all districts.An.melas with infected and infective filarial worms was found only in Ahanta West district.No differences were found in cibarial teeth numbers and shape for mosquito species in the surveyed districts.Reported MDA coverage was high in all districts.The average use of bednet and indoor residual spraying was 82.4 and 66.2%,respectively.There was high compliance in the five preceding MDA rounds in Ahanta West and Kassena Nankana West districts,both considered hotspots of lymphatic filariasis transmission.Conclusions:The study on persistent transmission of lymphatic filariasis in the two areas in Ghana present information that shows the importance of local understanding of factors affecting control and elimination of lymphatic filariasis.Unlike Kassena Nankana West district展开更多
Objective: To explore the antitumor and potential off-target effects of systemically delivered cholesterol-conjugatedlet-7a mimics(Chol-let-7a) and control mimics(Chol-miRCtrl) on hepatocellular carcinomain vivo.Metho...Objective: To explore the antitumor and potential off-target effects of systemically delivered cholesterol-conjugatedlet-7a mimics(Chol-let-7a) and control mimics(Chol-miRCtrl) on hepatocellular carcinomain vivo.Methods: The antitumor effects of two intravenous dosing regimens ofChol-let-7a on heptocellular carcinoma growth were compared using an orthotopic xenograft mouse model. Off-targets were analyzed with histopathological and ultrapathological features of heparenal tissue and cells in theChol-let-7a-, Chol-miRCtrl-, and saline-treated (blank) xenograft mice and normal control mice. Then,let-7a abundance in orthotopic tumors, corresponding paracancerous hepatic tissue, and normal liver tissue from healthy nude mice was examined by reverse transcription-polymerase chain reaction. The distribution ofChol-let-7a andChol-miRCtrl in vivo was examined by whole-animal imaging and frozen-sections observation. The experiments were approved by the Institutional Research Board of Peking Union Medical College Hospital.Results: Continuous treatment withChol-let-7a resulted in tumors that were 35.86% and 40.02% the size of those in theChol-miRCtrl and blank xenograft group (P < 0.01 andP < 0.01, respectively), while intermittent dosing withChol-let-7a resulted in tumors that were 65.42% and 56.66% the size of those in theChol-miRCtrl and the blank control group, respectively (P < 0.05 andP < 0.05). In addition, some histopathological and ultrapathological features were only observed after treatment with the two cholesterol-conjugated molecules, however mild with intermittent dosingChol-let-7a treatment, such as diffuse sinusoidal dilation and edema, primarily around the centrolobular vein in heptic tissues;mild hypercellularity with dilated capillary lumens in the renal tissue;and some organelle abnormalities found in heptic and renal cells. Furthermore, whole-animal imaging showed thatChol-let-7a andChol-miRCtrl were predominantly distributed in the liver, kidney, and bladder regions after injection, and that the concent展开更多
基金This work was kindly supported by Na-tional Natural Science Foundation of China(No.39670308)
文摘To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound expression of HO-1 protein as well as HO activity was 1.8- and 2.0-fold increased respectively in the transfected cells compared to the non-transfected ones. The treatment of VSMC with different concentrations of H2O2 led to the remarkable cell damage as indicated by survival rate and LDH leakage. However, the resistance of the HO-1 transfected VSMC against H2O2 was significantly raised. This protective effect was dramatically diminished when the transfected VSMC were pretreated with ZnPP-IX, a specific inhibitor of HO, for 24 h. In addition, we found that the growth potential of the transfected cells was significantly inhibited directly by increased activity of HO-1, and this effect might be related to decreased phosphorylation of MAPK. These results suggest that the overexpression of introduced hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation.
文摘目的为解决中药药性描述的抽象、模糊导致难以准确把握其本质特性的问题,提出一种基于多层前馈神经网络(BP神经网络)的药向量训练(quantitative model of traditional Chinese medicine’s properties based on BP neural network,QM-BP)模型,实现中药药性的量化表示。方法首先对中药及其对应的功效进行整理,获得"中药-功效"样本对;其次,构建"中药-药向量-功效"3层结构的QM-BP模型,并利用中药的药性数据对模型进行初始化;最后,基于QM-BP模型使用"中药-功效"样本进行训练,得到BP药向量。结果将《中药学》教材所涉及的474味中药及其528个功效基于QM-BP模型训练并结合临床分析,发现训练后得到的BP药向量比药性的初始量化值更能反映中药的属性特征。此外,由于BP药向量与词向量具有相似的性质,发现功效相似的药物对应的BP药向量在欧几里得距离中距离较近,而功效差异较大的中药药向量在欧几里得距离中距离较远。结论利用BP神经网络构建药向量训练模型,在中药药性与功效具有关联性的基础上,对药性量化值进行修正,以期使药性量化值更精确。今后可优化QM-BP模型并开展药对、复方分析,以期探明中药药性及组方配伍中蕴藏的内在规律。
文摘Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.
基金financial support of Tabriz University of Medical Science(Iran)
文摘Liver fibrosis results from chronic damages together with an accumulation of extracellular matrix,and no specific medical therapy is approved for that until now.Due to liver metabolic capacity for drugs,the fragility of drugs,and the presence of insurmountable physiological obstacles in the way of targeting,the development of efficient drug delivery systems for anti-fibrotics seems vital.We have explored articles with a different perspective on liver fibrosis over the two decades,then collected and summarized the information by providing corresponding in vitro and in vivo cases.We have discussed the mechanism of hepatic fibrogenesis with different ways of fibrosis induction in animals.Furthermore,the critical chemical and herbal anti-fibrotics,biological molecules such as micro-RNAs,siRNAs,and growth factors,which can affect cell division and differentiation,are mentioned.Likewise,drug and gene delivery and therapeutic systems on in vitro and in vivo models are summarized in the data tables.This review article enlightens recent advances in emerging drugs and nanocarriers and represents perspectives on targeting strategies employed in liver fibrosis treatment.
基金supported by the National Key Infectious Disease Project(No.2008ZX10003-006)National Natural Science Foundation(Grant No.81071316)+2 种基金Excellent PhD Thesis Fellowship of Southwest University(Nos.kb2009010 and ky2009009)the Fundamental Research Fund for the Central Universities(No.XDJK2009A003)Natural Science Foundation Project of CQ CSTC(No.2010BB5002)。
文摘Tuberculosis remains a public health threat of global proportions.Iron is a scarce resource indispensable to both host and pathogen during infection with Mycobacterium tuberculosis,the causative agent of tuberculosis.Siderophores are critical molecules for iron acquisition under iron-limiting conditions and,as a very efficient pathogen,M.tuberculosis has evolved elaborate siderophores knowledge of which is being intensively translated into clinical practice.This paper summarizes the structures,types and physiological functions of Mycobacterium siderophores with emphasis on siderophore-inspired design of drugs and drug delivery vehicles.
基金This study was supported by SightSavers International,Ghana and the Centre for Neglected Tropical Diseases,Liverpool School of Tropical MedicineSPB is grateful to the "Amt fur Ausbildungsbeitrage"of the canton of Basel-Stadt for a PhD fellowship.
文摘Background:Mass drug administration(MDA)programmes for the control of lymphatic filariasis in Ghana,have been ongoing in some endemic districts for 16 years.The current study aimed to assess factors that govern the success of MDA programmes for breaking transmission of lymphatic filariasis in Ghana.Methods:The study was undertaken in two"hotspot"districts(Ahanta West and Kassena Nankana West)and two control districts(Mpohor and Bongo)in Ghana.Mosquitoes were collected and identified using morphological and molecular tools.A proportion of the cibarial armatures of each species was examined.Dissections were performed onAnopheles gambiae for filarial worm detection.A questionnaire was administered to obtain information on MDA compliance and vector control activities.Data were compared between districts to determine factors that might explain persistent transmission of lymphatic filariasis.Results:High numbers of mosquitoes were sampled in Ahanta West district compared to Mpohor district(F=16.09,P=0.002).There was no significant difference between the numbers of mosquitoes collected in Kassena Nankana West and Bongo districts(F=2.16,P=0.185).Mansonia species were predominant in Ahanta West district.An.coluzzii mosquitoes were prevalent in all districts.An.melas with infected and infective filarial worms was found only in Ahanta West district.No differences were found in cibarial teeth numbers and shape for mosquito species in the surveyed districts.Reported MDA coverage was high in all districts.The average use of bednet and indoor residual spraying was 82.4 and 66.2%,respectively.There was high compliance in the five preceding MDA rounds in Ahanta West and Kassena Nankana West districts,both considered hotspots of lymphatic filariasis transmission.Conclusions:The study on persistent transmission of lymphatic filariasis in the two areas in Ghana present information that shows the importance of local understanding of factors affecting control and elimination of lymphatic filariasis.Unlike Kassena Nankana West district
基金supported partly by the National Human and Health Scientific Data Sharing Platform,Clinical Center of China(No.2004DKA20240-2014)National Program funded by the Ministry of Science and Technology of China(No.2015KJRK1L01).
文摘Objective: To explore the antitumor and potential off-target effects of systemically delivered cholesterol-conjugatedlet-7a mimics(Chol-let-7a) and control mimics(Chol-miRCtrl) on hepatocellular carcinomain vivo.Methods: The antitumor effects of two intravenous dosing regimens ofChol-let-7a on heptocellular carcinoma growth were compared using an orthotopic xenograft mouse model. Off-targets were analyzed with histopathological and ultrapathological features of heparenal tissue and cells in theChol-let-7a-, Chol-miRCtrl-, and saline-treated (blank) xenograft mice and normal control mice. Then,let-7a abundance in orthotopic tumors, corresponding paracancerous hepatic tissue, and normal liver tissue from healthy nude mice was examined by reverse transcription-polymerase chain reaction. The distribution ofChol-let-7a andChol-miRCtrl in vivo was examined by whole-animal imaging and frozen-sections observation. The experiments were approved by the Institutional Research Board of Peking Union Medical College Hospital.Results: Continuous treatment withChol-let-7a resulted in tumors that were 35.86% and 40.02% the size of those in theChol-miRCtrl and blank xenograft group (P < 0.01 andP < 0.01, respectively), while intermittent dosing withChol-let-7a resulted in tumors that were 65.42% and 56.66% the size of those in theChol-miRCtrl and the blank control group, respectively (P < 0.05 andP < 0.05). In addition, some histopathological and ultrapathological features were only observed after treatment with the two cholesterol-conjugated molecules, however mild with intermittent dosingChol-let-7a treatment, such as diffuse sinusoidal dilation and edema, primarily around the centrolobular vein in heptic tissues;mild hypercellularity with dilated capillary lumens in the renal tissue;and some organelle abnormalities found in heptic and renal cells. Furthermore, whole-animal imaging showed thatChol-let-7a andChol-miRCtrl were predominantly distributed in the liver, kidney, and bladder regions after injection, and that the concent
