AIM: Toll-like receptor 4 (TLR4) has been shown to be important for bacterial infection, especially to lipopolysaccharide signaling. Its possible role in HBV infection is studied in the present study. MATERIALS AND...AIM: Toll-like receptor 4 (TLR4) has been shown to be important for bacterial infection, especially to lipopolysaccharide signaling. Its possible role in HBV infection is studied in the present study. MATERIALS AND METHODS: pHBV3.6 plasmid, containing full-length HBV genome was used in the murine model of acute HBV expression by hydrodynamics in vivo transfection. TLR4 normal or mutant mouse strain was compared to investigate the possible role of TLR4 in acute HBV expression. RESULTS: After pHBV3.6 injection, the infiltrating leukocytes expressed TLR4 were observed nearby the HBsAg-expressing hepatocytes. The HBV antigenemia as well as the replication and transcription were higher in TLR4-mutant C3H/HeJ mice than in normal C3H/ HeN mice. The HBV-specific immune responses were impaired in the liver or spleen of the C3H/HeJ mice. Their inducible nitric oxide synthase (iNOS) expression on the hepatic infiltrating cells was also impaired. When adoptively transferring splenocytes from C3H/HeN mice to C3H/HeJ mice, the HBV replication was inhibited to the level as that of C3H/HeN. CONCLUSION: These results suggest that TLR4 plays an anti-HBV role in vivo through the induction of iNOSexpression and HBV-specific immune responses after HBV expression.展开更多
MicroRNAs (miRNAs) are an emerging class of highly conserved non-coding small RNAs that regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of ...MicroRNAs (miRNAs) are an emerging class of highly conserved non-coding small RNAs that regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of cellular activity, including differentiation and development, metabolism, proliferation, apoptotic cell death, viral infection and tumorigenesis. Recent studies provide clear evidence that miRNAs are abundant in the liver and modulate a diverse spectrum of liver functions. Deregulation of miRNA expression may be a key pathogenetic factor in many liver diseases including viral hepatitis, hepatocellular cancer and polycystic liver diseases. A clearer understanding of the mechanisms involved in miRNA deregulation will offer new diagnostic and therapeutic strategies to treat liver diseases. Moreover, better understanding of miRNA regulation and identification of tissue-specific miRNA targets employing transgenic/knockout models and/or modulating oligonucleotides will improve our knowledge of liver physiology and diseases.展开更多
Objective To evaluate the effects of environmental factors and microRNAs (miRNAs) (miR-126, miR-143, and miR-145) on the risk of coronary heart disease (CHD). Methods A frequency-matched case-control study (450...Objective To evaluate the effects of environmental factors and microRNAs (miRNAs) (miR-126, miR-143, and miR-145) on the risk of coronary heart disease (CHD). Methods A frequency-matched case-control study (450 patients, 450 controls) was conducted from April 2014 to December 2016 in Fuzhou City, China. Environmental factors were investigated using a self-administered questionnaire, and the expression levels of miR-126, rniR-143, and miR-145 were determined by quantitative real-time Polymerase Chain Reaction (PCR) in pe- ripheral blood mononuclear cells. Unconditional logistic regression models were used for statistical evaluation. Results Alcohol consumption, high-salt diets, high-intensity work, and lack of physical activity were significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. MiR-126, miR-143, and miR-145 were highly expressed in the CHD group compared with the control group. After adjustment for other environmental factors, unconditional logistic regression results revealed that miR-126, miR-143, and depression were the independent risk factors of CHD, and light diet was the independent protective factor of CHD. Conclusions Our data suggest that a family history of CHD, anxiety, and alcohol consumption was significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. Furthermore, miR-126 and miR-143 in combination with several risk factors, could play a joint role in the development of CHD. Therefore, it is necessary to manage patients with CHD in all directions and multiple level.展开更多
Nonalcoholic fatty liver disease(NAFLD) is associated with obesity,insulin resistance,and type 2 diabetes.NAFLD represents a large spectrum of diseases ranging from(1) fatty liver(hepatic steatosis);(2) steatosis with...Nonalcoholic fatty liver disease(NAFLD) is associated with obesity,insulin resistance,and type 2 diabetes.NAFLD represents a large spectrum of diseases ranging from(1) fatty liver(hepatic steatosis);(2) steatosis with inflammation and necrosis;to(3) cirrhosis.The animal models to study NAFLD/nonalcoholic steatohepatitis(NASH) are extremely useful,as there are still many events to be elucidated in the pathology of NASH.The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis,but these remain incompletely understood.The different mouse models can be classified in two large groups.The first one includes genetically modified(transgenic or knockout) mice that spontaneously develop liver disease,and the second one includes mice that acquire the disease after dietary or pharmacological manipulation.Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex,genetically modified animal models may be a key for the treatment of NAFLD.Ideal animal models for NASH should closely resemble the pathological characteristics observed in humans.To date,no single animal model has encompassed the full spectrum of human disease progression,but they can imitate particular characteristics of human disease.Therefore,it is important that the researchers choose the appropriate animal model.This review discusses various genetically modified animal models developed and used in research on NAFLD.展开更多
AIM: To determine the relationship between biliary stricture and pigment gallstone formation, and the prevention of pigment gallstones with medicine. METHODS: One hundred and eighteen male guinea pigs were randomly di...AIM: To determine the relationship between biliary stricture and pigment gallstone formation, and the prevention of pigment gallstones with medicine. METHODS: One hundred and eighteen male guinea pigs were randomly divided into four groups: stricture group (S, n = 30) underwent partial ligation of common bile duct, and fed on regular chow; S plus medicine group (S+M, n = 27) underwent the same operation but fed on medicinal chow (0.3 g chenodeoxycholic acid, 0.5 g glucurolactone, and 0.5 g aspirin were mixed up in 1.2 kg regular chow); medicinal control group (C+M, n = 30) was free of operation, and fed on medicinal chow; and control group (C, n = 31) was free of operation and fed on regular chow. One week later, laparotomy was performed, and the bile of gallbladder was collected, measured, and cultured. RESULTS: Gallstones were identif ied. Pigment gallstones were induced by biliary stricture in 95% (22/23) of S group. In the S+M group, the incidence of gallstone was reduced to 55% (11/20, vs S group, P < 0.01). The changes of indirect bilirubin and ionized calcium in the bile were consistent with gallstone incidences. CONCLUSION: Biliary stricture can cause pigment gallstone formation in guinea pigs, and the medicines used can lower the incidence of gallstones. The bilirubin and ionized calcium play important roles in pigment gallstone formation.展开更多
Objective: To investigate the effect of intratracheally administered BCG DNA on a murine model of asthma. Methods: BALB/C mice were divided into 4 groups: normal control group, asthma model group, BCG DNA administered...Objective: To investigate the effect of intratracheally administered BCG DNA on a murine model of asthma. Methods: BALB/C mice were divided into 4 groups: normal control group, asthma model group, BCG DNA administered before OVA sensitization group, BCG DNA administered after OVA challenge group. The asthma models were developed by immunizing BALB/C mice with OVA. A total of 100 μg BCG DNA was intratracheally administered before OVA sensitization and after OVA challenge. WBC count and eosinophil percentage (EOS%) in bronchoalveolar lavage fluid (BALF) were measured. Changes of IL 4 , IL 5,IL 12, IFN γ in BALF were determined by ELISA. Pulmonary inflammation was observed on normal pathological slides and the proliferation and mucus secretion of goblet cells stained by AB PAS were also observed. Results: IL 4 , IL 5,IL 12, IFN γ in BALF of normal control group were(32.3±5.7)pg/ml,(15.6±3.9)pg/ml,(80±8.5)pg/ml,(153.2±9.4)pg/ml respectively. IL 4,IL 5 in BALF of asthma model group increased to (299±15.6)pg/ml and (206.7±9.3)pg/ml, while IL 12 and IFN γ decreased to (20.4±4.1)pg/ml and (51.6±5.5) pg/ml respectively. BCG DNA administered intratracheally before OVA sensitization and after OVA challenge significantly increased IL 12 [(71.6±8.3)pg/ml,(67.8±8.1pg/ml)] and IFN γ [(119.0±11.3)pg/ml,(114.7±10.1)pg/ml] in the BALF. Meanwhile, BCG DNA decreased IL 4 [(82.1±6.1)pg/ml,(86.3±5.9)pg/ml] and IL 5 [(32.3±4.6)pg/ml,(37.4±5.3)pg/ml]. Eosinophil level in BALF was inhibited and the pulmonary inflammation was dramatically relieved compared to asthma model group. Conclusion: Intratracheally administered BCG DNA can induce IL 12 and IFN γ secretion,inhibit Th2 response which can relieve allergic airway inflammation and provide a new way in the treatment and prevention of asthma.展开更多
Cardiomyopathies are diseases that primarily affect the myocardium, leading to serious cardiac dysfunction and heart failure. Out of the three major categories of cardiomyopathies (hypertrophic, dilated and restrict...Cardiomyopathies are diseases that primarily affect the myocardium, leading to serious cardiac dysfunction and heart failure. Out of the three major categories of cardiomyopathies (hypertrophic, dilated and restrictive), restrictive cardiomyopathy (RCM) is less common and also the least studied. However, the prognosis for RCM is poor as some patients dying in their childhood. The molecular mechanisms behind the disease development and progression are not very clear and the treatment of RCM is very difficult and often ineffective. In this article, we reviewed the recent progress in RCM research from the clinical studies and the translational studies done on diseased transgenic animal models. This will help for a better understanding of the mechanisms underlying the etiology and development of RCM and for the design of better treatments for the disease.展开更多
AIM:To investigate the relationship between overexpression of urokinase plasminogen activator(uPA) and hepatitis B virus(HBV) related liver diseases in a transgenic mouse model.METHODS:Albumin-tetracycline reverse tra...AIM:To investigate the relationship between overexpression of urokinase plasminogen activator(uPA) and hepatitis B virus(HBV) related liver diseases in a transgenic mouse model.METHODS:Albumin-tetracycline reverse transcriptional activator and tetO-uPA transgenic mice were generated respectively through pronuclear injection and crossed to produce the double transgenic in-alb-uPA mice,for which doxycycline(Dox)-inducible and liver-specific over-expression of uPA can be achieved.Hydrodynamic transfection of plasmid adeno-associated virus(AAV)1.3HBV was performed through the tail veins of the Dox-induced in-alb-uPA mice.Expression of uPA and HBV antigens were analyzed through double-staining immunohistochemical assay.Cytokine production was detected by enzyme linked immunosorbent assay and α-fetoprotein(AFP) mRNA level was evaluated through real-time quantitative polymerase chain reaction.RESULTS:Plasmid AAV-1.3HBV hydrodynamic transfection in Dox-induced transgenic mice not only resulted in severe liver injury with hepatocarcinoma-like histological changes and hepatic AFP production,but also showed an increased serum level of HBV antigens and cytokines like interleukin-6 and tumor necrosis factor-α,compared with the control group.CONCLUSION:Over-expression of uPA plays a synergistic role in the development of liver injury,inflammation and regeneration during acute HBV infection.展开更多
Baculoviruses were first identified as insect-specific pathogens, and it was this specificity that lead to their use as safe, target specific biological pesticides. For the past 30 years, AcMNPV has served as the subj...Baculoviruses were first identified as insect-specific pathogens, and it was this specificity that lead to their use as safe, target specific biological pesticides. For the past 30 years, AcMNPV has served as the subject of intense basic molecular research into the baculovirus infectious cycle including the interaction of the virus with a continuous insect cell line derived from Spodoptera frugiperda. The studies on baculoviruese have led to an in-depth understanding of the physical organization of the viral genomes including many complete genomic sequences, the time course of gene expression, and the application of this basic research to the use of baculoviruses not only as insecticides, but also as a universal eukaryotic protein expression system, and a potential vector in gene therapy. A great deal has also been discovered about the viral genes required for the replication of the baculovirus genome, while much remains to be learned about the mechanism of viral DNA replication. This report outlines the current knowledge of the factors involved in baculovirus DNA replication, using data on AcMNPV as a model for most members of the Baculoviridae.展开更多
Prophylactic DNA vaccines against the influenza virus are promising alternatives to conventional vaccines. In this study, we generated two candidate gene-based influenza vaccines encoding either the seasonal or pandem...Prophylactic DNA vaccines against the influenza virus are promising alternatives to conventional vaccines. In this study, we generated two candidate gene-based influenza vaccines encoding either the seasonal or pandemic hemagglutinin antigen (HA) from the strains A/New Caledonia/20/99 (HIN1) (pV1AS) and A/Califorrtia/04/2009 (H1N1) (pVEH1), respectively. After verifying antigen expression, the immunogenicity of the vaccines delivered intramuscularly with electroporation was tested in a mouse model. Sera of immunized animals were tested in hemagglutination inhibition assays and by ELISA for the presence of HA-specific antibodies. HA-specific T-cells were also measured in IFN-γ ELISpot assays. The protective efficacy of the candidate influenza vaccines was evaluated by measuring mortality rates and body weight after a challenge with 100 LD50 of mouse-adapted A/New Caledonia/20/99 (H1N1). Mice immunized with either one of the two vaccines showed significantly higher T cell and humoral immune responses (P〈0.05) than the pVAX1 control group. Additionally, the pV1A5 vaccine effec- tively protected the mice against a lethal homologous mouse-adapted virus challenge with a survival rate of 100% compared with a 40% survival rate in the pVEH1 vaccinated group (P〈0.05). Our study indicates that the seasonal influenza DNA vac- cine completely protects against the homologous A/New Caledonia/20/99 virus (H1N1), while the pandemic influenza DNA vaccine only partially protects against this virus.展开更多
OBJECTIVE:To determine the effect of Houttuynia cordata Aetherolea on connective tissue growth factor and adiponectin in a rat model of diabetes mellitus(DM).METHODS:DM was induced in rats using streptozotocin(STZ) an...OBJECTIVE:To determine the effect of Houttuynia cordata Aetherolea on connective tissue growth factor and adiponectin in a rat model of diabetes mellitus(DM).METHODS:DM was induced in rats using streptozotocin(STZ) and high glucose-lipid animal feed.Animals were then treated with Houttuynia cordata Aetherolea for 8 weeks.Changes in connective tissue growth factor and adiponectin levels in rats were observed.RESULTS:Connective tissue growth factor and adiponectin levels in rats with DM improved after Houttuynia cordata Aetherolea treatment.CONCLUSION:Houttuynia cordata Aetherolea had a positive effect on rats with DM by reducing levels of connective tissue growth factor and increasing adiponectin levels.展开更多
Auditory neuropathy spectrum disorder is a unique group of hearing dysfunctions characterized by preserved outer hair cell function and abnormal neural conduction of the auditory pathway. However, the pathogenic mecha...Auditory neuropathy spectrum disorder is a unique group of hearing dysfunctions characterized by preserved outer hair cell function and abnormal neural conduction of the auditory pathway. However, the pathogenic mechanism underlying this disorder is not clear. We therefore performed a systematic review of genetic mouse models with different gene mutations to provide a valuable tool for better understanding of the process and the possible molecular mechanisms. Of the 18 articles retrieved, nine met the required criteria. All biochemical, histological, and electrophysiological results were recorded for each of the mouse models, as was the transgenic technology. This review provides a summary of different mouse models that may play an important role in the diagnosis and management of auditory neuropathy spectrum disorder in the future.展开更多
基金Supported by grant form National Science Council of Taiwan, No. NSC 93-2320-B006-026
文摘AIM: Toll-like receptor 4 (TLR4) has been shown to be important for bacterial infection, especially to lipopolysaccharide signaling. Its possible role in HBV infection is studied in the present study. MATERIALS AND METHODS: pHBV3.6 plasmid, containing full-length HBV genome was used in the murine model of acute HBV expression by hydrodynamics in vivo transfection. TLR4 normal or mutant mouse strain was compared to investigate the possible role of TLR4 in acute HBV expression. RESULTS: After pHBV3.6 injection, the infiltrating leukocytes expressed TLR4 were observed nearby the HBsAg-expressing hepatocytes. The HBV antigenemia as well as the replication and transcription were higher in TLR4-mutant C3H/HeJ mice than in normal C3H/ HeN mice. The HBV-specific immune responses were impaired in the liver or spleen of the C3H/HeJ mice. Their inducible nitric oxide synthase (iNOS) expression on the hepatic infiltrating cells was also impaired. When adoptively transferring splenocytes from C3H/HeN mice to C3H/HeJ mice, the HBV replication was inhibited to the level as that of C3H/HeN. CONCLUSION: These results suggest that TLR4 plays an anti-HBV role in vivo through the induction of iNOSexpression and HBV-specific immune responses after HBV expression.
基金Supported by National Institute of Health grant (R01 AI071321)the Tobacco Settlement Foundation of Nebraska (LB 692)
文摘MicroRNAs (miRNAs) are an emerging class of highly conserved non-coding small RNAs that regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of cellular activity, including differentiation and development, metabolism, proliferation, apoptotic cell death, viral infection and tumorigenesis. Recent studies provide clear evidence that miRNAs are abundant in the liver and modulate a diverse spectrum of liver functions. Deregulation of miRNA expression may be a key pathogenetic factor in many liver diseases including viral hepatitis, hepatocellular cancer and polycystic liver diseases. A clearer understanding of the mechanisms involved in miRNA deregulation will offer new diagnostic and therapeutic strategies to treat liver diseases. Moreover, better understanding of miRNA regulation and identification of tissue-specific miRNA targets employing transgenic/knockout models and/or modulating oligonucleotides will improve our knowledge of liver physiology and diseases.
文摘Objective To evaluate the effects of environmental factors and microRNAs (miRNAs) (miR-126, miR-143, and miR-145) on the risk of coronary heart disease (CHD). Methods A frequency-matched case-control study (450 patients, 450 controls) was conducted from April 2014 to December 2016 in Fuzhou City, China. Environmental factors were investigated using a self-administered questionnaire, and the expression levels of miR-126, rniR-143, and miR-145 were determined by quantitative real-time Polymerase Chain Reaction (PCR) in pe- ripheral blood mononuclear cells. Unconditional logistic regression models were used for statistical evaluation. Results Alcohol consumption, high-salt diets, high-intensity work, and lack of physical activity were significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. MiR-126, miR-143, and miR-145 were highly expressed in the CHD group compared with the control group. After adjustment for other environmental factors, unconditional logistic regression results revealed that miR-126, miR-143, and depression were the independent risk factors of CHD, and light diet was the independent protective factor of CHD. Conclusions Our data suggest that a family history of CHD, anxiety, and alcohol consumption was significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. Furthermore, miR-126 and miR-143 in combination with several risk factors, could play a joint role in the development of CHD. Therefore, it is necessary to manage patients with CHD in all directions and multiple level.
文摘Nonalcoholic fatty liver disease(NAFLD) is associated with obesity,insulin resistance,and type 2 diabetes.NAFLD represents a large spectrum of diseases ranging from(1) fatty liver(hepatic steatosis);(2) steatosis with inflammation and necrosis;to(3) cirrhosis.The animal models to study NAFLD/nonalcoholic steatohepatitis(NASH) are extremely useful,as there are still many events to be elucidated in the pathology of NASH.The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis,but these remain incompletely understood.The different mouse models can be classified in two large groups.The first one includes genetically modified(transgenic or knockout) mice that spontaneously develop liver disease,and the second one includes mice that acquire the disease after dietary or pharmacological manipulation.Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex,genetically modified animal models may be a key for the treatment of NAFLD.Ideal animal models for NASH should closely resemble the pathological characteristics observed in humans.To date,no single animal model has encompassed the full spectrum of human disease progression,but they can imitate particular characteristics of human disease.Therefore,it is important that the researchers choose the appropriate animal model.This review discusses various genetically modified animal models developed and used in research on NAFLD.
基金Supported by the National Natural Science Foundation of People’s Republic of China. No. 3860332
文摘AIM: To determine the relationship between biliary stricture and pigment gallstone formation, and the prevention of pigment gallstones with medicine. METHODS: One hundred and eighteen male guinea pigs were randomly divided into four groups: stricture group (S, n = 30) underwent partial ligation of common bile duct, and fed on regular chow; S plus medicine group (S+M, n = 27) underwent the same operation but fed on medicinal chow (0.3 g chenodeoxycholic acid, 0.5 g glucurolactone, and 0.5 g aspirin were mixed up in 1.2 kg regular chow); medicinal control group (C+M, n = 30) was free of operation, and fed on medicinal chow; and control group (C, n = 31) was free of operation and fed on regular chow. One week later, laparotomy was performed, and the bile of gallbladder was collected, measured, and cultured. RESULTS: Gallstones were identif ied. Pigment gallstones were induced by biliary stricture in 95% (22/23) of S group. In the S+M group, the incidence of gallstone was reduced to 55% (11/20, vs S group, P < 0.01). The changes of indirect bilirubin and ionized calcium in the bile were consistent with gallstone incidences. CONCLUSION: Biliary stricture can cause pigment gallstone formation in guinea pigs, and the medicines used can lower the incidence of gallstones. The bilirubin and ionized calcium play important roles in pigment gallstone formation.
文摘Objective: To investigate the effect of intratracheally administered BCG DNA on a murine model of asthma. Methods: BALB/C mice were divided into 4 groups: normal control group, asthma model group, BCG DNA administered before OVA sensitization group, BCG DNA administered after OVA challenge group. The asthma models were developed by immunizing BALB/C mice with OVA. A total of 100 μg BCG DNA was intratracheally administered before OVA sensitization and after OVA challenge. WBC count and eosinophil percentage (EOS%) in bronchoalveolar lavage fluid (BALF) were measured. Changes of IL 4 , IL 5,IL 12, IFN γ in BALF were determined by ELISA. Pulmonary inflammation was observed on normal pathological slides and the proliferation and mucus secretion of goblet cells stained by AB PAS were also observed. Results: IL 4 , IL 5,IL 12, IFN γ in BALF of normal control group were(32.3±5.7)pg/ml,(15.6±3.9)pg/ml,(80±8.5)pg/ml,(153.2±9.4)pg/ml respectively. IL 4,IL 5 in BALF of asthma model group increased to (299±15.6)pg/ml and (206.7±9.3)pg/ml, while IL 12 and IFN γ decreased to (20.4±4.1)pg/ml and (51.6±5.5) pg/ml respectively. BCG DNA administered intratracheally before OVA sensitization and after OVA challenge significantly increased IL 12 [(71.6±8.3)pg/ml,(67.8±8.1pg/ml)] and IFN γ [(119.0±11.3)pg/ml,(114.7±10.1)pg/ml] in the BALF. Meanwhile, BCG DNA decreased IL 4 [(82.1±6.1)pg/ml,(86.3±5.9)pg/ml] and IL 5 [(32.3±4.6)pg/ml,(37.4±5.3)pg/ml]. Eosinophil level in BALF was inhibited and the pulmonary inflammation was dramatically relieved compared to asthma model group. Conclusion: Intratracheally administered BCG DNA can induce IL 12 and IFN γ secretion,inhibit Th2 response which can relieve allergic airway inflammation and provide a new way in the treatment and prevention of asthma.
文摘Cardiomyopathies are diseases that primarily affect the myocardium, leading to serious cardiac dysfunction and heart failure. Out of the three major categories of cardiomyopathies (hypertrophic, dilated and restrictive), restrictive cardiomyopathy (RCM) is less common and also the least studied. However, the prognosis for RCM is poor as some patients dying in their childhood. The molecular mechanisms behind the disease development and progression are not very clear and the treatment of RCM is very difficult and often ineffective. In this article, we reviewed the recent progress in RCM research from the clinical studies and the translational studies done on diseased transgenic animal models. This will help for a better understanding of the mechanisms underlying the etiology and development of RCM and for the design of better treatments for the disease.
基金Supported by National Program of Infection Diseases,No. 2012ZX10004-502The National High Technology Program ("863" Program) of China,No.2007AA02Z151
文摘AIM:To investigate the relationship between overexpression of urokinase plasminogen activator(uPA) and hepatitis B virus(HBV) related liver diseases in a transgenic mouse model.METHODS:Albumin-tetracycline reverse transcriptional activator and tetO-uPA transgenic mice were generated respectively through pronuclear injection and crossed to produce the double transgenic in-alb-uPA mice,for which doxycycline(Dox)-inducible and liver-specific over-expression of uPA can be achieved.Hydrodynamic transfection of plasmid adeno-associated virus(AAV)1.3HBV was performed through the tail veins of the Dox-induced in-alb-uPA mice.Expression of uPA and HBV antigens were analyzed through double-staining immunohistochemical assay.Cytokine production was detected by enzyme linked immunosorbent assay and α-fetoprotein(AFP) mRNA level was evaluated through real-time quantitative polymerase chain reaction.RESULTS:Plasmid AAV-1.3HBV hydrodynamic transfection in Dox-induced transgenic mice not only resulted in severe liver injury with hepatocarcinoma-like histological changes and hepatic AFP production,but also showed an increased serum level of HBV antigens and cytokines like interleukin-6 and tumor necrosis factor-α,compared with the control group.CONCLUSION:Over-expression of uPA plays a synergistic role in the development of liver injury,inflammation and regeneration during acute HBV infection.
基金This research is supported by grants from the Canadian Institutes of Health Research
文摘Baculoviruses were first identified as insect-specific pathogens, and it was this specificity that lead to their use as safe, target specific biological pesticides. For the past 30 years, AcMNPV has served as the subject of intense basic molecular research into the baculovirus infectious cycle including the interaction of the virus with a continuous insect cell line derived from Spodoptera frugiperda. The studies on baculoviruese have led to an in-depth understanding of the physical organization of the viral genomes including many complete genomic sequences, the time course of gene expression, and the application of this basic research to the use of baculoviruses not only as insecticides, but also as a universal eukaryotic protein expression system, and a potential vector in gene therapy. A great deal has also been discovered about the viral genes required for the replication of the baculovirus genome, while much remains to be learned about the mechanism of viral DNA replication. This report outlines the current knowledge of the factors involved in baculovirus DNA replication, using data on AcMNPV as a model for most members of the Baculoviridae.
基金supported by the National High Technology Research and Development Program of China(Grant No.2006AA10A205)the National Key Technology Research and Development Program(Grant No. 2006BAD06A05)the National Key Program for Infectious Diseases of China(Grant No.2009ZX10004-103)
文摘Prophylactic DNA vaccines against the influenza virus are promising alternatives to conventional vaccines. In this study, we generated two candidate gene-based influenza vaccines encoding either the seasonal or pandemic hemagglutinin antigen (HA) from the strains A/New Caledonia/20/99 (HIN1) (pV1AS) and A/Califorrtia/04/2009 (H1N1) (pVEH1), respectively. After verifying antigen expression, the immunogenicity of the vaccines delivered intramuscularly with electroporation was tested in a mouse model. Sera of immunized animals were tested in hemagglutination inhibition assays and by ELISA for the presence of HA-specific antibodies. HA-specific T-cells were also measured in IFN-γ ELISpot assays. The protective efficacy of the candidate influenza vaccines was evaluated by measuring mortality rates and body weight after a challenge with 100 LD50 of mouse-adapted A/New Caledonia/20/99 (H1N1). Mice immunized with either one of the two vaccines showed significantly higher T cell and humoral immune responses (P〈0.05) than the pVAX1 control group. Additionally, the pV1A5 vaccine effec- tively protected the mice against a lethal homologous mouse-adapted virus challenge with a survival rate of 100% compared with a 40% survival rate in the pVEH1 vaccinated group (P〈0.05). Our study indicates that the seasonal influenza DNA vac- cine completely protects against the homologous A/New Caledonia/20/99 virus (H1N1), while the pandemic influenza DNA vaccine only partially protects against this virus.
基金Supported by the Project of Natural Foundation of Shanghai Science and Technology Committee (No. 10Zr28600)
文摘OBJECTIVE:To determine the effect of Houttuynia cordata Aetherolea on connective tissue growth factor and adiponectin in a rat model of diabetes mellitus(DM).METHODS:DM was induced in rats using streptozotocin(STZ) and high glucose-lipid animal feed.Animals were then treated with Houttuynia cordata Aetherolea for 8 weeks.Changes in connective tissue growth factor and adiponectin levels in rats were observed.RESULTS:Connective tissue growth factor and adiponectin levels in rats with DM improved after Houttuynia cordata Aetherolea treatment.CONCLUSION:Houttuynia cordata Aetherolea had a positive effect on rats with DM by reducing levels of connective tissue growth factor and increasing adiponectin levels.
基金supported by the National Key Basic Research Program of China (2014CB943001)the National Natural Science Foundation of China (81120108009, 81530032)
文摘Auditory neuropathy spectrum disorder is a unique group of hearing dysfunctions characterized by preserved outer hair cell function and abnormal neural conduction of the auditory pathway. However, the pathogenic mechanism underlying this disorder is not clear. We therefore performed a systematic review of genetic mouse models with different gene mutations to provide a valuable tool for better understanding of the process and the possible molecular mechanisms. Of the 18 articles retrieved, nine met the required criteria. All biochemical, histological, and electrophysiological results were recorded for each of the mouse models, as was the transgenic technology. This review provides a summary of different mouse models that may play an important role in the diagnosis and management of auditory neuropathy spectrum disorder in the future.