Background:Nonalcoholic fatty liver disease(NAFLD)is the main reason for cirrhosis and hepatocellular carcinoma.As a starting point for NAFLD,the treatment of nonalcoholic fatty liver(NAFL)is receiving increasing atte...Background:Nonalcoholic fatty liver disease(NAFLD)is the main reason for cirrhosis and hepatocellular carcinoma.As a starting point for NAFLD,the treatment of nonalcoholic fatty liver(NAFL)is receiving increasing attention.Mice fed a high-fat diet(HFD)and hereditary leptin deficiency(ob/ob)mice are important NAFL animal models.However,the comparison of these mouse models with human NAFL is still unclear.Methods:In this study,HFD-fed mice and ob/ob mice were used as NAFL animal models.Liver histopathological characteristics were compared,and liver transcriptome from both mouse models was performed using RNA sequencing(RNA-seq).RNAseq data obtained from the livers of NAFL patients was downloaded from the GEO database.Global gene expression profiles in the livers were further analyzed using functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway.Results:Our results showed that the biochemical parameters of both mouse models and human NAFL were similar.Compared with HFD-fed mice,ob/ob mice were more similar in histologic appearance to NAFL patients.The liver transcriptome characteristics partly overlapped in mice and humans.Furthermore,in the NAFL pathway,most genes showed similar trends in mice and humans,thus demonstrating that both types of mice can be used as models for basic research on NAFL,considering the differences.Conclusion:Our findings show that HFD-fed mice and ob/ob mice can mimic human NAFL partly in pathophysiological process.The comparative analysis of liver transcriptome profile in mouse models and human NAFL presented here provides insights into the molecular characteristics across these NAFL models.展开更多
To develop a new method of inducing mdrl multidrug resistance by establishinga nude mice model of orthotopic transplantation of liver carcinoma by sporadic abdominalchemotherapy at intervals. Methods: Hepatocellular c...To develop a new method of inducing mdrl multidrug resistance by establishinga nude mice model of orthotopic transplantation of liver carcinoma by sporadic abdominalchemotherapy at intervals. Methods: Hepatocellular carcinoma HepG2 cell was cultured and injectedsubcutaneously to form the tumor-supplying mice. The tumor bits from the tumor-supplying mice wereimplanted under the envelope of the mice liver and induced by abdominal chemotherapy withPharmorubicin. Physical examination, ultrasonography, spiral CT and operative inspection were usedto examine tumor progression. RT-PCR and immunohistochemistry were adopted to detect the expressionof mdr1-mRNA and its encoded protein P-gp protein (P-gp). Results: There was no operative dead, therate of implanting tumor successfully was 88% (22/25), the rate of implanting secondly successfullywas 100% (3/3), and the rate of inducing successfully was 80% (16/20). The expression of mdrl-mRNAand the P-gp in the inducing group was 23 folds and 13 folds in the control group respectively.Conclusion: We have established an in vivo model of mdr using nude mice transplanted with orthotopicliver neoplasm coupled to chemotherapy.展开更多
Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like m...Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis,antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vitro and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.展开更多
Deficits in spatial learning and memory are some of the earliest symptoms in mild cognitive impairment （MCI）. However, there are few valid MCI animal models available to evaluate putative therapeutic strategies. The...Deficits in spatial learning and memory are some of the earliest symptoms in mild cognitive impairment （MCI）. However, there are few valid MCI animal models available to evaluate putative therapeutic strategies. The aim of this study was to obtain a natural animal model of MCI. Outbred Kunming （aged 5 and 12.5 months） and ICR （7 and 12 months） mice were utilized in the present study. Morris water maze and radial six-arm water maze （RAWM） were simultaneously used to evaluate impaired spatial learning and memory in middle-aged mice （approximately 12 months of age）. Compared with younger mice in the respective groups, the middle-aged mice suffered visible impairment of spatial memory in the Morris water maze and RAWM, and mild spatial learning deficiency occurred in the RAWM study alone. Thus outbred Kunming and ICR mice could be utilized as a natural animal model for MCI, in particular for memory impairment studies.展开更多
Parkinson's disease,the most common movement disorder,has a strong neuroinflammatory aspect.This is evident by increased pro-inflammatory cytokines in the serum,and the presence of activated microglial cells,and i...Parkinson's disease,the most common movement disorder,has a strong neuroinflammatory aspect.This is evident by increased pro-inflammatory cytokines in the serum,and the presence of activated microglial cells,and inflammatory cytokines in the substantia nigra of post-mortem brains as well as cerebrospinal fluid of Parkinson's disease patients.The central and peripheral neuroinflammatory aspects of Parkinson's disease can be investigated in vivo via administration of the inflammagen lipopolysaccharide,a component of the cell wall of gram-negative bacteria.In this mini-review,we will critically evaluate different routes of lipopolysaccharide administration(including intranasal systemic and ste reotasic),their relevance to clinical Parkinson's disease as well as the recent findings in lipopolysaccharide mouse models.We will also share our own expe riences with systemic and intrastriatal lipopolysaccharide models in C57BL/6 mice and will discuss the usefulness of lipopolysaccharide mouse models for future research in the field.展开更多
The model of vaginal candidiasis in Kunming mice was constructed in order to search for the optima construction conditions and provide an economic animal model of Candida albicans (C. albicans) vaginitis. Estrogen ben...The model of vaginal candidiasis in Kunming mice was constructed in order to search for the optima construction conditions and provide an economic animal model of Candida albicans (C. albicans) vaginitis. Estrogen benzoate (E2) was given to mice at different concentrations ranging from 0.0 to 0.05 mg/mouse (4 levels) beginning 72 h prior to vaginal inoculation, then mice were in- oculated intravaginally with various concentrations of stationary-phase C. albicans blastoconidia (ATCC90028) (5 levels) in 20 μL of phosphate-buffered saline (PBS) in each E2 level. General state, scores of genital pathology, the hyphae and vaginal fungal burden (CFU) in vaginal lavage fluid, the hydrops rate of uterus and vaginal tissues for pathological section in mice were observed and ob- tained at day 2, 4, 7, 14 and 21 after inoculation. The results showed the infection rate in mice was related to the dosage of E2 and concentration of C. albicans blastoconidia. Additionally there was better cross-effect between the two treated factors. The infection rate was about 80% on the day 4, and could reach 100% on the day 7 until the end of experiment after inoculated intravaginally in groups of E2I3, E2 0.025 mg/mouse injected hypodermically and inoculated intravaginally with 5×104 C. albicans blastoconidia, and large amount of hyphae and blastoconidia could be observe in superfi- cial layer tissue and canal of vaginal by PAS. From the results in our experiment it was concluded that E2I3 was the optima construction condition in kunming mice.展开更多
OBJECTIVE Transgenic mouse model has been widely used in pathogenesis study and preclinical drug evaluation in Alzheimer disease(AD).However,key differences are found between current animal models and clinical AD pati...OBJECTIVE Transgenic mouse model has been widely used in pathogenesis study and preclinical drug evaluation in Alzheimer disease(AD).However,key differences are found between current animal models and clinical AD patients regarding phenotypes.Lack of complete models that recapitulate broad spectrum of human AD neuropathology restricts efficacy of research projects and leads to frequent failure in AD drug development at clinical trial stages.This study aims to develop better mouse models of AD through modifying key phenotype insufficiency.METHODS By crossing different single and double transgenic mice with different mutations of APP/PS1 or tau and under prion,Thy1 or PDGF-β promoter,as well as selected knockout mice,I produced a dozen of bigenic models for neuropathology screening.Further neurochemical,behavioral and pharmacological validations were conducted in the optimized mouse model.RESULTS Neuropathology phenotyping found remarkable differences in tau pathology and neurodegeneration among individual APP/PS1/tau transgenic models.I had identified a triple mouse model named FADT that showed(1) huge mature tau pathology in hippocampus and cortex;(2) abundant tau truncation,as seen in human AD brain;(3)progressive neurodegeneration;(4)selective brain atrophy in hippocampus and entorhinal cortex;(5) reproducible and late onset spatial memory defects,etc.Importantly,remarkable tau pathology in this FADT model is mainly driven by beta-amyloid pathology,which differs from high expression of tau in rTg4510 model.CONCLUSION I had developed a new triple transgenic mouse model that recapitulates broad spectrum of human AD neuropathology features.This study will not only establish a solid model basis for AD pathophysiology investigation and drug development,but also reveal important clues on the interaction of beta-amyloid and tau pathologies in the brain.展开更多
Objective: To establish a patient-like human ovary carcinoma /spontaneous metastasis model using orthotopic transplanation of histologically intact tumor tissue. Methods: An highly metastatic ovarian tumor line (HO-89...Objective: To establish a patient-like human ovary carcinoma /spontaneous metastasis model using orthotopic transplanation of histologically intact tumor tissue. Methods: An highly metastatic ovarian tumor line (HO-8910PM: Human serum carcinoma of the ovary )previously grown substaneously was transplanted into the ovicapsule using microsurgery technique .Histologically intact human ovary tumor pieces gained from implantation site were passaged between ovicapsules for four generations. Results: All mice developed ovary tumors and the metastatic rates were about 75%. The tumors only metastasized to liver but no other organs. The earliest appearance of metastasis was 14 d and the average survival period was 20.7±4.89 d.The microscopic appearance of the metastases was similar to the tumor observed in the substaneous xenografts and orthotopically transplanted. Chromosomes analysis exhibited the feature of human carcinoma and retained genetic stability during the processes of passage. Conclusion: Orthotopic implanation provides a suitable micro-enviroment in which ovarian cancer can express its intrinsic clinically-relevant properties. This approach is relevant to the spontaneous development of ovarian cancer and is thought to be a useful model for studies of metastatic mechanism and therapy for ovary cancer.展开更多
Insulin resistance is a hallmark of type 2 diabetes. In an effort to understand and treat this condition, re searchers have used genetic manipulation of mice to uncover insulin signaling pathways and determine the eff...Insulin resistance is a hallmark of type 2 diabetes. In an effort to understand and treat this condition, re searchers have used genetic manipulation of mice to uncover insulin signaling pathways and determine the effects of their perturbation. After decades of research much has been learned, but the pathophysiology o insulin resistance in human diabetes remains contro versial, and treating insulin resistance remains a chal lenge. This review will discuss limitations of mouse models lacking select insulin signaling molecule genes In the most influential mouse models, glucose metabo lism differs from that of humans at the cellular, organ and whole-organism levels, and these differences limi the relevance and benefit of the mouse models both in terms of mechanistic investigations and therapeutic development. These differences are due partly to im mutable differences in mouse and human biology, and partly to the failure of genetic modifications to produce an accurate model of human diabetes. Several fac tors often limit the mechanistic insights gained from experimental mice to the particular species and strain including: developmental effects, unexpected meta bolic adjustments, genetic background effects, and technical issues. We conclude that the limitations and weaknesses of genetically modified mouse models of insulin resistance underscore the need for redirection of research efforts toward methods that are more directly relevant to human physiology.展开更多
INTRODUCTIONThe T-cell dependent specific liver injury in mice induced by concanavalin A(ConA) is a newly cstablished experimental liver injury model,which is considered more eligible for the study on pathophysiology ...INTRODUCTIONThe T-cell dependent specific liver injury in mice induced by concanavalin A(ConA) is a newly cstablished experimental liver injury model,which is considered more eligible for the study on pathophysiology of several human liver discascs,such as viral hepatitis and autommune hepatitis[1-9].T cell activation and several cytokines release had been proven to play a critical role in ConA -induced liver injury[10-19].Cyclosprine A(CsA),an effective inhibitor of activation of T lymphocytc,hes been used widely in clinical treatment,especially in autoimmune diseases and organ transplantation[20-25].In this study,we investigated the possible effect of CsA on ConA-induced liver injury in Kunning mice.展开更多
AIM： To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique. METHODS： Using OB glue paste technique, orthtopic transplantation models were established by implant...AIM： To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique. METHODS： Using OB glue paste technique, orthtopic transplantation models were established by implanting SGC-7901 and NKN-45 human gastric cancer cell strains into the gastric wall of nude mice. Biological features, growth of the implanted tumors, the success rate of transplantation and the rate of auto-metastasis of the two models were observed. RESULTS： The success rates of orthotopic transplanration of the two models were 94.20% and 96%. The rates of hepatic metastasis, pulmonary metastasis, peritoneal metastasis, lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%, 48.43% and 57.97%, 30.83% and 36.96%, 67.30% and 84.06%, and 59.75% and 10.53%, respectively. The occurrence of ascites was 47.80% and 36.96%. CONCLUSION： OB glue paste technique is easy to follow. The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer, and, therefore, can be used as an ideal model for experimental research of proliferative metastasis of tumors.展开更多
基金Basic-Clinical Joint&Innovative Project of the First Affiliated Hospital of Xi’an Jiaotong University,Grant/Award Number:YXJLRH2022025Innovation Capability Support Program of Shaanxi,Grant/Award Number:2022PT-37National Natural Science Foundation of China,Grant/Award Number:82070470。
文摘Background:Nonalcoholic fatty liver disease(NAFLD)is the main reason for cirrhosis and hepatocellular carcinoma.As a starting point for NAFLD,the treatment of nonalcoholic fatty liver(NAFL)is receiving increasing attention.Mice fed a high-fat diet(HFD)and hereditary leptin deficiency(ob/ob)mice are important NAFL animal models.However,the comparison of these mouse models with human NAFL is still unclear.Methods:In this study,HFD-fed mice and ob/ob mice were used as NAFL animal models.Liver histopathological characteristics were compared,and liver transcriptome from both mouse models was performed using RNA sequencing(RNA-seq).RNAseq data obtained from the livers of NAFL patients was downloaded from the GEO database.Global gene expression profiles in the livers were further analyzed using functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway.Results:Our results showed that the biochemical parameters of both mouse models and human NAFL were similar.Compared with HFD-fed mice,ob/ob mice were more similar in histologic appearance to NAFL patients.The liver transcriptome characteristics partly overlapped in mice and humans.Furthermore,in the NAFL pathway,most genes showed similar trends in mice and humans,thus demonstrating that both types of mice can be used as models for basic research on NAFL,considering the differences.Conclusion:Our findings show that HFD-fed mice and ob/ob mice can mimic human NAFL partly in pathophysiological process.The comparative analysis of liver transcriptome profile in mouse models and human NAFL presented here provides insights into the molecular characteristics across these NAFL models.
基金This project was supported by a grant from the Medical Science and Technique Foundation of Ministry of Health of China(No. Wkz-2000-1-15).
文摘To develop a new method of inducing mdrl multidrug resistance by establishinga nude mice model of orthotopic transplantation of liver carcinoma by sporadic abdominalchemotherapy at intervals. Methods: Hepatocellular carcinoma HepG2 cell was cultured and injectedsubcutaneously to form the tumor-supplying mice. The tumor bits from the tumor-supplying mice wereimplanted under the envelope of the mice liver and induced by abdominal chemotherapy withPharmorubicin. Physical examination, ultrasonography, spiral CT and operative inspection were usedto examine tumor progression. RT-PCR and immunohistochemistry were adopted to detect the expressionof mdr1-mRNA and its encoded protein P-gp protein (P-gp). Results: There was no operative dead, therate of implanting tumor successfully was 88% (22/25), the rate of implanting secondly successfullywas 100% (3/3), and the rate of inducing successfully was 80% (16/20). The expression of mdrl-mRNAand the P-gp in the inducing group was 23 folds and 13 folds in the control group respectively.Conclusion: We have established an in vivo model of mdr using nude mice transplanted with orthotopicliver neoplasm coupled to chemotherapy.
基金Partly supporled by the State Key Basic Research Program Grant of China(G1998051211)Leading Speciality Grant of Shanghai Health Bureau.
文摘Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis,antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vitro and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.
基金the National Natural Science Foundation of China, No. 30872730
文摘Deficits in spatial learning and memory are some of the earliest symptoms in mild cognitive impairment （MCI）. However, there are few valid MCI animal models available to evaluate putative therapeutic strategies. The aim of this study was to obtain a natural animal model of MCI. Outbred Kunming （aged 5 and 12.5 months） and ICR （7 and 12 months） mice were utilized in the present study. Morris water maze and radial six-arm water maze （RAWM） were simultaneously used to evaluate impaired spatial learning and memory in middle-aged mice （approximately 12 months of age）. Compared with younger mice in the respective groups, the middle-aged mice suffered visible impairment of spatial memory in the Morris water maze and RAWM, and mild spatial learning deficiency occurred in the RAWM study alone. Thus outbred Kunming and ICR mice could be utilized as a natural animal model for MCI, in particular for memory impairment studies.
文摘Parkinson's disease,the most common movement disorder,has a strong neuroinflammatory aspect.This is evident by increased pro-inflammatory cytokines in the serum,and the presence of activated microglial cells,and inflammatory cytokines in the substantia nigra of post-mortem brains as well as cerebrospinal fluid of Parkinson's disease patients.The central and peripheral neuroinflammatory aspects of Parkinson's disease can be investigated in vivo via administration of the inflammagen lipopolysaccharide,a component of the cell wall of gram-negative bacteria.In this mini-review,we will critically evaluate different routes of lipopolysaccharide administration(including intranasal systemic and ste reotasic),their relevance to clinical Parkinson's disease as well as the recent findings in lipopolysaccharide mouse models.We will also share our own expe riences with systemic and intrastriatal lipopolysaccharide models in C57BL/6 mice and will discuss the usefulness of lipopolysaccharide mouse models for future research in the field.
基金the National "10th Five-Year"Key Technologies R&D (No.2004BA709B13-02)
文摘The model of vaginal candidiasis in Kunming mice was constructed in order to search for the optima construction conditions and provide an economic animal model of Candida albicans (C. albicans) vaginitis. Estrogen benzoate (E2) was given to mice at different concentrations ranging from 0.0 to 0.05 mg/mouse (4 levels) beginning 72 h prior to vaginal inoculation, then mice were in- oculated intravaginally with various concentrations of stationary-phase C. albicans blastoconidia (ATCC90028) (5 levels) in 20 μL of phosphate-buffered saline (PBS) in each E2 level. General state, scores of genital pathology, the hyphae and vaginal fungal burden (CFU) in vaginal lavage fluid, the hydrops rate of uterus and vaginal tissues for pathological section in mice were observed and ob- tained at day 2, 4, 7, 14 and 21 after inoculation. The results showed the infection rate in mice was related to the dosage of E2 and concentration of C. albicans blastoconidia. Additionally there was better cross-effect between the two treated factors. The infection rate was about 80% on the day 4, and could reach 100% on the day 7 until the end of experiment after inoculated intravaginally in groups of E2I3, E2 0.025 mg/mouse injected hypodermically and inoculated intravaginally with 5×104 C. albicans blastoconidia, and large amount of hyphae and blastoconidia could be observe in superfi- cial layer tissue and canal of vaginal by PAS. From the results in our experiment it was concluded that E2I3 was the optima construction condition in kunming mice.
基金Science and Technology Development Fund of Shanghai Pudong New District (PKJ2017-Y37)Shanghai Natural Science Foundation(18ZR1417900).
文摘OBJECTIVE Transgenic mouse model has been widely used in pathogenesis study and preclinical drug evaluation in Alzheimer disease(AD).However,key differences are found between current animal models and clinical AD patients regarding phenotypes.Lack of complete models that recapitulate broad spectrum of human AD neuropathology restricts efficacy of research projects and leads to frequent failure in AD drug development at clinical trial stages.This study aims to develop better mouse models of AD through modifying key phenotype insufficiency.METHODS By crossing different single and double transgenic mice with different mutations of APP/PS1 or tau and under prion,Thy1 or PDGF-β promoter,as well as selected knockout mice,I produced a dozen of bigenic models for neuropathology screening.Further neurochemical,behavioral and pharmacological validations were conducted in the optimized mouse model.RESULTS Neuropathology phenotyping found remarkable differences in tau pathology and neurodegeneration among individual APP/PS1/tau transgenic models.I had identified a triple mouse model named FADT that showed(1) huge mature tau pathology in hippocampus and cortex;(2) abundant tau truncation,as seen in human AD brain;(3)progressive neurodegeneration;(4)selective brain atrophy in hippocampus and entorhinal cortex;(5) reproducible and late onset spatial memory defects,etc.Importantly,remarkable tau pathology in this FADT model is mainly driven by beta-amyloid pathology,which differs from high expression of tau in rTg4510 model.CONCLUSION I had developed a new triple transgenic mouse model that recapitulates broad spectrum of human AD neuropathology features.This study will not only establish a solid model basis for AD pathophysiology investigation and drug development,but also reveal important clues on the interaction of beta-amyloid and tau pathologies in the brain.
文摘Objective: To establish a patient-like human ovary carcinoma /spontaneous metastasis model using orthotopic transplanation of histologically intact tumor tissue. Methods: An highly metastatic ovarian tumor line (HO-8910PM: Human serum carcinoma of the ovary )previously grown substaneously was transplanted into the ovicapsule using microsurgery technique .Histologically intact human ovary tumor pieces gained from implantation site were passaged between ovicapsules for four generations. Results: All mice developed ovary tumors and the metastatic rates were about 75%. The tumors only metastasized to liver but no other organs. The earliest appearance of metastasis was 14 d and the average survival period was 20.7±4.89 d.The microscopic appearance of the metastases was similar to the tumor observed in the substaneous xenografts and orthotopically transplanted. Chromosomes analysis exhibited the feature of human carcinoma and retained genetic stability during the processes of passage. Conclusion: Orthotopic implanation provides a suitable micro-enviroment in which ovarian cancer can express its intrinsic clinically-relevant properties. This approach is relevant to the spontaneous development of ovarian cancer and is thought to be a useful model for studies of metastatic mechanism and therapy for ovary cancer.
文摘Insulin resistance is a hallmark of type 2 diabetes. In an effort to understand and treat this condition, re searchers have used genetic manipulation of mice to uncover insulin signaling pathways and determine the effects of their perturbation. After decades of research much has been learned, but the pathophysiology o insulin resistance in human diabetes remains contro versial, and treating insulin resistance remains a chal lenge. This review will discuss limitations of mouse models lacking select insulin signaling molecule genes In the most influential mouse models, glucose metabo lism differs from that of humans at the cellular, organ and whole-organism levels, and these differences limi the relevance and benefit of the mouse models both in terms of mechanistic investigations and therapeutic development. These differences are due partly to im mutable differences in mouse and human biology, and partly to the failure of genetic modifications to produce an accurate model of human diabetes. Several fac tors often limit the mechanistic insights gained from experimental mice to the particular species and strain including: developmental effects, unexpected meta bolic adjustments, genetic background effects, and technical issues. We conclude that the limitations and weaknesses of genetically modified mouse models of insulin resistance underscore the need for redirection of research efforts toward methods that are more directly relevant to human physiology.
文摘INTRODUCTIONThe T-cell dependent specific liver injury in mice induced by concanavalin A(ConA) is a newly cstablished experimental liver injury model,which is considered more eligible for the study on pathophysiology of several human liver discascs,such as viral hepatitis and autommune hepatitis[1-9].T cell activation and several cytokines release had been proven to play a critical role in ConA -induced liver injury[10-19].Cyclosprine A(CsA),an effective inhibitor of activation of T lymphocytc,hes been used widely in clinical treatment,especially in autoimmune diseases and organ transplantation[20-25].In this study,we investigated the possible effect of CsA on ConA-induced liver injury in Kunning mice.
文摘AIM： To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique. METHODS： Using OB glue paste technique, orthtopic transplantation models were established by implanting SGC-7901 and NKN-45 human gastric cancer cell strains into the gastric wall of nude mice. Biological features, growth of the implanted tumors, the success rate of transplantation and the rate of auto-metastasis of the two models were observed. RESULTS： The success rates of orthotopic transplanration of the two models were 94.20% and 96%. The rates of hepatic metastasis, pulmonary metastasis, peritoneal metastasis, lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%, 48.43% and 57.97%, 30.83% and 36.96%, 67.30% and 84.06%, and 59.75% and 10.53%, respectively. The occurrence of ascites was 47.80% and 36.96%. CONCLUSION： OB glue paste technique is easy to follow. The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer, and, therefore, can be used as an ideal model for experimental research of proliferative metastasis of tumors.
