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
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
Alzheimer's disease and Parkinson's disease are two of the most prevalent and disabling neurodegenerative diseases globally.Both are proteinopathic conditions and while occasionally inherited,are largely spora...Alzheimer's disease and Parkinson's disease are two of the most prevalent and disabling neurodegenerative diseases globally.Both are proteinopathic conditions and while occasionally inherited,are largely sporadic in nature.Although the advances in our understanding of the two have been significant,they are far from complete and neither diagnosis nor the current practices in treatment and rehabilitation is adequately helpful.Animal models have historically found application as testing beds for novel therapeutics and continue to be valuable aids in pharmacological research.This review chronicles the development of those models in the context of Alzheimer's and Parkinson's disease,and highlights the shifting paradigms in studying two humanspecific conditions in non-human organisms.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
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
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 Iow 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-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I 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 antiangiogenesis, 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 vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.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
Parkinson's disease(PD)is a neurodegenerative disorder characterized by motor and non-motor symptoms that significantly impact an individual's quality of life.Voice changes have shown promise as early indicato...Parkinson's disease(PD)is a neurodegenerative disorder characterized by motor and non-motor symptoms that significantly impact an individual's quality of life.Voice changes have shown promise as early indicators of PD,making voice analysis a valuable tool for early detection and intervention.This study aims to assess and detect the severity of PD through voice analysis using the mobile device voice recordings dataset.The dataset consisted of recordings from PD patients at different stages of the disease and healthy control subjects.A novel approach was employed,incorporating a voice activity detection algorithm for speech segmentation and the wavelet scattering transform for feature extraction.A Bayesian optimization technique is used to fine-tune the hyperparameters of seven commonly used classifiers and optimize the performance of machine learning classifiers for PD severity detection.AdaBoost and K-nearest neighbor consistently demonstrated superior performance across various evaluation metrics among the classifiers.Furthermore,a weighted majority voting(WMV)technique is implemented,leveraging the predictions of multiple models to achieve a near-perfect accuracy of 98.62%,improving classification accuracy.The results highlight the promising potential of voice analysis in PD diagnosis and monitoring.Integrating advanced signal processing techniques and machine learning models provides reliable and accessible tools for PD assessment,facilitating early intervention and improving patient outcomes.This study contributes to the field by demonstrating the effectiveness of the proposed methodology and the significant role of WMV in enhancing classification accuracy for PD severity detection.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
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 implantin...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 MKN-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 transplan- tation 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
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 a relevant animal model ofhuman gastrointestinal cancer, which can beused for repetitive investigations, so as toimprove our understanding and management ofcarcinogenesis and cancer metastasis.METHODS...AIM To establish a relevant animal model ofhuman gastrointestinal cancer, which can beused for repetitive investigations, so as toimprove our understanding and management ofcarcinogenesis and cancer metastasis.METHODS Intact tissues of human colorectaland pancreatic cancers were transplanted innude mice. The biological characteristics of theoriginal and the corresponding transplantedtumors were investigated by HE staining, PASstaining and immunostaining. The metastases inthe livers and lungs of nude mice wereinvestigated by immunostaining withbiotinylated mab KL-1 and by RT-PCR using CK20specific primers.RESULTS There were totally 9 of 16 surgicalspecimens growing in nude mice subcutaneouslyand/.or orthotopically (4 of 6 colorectal and 5 of10 pancreatic cancer). Tumor cell content of thespecimens and freezing of tissue specimens areimportant factors influencing the growth oftransplanted tumor. In the group of fresh tumortissues with greater than 50% tumor cellcontent, the success rate of the transplantationwas 100% (3 cases of pancreatic cancer and 3cases of colorectal cancer). The orthotopicallytransplanted tumors resemble the original tumormorphologically and biologically, including TAAexpression such as CEA byimmunohistochemistry, and CEA level in theserum of mice. Ki-67 labeling index and theexpression of TAA especially K-ras, 17-lA andRA-96, are associated with the potential of tumorgrowth in nude mice. Micrometastases in thelungs and livers of tumor bearing mice can bedetected by immunostaining with biotinylatedmab KL-1 and CK20-specific RT-PCR.CONCLUSION An orthotopic transplantationmodel for human colon and pancreatic cancer innude mice has been set up. We have alsoestablished sensitive detection methods withCK-immunohistochemistry and CK20-RT-PCR tostudy xenotransplanted human cancer and itsmetastatic cancer cells in the liver and lung ofnude mice. This study may be helpful inunderstanding the mechanism of cancermetastasis and in developing new diagnosticmethods and therapeutic strategies formetastases including micrometastases.展开更多
Objective: To evaluate the influence of surgical trauma on liver cancer metastasis. Methods: A mouse model of experimental liver cancer metastasis was established by subcapsule injecting hepatoma ascites tumor cells (...Objective: To evaluate the influence of surgical trauma on liver cancer metastasis. Methods: A mouse model of experimental liver cancer metastasis was established by subcapsule injecting hepatoma ascites tumor cells (H22) into spleen of NIH mice. Simple intrasplenic inoculation, with sham operation, partial hepatectomy, total occlusion of hepatic blood inflow and blood loss and re-perfusion were performed and metastatic effects were observed. Results: There were significant higher metastasis-augmenting effects in sham operation and partial hepatectomy groups. Compared with no-blood transfusion, blood transfusion group was found to be potent to increase intrahepatic metastases. But, neither inhibition nor enhancement with total occlusion of hepatic blood inflow for 20 and 30 minutes was seen. Conclusions: Surgical trauma, especially partial hepatectomy and blood transfusion, are involved in enhancing metastasis, but total occlusion of hepatic blood inflow is not responsible for enhanced liver metastasis in the experimental metastasis model.展开更多
Objective: To study the treatmaient of non-small cell lung cancer, we established the HU-Prim allograft transplantation tumor model. Methods: The fresh tumor samples were transplanted in the right scapular subcutaneou...Objective: To study the treatmaient of non-small cell lung cancer, we established the HU-Prim allograft transplantation tumor model. Methods: The fresh tumor samples were transplanted in the right scapular subcutaneous layer of the severe combined immunodeficient Non-obese diabetic/severe combined immunodeficient(NOD/SCID) mice. The pathological features of the tumors were observed. Nonnecrotic tissue was inoculated subcutaneously into the right axillary. When the tumor in burdened rat grew approximately 100 mm3, according to the tumor size all the animals were divided into the following four groups, eight rats in each group: solvent control group, gefitinib group(100 mg/kg), erlotinib group(50 mg/kg), afatinib group(20 mg/kg). Aniamals were treated with drugs by intragastric(i.g.) administrated, once daily, for consecutively 14 days. Measure the tumor size 2-3 times every week. Results: Hu Prime1-NSCLC mutant sensitive xenograft model research data showed that reversible tyrosine kinase inhibitors gefitinib, erlotinib and irreversible tyrosine kinase inhibitor afatinib could effectively inhibit tumor growth in EGFR positive NSCLC allografts model. The pharmacodynamic activity of irreversible inhibitor was better than that of the reversible inhibitor. Specimens from clinical anthropogenic tumor retain characteristics of the human primary malignancy, histopathology, biological characteristics, and tumor markers, etc., which can more accurately reflect the characteristics of the tumor and the impact of interventions. Conclusion: The model is not only a good antitumor drug experimental platform, but also a new evaluation tool of individualized medication.展开更多
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SMI is funded by Department of Science and Technology,Science and Engineering Research Board Early Career grant to MT.SN is supported from Birla Institute of Technology and Science PhD student fellowship at Biological Sciences。
文摘Alzheimer's disease and Parkinson's disease are two of the most prevalent and disabling neurodegenerative diseases globally.Both are proteinopathic conditions and while occasionally inherited,are largely sporadic in nature.Although the advances in our understanding of the two have been significant,they are far from complete and neither diagnosis nor the current practices in treatment and rehabilitation is adequately helpful.Animal models have historically found application as testing beds for novel therapeutics and continue to be valuable aids in pharmacological research.This review chronicles the development of those models in the context of Alzheimer's and Parkinson's disease,and highlights the shifting paradigms in studying two humanspecific conditions in non-human organisms.
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.
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 Iow 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-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I 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 antiangiogenesis, 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 vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.
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Parkinson's disease(PD)is a neurodegenerative disorder characterized by motor and non-motor symptoms that significantly impact an individual's quality of life.Voice changes have shown promise as early indicators of PD,making voice analysis a valuable tool for early detection and intervention.This study aims to assess and detect the severity of PD through voice analysis using the mobile device voice recordings dataset.The dataset consisted of recordings from PD patients at different stages of the disease and healthy control subjects.A novel approach was employed,incorporating a voice activity detection algorithm for speech segmentation and the wavelet scattering transform for feature extraction.A Bayesian optimization technique is used to fine-tune the hyperparameters of seven commonly used classifiers and optimize the performance of machine learning classifiers for PD severity detection.AdaBoost and K-nearest neighbor consistently demonstrated superior performance across various evaluation metrics among the classifiers.Furthermore,a weighted majority voting(WMV)technique is implemented,leveraging the predictions of multiple models to achieve a near-perfect accuracy of 98.62%,improving classification accuracy.The results highlight the promising potential of voice analysis in PD diagnosis and monitoring.Integrating advanced signal processing techniques and machine learning models provides reliable and accessible tools for PD assessment,facilitating early intervention and improving patient outcomes.This study contributes to the field by demonstrating the effectiveness of the proposed methodology and the significant role of WMV in enhancing classification accuracy for PD severity detection.
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 MKN-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 transplan- tation 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.
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.
基金Supported by the German Foundation"Hensel-Stiftung"and Foundation of Health Ministry of China,No.D39901
文摘AIM To establish a relevant animal model ofhuman gastrointestinal cancer, which can beused for repetitive investigations, so as toimprove our understanding and management ofcarcinogenesis and cancer metastasis.METHODS Intact tissues of human colorectaland pancreatic cancers were transplanted innude mice. The biological characteristics of theoriginal and the corresponding transplantedtumors were investigated by HE staining, PASstaining and immunostaining. The metastases inthe livers and lungs of nude mice wereinvestigated by immunostaining withbiotinylated mab KL-1 and by RT-PCR using CK20specific primers.RESULTS There were totally 9 of 16 surgicalspecimens growing in nude mice subcutaneouslyand/.or orthotopically (4 of 6 colorectal and 5 of10 pancreatic cancer). Tumor cell content of thespecimens and freezing of tissue specimens areimportant factors influencing the growth oftransplanted tumor. In the group of fresh tumortissues with greater than 50% tumor cellcontent, the success rate of the transplantationwas 100% (3 cases of pancreatic cancer and 3cases of colorectal cancer). The orthotopicallytransplanted tumors resemble the original tumormorphologically and biologically, including TAAexpression such as CEA byimmunohistochemistry, and CEA level in theserum of mice. Ki-67 labeling index and theexpression of TAA especially K-ras, 17-lA andRA-96, are associated with the potential of tumorgrowth in nude mice. Micrometastases in thelungs and livers of tumor bearing mice can bedetected by immunostaining with biotinylatedmab KL-1 and CK20-specific RT-PCR.CONCLUSION An orthotopic transplantationmodel for human colon and pancreatic cancer innude mice has been set up. We have alsoestablished sensitive detection methods withCK-immunohistochemistry and CK20-RT-PCR tostudy xenotransplanted human cancer and itsmetastatic cancer cells in the liver and lung ofnude mice. This study may be helpful inunderstanding the mechanism of cancermetastasis and in developing new diagnosticmethods and therapeutic strategies formetastases including micrometastases.
文摘Objective: To evaluate the influence of surgical trauma on liver cancer metastasis. Methods: A mouse model of experimental liver cancer metastasis was established by subcapsule injecting hepatoma ascites tumor cells (H22) into spleen of NIH mice. Simple intrasplenic inoculation, with sham operation, partial hepatectomy, total occlusion of hepatic blood inflow and blood loss and re-perfusion were performed and metastatic effects were observed. Results: There were significant higher metastasis-augmenting effects in sham operation and partial hepatectomy groups. Compared with no-blood transfusion, blood transfusion group was found to be potent to increase intrahepatic metastases. But, neither inhibition nor enhancement with total occlusion of hepatic blood inflow for 20 and 30 minutes was seen. Conclusions: Surgical trauma, especially partial hepatectomy and blood transfusion, are involved in enhancing metastasis, but total occlusion of hepatic blood inflow is not responsible for enhanced liver metastasis in the experimental metastasis model.
基金National Natural Science Foundation of Tianjin,China(16JCYBJC27500)
文摘Objective: To study the treatmaient of non-small cell lung cancer, we established the HU-Prim allograft transplantation tumor model. Methods: The fresh tumor samples were transplanted in the right scapular subcutaneous layer of the severe combined immunodeficient Non-obese diabetic/severe combined immunodeficient(NOD/SCID) mice. The pathological features of the tumors were observed. Nonnecrotic tissue was inoculated subcutaneously into the right axillary. When the tumor in burdened rat grew approximately 100 mm3, according to the tumor size all the animals were divided into the following four groups, eight rats in each group: solvent control group, gefitinib group(100 mg/kg), erlotinib group(50 mg/kg), afatinib group(20 mg/kg). Aniamals were treated with drugs by intragastric(i.g.) administrated, once daily, for consecutively 14 days. Measure the tumor size 2-3 times every week. Results: Hu Prime1-NSCLC mutant sensitive xenograft model research data showed that reversible tyrosine kinase inhibitors gefitinib, erlotinib and irreversible tyrosine kinase inhibitor afatinib could effectively inhibit tumor growth in EGFR positive NSCLC allografts model. The pharmacodynamic activity of irreversible inhibitor was better than that of the reversible inhibitor. Specimens from clinical anthropogenic tumor retain characteristics of the human primary malignancy, histopathology, biological characteristics, and tumor markers, etc., which can more accurately reflect the characteristics of the tumor and the impact of interventions. Conclusion: The model is not only a good antitumor drug experimental platform, but also a new evaluation tool of individualized medication.