The distribution of ￣(3)H-mitoxantrone polybutyl cyanoacrylate nanospheres(￣(3)H-DHAQ-PBCA-NS)in the viscera,muscle and tumors of human hepatocellular carcinoma (HCC)model in nude mice was studied with liquid scinti...The distribution of ￣(3)H-mitoxantrone polybutyl cyanoacrylate nanospheres(￣(3)H-DHAQ-PBCA-NS)in the viscera,muscle and tumors of human hepatocellular carcinoma (HCC)model in nude mice was studied with liquid scintillation counting techniique. The results showed that the ￣(3)H-DHAQ-PBCA-NS had remarkable liver targeting effect. The content of ￣(3)H-DHAQ-PBCA-NSin liver and heterotopic liver tumor was found to be 71.31±10. 49% of total amount of drug in animal body. It was also found that the content of ￣(3)H-DHAQ-PBCA-NS in liver was higher than that in liver tissue, and the content of ￣(3)H-DHAQ-PBCA-NS in annpit tumor was higher than that in armpit muscle tissue,but had no significant difference;It provides an ideal preparation for the DHAQ admini-stration.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
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
[ Objectlve] This study aimed to investigate the antimicrobial effect of Chinese herbal preparation Yinqiaotiangan against Streptococcus suis serotype II in vivo. [ Method ] The prevention and treatment tests were con...[ Objectlve] This study aimed to investigate the antimicrobial effect of Chinese herbal preparation Yinqiaotiangan against Streptococcus suis serotype II in vivo. [ Method ] The prevention and treatment tests were conducted with Kunming mice weighing about 18 -22 g. In the prevention test, Kunming mice were inocu- lated with Streptococcus suis serotype II and simultaneously taken orally 0.5, 1.0 and 2.0 g/ml Chinese herbal preparation Yinqiaotiangan respectively for continu- ous 3 d, once a day; the incidence rate, mortality rate and protective rate were detected after 7 d. In the treatment test, Kunming mice were inoculated with Strepto- coccus suis serotype II to establish the Streptococcus suis serotype II pathogenic model, and then taken orally 0.5, 1.0 and 2.0 g/ml Chinese herbal preparation Yin- qiaotiangan respectively for continuous 3 d, twice a day; the mortality rate, cure rate and effective rate were detected after 7 d. [ Result ] Results of the prevention test showed that the protective rate in experimental groups was extremely significantly higher than that in control group （P 〈0.01 ）, while the incidence rate and mortality rate were extremely significantly lower than that in control group （P 〈0.01 ）. Results of the treatment test showed that the incidence rate in experimental groups was extremely significantly lower than that in control group （P 〈0.01 ）, the cure rate in 0.5 g/ml group was extremely significantly higher than that in 1.0 g/ml group and 2.0 g/ml group （P 〈 0.01 ）, the effective rate in 0.5 g/ml group was significantly higher than that in 1.0 g/ml group and 2.0 g/ml group （ P 〈 0.05 ）, with no significant difference from the positive group （P 〉 0.05 ）. [ Conclusion ] The pathologic model of Streptococcus su/s serotype II could be effec- tively prevented and treated by oral intake of low dose of Chinese herbal preparation Yinqiaotiangan in Kunming mice.展开更多
Summary： Patients with FLT3-ITD^mmutt/NPM1- cytogenetically normal acute myeloid leukemia （CN-AML）, as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is be...Summary： Patients with FLT3-ITD^mmutt/NPM1- cytogenetically normal acute myeloid leukemia （CN-AML）, as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD^mut/NPM1- CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD^mut/NPM1- CN-AML primary cells. The FLT3-ITD^mut/NPM1- CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary genera- tion models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully estab- lished xenotransplantation model of human FLT3-ITD^mut/NPM1- CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.展开更多
Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis s...Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.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
Objective: A BALB/c mice model of cytomegalovirus-induced myocarditis was established. Methods: Twenty-five inbred female BALB/c mice free of murine cytomegalovirus(MCMV) infection (5 weeks old, 16-18 g),were infected...Objective: A BALB/c mice model of cytomegalovirus-induced myocarditis was established. Methods: Twenty-five inbred female BALB/c mice free of murine cytomegalovirus(MCMV) infection (5 weeks old, 16-18 g),were infected with 1×10~4 PFU MCMV by the intraperitoneal (i.p.) administration. All experimental mice were sacrificed on day 3, 5, 7, 10,and 14 after i. p. administration. The hearts were removed under aseptic conditions, and were transected along the midline. Aliquots of hearts were handled with Bouin's fixative for histological examination. Residual hearts were immediately frozen in liquid nitrogen and stored at -80℃ until MCMV titre was determined by a plaque assay. Seurm cTnI level was assayed by ELISA. Results: MCMV in the heart was at extremely low level on day 3 after i. p. administration, reached to the peak on day 7-10, and then ran down. A mixed cellular infiltrate composed of polymorphonuclear neutrophils and mononuclear lymphocytes was observed on day 3, reaching to the peak on day 7-10 after MCMV infection, and was maintained for at least 3-4 months later. Seurm cTnI levels were elevated on day 3 after i.p. administration, reaching to the peak it day 7-10. Conclusion: The BALB/c mice model for cytomegalovirus-induced myocarditis was successfully established, that might make it possible to screen antiviral drugs for treating viral myocarditis and to investigate and evaluate the pathogenesis and prognosis of this disease.展开更多
An experimental model of hepatic Schistosoma japonicum egg granuloma was established in C57BL/6 mice sensitized with soluble egg antigen(SEA) by direct injection of vital egg suspension into the spleen. The mice infec...An experimental model of hepatic Schistosoma japonicum egg granuloma was established in C57BL/6 mice sensitized with soluble egg antigen(SEA) by direct injection of vital egg suspension into the spleen. The mice infected with cercariae of Schistosoma japonicum in abdominal skin were used for comparative studies. The results showed that morbidity of hepatic Schistosoma japonicum egg granulomas in the group sensitized with SEA was 100% and that the morphology, cellular constituents, developing process and the diameter and size of the egg granulomas in the group sensitized with SEA were similar to those of the group infected with cercariae. The authors suggest that this experimental model is a useful and appropriate tool for the study on egg granulomas of Schistosoma japonicum.展开更多
BACKGROUND Colon cancer(CC)is one of the most common malignant tumors in the gastrointestinal system.Overall,CC had the third highest incidence but the second highest mortality rate globally in 2020.Nowadays,CC is mai...BACKGROUND Colon cancer(CC)is one of the most common malignant tumors in the gastrointestinal system.Overall,CC had the third highest incidence but the second highest mortality rate globally in 2020.Nowadays,CC is mainly treated with capecitabine chemotherapy regimen,supplemented by radiotherapy,immunotherapy and targeted therapy,but there are still limitations,so Chinese medicine plays an important role.AIM To investigate the effects of invigorating-spleen and anticancer prescription(ISAP)on body weight,tumor inhibition rate and expression levels of proteins in extracellular-signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)signaling pathway in CC mice model.METHODS The CC mice model were established and the mice were randomly divided into 5 groups,including the control group,capecitabine group,the low-dose,mediumdose and high-dose groups of ISAP,with 8 mice in each group,respectively.After 2 weeks of intervention,the body weight and tumor inhibition rate of mice were observed,and the expression of RAS,ERK,phosphorylated ERK(p-ERK),C-MYC and matrix metalloproteinase 2(MMP2)proteins in the tissues of tumors were detected.RESULTS Compared with the control group,the differences of body weight before and after treatment was much smaller in the groups of ISAP,with the smallest difference in the high-dose group of ISAP,while the capecitabine group had the greatest difference,indicating ISAP had a significant inhibiting effect on the growth of transplanted tumor in mice.The expression of RAS protein was decreased in the low-and medium-dose groups of ISAP,and the change of p-ERK was significant in the medium-and high-dose groups of ISAP.MMP2 protein expression was significantly decreased in both the low-dose and medium-dose groups of ISAP.There were no significant changes in ERK in the ISAP group compared to the capecitabine group,while RAS,MMP2,and C-MYC protein expression were reduced in the ISAP group.The expression level of C-MYC protein decreased after treated with ISAP,and the decrease was the most significant in the medium-dose group of ISAP.CONCLUSION ISAP has a potential inhibiting effect on transplanted tumor in mice,and could maintain the general conditions,physical strength and body weight of mice.The expression levels of RAS,p-ERK,MMP2 and c-myc were also decreased to a certain extent.By inhibiting the expression of upstream proteins,the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased.Therefore,it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins.展开更多
Purpose: To establish model of retinoblastoma subcutaneously in NOD-SCID mice and study rules of formation and distribution of retinoblastoma metastasis.Methods: Retinoblastoma cells SO-RB50 were inoculated subcutaneo...Purpose: To establish model of retinoblastoma subcutaneously in NOD-SCID mice and study rules of formation and distribution of retinoblastoma metastasis.Methods: Retinoblastoma cells SO-RB50 were inoculated subcutaneously in NOD-SCID mice. Animal acts and tumor formation, growth and metastasis in NOD-SCID mice were observed. Primary and metastatic tumors were studied pathohistologically by HE and immunohistochemical staining.Results: The latent periods of tumor growth were 12～19 days and the taken rate of tumor was 100%. 32 days later, 5 NOD-SCID mice were found with tumors that had metastasized to areas mainly located in the abdominal cavity and the side of the kidney; the metastatic time of tumors in the mice also differed. The tumor cells of the primary nodules and the metastasis were similar with human retinoblastoma cells and positive in immunohistochemical staining of NSE.Conclusion: The subcutaneous model of retinoblastoma in NOD-SCID mice showed a high taken rate and a short latent period of tumor, which had a high metastatic rate and was the best model in research of behaviors of retinoblastoma at present.展开更多
Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune press...Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune pressure and host factors.Understanding these changes is crucial for epidemic control and variant research.Methods:Human angiotensin-converting enzyme 2(hACE2)transgenic mice were in-tranasally challenged with the original strain WH-09 and the variants Delta,Beta,and Omicron BA.1,while BALB/c mice were challenged with Omicron subvariants BA.5,BF.7,and XBB.1.To compare the pathogenicity differences among variants,we con-ducted a comprehensive analysis that included clinical symptom observation,meas-urement of viral loads in the trachea and lungs,evaluation of pulmonary pathology,analysis of immune cell infiltration,and quantification of cytokine levels.Results:In hACE2 mice,the Beta variant caused significant weight loss,severe lung inflammation,increased inflammatory and chemotactic factor secretion,greater mac-rophage and neutrophil infiltration in the lungs,and higher viral loads with prolonged shedding duration.In contrast,BA.1 showed a significant reduction in pathogenicity.The BA.5,BF.7,and XBB.1 variants were less pathogenic than the WH-09,Beta,and Delta variants when infected in BALB/c mice.This was evidenced by reduced weight loss,diminished pulmonary pathology,decreased secretion of inflammatory factors and chemokines,reduced macrophage and neutrophil infiltration,as well as lower viral loads in both the trachea and lungs.Conclusion:In hACE2 mice,the Omicron variant demonstrated the lowest pathogenic-ity,while the Beta variant exhibited the highest.Pathogenicity of the Delta variant was comparable to the original WH-09 strain.Among BALB/c mice,Omicron subvari-ants BA.5,BF.7,and XBB.1 showed no statistically significant differences in virulence.展开更多
BACKGROUND Ulcerative colitis(UC)is an inflammatory bowel disease that is difficult to diagnose and treat.To date,the degree of inflammation in patients with UC has mainly been determined by measuring the levels of no...BACKGROUND Ulcerative colitis(UC)is an inflammatory bowel disease that is difficult to diagnose and treat.To date,the degree of inflammation in patients with UC has mainly been determined by measuring the levels of nonspecific indicators,such as C-reactive protein and the erythrocyte sedimentation rate,but these indicators have an unsatisfactory specificity.In this study,we performed bioinformatics analysis using data from the National Center for Biotechnology Information-Gene Expression Omnibus(NCBI-GEO)databases and verified the selected core genes in a mouse model of dextran sulfate sodium(DSS)-induced colitis.AIM To identify UC-related differentially expressed genes(DEGs)using a bioinformatics analysis and verify them in vivo and to identify novel biomarkers and the underlying mechanisms of UC.METHODS Two microarray datasets from the NCBI-GEO database were used,and DEGs between patients with UC and healthy controls were analyzed using GEO2R and Venn diagrams.We annotated these genes based on their functions and signaling pathways,and then protein-protein interactions(PPIs)were identified using the Search Tool for the Retrieval of Interacting Genes.The data were further analyzed with Cytoscape software and the Molecular Complex Detection(MCODE)app.The core genes were selected and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed.Finally,colitis model mice were established by administering DSS,and the top three core genes were verified in colitis mice using real-time polymerase chain reaction(PCR).RESULTS One hundred and seventy-seven DEGs,118 upregulated and 59 downregulated,were initially identified from the GEO2R analysis and predominantly participated in inflammation-related pathways.Seven clusters with close interactions in UC formed:Seventeen core genes were upregulated[C-X-C motif chemokine ligand 13(CXCL13),C-X-C motif chemokine receptor 2(CXCR2),CXCL9,CXCL5,C-C motif chemokine ligand 18,interleukin 1 beta,matrix metallopeptidase 9,CXCL3,formyl peptide receptor 1,complement component 3,CXCL8,CXCL1,CXCL10,CXCL2,CXCL6,CXCL11 and hydroxycarboxylic acid receptor 3]and one was downregulated[neuropeptide Y receptor Y1(NYP1R)]in the top cluster according to the PPI and MCODE analyses.These genes were substantially enriched in the cytokinecytokine receptor interaction and chemokine signaling pathways.The top three core genes(CXCL13,NYP1R,and CXCR2)were selected and verified in a mouse model of colitis using real-time PCR Increased expression was observed compared with the control mice,but only CXCR2 expression was significantly different.CONCLUSION Core DEGs identified in UC are related to inflammation and immunity inflammation,indicating that these reactions are core features of the pathogenesis of UC.CXCR2 may reflect the degree of inflammation in patients with UC.展开更多
文摘The distribution of ￣(3)H-mitoxantrone polybutyl cyanoacrylate nanospheres(￣(3)H-DHAQ-PBCA-NS)in the viscera,muscle and tumors of human hepatocellular carcinoma (HCC)model in nude mice was studied with liquid scintillation counting techniique. The results showed that the ￣(3)H-DHAQ-PBCA-NS had remarkable liver targeting effect. The content of ￣(3)H-DHAQ-PBCA-NSin liver and heterotopic liver tumor was found to be 71.31±10. 49% of total amount of drug in animal body. It was also found that the content of ￣(3)H-DHAQ-PBCA-NS in liver was higher than that in liver tissue, and the content of ￣(3)H-DHAQ-PBCA-NS in annpit tumor was higher than that in armpit muscle tissue,but had no significant difference;It provides an ideal preparation for the DHAQ admini-stration.
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 "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Supported by Youth Science and Technology Start-up Fund of Liaoning Medical University(Y2012Z023)Project of Agricultural Science and Technology Achievement Transformation from the Ministry of Science and Technology of China(2012GB2B000097)
文摘[ Objectlve] This study aimed to investigate the antimicrobial effect of Chinese herbal preparation Yinqiaotiangan against Streptococcus suis serotype II in vivo. [ Method ] The prevention and treatment tests were conducted with Kunming mice weighing about 18 -22 g. In the prevention test, Kunming mice were inocu- lated with Streptococcus suis serotype II and simultaneously taken orally 0.5, 1.0 and 2.0 g/ml Chinese herbal preparation Yinqiaotiangan respectively for continu- ous 3 d, once a day; the incidence rate, mortality rate and protective rate were detected after 7 d. In the treatment test, Kunming mice were inoculated with Strepto- coccus suis serotype II to establish the Streptococcus suis serotype II pathogenic model, and then taken orally 0.5, 1.0 and 2.0 g/ml Chinese herbal preparation Yin- qiaotiangan respectively for continuous 3 d, twice a day; the mortality rate, cure rate and effective rate were detected after 7 d. [ Result ] Results of the prevention test showed that the protective rate in experimental groups was extremely significantly higher than that in control group （P 〈0.01 ）, while the incidence rate and mortality rate were extremely significantly lower than that in control group （P 〈0.01 ）. Results of the treatment test showed that the incidence rate in experimental groups was extremely significantly lower than that in control group （P 〈0.01 ）, the cure rate in 0.5 g/ml group was extremely significantly higher than that in 1.0 g/ml group and 2.0 g/ml group （P 〈 0.01 ）, the effective rate in 0.5 g/ml group was significantly higher than that in 1.0 g/ml group and 2.0 g/ml group （ P 〈 0.05 ）, with no significant difference from the positive group （P 〉 0.05 ）. [ Conclusion ] The pathologic model of Streptococcus su/s serotype II could be effec- tively prevented and treated by oral intake of low dose of Chinese herbal preparation Yinqiaotiangan in Kunming mice.
基金supported by the National Natural Science Foundation of China (No. 81200380)
文摘Summary： Patients with FLT3-ITD^mmutt/NPM1- cytogenetically normal acute myeloid leukemia （CN-AML）, as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD^mut/NPM1- CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD^mut/NPM1- CN-AML primary cells. The FLT3-ITD^mut/NPM1- CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary genera- tion models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully estab- lished xenotransplantation model of human FLT3-ITD^mut/NPM1- CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.
基金supported by the National Natural Science Foundation of China International Cooperation and Exchange Program(8161101193)the National Science and Technology Major Project(2016ZX10004222)to G.Wong
文摘Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.
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Objective: A BALB/c mice model of cytomegalovirus-induced myocarditis was established. Methods: Twenty-five inbred female BALB/c mice free of murine cytomegalovirus(MCMV) infection (5 weeks old, 16-18 g),were infected with 1×10~4 PFU MCMV by the intraperitoneal (i.p.) administration. All experimental mice were sacrificed on day 3, 5, 7, 10,and 14 after i. p. administration. The hearts were removed under aseptic conditions, and were transected along the midline. Aliquots of hearts were handled with Bouin's fixative for histological examination. Residual hearts were immediately frozen in liquid nitrogen and stored at -80℃ until MCMV titre was determined by a plaque assay. Seurm cTnI level was assayed by ELISA. Results: MCMV in the heart was at extremely low level on day 3 after i. p. administration, reached to the peak on day 7-10, and then ran down. A mixed cellular infiltrate composed of polymorphonuclear neutrophils and mononuclear lymphocytes was observed on day 3, reaching to the peak on day 7-10 after MCMV infection, and was maintained for at least 3-4 months later. Seurm cTnI levels were elevated on day 3 after i.p. administration, reaching to the peak it day 7-10. Conclusion: The BALB/c mice model for cytomegalovirus-induced myocarditis was successfully established, that might make it possible to screen antiviral drugs for treating viral myocarditis and to investigate and evaluate the pathogenesis and prognosis of this disease.
文摘An experimental model of hepatic Schistosoma japonicum egg granuloma was established in C57BL/6 mice sensitized with soluble egg antigen(SEA) by direct injection of vital egg suspension into the spleen. The mice infected with cercariae of Schistosoma japonicum in abdominal skin were used for comparative studies. The results showed that morbidity of hepatic Schistosoma japonicum egg granulomas in the group sensitized with SEA was 100% and that the morphology, cellular constituents, developing process and the diameter and size of the egg granulomas in the group sensitized with SEA were similar to those of the group infected with cercariae. The authors suggest that this experimental model is a useful and appropriate tool for the study on egg granulomas of Schistosoma japonicum.
基金Liaoning Provincial Science and Technology Department Project,No.2023JH2/101700149Open Fund Project of Liaoning University of Traditional Chinese Medicine,No.zyzx2205.
文摘BACKGROUND Colon cancer(CC)is one of the most common malignant tumors in the gastrointestinal system.Overall,CC had the third highest incidence but the second highest mortality rate globally in 2020.Nowadays,CC is mainly treated with capecitabine chemotherapy regimen,supplemented by radiotherapy,immunotherapy and targeted therapy,but there are still limitations,so Chinese medicine plays an important role.AIM To investigate the effects of invigorating-spleen and anticancer prescription(ISAP)on body weight,tumor inhibition rate and expression levels of proteins in extracellular-signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)signaling pathway in CC mice model.METHODS The CC mice model were established and the mice were randomly divided into 5 groups,including the control group,capecitabine group,the low-dose,mediumdose and high-dose groups of ISAP,with 8 mice in each group,respectively.After 2 weeks of intervention,the body weight and tumor inhibition rate of mice were observed,and the expression of RAS,ERK,phosphorylated ERK(p-ERK),C-MYC and matrix metalloproteinase 2(MMP2)proteins in the tissues of tumors were detected.RESULTS Compared with the control group,the differences of body weight before and after treatment was much smaller in the groups of ISAP,with the smallest difference in the high-dose group of ISAP,while the capecitabine group had the greatest difference,indicating ISAP had a significant inhibiting effect on the growth of transplanted tumor in mice.The expression of RAS protein was decreased in the low-and medium-dose groups of ISAP,and the change of p-ERK was significant in the medium-and high-dose groups of ISAP.MMP2 protein expression was significantly decreased in both the low-dose and medium-dose groups of ISAP.There were no significant changes in ERK in the ISAP group compared to the capecitabine group,while RAS,MMP2,and C-MYC protein expression were reduced in the ISAP group.The expression level of C-MYC protein decreased after treated with ISAP,and the decrease was the most significant in the medium-dose group of ISAP.CONCLUSION ISAP has a potential inhibiting effect on transplanted tumor in mice,and could maintain the general conditions,physical strength and body weight of mice.The expression levels of RAS,p-ERK,MMP2 and c-myc were also decreased to a certain extent.By inhibiting the expression of upstream proteins,the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased.Therefore,it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins.
基金This project was supported by a project grand of the Science and Technology of Guangdong Province (2003A3020302).
文摘Purpose: To establish model of retinoblastoma subcutaneously in NOD-SCID mice and study rules of formation and distribution of retinoblastoma metastasis.Methods: Retinoblastoma cells SO-RB50 were inoculated subcutaneously in NOD-SCID mice. Animal acts and tumor formation, growth and metastasis in NOD-SCID mice were observed. Primary and metastatic tumors were studied pathohistologically by HE and immunohistochemical staining.Results: The latent periods of tumor growth were 12～19 days and the taken rate of tumor was 100%. 32 days later, 5 NOD-SCID mice were found with tumors that had metastasized to areas mainly located in the abdominal cavity and the side of the kidney; the metastatic time of tumors in the mice also differed. The tumor cells of the primary nodules and the metastasis were similar with human retinoblastoma cells and positive in immunohistochemical staining of NSE.Conclusion: The subcutaneous model of retinoblastoma in NOD-SCID mice showed a high taken rate and a short latent period of tumor, which had a high metastatic rate and was the best model in research of behaviors of retinoblastoma at present.
基金National Science and Technology Infrastructure of China,Grant/Award Number:National Pathogen Resource Center-NPRC-32National Key Research and Development Program of China,Grant/Award Number:2023YFF0724800CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-035。
文摘Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune pressure and host factors.Understanding these changes is crucial for epidemic control and variant research.Methods:Human angiotensin-converting enzyme 2(hACE2)transgenic mice were in-tranasally challenged with the original strain WH-09 and the variants Delta,Beta,and Omicron BA.1,while BALB/c mice were challenged with Omicron subvariants BA.5,BF.7,and XBB.1.To compare the pathogenicity differences among variants,we con-ducted a comprehensive analysis that included clinical symptom observation,meas-urement of viral loads in the trachea and lungs,evaluation of pulmonary pathology,analysis of immune cell infiltration,and quantification of cytokine levels.Results:In hACE2 mice,the Beta variant caused significant weight loss,severe lung inflammation,increased inflammatory and chemotactic factor secretion,greater mac-rophage and neutrophil infiltration in the lungs,and higher viral loads with prolonged shedding duration.In contrast,BA.1 showed a significant reduction in pathogenicity.The BA.5,BF.7,and XBB.1 variants were less pathogenic than the WH-09,Beta,and Delta variants when infected in BALB/c mice.This was evidenced by reduced weight loss,diminished pulmonary pathology,decreased secretion of inflammatory factors and chemokines,reduced macrophage and neutrophil infiltration,as well as lower viral loads in both the trachea and lungs.Conclusion:In hACE2 mice,the Omicron variant demonstrated the lowest pathogenic-ity,while the Beta variant exhibited the highest.Pathogenicity of the Delta variant was comparable to the original WH-09 strain.Among BALB/c mice,Omicron subvari-ants BA.5,BF.7,and XBB.1 showed no statistically significant differences in virulence.
基金Chinese Medicine Inheritance and Innovation“One Hundred Million”Talent Project Qihuang Scholar(to Li JX)The National Key R&D Program of China during the 13th Five-Year Plan Period,No.2018YFC1705405and The 66th China Postdoctoral Science Foundation,No.2019M660575.
文摘BACKGROUND Ulcerative colitis(UC)is an inflammatory bowel disease that is difficult to diagnose and treat.To date,the degree of inflammation in patients with UC has mainly been determined by measuring the levels of nonspecific indicators,such as C-reactive protein and the erythrocyte sedimentation rate,but these indicators have an unsatisfactory specificity.In this study,we performed bioinformatics analysis using data from the National Center for Biotechnology Information-Gene Expression Omnibus(NCBI-GEO)databases and verified the selected core genes in a mouse model of dextran sulfate sodium(DSS)-induced colitis.AIM To identify UC-related differentially expressed genes(DEGs)using a bioinformatics analysis and verify them in vivo and to identify novel biomarkers and the underlying mechanisms of UC.METHODS Two microarray datasets from the NCBI-GEO database were used,and DEGs between patients with UC and healthy controls were analyzed using GEO2R and Venn diagrams.We annotated these genes based on their functions and signaling pathways,and then protein-protein interactions(PPIs)were identified using the Search Tool for the Retrieval of Interacting Genes.The data were further analyzed with Cytoscape software and the Molecular Complex Detection(MCODE)app.The core genes were selected and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed.Finally,colitis model mice were established by administering DSS,and the top three core genes were verified in colitis mice using real-time polymerase chain reaction(PCR).RESULTS One hundred and seventy-seven DEGs,118 upregulated and 59 downregulated,were initially identified from the GEO2R analysis and predominantly participated in inflammation-related pathways.Seven clusters with close interactions in UC formed:Seventeen core genes were upregulated[C-X-C motif chemokine ligand 13(CXCL13),C-X-C motif chemokine receptor 2(CXCR2),CXCL9,CXCL5,C-C motif chemokine ligand 18,interleukin 1 beta,matrix metallopeptidase 9,CXCL3,formyl peptide receptor 1,complement component 3,CXCL8,CXCL1,CXCL10,CXCL2,CXCL6,CXCL11 and hydroxycarboxylic acid receptor 3]and one was downregulated[neuropeptide Y receptor Y1(NYP1R)]in the top cluster according to the PPI and MCODE analyses.These genes were substantially enriched in the cytokinecytokine receptor interaction and chemokine signaling pathways.The top three core genes(CXCL13,NYP1R,and CXCR2)were selected and verified in a mouse model of colitis using real-time PCR Increased expression was observed compared with the control mice,but only CXCR2 expression was significantly different.CONCLUSION Core DEGs identified in UC are related to inflammation and immunity inflammation,indicating that these reactions are core features of the pathogenesis of UC.CXCR2 may reflect the degree of inflammation in patients with UC.
