Chinese Kun Ming (KM) mouse, an outbreed strain of laboratory animal, has been widely utilized in related pharmaceutical and genetic studies throughout China. However, the value of KM mice to the research community ...Chinese Kun Ming (KM) mouse, an outbreed strain of laboratory animal, has been widely utilized in related pharmaceutical and genetic studies throughout China. However, the value of KM mice to the research community has been severely limited, partially due to the fact that well-characterized inbred strain of KM mice is not available. Several expected inbred strains from KM mice have been bred, but their genetic purity remains uncertain. In this study, four expected inbred strains of KM mice (A1, T2, N2, and N4) were chosen and their inbred degree were compared with two classical inbred mouse lines (BALB/c and C57BL/6) by analyzing the genotypes of about 30 microsatellite markers. In the four strains, A1 and N4 were homozygous at all genotyped loci, but N2 and T2 were only heterozygous at locus D15Mit16. These results indicate that the level of genetic purity/homozygousity of A1, N4, N2, and T2 inbred line is comparable to those of BALB/c and C57BL/6. This study provided the first and solid evidence for genetic purity of four expected inbred strains of KM mice. These 4 inbred mice strains should be well maintained for further characterization and utilization in genetic studies.展开更多
Gender and genetic strain are two prominent variants that influence drug abuse. Although certain sexrelated behavioral responses have been previously characterized in ICR mice, little is known about the effects of sex...Gender and genetic strain are two prominent variants that influence drug abuse. Although certain sexrelated behavioral responses have been previously characterized in ICR mice, little is known about the effects of sex on morphine-induced behavioral responses in this outbred strain. Therefore, in this study, we investigated the sex differences of morphine-induced locomotion, anxiety-like and social behaviors in ICR mice. After morphine or saline exposure for four consecutive days(twice daily), increased locomotion, more time spent in the central area, as well as attenuated rearing and self-grooming behaviors were found in morphine-treated females in an open field; no differences were found in locomotion and the time spent in the central area between male and female controls. When interacting with the samesex individuals, female controls were engaged in more social investigation, following, body contacting and self-grooming behaviors than controls; morphine exposure reduced contacting and self-grooming behaviors in females; in contrast, these effects were not found in males. These results indicate that female ICR mice are more prosocial and are more susceptible to morphine exposure than males.展开更多
Objective:To analyze the hematological effects of administering Ipomoea batatas(I.batatas)and Phyllanthus niruri(P.niruri) in the ICR mice.Methods:Powdered leaves of /.batatas and P.nintri were fed to mice for 4 weeks...Objective:To analyze the hematological effects of administering Ipomoea batatas(I.batatas)and Phyllanthus niruri(P.niruri) in the ICR mice.Methods:Powdered leaves of /.batatas and P.nintri were fed to mice for 4 weeks.A total of six groups were used to determine the effect of the plants to the complete blood count of the mouse.Group A(blank control) mice were feed with pellets only;Group B(negative control) mice were fed with pellets coated with honey;Group C(low dosage) mice were fed with honey-coated pellets and powdered leaves of 1.batatas at 10 g/kg body weight of the mouse;Group D(high dosage) mice were fed with honey-coated pellets and powdered leaves of I,batatas at 20 g/kg body weight of the mouse;Group E(low dosage) mice were fed with honey-coated pellets and powdered leaves of P.niruri at 10 g/kg body weight of the mouse:and Group F(high dosage) mice were fed with honey-coated pellets and powdered leaves of P.niruri at 20 g/kg body weight of the mouse.Complete blood count was performed on Days 0.14 and 28.Results:It was shown that I.batatas can increase the values of hematocrit and hemoglobin on both the low dose and high dose at Day 28 and red blood cells(RBC) on both Days 14 and28 of testing.On the other hand.P.niruri can increase RBC.hematocrit and hemoglobin on Day 28 with only the low dose.There were no significant differences with white blood cell,absolute granulocyte,lymphocyte and monocyte,and platelet counts observed for both plant samples.Conclusions:I.batatas and P.niruri have effects on the hematocrit,RBC and hemoglobin levels in mice.展开更多
Objective: To examine the anti-hyperglycemic effects of aqueous Lenzites betulina(L. betulina) extracts on normoglycemic glucose-loaded mice.Methods: Different doses of aqueous extract from L. betulina were administer...Objective: To examine the anti-hyperglycemic effects of aqueous Lenzites betulina(L. betulina) extracts on normoglycemic glucose-loaded mice.Methods: Different doses of aqueous extract from L. betulina were administered to 45 ICR mice(Mus musculus) to determine whether there was an effect of L. betulina extracts on the blood glucose level of the ICR mice. Aqueous extracts of L. betulina were orally gavaged to mice using oral glucose tolerance test. A total of five groups were used to determine the effect of the fungi on blood glucose of the mice. Group A(positive control)was given 16.7 mg/kg glimepiride; Group B(negative control) was given distilled water;Group C(low dosage) was given 200 mg/kg aqueous extract; Group D(mid dosage) was given 400 mg/kg aqueous extract and Group E(high dosage) was given 800 mg/kg aqueous extract. Baseline blood glucose value was firstly acquired before induction of hyperglycemia through D-glucose, after which another check on blood glucose was made after 0.5 h. Immediately, after the acquisition of hyperglycemic blood glucose level, the individual administration of treatments were done. After that, three blood collections were done spanning 3 h with 1 h interval.Results: The low dose(200 mg/kg) and the mid dose(400 mg/kg) of L. betulina extracts were significantly different(P < 0.05) from their respective baseline values throughout the whole experiment with the latter surpassing its baseline value during the 3rd hour. On the other hand, the high dose(800 mg/kg) during the 1st hour after administration was not significantly different(P > 0.05) from its corresponding baseline value, acting faster than the positive control(glimepiride), which only became significantly different(P < 0.05) at the 2nd hour.Conclusions: Aqueous L. betulina extract is able to produce hypoglycemic effects on the mice with all doses, which are able to normalize blood glucose levels at varying times.展开更多
Morphine is a widely used analgesic, but its use in clinical precision medicine is limited by the variance in response among individuals. Although previous studies have shown that individual differences in morphine ca...Morphine is a widely used analgesic, but its use in clinical precision medicine is limited by the variance in response among individuals. Although previous studies have shown that individual differences in morphine can be explained in terms of pharmacodynamics and pharmacokinetics, genetic polymorphisms also play an important role. However, the genetic basis of different sensitivity and tolerance susceptibility to morphine remains ambiguous. Using 15 strains of inbred Genetic Diversity(GD) mice,a new resource with wide genetic and phenotypic variation, we demonstrated great variance in sensitivity to morphine analgesia and susceptibility to morphine tolerance between different GD strains. Among-i ndividual variance in response to morphine analgesia in the population can be modeled in GD mice. Two loci respectively may be associated with the among-i ndividual variance in morphine sensitivity and tolerance,confirming the role of genetic factors in among-i ndividual different responses to morphine. These results indicate that GD mice may be a potential tool for the identification of new biomarkers to improve the clinical administration of morphine.展开更多
A cell line designated as Ca 761-86 has been established from the solid mouse mammary cancer (Ca 761) by suspension culture. It has been passaged for more than 212 generations. Moderate round cells were predominant an...A cell line designated as Ca 761-86 has been established from the solid mouse mammary cancer (Ca 761) by suspension culture. It has been passaged for more than 212 generations. Moderate round cells were predominant and most of them were mononuclear. Some characteristics of malignant cells and A-type viral-like particles were observed by electron microscopy. The results of cytochemical studies (DNA, RNA, SDH, 5' AMPase, ACP etc.) were comparable to the ultramicroscopic results. It multiplied approximately 27.4 fold on day 5 with mitotic index reaching 1.8% on day 3. This cell line was a hyperdiploid with karyotype of 45 or 45, -2X, tril2, tri17, +M1-5. Cell agglutination was observed when treated with ConA (≥7 fig, ml). Spontaneous agglutination might also take place without adding any ConA. After 5×106 cells of Ca 761-86 suspension were transplanted into the normal inbred 615 mice by different ways (subcutan eous, intrafoot-pad or intraperitoneal), the transplan lability rate reached 100%. Spontaneous remission was never observed and its metastatic ability reserved. PPLO were not detected. Ca 761-86 may be of value for practical purposes.展开更多
Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The suscep...Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.展开更多
Effects of maternal dietary zinc deficiency on prenatal and postnatal brain development were investigated in ICR strain mice. From d 1 of pregnancy (E0) until postnatal d 20 (P20), maternal mice were fed experimental ...Effects of maternal dietary zinc deficiency on prenatal and postnatal brain development were investigated in ICR strain mice. From d 1 of pregnancy (E0) until postnatal d 20 (P20), maternal mice were fed experimental diets that contained 1 mg Zn/kg/day (severe zinc deficient, SZD), 5 mg Zn/kg/day (marginal zinc deficient, MZD), 30 mg Zn/kg/day (zinc adequately supplied, ZA) or 100 mg Zn/kg/day (zinc supplemented, ZS and pair-fed, PF). Brains of offspring from these dietary groups were examined at various developmental stages for expression of nestin, an intermediate filament protein found in neural stem cells and young neurons. Immunocytochemistry showed nestin expression in neural tube 10.5 d post citrus (dpc) as well as in the cerebral cortex and neural tube from 10.5 dpc to postnatal d 10 (P10). Nestin immunoreactivities in both brain and neural tube of those zinc-supplemented control groups (ZA, ZS, PF) were stronger than those in zinc-deficient groups (SZD and MZD). Western blot analysis confirmed that nestin levels in pooled brain extracts from each of the zinc-supplemented groups (ZA, ZS, PF) were much higher than those from the zinc-deficient groups (SZD and MZD) from 10.5 dpc to P10. Immunostaining and Western blots showed no detectable nestin in any of the experimental and control group brains after P20. These observations of an association between maternal zinc deficiency and decreased nestin protein levels in brains of offspring suggest that zinc deficiency suppresses development of neural stem cells, an effect which may lead to neuroanatomical and behavioral abnormalities in adults.展开更多
AIM: To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice. METHODS: AFP gene expression was examined by i...AIM: To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice. METHODS: AFP gene expression was examined by immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepatoma cell growth in vitro was determined using microculture tetrazolium assay. In vitro antitumor activities of S-ODNs were monitored by measuring tumor weight differences in treated and control mice bearing SMMC-7721 xenografts. Induction of cell apoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis. RESULTS: Antisense S-ODN treatment led to reduced AFP gene expression. Specific antisense S-ODNs, but not control S-ODNs, inhibited the growth of hepatoma cells in vitro. In vitro, only antisense S-ODNs exhibited obvious antitumor activities. FACS analysis revealed that the growth inhibition by antisense S-ODNs was associated with their cell apoptosis induction. CONCLUSION: Antisense S-ODNs targeted to AFP genes inhibit the growth of human hepatoma cells and solid hepatoma, which is related to their cell apoptosis induction.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 investigate the correlation between lymphogenous metastasis and matrix metalloproteinases (MMPs) activity and the expression of Fas ligand of tumor cells in lymph nodes. METHODS: Fifty-six inbred 615-mice were...AIM: To investigate the correlation between lymphogenous metastasis and matrix metalloproteinases (MMPs) activity and the expression of Fas ligand of tumor cells in lymph nodes. METHODS: Fifty-six inbred 615-mice were equally divided into 2 groups and inoculated with Hca-F and Hca-P cells. Their lymph node metastatic rates were examined. Growth fraction of lymphocytes in host lymph nodes was detected by flow cytometry. The Hca-F and Hca-P cells were cultured with extract of lymph node, liver or spleen. The quantity of MMPs in these supernatants was examined by zymographic analysis. The expression of Fas ligand, PCNA, Bcl-2 protein of Hca-F and Hca-P cells in the mice were examined by immunohistochemistry. The apoptosis signals of macro-phages in lymph nodes were observed with in situ DNA fragmentation. RESULTS: On the 28th day post-inoculation, the lymph node metastatic rate of HcaF was 80%(16/20), whereas that of Hca-P was 25%(5/20). The growth fraction of lymphocytes was as follows: in the Hca-F cells, the proliferating peak of lymphocytes appeared on the 14th day post inoculation and then decreased rapidly, while in HcaP cells, the peak appeared on the 7th day post inoculation and then kept at a high level. With the extract of lymph node, the quantity of the MMP-9 activity increased (P【0.01) and active MMP-9 and MMP-2 were produced by both Hca-F and Hca-P tumor cells, which did not produce MMPs without the extract of lymph node or with the extracts of the liver and spleen. The expression of Fas Ligand of Hca-F cells was stronger than that of Hca-P cells (P 【0.01). The expressions of PCNA and Bcl-2 protein of Hca-F cells in the tumors of inoculated area were the same as that of Hca-P cells. In situ DNA fragmentation showed that the positive signals of macrophages were around Hca-F cells. CONCLUSION: Secretion of MMPs which was associated with metastatic ability of Hca-F and Hca-P tumor cells depends on the environment of lymph nodes. The increased expression of Fas ligand protein of Hca-F tumor cells with high lymphogenous metastatic potential in lymph nodes may help tumor cells escape from being killed by host lymphocytes.展开更多
AIM:To purify the heat shock protein (HSP) 70-associated tumor peptides and to observe its non-MHC-I molecule restrictive antitumor effect.METHODS:By ConA-sepharose affinity chromatography,ADP-agarose affinity chromat...AIM:To purify the heat shock protein (HSP) 70-associated tumor peptides and to observe its non-MHC-I molecule restrictive antitumor effect.METHODS:By ConA-sepharose affinity chromatography,ADP-agarose affinity chromatography, and DEAE anion exchange chromatography, we were able to purify HSP70-associated peptides from mouse hepatoma (HCaF) cells treated in heat shock at 42℃. Specific active immunization and adoptive cellular immunization assay were adopted to observe the immunoprotective effect elicited by HSP70-associated peptide complexes isolated from HcaF.RESULTS: The finally purified HSP-associated peptides had a very high purity and specificity found by SDS-PAGE and Western blot. Mice immunized with HSP70-associated peptide complexes purified from HCaF cells were protected from HCaF living cell challenge. This effect was dose dependent.Adoptive immunization of immune spleen cells of mice immunized with HSP70-associated peptide complexes could elicit immunity against HCaF challenge, and the tumor-free mice could resist repeated challenges. This effect could be continuously enhanced by repeated challenge with HCaF living cells. The tumor-free mice could tolerate the challenge for as high as 1×10^7 HCaF cells. The mice immunized once with spleen cells pulsed with HSP70-associated peptide complexes in vitro could also result in a certain adoptive immunity against HCaF.CONCLUSION:High purity and specificity of HSP70-associated peptides could be achieved from tumor cells by the low-pressure affinity chromatography method used in this study. HSP70-associated peptide complexes derived from the HCaF can elicit non-MHC-I molecule restrictive immunoprotective effect against HCaF.This effect can be transferred by adoptive immunization to mice and enhanced by repeated challenge with HCaF live cells.展开更多
AIM: To construct the plasmid pcHEV23 containing fragments of HEV ORF2 and ORF3 chimeric gene and to assess its ability to elicit specific immunologic response in mice. METHODS: The gene encoding the structural prot...AIM: To construct the plasmid pcHEV23 containing fragments of HEV ORF2 and ORF3 chimeric gene and to assess its ability to elicit specific immunologic response in mice. METHODS: The gene encoding the structural protein of HEV ORF2 fragment and full-length ORF3 was amplified by PCR. The PCR products were cloned into an eucaryotic expression plasmid pcDNA3. The resulting plasmid pcHEV23 was used as a DNA vaccine to inoculate BALB/c mice intramuscularly thrice at a dose of 100 or 200 ug. Mice injected with empty pcDNA3 DNA or saline served as control and then specific immune responses in the mice were detected. RESULTS: After 2-3 times of inoculation, all mice injected with pcHEV23 had anti-HEV IgG seroconversion and specific T lymphocyte proliferation. The lymphocyte stimulation index in the group immunized with pcHEV23 (3.1+0.49) was higher than that in the control group (0.787±0.12, P〈0.01). None in the control group had a detectable level of anti-HEV IgG. CONCLUSION: DNA vaccine containing HEV ORF2 and ORF3 chimeric gene can successfully induce specific humoral and cellular immune response in mice.展开更多
The effects of ethanol extract of Bidens pilosa L.(EEB)on acute exercise fatigue and its underlying biochemical mechanism were investigated in this study.Sixty adult male ICR mice were divided into control,model,vitam...The effects of ethanol extract of Bidens pilosa L.(EEB)on acute exercise fatigue and its underlying biochemical mechanism were investigated in this study.Sixty adult male ICR mice were divided into control,model,vitamin C(VC)100,EEB40,EEB80,and EEB160 groups,receiving VC(100 mg/kg)or EEB(40,80,160 mg/kg)for 28 days(intragastrically,I.G.).The mice underwent tailsuspension,elevated plus maze(EPM),rotarod,and loaded swimming tasks and biochemical indices were measured.There were no significant differences in body weight,tail suspension time,EPM open arm time/entries and serum cortisone levels among the groups.Compared with the model group,there was an increase in rotarod latency in the VC100/EEB80 groups and an increase in loaded swimming time in the EEB80/EEB160 groups.Furthermore,the haptic and muscle glycogen levels decreased in the model group,while the haptic glycogen levels increased in the all VC/EEB groups.Similarly,the serum lactate and creatinine levels increased in the model group,but decreased in lactate(except for EEB160),creatinine(except for EEB40)and lactate dehydrogenase in the EEB80 group.In the liver,malonaldehyde(MDA)and oxidized glutathione(GSSG)levels increased in the model group;however,glutathione reductase(GR)(except for EEB40),glutathione(GSH)and GSH/GSSG ratios increased,with GSSG levels decreasing in all VC/EEB groups.In the quadriceps,the GR levels increased in the model,whereas it decreased in the VC100,EEB40 and EEB80 groups.These results suggest that EEB has anti-acute fatigue effect,potentially attributed to mitigate metabolite accumulation,enhancing glycogen reserves,and fortifying the antioxidant mechanism.展开更多
To approach the action of modified Yu Ping Feng Tang ([symbol: see text] Jade-Screen Decoction) on cellular immunity, an experiment was conducted in mice under amputation-induced stress. On the 3rd day after amputatio...To approach the action of modified Yu Ping Feng Tang ([symbol: see text] Jade-Screen Decoction) on cellular immunity, an experiment was conducted in mice under amputation-induced stress. On the 3rd day after amputation, acute atrophy was found in the thymus, the reactivities of T- and B-lymphocytes to Con-A and LPS were decreased, the IL-2 content and its activity reduced and the activity of NK cells lowered. The high, moderate and low concentrations of the modified Yu Ping Feng (YPF) Decoction all have antagonistic action on the above manifestations of immune inhibition.展开更多
Aim: To assess the effect of estradiol-17β (E2) and bisphenol A (BPA) administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups' reproductive system in ICR mice. Met...Aim: To assess the effect of estradiol-17β (E2) and bisphenol A (BPA) administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups' reproductive system in ICR mice. Methods: Female mice were implanted with a tube filled with 10 ng, 500 ng, 1 μg, or 10 μg of E2, or 100 μg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E2 was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 μg/day. Results: Most of the mice given 1 μg and 10 lag of E2 did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights (testes, epididymides and accessory reproductive glands) in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E2 and 5 mg of BPA than that in the control. Conclusion: Chronic exposure to E2 and BPA might disrupt spermatogenesis in male pups. (Asian JAndrol 2008 Mar; 10: 271-276)展开更多
We have previously shown that the lipofuscin in the brain seems to have in-creased in amount in autopsy cases of epidemic hemorrhagic fever.The purpose of thisstudy was to testify if there is really such an increase.L...We have previously shown that the lipofuscin in the brain seems to have in-creased in amount in autopsy cases of epidemic hemorrhagic fever.The purpose of thisstudy was to testify if there is really such an increase.Lipfuscin in 10 sections from everybrain of 10 autopsy cases,stained with Sudan Ⅳ,Sudan black and H.E.,was carefully es-timated and found to be greatly increased as compared with the controls of the same agewithout brain disease.Animal experiment was also conducted on 15 sucking BALB/c miceby I.P.inoculation of 100 LD<sub>50</sub>(0.05ml)of strain Chen of hemorrhagic fever virus,andon 15 mice without inoculation as controls.No lipofuscin was detected in the controls.However,in the brains of experimental mice,lipofuscin was found to be markedly in-creased,especially in the necrotic cells.The findings suggest that the over-productionand deposition of lipofuscin may be a mild change caused by the virus and its related fac-tors,which might be enhanced by hypotension and shock.展开更多
基金This work was supported by the National Natural Science Foundation of China (No. 03114121).
文摘Chinese Kun Ming (KM) mouse, an outbreed strain of laboratory animal, has been widely utilized in related pharmaceutical and genetic studies throughout China. However, the value of KM mice to the research community has been severely limited, partially due to the fact that well-characterized inbred strain of KM mice is not available. Several expected inbred strains from KM mice have been bred, but their genetic purity remains uncertain. In this study, four expected inbred strains of KM mice (A1, T2, N2, and N4) were chosen and their inbred degree were compared with two classical inbred mouse lines (BALB/c and C57BL/6) by analyzing the genotypes of about 30 microsatellite markers. In the four strains, A1 and N4 were homozygous at all genotyped loci, but N2 and T2 were only heterozygous at locus D15Mit16. These results indicate that the level of genetic purity/homozygousity of A1, N4, N2, and T2 inbred line is comparable to those of BALB/c and C57BL/6. This study provided the first and solid evidence for genetic purity of four expected inbred strains of KM mice. These 4 inbred mice strains should be well maintained for further characterization and utilization in genetic studies.
基金supported by the National Natural Science Foundation of China(31260513)the National Innovation Experiment Program for University Students(XJCX-2014-106)
文摘Gender and genetic strain are two prominent variants that influence drug abuse. Although certain sexrelated behavioral responses have been previously characterized in ICR mice, little is known about the effects of sex on morphine-induced behavioral responses in this outbred strain. Therefore, in this study, we investigated the sex differences of morphine-induced locomotion, anxiety-like and social behaviors in ICR mice. After morphine or saline exposure for four consecutive days(twice daily), increased locomotion, more time spent in the central area, as well as attenuated rearing and self-grooming behaviors were found in morphine-treated females in an open field; no differences were found in locomotion and the time spent in the central area between male and female controls. When interacting with the samesex individuals, female controls were engaged in more social investigation, following, body contacting and self-grooming behaviors than controls; morphine exposure reduced contacting and self-grooming behaviors in females; in contrast, these effects were not found in males. These results indicate that female ICR mice are more prosocial and are more susceptible to morphine exposure than males.
文摘Objective:To analyze the hematological effects of administering Ipomoea batatas(I.batatas)and Phyllanthus niruri(P.niruri) in the ICR mice.Methods:Powdered leaves of /.batatas and P.nintri were fed to mice for 4 weeks.A total of six groups were used to determine the effect of the plants to the complete blood count of the mouse.Group A(blank control) mice were feed with pellets only;Group B(negative control) mice were fed with pellets coated with honey;Group C(low dosage) mice were fed with honey-coated pellets and powdered leaves of 1.batatas at 10 g/kg body weight of the mouse;Group D(high dosage) mice were fed with honey-coated pellets and powdered leaves of I,batatas at 20 g/kg body weight of the mouse;Group E(low dosage) mice were fed with honey-coated pellets and powdered leaves of P.niruri at 10 g/kg body weight of the mouse:and Group F(high dosage) mice were fed with honey-coated pellets and powdered leaves of P.niruri at 20 g/kg body weight of the mouse.Complete blood count was performed on Days 0.14 and 28.Results:It was shown that I.batatas can increase the values of hematocrit and hemoglobin on both the low dose and high dose at Day 28 and red blood cells(RBC) on both Days 14 and28 of testing.On the other hand.P.niruri can increase RBC.hematocrit and hemoglobin on Day 28 with only the low dose.There were no significant differences with white blood cell,absolute granulocyte,lymphocyte and monocyte,and platelet counts observed for both plant samples.Conclusions:I.batatas and P.niruri have effects on the hematocrit,RBC and hemoglobin levels in mice.
基金Supported by the University Research Coordination Office of De La Salle University with Challenge Grant No.500-033
文摘Objective: To examine the anti-hyperglycemic effects of aqueous Lenzites betulina(L. betulina) extracts on normoglycemic glucose-loaded mice.Methods: Different doses of aqueous extract from L. betulina were administered to 45 ICR mice(Mus musculus) to determine whether there was an effect of L. betulina extracts on the blood glucose level of the ICR mice. Aqueous extracts of L. betulina were orally gavaged to mice using oral glucose tolerance test. A total of five groups were used to determine the effect of the fungi on blood glucose of the mice. Group A(positive control)was given 16.7 mg/kg glimepiride; Group B(negative control) was given distilled water;Group C(low dosage) was given 200 mg/kg aqueous extract; Group D(mid dosage) was given 400 mg/kg aqueous extract and Group E(high dosage) was given 800 mg/kg aqueous extract. Baseline blood glucose value was firstly acquired before induction of hyperglycemia through D-glucose, after which another check on blood glucose was made after 0.5 h. Immediately, after the acquisition of hyperglycemic blood glucose level, the individual administration of treatments were done. After that, three blood collections were done spanning 3 h with 1 h interval.Results: The low dose(200 mg/kg) and the mid dose(400 mg/kg) of L. betulina extracts were significantly different(P < 0.05) from their respective baseline values throughout the whole experiment with the latter surpassing its baseline value during the 3rd hour. On the other hand, the high dose(800 mg/kg) during the 1st hour after administration was not significantly different(P > 0.05) from its corresponding baseline value, acting faster than the positive control(glimepiride), which only became significantly different(P < 0.05) at the 2nd hour.Conclusions: Aqueous L. betulina extract is able to produce hypoglycemic effects on the mice with all doses, which are able to normalize blood glucose levels at varying times.
基金supported by the National Key R&D Program of China (2017YFA0105204)National Natural Science Foundation of China (81873963)Fundamental Research Funds of Chinese Academy of Medical Sciences (2016ZX310044)。
文摘Morphine is a widely used analgesic, but its use in clinical precision medicine is limited by the variance in response among individuals. Although previous studies have shown that individual differences in morphine can be explained in terms of pharmacodynamics and pharmacokinetics, genetic polymorphisms also play an important role. However, the genetic basis of different sensitivity and tolerance susceptibility to morphine remains ambiguous. Using 15 strains of inbred Genetic Diversity(GD) mice,a new resource with wide genetic and phenotypic variation, we demonstrated great variance in sensitivity to morphine analgesia and susceptibility to morphine tolerance between different GD strains. Among-i ndividual variance in response to morphine analgesia in the population can be modeled in GD mice. Two loci respectively may be associated with the among-i ndividual variance in morphine sensitivity and tolerance,confirming the role of genetic factors in among-i ndividual different responses to morphine. These results indicate that GD mice may be a potential tool for the identification of new biomarkers to improve the clinical administration of morphine.
文摘A cell line designated as Ca 761-86 has been established from the solid mouse mammary cancer (Ca 761) by suspension culture. It has been passaged for more than 212 generations. Moderate round cells were predominant and most of them were mononuclear. Some characteristics of malignant cells and A-type viral-like particles were observed by electron microscopy. The results of cytochemical studies (DNA, RNA, SDH, 5' AMPase, ACP etc.) were comparable to the ultramicroscopic results. It multiplied approximately 27.4 fold on day 5 with mitotic index reaching 1.8% on day 3. This cell line was a hyperdiploid with karyotype of 45 or 45, -2X, tril2, tri17, +M1-5. Cell agglutination was observed when treated with ConA (≥7 fig, ml). Spontaneous agglutination might also take place without adding any ConA. After 5×106 cells of Ca 761-86 suspension were transplanted into the normal inbred 615 mice by different ways (subcutan eous, intrafoot-pad or intraperitoneal), the transplan lability rate reached 100%. Spontaneous remission was never observed and its metastatic ability reserved. PPLO were not detected. Ca 761-86 may be of value for practical purposes.
基金National Natural Scientific Foundation of ChinaGrant/Award Number:81972975+2 种基金National Human Diseases Animal Model Resource CenterNational Science Foundation for Young Scientists of ChinaGrant/Award Number:81703170。
文摘Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.
基金grants from National Basic Research Program (G 1999054000) andNational Natural Science FOundation of China (No.39770643, 398702
文摘Effects of maternal dietary zinc deficiency on prenatal and postnatal brain development were investigated in ICR strain mice. From d 1 of pregnancy (E0) until postnatal d 20 (P20), maternal mice were fed experimental diets that contained 1 mg Zn/kg/day (severe zinc deficient, SZD), 5 mg Zn/kg/day (marginal zinc deficient, MZD), 30 mg Zn/kg/day (zinc adequately supplied, ZA) or 100 mg Zn/kg/day (zinc supplemented, ZS and pair-fed, PF). Brains of offspring from these dietary groups were examined at various developmental stages for expression of nestin, an intermediate filament protein found in neural stem cells and young neurons. Immunocytochemistry showed nestin expression in neural tube 10.5 d post citrus (dpc) as well as in the cerebral cortex and neural tube from 10.5 dpc to postnatal d 10 (P10). Nestin immunoreactivities in both brain and neural tube of those zinc-supplemented control groups (ZA, ZS, PF) were stronger than those in zinc-deficient groups (SZD and MZD). Western blot analysis confirmed that nestin levels in pooled brain extracts from each of the zinc-supplemented groups (ZA, ZS, PF) were much higher than those from the zinc-deficient groups (SZD and MZD) from 10.5 dpc to P10. Immunostaining and Western blots showed no detectable nestin in any of the experimental and control group brains after P20. These observations of an association between maternal zinc deficiency and decreased nestin protein levels in brains of offspring suggest that zinc deficiency suppresses development of neural stem cells, an effect which may lead to neuroanatomical and behavioral abnormalities in adults.
基金Supported by the National Postdoctoral Science Foundation of China,No.199711.
文摘AIM: To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice. METHODS: AFP gene expression was examined by immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepatoma cell growth in vitro was determined using microculture tetrazolium assay. In vitro antitumor activities of S-ODNs were monitored by measuring tumor weight differences in treated and control mice bearing SMMC-7721 xenografts. Induction of cell apoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis. RESULTS: Antisense S-ODN treatment led to reduced AFP gene expression. Specific antisense S-ODNs, but not control S-ODNs, inhibited the growth of hepatoma cells in vitro. In vitro, only antisense S-ODNs exhibited obvious antitumor activities. FACS analysis revealed that the growth inhibition by antisense S-ODNs was associated with their cell apoptosis induction. CONCLUSION: Antisense S-ODNs targeted to AFP genes inhibit the growth of human hepatoma cells and solid hepatoma, which is related to their cell apoptosis induction.
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the Mational Natural Science Foundation of China,No.39470776
文摘AIM: To investigate the correlation between lymphogenous metastasis and matrix metalloproteinases (MMPs) activity and the expression of Fas ligand of tumor cells in lymph nodes. METHODS: Fifty-six inbred 615-mice were equally divided into 2 groups and inoculated with Hca-F and Hca-P cells. Their lymph node metastatic rates were examined. Growth fraction of lymphocytes in host lymph nodes was detected by flow cytometry. The Hca-F and Hca-P cells were cultured with extract of lymph node, liver or spleen. The quantity of MMPs in these supernatants was examined by zymographic analysis. The expression of Fas ligand, PCNA, Bcl-2 protein of Hca-F and Hca-P cells in the mice were examined by immunohistochemistry. The apoptosis signals of macro-phages in lymph nodes were observed with in situ DNA fragmentation. RESULTS: On the 28th day post-inoculation, the lymph node metastatic rate of HcaF was 80%(16/20), whereas that of Hca-P was 25%(5/20). The growth fraction of lymphocytes was as follows: in the Hca-F cells, the proliferating peak of lymphocytes appeared on the 14th day post inoculation and then decreased rapidly, while in HcaP cells, the peak appeared on the 7th day post inoculation and then kept at a high level. With the extract of lymph node, the quantity of the MMP-9 activity increased (P【0.01) and active MMP-9 and MMP-2 were produced by both Hca-F and Hca-P tumor cells, which did not produce MMPs without the extract of lymph node or with the extracts of the liver and spleen. The expression of Fas Ligand of Hca-F cells was stronger than that of Hca-P cells (P 【0.01). The expressions of PCNA and Bcl-2 protein of Hca-F cells in the tumors of inoculated area were the same as that of Hca-P cells. In situ DNA fragmentation showed that the positive signals of macrophages were around Hca-F cells. CONCLUSION: Secretion of MMPs which was associated with metastatic ability of Hca-F and Hca-P tumor cells depends on the environment of lymph nodes. The increased expression of Fas ligand protein of Hca-F tumor cells with high lymphogenous metastatic potential in lymph nodes may help tumor cells escape from being killed by host lymphocytes.
基金Supported by the National Natural Science Foundation of China,No.3973440-Ⅱ
文摘AIM:To purify the heat shock protein (HSP) 70-associated tumor peptides and to observe its non-MHC-I molecule restrictive antitumor effect.METHODS:By ConA-sepharose affinity chromatography,ADP-agarose affinity chromatography, and DEAE anion exchange chromatography, we were able to purify HSP70-associated peptides from mouse hepatoma (HCaF) cells treated in heat shock at 42℃. Specific active immunization and adoptive cellular immunization assay were adopted to observe the immunoprotective effect elicited by HSP70-associated peptide complexes isolated from HcaF.RESULTS: The finally purified HSP-associated peptides had a very high purity and specificity found by SDS-PAGE and Western blot. Mice immunized with HSP70-associated peptide complexes purified from HCaF cells were protected from HCaF living cell challenge. This effect was dose dependent.Adoptive immunization of immune spleen cells of mice immunized with HSP70-associated peptide complexes could elicit immunity against HCaF challenge, and the tumor-free mice could resist repeated challenges. This effect could be continuously enhanced by repeated challenge with HCaF living cells. The tumor-free mice could tolerate the challenge for as high as 1×10^7 HCaF cells. The mice immunized once with spleen cells pulsed with HSP70-associated peptide complexes in vitro could also result in a certain adoptive immunity against HCaF.CONCLUSION:High purity and specificity of HSP70-associated peptides could be achieved from tumor cells by the low-pressure affinity chromatography method used in this study. HSP70-associated peptide complexes derived from the HCaF can elicit non-MHC-I molecule restrictive immunoprotective effect against HCaF.This effect can be transferred by adoptive immunization to mice and enhanced by repeated challenge with HCaF live cells.
基金Supported by the Grants from the Natural Science Foundation of Zhejiang Province, No. RC01054, Science Technology Department of Zhejiang Province, No. F11023 and Key Project of Health Bureau of Zhejiang Province
文摘AIM: To construct the plasmid pcHEV23 containing fragments of HEV ORF2 and ORF3 chimeric gene and to assess its ability to elicit specific immunologic response in mice. METHODS: The gene encoding the structural protein of HEV ORF2 fragment and full-length ORF3 was amplified by PCR. The PCR products were cloned into an eucaryotic expression plasmid pcDNA3. The resulting plasmid pcHEV23 was used as a DNA vaccine to inoculate BALB/c mice intramuscularly thrice at a dose of 100 or 200 ug. Mice injected with empty pcDNA3 DNA or saline served as control and then specific immune responses in the mice were detected. RESULTS: After 2-3 times of inoculation, all mice injected with pcHEV23 had anti-HEV IgG seroconversion and specific T lymphocyte proliferation. The lymphocyte stimulation index in the group immunized with pcHEV23 (3.1+0.49) was higher than that in the control group (0.787±0.12, P〈0.01). None in the control group had a detectable level of anti-HEV IgG. CONCLUSION: DNA vaccine containing HEV ORF2 and ORF3 chimeric gene can successfully induce specific humoral and cellular immune response in mice.
基金Supported by the National Natural Science Foundation of China(31760278)。
文摘The effects of ethanol extract of Bidens pilosa L.(EEB)on acute exercise fatigue and its underlying biochemical mechanism were investigated in this study.Sixty adult male ICR mice were divided into control,model,vitamin C(VC)100,EEB40,EEB80,and EEB160 groups,receiving VC(100 mg/kg)or EEB(40,80,160 mg/kg)for 28 days(intragastrically,I.G.).The mice underwent tailsuspension,elevated plus maze(EPM),rotarod,and loaded swimming tasks and biochemical indices were measured.There were no significant differences in body weight,tail suspension time,EPM open arm time/entries and serum cortisone levels among the groups.Compared with the model group,there was an increase in rotarod latency in the VC100/EEB80 groups and an increase in loaded swimming time in the EEB80/EEB160 groups.Furthermore,the haptic and muscle glycogen levels decreased in the model group,while the haptic glycogen levels increased in the all VC/EEB groups.Similarly,the serum lactate and creatinine levels increased in the model group,but decreased in lactate(except for EEB160),creatinine(except for EEB40)and lactate dehydrogenase in the EEB80 group.In the liver,malonaldehyde(MDA)and oxidized glutathione(GSSG)levels increased in the model group;however,glutathione reductase(GR)(except for EEB40),glutathione(GSH)and GSH/GSSG ratios increased,with GSSG levels decreasing in all VC/EEB groups.In the quadriceps,the GR levels increased in the model,whereas it decreased in the VC100,EEB40 and EEB80 groups.These results suggest that EEB has anti-acute fatigue effect,potentially attributed to mitigate metabolite accumulation,enhancing glycogen reserves,and fortifying the antioxidant mechanism.
文摘To approach the action of modified Yu Ping Feng Tang ([symbol: see text] Jade-Screen Decoction) on cellular immunity, an experiment was conducted in mice under amputation-induced stress. On the 3rd day after amputation, acute atrophy was found in the thymus, the reactivities of T- and B-lymphocytes to Con-A and LPS were decreased, the IL-2 content and its activity reduced and the activity of NK cells lowered. The high, moderate and low concentrations of the modified Yu Ping Feng (YPF) Decoction all have antagonistic action on the above manifestations of immune inhibition.
文摘Aim: To assess the effect of estradiol-17β (E2) and bisphenol A (BPA) administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups' reproductive system in ICR mice. Methods: Female mice were implanted with a tube filled with 10 ng, 500 ng, 1 μg, or 10 μg of E2, or 100 μg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E2 was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 μg/day. Results: Most of the mice given 1 μg and 10 lag of E2 did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights (testes, epididymides and accessory reproductive glands) in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E2 and 5 mg of BPA than that in the control. Conclusion: Chronic exposure to E2 and BPA might disrupt spermatogenesis in male pups. (Asian JAndrol 2008 Mar; 10: 271-276)
基金Project was supported by the National Natural Science Foundation of China No.38 970 335
文摘We have previously shown that the lipofuscin in the brain seems to have in-creased in amount in autopsy cases of epidemic hemorrhagic fever.The purpose of thisstudy was to testify if there is really such an increase.Lipfuscin in 10 sections from everybrain of 10 autopsy cases,stained with Sudan Ⅳ,Sudan black and H.E.,was carefully es-timated and found to be greatly increased as compared with the controls of the same agewithout brain disease.Animal experiment was also conducted on 15 sucking BALB/c miceby I.P.inoculation of 100 LD<sub>50</sub>(0.05ml)of strain Chen of hemorrhagic fever virus,andon 15 mice without inoculation as controls.No lipofuscin was detected in the controls.However,in the brains of experimental mice,lipofuscin was found to be markedly in-creased,especially in the necrotic cells.The findings suggest that the over-productionand deposition of lipofuscin may be a mild change caused by the virus and its related fac-tors,which might be enhanced by hypotension and shock.