Immunomodulatory effect of human adipose derived mesenchymal stem cells on skin transplantation between different mouse strains / 中国组织工程研究

BACKGROUND: Skin transplantation is one of the most effective methods for treating large-area burns. How to effectively suppress the immune rejection after allogeneic skin transplantation is a problem that needs to be solved urgently. OBJECTIVE: To investigate the effect of human adipose derived mesenchymal stem cells (hADSCs) on the immunoregulation of skin grafts in different strains of mice. METHODS: Isolated hADSCs were cultured to the 3rd generation. Sixty ICR neonatal mice, 2-4 days of age, were randomly divided into four groups (n=15). The skin tissues of ICR neonatal mice were transplanted into adult C57BL/6 mice to establish a different strain of mouse skin graft immune rejection model. PBS and low dose (5×104), medium dose (10×104), high dose (20×104) hADSCs were injected into the model mice through tail vein, and the survival time of transplanted skin in each group was recorded. On the 7th day after operation, five mice from each group were randomly selected to remove their spleen and serum, and the expression of immune factors interleukin-10, tumor necrosis factor-α and interferon-γ were detected by RT-PCR and ELISA respectively. The transplanted part of the skin was taken to make pathological sections for observing the infiltration of lymphocytes. RESULTS AND CONCLUSION: Compared with the PBS group, the survival time of the skin was prolonged in the low dose hADSCs group; however, there was no significant difference between the two groups (P > 0.05). Compared with the PBS and low dose hADSCs groups, the survival time of the skin was significantly increased in the medium and high dose groups (P 0.05). Compared with the PBS group, the relative expression of tumor necrosis factor-α and interferon-γ in the spleen and serum was significantly decreased in the low, medium and high dose hADSCs groups (P < 0.05), whereas the level of interleukin-10 was significantly elevated in the medium and high dose hADSCs groups (P < 0.05). To conclude, the appropriate dose of hADSCs can significantly prolong the survival time of transplanted skin between different strains of mice, by regulating the expression of related immune factors in the recipient mice.

Abrupt Change in Electrophysiological Properties Begins From Postnatal Day 7 Before Hearing Onset in the Developing Mice Auditory Cortical Layer II/III Neurons

OBJECTIVES: In the developing auditory cortex, maturation of electrophysiological properties and cell types before and after hearing onset has been reported previously. However, the exact timing of firing pattern change has not been reported. In this study, firing pattern change was investigated from postnatal day 3 (P3) to P12 in auditory cortical layer II/III neurons to investigate whether firing pattern changes dramatically after a specific point during development. METHODS: ICR mice pups aged from P3 to P12 were sacrificed to obtain 300-mm-thick brain slices containing the primary auditory cortex. From cortical layer II/III neurons, the patterns of action potential firing generated by current injection were examined using whole cell current clamp technique and the characteristics of Na⁺ currents involved in action potential firing were investigated using whole cell voltage clamp technique. RESULTS: From P3 to P6, most cells did not show action potential firing (29 of 46 cells), and some cells responding to current injection showed a single action potential at the initial depolarizing current step (17 of 46 cells). This firing pattern changes from P7. From P7 to P9, cells begin to show regular spiking to current injection. The spiking frequency increased after P10. In studying Na⁺ current with whole cell voltage clamp, Na⁺ current densities increased gradually (32.0±2.0 pA/pF [P3–P6, n=7], 51.2±2.0 pA/pF [P7–P9, n=13], and 69.5±3.7 pA/pF [P10–P12, n=13]) in low external [Na⁺] condition. Na⁺ current recovery was accelerated and inactivation curves shifted to hyperpolarization with age. CONCLUSION: As regular spiking cells were observed from P7 but never from P3 to P6, P7 might be regarded as an important milestone in the development of auditory cortical layer II/III neurons. This change might mainly result from the increase in Na⁺ current density.

Comparison of the anesthetic effects of 2,2,2-tribromoethanol on ICR mice derived from three different sources / 한국실험동물학회지

This study was conducted to compare the anesthetic effects of 2,2,2-tribromoethanol (TBE, Avertin®) in ICR mice obtained from three different sources. TBE (2.5%) was intraperitoneally injected at three doses: high-dose group (500 mg/kg), intermediate-dose group (250 mg/kg), and low-dose group (125 mg/kg). Anesthesia time, recovery time, end-tidal peak CO2 (ETCO₂), mean arterial blood pressure, heart rate, oxygen saturation (SpO₂), body temperature, pH, PCO₂, and PO₂ of the arterial blood were measured. Stable anesthesia was induced by all doses of TBE and the anesthesia time was maintained exhibited dose dependency. No significant differences in anesthetic duration were found among the three different strains. However, the anesthesia time was longer in female than in male mice, and the duration of anesthesia was significantly longer in female than in male mice in the high-dose group. The recovery time was significantly longer for female than male mice in the intermediate- and high-dose groups. In the ICR strains tested, there were no significant differences in the mean arterial blood pressure, SPO₂, arterial blood PCO₂, and PO₂, which decreased after TBE anesthesia, or in heart rate and ETCO₂, which increased after TBE anesthesia. In addition, body temperature, blood biochemical markers, and histopathological changes of the liver, kidney, and lung were not significantly changed by TBE anesthesia. These results suggested that ICR mice from different sources exhibited similar overall responses to a single exposure to TBE anesthesia. In conclusion, TBE is a useful drug that can induce similar anesthetic effects in three different strains of ICR mice.

Comparison of the response using ICR mice derived from three different sources to multiple low-dose streptozotocin-induced diabetes mellitus / 한국실험동물학회지

This study was conducted to compare the multiple low-dose streptozotocin (MLDS)-induced diabetic patterns of Korl:ICR, A:ICR, and B:ICR mice obtained from three different sources. Six-week-old male ICR mice were obtained from three difference sources. Korl:ICR mice were kindly provided by the National Institute of Food and Drug Safety Evaluation (NIFDS). The other two groups of ICR mice were purchased from different vendors located in the United States (A:ICR) and Japan (B:ICR). All ICR mice that received MLDS exhibited overt diabetic symptoms throughout the study, and the incidence and development of diabetes mellitus were similar among the three ICR groups. The diabetic mice exhibited hyperglycemia, loss of body weight gain, decreased plasma insulin levels, impaired glucose tolerance, decreased number of insulin-positive cells, and decreased size of β-cells in the pancreas. The diabetes symptoms increased as the blood glucose level increased in the three ICR groups. In particular, the level of blood glucose in the STZ-treated group was higher in Korl:ICR and A:ICR mice than in B:ICR mice. The plasma insulin levels, glucose tolerance, blood chemistry, and morphological appearance of the pancreas were very similar in the ICR groups obtained from the three different sources. In conclusion, our results suggest that Korl:ICR, A:ICR, and B:ICR mice from different sources had similar overall responses to multiple low-dose STZ to induce diabetes mellitus.

Annual tendency of research papers used ICR mice as experimental animals in biomedical research fields / 한국실험동물학회지

Institute of Cancer Research (ICR) mice have been widely used in various research fields including toxicology, oncology, pharmacology, and pharmaceutical product safety testing for decades. However, annual tendency of research papers involving ICR mice in various biomedical fields has not been previously analyzed. In this study, we examined the numbers of papers that used ICR mice as experimental animals in the social science, natural science, engineering, medicine-pharmacy, marine agriculture-fishery, and art-kinesiology fields by analyzing big data. Numbers of ICR mouse-used papers gradually increased from 1961 to 2014, but small decreases were observed in 2015 and 2016. The largest number of ICR-used papers were published in the medicine-pharmacy field, followed by natural science and art-kinesiology fields. There were no ICR mouse-used papers in other fields. Furthermore, ICR mice have been widely employed in cell biology studies within the natural science field as well as in biochemistry and pathology in the medicine-pharmacy field. Few ICR mouse-used papers were published in exercise biochemistry and exercise nutrition in the art-kinesiology field. Regardless in most fields, the total numbers of published papers involving ICR mice were higher in 2014 than in other years, although the numbers in some fields including dentistry, veterinary science, and dermatology were high in 2016. Taken together, the present study shows that various ICR stocks, including Korl:ICR mice, are widely employed as experimental animals in various biomedical research fields.

Comparison of therapeutic responses to an anticancer drug in three stocks of ICR mice derived from three different sources / 한국실험동물학회지

Korl:ICR mice, established by the Korean National Institute of Food and Drug Safety Evaluation (NIFDS), are characterized based on their genetic variation, response to gastric injury, and response to constipation inducers. To compare the inhibitory responses of ICR stocks obtained from three different sources to the anticancer drug cisplatin (Cis), alterations in tumor volume, histopathological structure, and toxicity were examined in Sarcoma 180 tumor-bearing Korl:ICR, A:ICR (USA source), and B:ICR (Japan source) mice treated with low and high concentrations of Cis (L-Cis and H-Cis, respectively). Tumor size and volume were lower in H-Cis-treated mice than in L-Cis-treated mice in all three ICR stocks with no significant differences among stocks. There was a significant enhancement of the necrotizing areas in the histological structures in the L-Cis- and H-Cis-treated groups relative to that in the untreated group. The necrotizing area changes were similar in the Sarcoma 180 tumor-bearing Korl:ICR, A:ICR, and B:ICR mice. However, there were stock-bases differences in the serum biomarkers for liver and kidney toxic effects. In particular, the levels of AST, ALT and BUN increased differently in the three H-Cis-treated ICR stocks, whereas the levels of ALP and CRE were constant. Taken together, the results of the present study indicate that Korl:ICR, A:ICR, and B:ICR mice have similar overall inhibitory responses following Cis treatment of Sarcoma 180-derived solid tumors, although there were some differences in the magnitude of the toxic effects in the three ICR stocks.

Acute and 13-week subchronic toxicological evaluations of turanose in mice

BACKGROUND/OBJECTIVES: Turanose, α-D-glucosyl-(1→3)-α-D-fructose, is a sucrose isomer which naturally exists in honey. To evaluate toxicity of turanose, acute and subchronic oral toxicity studies were conducted with ICR mice. MATERIALS AND METHODS: For the acute oral toxicity study, turanose was administered as a single oral dose [10 g/kg body weight (b.w.)]. In the subchronic toxicity study, ICR mice were administered 0, 1.75, 3.5, and 7 g/kg b.w. doses of turanose daily for 13 weeks. RESULTS: No signs of acute toxicity, including abnormal behavior, adverse effect, or mortality, were observed over the 14-day study period. In addition, no changes in body weight or food consumption were observed and the median lethal dose (LD₅₀) for oral intake of turanose was determined to be greater than 10 g/kg b.w. General clinical behavior, changes in body weight and food consumption, absolute and relative organ weights, and mortality were not affected in any of the treatment group for 13 weeks. These doses also did not affect the macroscopic pathology, histology, hematology, and blood biochemical analysis of the mice examined. CONCLUSION: No toxicity was observed in the acute and 13-week subchronic oral toxicology studies that were conducted with ICR mice. Furthermore, the no-observed-adverse-effect level is greater than 7 g/kg/day for both male and female ICR mice.

Drug therapy and mechanism of pain in mice with induced adenomyosis / 中国实验动物学报

Objective To investigate the effects of different drugs and to explore the mechanism of pain in mice with adenomyosis ( ADM) .Methods The mouse model of adenomyosis was induced by oral administration of tamoxifen. The vaginal smear was examined by cytology, and serum levels of 5-HT, GnRH-R, NGF and NF were determined.Results Higher level of 5-HT was detected in the controls compared with the models.The expression of GnRH-R and NGF in nor-mal endometrium and eutopic endometrium were significantly lower than those in ectopic endometrium.The expression on NF in normal endometrium was significantly lower than that in the eutopic and ectopic endometria.Conclusions Similar with regular dose of GnRH-a, half dose of GnRH-a can slow down the progress of ADM as well as reducing pain.Combina-tion of regular dose of GnRH-a and Diane-35 could consolidate the therapeutic effect and even achieve pathological cure.5-HT may take an active part in the mechanism of pain in ADM.

Establishment of mice model of C6 glioma stem cells and its evaluation / 中国药理学通报

Aim To establish ICR animal model with C6 glioma stem cells, to provide the ideal model for the further study of gli-oma stem cells in brain glioma model. Methods C6 glioma stem cell was cultured in vitro by suspension,and was identified with Nestin antibody. C6 stem cells of ICR mouse glioma model were used to investigate survival state and tumor volume in mice after the operation. HE staining and CD133 immunohistochemi-cal study were adopted to investigate the postoperative pathologi-cal changes in mice. Results The expression of Nestin was 96. 01% in C6 glioma stem cells, and Nestin was highly ex-pressed in the cultured C6 glioma stem cells. Mice were inocula-ted with tumor after loss of appetite, weight, behavior and slow, sluggish reaction. Tumor volume at day 21 after modeling was (9. 77 ± 6. 58) mm3 . After HE staining, the model showed the invasive growth, tumor cell shrinkage and derangement. Immu-nohistochemical CD133 staining revealed that tumor cytoplasm color was brown. Conclusion Glioma model can be established based on glioma stem cells into a high rate of tumor, the tumor cycle is short, which can be used as an ideal model for glioma.

Comparison of the response using ICR mice derived from three different sources to ethanol/hydrochloric acid-induced gastric injury / 한국실험동물학회지

Animal models for gastric ulcers produced by physical, pharmacological and surgical methods have been widely employed to evaluate therapeutic drugs and investigate the mechanism of action of this disease. ICR mice were selected to produce this model, even though several mice and rats have been widely used in studies of gastric ulcers. To compare the responses of ICR mice obtained from three different sources to gastric ulcer inducers, alterations in gastric injury, histopathological structure, and inflammation were measured in Korl:ICR (Korea NIFDS source), A:ICR (USA source) and B:ICR (Japan source) treated with three concentrations of ethanol (EtOH) (50, 70, and 90%) in 150 mM hydrochloric acid (HCl) solution. Firstly, the stomach lesion index gradually increased as the EtOH concentration increased in three ICR groups. Moreover, a significant increase in the level of mucosal injury, edema and the number of inflammatory cells was similarly detected in the EtOH/HCl treated group compared with the vehicle treated group in three ICR groups. Furthermore, the number of infiltrated mast cells and IL-1β expression were very similar in the ICR group derived from three different sources, although some differences in IL-1β expression were detected. Especially, the level of IL-1β mRNA in 50 and 90EtOH/HCl treated group was higher in Korl:ICR and A:ICR than B:ICR. Overall, the results of this study suggest that Korl:ICR, A:ICR and B:ICR derived from different sources have an overall similar response to gastric ulcer induced by EtOH/HCl administration, although there were some differences in the magnitude of their responses.

Anti-hyperglycemic effects of aqueous Lenzites betulina extracts from the Philippines on the blood glucose levels of the ICR mice (Mus musculus)

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 μg/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 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.

A study on the effect of Ethyl Carbamate on the immune function of ICR mice / 预防医学

Objective To evaluate the effects of low dose Ethyl Carbamate (EC)on the immune function of ICR mice and to provide evidences for developing food safety standard.Methods The ICR mice were divided into four groups,and three groups were treated with 0.1 7,0.83,1 .67 mg/kg·bw EC respectively and the control group was treated with distilled water only.The immune function of ICR mice was determined by five aspects,including cellular immunity,humoral immunity,mononuclear macrophages's phagocytosis,natural killer cell activity and the organ coefficients of immune organs. Results Compared with the control group,the 1 .67 mg/kg·bw EC significantly inhibited the proliferation of spleen lymphocyte,natural killer cell activity and the hemolysis plaque -forming ability induced by ConA (P <0.05 ). Conclusion EC can cause the inhibition of normal mouse's immune function.

Observation of estrous cycle in sexual maturation and ovariectomized fe-male ICR mice / 中国病理生理杂志

AIM:To observe the characteristics of estrous cycle of female ICR mice and ovariectomized mice that had reached sexual maturity stage .METHODS:ICR mice were randomly divided into 3 groups, normal group, sham operation group and ovariectomized group .After ovariectomy and sham operating , at the 8th day, the mice were taken vagi-nal smears twice daily (09:00 and 16:00) for 12 consecutive days.The feature of vulva in the mice and vaginal smear cy-tology, occurrence rate of regular estrous cycle , duration of estrous cycle and each stage duration of estrous cycle were re -corded and observed .RESULTS:The characteristics of estrous cycle in normal group and sham operation group were simi-lar.Nearly 85%of the ICR mice in sexual maturity stage showed regular estrous cycle .The majority manifested 6-day cy-cle (83%), and only a small number exhibited 5-day cycle (17%).Compared with 5-day group, the duration of oestrus was significantly increased in 6-day group (P<0.05).The number and kind of the cells in vaginal smear were a little dif-ferent between 5-day and 6-day groups.The ovariectomized mice which showed irregular estrous cycle (76%) were charac-terized by continuous diestrus .CONCLUSION:Female ICR mice have the strain characteristics of estrus cycle .

Expression of HGF/c-met in the hair follicle growth cycle in mice / 中国实验动物学报

Objective HGF and its receptor ( c-met) are principal mediators of mesenchymal-epithelial interac-tion in several different systems.Moreover, hair follicle is a model of mesenchymal-epithelial interaction.The aim of this study was to explore whether HGF/c-met signal plays a role in the control of hair follicle growth cycle.Methods To ex-amine the localization of HGF/c-met in anagen, catagen and telogen in the hair follicle of ICR mice.Results HGF was mainly located in the dermal papilla and sebaceous gland, and c-Met in the hair matrix, root sheath and epidermis.Both HGF and c-met expressions peaked during anagen, not found in catagen, and increased during telogen-anagen phase.Con-clusions Our results demonstrate a regulatory role of HGF and c-met in the control of hair follicle growth in ICR mice.

The protective effect of pyrrolidine dithiocarbamate on acute radiation injury in mice / 中华放射医学与防护杂志

Objective To study the protective effect of pyrrolidine dithiocarbamate (PDTC) on acute irradiated mice.Methods The 6-8 weeks old male ICR mice were randomly divided into five groups:irradiation alone group (IR),positive control group (amifostine WR-2721 250 mg/kg) and PDTC of 30,60 and 90 mg/kg dose groups.Each group had 10 mice and the drug was given at 0.5 h before whole body irradiation.At 30 d post-irradiation of 7.5 Gy 137 Cs γrays,the mice survival were observed.At 8 d post-irradiation of 5.0 Gy 137 Cs γ-rays,the peripheral blood,hematopoietic system and organ indexes were observed to evaluate the radiation protective effect of PDTC.Results PDTC increased the 30-day survival rates and 60 mg/kg dose had the most obvious effect by increase the survival to 60％ (6/10).The survivals of irradiation alone group and the amifostine positive control group was 10％ (1/10) and 70％ (7/10),respectively.Compared with the irradiation alone group,60 mg/kg PDTC group had the significant difference in spleen index,WBC,HGB,PLT,bone marrow nucleated cells and colony forming unit of spleen (t =2.354,4.793,2.342,6.542,2.649,3.982,P ＜ 0.05).Conclusions PDTC is effective in radiation protection with an optimum dose of 60 mg/kg.

Influence of various photoperiods on stress hormone production, immune function, and hematological parameters in ICR mice / 대한수의학회지

In the present study, the effects of different photoperiods on stress, immunity, and hematological parameters in ICR mice were evaluated. Fifty male ICR mice 7 weeks old (body weight, 27.3 +/- 2.5 g) were divided into five groups: DP-0 (0/24-h light/dark cycle), DP-6 (6/18-h light/dark cycle), DP-12 (12/12-h light/dark cycle), DP-18 (18/ 6-h light/dark cycle), and DP-24 (24/0-h light/dark cycle). During the experimental period, no significant differences in body weight or feed intake were observed between the groups. Hematological analysis revealed that white blood cell, red blood cell, and hemoglobin values for the DP-0 group were significantly different compared to those of the other groups. After 28 days, no significant difference in serum cortisol concentration was observed among the groups, but serum cortisol levels increased in a light exposure-dependent manner. Total serum immunoglobulin G (IgG) concentrations of the DP-0 and PD-6 groups were significantly increased compared to those of the other groups (P < 0.05), and serum total IgG levels decreased in a light exposure-dependent manner. Results of the present study indicated that various photoperiods affect hematological parameters and total serum IgG levels in ICR mice while having no significant effects on body weight, feed intake, or cortisol levels.

Hematological effects of Ipomoea batatas (camote) and Phyllanthus niruri (sampa-sampalukan) from Philippines in the ICR mice (Mus musculus)

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 I. batatas and P. niruri 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 I. 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 and 28 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.

Effect of different doses of HS6101 on hematopoietic function of ICR mice treated with cyclophosphamide / 国际药学研究杂志

Objective: To observe the effect of different doses of HS6101 on the recovery of hematopoietic injury in ICR mice treated with cyclophosphamideCTX. Methods: Normal ICR mice were intraperitoneally injected with CTX at 100 mg/kg once a day for 3 consecutive days， and the mouse model of chemotherapy-induced hematopoietic injury was established. Three groups of mice with 20 per group， were respectively injected with HS6101 at 0， 9 or 27 μg subcutaneously at one hour before the first administration of CTX. The peripheral blood cell counts of the mice were observed once every 2 days. Hematopoietic progenitor cell colony counting and histopathological assessment of bone marrow cells were evaluated at 4 d and 9 d after the first administration of CTX. Results: In ICR mice after chemotherapy with CTX， all doses of HS6101 significantly increased peripheral leukocytes and neutrophils P<0.05， elevated the number of multilineage hematopoietic progenitor cell colonies of bone marrow， and stimulated the proliferation of bone marrow cells after CTX injury. Mice receiving 27 μg HS6101 were better than those of the other two groups. Conclusion: HS6101 at 27 μg could significantly promote the recovery of hematopoiesis in ICR mice treated with CTX chemotherapy.

Improving effects of dammarane sapogenins on sleep interruption-induced learning and memory impairment in mice / 中国比较医学杂志

Objective To study the effects of dammarane sapogenins ( DS-1226 ) on sleep interruption-induced learning and memory impairment in mice.Methods 130 SPF healthy 5 -6-week old male ICR mice were randomly divided into control, model, DS-1226 low dose, DS-1226 medium dose and DS-1226 high dose groups.The behavioral alterations in open field (OF), Morris water maze (MWM) and step-through (ST) tests were detected at 15 days after rotating drum-induced sleep interruption ( SI) .Results The total distance, movement speed, total duration of movement were increased in OF test ( P<0.05, vs.the model group) after treatment.The latency of place navigation was increased from day 5 in the MWM test after 15 d sleep interruption, and the number of crossing in the target quadrant and the percent distance in target quadrant were decreased after 15 d sleep interruption ( P <0.05, vs.the control group), while the latency of place navigation was decreased, and the percent distance in target quadrant and percent time in target quadrant after high dose DS-1226 oral administration ( P<0.05, vs.the model group) were increased.Error times, distance in dark chamber, time in dark chamber and immobility time in dark chamber were increased in training of step through test ( P<0.05, vs.the control group);while these indexes were decreased after DS-1226 oral administration ( P<0.05, vs.the model group) .But there was no significant difference in the step through testing course.Conclusions The results show that orally administrated DS-1226 can ameliorate SI-induced learning and memory impairment, and there is a significant dosage-effect relationship.

Anti-tumor effects of OK432 optimized umbilical vein endothelial cell vaccine in murine breast cancer / 中国药理学通报

Aim To investigate the anti-EAC breast cancer effects of viable human umbilical vein endothe-lial cells ( HUVECs) vaccine. Methods Subconflu-ent HUVECs were mixed with OK432 to prepare HU-VECs-OK432 vaccine, and the anti-tumor efficacy of HUVECs-OK432 was investigated using a subcutaneous tumor model of EAC breast cancer. ELISA, splenic lymphocyte proliferation assay and cytotoxic T lympho-cytes ( CTL ) killing assay were adopted to detect the humoral and cellular immune responses after HUVECs-OK432 immunization. Results HUVECs-OK432 im-munization significantly inhibited the growth of EAC tumor in mice in the prophylactic procedures. High ti-ter of anti-HUVEC antibody was elicited by HUVECs-OK432 immunization. The proliferation activity of splenocytes from mice immunized with HUVECs-OK432 was significantly increased. T lymphocytes iso-lated from HUVECs-OK432-immunized mice were dose dependently killing HUVECs in vitro. Conclusion Strong humoral and cellular immune responses targeting HUVEC are elicited by HUVECs-OK432 immuniza-tion, which results in a significant inhibition on the growth of EAC tumor in mice.