Abstract:Objective To evaluate the effect of Axl over expression on subcutaneous tumorigenesis of gastriccancer cell lines in nude mice. Methods The relationship between Axl and gastric cancer was analyzed by immunohistochemical staining. Axl-overexpressing gastric cancer cells were constructed through lentivirus transfection. The nude mouse model was established by subcutaneous injection of gastric cancer cells, and tumor sizes were evaluated byimaging of live animals. Results Immunohistochemical result revealed significantly higher Axl expression in gastric cancertissues compared with adjacent tissues. Axl expression in the Axl-overexpression gastric cancer cell line was increased by2. 4-fold. Live imaging of model mice revealed that after subcutaneous injection of cell lines for 2 weeks, tumors constructedwith the Axl-overexpression cell line were significantly larger than that of the control group, and this difference was moresignificant after 4 weeks ( P < 0. 01). Finally, the volume and weight of subcutaneous tumors formed by gastric cancer cells with high Axl expression were significantly increased compared with the control group. Conclusions Axl overexpression can enhance the subcutaneous tumorigenicity of SGC-7901 cells.

Abstract:Objective To screen for differentially expressed long non-coding RNA (LncRNA) in oral squamouscell carcinoma tissue samples from Chinese hamsters and predict their target genes, and explore the biological functions and enrichment signaling pathways of these target genes. Methods The squamous cell carcinoma model was established inChinese hamsters by 9,10-dimethyl-1,2-benzanthracene smear method. The profile of differentially expressed LncRNA wasconstructed by high-throughput sequencing technology. Differentially expressed LncRNAs were screened by biosignaltechnology and target genes were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)enrichment analyses were used to predict the biological function of differentially expressed genes and enriched signaling pathways, respectively. Results Compared with normal tissue samples, 54 differentially expressed LncRNAs werescreened from squamous cell carcinoma tissue samples, of which 31 were upregulated and 23 were downregulated.Functional analysis identified 73 GO entries associated with oral cancer, and 25 enriched KEGG signaling pathways.Conclusions Differentially expressed LncRNA in Chinese hamster oral squamous cell carcinoma samples likely play a rolein regulating various biological functions and oral cancer-related signaling pathways by targeting numerous genes, and may play an important role in the development of oral squamous cell carcinoma.

Abstract:Objective To observe the exact effect of microbubble-enhanced ultrasound cavitation combined with natural killer (NK) cells on microwave ablation of rabbit liver VX2 tumors. Methods Forty rabbits with VX2 liver tumors were randomly divided into five groups (eight animals per group): microwave ablation (MW), ultrasonic cavitation (CA), NK cell injection (NK), microwave ablation plus ultrasonic cavitation and NK cell injection (MW+CA+NK), and blank control (BL). Each group was administered their respective treatment intervention. Two-dimensional and contrastenhanced ultrasound imaging techniques were used to evaluate changes in tumor volume and maximum diameter 10 days after treatment. Tumor blood flow was evaluated by contrast-enhanced ultrasound imaging after treatment. Results Tumor volume and maximum diameter of the MW+CA+NK group were both significantly reduced compared with other groups 10 days after treatment ( P < 0. 05). In addition, blood flow of the MW+CA+NK group was significantly decreased compared with the other groups ( P < 0. 05). Conclusions Microbubble-enhanced ultrasound cavitation combined with NK cell could significantly enhance the effects of microwave thermal ablation of rabbit liver VX2 tumors.

Abstract:Objective To establish a model of primary liver cancer in mice using three method , and to compare their advantages and disadvantages. Methods Eighty male C57BL/6 mice aged 14 – 16 days were randomly divided into four groups: control, low-dose diethylnitrosamine (DEN), high-dose DEN, and DEN + carbon tetrachloride (CCl₄). Mice in the DEN+CCl₄ group were intraperitoneally injected with 2 mg/ kg DEN, and then two weeks later CCl₄(5 mL/ kg, 20%) was intraperitoneally injected twice a week for 16 weeks. The control group was not administered any treatment. Mice in the low-dose DEN group were injected intraperitoneally with 25 mg/ kg DEN, while mice in the high-dose DEN group were intraperitoneally injected with 40 mg/ kg DEN. Survival curves were generated for mice in each group. Twenty-four weeks after establishing the model, mice in each group were anesthetized and sacrificed, and the liver was dissected. The appearance of liver, incidence of tumors, number of tumors, and serum levels of alanine aminotransferase ( ALT), aspartate aminotransferase (AST), Golgi protein 73 ( GP73), alpha fetoprotein ( AFP) were measured. Results Compared with the control group, ALT ( P < 0. 001), AST ( P < 0. 001), GP73 ( P < 0. 001), AFP ( P < 0. 01), tumor incidence ( P < 0. 001), and tumor number in the three groups were significantly increased ( P < 0. 001). By 24 weeks after modeling, three mice in the low-dose DEN group had died, while six out of the 17 surviving mice developed liver cancer, resulting in an incidence of 35%. In the high-dose DEN group, six mice died and 12 out of the 14 surviving mice developed liver cancer, resulting in an incidence rate of 86%. In the DEN+CCl₄ group, four mice died and 9 out of the 16 surviving mice developed liver cancer, resulting in an incidence rate of 56%. All mice in the control group survived and no liver abnormalities were observed. Conclusions The liver cancer mouse model was successfully established in all experimental groups, but the high-dose DEN group exhibited obvious advantages with regard to successful establishment of a primary liver cancer model with high incidence and stability in a short period of time. Our result provide a new method for the establishment of a liver cancer model in mice.

Abstract:Objective To observe the effect of overexpression of a long noncoding RNA (LncRNA) LINC00152 on the tumor growth of human glioma U251 tumor-bearing mice and to explore its related mechanisms. Methods Lentiviral transfection upregulated the expression of LINC00152 in U251 cells. LINC00152 overexpression (LV-LINC00152 group) and empty control (LV group) cells were established, and normal U251 cells were used as the blank group (Control group). qRT-PCR was used to detect the expression of LINC00152. A U251 tumor-bearing mouse model was established. The p-YAP inhibitor XMU-MP-1 was administered to mice and the tumor volume was measured and the tumor weight was weighed at the end of the experiment. Immunohistochemical staining was used to observe the expression of Ki67 in tumor tissues. The expressions of YAP, p-YAP, LATS1 and p-LATS1 proteins were detected by Western blotting. Results Compared with the LV group, the expression of LINC00152 in the LV-LINC00152 group was significantly upregulated ( P < 0. 01). End of experiment, compared with the LV tumor-bearing mice, the tumor volume and tumor weight in the LVLINC00152 group were increased significantly ( P <0. 01). XMU-MP-1 (1 and 3 mg/ kg) treatment significantly reduced the tumor volume and tumor weight of LV-LINC00152 tumor-bearing mice in a dose-dependent manner ( P <0. 01). Ki67 staining in the LV group was weakly positive but strongly positive in the LV-LINC00152 group. After XMU-MP-1 (1 and 3 mg/ kg) treatment, Ki67 was weakly positive in the tumor tissues of the LV-LINC0015 group. Compared with the LV group, the expression of p-YAP and p-LATS1 protein in the LV-LINC00152 group was significantly upregulated ( P <0. 01), and XMU-MP-1 (1 and 3 mg/ kg) treatment reversed the p-YAP and p-LATS1 protein expression ( P <0. 01). Conclusions The long noncoding RNA LINC00152 induces YAP phosphorylation to promote glioma growth, while the p-YAP inhibitor XMU-MP-1 inhibits the above biological effects of the long noncoding RNA LINC00152.

Abstract:Objective To investigate the mechanism of ginsenoside Rg3 ( GS-Rg3 ) regulation of lymphangiogenesis in nude mice bearing human lung cancer by the transforming growth factor-β1 (TGF-β1) / extracellular regulatory protein kinase (ERK) signaling pathway. Methods Sixty nude mice were randomly divided into three groups: model group, GS-Rg3 group and SCH772984 group. The orthotopic transplantation model of human lung cancer in nude mice was established in the GS-Rg3 and SCH772984 groups. The GS-Rg3 mice were gavaged with GS-Rg3. Mice in the SCH772984 group were intraperitoneally injected with the ERK inhibitor SCH772984. Modeling and lymphatic metastasis of each group of mice were observed. Lymphangiogenesis, TGF-β1/ ERK signaling pathway and vascular endothelial growth factor (VEGF) expression in tumor tissues of each group were analyzed. Results Pathological examination using HE staining confirmed the lung cancer and its lymphatic metastasis. The proportion of lymphatic metastasis, tumor volume and tumor mass in the GS-Rg3 group and the SCH772984 group were significantly lower than those in the model group. There was no significant difference between the GS-Rg3 group and the SCH772984 group. Podoplanin protein expression level and relative density of lymphatic vessels were significantly lower in the GS-Rg3 group and the SCH772984 group than in the model group when using the podoplanin protein to label lymphatic vessels. There was no significant difference between the GS-Rg3 group and the SCH772984 group. GS-Rg3 and SCH772984 significantly inhibited activation of the TGF-β1/ ERK pathway. The expression levels of VEGF-C and VEGF-3 in the GS-Rg3 group and the SCH772984 group were lower than those in the model group. There was no significant difference between the GS-Rg3 group and the SCH772984 group. Conclusions GS-Rg3 can inhibit the expressions of VEGF-C and VEGF-3 by downregulating the transduction level of the TGF-β1/ ERK signaling pathway, thereby inhibiting lymphangiogenesis and reducing the lymphatic metastasis rate of lung cancer.

Abstract:Objective To investigate the effects of calycosin on the injury of oxygen and glucose deprivation/ reoxygenation PC12 cells. Methods PC12 cells were randomly divided into 5 groups: control group; oxygen and glucose deprivation/ reoxygenation (OGD/ R) (model group); and high, medium, and low (0. 140 μmol/ L, 0. 070 μmol/ L, 0. 035 μmol/ L) dose groups of calycosin. The CCK-8 method was used to detect cell viability, the lactate dehydrogenase leakage rate in cells was determined with the LDH method , cell morphology was observed with an inverted microscope, cell membrane integrity was detected with PI fluorescence staining, caspase-3 expression was detected by immunohistochemistry, and Bax and Bcl-2 immunofluorescence staining was used to detect apoptosis. Results The cells in the control group grew well. Compared with the control group, the number of cells in the model group decreased, the cells appeared to shrink, cell membranes were destroyed, cell activity decreased significantly ( P < 0. 05), the lactate dehydrogenase leakage rate was significantly increased ( P < 0. 05), the number of PI red-stained cells increased significantly ( P < 0. 05), the expression of caspase-3 was significantly increased ( P < 0. 05), and the ratio of Bax/ Bcl-2 increased significantly ( P < 0. 05). There were no significant differences observed between the model group and the high dose group ( P > 0. 05). However, the number of cells in the middle and low dose groups increased, the cells showed regular morphology, the membrane damage was reduced ( P < 0. 05), the cell viability was significantly increased ( P < 0. 05), the lactate dehydrogenase leakage rate was significantly decreased ( P < 0. 05), the number of PI red-stained cells decreased ( P < 0. 05), the expression of caspase-3 was significantly decreased ( P < 0. 05), and the ratio of Bax/ Bcl-2 was significantly lower ( P < 0. 05). The changes in the above indicators were more significant in the middle dose group, with the differences between the high dose group and the model group not reaching statistical significance ( P > 0. 05). Conclusions Calycosin can optimize the growth status of PC12 cells following injury through oxygen and glucose deprivation/ reoxygenation, improve cell viability, inhibit lactate dehydrogenase leakage, and inhibit cell apoptosis by reducing caspase-3 expression and the Bax/ Bcl-2 ratio, effectively alleviating cell damage and playing a protective role.

Abstract:Objective To observe the changes in hematopoietic and immune function at 6 months post 4 Gy or 6 Gy γ-ray total body irradiation (TBI) in C57BL/6 J mice. Methods C57BL/6 J mice of 8- 12 weeks of age were irradiated with 4 Gy or 6 Gy TBI. At 6 months after irradiation exposure, the peripheral blood cell count and classification, immune organ coefficient, immune phenotyping of the peripheral blood and spleen cells, and expression level of splenic T cell p16 were detected. Results Six months after irradiation exposure, the peripheral blood leukocyte and red blood cell count in the mice exposed to TBI remained significantly lower than those in the control group. There was no significant difference in the count of platelets in the irradiated mice compared to the control group. The result of the peripheral blood cell classification showed that the proportion of neutrophils in the irradiated mice group increased and the proportion of lymphocytes decreased, indicating a skew in blood cell differentiation. Compared with the control group, the thymus coefficient in the irradiated mice was significantly decreased at 6months post 6 Gy TBI ( P <0. 05). There was no significant difference in the spleen coefficient. Phenotyping of the peripheral blood cells was performed by flow cytometry. The result showed that the proportion of B lymphocytes and NK cells in the irradiated mice remained lower than those in the control group, while the proportion of CD4 lymphocytes in the irradiated group was higher than that in the control group. There was no significant difference between CD8 lymphocytes and monocyte levels in the irradiated group compared with the control group. The proportion of B220 cells was clearly decreased in the irradiated mice compared with the control group based on the splenic immune phenotyping assay ( P <0. 01). Compared with the control group, the expression of p16 in the splenic T cells of the 6 Gy TBI mice was increased but not significantly ( P > 0. 05). Conclusions Hematopoietic immune phenotyping indicated the recovery at 6 months after the sublethal dose of TBI but the neutrophils in the peripheral blood continued to be increased, and the thymus coefficient and the proportion of B lymphocytes in the peripheral blood and spleen were still lower than those in the control group, suggesting a long-term injury. These experimental result provide basic data for the study of total body irradiation-induced long-term injury of hematopoietic immune function.

Abstract:Objective To compare the efficiency of single or combined application of simvastatin and risedronate sodium on a disused osteopenia rat model with tail suspension. Methods Thirty 12-week-old C57BL6 mice were assigned to five groups of six mice each: control (A), tail suspension (B), simvastatin treatment (C), risedronate sodium treatment (D), and combined treatment (E). All but group A received tail suspension, and the groups were treated with the vehicle, simvastatin (5 mg/ (kg·d)), risedronate sodium (1 mg/ (kg·d)) or a combination of both, respectively. All mice were sacrificed after 3 weeks. Micro-CT was performed on the left tibia to determine the bone mass and microstructure of both the trabecular and cortical bones. Three-point bending test was used for biomechanical analysis of the left femur. The right tibias were subjected to RNA extraction and PCR analysis of OPG and RANKL expression, and the right femurs were used for protein level detection by western blot. Results Micro-CT: BV/ TV and Tb.N in group B were significantly lower than those of the other groups ( P < 0. 05), the Tb.Sp in group B was significantly higher than that of the other groups. BV/ TV in groups C and D were significantly lower than those in groups A and E, while Tb. Sp in groups C and D was significantly higher than that in group A ( P < 0. 05). ② Biomechanical test: maximal loading and the elastic modulus in group B were significantly lower than those of groups A and E ( P < 0. 05). ③ PCR: the mRNA level of OPG in groups C and E was significantly higher than that in group B ( P < 0. 05), and RANKL was expressed significantly higher in group B than that in group A ( P < 0. 05). ④ Western blot: the protein level of OPG in group A was markedly higher than that in the other groups ( P < 0. 05), OPG in group E was significantly higher than that in group B ( P < 0. 05), and the protein level of RANKL in group A was significantly lower than that in the other groups ( P < 0. 05). Conclusions Tail suspension caused bone loss and deterioration of bone quality in mice, and simvastatin combined with risedronate sodium treatment showed more substantial attenuation of these effects than treatment with either drug alone.

Abstract:Objective To study the effects of sleep interruption (SI) on the gait performance and cognitive ability of SD rats. Methods SD rats were randomly divided into eight groups: SI 2 days, SI 5 days, SI 10 days, SI 15 days, and their corresponding control groups, 8 rats in each group. Behavioral alterations in the gait detection (GD), open field (OF), and Morris water maze (MWM) tests were detected after SI for the indicated time periods. Results For the OF test, the total distance, movement speed, total duration of movement, and movement time in the peripheral area decreased following SI, and the total resting duration increased in the 5-day and 10-day SI groups compared with the control group ( P < 0. 05). The GD result showed that compared with the control group, the stride time decreased in the 5-day SI group; the walking speed, Lh-Rf double support time, and Lf-Rh double support time all decreased in the 2-day and 15-day groups, while the Rh-Lh-Rf three support time increased in the 2-day and 15-day SI groups; and the Rh stride length decreased in the 2-day, 5-day, and 15-day SI groups ( P < 0. 05). For the MWM test, compared with the control group, the latency of place navigation of MWM increased between days 1 and 4 in the 5-day SI group, increased between days 2 and 4 in the 10- day SI group, and increased between days 1 and 5 in the 15-day SI group. Conclusions Different durations of SI have varying effects on the result of the GD, OF, and MWM tests in SD rats. The GD test is a more sensitive method for evaluating the SI model than the OF and MWM tests.

Abstract:Objective To determine the effects of urate oxidase (Uox) gene knockout ( Uox ^{-/ -} )-induced spontaneous hyperuricemia on the body weight, blood pressure, and blood physiological and biochemical parameters of C57BL/6 J mice. Methods Both female and male C57BL/6 J mice at six- and twelve- week-old were contained, including wild-type ( Uox ^{+/ +} ), urate oxidase knockout heterozygotes ( Uox ^{+/ -} ) and urate oxidase knockout homozygous ( Uox ^{-/ -} ) mice. Mice body weight, blood pressure, and major blood physiological and biochemical parameters were observed. Results The average body weight of the 6-week-old female Uox ^{-/ -} mice and all male Uox ^{-/ -} mice was significantly lower than that of the Uox ^{+/ +} mice ( P < 0. 05). The body weight of the male Uox ^{+/ +} and Uox ^{+/ -} mice was significantly higher than that of the female mice of the same genotype and age ( P < 0. 05), but the body weight showed no statistical differences between the Uox ^{-/ -} mice of different sex. Compared with Uox ^{+/ +} and Uox ^{+/ -} mice of the same age, 6-week-old female Uox ^{-/ -} mice and 12-week-old male Uox ^{-/ -} mice had significantly higher blood pressure ( P < 0. 05). Blood physiological parameters showed that the red blood cell (RBC), hematocrit (HCT), mean corpuscular volume (MCV), and hemoglobin (HGB) of the Uox ^{-/ -} mice were significantly lower than those of the Uox ^{+/ +} mice ( P < 0. 05), and their mean corpuscular hemoglobin concentration (MCHC) and plateletcrit (PCT) were higher than those of the Uox ^{+/ +} mice ( P < 0. 05). Compared with the Uox ^{+/ +} mice, RBC, HCT and HGB of the Uox ^{+/ -} mice were significantly decreased ( P < 0. 05), while PCT was significantly increased ( P < 0. 05). The blood biochemical parameters showed that albumin ( ALB), total bilirubin (TBIL), and direct bilirubin (DBIL) of the Uox ^{-/ -} mice were lower than those of the Uox ^{+/ +} mice ( P < 0. 05), and their uric acid (UA), creatinine (CREA), blood urea nitrogen (BUN), cholesterol (CHOL), and low density lipoprotein (LDL) were significantly higher than those of the Uox ^{+/ +} mice ( P < 0. 05). Conclusions The basic biological data of C57BL/6 J mice with the urate oxidase gene knockout were established. Uox ^{-/ -} -induced spontaneous hyperuricemia could cause abnormal changes in body weight, blood pressure, kidney function, and lipid metabolism of mice.

Abstract:Objective To investigate the regulatory effect of nuclear transcription factors thyroxine receptor (TRB) and retinoic acid receptor X (RXR), as well as the agonist T4, on Cdc42-interacting protein 4 ( Cip 4) gene expression. Methods The Cip 4 gene promoter of Mongolian gerbils was cloned into the luciferase-reporter sequence of pGL3 basic to construct a new plasmid pGL3- Cip 4. Coding sequences of transcription factors TRB and RXR were cloned into pcDNA3. 1 eukaryotic expression vectors. pGL3- Cip 4, pcDNA3. 1-TRB, pcDNA3. 1-RXR, and pRL-TK (reference plasmid) vectors were used to transfect HEK-293 cells to form a luciferase double-reporter system for the Cip 4 gene. Transfection efficiency was optimized by adjusting the ratio of these plasmids. The agonist T4 was used to analyze transcriptional activity. Results Transfection efficiency and luciferase activity were the highest when a total amount of 2 μg plasmid and a ratio of 20∶1 between the (promoter + transcription factor) and pRL-TK. RXR could significantly increase Cip 4 gene transcription of ( P < 0. 05), whereas TRB did not alter Cip 4 transcription ( P > 0. 05). Thyroxine T4 could enhance RXR upregulation ( P < 0. 001), while a combination of T4 and TRB downregulated Cip 4 transcription ( P < 0. 05). Levels of Cip 4 transcription were significantly downregulated in the presence of T4, RXR, and TRB ( P < 0. 01). Conclusions T4, TRB, and RXR had coregulatory effects on Cip 4 gene transcription in Mongolian gerbils; moreover, they simulated the process of ligand T4 agonizing TRB/ RXR to activate Cip 4 gene transcription. These result indicating that Cip 4 transcription was significantly affected by the RXR signaling pathway lay the foundation for revealing thyroxine’ s mechanism of action in human nonalcoholic fatty liver disease, as well as the study of ligand-agonizing nuclear transcription factor regulation of Cip 4 gene expression and related drug screening.

Abstract:Objective To establish an ELISA assay for the detection of mouse IgG antibody to rabies virus. Methods Orthogonal experiments were used to determine the optimal dilution of the sample and optimal concentration of the secondary antibody. The stability, specificity and sensitivity test of the assay was determined. The assay result of these samples were compared with those of a commercial kit. Results The optimal dilution of the sample was 1∶100, the optimal concentration of the secondary antibody was 40 ng/ mL, and the cutoff value was 0. 121. There was no crossover with the common mouse viruses, and the minimum detection sensitivity was 129 μg/ mL, and the coefficient variation of the three replicates of the sample was less than 10%. The coincidence rate with the commercial kit was 100%. Conclusions An ELISA assay for the detection of a mouse IgG antibody to rabies virus was successfully established, which can be used for detection and analysis of rabies mouse models.

Abstract:Objective To collect the results of peripheral blood lymphocyte subsets determination conducted in National Center for Safety Evaluation of Drugs from 2007 to 2019 in accordance with Good Laboratory Practice (GLP), and establish reference ranges for corresponding normal values in BALB/ c mice, Sprague Dawley (SD) rats, and cynomolgus monkeys. Methods Peripheral blood samples were collected from animals and put into heparin sodium anticoagulant tubes. Blood samples from 303 BALB/ c mice, 359 SD rats, and 460 cynomolgus monkeys were stained with different combinations of fluorescent antibodies, and lymphocytes were classified and counted by their expression of CD3⁺ , CD4⁺ , CD8⁺ , and CD20⁺(cynomolgus monkeys only) using flow cytometry. For each species,the data were classified by gender and age (rat and mouse) and then calculated for normal reference range and 95% confidence interval, respectively. Results The range of CD4⁺ / CD8⁺ lymphocytes ratio was 1. 07-8. 59 in BALB/ c mice and 0. 54-11. 67 in SD rats. Ranges of CD4⁺ / CD8⁺ lymphocytes ratio and the percentage of CD3^- CD20⁺ lymphocytes in cynomolgus monkeys aged 3-4 years were 0. 35-4. 22 and 1. 40%-51. 99%, respectively. Conclusions Classified counts of lymphocyte subsets provide an important reference index for evaluating the immunotoxicity of biological products. The collection and establishment of relevant background data will facilitate more reasonable evaluations of drug toxicity.

Abstract:The term “humanized mouse” refers to the use of a mouse model with human cells, tissues, or organs. Transplantation of human immune cells into immunodeficient mice is an established humanized mouse model of the immune system that effectively simulates characteristics of the human immune system. Indeed, it provides an ideal experimental tool for studying interactions between the immune system and tumors. In this article, we review the construction method , advantages, and disadvantages of different types of humanized mouse models of the immune system, and further illustrate their applications for tumor immunotherapy.

Abstract:Increasing evidence suggests that epoxyeicosatrienoic acids (EETs) play a protective role in tissue and organ ischemia/ reperfusion ( I/ R) injury through a variety of mechanisms, and the mitochondrial pathway plays an important role in these mechanisms. However, as an important target for I/ R injury prevention and treatment, the mitochondrial pathway has not been explored in depth for EET-mediated protective mechanisms in I/ R injury. This review summarizes the role of mitochondrial K+ channels, mitochondrial permeability transition pores, mitochondrial proapoptotic proteins, and mitochondrial structural integrity in EET-mediated reductions of I/ R injury, providing a theoretical basis for further research. This is of great significance for preventing and treating I/ R injury of organs, and improving the prognosis of this disease.

Abstract:With the observed decline in human fertility, reproductive toxicity research has become increasingly important. It is crucial to select appropriate animal models for evaluating the toxicity of compounds of interest. Because of similarities in their reproductive system, non-rodent animals are valuable models for researching reproductive health and disorders. In this review, we summarized the characteristics of non-rodent animal models and their current applications in reproductive toxicity studies. The aim of this study was to expand the range of animal models available for selection and to provide new approaches for nonclinical reproductive toxicity studies.

Abstract:Animal research, which plays a critical role in drug discovery, has been of central importance for the production of background knowledge for clinical investigations and the optimization of procedures prior to human trials. An important feature of in vivo modeling is matching of the age of animals used in preclinical research to the age of peak incidence for a disease state in humans. Indeed, it is clear that animal models must match humans at a similar stage of life to be used as successful platforms for clinical translation, as many conditions that are targeted for drug treatment are age dependent. Valid age matching is critical for successful use of animal modelling in biomedical research in general and, in particular, drug discovery. It is important for researchers to understand that relative ages are different depending upon the stage of life. Therefore, one has to determine the relevant age under investigation and what factors are being analyzed. For this, special attention is needed to verify the phase of life of the animal (in days) and its correlation with the age of humans (in years). In this article, we focus on an even more specific issue: the degree to which similarities between species reflect fundamentally similar biological processes at a particular stage of development or age.

Abstract:Rabbits have similar evolutionary history to primates, similar cerebral vascular morphological features to humans, and easily localized basal ganglia. Moreover, as their success rates for cerebral hemorrhage modeling are high, while long-term mortality is low, rabbits are considered to be an ideal research model of cerebral hemorrhage. At present, there are several method for inducing a rabbit cerebral hemorrhage model: ① autologous blood injection, ② collagenase induction, ③ trauma, and ④ caused by puncturing middle cerebral artery. Whether the model has been successfully established can be assessed through the following aspects: behavioral analysis, gross anatomy, imaging, pathology, and so on. And the successfully established models can be used to study the pathophysiological mechanisms of cerebral hemorrhage and early diagnosis method , and to explore new treatment method , etc. This article mainly reviews the rabbit model of cerebral hemorrhage.