1.Establishment of a standardized daily behavior collection and analysis system for brain disease models of rhesus and cynomolgus monkeys and its application in autism spectrum disorder.
Xiaofeng REN ; Huimin WANG ; Xiaoman LV ; Yi ZHOU ; Yingyin FAN ; Yanjun YU ; Christoph W TURCK ; Yuhui CHEN ; Longbao LV ; Yingzhou HU ; Hao LI ; Wenchao WANG ; Dongdong QIN ; Xiaoli FENG ; Xintian HU
Journal of Zhejiang University. Science. B 2024;25(11):972-995
Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.
Animals
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Autism Spectrum Disorder
;
Macaca mulatta
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Disease Models, Animal
;
Behavior, Animal
;
Macaca fascicularis
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Male
;
Humans
2.Cardiac electrical activity after autologous pericardium transplantation
Li XIE ; Xiaogang ZHANG ; Lv HUANG ; Yonglin LI ; Xiaoman TANG ; Hui ZHANG
Chinese Journal of Tissue Engineering Research 2014;(27):4395-4400
BACKGROUND:The treatment of autologous pericardium transplantation has been widely applied in clinics, mainly involving cardiovascular repair and reconstruction, the treatment of ocular surface disease. The study addressing protection effects of autologous pericardium transplantation on the heart with ischemia injury is rarely reported. The investigations on the safety and protection effects of autologous pericardial transplantation on the heart with ischemia injury are of important significance.
OBJECTIVE:To explore effect of autologous pericardial transplantation on cardiac electrical activity and the protective effects on myocardial ischemia.
METHODS:Rongchang pork pigs and Sprague-Dawley rats were randomly divided into three groups:autologous pericardium transplantation, myocardial ischemia, and myocardial ischemia+autologous pericardium transplantation. The model of myocardial ischemia was established by ligation of the left anterior descending coronary artery in the groups of myocardial ischemia and myocardial ischemia+autologous pericardium transplantation. The model of transplantation was established by autologous pericardium transplant with flap in the groups of autologous pericardium transplantation and myocardial ischemia+autologous pericardium transplantation.
RESULTS AND CONCLUSION:Porcine electrocardiogram monitoring results showed that, superventricular premature beat was frequently observed in each group of pigs;the ventricular premature beat was occasional observed in autologous pericardium transplantation group, ventricular tachycardia and ventricular fibril ation did not appear. Compared with myocardial ischemia group, the ventricular premature beat decreased and the heart function was improved in myocardial ischemia+autologous pericardium transplantation group (P<0.05). Rat electrocardiogram monitoring results showed that, the ventricular fibril ation did not appear in autologous pericardium transplantation group, the lethal ventricular fibril ation did not appear in myocardial ischemia and myocardial ischemia+autologous pericardium transplantation groups. Compared with myocardial ischemia group, the heart function was improved, the apoptosis index decreased, the expressions of Bcl-2 protein increased, the expressions of Caspase-3 protein decreased in myocardial ischemia+autologous pericardium transplantation group (P<0.05). The autologous pericardium transplantation with flap cannot induce malignant ventricular arrhythmia and is relatively safe;the ventricular premature beat is reduced, the cardiac function is improved, which is possibly related to the inhibition of apoptosis in myocardial ischemic area.
3.Effect of surface electric-impulse stimulation on cardiac electrical activity of Kunming mice
Yonglin LI ; Hui ZHANG ; Ruofei SHI ; Xiaoman TANG ; Li XIE ; Lv HUANG ; Xiaogang ZHANG
Chinese Journal of Tissue Engineering Research 2014;(27):4318-4323
BACKGROUND: Electrical stimulation at different intensity, frequency and time on the human body may produce a variety of pathophysiological reactions. OBJECTIVE: To observe the effects of surface electric-impulse stimulation on heart rhythm and heart rate in mice. METHODS: Thirty Kunming mice were randomly divided into three groups, each group contained 10 mice. Electrical stimulation at different voltage, time and frequency was respectively applied to the three groups. The stimulus power was supplied by BL-420F Data Acquisition & Analysis System. The II lead electrocardiogram was recorded. The systemic reactions and local body changes of mice were observed.
4.Selective expansion and enhanced anti-tumor effect of antigen-specific CD4(+) T cells by retrovirus-mediated IL-15 expression.
Jizhou LV ; Ning TAO ; Hao WU ; Xiaoman LIU ; Xia XU ; Yingxin XU ; Zhihai QIN
Protein & Cell 2011;2(7):585-599
Mounting evidence has demonstrated that CD4(+) T cells play an important role in anti-tumor immune responses. Thus, adoptive transfer of these cells may have great potential for anti-cancer therapy. However, due to the difficulty to generate sufficient tumor-specific CD4(+) T cells, the use of CD4(+) T cells in tumor therapy is limited. It has been found that IL-15 transfection enhances the proliferation and anti-tumor activity of tumor-specific CD8(+) T cells, but the effect of IL-15 transfection on CD4(+) T cells remains unknown. Here, the effects of retrovirus-mediated IL-15 expression in Ova-specific CD4(+) T cells from Do11.10 mice were evaluated and it was discovered that IL-15 transfected CD4(+) T cells expressed both soluble and membrane-bound IL-15. Retrovirus-mediated IL-15 expression led to a selective expansion of antigen-specific CD4(+) T cells by inhibiting their apoptosis. In vivo IL-15 transfected CD4(+) T cells were more effective in suppressing tumor growth than control retroviral vector transfected ones. To ensure the safety of the method, the employment of thymidine kinase gene made it possible to eliminate these transgenic CD4(+) T cells following ganciclovir treatment. Together, we show that IL-15 transfection induced a selective expansion of antigen-specific CD4(+) T cells ex vivo and enhanced their tumor-suppression effects in vivo. This has an important significance for improving the efficacy of adoptive T cell therapy.
Animals
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Antineoplastic Agents
;
pharmacology
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CD4-Positive T-Lymphocytes
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cytology
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drug effects
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immunology
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Cell Proliferation
;
drug effects
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Cells, Cultured
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Gene Expression Regulation
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Genetic Vectors
;
genetics
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Humans
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Interleukin-15
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metabolism
;
Mice
;
Mice, Transgenic
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Neoplasms
;
drug therapy
;
Recombinant Fusion Proteins
;
genetics
;
Retroviridae
;
genetics

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