Abstract:Objective To explore the effects of resistance training on hypoxia?induced skeletal muscle atrophy in rats and provide a theoretical basis to solve the problem of skeletal muscle atrophy of athletes in altitude training. Methods 24 male 8?week?old SD rats (mean body weight 230 g) were divided into 4 groups: normoxia control group (C), resistance training group (R), hypoxia group (H) and hypoxia and resistance training group (HR). The groups H and HR were placed into environment simulated 4000 m altitude (12. 4%, O2 %). Moreover, the groups R and HR received resistance training. After the 4?week hypoxia and resistance training intervention, the body composition, wet weight of skeletal muscle (soleus, musculus gastrocnemius, extensor digitorum longus and musculus biceps brachii) and skeletal muscle cross?sectional area (CSA) were measured and analyzed. Results The muscle mass of HR group was significantly higher than the group H ( P < 0. 01). The wet weight and CSA of musculus biceps brachii in the group HR were also significantly higher than the group H ( P < 0. 05). Conclusions Resistance training can help to prevent the occurrence of hypoxia?induced skeletal muscle atrophy. Resistance ladder training can stimulate the hypertrophy of biceps brachii.

Abstract:Objective The aim of this work was to investigate the protective effects of 13?methyltetradecanoic acid (13?MTD) on focal cerebral ischemia in rats and oxygen paradox in cultured astrocytes in vitro. Methods Almost pure astrocytes were obtained after primary culture and subculture from cerebral cortex of neonatal rats, and then the OGD 10 h/R 24 h cell model was generated by treatment with oxygen?glucose deprivation for 10 h/ reperfusion for 24 h. 13?MTD 20, 40, 80 μg/ mL was administered immediately after reperfusion. Microscopy was used to observe the changes of cell morphology dynamically. MTT assay was employed to detect mitochondrial activity, and immunohistochemistry was done to determine the expressions of GFAP and AQP4. Results After oxygen paradox, damages of the cerebral cortical astrocytes of neonatal rats were observed, the mitochondrial activity was decreased significantly ( P < 0. 01), and AQP4 protein expression was increased significantly ( P < 0. 01). Compared with the vehicle control, 13?MTD 20, 40, 80 μg/ mLimproved the above parameters ( P < 0. 01), with optimal effect being obtained at 80 μg/ mL. Conclusions 13?MTD can down?regulated AQP4 protein expression, improve the mitochondrial activity, decrease cell edema, and protected the astrocytes damage from oxygen paradox.

Abstract:Objective To established a rat model for type II diabetes and to investigate the gradual changes of myocardial fibrosis and myocardial AGEs/ RAGE levels in type II diabetes. Methods Male SD rats were fed high?fat fodder for 6 weeks, and then injected a small dose of streptozotocin (STZ, 30 mg/ kg) after overnight fasting for 12 h. The random blood GLU was detected on the 3th and 7th days, respectively, after STZ injection. The rats with random blood GLU concentration higher or equal to 16. 7 mmol/ L detected twice were considered as successful rat model of type II diabetes. Six rats of group C and six rats of group D fasting for 12 h were killed after intraperitoneal anesthesia at the 4th, 8th and 12th weeks after the successful establishment of type II diabetes models. Blood samples were taken for FBG and insulin detection. A portion of the left ventricle tissue was used for Masson staining and immunohistochemical detection of RAGE, and the other portion of the left ventricle was used for the detection of content of AGEs and Hyp. Results The FBG levels of group D were significantly higher, and the body weights of group D were significantly lower than group C at the same weeks. Blood insulin of the group D at the 12th week was significantly higher than that of the group C at the 12th week and group D at the 4th week. Myocardial Hyp, CVF, AGEs and RAGE of group D were significantly higher than those of the group C at the 8th, 12th weeks. The AGEs/ RAGE level of myocardium in the diabetic rats was positively correlated with CVF. Conclusions The model of type II diabetes is successfully established through intraperitoneal injecting a low?dose streptozotocin to SD rats which had been fed high?fat fodder. The rat models of type II diabetes demonstrate myocardial fibrosis at the 12th week after the successful establishment of diabetes. With the further development of diabetes, the myocardial fibrosis, content of myocardial AGEs, RAGE protein expression of the diabetic rats show an upward trend. The level of AGEs/ RAGE is positively correlated with the degree of myocardial fibrosis of type II diabetic rats.

Abstract:Objective To investigate the role of autonomic nervous function and the effect of royal jelly intervention on rabbit models of atherosclerosis (AS). Methods Eighteen healthy 3 - 4?month old male Japanese white rabbits were randomly divided into normal control (NC) group, high?fat high?sugar diet (HFHSD) group and royal jelly intervention (RJ) group, 6 rabbits in each group. The rabbits received high?fat and high?sugar diet for 12 weeks to induce atherosclerosis model. At the same time, the RJ group was orally given 200 mg/ kg royal jelly daily, twice a day, for consecutive 12 weeks. The plasma levels of total cholesterol (TC), triglyceride (TG), low?density lipoprotein cholesterol (LDL?C) and high?density lipoprotein cholesterol (HDL?C), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) were detected. The electrocardiogram and blood pressure were monitored, and the heart rate variability (HRV) and baroreflex sensitivity (BRS) were analyzed. The pathological changes in the abdominal aorta tissues were observed using H&E and Sudan IV staining, respectively. Results Compared with the NC group, the levels of serum lipids in the HFHSD group were significantly increased ( P < 0. 05). The lipid deposition and atherosclerotic plaque sizes in the abdominal aorta were significantly increased ( P < 0. 05). The plasma SOD and NO levels were decreased and the MDA content was increased ( P < 0. 05, P < 0. 01). The reduction of cardiac function was accompanied by a decrease of HRV and BRS values ( P < 0. 05, P < 0. 01). Compared with the HFHSD group, RJ significantly improved the above indicators. Conclusions High fat and high sugar diet can lead to cardiac autonomic nervous dysfunction and to further form atherosclerosis in rabbits. Royal jelly intervention can regulate cardiac autonomic nervous function and delay the development of atherosclerotic lesions.

Abstract:Objective To establish a Bama minipig model of hypertension induced by high?fat and high?salt diet and to explore its mechanism. Methods Eighteen healthy male Bama minipigs were randomly divided into 3 groups: normal control (NC) group, high?fat (HF) diet group and high?fat/ high?salt diet (HFHS) group, 6 in each group. The NC group was fed normal basal diet, the HF group and HFHS group were fed with high?fat diet and high?fat/ high?salt diet for 24 weeks, respectively. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at 8, 16 and 24 weeks of modeling. The minipigs were weighed and the levels of blood glucose, lipids, liver and kidney function as well as the levels of endothelin - 1 (ET - 1), renin, angiotensin II (Ang?II), aquaporin - 2 (AQP - 2), vasopressin (AVP) and vascular endothelial growth factor (VEGF) were determined at 24 weeks after modeling. Meanwhile, samples of liver and kidney tissues were taken for histopathological examination. Results Compared with the NC group, SBP and DBP were significantly increased in the HF and HFHS groups after 8 weeks of modeling and showed a continuous rising trend, and the HFHS group was higher than that in the HF group. The body weight and liver and kidney coefficients were significantly increased in the HF and HFHS groups ( P < 0. 05), and levels of plasma TC, CREA and ET - 1 were significantly increased ( P < 0. 05, P < 0. 01). In addition, the level of BUN was significantly decreased ( P < 0. 05) and the levels of renin, Ang?II, AQP - 2 and AVP in the HFHS group were significantly increased ( P < 0. 05, P <0. 01). Oil red “O” staining showed lipid deposition in the liver and kidney tissues, and thickening of renal arterial wall and other pathological changes in the HF and HFHS groups. Conclusions A Bama minipig model of hypertension is successfully established by high fat and high salt diet for 8 weeks. Its pathogenesis may be related to the effect of alteration in renal function and activation of RAS system and AVP?AQP -2.

Abstract:Objective To compare and analyze the auxiliary preventive and therapeutic lipid?lowering effects of Antarctic krill oil on high?fat high?cholesterol diet?induced hyperlipidemia rat models. Methods Forty?eight 5 - 6?week old SPF male Sprague?Dawley rats were divided into four groups: the blank normal group, hyperlipidemia model group, krill oil prevention group and krill oil treatment group. The rat model of hyperlipidemia was established by high?fat high cholesterol diet feeding. The krill oil prevention group was continuously administered krill oil for 14 days before and 12 days during the establishment of hyperlipidemia models. Meanwhile,the krill oil treatment group received krill oil for 12 days only during the hyperlipidemia modeling period. Serum total cholesterol (TC), triglyceride (TG), high?density lipoprotein cholesterol (HDL?C), and low?density lipoprotein cholesterol (LDL?C) in the rats were measured and pathological examination of liver tissues was performed to assess and compare the preventive and therapeutic effects of krill oil on hyperlipidemia and hypercholesterolemia in the rats. Results The preventive administration of krill oil significantly reduced serum TC and LDL?C ( P < 0. 05), paralleled by the milder fatty degeneration of liver tissues, while no significant changes of serum TG and HDL?C ( P > 0. 05). After therapeutic administration of Antarctic krill oil, there was no significant difference in serum concentration of TC, TG, HDL?C and LDL?C ( P > 0. 05) compared with the model group, and no significant auxiliary lipid?lowering effect was observed on the hyperlipidemia rats. Conclusions There is a significant auxiliary lipid?lowering effect and reducing serum total cholesterol after preventive administration of Antarctic krill oil.

Abstract:Drosophila melanogaster is an ideal model organism for diverse topics in biomedical research with various advantages. However, the limitation of genetic tools and fly strains always hampers further studies of related topics. To promote our research, we developed and optimized the CRISPR/ Cas9 genome editing system, developed CRISPR/ dCas9 based transcriptional activation system and the next generation of transgenic RNAi technique in Drosophila. Equipped with these techniques, we can simply, efficiently and specifically regulate the genes of interest. Meanwhile, taking advantage of these novel genetic techniques, we built the library of mutant flies, transgenic transcriptional activation flies and transgenic RNAi flies. These genetic tools together with corresponding fly resources make Tsinghua Fly Center (THFC) to be one of the most important centers of Drosophila techniques and resources around the world. Importantly, both these techniques and the fly strains are widely used in the entire Drosophila research field, and have broad impact on the research efforts in understanding development and diseases.

Abstract:Mugilogobius chulae is a laboratory marine fish resource with Chinese characteristics. In this paper, we outlined the research on the laboratory marine fish resource of yellowstripe goby (Mugilogobius chulae) in biological characteristics, closed colony, inbred strain and method of quality control. Also the development of application of Mugilogobius chulae in ocean environment monitoring and aquatic ecotoxicology was reviewed. Three key aspects of application are emphasized in this view, including quality control standards for Mugilogobius chulae, the establishment of inbred strain and the further research on the functional genomics.

Abstract:Objective To analyze and evaluate the genetic quality of closed populations and inbred population of tiger barb,Puntius tetrazona. Method The microsatellite sequences with abundant polymorphism in tiger barb were screened,and two multiple PCR reaction systems were established. Then four populations were analyzed by capillary electrophoresis to identify the genotype and evaluate the genetic diversity. Result The average number of alleles in the wild group,WT closed group,BT closed group,and inbred group were 6. 5833,3. 1667,3. 0833,and 3. 1818. The average polymorphic information contents were 0. 5969,0. 3748,0. 4159 and 0. 4241,respectively. The analysis of population genetic quality showed that the result of genetic differentiation between the four groups were consistent with the process of the inbred population bred from the wild and closed group gradually. Conclusion These microsatellite markers can be used to analyze the genetic quality of different populations of tiger barb,providing a method ological basis for their genetic quality controland monitoring.

Abstract:The Mongolian gerbil is a potential laboratory animal model in diabetes research. However, the frequency of diabetes in common gerbil population is too low to meet the requirement for scientific research. During the process of inbreeding Mongolian gerbils, we found that a sub?line of inbred gerbils is with a higher incidence of blood glucose. After selectively inbred by sister?brother mating for 20 generations, a spontaneous diabetic model of inbred gerbil was established with an incidence of about 60%. The model also displayed typical characteristics of high fasting serum glucose, glucose intolerance, insulin resistance, multiple?tissue injury, and dysfunction of several diabetes?related genes. We further studied the pathogenetic mechanism of diabetes by this model and found that the non?obesity diabetes and obesity diabetes gerbils are totally different in the distribution and adipocyte size. These data indicate that our diabetic inbred gerbil is an ideal model of type 2 diabetes. It could be a new material and provide the new inspirations for the relevant diabetes researches such as diabetic pathogenesis mechanism, the function of adipose tissue in diabetes, and screening of sensitive drugs for treating diabetes.

Abstract:Mongolian gerbil has cerebral vascular variation. It is a good laboratory animal model in cerebral ischemia research. However, the low successful rate affects the stability of research result and does not meet the animal welfare requirements. Our group proved that the cerebral vascular variation is a genetic trait. Next, an ischemia?prone gerbil group was established by the through selecting and breeding. Our group bred a cerebral ischemia inbred gerbil with 76. 62% of animals missing circle of Willis and 88. 89% of animals with cerebral ischemia by selectively inbreed by sister?brother mating. The method of genetic monitor for inbred Mongolian gerbil were established based on biochemical loci and microsatellite DNA. The characteristics of growth and development, blood physiology and biochemistry of the inbred cerebral ischemia Mongolian gerbil were analyzed, which provides a foundation for the application of this model. We found that VEGFA gene, and signal pathway of AKT/ PI3K and Notch are correlated with Mongolian gerbil cerebrovascular development. Moreover, four genes related to the development of cerebral blood vessels were screened by suppression subtractive hybridization ( SHH). The cerebral ischemia inbred gerbil successfully solves the problem of model low incidence, reduces animal use, improves the reliability and stability of result, and promotes the related research of its mechanism.

Abstract:Naked mole?rats ( NMR, Heterocephalus glaber) are a unique species of rodents exhibiting high longevity, tumor resistance, hypoxia tolerance and pain insensitivity. These features make NMRs widely used mammalian models for biomedical research in aging, cancer, neurobiology and other fields. Their laboratory animalization and application are very important. Thus, our research team carried out a systematic study on the establishment of laboratory animalization and standardization of NMRs. Through the study of reproduction, genetics, microbiology and nutrition of NMRs, the difficulties of low reproductive rate, unclear genetic background and unidentified pathogenic microorganisms have been overcome. The population of the ordinary closed NMRs was successfully established, and the present population has been propagated to the sixth generation. At the same time, the biological characteristics of the population have been systematically studied, such as hypoxia tolerance, tumor resistance and longevity, which will provide new strategies for the prevention and treatment for related diseases.

Abstract:Patient?derived xenograft (PDX) models have high consistency with their primary tumors in terms of genetics, pathology, and biological characteristics. Being perfect in clinical response to drugs, this model shows a good prospect in tumor individualized treatment. It can be used to screen tumor target drug and effectively guide clinical medication. In this review, we focused on the evaluation strategy of PDX models based on chemotherapeutics screening, summarized the standards and quality control requirements of PDX models. We proposed four different ways to evaluate the traceability of models, including histological detection, sequencing analysis, tumor specific marker determination and short tandem repeat (STR) testing. Furthermore, chemotherapeutics effect can be evaluated by measuring drug toxicity, changes of tumor volume and establishment of TGD mathematical model. All these method applied in the PDX models provide perfect strategy for guiding tumor individualized treatment.

Abstract:Monoclonal antibodies (mAbs) have become one of the fastest?growing areas in the bio?pharmaceutical industry because of their unique advantages such as high specificity, high potency, and low drug resistance, and they have been successfully used in the treatment of various cancers, autoimmune diseases and other diseases. From the initial development of murine monoclonal antibodies to the current whole human monoclonal antibodies, new preparation techniques, such as single cell sorting and sequencing techniques, have been emerging. Meanwhile, it will help to further improve its stability and affinity by changing the glycosylation level of whole human monoclonal antibody and optimizing the affinity maturation technology of monoclonal antibodies. At present, the efficacy and safety of whole human monoclonal antibodies are still concerned by the industry, and they also face many challenges, such as how to balance them while reducing their immunogenicity, and further improve their affinity, are still promising new technologies or strategies.

Abstract:Iodoacetomide is the alkylation reagent of cysteine and histidine in proteomics, it can inhibit protease vigor and even disappear without protein degeneration, induce cell hypoxia, mucosal injury, anxiety and depression, can basically simulate digestive system diseases such as chronic gastritis, functional dyspepsia, ulcerative colitis pathophysiological mechanism. So it is widely used in the establishment and research of the animal models of chronic gastritis, functional dyspepsia and ulcerative colitis. In this paper, the mechanism and modeling method of the animal models of digestive system diseases are summarized as follows.