Abstract:Objective 　To observe the effect of miR-328-3p on the growth and apoptosis of glioma cells, and explore the role and mechanism of the miR-328-3p-Akt/ mTOR axis in inhibition of glioma cell growth by triptolide using U251 cells and a xenograft model in nude mice. Methods　miR-328-3p overexpression were induced after treatment of with triptolide in U251 cells. qRT-PCR, CCK-8, colony formation assays, flow cytometry, and Western Blot were performed to assess the role of miR-328-3p in inhibition of U251 cells by triptolide. A xenotransplanted tumor model was established with stable miR-328-3p expression to verify the role of miR-328-3p in inhibition of glioma cells by triptolide using qRT-PCR and small animal imaging in vivo. Results 　miR-328-3p expression in glioma cells and tissues was decreased, and its expression level was positively correlated to the overall survival rate of patients with primary and recurrent glioma. the Akt/ mTOR signaling pathway. Conclusions　miR-328-3p is a tumor suppressor gene in glioma. Triptolide promotes apoptosis of glioma cells, inhibits activation of the Akt/ mTOR signal pathway, and inhibits glioma cell growth through miR-328-3p.

Abstract:Objective 　To observe changes on pathological morphology and iron content in brain tissue of spontaneously hypertensive rats (SHR) with multiple risk factors (high fat, salt, and carbohydrate diets). Methods Fourteen-week-old SPF grade, 8 rats in each group, normal control group(share the same genetic background, the WKY group). SHR rats were randomly divided into four groups: control group (SHRs group), high fat diet group (HFAT-SHRs group), high salt diet group (HSAIL-SHRs group), and high glucose and fat diet group (DM-SHRs group was established by intraperitoneal injection of 1% streptozotocin. And at the same time and blood glucose content was kept above 11. 1 mmol/ L was regarded to be the diabetes model standard). WKY group and SHRs group was fed an ordinary diet, and the model groups were fed high fat, salt, or sugar diets. The treatments were carried out for 32 weeks. Changes in iron content in serum and brain tissue were measured, pathological morphology and iron content (Prussian blue staining) of brain tissue were observed under a light microscope, and the levels of inflammatory factors, and cholinergic and β-AP contents were measured by ELISA. Results 　Compared with the WKY group, brain cells in each model group showed a disordered arrangement, nuclear pyrosis, and decreased or absent Nissl bodies. Iron staining showed expansion of the iron area, especially in the DM-SHRs group. ACh and AChE contents in the SHRs group and three model groups were decreased, while IL-1β and IL-6 contents were increased (P< 0. 05, P< 0. 05), and iron content in serum and brain tissue was increased (P< 0. 05, P< 0. 05). There was no statistical significance within groups (P> 0. 05). Conclusions　High fat, salt, and sugar are factors that change the morphology of brain cells, promote iron deposition, and inhibit endogenous antioxidant activity. Iron overload may lead to cognitive impairment by hypertensive brain damage.

Abstract:Objective　To study the effect of curcumin (Cur) combined with monoamine oxidase A (MAOA) inhibitor clorgyline ( Clo) on lung cancer cell proliferation and its mechanism. Methods 　The effect of various concentrations of Cur and Clo on proliferation of the lung cancer cell line H460 was assessed by a CCK-8 assay. Western Blot was used to analyze the effect of Cur, Clo, and Cur combined with Clo on MAOA expression in H460 cells. The inhibitory effect of Cur, Clo, and Cur combined with Clo on H460 cell proliferation was further examined in a xenograft model in nude mice. Immunohistochemistry was used to assess the effect of Clo on Ki67 protein expression in tumor tissue of the xenograft model. TUNEL staining was used to detect apoptosis in various treatment groups of xenografted tumor tissue. Results 　Cur, Clo, and Cur combined with Clo inhibited H460 cell proliferation in a dose-dependent manner and H460 cell growth in the xenograft model (P< 0. 01), decreased the Ki67 expression, and increased apoptosis. Importantly, the combined treatment group showed more significant inhibitory effects (P< 0. 01). Conclusions　Cur combined with Clo inhibits the proliferation of H460 lung cancer cells, which may be related to reducing expression of the cell proliferation protein Ki67 and increasing apoptosis.

Abstract:Objective　To explore the intrinsic biomaterial basis of the TCM syndrome of type 2 diabetes in adult SD rats through differential metabolic markers and metabolic pathways using urine untargeted metabolomics. Methods　SD rats were randomly divided into normal and T2DM groups with deficiency of both qi and yin. The T2DM group with deficiency of both qi and yin was established by feeding a high fat and sugar diet combined with intraperitoneal injection of a small dose of streptozotocin (35 mg/ kg) and intragastric administration of Qingpi Fuzi powder granules. Untargeted metabonomic analysis of urine was performed by liquid chromatography-tandem mass spectrometry. Potential biomarkers and pathway enrichment were identified by principal component analysis, partial least squares discriminant analysis, KEGG database, HMDB database, LIPIDMaps database, and MS/ MS tandem ion fragment information. Results 　Metabolite changes related to diabetes were found to involve nine carbohydrate, twelve lipid, nine amino acid, and two energy metabolic pathways. Conclusions　There are carbohydrate, lipid, amino acid, and bioenergy metabolism disorders in the biological model of qi yin deficiency in diabetes. Metabonomics are helpful to reveal the material basis of TCM syndromes.

Abstract:Objective 　To investigate whether postmenopausal lipid metabolism disorder is involved in the development of depressive symptoms. Methods　Twenty-four LDLR^{-/ -} and sixteen WT C57BL/6J female mice were divided into five groups (n= 8): WT + normal diet group(WT), WT + high-fat diet group(WT-H), ovariectomized LDLR^{-/ -} +normal diet group(LDLR^{-/ -} ), ovariectomized LDLR^{-/ -} + high-fat diet group(LDLR^{-/ -} -H), and ovariectomized LDLR^{-/ -} +high-fat diet + simvastatin group(XF). Mice were fed continuously for 3 months. The postmenopausal lipid metabolism disorder model was established in LDLR^{-/ -} female mice after bilateral ovariectomy combined with a high-fat diet. Body weight, total cholesterol (TC), ERα, and ERβ levels in the hippocampus, depressive behavior, and 5-HT levels in the brain were determined. The correlation between the brain TC level and depression-related indexes was analyzed. Results (1)The LDLR^{-/ -} -H group successfully replicated the characteristics of postmenopausal lipid metabolism disorder, which showed a significant increase in body weight, a notable increase in the brain TC level, and a significant decrease in expression of ERβ in the hippocampus. (2) Horizontal and vertical locomotor activities of the LDLR^{-/ -} -H group were significantly decreased, the immobilized time of TST was significantly increased, and the brain 5-HT level was significantly decreased. (3) The brain TC level of the XF group was significantly decreased, depressive behavior was significantly improved, and the 5-HT level was significantly increased. (4) Correlation analysis showed that the TC level in the brain was significantly correlated to the 5-HT level and depression-like behaviors. Conclusions Postmenopausal lipid metabolism disorder induces depressive symptoms, and depression symptoms can be significantly improved by regulating lipid metabolism disorder.

Abstract:Objective　To compare changes in microbial diversity in the intestines of male and female rats with obesity and depression. Methods　An obesity and depression model was established by feeding rats a high fat diet and the cums classic depression making method. SD rats were randomly divided into control group (Group C), obese group (Group F), the depression group (Group Y), the obesity and depression group (Group FY). Five months were required for modeling. Depression-like behavior was evaluated by the sugared water preference test, open field test, and forced swimming test. The serum estrogen level and blood lipids were measured. Fecal samples were also collected. Highthroughput sequencing of 16S rDNA was performed and the result were analyzed by bioinformation analysis software. Changes in intestinal flora diversity of rats in each group were compared. Results　Obesity depression model rats were successfully established by a high-fat diet and cums method in the same countries. The estrogen level of obesity and obesity depression female rats was significantly increased, while there no significant difference was observed in the estrogen level between male groups. There was a significant difference in diversity of intestinal flora in Group FY. The B/ F value was lower than that of in obesity and depression groups, and the B/ F value of obesity and depression in male rats was only approximately half that of female rats. At the genus level, changes in Blautia and the other eight flora in the Group FY and Group F of male and female rats were consistent, but changes in a small number of flora in Bacteroides and other genera in females and males were inconsistent. In the male and female obesity and depression model, there were differences in the composition of Gram-positive and -negative bacteria among the intestinal flora. The composition of G⁺ was Firmicutes and actinomycetes, but the proportions were different. G^- males mainly had Firmicutes, Bacteroides, and desulfitobacteria, whereas females mainly had Bacteroides, verruciformis, and desulfitobacteria with different composition ratios. Conclusions Significant changes in the composition and structure of intestinal flora in male and female obese and depressed rats may be related to estrogen.

Abstract:Objective　To establish a rat model of hypertensive disorder complicating pregnancy (HDCP) and observe the effect of HDCP on thyroid morphology and function in preterm rats at various gestational ages. Methods　Tenweek-old SD pregnant rats were randomly divided into control and HDCP groups. Rats in the HDCP group were subcutaneously injected with L-nitroarginine methyl ester (L-NAME; 250 mg/ (kg·d)). Rats in the control group were subcutaneously injected with the same volume of normal saline. Preterm rats were obtained by cesarean section at 18 ~ 21 days of gestation. Body weight and length of the preterm rats were recorded. The liver and thyroid gland were isolated, thyroid hormone levels were measured in a liver homogenate, and thyroid morphology and ultrastructure were observed. Results　Compared with the control group, blood pressure and urinary proteins of rats were significantly increased in the HDCP group (P< 0. 05). The weight and length of premature rats in the HDCP group were significantly lower than those in the control group (P< 0. 01). Compared with the control group, the TSH level of premature rats was significantly increased in the HDCP group on days 19, 20, and 21 (P< 0. 01), and there was no significant difference in T3 and T4 levels. HE staining showed that the follicular cavity appeared at 18 days of gestation in the control group, whereas the follicular cavity appeared at 19 days of gestation in the HDCP group, and the number of follicular lumens was decreased significantly. Transmission electron microscopy showed that the rough endoplasmic reticulum in the HDCP group was significantly swollen and degranulated, which were accompanied by retention. Conclusions 　An HDCP rat model was established successfully. Compared with the control group, premature rats in the HDCP group had intrauterine growth restriction, hypothyroidism, and delayed thyroid histological development, which may be caused by endoplasmic reticulum dysfunction.

Abstract:Objective　To investigate the mechanism of resveratrol protecting exercise-induced liver injury in rats. Methods　Thirty-two 7-week-old male SPF SD rats were randomly divided into a control group (Group C), resveratrol RM) with eight rats in each group. Group C and Group R did not undergo any exercise. Group M and Group RM underwent 4 weeks of high-intensity treadmill training (10° slope; velocity started from 10 m/ min, which was increased by 5 m/ min every 5 min and would not increase until 35 m/ min, and then the rats were trained to exhaustion). One hour before training, Group R and Group RM were intragastrically injected with 150 mg/ (kg·bw) resveratrol in 5 mL/ (kg·bw). Group C and Group M were injected with an equal volume of solvent at the same time point. Rats were sacrificed at 24 hours after the end of the last training session, and blood and liver were collected. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity were detected by an automatic biochemical analyzer. Hepatic histomorphology was observed by hematoxylin-eosin (HE) staining. Hepatic nuclear factor-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), apoptosis-related protein B-cell lymphoma-2 (Bcl-2), and bcl-2-associated X protein (Bax) protein expression was detected by immunohistochemistry. Hepatic apoptosis was detected by TdT-mediated dUTP nick-end labeling. Hepatic superoxide dismutase (SOD) and malondialdehyde (MDA) activity was detected by colorimetry. Results　Compared with Group M, serum ALT, AST activity, the hepatic MDA level, and hepatic apoptosis were significantly decreased in Group RM (P< 0. 05 or P< 0. 01), hepatic Nrf2 and HO-1 protein expression, SOD activity, the and Bcl-2/ Bax ratio were increased significantly (P< 0. 05 or P< 0. 01), and liver histopathological changes had effectively improved. Conclusions Four weeks of resveratrol treatment alleviates exercise-induced liver injury in rats, and the mechanism of its protective effect might be related to activation of the Nrf2 signaling pathway, which relieved oxidative stress in the liver, thereby antagonizing excessive occurrence of apoptosis induced by oxidative stress.

Abstract:Objective　To investigate the effect of μ opioid receptor (μRs) blockers on the exercise ability and behavior of learned helplessness mice. Methods　Mice were randomly divided into a learning-regression group, conjugate group, and control group. Before the mice learned to avoid the electric shock stimulus experiment, the μRs blocker β-FNA or normal saline (Sal) was used to predict the treatment. Mouse movement distances in the open field experiment were compared by T test to determine the effect of the intervention on the mobility of mice. The helplessness behavior of mice after blocking μRs was investigated by shuttling box, forced swimming, elevated cross maze, and open field experiments. Results　There was no significant difference in exercise distance between the two groups compared with the control group. There was no difference in the time of electric shock between the two treatment groups during the three-day learning period. There was a significant difference between the two treatment groups for the total number of times touching the nasal contact devices on the second and third days (P< 0. 001). Conclusions　The μRs blocker had no effect on the exercise ability of learned helplessness mice, and μRs played an important role in the formation of aversive behavior in mice.

Abstract:Objective　To systematically sort and integrate literature on drug screening and evaluation data based on cell and animal models, extract important fields, and construct an animal model drug screening database. Methods We formulated animal model drug screening data collection forms and collection specifications, retrieved animal model drug screening literature in accordance with the retrieval strategy, extracted keywords and data, pretreatment, integration, and analysis, visually displayed the drug screening experimental data. Results　The animal model drug screening database was mainly based on cell and animal model drug evaluation experiments, covering basic information, experimental grouping, experimental method, animal phenotypes, and drug evaluation information, and visualizing the phenotypic data. A total of 691 animal model drug screening experimental datasets were obtained, which realized the integration and sharing of animal model drug screening experimental data. Conclusions　We established an animal model drug screening database, mainly based on cell and animal data to provide data support for drug screening and promote data-driven biomedical innovation research and novel drug discovery.

Abstract:Atherosclerosis (AS) is the pathological basis of common cardiovascular diseases such as heart disease and stroke, and its causative factors are complex and diverse. With the advancement of mature genetic modifications, mouse models have provided an important basis to study the pathogenesis of AS and validating drug efficacy. In this article, we review the pathological characteristics of traditional transgenic and novel mouse models on the basis of lipoprotein metabolism and histopathological changes, as well as their potential and limitations for preclinical application in drug development, so that future studies on mechanisms related to this disease can be targeted to select models.

Abstract:Humans can mimic the behavior of others and produce the same emotional experiences, a phenomenon known as emotional contagion. Rodents (mainly rats and mice) are commonly used as experimental animals in medical research. These animals can also suffer from emotional contagion associated with negative emotions such as fear, anxiety, and depression. To further understand the process of the transmission of different emotions among animals, we review the definition and process of emotional contagion, as well as the influencing factors and the main types and their physiological mechanisms, to provide a reference for subsequent studies.

Abstract:Animal behavioral experiments are basic experimental method used to evaluate the learning and memory of animals and are widely used in physiological and pathological mechanism research and pharmacodynamic evaluation. The assessment method to evaluate the learning and memory behavior of rats can be divided into three categories by the experimental principle: punitive, spontaneous, and rewarding. On the basis of the reward principle and Skinner’ s conditional reflex principle, the reward-directed operant conditioning method provides a more comprehensive and detailed assessment method to assess advanced cognitive functions in the learning and memory of animals, which is particularly suitable to evaluate the cognitive state when performing complex operational tasks under modern high-tech conditions. This study summarizes the development process, experimental devices, experimental method, and application fields of the reward-directed operant conditioning method, providing reference for future research and the application of this method in the field of animal behavioral experiments of learning and memory in China.

Abstract:Depression is a serious mental disorder that affects a wide range and a large number of people. Pathogenic hypotheses for the condition include classical hypothalamic-pituitary-adrenocortical (HPA) axis dysfunction and monoamine and neural plasticity deficiencies. More in-depth investigations are required to fully reveal the complexities of the pathogenesis and interactions between multiple pathogenic factors. Chronic stress is the main clinical factor that induces depression; therefore, it is vital to fully reveal the complex pathological mechanisms and the changes that occur during chronic stress exposure for the rapid and effective transformation of translational findings and the efficient prevention and treatment of the disease. Existing reviews related to depression pathogenesis have mainly focused on the classical hypotheses of HPA axis dysfunction and monoamine deficiency, as well as morphological and functional abnormalities of different brain subregions, neurons, central neurotransmitters, factors, and the corresponding receptors. The present review summarizes current depression research hotspots and new findings that have surfaced in recent years, such as genetic variants and epigenetic modifications, structural and functional abnormalities of glial cells (astrocytes and microglia), mitochondrial dysfunction, and systematic abnormalities (oxidative stress, immune inflammatory response, microbial-gut-brain). This paper systematically presents the research progress made into the mechanisms underlying chronic-stress-induced depressivelike behavior in animals, to benefit further in-depth studies into the pathogenesis, and to provide novel ideas for the clinical prevention and treatment of the disease.

Abstract:Bite force is an important indicator of animal viability. Measuring canine bite force has positive implications for canine restoration, canine food, toy evaluation, police screening, and the use of dogs. Chinese research on canine bite force testing is more police personnel and dominated by product development, which rarely investigates actual measurement work. This review summarizes various method of dog bite force testing, such as the bite method, electromyography, lever model method, and finite element analysis to provide a to study dog bite force.

Abstract:The flap ischemia-reperfusion injury (FIRI) animal model provides valuable information to understand the pathogenesis and treatment of necrosis after flap transplantation. Establishing a suitable FIRI animal model is a necessary prerequisite to comprehend the pathophysiology of FIRI and test novel preventive and therapeutic method. When designing an FIRI animal model, it is important to understand the characteristics, modeling method, unique performance of each animal model, and which tissue structures or functions of the selected animal model are similar to human flaps. For over half a century, researchers have used rats to establish abdominal and dorsal island flap models, rat dorsal random flap models, and some novel FIRI models. However, so far there is no ideal model that fully simulates the complex mechanism of necrosis after human flap transplantation or its prevention and treatment method. Therefore, this review summarizes the most commonly used rat models to establish FIRI models, which may facilitate choosing suitable parts and method for modeling in accordance with the research design and the smooth conduct of experiments.