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357条结果
  • 机译 牙龈卟啉单胞菌在肠上皮结肠炎和体内平衡中的意义
    摘要:Monitoring of colitic mice. ( ) Body weight loss and lethality of mice were monitored for 12 days. The body weight of each mouse at day 0 was calculated as 100%. Numbers in parentheses mean the percentage of dead mice. In ‘DSS + PBS’ group, 2 mice at day 11 and 1 mouse at day 12 died. In ‘DSS + LPS’ and ‘DSS +  LPS’ group, 1 mouse at day12 died, respectively. ( ) Disease activity index indicating colitis severity was scored at day 12. 6 mice per group were used. In ( ), -value significance was calculated by comparing other groups against (+) group (marked as +). **
  • 机译 TW-37,一种BH3模拟物在人类口腔癌中的抗肿瘤作用
    摘要:Effect of TW-37 on the viability in human oral cancer cell lines. MC-3 and HSC-3 cell lines were treated with DMSO or 5 μM of TW-37 for 48 h. Cell viability (%) was assessed by trypan blue exclusion assay. The data shown in the graph represent the mean ± SD of triplicate experiments. *,  b Cytotoxic effect of TW-37 was determined by Live/dead assay kit. Live cells (green fluorescence) and dead cells (red fluorescence) were observed under a light microscope (magnification, × 200)
  • 机译 咖啡对高果糖饮食喂养的雄性白化Wistar大鼠体重,血糖,尿酸和脂质分布水平的影响
    摘要:The mean consumption of chow and liquid of the rats. The values are expressed as mean. Sample size (n) is 5 for each group. Liquid - refers to fructose solution for all groups, except for group I where it refers to plain tap water. Group I – Normal control group; Group II-Fructose control group; Group (III- VI) –Treatment groups (received 71, 142, 213 and 284 mg/kg BW/day of coffee) respectively
  • 机译 抑制STAT3信号传导诱导细胞凋亡并抑制肺癌的生长:好与坏
    摘要:Suppression of STAT3 target-gene expressions by STX-0119 in lung cancer cells. Effect of STX-0119 on Tyr705 phosphorylation of STAT3 in A549 cells. Cells were treated with indicated doses of STX-0119 for 48 h. Subcellular localization of STAT3 in STX-0119-treated A549 cells. Protein expressions of c-Myc, cyclin D1, and survivin in A549 cells after STX-0119 treatment for 48 h
  • 机译 长期口服西番莲提取物对小鼠的代谢和行为参数无异常影响,但可诱发睡眠
    摘要:GABA activation and sleep-related hormone levels by repeated oral PI extract administration. Hippocampal and hypothalamic calretinin expressions were analyzed by Western blotting. Significant increases in expression were observed in the PI-treated group, shown by the relative expression of the proteins at the hippocampus and hypothalamus in the control (Veh) and experimental groups (PI 500). Changes in body weight, and changes in sleeping-related hormones in animals after repeated PI extract administration. There was no change in body weight between the two groups. Serum levels of melatonin and serotonin were increased in the PI group. Serum serotonin tended to increase in the PI-treated group, but was not statistically significant, and melatonin showed a significant increase. The error bar represent mean ± standard error (SE). ( ,
  • 机译 四种氨基酸作为抗血清作用的血清生物标志物,在用芦笋提取物处理的卵白蛋白诱导的哮喘小鼠模型中
    摘要:Number of immune cells and level of OVA-specific IgE in BALF. Experimental scheme for OVA-induced asthma model and BAW treatment. After the collection of BALF from the lungs, total cells were separated by centrifugation, and stained with May-Giemsa solution. Total cells, eosinophils and macrophages were measured within a 1 mm area under a light microscope at 400× magnification. The concentration of OVA-specific IgE was quantified in BALF by an enzyme-linked immunosorbent assay (ELISA). The minimum detectable concentration of this kit is 20.7 pg/mL. The data shown represent the means ± SD of duplicates. *,  P
  • 机译 肝巨噬细胞在非酒精性脂肪肝和非酒精性脂肪性肝炎中的作用
    摘要:Nonalcoholic steatohepatitis (NASH) is becoming common chronic liver disease because of the increasing global prevalence of obesity and consequently Nonalcoholic fatty liver disease (NAFLD). However, the mechanism for progression of NAFLD to NASH and then cirrhosis is not completely understood, yet. The triggering of these hepatic diseases is thought from hepatocyte injury caused by over-accumulated lipid toxicity. Injured hepatocytes release damage-associated molecular patterns (DAMPs), which can stimulate the Kupffer cells (KCs), liver-resident macrophages, to release pro-inflammatory cytokines and chemokines, and recruit monocyte-derived macrophages (MDMs). The increased activation of KCs and recruitment of MDMs accelerate the progression of NAFLD to NASH and cirrhosis. Therefore, characterization for activation of hepatic macrophages, both KCs and MDMs, is a baseline to figure out the progression of hepatic diseases. The purpose of this review is to discuss the current understanding of mechanisms of NAFLD and NASH, mainly focusing on characterization and function of hepatic macrophages and suggests the regulators of hepatic macrophages as the therapeutic target in hepatic diseases.
  • 机译 FXR和TGR5之间的串扰控制胰高血糖素样肽1的分泌,以维持血糖稳态
    摘要:Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance. As consistent, numerous studies have reported alteration of bile acid signaling pathways in type II diabetes patients. Interestingly, bile acids have shown to activate TGR5 in intestinal L cells and enhance secretion of glucagon-like peptide 1 (GLP-1) to potentiate insulin secretion in response to glucose. Moreover, FXR has been shown to crosstalk with TGR5 to control GLP-1 secretion. Altogether, bile acid receptors, FXR and TGR5 are potent therapeutic targets for the treatment of metabolic diseases, including type II diabetes.
  • 机译 小鼠Cre-LoxP系统:确定靶基因的组织特异性作用的一般原则
    摘要:Genetically engineered mouse models are commonly preferred for studying the human disease due to genetic and pathophysiological similarities between mice and humans. In particular, Cre-loxP system is widely used as an integral experimental tool for generating the conditional. This system has enabled researchers to investigate genes of interest in a tissue/cell (spatial control) and/or time (temporal control) specific manner. A various tissue-specific Cre-driver mouse lines have been generated to date, and new Cre lines are still being developed. This review provides a brief overview of Cre-loxP system and a few commonly used promoters for expression of tissue-specific Cre recombinase. Also, we finally introduce some available links to the Web sites that provides detailed information about Cre mouse lines including their characterization.
  • 机译 临床前研究中的乳腺癌小鼠模型
    摘要:Breast cancer remains the second leading cause of cancer death among woman, worldwide, despite advances in identifying novel targeted therapies and the development of treating strategies. Classification of clinical subtypes (ER+, PR+, HER2+, and TNBC (Triple-negative)) increases the complexity of breast cancers, which thus necessitates further investigation. Mouse models used in breast cancer research provide an essential approach to examine the mechanisms and genetic pathway in cancer progression and metastasis and to develop and evaluate clinical therapeutics. In this review, we summarize tumor transplantation models and genetically engineered mouse models (GEMMs) of breast cancer and their applications in the field of human breast cancer research and anti-cancer drug development. These models may help to improve the knowledge of underlying mechanisms and genetic pathways, as well as creating approaches for modeling clinical tumor subtypes, and developing innovative cancer therapy.
  • 机译 CRISPR / Cas9介导的敲除Rag-2导致FVB小鼠系统性淋巴减少症和淋巴器官发育不良
    摘要:Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. RAG-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of RAG-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of RAG-2, we recently established a new RAG-2 knockout FVB mouse line (RAG-2−/−) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. RAG-2−/− mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in RAG-2−/− mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in RAG-2−/− mice. These findings indicate that our RAG-2−/− mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.
  • 机译 2型糖尿病动物模型海马髓鞘碱性蛋白的变化
    摘要:In this study, we observed chronological changes in the immunoreactivity and expression level of myelin basic protein (MBP), one of the most abundant proteins in the central nervous system, in the hippocampus of Zucker diabetic fatty (ZDF) rats and their control littermates (Zucker lean control; ZLC). In the ZLC group, body weight steadily increased with age; the body weight of the ZDF group, however, peaked at 30 weeks of age, and subsequently decreased. Based on the changes of body weight, animals were divided into the following six groups: early (12-week), middle (30-week), and chronic (52-week) diabetic groups and their controls. MBP immunoreactivity was found in the alveus, strata pyramidale, and lacunosum-moleculare of the CA1 region, strata pyramidale and radiatum of the CA3 region, and subgranular zone, polymorphic layer, and molecular layer of the dentate gyrus. MBP immunoreactivity was lowest in the hippocampus of 12-week-old rats in the ZLC group, and highest in 12-week-old rats in the ZDF group. Diabetes increased MBP levels in the 12-week-old group, while MBP immunoreactivity decreased in the 30-week-old group. In the 52-week-old ZLC and ZDF groups, MBP immunoreactivity was detected in the hippocampus, similar to the 30-week-old ZDF group. Western blot results corroborated with immunohistochemical results. These results suggested that changes in the immunoreactivity and expression of MBP in the hippocampus might be a compensatory response to aging, while the sustained levels of MBP in diabetic animals could be attributed to a loss of compensatory responses in oligodendrocytes.
  • 机译 生长中的猪根据其转录因子7-like 2基因多态性而发展出链脲佐菌素诱导的不同类型的糖尿病
    摘要:The different polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene promote variances in diabetes susceptibility in humans. We investigated whether these genotypes also promote differences in diabetic susceptibility in commercial pigs. Growing pigs (Landrace, both sex, 50–60 kg) with the C/C (n=4) and T/T (n=5) TCF7L2 genotypes were identified and intravenously injected with streptozotocin (STZ, 40 mg/kg) twice in weekly intervals, then a high-energy diet was offered. Oral glucose tolerance tests, blood analyses and the homeostasis model assessment-insulin resistance (HOMA-IR) index calculations were performed. The animals were sacrificed at the end of 12 weeks of treatment to reveal the pancreas histomorphometry. The results showed that all of the treated pigs grew normally despite exhibiting hyperglycemia at two weeks after the induction. The glycemic level of the fasting or postprandial pigs gradually returned to normal. The fasting insulin concentration was significantly decreased for the T/T carriers but not for the C/C carriers, and the resulting HOMA-IR index was significantly increased for the C/C genotype, indicating that the models of insulin dependence and resistance were respectively developed by T/T and C/C carriers. The histopathological results illustrated a significant reduction in the pancreas mass and insulin active sites, which suggested increased damage. The results obtained here could not be compared with previous studies because the TCF7L2 background has not been reported. Growing pigs may be an excellent model for diabetic in children if the animals are genetically pre-selected.
  • 机译 高血糖加剧大脑中动脉闭塞模型中α-突触核蛋白表达的下降
    摘要:Hyperglycemia is one of the major risk factors for stroke. Hyperglycemia can lead to a more extensive infarct volume, aggravate neuronal damage after cerebral ischemia. α-Synuclein is especially abundant in neuronal tissue, where it underlies the etiopathology of several neurodegenerative diseases. This study investigated whether hyperglycemic conditions regulate the expression of α-synuclein in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury. Male Sprague-Dawley rats were treated with streptozotocin (40 mg/kg) via intraperitoneal injection to induce hyperglycemic conditions. MCAO were performed four weeks after streptozotocin injection to induce focal cerebral ischemia, and cerebral cortex tissues were obtained 24 hours after MCAO. We confirmed that MCAO induced neurological functional deficits and cerebral infarction, and these changes were more extensive in diabetic animals compared to non-diabetic animals. Moreover, we identified a decrease in α-synuclein after MCAO injury. Diabetic animals showed a more serious decrease in α-synuclein than non-diabetic animals. Western blot and reverse-transcription PCR analyses confirmed more extensive decreases in α-synuclein expression in MCAO-injured animals with diabetic condition than these of non-diabetic animals. It is accepted that α-synuclein modulates neuronal cell death and exerts a neuroprotective effect. Thus, the results of this study suggest that hyperglycemic conditions cause more serious brain damage in ischemic brain injuries by decreasing α-synuclein expression.
  • 机译 重复的束缚压力促进小鼠海马神经元纤毛发生和增殖
    摘要:Stress severely disturbs physiological and mental homeostasis which includes adult neurogenesis in hippocampus. Neurogenesis in hippocampus is a key feature to adapt to environmental changes and highly regulated by multiple cellular signaling pathways. The primary cilium is a cellular organelle, which acts as a signaling center during development and neurogenesis in adult mice. However, it is not clear how the primary cilia are involved in the process of restraint (RST) stress response. Using a mouse model, we examined the role of primary cilia in repeated and acute RST stress response. Interestingly, RST stress increased the number of ciliated cells in the adult hippocampal dentate gyrus (DG). In our RST model, cell proliferation in the DG also increased in a time-dependent manner. Moreover, the analysis of ciliated cells in the hippocampal DG with cell type markers indicated that cells that were ciliated in response to acute RST stress are neurons. Taken together, these findings suggest that RST stress response is closely associated with an increase in the number of ciliated neurons and leads to an increase in cell proliferation.
  • 机译 用雌性狗的血清诱导成熟小鼠和大鼠超排卵。
    摘要:The following experiments were designed to examine the effect of serum of spayed dogs on superovulation response in mice and rats. In Experiment 1, female mice at diestrus (n=30) were divided into three equal groups and superovulated with either administration of 5 IU pregnant mare serum gonadotropin (PMSG) or recombinant follicle stimulating hormone (rFSH) (reducing dose from 2.5 to 0.5 IU) and 5 IU human chorionic gonadotropin (hCG) administered 48h later. Serum of spayed dogs was administered intraperitoneally at a reduced dose from 0.1 to 0.025 mL in a 48 h period. In Experiment 2, female rats (n=30) at diestrus stage were divided into three equal groups. Superovulation was induced using either 30 IU PMSG, or a dose reduced from 5 to 1 IU rFSH and 25 IU hCG administered 48h later. Serum of spayed dogs was administered in a reduced dose from 0.6 to 0.1 mL in a 48 hour period. Female mice and rats were mated 24 h following hCG administration. On day 14 after mating, animals were euthanized and ovarian sections were fixed for histopathological evaluation and corpus luteum (CL) counting. No significant difference observed in mean (±SEM) number of CLs between the PMSG group and the mice that received serum of spayed dog (10.4±1.3 vs 9.2±1.0). Mean (±SEM) number of CLs tended to be lower in rats that received serum of spayed dog than those of rats which received either PMSG or rFSH (15.1±1.9 vs 23.6±3.1 and 23.1±2.9, P=0.06, respectively). In conclusion, serum of spayed dogs is able to induce a superovulatory response in mice and rats.
  • 机译 副干酪乳杆菌HP7对幽门螺杆菌的体外和体内抑制
    摘要:The efficacy of standard therapeutic strategies for Helicobacter pylori (H. pylori) infection is decreasing over time due to the emergence of drug-resistant strains. As an alternative, the present study investigated the capacity of Lactobacilllus paracasei (L. paracasei) HP7, isolated from kimchi, to inhibit H. pylori growth. The effects of L. paracasei HP7 on H. pylori adhesion and H. pylori-induced inflammation were examined in AGS human gastric adenocarcinoma epithelial cells and a mouse model of H. pylori SS1 infection. L. paracasei HP7 reduced H. pylori adhesion to AGS cells and suppressed the inflammatory response in infected cells by downregulating interleukin-8. H. pylori colonization in the stomach of C57BL/6 mice was demonstrated by rapid urease test, and results showed significant decrease in mice post-treated with L. paracasei HP7. Additionally, L. paracasei HP7 decreased gastric inflammation and epithelial lesions in the stomach of H. pylori-infected mice. These results demonstrate that L. paracasei HP7 treatment can inhibit H. pylori growth and is thus a promising treatment for patients with gastric symptoms such as gastritis that are caused by H. pylori infection.
  • 机译 洛哌丁胺致SD大鼠便秘中加洛宁丰富提取物中富含单宁的肠胃通便过程中胃肠激素的调节
    摘要:Regulation of gastrointestinal hormones have been reported in animal models for constipation undergoing laxative therapy when administered herbal products. We undertook to investigate whether the laxative activity of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) affects the regulation of gastrointestinal hormones, by examining the concentration of four hormones and the activation of their receptors in the loperamide (Lop)-induced constipation model. Stool parameters, including number, weight and water content, were significantly recovered in the Lop+GEGR treated group, relative to the Lop+vehicle treated group; however, food intake and water consumption were maintained at a constant level. Also, a similar recovery was detected for thickness of mucosa, muscle and flat luminal surface in the Lop+GEGR treated group. Furthermore, concentration of the four gastrointestinal hormones evaluated, namely, cholecystokinin (CCK), gastrin (GAS), somatostatin (SS) and motilin (MTL), were lower in the Lop+vehicle treated group than the No treated group, but were remarkably enhanced in the Lop+GEGR treated group. Moreover, the downstream signaling pathway of MTL and SS receptors were recovered after GEGR administration. Results of the present study therefore indicate that the laxative effects of GEGR treatment may be tightly related with the regulation of gastrointestinal hormones in the Lop-induced constipation model.
  • 机译 不同来源的1型糖尿病C57BL / 6N小鼠代谢组学变化的比较
    摘要:Animal models have been used to elucidate the pathophysiology of varying diseases and to provide insight into potential targets for therapeutic intervention. Although alternatives to animal testing have been proposed to help overcome potential drawbacks related to animal experiments and avoid ethical issues, their use remains vital for the testing of new drug candidates and to identify the most effective strategies for therapeutic intervention. Particularly, the study of metabolic diseases requires the use of animal models to monitor whole-body physiology. In line with this, the National Institute of Food and Drug Safety Evaluation (NIFDS) in Korea has established their own animal strains to help evaluate both efficacy and safety during new drug development. The objective of this study was to characterize the response of C57BL/6NKorl mice from the NIFDS compared with that of other mice originating from the USA and Japan in a chemical-induced diabetic condition. Multiple low-dose treatments with streptozotocin were used to generate a type-1 diabetic animal model which is closely linked to the known clinical pathology of this disease. There were no significantly different responses observed between the varying streptozotocin-induced type-1 diabetic models tested in this study. When comparing control and diabetic mice, increases in liver weight and disturbances in serum amino acids levels of diabetic mice were most remarkable. Although the relationship between type-1 diabetes and BCAA has not been elucidated in this study, the results, which reveal a characteristic increase in diabetic mice of all origins are considered worthy of further study.

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