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Dietary emulsifiers impact mouse health 膳食乳化剂对小鼠健康的影响
IF 5.9 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-08-01 DOI: 10.1038/s41684-024-01420-4
Alexandra Le Bras
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引用次数: 0
Hypoxic ischemia impairs mice social calls 缺氧缺血会损害小鼠的社交呼叫能力
IF 5.9 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-08-01 DOI: 10.1038/s41684-024-01422-2
Jorge Ferreira
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引用次数: 0
Triple-negative breast cancer fly 三阴性乳腺癌苍蝇。
IF 5.9 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-08-01 DOI: 10.1038/s41684-024-01416-0
Jorge Ferreira
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引用次数: 0
Refined tamoxifen administration in mice by encouraging voluntary consumption of palatable formulations 通过鼓励小鼠自愿食用适口制剂来改进他莫昔芬的给药方法
IF 5.9 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-07-30 DOI: 10.1038/s41684-024-01409-z
Dominique Vanhecke, Viola Bugada, Regula Steiner, Bojan Polić, Thorsten Buch
Drug administration in preclinical rodent models is essential for research and the development of novel therapies. Compassionate administration methods have been developed, but these are mostly incompatible with water-insoluble drugs such as tamoxifen or do not allow for precise timing or dosing of the drugs. For more than two decades, tamoxifen has been administered by oral gavage or injection to CreERT2–loxP gene-modified mouse models to spatiotemporally control gene expression, with the numbers of such inducible models steadily increasing in recent years. Animal-friendly procedures for accurately administering tamoxifen or other water-insoluble drugs would, therefore, have an important impact on animal welfare. On the basis of a previously published micropipette feeding protocol, we developed palatable formulations to encourage voluntary consumption of tamoxifen. We evaluated the acceptance of the new formulations by mice during training and treatment and assessed the efficacy of tamoxifen-mediated induction of CreERT2–loxP-dependent reporter genes. Both sweetened milk and syrup-based formulations encouraged mice to consume tamoxifen voluntarily, but only sweetened milk formulations were statistically noninferior to oral gavage or intraperitoneal injections in inducing CreERT2-mediated gene expression. Serum concentrations of tamoxifen metabolites, quantified using an in-house-developed cell assay, confirmed the lower efficacy of syrup- as compared to sweetened milk-based formulations. We found dosing with a micropipette to be more accurate than oral gavage or injection, with the added advantage that the method requires little training for the experimenter. The new palatable solutions encourage voluntary consumption of tamoxifen without loss of efficacy compared to oral gavage or injections and thus represent a refined administration method. Pairing palatable formulations with micropipette dosing for administration of water-insoluble drugs such as tamoxifen in mice promotes voluntary consumption without loss of efficacy compared to more invasive administration methods.
在临床前啮齿动物模型中给药对于研究和开发新型疗法至关重要。目前已经开发出了一些体贴的给药方法,但这些方法大多与他莫昔芬等水不溶性药物不兼容,或者无法精确掌握给药时间或剂量。二十多年来,人们通过给 CreERT2-loxP 基因修饰小鼠模型口服或注射他莫昔芬来控制基因表达的时空,近年来这种可诱导模型的数量稳步增加。因此,准确施用他莫昔芬或其他水不溶性药物的动物友好型程序将对动物福利产生重要影响。在之前公布的微量移液管喂药方案的基础上,我们开发了适口的制剂,以鼓励动物自愿服用他莫昔芬。我们评估了小鼠在训练和治疗过程中对新配方的接受程度,并评估了他莫昔芬介导的 CreERT2-loxP 依赖性报告基因的诱导效果。甜牛奶和糖浆制剂都能鼓励小鼠自愿服用他莫昔芬,但在诱导CreERT2-介导的基因表达方面,只有甜牛奶制剂在统计学上不优于口服灌胃或腹腔注射。使用内部开发的细胞测定法对血清中他莫昔芬代谢物的浓度进行量化,结果证实糖浆制剂的疗效低于甜牛奶制剂。我们发现用微量移液管给药比口服或注射更准确,而且这种方法对实验者的培训要求不高。与口服给药或注射给药相比,新的适口溶液可鼓励患者自愿服用他莫昔芬而不会降低药效,因此是一种经过改进的给药方法。
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引用次数: 0
Standardizing zebrafish laboratory husbandry to ensure replicability and reproducibility of data in neurobehavioral research 实现斑马鱼实验室饲养标准化,确保神经行为研究数据的可复制性和可重复性
IF 5.9 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-07-26 DOI: 10.1038/s41684-024-01411-5
Murilo S. de Abreu, Matthew O. Parker, Allan V. Kalueff
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引用次数: 0
In vivo monitoring of active subretinal fibrosis in mice using collagen hybridizing peptides 利用胶原杂交肽对小鼠视网膜下活动性纤维化进行体内监测
IF 5.9 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-07-26 DOI: 10.1038/s41684-024-01408-0
Markus Linder, Lucas Bennink, Richard H. Foxton, Mike Kirkness, Peter D. Westenskow
Subretinal fibrosis is associated with worse visual outcomes in patients with neovascular age-related macular degeneration. As there is a lack of optimal biomarkers and no method that directly detects collagen in the back of the eye, novel tools that monitor fibrosis-related changes in neovascular age-related macular degeneration are needed. Here, using two mouse models (the laser-induced choroidal neovascularization model, and the JR5558 mouse presenting with spontaneous subretinal neovascularization with fibrosis), we imaged active fibrotic lesions using fluorescently labeled collagen hybridizing peptides (CHPs), short peptides that bind to single α-chain collagen structures during collagen remodeling. JR5558 retinal pigment epithelium/choroid flat mounts showed CHP co-staining with fibrosis and epithelial mesenchymal transition-related markers; additionally, CHP histopathology staining correlated with in vivo CHP imaging. After laser-induced choroidal neovascularization, in vivo CHP binding correlated with laser intensity, histopathology CHP and fibronectin staining. Laser-induced choroidal neovascularization showed decreased CHP intensity over time in healing/regressing versus active scars in vivo, whereas increased CHP binding correlated with elevated fibrosis in JR5558 mouse eyes with age. In bispecific angiopoietin 2/vascular endothelial growth factor antibody-treated JR5558 mice, CHPs detected significantly decreased collagen remodeling versus immunoglobulin G control. These results demonstrate the first use of CHPs to directly image remodeling collagen in the eye and as a potential clinical optical biomarker of active subretinal fibrosis associated with ocular neovascularization. This study reports the use of fluorescently labeled collagen hybridizing peptides to directly image collagen remodeling and monitor fibrosis in two mouse models of ocular neovascularization.
视网膜下纤维化与新生血管性老年黄斑变性患者视力下降有关。由于缺乏最佳生物标志物,也没有直接检测眼底胶原蛋白的方法,因此需要新型工具来监测新生血管性老年黄斑变性中与纤维化相关的变化。在这里,我们利用两种小鼠模型(激光诱导的脉络膜新生血管模型和自发性视网膜下新生血管伴纤维化的 JR5558 小鼠),使用荧光标记的胶原杂交肽(CHPs)对活跃的纤维化病变进行成像,CHPs 是在胶原重塑过程中与单个 α 链胶原结构结合的短肽。JR5558 视网膜色素上皮/脉络膜平片显示 CHP 与纤维化和上皮间质转化相关标记物共同染色;此外,CHP 组织病理学染色与体内 CHP 成像相关。激光诱导脉络膜新生血管后,体内 CHP 结合与激光强度、组织病理学 CHP 和纤维连接蛋白染色相关。激光诱导的脉络膜新生血管在体内愈合/退行性疤痕与活动性疤痕中的 CHP 强度随时间推移而降低,而 CHP 结合力的增加与 JR5558 小鼠眼球纤维化程度随年龄增长而升高有关。在双特异性血管生成素 2/血管内皮生长因子抗体处理的 JR5558 小鼠中,CHPs 检测到的胶原重塑与免疫球蛋白 G 对照组相比明显减少。这些结果表明,CHPs 首次用于直接成像眼球中重塑的胶原蛋白,并可作为一种潜在的临床光学生物标记,用于检测与眼球新生血管相关的活动性视网膜下纤维化。
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引用次数: 0
Optimal conditions, experimentation and drug testing 最佳条件、实验和药物测试
IF 5.9 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-07-15 DOI: 10.1038/s41684-024-01412-4
Hippokratis Kiaris
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引用次数: 0
JNK1 role in zebrafish anxiety JNK1 在斑马鱼焦虑症中的作用
IF 5.9 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-07-02 DOI: 10.1038/s41684-024-01403-5
Jorge Ferreira
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引用次数: 0
Tracking peroxisomes 跟踪过氧物酶体
IF 5.9 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-07-02 DOI: 10.1038/s41684-024-01398-z
Alexandra Le Bras
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引用次数: 0
zAvatars pass the test zAvatars通过测试
IF 5.9 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-07-02 DOI: 10.1038/s41684-024-01397-0
Alexandra Le Bras
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引用次数: 0
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