Animal Models and Experimental Medicine最新文献_第2页

Hypoxia adaptation in the cornea: Current animal models and underlying mechanisms. 角膜的缺氧适应：当前的动物模型和潜在机制。

Animal Models and Experimental Medicine Pub Date : 2021-11-28 eCollection Date: 2021-12-01 DOI: 10.1002/ame2.12192

Kunpeng Pang, Anton Lennikov, Menglu Yang

{"title":"Hypoxia adaptation in the cornea: Current animal models and underlying mechanisms.","authors":"Kunpeng Pang, Anton Lennikov, Menglu Yang","doi":"10.1002/ame2.12192","DOIUrl":"10.1002/ame2.12192","url":null,"abstract":"The cornea is an avascular, transparent tissue that is essential for visual function. Any disturbance to the corneal transparency will result in a severe vision loss. Due to the avascular nature, the cornea acquires most of the oxygen supply directly or indirectly from the atmosphere. Corneal tissue hypoxia has been noticed to influence the structure and function of the cornea for decades. The etiology of hypoxia of the cornea is distinct from the rest of the body, mainly due to the separation of cornea from the atmosphere, such as prolonged contact lens wearing or closed eyes. Corneal hypoxia can also be found in corneal inflammation and injury when a higher oxygen requirement exceeds the oxygen supply. Systemic hypoxic state during lung diseases or high altitude also leads to corneal hypoxia when a second oxygen consumption route from aqueous humor gets blocked. Hypoxia affects the cornea in multiple aspects, including disturbance of the epithelium barrier function, corneal edema due to endothelial dysfunction and metabolism changes in the stroma, and thinning of corneal stroma. Cornea has also evolved mechanisms to adapt to the hypoxic state initiated by the activation of hypoxia inducible factor (HIF). The aim of this review is to introduce the pathology of cornea under hypoxia and the mechanism of hypoxia adaptation, to discuss the current animal models used in this field, and future research directions.","PeriodicalId":7840,"journal":{"name":"Animal Models and Experimental Medicine","volume":"4 4","pages":"300-310"},"PeriodicalIF":0.0,"publicationDate":"2021-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c8/70/AME2-4-300.PMC8690994.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9699527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Folic acid-induced animal model of kidney disease. 叶酸诱导的肾病动物模型。

Animal Models and Experimental Medicine Pub Date : 2021-11-24 eCollection Date: 2021-12-01 DOI: 10.1002/ame2.12194

Liang-Jun Yan

{"title":"Folic acid-induced animal model of kidney disease.","authors":"Liang-Jun Yan","doi":"10.1002/ame2.12194","DOIUrl":"10.1002/ame2.12194","url":null,"abstract":"The kidneys are a vital organ that is vulnerable to both acute kidney injury (AKI) and chronic kidney disease (CKD) which can be caused by numerous risk factors such as ischemia, sepsis, drug toxicity and drug overdose, exposure to heavy metals, and diabetes. In spite of the advances in our understanding of the pathogenesis of AKI and CKD as well AKI transition to CKD, there is still no available therapeutics that can be used to combat kidney disease effectively, highlighting an urgent need to further study the pathological mechanisms underlying AKI, CKD, and AKI progression to CKD. In this regard, animal models of kidney disease are indispensable. This article reviews a widely used animal model of kidney disease, which is induced by folic acid (FA). While a low dose of FA is nutritionally beneficial, a high dose of FA is very toxic to the kidneys. Following a brief description of the procedure for disease induction by FA, major mechanisms of FA-induced kidney injury are then reviewed, including oxidative stress, mitochondrial abnormalities such as impaired bioenergetics and mitophagy, ferroptosis, pyroptosis, and increased expression of fibroblast growth factor 23 (FGF23). Finally, application of this FA-induced kidney disease model as a platform for testing the efficacy of a variety of therapeutic approaches is also discussed. Given that this animal model is simple to create and is reproducible, it should remain useful for both studying the pathological mechanisms of kidney disease and identifying therapeutic targets to fight kidney disease.","PeriodicalId":7840,"journal":{"name":"Animal Models and Experimental Medicine","volume":" ","pages":"329-342"},"PeriodicalIF":0.0,"publicationDate":"2021-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/74/04/AME2-4-329.PMC8690981.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39780137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Implication of proliferation gene biomarkers in pulmonary hypertension. 肺高压增生基因生物标志物的意义。

Animal Models and Experimental Medicine Pub Date : 2021-11-22 eCollection Date: 2021-12-01 DOI: 10.1002/ame2.12191

Yi Yan, Rong Jiang, Ping Yuan, Li Wen, Xiao-Bin Pang, Zhi-Cheng Jing, Yang-Yang He, Zhi-Yan Han

{"title":"Implication of proliferation gene biomarkers in pulmonary hypertension.","authors":"Yi Yan, Rong Jiang, Ping Yuan, Li Wen, Xiao-Bin Pang, Zhi-Cheng Jing, Yang-Yang He, Zhi-Yan Han","doi":"10.1002/ame2.12191","DOIUrl":"10.1002/ame2.12191","url":null,"abstract":"Objective/background: Proliferation is a widely recognized trigger for pulmonary hypertension (PH), a life-threatening, progressive disorder of pulmonary blood vessels. This study was aimed to identify some proliferation associated genes/targets for better comprehension of PH pathogenesis.Methods: Human pulmonary arterial smooth muscle cells (hPASMCs) were cultured in the presence or absence of human recombinant platelet derived growth factor (rhPDGF)-BB. Cells were collected for metabolomics or transcriptomics study. Gene profiling of lungs of PH rats after hypoxia exposure or of PH patients were retrieved from GEO database.Results: 90 metabolites (VIP score >1, fold change >2 or <0.5 and p < .05) and 2701 unique metabolism associated genes (MAGs) were identified in rhPDGF-BB treated hPASMCs compared to control cells. In addition, 1151 differentially expressed genes (313 upregulated and 838 downregulated) were identified in rhPDGF-BB treated hPASMCs compared to control cells (fold change >2 or <0.5 and p < .05). 152 differentially expressed MAGs were then determined, out of which 9 hub genes (IL6, CXCL8, CCL2, CXCR4, CCND1, PLAUR, PLAU, HBEGF and F3) were defined as core proliferation associated hub genes in protein proten interaction analysis. In addition, the hub gene-based LASSO model can predict the occurrence of PH (AUC = 0.88). The expression of CXCR4, as one of the hub genes, was positively correlated to immune cell infiltrates.Conclusion: Our findings revealed some key proliferation associated genes in PH, which provide the crucial information concerning complex metabolic reprogramming and inflammatory modulation in response to proliferation signals and might offer therapeutic gains for PH.","PeriodicalId":7840,"journal":{"name":"Animal Models and Experimental Medicine","volume":" ","pages":"369-380"},"PeriodicalIF":0.0,"publicationDate":"2021-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8690983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39780139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

In-depth examination of hyperproliferative healing in two breeds of Sus scrofa domesticus commonly used for research. 深入研究两个常用于研究的家猪品种的过度增殖性愈合。

Animal Models and Experimental Medicine Pub Date : 2021-11-22 eCollection Date: 2021-12-01 DOI: 10.1002/ame2.12188

Colton H Funkhouser, Liam D Kirkpatrick, Robert D Smith, Lauren T Moffatt, Jeffrey W Shupp, Bonnie C Carney

{"title":"In-depth examination of hyperproliferative healing in two breeds of Sus scrofa domesticus commonly used for research.","authors":"Colton H Funkhouser, Liam D Kirkpatrick, Robert D Smith, Lauren T Moffatt, Jeffrey W Shupp, Bonnie C Carney","doi":"10.1002/ame2.12188","DOIUrl":"10.1002/ame2.12188","url":null,"abstract":"Background: Wound healing can result in various outcomes, including hypertrophic scar (HTS). Pigs serve as models to study wound healing as their skin shares physiologic similarity with humans. Yorkshire (Yk) and Duroc (Dc) pigs have been used to mimic normal and abnormal wound healing, respectively. The reason behind this differential healing phenotype was explored here.Methods: Excisional wounds were made on Dc and Yk pigs and were sampled and imaged for 98 days. PCR arrays were used to determine differential gene expression. Vancouver Scar Scale (VSS) scores were given. Re-epithelialization was analyzed. H&E, Mason's trichrome, and immunostains were used to determine cellularity, collagen content, and blood vessel density, respectively.Results: Yk wounds heal to a \"port wine\" HTS, resembling scarring in Fitzpatrick skin types (FST) I-III. Dc wounds heal to a dyspigmented, non-pliable HTS, resembling scarring in FST IV-VI. Gene expression during wound healing was differentially regulated versus uninjured skin in 40/80 genes, 15 of which differed between breeds. Yk scars had a higher VSS score at all time points. Yk and Dc wounds had equivalent re-epithelialization, collagen disorganization, and blood vessel density.Conclusions: Our findings demonstrate that Dc and Yk pigs can produce HTS. Wound creation and healing were consistent among breeds, and differences in gene expression were not sufficient to explain differences in resulting scar phenotype. Both pig breeds should be used in animal models to investigate novel therapeutics to provide insight into a treatment's effectiveness on various skin types.","PeriodicalId":7840,"journal":{"name":"Animal Models and Experimental Medicine","volume":" ","pages":"406-417"},"PeriodicalIF":0.0,"publicationDate":"2021-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/eb/6c/AME2-4-406.PMC8690996.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39782525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Closed cranial window rodent model for investigating hemodynamic response to elevated intracranial pressure. 用于研究颅内压升高时血液动力学反应的闭颅窗啮齿动物模型。

Animal Models and Experimental Medicine Pub Date : 2021-11-19 eCollection Date: 2021-12-01 DOI: 10.1002/ame2.12187

Matt T Oberdier, James F Antaki, Alexander Kharlamov, Stephen C Jones

{"title":"Closed cranial window rodent model for investigating hemodynamic response to elevated intracranial pressure.","authors":"Matt T Oberdier, James F Antaki, Alexander Kharlamov, Stephen C Jones","doi":"10.1002/ame2.12187","DOIUrl":"10.1002/ame2.12187","url":null,"abstract":"Background: Elevated intracranial pressure (ICP) occurs in several physiological and pathological conditions, yet long-term sequellae are not common, which implies that blood flow is preserved above ischemic thresholds.Methods: This pilot study sought to confirm this hypothesis using a closed cranial window model in a rat in which ICP was elevated to 120 mmHg for 12 min, and superficial cortical perfusion was measured by laser Doppler flowmetry and laser speckle flowmetry.Results: Following a transient increase, cortical blood flow decreased to between 25% and 75% of baseline. These levels correspond to disrupted metabolism and decreased protein synthesis but did not exceed thresholds for electrical signaling or membrane integrity. This may partially explain how some episodes of elevated ICP remain benign.Conclusion: The closed cranial window model provides a platform for prospective study of physiologic responses to artificially elevated ICP during neurosurgery to promote hemostasis.","PeriodicalId":7840,"journal":{"name":"Animal Models and Experimental Medicine","volume":" ","pages":"391-397"},"PeriodicalIF":0.0,"publicationDate":"2021-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/af/AME2-4-391.PMC8690993.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39780141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a unilateral ureteral obstruction model in cynomolgus monkeys. 猴单侧输尿管梗阻模型的开发

Animal Models and Experimental Medicine Pub Date : 2021-11-19 eCollection Date: 2021-12-01 DOI: 10.1002/ame2.12185

Linghong Huang, Jia Ni, Tanika Duncan, Zhizhan Song, Timothy S Johnson

{"title":"Development of a unilateral ureteral obstruction model in cynomolgus monkeys.","authors":"Linghong Huang, Jia Ni, Tanika Duncan, Zhizhan Song, Timothy S Johnson","doi":"10.1002/ame2.12185","DOIUrl":"10.1002/ame2.12185","url":null,"abstract":"Background: Chronic kidney disease (CKD) has a high global prevalence and large unmet need. Central to developing new CKD therapies are in vivo models in CKD. However, next-generation antibody, protein, and gene therapies are highly specific, meaning some do not cross-react with rodent targets. This complicates preclinical development, as established in vivo rodent models cannot be utilized unless tool therapeutics are also developed. Tool compounds can be difficult to develop and, if available, typically have different epitopes, sequences, and/or altered affinity, making it unclear how efficacious the lead therapeutic may be, or what dosing regimen to investigate. To address this, we aimed to develop a nonhuman primate model of CKD.Methods: In vivo rodent unilateral ureteral obstruction (UUO) models kidney fibrosis and is commonly used due to its rapidity, consistency, and ease. We describe translation of this model to the cynomolgus monkey, specifically optimizing the model duration to allow adequate time for assessment of novel therapeutics prior to the fibrotic plateau.Results: We demonstrated that disease developed more slowly in cynomolgus monkeys than in rodents post-UUO, with advanced fibrosis developing by 6 weeks. The tubulointerstitial fibrosis in cynomolgus monkeys was more consistent with human obstructive disease than in rodents, having a more aggressive tubular basement expansion and a higher fibroblast infiltration. The fibrosis was also associated with increased transglutaminase activity, consistent with that seen in patients with CKD.Conclusion: This cynomolgus monkey UUO model can be used to test potential human-specific therapeutics in kidney fibrosis.","PeriodicalId":7840,"journal":{"name":"Animal Models and Experimental Medicine","volume":" ","pages":"359-368"},"PeriodicalIF":0.0,"publicationDate":"2021-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8690991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39780138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Establishment of an oligoasthenospermia mouse model based on TAp73 gene suppression. 基于 TAp73 基因抑制的少精子症小鼠模型的建立

Animal Models and Experimental Medicine Pub Date : 2021-11-09 eCollection Date: 2021-12-01 DOI: 10.1002/ame2.12186

Hong-Juan Liu, Meng-Yun Deng, Yan-Yan Zhu, De-Ling Wu, Xiao-Hui Tong, Li Li, Lei Wang, Fei Xu, Tong-Sheng Wang

{"title":"Establishment of an oligoasthenospermia mouse model based on TAp73 gene suppression.","authors":"Hong-Juan Liu, Meng-Yun Deng, Yan-Yan Zhu, De-Ling Wu, Xiao-Hui Tong, Li Li, Lei Wang, Fei Xu, Tong-Sheng Wang","doi":"10.1002/ame2.12186","DOIUrl":"10.1002/ame2.12186","url":null,"abstract":"Background: Oligoasthenospermia is one of the main causes of male infertility. Researchers usually use chemical drugs to directly damage germ cells to prepare oligoasthenospermia models, which disregards the adhesion and migration between spermatogenic cells and Sertoli cells. TAp73 is a critical regulator of the adhesin of germ cell; thus, we sought to explore a novel oligoasthenospermia model based on TAp73 gene suppression.Methods: Mice in the Pifithrin-α group were injected intraperitoneally with 2.5 mg/kg Pifithrin-α (TAp73 inhibitor) daily for 30 consecutive days. Reproductive hormone levels and epididymal sperm quality, as well as the network morphology of Sertoli cells were tested.Results: Sperm density, motility, and the relative protein and mRNA expression of TAp73 and Nectin 2 were obviously decreased in the Pifithrin-α group compared with the normal control group. No significant distinction was observed in the relative mRNA and protein expression of ZO-1. Furthermore, the tight junctions (TJs) and apical ectoplasmic specialization (ES) were destroyed in the Pifithrin-α group.Conclusion: The above results indicate that we successfully established a new oligoasthenospermia mouse model. This study provides a foundation for further exploration of the roles of TAp73 genes during spermatogenesis and provides new research objects for further oligospermia research and future drug discovery.","PeriodicalId":7840,"journal":{"name":"Animal Models and Experimental Medicine","volume":" ","pages":"351-358"},"PeriodicalIF":0.0,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/66/c9/AME2-4-351.PMC8690982.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39780136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The hypoxia adaptation of small mammals to plateau and underground burrow conditions. 高原和地下洞穴条件下小型哺乳动物的缺氧适应。

Animal Models and Experimental Medicine Pub Date : 2021-10-21 eCollection Date: 2021-12-01 DOI: 10.1002/ame2.12183

Mengke Li, Dan Pan, Hong Sun, Lei Zhang, Han Cheng, Tian Shao, Zhenlong Wang

{"title":"The hypoxia adaptation of small mammals to plateau and underground burrow conditions.","authors":"Mengke Li, Dan Pan, Hong Sun, Lei Zhang, Han Cheng, Tian Shao, Zhenlong Wang","doi":"10.1002/ame2.12183","DOIUrl":"10.1002/ame2.12183","url":null,"abstract":"Oxygen is one of the important substances for the survival of most life systems on the earth, and plateau and underground burrow systems are two typical hypoxic environments. Small mammals living in hypoxic environments have evolved different adaptation strategies, which include increased oxygen delivery, metabolic regulation of physiological responses and other physiological responses that change tissue oxygen utilization. Multi-omics predictions have also shown that these animals have evolved different adaptations to extreme environments. In particular, vascular endothelial growth factor (VEGF) and erythropoietin (EPO), which have specific functions in the control of O2 delivery, have evolved adaptively in small mammals in hypoxic environments. Naked mole-rats and blind mole-rats are typical hypoxic model animals as they have some resistance to cancer. This review primarily summarizes the main living environment of hypoxia tolerant small mammals, as well as the changes of phenotype, physiochemical characteristics and gene expression mode of their long-term living in hypoxia environment.","PeriodicalId":7840,"journal":{"name":"Animal Models and Experimental Medicine","volume":" ","pages":"319-328"},"PeriodicalIF":0.0,"publicationDate":"2021-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/fb/AME2-4-319.PMC8690988.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39869470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Refining murine heterotopic heart transplantation: A model to study ischemia and reperfusion injury in donation after circulatory death hearts. 改良小鼠异位心脏移植:研究循环死亡心脏捐献后缺血再灌注损伤的模型。

Animal Models and Experimental Medicine Pub Date : 2021-07-07 eCollection Date: 2021-09-01 DOI: 10.1002/ame2.12176

Mohammed Quader, Renee Cholyway, Niluka Wickramaratne, Oluwatoyin Akande, Martin Mangino, Eleonora Mezzaroma, Adolfo G Mauro, Qun Chen, Alexander Kantlis, Stefano Toldo

引用次数: 3