Animal Models and Experimental Medicine

Abstract The mouse genome has a high degree of homology with the human genome, and its physiological, biochemical, and developmental regulation mechanisms are similar to those of humans; therefore, mice are widely used as experimental animals. However, it is undeniable that interspecies differences between humans and mice can lead to experimental errors. The differences in the immune system have become an important factor limiting current immunological research. The application of immunodeficient mice provides a possible solution to these problems. By transplanting human immune cells or tissues, such as peripheral blood mononuclear cells or hematopoietic stem cells, into immunodeficient mice, a human immune system can be reconstituted in the mouse body, and the engrafted immune cells can elicit human‐specific immune responses. Researchers have been actively exploring the development and differentiation conditions of host recipient animals and grafts in order to achieve better immune reconstitution. Through genetic engineering methods, immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts. From initially only being able to reconstruct single T lymphocyte lineages, it is now possible to reconstruct lymphoid and myeloid cells, providing important research tools for immunology‐related studies. In this review, we compare the differences in immune systems of humans and mice, describe the development history of human immune reconstitution from the perspectives of immunodeficient mice and grafts, and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution, aiming to provide important references for immunological related researches.

Yixiao Bin

Jing Ren

Haowei Zhang

Tianjiao Zhang

Peijuan Liu

Zhiqian Xin

Haijiao Yang

Zhuan Feng

Zhinan Chen

Hai Zhang

Against all odds: The road to success in the development of human immune reconstitution mice

逆境求生：人类免疫重建小鼠的研发之路

Abstract Background How AMP activated protein kinase (AMPK) signaling regulates mitochondrial functions and mitophagy in human trophoblast cells remains unclear. This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA‐seq. Methods We compared ATP production in protein kinase AMP‐activated catalytic subunit alpha 1/2 ( PRKAA1/2) knockdown (AKD) and control BeWo cells using the Seahorse real‐time ATP rate test, then analyzed gene expression profiling by RNA‐seq. Differentially expressed genes (DEG) were examined by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then protein–protein interactions (PPI) among mitochondria related genes were further analyzed using Metascape and Ingenuity Pathway Analysis (IPA) software. Results Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells (CT), with a greater reduction of mitochondrial ATP production. A total of 1092 DEGs were identified, with 405 upregulated and 687 downregulated. GO analysis identified 60 genes associated with the term ‘mitochondrion’ in the cellular component domain. PPI analysis identified three clusters of mitochondria related genes, including aldo‐keto reductase family 1 member B10 and B15 (AKR1B10, AKR1B15), alanyl‐tRNA synthetase 1 (AARS1), mitochondrial ribosomal protein S6 (MRPS6), mitochondrial calcium uniporter dominant negative subunit beta (MCUB) and dihydrolipoamide branched chain transacylase E2 (DBT). Conclusions In summary, this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells, and among them, three clusters of genes may potentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.

Bin Wu

Albert Gao

Bin He

Yun Chen

Xiangfeng Kong

Fayuan Wen

Haijun Gao

<scp>RNA</scp>‐seq analysis of mitochondria‐related genes regulated by <scp>AMPK</scp> in the human trophoblast cell line <scp>BeWo</scp>

<scp>RNA</scp>测序分析人类滋养层细胞系<scp>BeWo</scp>中受<scp>AMPK</scp>调控的线粒体相关基因

Abstract Hypertension is an important global public health issue because of its high morbidity as well as the increased risk of other diseases. Recent studies have indicated that the development of hypertension is related to the dysbiosis of the gut microbiota in both animals and humans. In this review, we outline the interaction between gut microbiota and hypertension, including gut microbial changes in hypertension, the effect of microbial dysbiosis on blood pressure (BP), indicators of gut microbial dysbiosis in hypertension, and the microbial genera that affect BP at the taxonomic level. For example, increases in Lactobacillus , Roseburia , Coprococcus , Akkermansia , and Bifidobacterium are associated with reduced BP, while increases in Streptococcus , Blautia , and Prevotella are associated with elevated BP. Furthermore, we describe the potential mechanisms involved in the regulation between gut microbiota and hypertension. Finally, we summarize the commonly used treatments of hypertension that are based on gut microbes, including fecal microbiota transfer, probiotics and prebiotics, antibiotics, and dietary supplements. This review aims to find novel potential genera for improving hypertension and give a direction for future studies on gut microbiota in hypertension.

Dong Yan

Ye Sun

Xiaoyue Zhou

Wenhao Si

Jieyu Liu

Min Li

Minna Wu

Anim Models and Exp Med

Regulatory effect of gut microbes on blood pressure

肠道微生物对血压的调节作用

Abstract Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed single‐stranded transcript. They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets. Using the most powerful RNA sequencing and bioinformatics techniques, a large number of circRNAs have been identified and further functional studies have been performed. It is known that circRNAs act as potential biomarkers, sponges for microRNAs (miRNAs) and RNA‐binding proteins (RBPs), and regulators of mRNA transcription. They also participate in the translation of peptides or proteins. Many types of circRNAs are dysregulated in plasma or lung tissues, and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs), leading to pulmonary vascular remodeling in pulmonary hypertension (PH). One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge. However, other potential mechanisms of action of circRNAs are still being actively explored in PH. This paper presents a systematic review of the biogenesis, biological characterization, relevant underlying functions, and future perspectives for studies of circRNAs in the pathogenesis of PH.

Qian Wang

Yuanyuan Sun

Qinhua Zhao

Wenhui Wu

Lan Wang

Yuqing Miao

Ping Yuan

Circular RNAs in pulmonary hypertension: Emerging biological concepts and potential mechanism

肺动脉高压中的环状RNA：新兴的生物学概念与潜在机制

Zinc-finger E-box-binding homeobox-1 (ZEB1) is predominantly found in type-H vessels. However, the roles of ZEB1 and type-H vessels in steroid-induced osteonecrosis of the femoral head (SONFH) are unclear.

Guangyang Zhang

Yuanqing Cai

Jialin Liang

Zhaopu Jing

Wang Wei

Leifeng Lv

Xiaoqian Dang

Qichun Song

The decrease in zinc‐finger E‐box‐binding homeobox‐1 could accelerate steroid‐induced osteonecrosis of the femoral head by repressing type‐H vessel formation via <i>Wnt/β‐catenin</i> pathway

锌指E盒结合同源框-1的减少可能通过<i>Wnt/β-catenin</i>通路抑制H型血管形成，从而加速类固醇诱导的股骨头坏死

Abstract Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fibrosis, which appears to be a leading cause of cardiovascular diseases. Cardiac fibrosis is characterized by the accumulation of extracellular matrix proteins, mainly collagen in the cardiac interstitium. Many experimental studies have demonstrated that fibrotic injury in the heart is reversible; therefore, it is vital to understand different molecular mechanisms that are involved in the initiation, progression, and resolution of cardiac fibrosis to enable the development of antifibrotic agents. Of the many experimental models, one of the recent models that has gained renewed interest is isoproterenol (ISP)–induced cardiac fibrosis. ISP is a synthetic catecholamine, sympathomimetic, and nonselective β‐adrenergic receptor agonist. The overstimulated and sustained activation of β‐adrenergic receptors has been reported to induce biochemical and physiological alterations and ultimately result in cardiac remodeling. ISP has been used for decades to induce acute myocardial infarction. However, the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis; this practice has increased in recent years. Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy. The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is considered the initiating mechanism of myocardial fibrosis. ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals. In recent years, numerous phytochemicals and synthetic molecules have been evaluated in ISP‐induced cardiac fibrosis. The present review exclusively provides a comprehensive summary of the pathological biochemical, histological, and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy. It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as synthetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.

Lujain Bader Eddin

Mohamed Fizur Nagoor Meeran

Niraj Kumar Jha

Samer N. Goyal

Shreesh Ojha

Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals

异丙肾上腺素诱导心肌纤维化的机制及其作为评估植物化学物质和药物疗效潜力的实验模型的应用

Intestinal organoids are promising tools in the context of animal experiment reduction but a thorough characterization of the impact of the origin of intestinal stem cells (ISC) on organoid phenotype is needed to routinely use this cellular model. Our objective was to evaluate the effect of ISC donor age on the growth, morphology and cellular composition of intestinal organoids derived from pig.

Camille Duchesne

Gwénaëlle Randuineau

Laurence Le Normand

Véronique Romé

Samia Laraqui

Alexis Pierre Arnaud

Gaëlle Boudry

Initial pig developmental stage influences intestinal organoid growth but not cellular composition

初始猪发育阶段影响肠类器官生长但不影响细胞组成

Abstract Background Allergic rhinitis (AR) is a kind of immune disease mediated by IgE. We are intrigued by the potential role of DEK proto‐oncogene (DEK) in inflammation‐related diseases. We investigated the effects and mechanisms of DEK in treating AR, aiming to identify potential new treatment targets for AR. Methods The AR mouse model was induced by house dust mite (HDM) (1 mg/mL). HNEpCs stimulated by HDM (1 mg/mL) were pretreated for 24 h with or without DEK lentivirus. The effect of DEK knockout or knockdown on AR was evaluated in vitro and in vivo using western blotting, ELISA, flow cytometry, real‐time quantitative PCR, immunohistochemistry, HE staining, PAS staining, Diff staining, and immunofluorescence. Results After DEK knockdown, the inflammatory response of AR mice was reduced. In addition, DEK deletion mitigated nasal tissue damage and mitochondrial division. Our further studies showed that DEK deletion or inhibition led to the down‐regulation of RhoA activity and decreased phosphorylation of Ezrin and Drp1 proteins, and inhibited mitochondrial division. Overall, DEK deficiency mitigated AR by down‐regulating RhoA/Ezrin/Drp1 pathway activity. Conclusion DEK alleviates AR through RhoA/Ezrin/Drp1 signaling pathway, which provides a new perspective for developing improved therapies and understanding the pathogenesis of AR.

Longzhu Dai

Yongde Jin

Jingmei Chai

Jianing Yang

Jiangang Wang

Mu Chen

Liangchang Li

Chongyang Wang

Guanghai Yan

Deficiency of <scp>DEK</scp> proto‐oncogene alleviates allergic rhinitis by inhibiting <scp>RhoA</scp>/Ezrin‐mediated mitochondrial fission

<scp>DEK</scp>原癌基因缺陷通过抑制<scp>RhoA</scp>/Ezrin介导的线粒体分裂减轻过敏性鼻炎

Abstract Background Native cartilage has low capacity for regeneration because it has very few progenitor cells. Human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSCs) and human umbilical cord‐derived MSCs (hUC‐MSCs) have been employed as promising sources of stem cells for cartilage injury repair. Reproduction of hyaline cartilage from MSCs remains a challenging endeavor. The paracrine factors secreted by chondrocytes possess the capability to induce chondrogenesis from MSCs. Methods The conditioned medium derived from chondrocytes was utilized to induce chondrogenic differentiation of hUCB‐MSCs and hUC‐MSCs. The expression levels of collagen type I alpha 1 chain ( Col1a1 ), collagen type II alpha 1 chain ( Col2a1 ), and SRY‐box transcription factor 9 ( SOX9 ) were assessed through quantitative real‐time polymerase chain reaction (qRT‐PCR), Western blot (WB), and immunofluorescence (IF) assays. To elucidate the mechanism of differentiation, the concentration of transforming growth factor‐β1 (TGF‐β1) in the conditioned medium of chondrocytes was quantified using enzyme‐linked immunosorbent assay (ELISA). Meanwhile, the viability of cells was assessed using Cell Counting Kit‐8 (CCK‐8) assays. Results The expression levels of Col2a1 and SOX9 were found to be higher in induced hUC‐MSCs compared to those in induced hUCB‐MSCs. The conditioned medium of chondrocytes contained TGF‐β1. The CCK‐8 assays revealed that the proliferation rate of hUC‐MSCs was significantly higher compared to that of hUCB‐MSCs. Conclusions The chondrogenic potential and proliferation capacity of hUC‐MSCs surpass those of hUCB‐MSCs, thereby establishing hUC‐MSCs as a superior source of seed cells for cartilage tissue engineering.

Xingfu Li

Zhenhan Deng

Wei Lu

Chondrogenic commitment of human umbilical cord blood and umbilical cord‐derived mesenchymal stem cells induced by the supernatant of chondrocytes: A comparison study

人脐带血和脐带源间充质干细胞的软骨形成能力诱导：软骨细胞上清液的比较研究

Abbreviation	Anim Models and Exp Med
Journal Impact	3.67
Quartiles(Global)	MEDICINE, RESEARCH & EXPERIMENTAL(Q2)

ISSN	2096-5451, 2576-2095
h-index	25

Publication Information	Publisher: John Wiley and Sons Inc，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2018，Proportion of original research papers: ，Self Citation Rate:， Gold OA Rate:

Animal Models and Experimental Medicine

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