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1Redox imbalance stress in diabetes mellitus: Role of the polyol pathway显示文摘In diabetes mellitus, the polyol pathway is highly active and consumes approximately 30% glucose in the body. This pathway contains 2 reactions catalyzed by aldose reductase(AR) and sorbitol dehydrogenase, respectively. AR reduces glucose to sorbitol at the expense of NADPH, while sorbitol dehydrogenase converts sorbitol to fructose at the expense of NAD+, leading to NADH production. Consumption of NADPH, accumulation of sorbitol, and generation of fructose and NADH have all been implicated in the pathogenesis of diabetes and its complications. In this review, the roles of this pathway in NADH/NAD+redox imbalance stress and oxidative stress in diabetes are highlighted. A potential intervention using nicotinamide riboside to restore redox balance as an approach to fighting diabetes is also discussed.Liang-jun Yan 2018Animal Models and Experimental Medicine2018,1,1:22
2Age-related rhesus macaque models of COVID-19显示文摘Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.Pin Yu Feifei Qi Yanfeng Xu Fengdi Li Peipei Liu Jiayi Liu Linlin Bao Wei Deng Hong Gao Zhiguang Xiang Chong Xiao Qi Lv Shuran Gong Jiangning Liu Zhiqi Song Yajin Qu Jing Xue Qiang Wei Mingya Liu Guanpeng Wang Shunyi Wang Haisheng Yu Xing Liu Baoying Huang Wenling Wang Li Zhao Huijuan Wang Fei Ye Weimin Zhou Wei Zhen Jun Han Guizhen Wu Qi Jin Jianwei Wang Wenjie Tan Chuan Qin 2020Animal Models and Experimental Medicine2020,3,1:22
3Chinese herb feed additives improved the growth performance, meat quality, and nutrient digestibility parameters of pigs显示文摘Background:Since the use of antibiotics in animal feed has become a critical concern worldwide due to severe threats to human health and environment,we are in need of finding alternatives to antibiotics in pig breeding,maintaining the health of pigs,and getting high-quality pork.As traditional Chinese herbs(TCH)are rich natural resources in China and show great benefits to human health we propose to transfer this abundant resource into animal production industry as additives.Methods:Three groups of Chinese herbs(groups A,B,and C)were used as feed additives in the diet for pigs.In total 32 pigs were arranged in four groups(groups A,B,C,and control group,NC),fed in the same facility,eight pigs(one group)in each colony,free drinking,for 120 days.The feed:gain ratio(F/G),meat quality,total protein,and amino acid concentration of muscle were checked in the experiments.Results:After 120 days of feeding,the feed:gain ratio(F/G)of pigs in groups A,B,and C was decreased 17.56%,9.31%,and 13.86%compared with NC treatment,respectively.The diets supplemented with Chinese herbs improved meat quality,increased loin eye area(especially group A and C showed significant difference,P<.001),the total protein(increased ratio vs NC was A=4.54%,B=0.38%and C=3.53%),amino acid concentration of muscle,increased the villus height:crypt depth ratio,and induced positive effects on serum biochemical parameters and immune function(serum TC and TG concentrations were significantly lower than those in the NC group,P<.05.).Conclusions:The use of Chinese herbal feed additives can reduce the cost of pig breeding and produce high-quality pock.The combination of these effects would contribute to better absorption ability of the intestinal tract and yield a better growth performance.Zhong-ning Lin Li Ye Zhen-wu Li Xiu-sheng Huang Zheng Lu You-quan Yang Huan-wei Xing Jie-ying Bai Zhao-yang Ying 2020Animal Models and Experimental Medicine2020,3,1:17
4Long noncoding RNAs in neurodevelopment and Parkinson’s disease显示文摘Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.Ying Lyu Lin Bai Chuan Qin 2019Animal Models and Experimental Medicine2019,2,4:10
5Animal models of stroke显示文摘Stroke is a devastating disease with high morbidity and mortality.Animal models are indispensable tools that can mimic stroke processes and can be used for investigating mechanisms and developing novel therapeutic regimens.As a heterogeneous disease with complex pathophysiology,mimicking all aspects of human stroke in one animal model is impossible.Each model has unique strengths and weaknesses.Models such as transient or permanent intraluminal thread occlusion middle cerebral artery oc-clusion(MCAo)models and thromboembolic models are the most commonly used in simulating human ischemic stroke.The endovascular filament occlusion model is characterized by easy manipulation and accurately controllable reperfusion and is suitable for studying the pathogenesis of focal ischemic stroke and reperfusion in-jury.Although the reproducibility of the embolic model is poor,it is more conveni-ent for investigating thrombolysis.Rats are the most frequently used animal model for stroke.This review mainly outlines the stroke models of rats and discusses their strengths and shortcomings in detail.Yanyu Li Jingjing Zhang 2021Animal Models and Experimental Medicine2021,4,3:9
6Research progress on the relationship between intestinal microecology and intestinal bowel disease显示文摘Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are interdependent and establish a complex interaction network that restricts each other.According to the impact on the human body,there are three categories of symbiotic bacteria,opportunistic pathogens,and pathogenic bacteria.The intestinal microecology participates in digestion and absorption,and material metabolism,and inhibits the growth of pathogenic microorganisms.It also acts as the body’s natural immune barrier,regulates the innate immunity of the intestine,controls the mucosal barrier function,and also participates in the intestinal epithelial cells’physiological activities such as hyperplasia or apoptosis.When the steady-state balance of the intestinal microecology is disturbed,the existing core intestinal microbiota network changes and leads to obesity,diabetes,and many other diseases,especially irritable bowel syndrome,inflammatory bowel disease(IBD),and colorectal malignancy.Intestinal diseases,including tumors,are particularly closely related to intestinal microecology.This article systematically discusses the research progress on the relationship between IBD and intestinal microecology from the pathogenesis,treatment methods of IBD,and the changes in intestinal microbiota.Qianhui Fu Tianyuan Song Xiaoqin Ma Jian Cui 2022Animal Models and Experimental Medicine2022,5,4:9
7The intestinal microbiome and Alzheimer's disease: A review显示文摘Alzheimer's disease(AD) is an increasingly common neurodegenerative disease.Since the intestinal microbiome is closely related to nervous system diseases, alterations in the composition of intestinal microbiota could potentially contribute to the pathophysiology of AD. However, how the initial interactions with intestinal microbes alter events later in life, such as during neurodegenerative diseases, is still unclear. This review summarizes what is known about the relationship between the intestinal microbiome and AD.Zhuo Li Hua Zhu Ling Zhang Chuan Qin 2018Animal Models and Experimental Medicine2018,1,3:8
8Application of bone transgenic zebrafish in anti-osteoporosis chemical screening显示文摘Background: The zebrafish(Danio rerio) has recently been shown to be an ideal model to study bone disease including osteoporosis. The zebrafish osteoporosis model could be induced by glucocorticoid treatment with chemical staining for reflecting the level of bone mineralization. However, this methodology was unstable.Here, we developed a novel methodology to directly evaluate the bone mass and density.Methods: We generated and used the bone of transgenic zebrafish Tg(ola.sp7:nlsGFP) to evaluate the bone mass and density by measuring the areal extent and the integrated optical density(IOD) of enhanced green fluorescent protein(eGFP).This methodology was further compared with the traditional chemically stained method showing the bone mineralization. Furthermore, genes related to zebrafish osteoporosis were analyzed by quantitative reverse transcription-polymerase chain reaction(qRT-PCR).Results: Our results of new methods were consistent with those from chemically stained fish, following glucocorticoid-induction or epimedium flavonoid(FE)-rescue treatments. q RT-PCR analyses on mRNA levels revealed that glucocorticoid induces osteoporosis by downregulating the expression of osteoblast-related factors osterix,osteocalcin, and osteopontin, and upregulating the expression of osteoclast-related factor tartrate-resistant acid phosphatase. In FE-rescued fish, the expression of osteogenic factors osterix, osteocalcin, and osteopontin were increased.Conclusion: Compared to the traditional chemical staining methods, the new osteoporosis model using Tg(ola.sp7:nlsGFP) is more convenient and efficient for studying osteoporosis in vivo, and especially for high-throughput anti-osteoporosis drug screening.Hong-xin Huang Hao Lin Fen Lan Yong-fu Wu Zhen-guo Yang Jing-jing Zhang 2018Animal Models and Experimental Medicine2018,1,1:8
9Guidelines for the ethical review of laboratory animal welfare People’s Republic of China National Standard GB/T 35892-2018 [Issued 6 February 2018 Effective from 1 September 2018]显示文摘These Chinese National Guidelines(GB/T 35892-20181)were issued February 06,2018 and became effective September 01,2018.The authors recognized the urgent need for an authentic English translation to inform the international community of the compliance requirements in China.It was appreciated that the final translation must reflect the specialist understanding of those working under the Guideline whilst remaining faithful to the meaning of the original Chinese text.A three-step translation process was therefore determined.Step 1:A professional interpretation service(KL Communications,UK)was commissioned to prepare a literal translation of the Chinese text.Supportive documents were provided which explained specialist terminology.This translation was checked by two bilingual experts.Step 2:A workshop was held in Nanjing in May 2019 to which were invited experts in laboratory animal welfare and ethical use.These included international native English-speaking and Chinese-speaking delegates.The delegates worked in multilingual teams to review sections of the literal translation ahead of the workshop,and to agree an authentic interpretation during the workshop.Step 3:Following the workshop,three bilingual experts(two native Chinese speakers and one native English speaker)reviewed the entire document to ensure consistency of terminology and general accuracy.This document is thus not a“literal translation”but an“accurate interpretation”of the original text.Any challenge of work being performed under these Guidelines should rely on the Chinese text in the first place.However,this translation may be used as mitigating evidence,especially where those performing the work are non-Chinese speakers.Judy A.MacArthur Clark Deming Sun 2020Animal Models and Experimental Medicine2020,3,1:8
10To develop a novel animal model of myocardial infarction:A research imperative显示文摘Although great progress has been made in therapeutic interventions for coronary artery disease(CAD), it is still the deadliest disease in the world. Currently animals that are similar to human beings in their cardiovascular pathophysiology are being used to explore the pathogenesis and therapy of CAD. There have been a series of developments in creating CAD animal models using mice, rats,rabbits, dogs, and pigs, but unfortunately there is still no acceptable model for human CAD. The ideal CAD animal model should satisfy several conditions as follows. First of all, it should have a pathophysiological process for CAD that is similar to humans. Second, it should be useable for assessing drug efficacy. The last and most important condition is that the model can be used to duplicate clinical therapeutic skills. The limitations of current methods for making animal models have meant that these models not only do not duplicate the actual pathogenesis, but also cannot be used to simulate clinical therapy, and do not support scientific evaluation of drug efficacy. Therefore, the development of a fit-for-purpose animal model for CAD is imperative for future research. Such a development will lead to rapid progress and greater efficiency in CAD research.This paper summarizes the present situation in the field of CAD animal models,and puts forwards ideas for developing a novel animal model of myocardial infarction.Yao-ping Tang Ying Liu Yong-jie Fan Yang-yang Zhao Jiao-qun Feng Yuan Liu 2018Animal Models and Experimental Medicine2018,1,1:7
11Optimization of food deprivation and sucrose preference test in SD rat model undergoing chronic unpredictable mild stress显示文摘Background:The chronic unpredictable mild stress(CUMS)model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression.However,there are no widely recognised standards for strategies for modeling and for behavioral testing.The present study aimed to optimize the protocols for food deprivation and the sucrose preference test(SPT)for the CUMS model.Methods:We first evaluated the effects of different long periods of food deprivation on the body weight of Sprague Dawley(SD)rats by testing food deprivation for 24 hours(8:00-8:00^+),food deprivation for 12 hours during the daytime(8:00-20:00)and food deprivation for 12 hours at night(20:00-8:00^+).Next,we established a SD rat CUMS model with 15 different stimulations,and used body weight measurement,SPT,forced swim test(FST),open field test(OFT)and Morris water maze(MWM)test to verify the success of the modeling.In the SPT,consumption of sucrose and pure water within 1 and 12 hours was measured.Results:Twelve hours of food deprivation during the daytime(8:00-20:00)had no effect on body weight,while 12 hours of food deprivation at night(20:00-8:00^+)and 24 hours of food deprivation(8:00-8:00^+)significantly reduced the mean body weight of the SD rats.When SPT was used to verify the successful establishment of the CUMS rat model,sucrose consumption measured within 12 hours was less variable than that measured within 1 hour.Conclusions:Twelve hours of food deprivation in the daytime(8:00-20:00)may be considered a mild stimulus for the establishment of a CUMS rat model.Measuring sucrose consumption over 12 hours is recommended for SPT.Li-Wen He Li Zeng Na Tian Yi Li Tong He Dong-Mei Tan Qian Zhang Yi Tan 2020Animal Models and Experimental Medicine2020,3,1:7
12Animal models of acute gastric mucosal injury: Macroscopic and microscopic evaluation显示文摘Acute gastric mucosal injury is a common disorder of the gastrointestinal tract and the search for new therapeutics is ongoing. The aim of this study is to update and expand the information related to the most widely used rat models of acute gastric ulcer, the ethanol‐induced ulcer and the indomethacin‐induced ulcer. These two models are compared in terms of macroscopic and microscopic features. Experimentally, ethanol was given orally in a single dose and indomethacin was subcutaneously injected into male Wistar rats. After ulcerative challenges, the stomachs were removed and visually inspected. Anti‐ulcerative drugs were used to validate the models. Histological analysis of the stomachs determined the microscopic score. The methodology used for model evaluation applied to macroscopic and microscopic gastric lesions. With these methods it was possible to induce lesions in the gastric mucosa. Microscopic evaluation permitted assessment of the inflammatory and apoptotic impact in the mucosa not observable by macroscopic evaluation. Groups of animals were treated with two standard drugs: sulcralfate suspension or lansoprazole solution. Both drugs reduced macroscopic and microscopic lesions, particularly the hemorrhagic ones. Both models induced acute gastric mucosal injury and no single evaluation method can address all the aspects of the pathology of gastric lesions. As a complement to macroscopic evaluation, microscopy appears to be a relevant tool to selectively identify specific aspects of the development of mucosal injury, quantify the extent of lesions, and contribute to an appropriate interpretation of results. The score systems established here offer a reliable method for testing antiulcer drugs.Sandra Simoes Rui Lopes Maria Celeste Dias Campos Maria Joao Marruz Maria Eugenia Meirinhos da Cruz Luisa Corvo 2019Animal Models and Experimental Medicine2019,2,2:7
13The battle against SARS and MERS coronaviruses: Reservoirs and Animal Models显示文摘In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus(SARS-CoV) and the emerging Middle East respiratory syndrome coronavirus(MERS-CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.Shu-ran Gong Lin-lin Bao 2018Animal Models and Experimental Medicine2018,1,2:6
14Protective effect of hydroxychloroquine on rheumatoid arthritis-associated atherosclerosis显示文摘Background: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis. Methods: We created three groups of K/BxN female mice that were positive for the anti‐glucose‐6‐phosphate isomerase (GPI) antibody: control diet (CD), high fat diet (HFD), and HFD with hydroxychloroquine (HFD + HCQ). Serological tests were used to detect the serum levels of total cholesterol (TCHO), low‐density lipoprotein cholesterol (LDL‐C), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), anti‐ GPI antibody titers, and serum cytokines. Atherosclerotic plaque was determined by histological analysis, and gut microbiota were determined by 16sV4 sequencing. Results: Relative to mice given the CD, those receiving the HFD had increased serum levels of LDL‐C, TCHO, and TG, decreased serum levels of HDL‐C, increased atherosclerotic lesions in the aortic root, and altered gut microbiota. Addition of HCQ to HFD decreased the serum levels of LDL‐C, TCHO, and TG, increased serum levels of HDL‐C, and decreased the atherosclerotic lesions in the aortic root. Mice receiving HFD + HCQ also had the greatest bacterial diversity among the three experimental groups. Moreover, HCQ treatment significantly increased the abundance of Akkermansia and Parabacteroides, and decreased the abundance of Clostridium sensu stricto cluster 1, and therefore may be responsible for the reduced RA‐associated atherosclerosis and dyslipidemia. Conclusion: Our mouse model of RA indicated that HFD increased ankle width and aggravated a therosclerosis a nd d yslipidemia, a nd t hat H CQ a lleviated t he d yslipidemia and atherosclerosis, but had no effect on ankle width.Na Shi Shuangyue Zhang Gregg Silverman Mengtao Li Jun Cai Haitao Niu 2019Animal Models and Experimental Medicine2019,2,2:6
15Microarray microRNA profiling of urinary exosomes in a 5XFAD mouse model of Alzheimer’s disease显示文摘Background:Alzheimer's disease(AD)is an incurable and irreversible neurodegen-erative disease,without a clear pathogenesis.Therefore,identification of candidates before amyloid-βplaque(Aβ)deposition proceeds is of major significance for earlier intervention in AD.Methods:To explore the potential noninvasive earlier biomarkers of AD in a 5XFAD mouse model,microRNAs(miRNAs)from urinary exosomes in 1-month-old pre-Aβaccumulation 5XFAD mice models and their littermate controls were profiled by mi-croarray analysis.The differentially expressed miRNAs were further analyzed via droplet digital PCR(ddPCR).Results:Microarray analysis demonstrated that 48 differentially expressed miRNAs(18 upregulated and 30 downregulated),of which six miRNAs-miR-196b-5p,miR-339-3p,miR-34a-5p,miR-376b-3p,miR-677-5p,and miR-721-were predicted to display gene targets and important signaling pathways closely associated with AD pathogenesis and verified by ddPCR.Conclusions:Urinary exosomal miRNAs showing differences in expression prior to Aβ-plaque deposition were identified.These exosomal miRNAs represent potential noninvasive biomarkers that may be used to prevent AD in clinical applications.Zhiqi Song Yajin Qu Yanfeng Xu Ling Zhang Li Zhou Yunlin Han Wenjie Zhao Pin Yu Yu Zhang Xianglei Li Chuan Qin 2021Animal Models and Experimental Medicine2021,4,3:6
16Current state of research on non-human primate models of Alzheimer’s disease显示文摘With the increasingly serious aging of the global population, dementia has already become a severe clinical challenge on a global scale. Dementia caused by Alzheimer’s disease(AD) is the most common form of dementia observed in the elderly, but its pathogenetic mechanism has still not been fully elucidated. Furthermore, no effective treatment strategy has been developed to date, despite considerable efforts. This can be mainly attributed to the paucity of animal models of AD that are sufficiently similar to humans. Among the presently established animal models, non-human primates share the closest relationship with humans, and their neural anatomy and neurobiology share highly similar characteristics with those of humans. Thus, there is no doubt that these play an irreplaceable role in AD research. Considering this, the present literature on non-human primate models of AD was reviewed to provide a theoretical basis for future research.Hong-Wei Li Ling Zhang Chuan Qin 2019Animal Models and Experimental Medicine2019,2,4:6
17Outlining key inflammation-associated parameters during early phase of an experimental gram-negative sepsis model in rhesus macaques(Macaca mulatta)显示文摘The aim of this study was to identify inflammation-associated markers during the early phase of sepsis in rhesus macaque. Four rhesus macaques were given an intravenous dose of 1010 CFU/kg of E. coli. Blood samples were collected before, or 30 minutes, 2, 4, 6 and 8 hours after E. coli infusion. Physiological parameters, bacteremia, endotoxemia, C-reactive protein(CRP), procalcitonin(PCT), and plasma cytokines/chemokines were determined for each animal. Bacteremia was present in all animals from 30 minutes to 3 hours after E. coli infusion whereas endotoxin was detected during the full-time course. CRP and PCT levels remained at detectable levels during the whole experimental window suggesting an ongoing inflammatory process. Signature cytokines and chemokines such as TNF-α, MIP-1α, and MIP-1β peaked about 2 hours after E. coli infusion and decreased thereafter. Plasma IL-6, IL-12 p40, IFN-γ, and IL-1 Ra, as well as I-TAC, MIG, IP-10 and MCP-1, remained at detectable levels after 4 hours of E. coli infusion. This nonhuman primate model could be useful for the assessment of new therapeutics aiming to suppress key inflammatory markers throughout sepsis early phases.Jose J.Rosado-Franco Marcos J.Ramos-Benitez Laura M.Parodi Derick Rosario Nicole Compo Luis D.Giavedoni Ana M.Espino 2019Animal Models and Experimental Medicine2019,2,4:5
18The promises and challenges of patient-derived tumor organoids in drug development and precision oncology显示文摘In the era of precision medicine,cancer researchers and oncologists are eagerly searching for more realistic,cost effective,and timely tumor models to aid drug development and precision oncology.Tumor models that can faithfully recapitulate the histological and molecular characteristics of various human tumors will be extremely valuable in increasing the successful rate of oncology drug development and discovering the most efficacious treatment regimen for cancer patients.Two‐dimensional(2D)cultured cancer cell lines,genetically engineered mouse tumor(GEMT)models,and patient‐derived tumor xenograft(PDTX)models have been widely used to investigate the biology of various types of cancers and test the efficacy of oncology drug candidates.However,due to either the failure to faithfully recapitulate the complexity of patient tumors in the case of 2D cultured cancer cells,or high cost and untimely for drug screening and testing in the case of GEMT and PDTX,new tumor models are urgently needed.The recently developed patient‐derived tumor organoids(PDTO)offer great potentials in uncovering novel biology of cancer development,accelerating the discovery of oncology drugs,and individualizing the treatment of cancers.In this review,we will summarize the recent progress in utilizing PDTO for oncology drug discovery.In addition,we will discuss the potentials and limitations of the current PDTO tumor models.Lauren M.Granat Ooha Kambhampati Stephanie Klosek Brian Niedzwecki Kian Parsa Dong Zhang 2019Animal Models and Experimental Medicine2019,2,3:5
19The role of mouse models in colorectal cancer research—The need and the importance of the orthotopic models显示文摘Colorectal cancer is a worldwide health burden,with high incidence and mortality,especially in the advanced stages of the disease.Preclinical models are very important and valuable to discover and validate early and specific biomarkers as well as new therapeutic targets.In order to accomplish that,the animal models must replicate the clinical evolution of the disease in all of its phases.In this article,we review the existent mouse models,with their strengths and weaknesses in the replication of human cancer disease progression,with major focus on orthotopic models.Rui C.Oliveira Ana Margarida Abrantes JoseGuilherme Tralhao Maria Filomena Botelho 2020Animal Models and Experimental Medicine2020,3,1:5
20TRDMT1 exhibited protective effects against LPS-induced inflammation in rats through TLR4-NF-κB/MAPK-TNF-αpathway显示文摘Background:Inflammation is a complex physiological and pathological process.Although many types of inflammation are well characterized,their physiological func-tions are largely unknown.tRNA aspartic acid methyltransferase 1(TRDMT1)has been implicated as a stress-related protein,but its intrinsic biological role is unclear.Methods:We constructed a Trdmt1 knockout rat and adopted the LPS-induced sepsis model.Survival curve,histopathological examination,expression of inflammatory fac-tors,and protein level of TLR4 pathway were analyzed.Results:Trdmt1 deletion had no obvious impact on development and growth.Trdmt1 de-letion slightly increased the mortality during aging.Our data showed that Trdmt1 strongly responded in LPS-treated rats,and Trdmt1 knockout rats were vulnerable to LPS treat-ment with declined survival rate.We also observed more aggravated tissue damage and more cumulative functional cell degeneration in LPS-treated knockout rats compared with control rats.Further studies showed upregulated TNF-αlevel in liver,spleen,lung,and serum tissues,which may be explained by enhanced p65 and p38 phosphorylation.Conclusions:Our data demonstrated that Trdmt1 plays a protective role in inflamma-tion by regulating the TLR4-NF-κB/MAPK-TNF-αpathway.This work provides useful information to understand the TRDMT1 function in inflammation.Zhengguang Li Xiaolong Qi Xu Zhang Lei Yu Lijuan Gao Weining Kong Wei Chen Wei Dong Lijun Luo Dan Lu Lianfeng Zhang Yuanwu Ma 2022Animal Models and Experimental Medicine2022,5,2:5
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