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| 1 | Role of the Wnt/β-catenin pathway in gastric cancer: An indepth literature review显示文摘Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancerrelated deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas.The aberrant activation of the Wnt/β-catenin signaling pathway is involved in the development and progression of a significant proportion of gastric cancer cases. This review focuses on the participation of the Wnt/b-catenin pathway in gastric cancer by offering an analysis of the relevant literature published in this field. Indeed, it is discussed the role of key factors in Wnt/β-catenin signaling and their downstream effectors regulating processes involved in tumor initiation, tumor growth, metastasis and resistance to therapy. Available data indicate that constitutive Wnt signalling resulting from Helicobacter pylori infection and inactivation of Wnt inhibitors(mainly by inactivating mutations and promoter hypermethylation) play an important role in gastric cancer. Moreover, a number of recent studies confirmed CTNNB1 and APC as driver genes in gastric cancer. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput 'omics' approaches will help in the search for Wnt pathway antagonist in the near future. | Miguel Angel Chiurillo | 2015 | World Journal of Experimental Medicine2015，5，2： | 58 |
| 2 | Consolidated and emerging inflammatory markers in coronary artery disease显示文摘Coronary artery disease is an event of atherosclerosis characterized by a chronic vascular inflammation. Risk factors like obesity, diabetes mellitus, hypertension,smoking, hypercholesterolemia and positive family history sometimes are not sufficiently adequate to the enhancement of cardiovascular risk assessment. In the past years numerous biomarkers, like C reactive protein,cytokines and adhesion molecules, have been observed to be related to adverse cardiovascular prognosis. Recently,several studies found an association among inflammatory biomarkers and cardiovascular diseases suggesting their utility to identify the risk of an acute ischemic event and the detection of vulnerable plaques. The emerginginflammatory markers are well divided for diagnosis and prognosis and plaque instability of coronary artery disease. Some of them, the lectin-like oxidized low density lipoprotein receptor-1 can be important both in diagnosis and in the evaluation of plaque instability, other are inserted in the above reported classification. The emerging inflammatory markers in acute-phase include amyloid A, fibrinogen and pentraxin 3 while myeloperoxidase, myeloid-related protein 8/14 and pregnancy-associated plasma protein-A are recognize markers of plaque instability. Lastly, some studies demonstrated that circulating mi RNAs are involved in coronary artery disease, acute myocardial infarction and heart failure. | Valter Lubrano Silvana Balzan | 2015 | World Journal of Experimental Medicine2015，5，1： | 29 |
| 3 | Selected suitable seed cell, scaffold and growth factor could maximize the repair effect using tissue engineering method in spinal cord injury显示文摘Spinal cord injury usually leads to permanent disability, which could cause a huge financial problem to the patient. Up to now there is no effective method to treat this disease. The key of the treatment is to enable the damage zone axonal regeneration and luckily it could go through the damage zone; last a connection can be established with the target neurons. This study attempts to combine stem cell, material science and genetic modification technology together, by preparing two genes modified adipose-derived stem cells and inducing them into neuron direction; then by compositing them on the silk fibroin/chitosan scaffold and implanting them into the spinal cord injury model, seed cells can have features of neuron cells. At the same time, it could stably express the brain-derived neurotrophic factor and neurotrophin-3, both of which could produce synergistic effects, which have a positive effect on the recovery of spinal cord. The spinal cord scaffold bridges the broken end of the spinal cord and isolates with the surrounding environment, which could avoid a scar effect on the nerve regeneration and provide three-dimensional space for the seed cell growth, and at last we hope to provide a new treatment for spinal cord injury with the tissue engineering technique. | Wen-Chen Ji Xiao-Wei Zhang Yu-Sheng Qiu | 2016 | World Journal of Experimental Medicine2016，6，3： | 23 |
| 4 | Redox 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 | 2018 | Animal Models and Experimental Medicine2018，1，1： | 22 |
| 5 | Age-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 | 2020 | Animal Models and Experimental Medicine2020，3，1： | 22 |
| 6 | Chinese 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 | 2020 | Animal Models and Experimental Medicine2020，3，1： | 17 |
| 7 | Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus显示文摘Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine(ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM(T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2 DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin(U-Alb), mean intimal-medial thickness(IMT) and ankle brachial index(ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA(standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects. | Hiroyuki Konya Masayuki Miuchi Kahori Satani Satoshi Matsutani Yuzo Yano Taku Tsunoda Takashi Ikawa Toshihiro Matsuo Fumihiro Ochi Yoshiki Kusunoki Masaru Tokuda Tomoyuki Katsuno Tomoya Hamaguchi Jun-ichiro Miyagawa Mitsuyoshi Namba | 2015 | World Journal of Experimental Medicine2015，5，2： | 16 |
| 8 | Endoplasmic reticulum stress-mediated pathways to both apoptosis and autophagy: Significance for melanoma treatment显示文摘Melanoma is the most aggressive form of skin cancer.Disrupted intracellular signaling pathways are responsible for melanoma's extraordinary resistance to current chemotherapeutic modalities. The pathophysiologic basis for resistance to both chemo- and radiation therapy is rooted in altered genetic and epigenetic mechanisms that, in turn, result in the impairing of cell death machinery and/or excessive activation of cell growth and survival-dependent pathways. Although most current melanoma therapies target mitochondrial dysregulation,there is increasing evidence that endoplasmic reticulum(ER) stress-associated pathways play a role in the potentiation,initiation and maintenance of cell death machinery and autophagy. This review focuses on the reliability of ER-associated pathways as therapeutic targets for melanoma treatment. | Mohamed Hassan Denis Selimovic Matthias Hannig Youssef Haikel Robert T Brodell Mossaad Megahed | 2015 | World Journal of Experimental Medicine2015，5，4： | 15 |
| 9 | Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?显示文摘Beside many efforts to improve outcome, sepsis is still one of the most frequent causes of death in critically ill patients. It is the most common condition with high mortality in intensive care units. The complexity of the septic syndrome comprises immunological aspects- i.e.,sepsis induced immunosuppression- but is not restricted to this fact in modern concepts. So far, exact mechanisms and variables determining outcome and mortality stay unclear. Since there is no typical risk profile, early diagnosis and risk stratification remain difficult, which hinders rapid and effective treatment initiation. Due to the heterogeneous nature of sepsis, potential therapy options should be adapted to the individual. Biomarkers like C-reactive protein and procalcitonin are routinely used as complementary tools in clinical decision-making. Beyond the acute phase proteins, a wide bunch of promising substances and non-laboratory tools with potential diagnostic and prognostic value is under intensive investigation. So far, clinical decision just based on biomarker assessment is not yet feasible. However, biomarkers should be considered as a complementary approach. | Dubravka Kojic Benedikt H Siegler Florian Uhle Christoph Lichtenstern Peter P Nawroth Markus A Weigand Stefan Hofer Thorsten Brenner | 2015 | World Journal of Experimental Medicine2015，5，2： | 14 |
| 10 | High-level disinfection of gastrointestinal endoscope reprocessing显示文摘High level disinfection(HLD) of the gastrointestinal(GI)endoscope is not simply a slogan, but rather is a form of experimental monitoring-based medicine. By definition,GI endoscopy is a semicritical medical device. Hence,such medical devices require major quality assurance for disinfection. And because many of these items are temperature sensitive, low-temperature chemical methods, such as liquid chemical germicide, must be used rather than steam sterilization. In summarizing guidelines for infection prevention and control for GI endoscopy, there are three important steps that must be highlighted: manual washing, HLD with automated endoscope reprocessor, and drying. Strict adherence to current guidelines is required because compared to any other medical device, the GI endoscope is associated with more outbreaks linked to inadequate cleaning or disinfecting during HLD. Both experimental evaluation on the surveillance bacterial cultures and in-use clinical results have shown that, the monitoring of the stringent processes to prevent and control infection is an essential component of the broader strategy to ensure the delivery of safe endoscopy services, because endoscope reprocessing is a multistep procedure involving numerous factors that can interfere with its efficacy. Based on our years of experience in the surveillance of culture monitoring of endoscopic reprocessing, we aim in this study to carefully describe what details require attention in the GI endoscopy disinfection and to share our experience so that patients can be provided with high quality and safe medical practices. Quality management encompasses all aspects of pre- and postprocedural care including the efficiency of the endoscopy unit and reprocessing area, as well as the endoscopic procedure itself. | King-Wah Chiu Lung-Sheng Lu Shue-Shian Chiou | 2015 | World Journal of Experimental Medicine2015，5，1： | 13 |
| 11 | Obstructive sleep apnea syndrome and cardiovascular disease: The influence of C-reactive protein显示文摘Obstructive sleep apnea syndrome(OSAS) is a common medical condition, associated with atherosclerosis and cardiovascular disease(CVD). The underlying pathophysiologic mechanisms of this association have not been completely understood and may be multifactorial in origin. A number of studies suggest that inflammatory processes have emerged critical in the pathogenesis of CVD in OSAS. A range of circulating inflammatory molecules has been identified and measured, with a view to assess inflammation and predict vascular damage risk, such as plasma cytokines, adhesion molecules, and C-reactive protein(CRP). CRP is a relevant marker worthy of further study, because not only is elevated in patients with OSAS, but also is rapidly becoming a risk factor for cardiac disease. Furthermore, in selected OSAS patients, aggressive treatment of the disorder may lead to retarding or even improvement of CVD progression. However, still there is a debate on the true correlation between CRP and OSAS, as well as the clinical effect of any reduction after OSAS treatment. Further research is required to define those OSAS patients who will have a considerable reduction with treatment, as well as to understand the significance of the interaction between cardiovascular risk factor and CRP reduction in patients with OSAS. | Izolde Bouloukaki Charalampos Mermigkis Eleftherios M Kallergis Violeta Moniaki Eleni Mauroudi Sophia E Schiza | 2015 | World Journal of Experimental Medicine2015，5，2： | 12 |
| 12 | Hepatocellular carcinoma: Where are we?显示文摘Hepatocellular carcinoma(HCC) is the second cause of death due to malignancy in the world, following lung cancer. The geographic distribution of this disease accompanies its principal risk factors: Chronic hepatitis B virus and hepatitis C virus infection, alcoholism, aflatoxin B1 intoxication, liver cirrhosis, and some genetic attributes. Recently, type Ⅱ diabetes has been shown to be a risk factor for HCC together with obesity and metabolic syndrome. Although the risk factors are quite well known and it is possible to diagnose HCC when the tumor is less than 1 cm diameter, it remains elusive at the beginning and treatment is often unsuccessful. Liver transplantation is thus far considered the best treatment for HCC as it cures HCC and the underlying liver disease. Using the Milan criteria, overall survival after liver transplantation for HCC is about 70% after 5 years. Many attempts have been made to go beyond the Milan Criteria and according to recent works reasonably good results have been achieved by using a histochemical marker such as cytokeratine 19 and the so-called 'up to seven criteria' to divide patients into categories according to their risk of relapse. In addition to liver transplantation other therapies have been proposed such as resection, tumor ablation by different means, embolization and chemotherapy. An important step in the treatment of advanced HCC has been the introduction of sorafenib, the first oral, systemic drug that has provided significant improvement in survival. Treatment of HCC patients must be multidisciplinary and by using the different approaches discussed in this review it is possible to offer prolonged survival and quite good and sometimes even excellent quality of life to many patients. | Roberto Mazzanti Umberto Arena Renato Tassi | 2016 | World Journal of Experimental Medicine2016，6，1： | 10 |
| 13 | Long 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 | 2019 | Animal Models and Experimental Medicine2019，2，4： | 10 |
| 14 | Treg/Th17 cell balance and phytohaemagglutinin activation of T lymphocytes in peripheral blood of systemic sclerosis patients显示文摘AIM To investigate T-cell activation, the percentage of peripheral T regulatory cells(Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis(SSc).METHODS We enrolled a total of 24 SSc patients and 16 healthy controls in the study and divided the patients as having diffuse cutaneous SSc(dc SSc, n = 13) or limited cutaneous SSc(lc SSc, n = 11). We performed a further subdivision of the patients regarding the stage of the disease-early, intermediate or late. Peripheral venous blood samples were collected from all subjects. We performed flow cytometric analysis of the activationcapacity of T-lymphocytes upon stimulation with PHA-M and of the percentage of peripheral Tregs and Th17 cells in both patients and healthy controls. We used ELISA to quantitate serum levels of human interleukin(IL)-6, IL-10, tissue growth factor-β1(TGF-β1), and IL-17 A.RESULTS We identified a decreased percentage of CD3+CD69+ cells in PHA-stimulated samples from SSc patients in comparison with healthy controls(13.35% ± 2.90% vs 37.03% ± 2.33%, P < 0.001). However, we did not establish a correlation between the down-regulated CD3+CD69+ cells and the clinical subset, nor regarding the stage of the disease. The activated CD4+CD25+ peripheral lymphocytes were represented in decreased percentage in patients when compared to controls(6.30% ± 0.68% vs 9.36% ± 1.08%, P = 0.016). Regarding the forms of the disease, dc SSc patients demonstrated lower frequency of CD4+CD25+ T cells against healthy subjects(5.95% ± 0.89% vs 9.36% ± 1.08%, P = 0.025). With regard to Th17 cells, our patients demonstrated increased percentage in comparison with controls(18.13% ± 1.55% vs 13.73% ± 1.21%, P = 0.031). We detected up-regulated Th17 cells within the lc SSc subset against controls(20.46% ± 2.41% vs 13.73% ± 1.21%, P = 0.025), nevertheless no difference was found between dc SSc and lc SSc patients. Flow cytometric analysis revealed an increased percentage of CD4+CD25-Foxp3+ in dc SSc patients compared to controls(10.94% ± 1.65% vs 6.88% ± 0.91, P = 0.032). Regarding the peripheral cytokine profile, we detected raised levels of IL-6 [2.10(1.05-4.60) pg/m L vs 0.00 pg/m L, P < 0.001], TGF-β1(19.94 ± 3.35 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.02), IL-10(2.83 ± 0.44 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.008), and IL-17 A [6.30(2.50-15.60) pg/m L vs 0(0.00-0.05) pg/m L, P < 0.001] in patients when compared to healthy controls. Furthermore, we found increased circulating IL-10, TGF-β, IL-6 and IL-17 A in the lc SSc subset vs control subjects, as it follows: IL-10(3.32 ± 0.59 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.003), TGF-β1(22.82 ± 4.99 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.031), IL-6 [2.08(1.51-4.69) pg/m L vs 0.00 pg/m L, P < 0.001], and IL-17 A [14.50(8.55-41.65) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001]. Furthermore, circulating IL-17 A was higher in lc SSc as opposed to dc SSc subset(31.99 ± 13.29 pg/m L vs 7.14 ± 3.01 pg/m L, P = 0.008). Within the dc SSc subset, raised levels of IL-17 A and IL-6 were detected vs healthy controls: IL-17 A [2.60(0.45-9.80) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001], IL-6 [2.80(1.03-7.23) pg/m L vs 0.00 pg/m L, P < 0.001]. Regarding the stages of the disease, TGF-β1 serum levels were increased in early stage against late stage, independently from the SSc phenotype(30.03 ± 4.59 ng/m L vs 13.08 ± 4.50 ng/m L, P = 0.017).CONCLUSION It is likely that the altered percentage of Th17 and CD4+CD25-Fox P3+ cells along with the peripheral cytokine profile in patients with SSc may play a key role in the pathogenesis of the disease. | Ekaterina Krasimirova Tsvetelina Velikova Ekaterina Ivanova-Todorova Kalina Tumangelova-Yuzeir Desislava Kalinova Vladimira Boyadzhieva Nikolay Stoilov Tsvetelina Yoneva Rasho Rashkov Dobroslav Kyurkchiev | 2017 | World Journal of Experimental Medicine2017，7，3： | 10 |
| 15 | Animal 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 | 2021 | Animal Models and Experimental Medicine2021，4，3： | 9 |
| 16 | MicroRNA-regulated viral vectors for gene therapy显示文摘Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent posttranscriptional suppression of transgene expression has been emerging as powerful new technology to increase the specificity of vector-mediated transgene expression. Micro RNAs are small non-coding RNAs and often expressed in a tissue-, lineage-, activation- or differentiation-specific pattern. They typically regulate gene expression by binding to imperfectly complementary sequences in the 3' untranslated region(UTR) of the m RNA. To control exogenous transgene expression, tandem repeats of artificial micro RNA target sites are usually incorporated into the 3' UTR of the transgene expression cassette, leading to subsequent degradation of transgene m RNA in cel s expressing the corresponding micro RNA. This targeting strategy, first shown for lentiviral vectors in antigen presenting cells, has now been used for tissue-specific expression of vector-encoded therapeutic transgenes, to reduce immune response against the transgene, to control virus tropism for oncolytic virotherapy, to increase safety of live attenuated virus vaccines and to identify and select cell subsets for pluripotent stem cell therapies, respectively. This review provides an introduction into the technical mechanism underlying micro RNA-regulation, highlights new developments in this field and gives an overview of applications of micro RNA-regulated viral vectors for cardiac, suicide gene cancer and hematopoietic stem cell therapy, as well as for treatment of neurological and eye diseases. | Anja Geisler Henry Fechner | 2016 | World Journal of Experimental Medicine2016，6，2： | 9 |
| 17 | Research 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 | 2022 | Animal Models and Experimental Medicine2022，5，4： | 9 |
| 18 | Disease control by regulation of P-glycoprotein on lymphocytes in patients with rheumatoid arthritis显示文摘The main purpose of treatment of rheumatoid arthritis(RA) with disease modifying antirheumatic drugs(DMARDs) is to control activation of lymphocytes,although some patients do not respond adequately to such treatment. Among various mechanisms of multidrug resistance, P-glycoprotein(P-gp), a member of ATP-binding cassette transporters, causes drugresistance by efflux of intracellular drugs. Certain stimuli,such as tumor necrosis factor-α, activate lymphocytes and induce P-gp expression on lymphocytes, as evident in active RA. Studies from our laboratories showed spontaneous nuclear accumulation of human Y-boxbinding protein-1, a multidrug resistance 1 transcription factor, in unstimulated lymphocytes, and surface overexpression of P-gp on peripheral lymphocytes of RA patients with high disease activity. The significant correlation between P-gp expression level and RA disease activity is associated with active efflux of drugs from the lymphocyte cytoplasm and in drugresistance.However, the use of biological agents that reduce P-gp expression as well as P-gp antagonists(e.g., cyclosporine) can successfully reduce the efflux of corticosteroids from lymphocytes in vitro, suggesting that both types of drugs can be used to overcome drug-resistance and improve clinical outcome. We conclude that lymphocytes activated by various stimuli in RA patients with highly active disease acquire P-gpmediated multidrug resistance against corticosteroids and probably some DMARDs, which are substrates of P-gp. Inhibition/reduction of P-gp could overcome such drug resistance. Expression of P-gp on lymphocytes is a promising marker of drug resistance and a suitable therapeutic target to prevent drug resistance in patients with active RA. | Shizuyo Tsujimura Yoshiya Tanaka | 2015 | World Journal of Experimental Medicine2015，5，4： | 8 |
| 19 | Immunology of tuberculosis显示文摘Various T cells and macrophages as well as cytokines are involved in the immunopathogenesis of tuberculosis(TB). A better understanding of immunology of TB can not only lead to the discovery of new immunodiagnostic tools, accelerate and facilitate the assessment of new therapeutic methods, but also find new treatment regimens. In this highlight topic we cover the latest developments in the role of T cells, macrophages, Natural killer(NK) cells, invariant NK T(iN KT) cells and γδ T cells with TB infection. Histologically, TB displays exudative inflammation, proliferative inflammation and productive inflammation depending on the time course. T cells first recognize antigen within the mycobacterially-infected lung, and then activate, differentiate, but the first T cell activation occurs in the draining lymph nodes of the lung. When protective T cells reach sufficient numbers, they can stop bacterial growth. Except for T cells, neutrophils also participate actively in defense against early-phase TB. NK cells are innate lymphocytes which are a first line of defense against mycobacterial infection. Human NK cells use the NKp46, NCRs and NKG2 D receptors to lyse Mycobacterium TB-infected monocytes and alveolar macrophages. NK cells produce not only interferon-γ, but also interleukin(IL)-22, which is induced by IL-15 and DAP-10. iN KT cells show different phenotypes and functions. Many iN KT cells are CD4+,few iN KT cells are CD8+, while an additional fraction of iN KT cells are negative for both CD4 and CD8. γδ T cells represent an early innate defense in antimycobacterial immunity. Studies done in humans and animal models have demonstrated complex patterns of γδ T cell immune responses during chronic TB. Human alveolar macrophages and monocytes can serve as antigen presentation cells for γδ T cells. Furthermore, the predominance of Vγ9Vδ2 T cells in TB has been confirmed. | Qing Zhang Isamu Sugawara | 2012 | World Journal of Experimental Medicine2012，2，4： | 8 |
| 20 | Autonomic function and ventricular tachyarrhythmias during acute myocardial infarction显示文摘Most cases of sudden cardiac death are attributed to sustained ventricular tachyarrhythmias(VTs), triggered by acute coronary occlusion. Autonomic dysfunction, an important arrhythmogenic mechanism in this setting, is being actively investigated, aiming at the advent of preventive strategies. Recent experimental studies have shown vagal withdrawal after anterior myocardial infarction, coinciding with high incidence of VTs, followed by more gradual sympathetic activation coinciding with a second arrhythmia peak. This article summarizes recent knowledge on this intriguing topic, generating hypotheses that can be investigated in future experimental and clinical studies. | Theofilos M Kolettis | 2018 | World Journal of Experimental Medicine2018，8，1： | 8 |
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