• Title/Summary/Keyword: mouse model

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Classification of Mouse Lung Metastatic Tumor with Deep Learning

  • Lee, Ha Neul;Seo, Hong-Deok;Kim, Eui-Myoung;Han, Beom Seok;Kang, Jin Seok
    • Biomolecules & Therapeutics
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    • v.30 no.2
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    • pp.179-183
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    • 2022
  • Traditionally, pathologists microscopically examine tissue sections to detect pathological lesions; the many slides that must be evaluated impose severe work burdens. Also, diagnostic accuracy varies by pathologist training and experience; better diagnostic tools are required. Given the rapid development of computer vision, automated deep learning is now used to classify microscopic images, including medical images. Here, we used a Inception-v3 deep learning model to detect mouse lung metastatic tumors via whole slide imaging (WSI); we cropped the images to 151 by 151 pixels. The images were divided into training (53.8%) and test (46.2%) sets (21,017 and 18,016 images, respectively). When images from lung tissue containing tumor tissues were evaluated, the model accuracy was 98.76%. When images from normal lung tissue were evaluated, the model accuracy ("no tumor") was 99.87%. Thus, the deep learning model distinguished metastatic lesions from normal lung tissue. Our approach will allow the rapid and accurate analysis of various tissues.

The latest study tendency in mouse model of skin pruritus - Mainly on scratching behavior model (피부 소양 마우스 모델의 최근 연구 동향 -Scratching behavior model을 중심으로)

  • Kim, Keoo-Seok;Kim, Yoon-Bum
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.20 no.2 s.33
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    • pp.142-150
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    • 2007
  • Objectives : This study was carried out to investigate the latest study tendency in mouse model of skin pruritus published since 2005 and to arrange various experimental methods. Methods : We examined the journal(such as Experimental dermatology and British journal of dermatology) and in Pubmed since 2005, regarded pruritus and scratching behavior model as key words. Results and Conclusion : 1. BALB/c, hairless, NC/Nga and ICR mice were the most used in scratching behavior model. According to scratching-induced agents. we need to select experimental mice. 2. There are various methods inducing skin pruritus; by cohabitation with NC/Nga mice having severe skin lesions, by injection intradermally(or subcutaneously) with agent inducing inflammation, by inducing contact dermatitis with TNCB, TNFB, destruction of skin barrier and by transgenic mice. 3. Injection intradermally(or subcutaneously) with agent inducing inflammation is the most used out of methods inducing skin pruritus. Compound 48/80, histamine, substance P and others(chloroquine, serotonin, carrageenin, TPA etc.) were included in agents inducing inflammation and pruritus in skin pruritus model. 4. Video camera, SCLABA system, MicroAct and acoustic evaluation system were included in evaluation methods of scratching behavior mouse model.

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An Arachidonic Acid Metabolizing Enzyme, 8S-Lipoxygenase, in Mouse Skin Carcinogenesis

  • Kim Eun-Jung
    • Nutritional Sciences
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    • v.9 no.3
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    • pp.212-226
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    • 2006
  • The involvement of arachidonic acid (AA) metabolizing enzyme, lipoxygenase (LOX), in the development of particular tumors in humans has gradually been acknowledged and LOX has emerged as a novel target to prevent or treat human cancers. In the mouse skin carcinogenesis model, which provides an excellent model to study multistage nature of human cancer development, many studies have shown that some of the LOXs are constitutively upregulated in their expression. Moreover, application of LOX inhibitors effectively reduced tumor burdens, which implicates the involvement of LOX in mouse skin tumor development as well. 8S-LOX is a recently cloned LOX, which is specifically expressed in mouse skin after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment but not in normal skin. Unlike other members of the LOX 'family' expressed in mouse skin, this TPA-induced expression of 8S-LOX is prominent only in the skin of the TPA tumor promotion-sensitive strains of mice (SENCAR, CD-1, and NMRI) but not in the promotion-resistant C57BL/6J mice. This is a very unique phenomenon among strains of mice. Constitutive upregulation of 8S-LOX was also found in early stage papillomas and the expression was gradually reduced as the tumors became malignant. Based on these observations, it has been thought that 8S-LOX is involved in TPA-induced tumor promotion as well as in tumor conversion from papillomas to carcinomas. In accordance with this hypothesis, several studies have suggested possible roles of 8S-hydroxyeicosatetraenoic acid (HETE), an AA metabolite of 8S-LOX, in mouse skin tumor development. A clastogenic activity of 8S-HETE was demonstrated in primary keratinocytes and a close correlation between the levels of etheno-DNA adducts and 8S-HETE during skin carcinogenesis was also reported. On the other hand, it has been reported that 8S-LOX protein expression is restricted to a differentiated keratinocyte compartment Moreover, reported findings on the ability of 8S-HETE to cause keratinocyte differentiation appear to be contrary to the procarcinogenic features of the 8S-LOX expression, presenting a question as to the role of 8S-LOX during mouse skin carcinogenesis. In this review, molecular and biological features of 8S-LOX as well as current views on the functional role of 8S-LOX/8S-HETE during mouse skin carcinogenesis are presented.

The Protective Effects of Sopung-tang on Brain Damage in Photothrombotic Ischemia Mouse Model (뇌경색 마우스의 뇌손상에 대한 소풍탕(疎風湯)의 보호효과)

  • Jang, Seok-O;Choi, Ji-Hye;Lee, John Dong-Yeop;Choi, Yong-Jun;Lee, In;Moon, Byung-Soon
    • The Journal of Internal Korean Medicine
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    • v.30 no.3
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    • pp.612-623
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    • 2009
  • Objectives : The water extract of Sopung-tang (SPT) has been traditionally used in the treatment of acute stroke in Oriental Medicine. Pro-inflammatory cytokines play a critical role in the onset of post-ischemic inflammatory cascades. The present study was designed to investigate the effects of SPT on pro-inflammatory cytokine production in a photothrombotic ischemia mouse model. Methods : After SPT oral administration to the mice for five days, with using Rose Bengal and cold light, photothrombotic ischemia lesion was induced in stereotactically held male BALB/c mice. Also, results including, gross finding lesion size, histopathological finding changes, and inflammatory cytokine expression changes from the photothrombotic ischemia mouse model were observed. Results : The photothrombotic ischemia lesion was decreased by the oral injection of SPT. Also, SPT inhibited the expression of TNF-$\alpha$, IL-$1{\beta}$, IL-6, the active form of caspase-3 protease, and transglutaminase-2 in the photothrombotic ischemia lesion. Conclusions : These results suggest that SPT protects the ischemic death of brain cells through suppression of the production of anti-inflammatory cytokines and catalytic activation of caspase-3 protease in the photothrombotic ischemia mouse model.

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Combination Treatment with SIP-3 Herb Formula and Donepezil: An NGS Study in the Mouse Model of Alzheimer's Disease Induced by Amyloid-β (SIP-3 한약 처방 및 도네페질의 병용 치료: 아밀로이드 베타로 유도된 알츠하이머병 생쥐 모델에서의 NGS 연구)

  • Oh, Young-je;Song, Sue-jin;Liu, Quan Feng;Son, Tae-kwon;Kim, Geun-woo;Koo, Byung-soo
    • Journal of Oriental Neuropsychiatry
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    • v.30 no.4
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    • pp.327-340
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    • 2019
  • Objectives: Alzheimer's disease (AD) is a complex disease accompanied by slow impairment of memory and coordination leading to behavioral changes. To date, the only treatment option is to delay the progress of the disease. The purpose of this study was to investigate the synergistic effects of combination treatment with donepezil and three herbal extracts SIP-3 in the AD mouse model induced by amyloid-β (Aβ). Methods: We tested SIP-3 extracts for the cytotoxicity on Aβ-treated SH-SY5Y cells. Then the synergistic effects of SIP-3 and donepezil were evaluated in the AD mouse model using animal experiments and the next generation sequencing (NGS) study. Results: We found that co-treatment with SIP-3 extracts and donepezil increased the viability in Aβ-treated SH-SY5Y cells. The beneficial effects of the co-treatment were also observed in the Aβ-induced AD mouse model. The NGS study was performed to show that the co-treatment of SIP-3 and donepezil restored the disease phenotype closely to the normal level in the AD mouse model in terms of mRNA expression. However, the phenotypes were only partially restored. Conclusions: This study suggests that the combination treatment has a potential to be used for the treatment of AD. However, longer periods of treatment may be required.

Potential Therapeutic Strategy in Chronic Obstructive Pulmonary Disease Using Pioglitazone-Augmented Wharton's Jelly-Derived Mesenchymal Stem Cells

  • Park, Jin-Soo;Kim, Hyun Kuk;Kang, Eun-Young;Cho, RyeonJin;Oh, Yeon-Mok
    • Tuberculosis and Respiratory Diseases
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    • v.82 no.2
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    • pp.158-165
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    • 2019
  • Background: A recent study reported that mesenchymal stem cells possess potential cellular therapeutic properties for treating patients with chronic obstructive pulmonary disease, which is characterized by emphysema. We examined the potential therapeutic effect of Wharton's Jelly-derived mesenchymal stem cells (WJMSCs), following pretreatment with pioglitazone, in lung regeneration mouse emphysema models. Methods: We used two mouse emphysema models, an elastase-induced model and a cigarette smoke-induced model. We intravenously injected WJMSCs ($1{\times}10^4/mouse$) to mice, pretreated or not, with pioglitazone for 7 days. We measured the emphysema severity by mean linear intercepts (MLI) analysis using lung histology. Results: Pioglitazone pretreated WJMSCs (pioWJMSCs) were associated with greater lung regeneration than non-augmented WJMSCs in the two mouse emphysema models. In the elastase-induced emphysema model, the MLIs were $59.02{\pm}2.42{\mu}m$ (n=6), $72.80{\pm}2.87{\mu}m$ (n=6), for pioWJMSCs injected mice, and non-augmented WJMSCs injected mice, respectively (p<0.01). Both pioWJMSCs and non-augmented WJMSCs showed regenerative effects in the cigarette smoke emphysema model (MLIs were $41.25{\pm}0.98$ [n=6] for WJMSCs and $38.97{\pm}0.61{\mu}m$ [n=6] for pioWJMSCs) compared to smoking control mice ($51.65{\pm}1.36{\mu}m$, n=6). The mean improvement of MLI appeared numerically better in pioWJMSCs than in non-augmented WJMSCs injected mice, but the difference did not reach the level of statistical significance (p=0.071). Conclusion: PioWJMSCs may produce greater lung regeneration, compared to non-augmented WJMSCs, in a mouse emphysema model.

Evaluation of host and bacterial gene modulation during Lawsonia intracellularis infection in immunocompetent C57BL/6 mouse model

  • Kirthika, Perumalraja;Park, Sungwoo;Jawalagatti, Vijayakumar;Lee, John Hwa
    • Journal of Veterinary Science
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    • v.23 no.3
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    • pp.41.1-41.15
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    • 2022
  • Background: Proliferative enteritis caused by Lawsonia intracellularis undermines the economic stability of the swine industry worldwide. The development of cost-effective animal models to study the pathophysiology of the disease will help develop strategies to counter this bacterium. Objectives: This study focused on establishing a model of gastrointestinal (GI) infection of L. intracellularis in C57BL/6 mice to evaluate the disease progression and lesions of proliferative enteropathy (PE) in murine GI tissue. Methods: We assessed the murine mucosal and cell-mediated immune responses generated in response to inoculation with L. intracellularis. Results: The mice developed characteristic lesions of the disease and shed L. intracellularis in the feces following oral inoculation with 5 × 107 bacteria. An increase in L. intracellularis 16s rRNA and groEL copies in the intestine of infected mice indicated intestinal dissemination of the bacteria. The C57BL/6 mice appeared capable of modulating humoral and cell-mediated immune responses to L. intracellularis infection. Notably, the expression of genes for the vitamin B12 receptor and for secreted and membrane-bound mucins were downregulated in L. intracellularis -infected mice. Furthermore, L. intracellularis colonization of the mouse intestine was confirmed by the immunohistochemistry and western blot analyses. Conclusions: This is the first study demonstrating the contributions of bacterial chaperonin and host nutrient genes to PE using an immunocompetent mouse model. This mouse infection model may serve as a platform from which to study L. intracellularis infection and develop potential vaccination and therapeutic strategies to treat PE.

Controlled Partial Skin Thickness Burns: Rabbit Ear as a 2nd Degree Burn Wound Model for Studies of Topical Therapy

  • Cho, Lee Ae-Ri;Moon, Hee-Kyung
    • Journal of Pharmaceutical Investigation
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    • v.36 no.5
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    • pp.339-342
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    • 2006
  • This study was designed to prepare an animal model for partial thickness bum wound which can be employed for testing topical therapy. We first evaluated whether rabbit ear and mouse back skin wound model could differentiate the wound healing process in terms of degree of re epithelialization, required days for complete wound closure, presence of scarring. $2^{nd}$ degree wet bum were prepared on mouse back skin and rabbit ear by applying 5 mL hot water($85{\pm}0.1^{\circ}C$) for 7 see followed by 5 mL ice-cold 0.5% acrynol solution for cooling and disinfecting the inflicted area. After removing the dead epidermis layer at 24 hr, tested dressings were applied for specified time and wound progression was investigated. In mouse model, wound contraction was the primary wound closing mechanism, which is quite different from human wound healing process. In rabbit ear model, epidermal regeneration was the major wound healing process rather than wound contraction and the difference in wound healing property among tested dressings could be clearly demonstrated. A rabbit ear model could differentiate the wound progression among open, occluded and epidermal growth factor(EGF) treated wound. Four sites of circular wound(diameter: 1 cm) on the anterior part of rabbit ear could be employed for the comparative wound healing study. For obtaining reproducible bum wound, degree of bum depth and bum sites should be carefully controlled in addition, employing rabbits of same strain and weight. The result suggests that rabbit ear could be employed as a reliable and human-resembled wound model.

A Role of Natural Killer Cell in Mouse Infected Herpes Simplex Virus (Herpes Simplex Virus에 감염된 Mouse의 NK세포역할)

  • Lee, Yun-Tai;Lee, Chong-Hoon
    • The Journal of the Korean Society for Microbiology
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    • v.17 no.1
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    • pp.7-14
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    • 1982
  • A model of induction of neoplasia by viruses has develpoed from experimental studies in animals and in cultured cells and oncogenic transformation of cells is the result of integration of viral genetic information into the cellular DNA. The evidence for these associations was derived primarily from seroepidemiologic investigation. However, data indicating that the relation between HSV-2 and cervical cancer fits the model derived from experimental animal studies are not yet sufficient to draw conclusion with regard to the etiologic role the virus in the development of the neoplasms. In other hand, the K562 tumor cell is highly susceptible target for natural killer cell lysis by the lymphocytes of human and murine periperal blood. The characteristics of this effector cell type has been investigated. A study on natural killer cell mediated cytotoxicity(NKMC) against $^{51}Cr$-K562 as target cell was studed in HSV-2 infected ICR mouse. We have studied for susceptibility of HSV-2 against mouse embryo fibroblast(MEF) cells and NKMC from HSV-2 infected mouse. The results obtained that the mouse embryo fibroblast cells culture, the number and size of the cells were markedly increased and formed a monolayers relatively rapid, and become complete monolayer sheet around 72 hrs. Duration of cytopathic effect on MEF cells was rapid by serial passing of HSV-2. The morphology of the HSV-2 infected cells appear to be mainly round, ovium, spindle form and some of them was forming large giant cells. The NKMC was decrease in mouse with HSV-2 and comparison between effector/target cells ratio as 25:1 and 50:1 respectively, the NKMC was found to be more significantly decreased than normal control we have concluded that the natural killer cell activity of the viral infected mouse was shown as a suppressed during the HSV-2 infection, day 7th and 14th.

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Generation of Transgenic Mice Overexpression Mouse RESISTIN

  • J. R. Chun;S. J. Song;J. T. Do;K. S. Chung;Lee, H. T.
    • Proceedings of the Korean Society of Embryo Transfer Conference
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    • 2002.11a
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    • pp.99-99
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    • 2002
  • The hormone resistin is associated with typeII diabetes mellitus in rodent model. Resistin impairs glucose tolerance and insulin action. A new class of anti-diabetic drugs were called thiazolidinediones (TZDs) downregulates a resistin which is induced during adipocyte differentiation. But the connection between increased adiposity and resistin remains unknown. The objectives of this study was to clone a mouse resistin cDNA and to generate transgenic mice overexpressing mouse resistin gene. The 555 bp of mouse resistin was amplified from mob cDNAS by polymerase chain reaction (PCR) and cloned into pCR$\^$(R)/ 2.1 TOPO T-vector. Mouse resistin mRNA on the basis of Genbank sequence (acession no. AF323080). Then, the PCR product was cloned into pTargeT$\^$TM/ mammalian expression vector that has pCMV promoter and chimeric intron. Restriction enzyme analysis with BamH I and Not I was carried out to determine an orientation of the insert in the vector. The pCMV-mus/resistin gene was prepared from previous recombinant pTargeT$\^$TM/-mus/resistin by digestion of Bgl II, and has used for microinjection into pronuclei of one cell embryos. The microinjected embryos were transfered to pseudopregnant foster-mother. Mouse resistin expression was detected in transgenic F1 mice by Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR). Resistin gene expression mouse has heavier body weight which was measured higher level of plasma glucose than that of normal mouse. And in diet-induced experiments, the abdominal fat pads were isolated from each 24h starvation and re-feeding after fasting group mice that were assessed by RT-PCR analysis. In fasting group mice, resistin expression was higher than that of re-feeding group mice. This result suggests that the resistin gene overexpressing mice may be became to obesity and be useful as an animal disease model to be diabetes mellitus caused by insulin resistance of resistin.

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