• Title/Summary/Keyword: disease-model animal

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TNBS 동물 모델과 loperamide 동물 모델에서 해삼 건조 분말의 대장염 및 변비 개선 효과 (Improving Effects of Stichopus Japonicus on TNBS-Induced Colitis and Loperamide-Induced Constipation in Animal Disease Models)

  • 김정훈;오홍근;강영례;박정우;문대인;서민영;박상훈;강양규;최충현;박인선;김주;유강렬;김재경;김옥진;황홍연;류도곤;이영래;이학용
    • 동의생리병리학회지
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    • 제26권5호
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    • pp.672-678
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    • 2012
  • Colitis and constipation are the most common intestinal complaints worldwide. This study examined the beneficial effects of sea cucumber powder for TNBS-induced colitis in ICR mice(n=6/group) and loperamide-induced constipation in rats(n=8/group). Animals were divided into normal and four dried see cucumber treated groups that were named Nor, Con(0 mg/kg), GI(30 mg/kg), GII(100 mg/kg) and GIII(300 mg/kg). In order to induce colitis and constipation, 5% TNBS was injected into distal colon and loperamide (2 mg/kg, twice a day, peroral) was treated for 5 day in the four experimental groups but not the normal group. Gross finding score was decreased tendency by oral administration of sea cucumber in colitis-induced animal model, but colonic weight was not different. Excreted fecal pellet number, weight and water content were increased in the sea cucumber-treated group compared to the non-treated group. The fecal pellet number was reduced within distal colon of the sea cucumber-treated groups. Interestingly, intestinal transit length was increased compared to the non-treated group. Our results demonstrated that colitis and constipation were improved by sea cucumber treatment in the animal models. Specifically, gross finding score in TNBS-induced colitis model was improved by sea cucumber. After animals being fed sea cucumber, excreted fecal number, weight, water contents, and fecal number within distal colon and colonic transit length also get better in loperamide-induced constipation model.

The Endophyte Curtobacterium flaccumfaciens Reduces Symptoms Caused by Xylella fastidiosa in Catharanthus roseus

  • Lacava, Paulo Teixeira;Li, Wenbin;Araujo, Welington Luiz;Azevedo, Joao Lucio;Hartung, John Stephen
    • Journal of Microbiology
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    • 제45권5호
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    • pp.388-393
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    • 2007
  • Citrus variegated chlorosis (CVC) is a disease of the sweet orange [Citrus sinensis (L.)], which is caused by Xylella fastidiosa subsp. pauca, a phytopathogenic bacterium that has been shown to infect all sweet orange cultivars. Sweet orange trees have been occasionally observed to be infected by Xylella fastidiosa without evidencing severe disease symptoms, whereas other trees in the same grove may exhibit severe disease symptoms. The principal endophytic bacterial species isolated from such CVC-asymptomatic citrus plants is Curtobacterium flaccumfaciens. The Madagascar periwinkle [Citrus sinensis (L.)] is a model plant which has been used to study X. fastidiosa in greenhouse environments. In order to characterize the interactions of X. fastidiosa and C. flaccumfaciens, periwinkle plants were inoculated separately with C. flaccumfaciens, X. fastidiosa, and both bacteria together. The number of flowers produced by the plants, the heights of the plants, and the exhibited disease symptoms were evaluated. PCR-primers for C. flaccumfaciens were designed in order to verify the presence of this endophytic bacterium in plant tissue, and to complement an existing assay for X. fastidiosa. These primers were capable of detecting C. flaccumfaciens in the periwinkle in the presence of X. fastidiosa. X. fastidiosa induced stunting and reduced the number of flowers produced by the periwinkle. When C. flaccumfaciens was inoculated together with X. fastidiosa, no stunting was observed. The number of flowers produced by our doubly- inoculated plants was an intermediate between the number produced by the plants inoculated with either of the bacteria separately. Our data indicate that C. flaccumfaciens interacted with X. fastidiosa in C. roseus, and reduced the severity of the disease symptoms induced by X. fastidiosa. Periwinkle is considered to be an excellent experimental system by which the interaction of C. flaccumfaciens and other endophytic bacteria with X. fastidiosa can be studied.

Recombinant Human HAPLN1 Mitigates Pulmonary Emphysema by Increasing TGF-β Receptor I and Sirtuins Levels in Human Alveolar Epithelial Cells

  • Yongwei Piao;So Yoon Yun;Zhicheng Fu;Ji Min Jang;Moon Jung Back;Ha Hyung Kim;Dae Kyong Kim
    • Molecules and Cells
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    • 제46권9호
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    • pp.558-572
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    • 2023
  • Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2030. One of its components, emphysema, has been defined as a lung disease that irreversibly damages the lungs' alveoli. Treatment is currently unavailable for emphysema symptoms and complete cure of the disease. Hyaluronan (HA) and proteoglycan link protein 1 (HAPLN1), an HA-binding protein linking HA in the extracellular matrix to stabilize the proteoglycan structure, forms a bulky hydrogel-like aggregate. Studies on the biological role of the full-length HAPLN1, a simple structure-stabilizing protein, are limited. Here, we demonstrated for the first time that treating human alveolar epithelial type 2 cells with recombinant human HAPLN1 (rhHAPLN1) increased TGF-β receptor 1 (TGF-β RI) protein levels, but not TGF-β RII, in a CD44-dependent manner with concurrent enhancement of the phosphorylated Smad3 (p-Smad3), but not p-Smad2, upon TGF-β1 stimulation. Furthermore, rhHAPLN1 significantly increased sirtuins levels (i.e., SIRT1/2/6) without TGF-β1 and inhibited acetylated p300 levels that were increased by TGF-β1. rhHAPLN1 is crucial in regulating cellular senescence, including p53, p21, and p16, and inflammation markers such as p-NF-κB and Nrf2. Both senile emphysema mouse model induced via intraperitoneal rhHAPLN1 injections and porcine pancreatic elastase (PPE)-induced COPD mouse model generated via rhHAPLN1-containing aerosols inhalations showed a significantly potent efficacy in reducing alveolar spaces enlargement. Preclinical trials are underway to investigate the effects of inhaled rhHAPLN1-containing aerosols on several COPD animal models.

A comparison study of pathological features and drug efficacy between Drosophila models of C9orf72 ALS/FTD

  • Davin Lee;Hae Chan Jeong;Seung Yeol Kim;Jin Yong Chung;Seok Hwan Cho;Kyoung Ah Kim;Jae Ho Cho;Byung Su Ko;In Jun Cha;Chang Geon Chung;Eun Seon Kim;Sung Bae Lee
    • Molecules and Cells
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    • 제47권1호
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    • pp.100005.1-100005.15
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    • 2024
  • Amyotrophic lateral sclerosis is a devastating neurodegenerative disease with a complex genetic basis, presenting both in familial and sporadic forms. The hexanucleotide (G4C2) repeat expansion in the C9orf72 gene, which triggers distinct pathogenic mechanisms, has been identified as a major contributor to familial and sporadic Amyotrophic lateral sclerosis cases. Animal models have proven pivotal in understanding these mechanisms; however, discrepancies between models due to variable transgene sequence, expression levels, and toxicity profiles complicate the translation of findings. Herein, we provide a systematic comparison of 7 publicly available Drosophila transgenes modeling the G4C2 expansion under uniform conditions, evaluating variations in their toxicity profiles. Further, we tested 3 previously characterized disease-modifying drugs in selected lines to uncover discrepancies among the tested strains. Our study not only deepens our understanding of the C9orf72 G4C2 mutations but also presents a framework for comparing constructs with minute structural differences. This work may be used to inform experimental designs to better model disease mechanisms and help guide the development of targeted interventions for neurodegenerative diseases, thus bridging the gap between model-based research and therapeutic application.

Prevalence, Associated Risk Factors, and Phylogenetic Analysis of Toxocara vitulorum Infection in Yaks on the Qinghai Tibetan Plateau, China

  • Li, Kun;Lan, Yanfang;Luo, Houqiang;Zhang, Hui;Liu, Dongyu;Zhang, Lihong;Gui, Rui;Wang, Lei;Shahzad, Muhammad;Sizhu, Suolang;Li, Jiakui;Chamba, Yangzom
    • Parasites, Hosts and Diseases
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    • 제54권5호
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    • pp.645-652
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    • 2016
  • Toxocara vitulorum has been rarely reported in yaks at high altitudes and remote areas of Sichuan Province of Tibetan Plateau of China. The current study was designed to investigate the prevalence, associated risk factors, and phylogenetic characteristics of T. vitulorum in yak calves on the Qinghai Tibetan plateau. Fecal samples were collected from 891 yak calves and were examined for the presence of T. vitulorum eggs by the McMaster technique. A multivariable logistic regression model was employed to explore variables potentially associated with exposure to T. vitulorum infection. T. vitulorum specimens were collected from the feces of yaks in Hongyuan of Sichuan Province, China. DNA was extracted from ascaris. After PCR amplification, the sequencing of ND1 gene was carried out and phylogenetic analyses was performed by MEGA 6.0 software. The results showed that 64 (20.1%; 95% CI 15.8-24.9%), 75 (17.2; 13.8-21.1), 29 (40.9; 29.3-53.2), and 5 (7.6; 2.5-16.8) yak calves were detected out to excrete T. vitulorum eggs in yak calve feces in Qinghai, Tibet, Sichuan, and Gansu, respectively. The present study revealed that high infection and mortality by T. vitulorum is wildly spread on the Qinghai Tibetan plateau, China by fecal examination. Geographical origin, ages, and fecal consistencies are the risk factors associated with T. vitulorum prevalence by logistic regression analysis. Molecular detection and phylogenetic analysis of ND1 gene of T. vitulorum indicated that T. vitulorum in the yak calves on the Qinghai Tibetan plateau are homologous to preveiously studies reported.

정신분열병의 실험적 모델 (Experimental Models of Schizophrenia)

  • 전진숙
    • 생물정신의학
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    • 제6권2호
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    • pp.153-160
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    • 1999
  • 동물모형은 정신장애의 연구와 치료에 유용한 도구를 제공할 수 있다. 정신장애의 동물모형으로서의 적합성에 대한 평가 기준은 첫째, 유도된 상태의 유사성, 둘째, 행동상의 유사성, 셋째, 공통된 근저의 신경생물학적 기전, 넷째, 임상적으로 효과적인 치료 기술에 의한 역전 등 4가지이다. 저자는 정신분열병의 연구에 유용한 도구로 사용할 수 있는 실험적 모델을 간략히 소개하였다. 정신분열병의 실험적 모델로서는 L-dopa 모델, phenylethylamine 모델, hallucinogen 모델, amphetamine 모델, phencyclidine(이하 PCP) 모델, NE 보상계병소 모델, 망상계자극 모델, 사회격리 모델, 조건화된 회피반응, catalepsy 시험, paw 시험, 자기자극 paradigm, latent inhibition paradigm, blocking paradigm, 경악반사의 prepulse inhibition, 설치류 상호작용, 원숭이의 사회적 행위, 해마손상, 선택적 breeding을 사용한 모델, 고기압 모델, 각성 모델, 감각운동 gating 모델 등이 제시되고 있다. 저자는 이중에서 특히 정신분열병의 실험적 모델로서 face validity, predictive validity, construct validity가 높은 몇 가지 방법에 대해서 중점적으로 설명하였다. 임상경험 및 동물실험에서 PCP 및 ketamine 등 PCP 유사물질은 양성증상 뿐만아니라 음성증상, 파과형, 인지장애군에 좀 더 가까운 비망상형의 정신분열병에도 적용시키기가 좋은 것으로 알려졌다. 임신이나 출생 시 합병증에 의한 해마병소화, 내재적 신경독성에 의한 NE 보상계 병소, 스테로이드 증가에 의한 해마변화 등에 의해서 정신분열병이 유도될 수 있음은 해마병소화 모델이 정신분열병의 실험적 모델로서의 첫번째 기준을 충족시킴을 입증한다. 해마 병소화 후에 정신분열병 환자에서 흔히 볼 수 있는 주의집중력 장애, 공간 및 문맥 정보의 이해결핍, 기억구성, 인식기억, 고전적 조건화, 일반화, 복합적 학습, 상동적 행동, 미신적 행동, 과잉각성, 소멸과 습관형성, 피부전도 실험 등의 이상이 관찰됨은 정신분열병의 실험적 모델로서 두 번째의 기준에 합당한 것이다. 사후 부검한 뇌조직 및 여러 신경영상화 연구에서 해마의 구조적 이상 및 신경전달물질의 수용체 변화가 보고됨은 세 번째 조건을 만족시키는 것이며, 정신분열병의 여러 치료약물을 투여함으로써 상기 변화가 반전됨은 해마병소화 모델이 정신분열병의 실험적 모델로서 타당도가 높음을 시사한다. 정신분열병의 양성증상, 음성증상, 인지장애를 모두 포괄적으로 반영할 수 있는 실험적 모델로서 ketamine 모델과 해마병소화 모델 등이 보다 유용한 도구로 제시될 수 있다. 그러나 현재까지 어떠한 정신분열병의 모형도 정신분열병 전체를 대표할 수 있는 것은 없다. 따라서 동물모형을 사용한 연구의 결과는 매우 조심스럽게 해석되어야 한다. 또한 동물모형을 발전시키고 타당화 시키려는 노력은 인간에서의 현상을 신빙성있게 측정하는 방법을 규명하는 과정과 공동으로 이루어져야 한다.

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A Minimally Invasive Rabbit Model of Progressive and Reproducible Disc Degeneration Confirmed by Radiology, Gene Expression, and Histology

  • Kwon, Young-Joon
    • Journal of Korean Neurosurgical Society
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    • 제53권6호
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    • pp.323-330
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    • 2013
  • Objective : To develop a simple, reproducible model of disc degeneration in rabbits through percutaneous annular puncture and to confirm the degree of degeneration over time. Methods : Fifteen New Zealand white rabbits (4 to 5 months old and weighing approximately 3 to 3.5 kg each) underwent annular puncture of the L2-L3, L3-L4, and L4-L5 discs. Rabbits were sacrificed at 4, 8, or 20 weeks after puncture. For a longitudinal study to assess changes in disc height over time, serial X-rays were performed at 0, 2, 4, 8, and 20 weeks for rabbits in the 20-week group. Upon sacrifice, the whole spinal column and discs were extracted and analyzed with magnetic resonance imaging (MRI), real time reverse transcriptase-polymerase chain reaction, and histological staining. Results : The X-rays showed a slow, progressive decrease in disc height over time. Significant disc space narrowing compared to preoperative disc height was observed during the time period (p<0.001). The MRI grade, aggrecan, and matrix metalloprotease-13 mRNA expression and hematoxylin and eosin/safranin O/anti-collagen II staining were consistently indicative of degeneration, supporting the results of the X-ray data. Conclusion : Percutaneous annular puncture resulted in slow, reproducible disc degeneration that was confirmed by radiology, biochemistry, and histology. This in vivo model can be used to study and evaluate the safety and efficacy of biologic treatments for degenerative disc disease.

새로운 치료 방법 접근을 위한 C26 선암세포 기반의 Cancer Cachexia 동물모델 수립 (Model for Cancer Cachexia using C26 Adenocarcinoma-Induced Wasting Syndrome for Newer Therapeutic Approach)

  • 강은아;박종민;한영민;홍성표;조주영;유인경;오지영;함기백
    • Journal of Digestive Cancer Research
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    • 제5권2호
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    • pp.97-104
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    • 2017
  • Cancer cachexia는 지방조직과 근육계 조직의 손실에 따른 체중의 현격한 감소를 특징으로 하고 있어 궁극적으로는 암 치료제에 대한 반응을 낮출 뿐만 아니라, 삶의 양은 물론 질도 낮추게 되는 시급히 해결되어야 하는 미충족 의료수요중의 하나이다. 아직까지 임상에서는 수많은 노략에도 불구하고 일부 완화시킬 수 있는 약제가 있기는 하나, 전반적으로 해결이 가능한 약제나 치료 방법이 아직은 없는 실정이다. 그러므로 이를 해결할 수 있는 방법으로 동물모델이 필요한 질환이라 하겠다. 이러한 배경하에 연구자 등은 우선 동물모델을 수립하고 이를 기반으로 적절한 치료제를 개발하기 목적으로 본 연구에서는 C26 대장 선암 세포를 이용한 Cancer cachexia 동물모델을 수립하여 이 모델에서의 변화를 소개함으로써 향후 더 진보된 치료제 개발이나 병태생리를 연구하는데 도움을 주고자 본 연구를 시행하여 다음과 같은 결과를 얻을 수 있었다. C26 adenocarcinoma를 대퇴부 주입 후 시간 경과에 따라 몸무게의 변화가 현저하여 2주 이후에 유의한 몸무게의 감소, 식욕부진, 활동감소가 관찰되었고, 이때의 혈청 Cytokine 및 이를 조절하는 여러가지 전사인자의 변화가 선행되었고, 현저한 근육계의 근감소가 관찰되었으며, 실험동물은 3주에 40%가 사망하는 변화를 보였다. 연구자 등은 본 동물모델은 향후 새로운 치료약제 개발이나 Cancer cachexia 병태생리 연구에 매우 도움이 되는 수립하기 간편하며, 기저 분자생물학적 변화를 관찰할 수 있는 우수한 Cancer cachexia 모델이라 결론지을 수 있었다.

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Protective effects of PEP-1-Catalase on stress-induced cellular toxicity and MPTP-induced Parkinson's disease

  • Eom, Seon Ae;Kim, Dae Won;Shin, Min Jea;Ahn, Eun Hee;Chung, Seok Young;Sohn, Eun Jeong;Jo, Hyo Sang;Jeon, Su-Jeong;Kim, Duk-Soo;Kwon, Hyeok Yil;Cho, Sung-Woo;Han, Kyu Hyung;Park, Jinseu;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • 제48권7호
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    • pp.395-400
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    • 2015
  • Parkinson's disease (PD) is a neurodegenerative disability caused by a decrease of dopaminergic neurons in the substantia nigra (SN). Although the etiology of PD is not clear, oxidative stress is believed to lead to PD. Catalase is antioxidant enzyme which plays an active role in cells as a reactive oxygen species (ROS) scavenger. Thus, we investigated whether PEP-1-Catalase protects against 1-methyl-4-phenylpyridinium (MPP+) induced SH-SY5Y neuronal cell death and in a 1-methyl-4-phenyl-1,2,3,6-trtrahydropyridine (MPTP) induced PD animal model. PEP-1-Catalase transduced into SH-SY5Y cells significantly protecting them against MPP+-induced death by decreasing ROS and regulating cellular survival signals including Akt, Bax, Bcl-2, and p38. Immunohistochemical analysis showed that transduced PEP-1-Catalase markedly protected against neuronal cell death in the SN in the PD animal model. Our results indicate that PEP-1-Catalase may have potential as a therapeutic agent for PD and other oxidative stress related diseases. [BMB Reports 2015; 48(7): 395-400]