• 제목/요약/키워드: translational research

검색결과 527건 처리시간 0.023초

CRISPR/Cas9-mediated knockout of CD47 causes hemolytic anemia with splenomegaly in C57BL/6 mice

  • Kim, Joo-Il;Park, Jin-Sung;Kwak, Jina;Lim, Hyun-Jin;Ryu, Soo-Kyung;Kwon, Euna;Han, Kang-Min;Nam, Ki-Taek;Lee, Han-Woong;Kang, Byeong-Cheol
    • Laboraroty Animal Research
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    • 제34권4호
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    • pp.302-310
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    • 2018
  • CD47 (integrin-associated protein), a multi-spanning transmembrane protein expressed in all cells including red blood cells (RBCs) and leukocytes, interacts with signal regulatory protein ${\alpha}$ ($SIRP{\alpha}$) on macrophages and thereby inhibits phagocytosis of RBCs. Recently, we generated a novel C57BL/6J CD47 knockout ($CD47^{-/-}$ hereafter) mouse line by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease, and here report their hematological phenotypes. On monitoring their birth and development, $CD47^{-/-}$ mice were born viable with a natural male-to-female sex ratio and normally developed from birth through puberty to adulthood without noticeable changes in growth, food/water intake compared to their age and sex-matched wild-type littermates up to 26 weeks. Hematological analysis revealed a mild but significant reduction of RBC counts and hemoglobin in 16 week-old male $CD47^{-/-}$ mice which were aggravated at the age of 26 weeks with increased reticulocyte counts and mean corpuscular volume (MCV), suggesting hemolytic anemia. Interestingly, anemia in female $CD47^{-/-}$ mice became evident at 26 weeks, but splenomegaly was identified in both genders of $CD47^{-/-}$ mice from the age of 16 weeks, consistent with development of hemolytic anemia. Additionally, helper and cytotoxic T cell populations were considerably reduced in the spleen, but not in thymus, of $CD47^{-/-}$ mice, suggesting a crucial role of CD47 in proliferation of T cells. Collectively, these findings indicate that our $CD47^{-/-}$ mice have progressive hemolytic anemia and splenic depletion of mature T cell populations and therefore may be useful as an in vivo model to study the function of CD47.

언해의서 비교고찰을 통한 한의학용어의 번역표준안 - 『언해두창집요』, 『언해구급방』, 『언해태산집요』를 중심으로 (Standard Translation of Terms of Korean Medicine through Consideration of Chinese-Korean Collated Medical Classics - With focus on 『Eonhaegugeupbang』, 『Eonhaetaesanjipyo』 and 『Eonhaetaesanjipyo』 -)

  • 구현희;김현구;이정현;오준호;권오민
    • 한국한의학연구원논문집
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    • 제18권3호
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    • pp.49-61
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    • 2012
  • This article set out to develop an old Chinese - modern Korean collated terminology by analyzing and paralleling Chinese-Korean translational terms relevant to Korean medicine at a minimum meaning unit from "Eonhaegugeupbang", "Eonhaetaesanjipyo" and "Eonhaetaesanjipyo". Those are composed of original Chinese texts and their subsequent corresponding Korean translations. It tries to make a list of translational standards of Korean medicine terms by classifying the cases of translational ambiguity in terms of disease, body position, thumbnail-pressing acupuncture method, and disease-curing method. The above-mentioned ancient books are medical classics written by Huh Jun, the representative medical physician, and published by the Joseon government. Thus, they are appropriate enough as historically legitimate medical documents, from which are drawn out words and terms to form an old Chinese - modern Korean collation dictionary. This collation glossary will contribute to the increased relevance of data ming, or information retrieval. in a database system and information search engine of massive Korean medical records, by means of providing a novel way to obtaining synchronized results between the original writings of old Chinese and the secondary translated ones of modern Korean. The glossary will promote the collective but consistent translation of numerous old archives of Korean medicine and in other related fields as well.

TJP1 Contributes to Tumor Progression through Supporting Cell-Cell Aggregation and Communicating with Tumor Microenvironment in Leiomyosarcoma

  • Lee, Eun-Young;Kim, Minjeong;Choi, Beom K.;Kim, Dae Hong;Choi, Inho;You, Hye Jin
    • Molecules and Cells
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    • 제44권11호
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    • pp.784-794
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    • 2021
  • Leiomyosarcoma (LMS) is a mesenchymal malignancy with a complex karyotype. Despite accumulated evidence, the factors contributing to the development of LMS are unclear. Here, we investigated the role of tight-junction protein 1 (TJP1), a membrane-associated intercellular barrier protein during the development of LMS and the tumor microenvironment. We orthotopically transplanted SK-LMS-1 cells and their derivatives in terms of TJP1 expression by intramuscular injection, such as SK-LMS-1 Sh-Control cells and SK-LMS-1 Sh-TJP1. We observed robust tumor growth in mice transplanted with LMS cell lines expressing TJP1 while no tumor mass was found in mice transplanted with SK-LMS-1 Sh-TJP1 cells with silenced TJP1 expression. Tissues from mice were stained and further analyzed to clarify the effects of TJP1 expression on tumor development and the tumor microenvironment. To identify the TJP1-dependent factors important in the development of LMS, genes with altered expression were selected in SK-LMS-1 cells such as cyclinD1, CSF1 and so on. The top 10% of highly expressed genes in LMS tissues were obtained from public databases. Further analysis revealed two clusters related to cell proliferation and the tumor microenvironment. Furthermore, integrated analyses of the gene expression networks revealed correlations among TJP1, CSF1 and CTLA4 at the mRNA level, suggesting a possible role for TJP1 in the immune environment. Taken together, these results imply that TJP1 contributes to the development of sarcoma by proliferation through modulating cell-cell aggregation and communication through cytokines in the tumor microenvironment and might be a beneficial therapeutic target.

Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells

  • Park, Seulki;Kim, Kidae;Haam, Keeok;Ban, Hyun Seung;Kim, Jung-Ae;Park, Byoung Chul;Park, Sung Goo;Kim, Sunhong;Kim, Jeong-Hoon
    • BMB Reports
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    • 제54권6호
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    • pp.305-310
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    • 2021
  • Cereblon (CRBN) is a multi-functional protein that acts as a substrate receptor of the E3 ligase complex and a molecular chaperone. While CRBN is proposed to function in mitochondria, its specific roles are yet to be established. Here, we showed that knockdown of CRBN triggers oxidative stress and calcium overload in mitochondria, leading to disruption of mitochondrial membrane potential. Notably, long-term CRBN depletion using PROteolysis TArgeting Chimera (PROTAC) induced irreversible mitochondrial dysfunction, resulting in cell death. Our collective findings indicate that CRBN is required for mitochondrial homeostasis in cells.

Added Mass Estimation of Square Sections Coupled with a Liquid Using Finite Element Method

  • Jeong, Kyeong Hoon;Jhung, Myung Jo
    • Nuclear Engineering and Technology
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    • 제49권1호
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    • pp.234-244
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    • 2017
  • Natural frequencies of immersed square sections decrease due to a contribution of added mass to the movement of square sections. In this study, natural frequencies of square sections are obtained as a function of gap size between the square section and a rigid square wall using the finite element method. Additionally, they are used to extract the added mass effect on translational and rotation motions. Published information and studies on the translational and torsional vibration of square beams are also examined for practical use. D coupling of a square section is also investigated for multiple square sections. The suggested added mass estimation can be applicable to the spent fuel storage design of a pressurized light water modulated nuclear power plant.

New Digital Esthetic Rehabilitation Technique with Three-dimensional Augmented Reality: A Case Report

  • Hang-Nga, Mai;Du-Hyeong, Lee
    • Journal of Korean Dental Science
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    • 제15권2호
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    • pp.166-171
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    • 2022
  • This case report describes a dynamic digital esthetic rehabilitation procedure that integrates a new three-dimensional augmented reality (3D-AR) technique to treat a patient with multiple missing anterior teeth. The prostheses were designed using computer-aided design (CAD) software and virtually trialed using static and dynamic visualization methods. In the static method, the prostheses were visualized by integrating the CAD model with a 3D face scan of the patient. For the dynamic method, the 3D-AR application was used for real-time tracking and projection of the CAD prostheses in the patient's mouth. Results of a quick survey on patient satisfaction with the two visualization methods showed that the patient felt more satisfied with the dynamic visualization method because it allowed him to observe the prostheses directly on his face and be more proactive in the treatment process.

TRAIL Based Therapy: Overview of Mesenchymal Stem Cell Based Delivery and miRNA Controlled Expression of TRAIL

  • Attar, Rukset;Sajjad, Farhana;Qureshi, Muhammad Zahid;Tahir, Fizza;Hussain, Ejaz;Fayyaz, Sundas;Farooqi, Ammad Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권16호
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    • pp.6495-6497
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    • 2014
  • Rapidly increasing number of outstanding developments in the field of TRAIL mediated signaling have revolutionized our current information about inducing and maximizing TRAIL mediated apoptosis in resistant cancer cells. Data obtained with high-throughput technologies have provided finer resolution of tumor biology and now it is known that a complex structure containing malignant cells strictly coupled with a large variety of surrounding cells constitutes the tumor stroma. Utility of mesenchymal stem cells (MSCs) as cellular vehicles has added new layers of information. There is sufficient experimental evidence substantiating efficient gene deliveries into MSCs by retroviral, lentiviral and adenoviral vectors. Moreover, there is a paradigm shift in molecular oncology and recent high impact research has shown controlled expression of TRAIL in cancer cells on insertion of complementary sequences for frequently downregulated miRNAs. In this review we have attempted to provide an overview of utility of TRAIL engineered MSCs for effective killing of tumor and potential of using miRNA response elements as rheostat like switch to control expression of TRAIL in cancer cells.

Functional roles and mechanisms of ginsenosides from Panax ginseng in atherosclerosis

  • Xue, Qianqian;He, Ningning;Wang, Zhibin;Fu, Xiuxiu;Aung, Lynn Htet Htet;Liu, Yan;Li, Min;Cho, Jae Youl;Yang, Yanyan;Yu, Tao
    • Journal of Ginseng Research
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    • 제45권1호
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    • pp.22-31
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    • 2021
  • Atherosclerosis (AS) is a leading cause of cardiovascular diseases (CVDs) and it results in a high rate of death worldwide, with an increased prevalence with age despite advances in lifestyle management and drug therapy. Atherosclerosis is a chronic progressive inflammatory process, and it mainly presents with lipid accumulation, foam cell proliferation, inflammatory response, atherosclerotic plaque formation and rupture, thrombosis, and vascular calcification. Therefore, there is a great need for reliable therapeutic drugs or remedies to cure or alleviate atherosclerosis and reduce the societal burden. Ginsenosides are natural steroid glycosides and triterpene saponins obtained mainly from the plant ginseng. Several recent studies have reported that ginsenosides have a variety of pharmacological activities against several diseases including inflammation, cancer and cardiovascular diseases. This review focuses on describing the different pharmacological functions and underlying mechanisms of various active ginsenosides (Rb1,-Rd, -F, -Rg1, -Rg2, and -Rg3, and compound K) for atherosclerosis, which could provide useful insights for developing novel and effective anti-cardiovascular drugs.

The Alcohol-inducible form of Cytochrome P450 (CYP 2E1): Role In Toxicology and Regulation of Expression

  • Novak, Raymond F.;Woodcroft, Kimberley J.
    • Archives of Pharmacal Research
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    • 제23권4호
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    • pp.267-282
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    • 2000
  • Cytochrome P45O (CYP) 2E1 catalyzes the metabolism of a wide variety of therapeutic agents, procarcinogens, and low molecular weight solvents. CYP2E1-catalyzed metabolism may cause toxicity or DNA damage through the production of toxic metabolites, oxygen radicals, and lipid peroxidation. CYP2E1 also plays a role in the metabolism of endogenous compounds including fatty acids and ketone bodies. The regulation of CYP2E1 expression is complex, and involves transcriptional, post-transcriptional, translational, and post-translational mechanisms. CYP2E1 is transcriptionally activated in the first few hours after birth. Xenobiotic inducers elevate CYP2E1 protein levels through both increased translational efficiency and stabilization of the protein from degradation, which appears to occur primarily through ubiquitination and proteasomal degradation. CYP2E1 mRNA and protein levels are altered in response to pathophysiologic conditions by hormones including insulin, glucagon, growth hormone, and leptin, and growth factors including epidermal growth factor and hepatocyte growth factor, providing evidence that CYP2E1 expression is under tight homeostatic control.

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