• Title/Summary/Keyword: bone disease

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CRISPR/Cas9-mediated knockout of Rag-2 causes systemic lymphopenia with hypoplastic lymphoid organs in FVB mice

  • Kim, Joo-Il;Park, Jin-Sung;Kim, Hanna;Ryu, Soo-Kyung;Kwak, Jina;Kwon, Euna;Yun, Jun-Won;Nam, Ki-Taek;Lee, Han-Woong;Kang, Byeong-Cheol
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.166-175
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    • 2018
  • Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. Rag-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of Rag-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of Rag-2, we recently established a new Rag-2 knockout FVB mouse line ($Rag-2^{-/-}$) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. $Rag-2^{-/-}$ mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in $Rag-2^{-/-}$ mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in $Rag-2^{-/-}$ mice. These findings indicate that our $Rag-2^{-/-}$ mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.

Cytological Study on the Cause of the Osteoporotic Side Effects of Adefovir Dipivoxil (아데포비어의 부작용인 골다공증 원인 규명을 위한 세포학적 연구)

  • Park, Ho
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.3
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    • pp.379-385
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    • 2019
  • Osteoporosis is a disease that increases the risk of fractures by inducing a decrease in bone strength by the changes in hormones and a decrease in minerals. Recent reports have indicated that the long-term administration of Adefovir dipivoxil (ADV), which is used as a treatment for the hepatitis virus and AIDS, may have osteoporotic side effects. On the other hand, there are few studies on the cytopathic correlation of these causes. In this study, the biological relevance of ADV was evaluated using osteoblast hFOB1.19 and vascular endothelial cell HUVEC. First, the cells were treated with ADV at different concentrations, and DAPI and crystal violet staining were performed for morphological analysis of each cell and nucleus. A CCK-8 assay, real-time PCR, alkaline phosphatase (ALP) staining, and activity was performed to evaluate the drug effects on cell proliferation, gene expression, and osteoblast differentiation. As a result, ADV induced cell hypertrophy in hFOB1.19 cells and HUVEC cells. Furthermore, ADV not only inhibited cell proliferation and TGF-${\beta}$ expression but was also involved in osteoblast differentiation. Overall, these results provide basic data to help better understand the mechanism of ADV-induced osteoporosis and its clinical implications.

A Novel Anti-PD-L1 Antibody Exhibits Antitumor Effects on Multiple Myeloma in Murine Models via Antibody-Dependent Cellular Cytotoxicity

  • Ahn, Jae-Hee;Lee, Byung-Hyun;Kim, Seong-Eun;Kwon, Bo-Eun;Jeong, Hyunjin;Choi, Jong Rip;Kim, Min Jung;Park, Yong;Kim, Byung Soo;Kim, Dae Hee;Ko, Hyun-Jeong
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.166-174
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    • 2021
  • Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

Home Healing Cases for Gangrene Sores and Diseases Using Fake Energy Salts (Fake Energy Salts을 이용한 욕창 및 질병의 자택치유 사례)

  • Kim, Min-Ju
    • Journal of Naturopathy
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    • v.9 no.2
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    • pp.71-78
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    • 2020
  • Purpose: This study was to present home-care cases of gangrene sores or prevalent diseases using fake energy salt (FES) water containing energy. Methods: The health functional foods used for disease management were FES Water. Each product was Myeongil Leaf powder, dried yeast, propolis, fermented organic calcium, and royal jelly. Changes were investigated after taking this food. Some of them were combined with hospital treatment, and most of them were experienced by patients at home while managing the affected area. Results: One patient with high fever swine flu, who was treated in a hospital, had a fever dropping to the normal range in 2 hours, and one patient with a leg fracture healed in about six weeks, and one patient had bone adhesion in 2 weeks. Patients with rhinitis recovered after taking FES, and the intraocular pressure of patients with damaged retinopathy fell from 40 mmHg to 20 mmHg after taking FES. One patient with postpartum sequelae was said to have improved their aching limbs four days, and a Covid-19 confirmed patient admitted to the hospital was discharged ten days after starting taking FES during treatment. The size of the gangrene sores in 19 subjects initially ranged from 1 to 7 cm. Most of them were alleviated or healed by continuing to manage them at home with health functional food intake and FES for two weeks to a year. Conclusions: The above results are personal experiences and health functions, such as fake energy salts. It was possible to recognize that food was helpful for health promotion, but no final medical diagnosis was made.

Long-term Stability after Reduction of Mandible Fracture by Keyhole Plate: Evaluation at the Time of Plate Removal

  • Cheon, Kyeong-Jun;Cho, Seoung-Won;Jang, Won-Seok;Kim, Ju-Won;Yang, Byoung-Eun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.42
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    • pp.6.1-6.6
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    • 2020
  • Background: Various types of miniplates have been developed and used for the reduction of facial bone fractures. We introduced Yang's Keyhole (YK) plate, and reported on its short-term stability. The purpose of this study was to evaluate the long-term stability of the YK plate, as a follow-up study, by examining the patients who had used the YK plate among the patients with the reduction of mandible fractures and who visited for plate removal. Methods: We reviewed the medical records of 16 patients who underwent mandibular fracture fixation using a YK plate (group I) and 17 patients who underwent mandibular fracture fixation using a conventional plate (group II). Assessment was then made on malunion, occlusal stability, discomfort during the application, and clinical symptoms. Results: From January 2015 to December 2017, a total of 36 patients underwent mandibular fracture surgery using a YK plate. A total of 16 patients received plate removal. Among them, 15 were male and 1 female. The average age was 26 years. The applied surgical sites were the 12 on mandibular angle, 4 on mandibular symphysis, and 2 on subcondyle. The application period of YK plate was an average of 335 days. During the same period, 45 people underwent surgery on the conventional plate. A total of 17 patients received plate removal. Among them, 15 were male and 2 females. The average age was 36 years. The applied surgical sites were the 8 on mandibular angle, 4 on mandibular symphysis, and 2 on subcondyle. The application period of the conventional plate was an average of 349 days. No malocclusion occurred at the time of removal, and occlusion was stable. No patient complained of joint disease or discomfort. Conclusion: The YK plate system, in which the screw was first inserted and the plate was applied, for clinical convenience did not cause any particular problem and no significant difference from the conventional plate.

The Development of Web-based Nutrition Information Contents for Older Adults : Content Analysis and Card-sorting process (노인대상 영양정보 웹사이트 컨텐츠 개발 : 내용분석과 카드소팅과정(Card-sorting process))

  • Chae, In-Sook;Yang, Il-Sun;Lee, Pil-Soon;Chung, Yoo-Sun;Kim, Young-Shin;Jang, Yoon-Jung
    • Journal of the Korean Society of Food Culture
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    • v.22 no.2
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    • pp.235-245
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    • 2007
  • This study was undertaken to develop web-based nutrition information contents for the older adults. Twenty six domestic web-sites were analyzed and then 12 foreign web-sites and 4 education materials for the elderly of foreign university were benchmarked. Also a lot of literatures on elderly education program were reviewed. A card-sorting task was performed with 8 older adults to ascertain how the target audience organized information about nutrition. The results were as fellows. Among 26 domestic web-sites, 2 sites(7.7%) were only for the elderly. Main topics of information contents for the elderly included 'Importance of Healthy Eating', 'DRI', 'Dietary Guidelines'. Four of twelve foreign web-sites were for the elderly nutrition education. Topics of 'Dietary Guideline', 'Meal Program' were found in 4 sites and 'Importance of Healthy Eating', 'Diet & Disease', 'DRI, 'Food Guide Pyramid', 'Nutrition Fact Labels' were found in 3 sites. Education materials of foreign university dealt with basic information on 'nutrient needs changes related with aging', 'Heart & Bone Healthy Eating Plan', 'Food Guide Pyramid'. Also topics on 'Eating on a budget', 'Eating Out Guideline' were included for practical use for the elderly. Based on card-sorting process, contents framework for web-site was developed and 4 main menus for framework were respectively named as 'Nutrition', 'Meals', 'Foods'. 'Check up Nutritional Health' by panel discussion. Finally we developed nutrition information contents for 4 main menus. We focused on helping older adults recognize the importance of healthy eating and apply the nutrition information to practical use. We expect that the developed framework of contents can be a guideline for indentifying the information needs of older adults in developing effective nutrition intervention program. And we suggest that the survey for target people should be peformed for the web-site to be user-friendly designed and the developed contents be evaluated and revised in the near future.

Modulation of Inflammation by Plant Resources (식물 자원을 활용한 염증반응 조절)

  • Ha-Nul Lee;Su Hui Seong;Bo-Ram Kim;Jin-Ho Kim;Chan Seo;Sua Im;Jung Eun Kim;Ji Min Jung;Jin-Woo Jeong
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2023.04a
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    • pp.17-17
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    • 2023
  • Chrysanthemum zawadskii (C. zawadskii) is used in traditional East Asian medicine for the treatment of various diseases, including inflammatory disease. However, it has remained unclear whether extracts of C. zawadskii inhibit inflammasome activation in macrophages. The present study assessed the inhibitory effect of an ethanol extract of C. zawadskii (CZE) on the activation of the inflammasome in macrophages and the underlying mechanism. Bone marrow[-derived macrophages (BMDMs) were obtained from wild-type C57BL/6 mice. The release of IL-1β and lactate dehydrogenase in response to nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activators, such as ATP, nigericin and monosodium urate (MSU) crystals, was significantly decreased by CZE in lipopolysaccharide(LPS)-primed BMDMs. Western blotting revealed that CZE inhibited ATP-induced caspase-1 cleavage and IL-1β maturation. To investigate whether CZE inhibits the priming step of the NLRP3 inflammasome, we confirmed the role of CZE at the gene level using RT-qPCR. CZE also downregulated the gene expression of NLRP3 and pro-IL-1β as well as NF-κB activation in BMDMs in response to LPS. Apoptosis associated speck-like protein containing a caspase-recruitment domain (CARD) oligomerization and speck formation by NLRP3 inflammasome activators were suppressed by CZE. By contrast, CZE did not affect NLR family CARD domain containing protein 4 (NLRC4) or absent in melanoma 2 (AIM2) inflammasome activation in response to Salmonella typhimurium and poly(dA:dT) in LPS-primed BMDMs, respectively. The results revealed that three key components of CZE, namely linarin, 3,5-dicaffeoylquinic acid and chlorogenic acid, decreased IL-1β secretion in response to ATP, nigericin and MSU. These findings suggest that CZE effectively inhibited activation of the NLRP3 inflammasome.

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The correlation between 『Shanghanlun』 'Seizure' and epilepsy : Case series (『상한론(傷寒論)』 '발작(發作)'과 뇌전증의 연관성 : 다수증례보고)

  • Sung Jun Lee;Min hwan Kim;Young Gap Yun;Kyu Sang Lim;Soong-in Lee
    • 대한상한금궤의학회지
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    • v.14 no.1
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    • pp.1-26
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    • 2022
  • Objectives: We aimed to confirm the safety and effectiveness of the decoction of Sibjo-tang, which is a powder type purgative. In addition, we checked whether the '發作' of 『Shanghanlun』 can be interpreted to have the same meaning as "seizure" in English. By confirming these objectives, we intend to lead the progress in the application of Sibjo-tang and to expand the clinical application of the 152nd provision and Sibjo-tang. Methods: We analyzed the medical records of patients who visited Apgujeongjeongin Oriental Clinic and Almyeon Oriental Clinic for seizures. We confirmed side effects in patients who took Sibjo-tang for a long time. Sibjo-tang was prepared as a hot water extract by using 5 g each of Euphorbiae Pekinensis Radix, Eurphobiae Kansui Radix, and Genkwae Flos and 15 g of Zizyphi Fructus. The "seizure" recorded in the 152nd provision was interpreted through the shape analysis of Oracle bone scripts. The seizure frequency of patients diagnosed with epilepsy after taking Sibjo-tang was compared, and we analyzed other symptoms and psychosocial conditions associated with seizures at the first episode. Results: No side effects were found in 7 patients who took Sibjo-tang for 16.57 ± 14.10 months. Seizures were eliminated in 6 cases while taking Sibjo-tang and significantly decreased in 1 case. Frequent indigestion (in 7 cases), mild exhaustion (in 5 cases), and inferiority complex (in 5 cases) were identified as accompanying pathogenic conditions. The "seizure" in the 152nd provision was interpreted as "a state of being stabbed by a sharp substance in clothes", confirming a deep connection with epileptic seizures. Conclusions: The results suggest that using a decoction of Sibjo-tang is safe and efficacious. In addition, the necessity of conducting an advanced study on epileptic seizures accompanied by frequent indigestion using Sibjo-tang was confirmed.

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Susceptibility-Weighted Imaging as a Distinctive Imaging Technique for Providing Complementary Information for Precise Diagnosis of Neurologic Disorder (신경계 질환에 관한 정확한 진단을 위해 다양한 보완 정보를 제공하는 독특한 영상 기법으로서의 자기화율 강조 영상)

  • Byeong-Uk Jeon;In Kyu Yu;Tae Kun Kim;Ha Youn Kim;Seungbae Hwang
    • Journal of the Korean Society of Radiology
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    • v.82 no.1
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    • pp.99-115
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    • 2021
  • Various sequences have been developed for MRI to aid in the radiologic diagnosis. Among the various MR sequences, susceptibility-weighted imaging (SWI) is a high-spatial-resolution, three-dimensional gradient-echo MR sequence, which is very sensitive in detecting deoxyhemoglobin, ferritin, hemosiderin, and bone minerals through local magnetic field distortion. In this regard, SWI has been used for the diagnosis and treatment of various neurologic disorders, and the improved image quality has enabled to acquire more useful information for radiologists. Here, we explain the principle of various signals on SWI arising in neurological disorders and provide a retrospective review of many cases of clinically or pathologically proven disease or components with distinctive imaging features of various neurological diseases. Additionally, we outline a short and condensed overview of principles of SWI in relation to neurological disorders and describe various cases with characteristic imaging features on SWI. There are many different types diseases involving the brain parenchyma, and they have distinct SWI features. SWI is an effective imaging tool that provides complementary information for the diagnosis of various diseases.

Pathophysiology and MRI Findings of Infectious Spondylitis and the Differential Diagnosis (감염성 척추염과 감별질환의 병태생리와 MRI 소견)

  • Sunjin Ryu;Yeo Ju Kim;Seunghun Lee;Jeongah Ryu;Sunghoon Park;Jung Ui Hong
    • Journal of the Korean Society of Radiology
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    • v.82 no.6
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    • pp.1413-1440
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    • 2021
  • On MRI, abnormal signals of the intervertebral disc, destruction of the upper and lower vertebral body endplate around the disc, and bone marrow edema around the endplate are considered typical findings of infectious spondylitis. These findings can also appear in various non-infectious spinal diseases, such as degenerative changes, acute Schmorl's node, spondyloarthropathy, synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO), chronic recurrent multifocal osteomyelitis, and calcium pyrophosphate dihydrate crystal deposition disease. The imaging findings of infectious spondylitis that can be differentiated from these non-infectious spinal diseases on MRI are high signal intensity and abscess of the disc space, an abscess in the paraspinal soft tissue, and the loss of the linear low signal intensity on T1-weighted images of the bony endplate. However, these differentiation points do not always apply since there are many similarities in the imaging findings of infectious and non-infectious diseases. Therefore, for an accurate diagnosis, it is important to know the imaging characteristics related to the pathophysiology of not only infectious spondylitis but also non-infectious spinal diseases, which requires differentiation from infection.