• 제목/요약/키워드: translational medicine

검색결과 402건 처리시간 0.03초

Role of post-translational modifications on the alpha-synuclein aggregation-related pathogenesis of Parkinson's disease

  • Yoo, Hajung;Lee, Jeongmin;Kim, Bokwang;Moon, Heechang;Jeong, Huisu;Lee, Kyungmi;Song, Woo Jeung;Hur, Junho K.;Oh, Yohan
    • BMB Reports
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    • 제55권7호
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    • pp.323-335
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    • 2022
  • Together with neuronal loss, the existence of insoluble inclusions of alpha-synuclein (α-syn) in the brain is widely accepted as a hallmark of synucleinopathies including Parkinson's disease (PD), multiple system atrophy, and dementia with Lewy body. Because the α-syn aggregates are deeply involved in the pathogenesis, there have been many attempts to demonstrate the mechanism of the aggregation and its potential causative factors including post-translational modifications (PTMs). Although no concrete conclusions have been made based on the previous study results, growing evidence suggests that modifications such as phosphorylation and ubiquitination can alter α-syn characteristics to have certain effects on the aggregation process in PD; either facilitating or inhibiting fibrillization. In the present work, we reviewed studies showing the significant impacts of PTMs on α-syn aggregation. Furthermore, the PTMs modulating α-syn aggregation-induced cell death have been discussed.

Efficacy of Korean Red Ginseng Supplementation on Eradication Rate and Gastric Volatile Sulfur Compound Levels after Helicobacter pylori Eradication Therapy

  • Lee, So-Jung;Park, Ji-Young;Choi, Ki-Seok;Ock, Chan-Young;Hong, Kyung-Sook;Kim, Yoon-Jae;Chung, Jun-Won;Hahm, Ki-Baik
    • Journal of Ginseng Research
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    • 제34권2호
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    • pp.122-131
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    • 2010
  • This clinical study was performed to evaluate whether supplementation of proton pump inhibitor (PPI)-based triple therapy with Korean red ginseng can enhance Helicobacter pylori (H. pylori) eradication and reduce levels of halitosis-associated volatile sulfur compounds (VSCs) in the stomach. Seventy-six patients were randomized into an eradication regimen-only group (n=45) or an eradication regimen plus 10 weeks of Korean red ginseng supplementation group (n=31). The eradication regimen consisted of PPI b.i.d., clarithromycin 500 mg b.i.d., and amoxicillin 1 g b.i.d.. for seven days. Korean red ginseng supplementation commenced on the last day of the eradication regimen. $^{13}C$-urea breath test and halimeter measurements were performed prior to protocol repetition. By intention-to-treat analysis, the H. pylori eradication rate in the Korean red ginseng group (77.4%, 24 of 31) was higher than that in the control group (45.0%, 26 of 45). However, by per protocol analysis, the eradication rate in the Korean red ginseng group was significantly higher than that in the control group (92.3%, 24/26 vs. 69.4%, 26/38; p<0.05). H. pylori infection was significantly associated with increased VSC levels. However, VSC levels decreased significantly in the Korean red ginseng group (p<0.05). In conclusion, supplementation of triple therapy with Korean red ginseng increased the H. pylori eradication rate and led to significant reductions in VSC levels, suggesting the usefulness of this substance in combating H. pylori infection.

BIOPAK을 이용한 하악의 회전운동에 관한 연구 (A Study on the Mandibular Rotational Movement using Biopak Sysytem)

  • Kyung-Soo Han
    • Journal of Oral Medicine and Pain
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    • 제19권2호
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    • pp.193-203
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    • 1994
  • The author performed this study for investigation of the magnitude of mandibular positional change caused by joint sound during mandibular opening and closing movement. There have been many studies stated mandibular border movement or other functional movement, and there also have been many studies reported clicking sound related to mandibular movement speed, trajectory and clinicl course of temporomandibular disorders(TMDs), but there have not been so many studies stated spatial mandibular position accompanied by joint sound. For this study 46 TM joint from the patients with TMDs were used and they were compared by character and occuring phase of the joint sound. Synchronized data which were amplitude and frequency of joint sound and amount of mandibular positional change were collected through sonopak and BioEGN rotate of Biopak system, respectively. Mandibular position was analyzed for translational and rotational movement change between before and after joint sound. The obtained data were processed with SAS program and summary of this paper were as follows : 1. Mean value of the amount of translational movement in whole joints were 6.0mm in vertical direction, 3.3mm in anteroposterior direction and 0.8mm in lateral direction between before and after joint sound. 2. Mean value of the amount of translational movement in clicking joinnts showed slightly increased tendency than in popping joints. 3. The amount of mandibular change in translational movement during closing phase were more than during opening phase. 4. The amount of mandibular rotational change in whole joints were $1.1^{\circ}$, 1.0mm in frontal plane and $0.9^{\circ}$, and 0.8mm in horizontal plane. 5. The amount of rotational movement were more in clicking joints than in popping joints and were more during closing phase than during opening phase, but statistically significance were showed only in frontal plane.

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Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

  • Lee, Eunjo;Song, Min-ji;Lee, Hae-Ahm;Kang, Seol-Hee;Kim, Mina;Yang, Eun Kyoung;Lee, Do Young;Ro, Seonggu;Cho, Joong Myung;Kim, Inkyeom
    • The Korean Journal of Physiology and Pharmacology
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    • 제20권5호
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    • pp.477-485
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    • 2016
  • CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

Increase of Vδ2+ T Cells That Robustly Produce IL-17A in Advanced Abdominal Aortic Aneurysm Tissues

  • In-Ho Seo;Seung-Jun Lee;Tae Wook Noh;Jung-Hwan Kim;Hyun-Chel Joo;Eui-Cheol Shin;Su-Hyung Park;Young-Guk Ko
    • IMMUNE NETWORK
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    • 제21권2호
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    • pp.17.1-17.10
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    • 2021
  • Abdominal aortic aneurysm (AAA) is a chronic dilation of the aorta with a tendency to enlarge and eventually rupture, which constitutes a major cause of cardiovascular mortality. Although T-cell infiltrates have been observed in AAA, the cellular, phenotypic, and functional characteristics of these tissue-infiltrating T cells are not fully understood. Here, we investigated the proportional changes of T-cell subsets-including CD4+ T cells, CD8+ T cells, and γδ T cells-and their effector functions in AAAs. We found that Vδ2+ T cells were presented at a higher frequency in aortic aneurysmal tissue compared to normal aortic tissue and PBMCs from patients with AAA. In contrast, no differences were observed in the frequencies of CD4+, CD8+, and Vδ1+ T cells. Moreover, we observed that the Vδ2+ T cells from AAA tissue displayed immunophenotypes indicative of CCR5+ non-exhausted effector memory cells, with a decreased proportion of CD16+ cells. Finally, we found that these Vδ2+ T cells were the main source of IL-17A in abdominal aortic aneurysmal tissue. In conclusion, our results suggest that increased Vδ2+ T cells that robustly produce IL-17A in aortic aneurysmal tissue may contribute to AAA pathogenesis and progression.

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.

Detection of MicroRNA-21 Expression as a Potential Screening Biomarker for Colorectal Cancer: a Meta-analysis

  • Jiang, Jian-Xin;Zhang, Na;Liu, Zhong-Min;Wang, Yan-Ying
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권18호
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    • pp.7583-7588
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    • 2014
  • Background: Colorectal cancer (CRC) is a major cause of cancer-related death and cancer-related incidence worldwide. The potential of microRNA-21 (miR-21) as a biomarker for CRC detection has been studied in several studies. However, the results were inconsistent. Therefore, we conducted the present meta-analysis to systematically assess the diagnostic value of miR-21 for CRC. Materials and Methods: Using a random-effect model, the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to evaluate the diagnostic performance of miR-21 for CRC. A summary receiver operating characteristic (SROC) curve and an area under the curve (AUC) were also generated to assess the diagnosis accuracy of miR-21 for CRC. Q test and I2 statistics were used to assess between-study heterogeneity. Publication bias was evaluated by the Deeks' funnel plot asymmetry test. Results: A total of 986 CRC patients and 702 matched healthy controls from 8 studies were involved in the meta-analysis. The pooled results for SEN, SPE, PLR, NLR, DOR, and AUC were 57% (95%CI: 39%-74%), 87% (95%CI: 78%-93%), 4.4 (95%CI: 2.4-8.0), 0.49 (95%CI: 0.32-0.74), 9 (95%CI: 4-22), and 0.83 (95%CI: 0.79-0.86), respectively. Subgroup analyses further suggested that blood-based studies showed a better diagnostic accuracy compared with feces-based studies, indicating that blood may be a better matrix for miR-21 assay and CRC detection. Conclusions: Our findings suggest that miR-21 has a potential diagnostic value for CRC with a moderate level of overall diagnostic accuracy. Hence, it could be used as auxiliary means for the initial screening of CRC and avoid unnecessary colonoscopy, which is an invasive and expensive procedure.

굴곡과 신전 수동운동 상태에서 개별경추의 진자운동 및 병진운동의 운동학적인 특징 (Kinematical Characteristics of the Translational and Pendular Movements of each Cervical Vertebra at the Flexion and Extension Motion)

  • 박성혁;최한성;홍훈표;고영관
    • Journal of Trauma and Injury
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    • 제19권2호
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    • pp.126-134
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    • 2006
  • Purpose: The aim of this study was to determine the kinematical characteristics of the pendular and the translational movements of each cervical vertebra at flexion and extension for understanding the mechanism of injury to the cervical spine. Methods: Twenty volunteers, young men (24~37 years), with clinically and radiographically normal cervical spines were studied. We induced two directional passive movements and then took X-ray pictures. The range of pendular movement could be measured by measuring the variation of the distance between the center point of two contiguous cervical vertebrae, and the range of translational movement could be measured by measuring the variation of the shortest distance between the center point of a vertebra and an imaginary line connecting the center points of two lower contiguous cervical vertebrae. The measurements were done by using a picture archiving and communicating system (PACS). Results: The total length of all cervical vertebrae in the neutral position was, on average, 133.66 mm, but in both flexion and extension, the lengths were widened to 134.83 mm and 134.79 mm, respectively. The directions of both the pendular and the translational movements changed at the $2^{nd}$ cervical vertebra, and the ranges of both movements were significantly larger from the $5^{th}$ cervical vertebra to the $7^{th}$ cervical vertebra for flexion and combined flexion and extension motion (p<0.05). Conclusion: The kinematical characteristics for flexion and extension motions were variable at each level of cervical vertebrae. The $1^{st}$ and the $2^{nd}$ cervical vertebrae and from the $5^{th}$ to the $7^{th}$ cervical vertebrae were the main areas of cervical spinal injury. This shows, according to "Hook's law," that the tissues supporting this area could be weak, and that this area is sensitive to injury.