• 제목/요약/키워드: Human trials

검색결과 386건 처리시간 0.03초

Limited in vitro differentiation of porcine induced pluripotent stem cells into endothelial cells

  • In-Won Lee;Hyeon-Geun Lee;Dae-Ky Moon;Yeon-Ji Lee;Bo-Gyeong Seo;Sang-Ki Baek;Tae-Suk Kim;Cheol Hwangbo;Joon-Hee Lee
    • 한국동물생명공학회지
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    • 제38권3호
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    • pp.109-120
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    • 2023
  • Background: Pluripotent stem cells (PSCs) including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) offer the immense therapeutic potential in stem cell-based therapy of degenerative disorders. However, clinical trials of human ESCs cause heavy ethical concerns. With the derivation of iPSCs established by reprogramming from adult somatic cells through the transgenic expression of transcription factors, this problems would be able to overcome. In the present study, we tried to differentiate porcine iPSCs (piPSCs) into endothelial cells (ECs) for stem cell-based therapy of vascular diseases. Methods: piPSCs (OSKMNL) were induced to differentiation into ECs in four differentiation media (APEL-2, APEL-2 + 50 ng/mL of VEGF, EBM-2, EBM-2 + 50 ng/mL of VEGF) on cultured plates coated with matrigel® (1:40 dilution with DMEM/F-12 medium) for 8 days. Differentiation efficiency of these cells were exanimated using qRT-PCR, Immunocytochemistry, Western blotting and FACS. Results: As results, expressions of pluripotency-associated markers (OCT-3/4, SOX2 and NANOG) were higher observed in all porcine differentiated cells derived from piPSCs (OSKMNL) cultured in four differentiation media than piPSCs as the control, whereas endothelial-associated marker (CD-31) in the differentiated cells was not expressed. Conclusions: It can be seen that piPSCs (OSKMNL) were not suitable to differentiate into ECs in the four differentiation media unlike porcine epiblast stem cells (pEpiSCs). Therefore, it would be required to establish a suitable PSCs for differentiating into ECs for the treatment of cardiovascular diseases.

육상 창던지기 기록에 미치는 운동학적 요인의 탐색: 다차원적 다중회귀를 활용한 성과 예측 변수 분석 (Investigation of Biomechanical Factors in Track and Field Javelin Performance: A Multidimensional Analysis of Predictive Variables through Multiple Regression Analysis)

  • Ho-Jong Gil;Jin Joo Yang;Jong Chul Park;Young Sun Lee;Jae Myoung Park
    • 한국운동역학회지
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    • 제33권4호
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    • pp.175-184
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    • 2023
  • Objective: The purpose of this study is to investigate the effects of human motion and javelin kinematics during the energy transfer in javelin throwing on records, and to provide evidence-based training insights for athletes and coaches to enhance records. Method: Three javelin throw athletes (age: 22.67 ± 0.58 years, height: 178.33 ± 7.37 cm, weight: 83.67 ± 1.15 kg) were recruited for this study. Each athlete attempted ten maximum record trials, and the kinematic data from each performance were analyzed to determine their influence on the records. The Theia3d Markerless system was used for motion analysis. Results: Key factors were modeled and identified at each moment. In E1, main variables were COM Y (𝛽 8.162, p<.05) and COM velocity Z (𝛽 -72.489, p<.05); in E2, COM X (𝛽 -17.604, p<.05); in E3, COM X (𝛽 -18.606, p<.05), COM velocity Y (𝛽 38.694, p<.05), and COM velocity X (𝛽 66.323, p<.05). For the javelin throw dynamics in E3, key determinants were Attitude angle and Javelin velocity in the Y-axis. Conclusion: The study reveals that controlled vertical movement, center of mass management during braking, and enhanced pelvic rotation significantly improve javelin throw performance. These kinematic strategies are critical for record enhancement in javelin throwing.

Gut microbiota-generated metabolites: missing puzzles to hosts' health, diseases, and aging

  • Yan Zhang;Shibo Wei;Hang Zhang;Yunju Jo;Jong-Sun Kang;Ki-Tae Ha;Jongkil Joo;Hyun Joo Lee;Dongryeol Ryu
    • BMB Reports
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    • 제57권5호
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    • pp.207-215
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    • 2024
  • The gut microbiota, an intricate community of bacteria residing in the gastrointestinal system, assumes a pivotal role in various physiological processes. Beyond its function in food breakdown and nutrient absorption, gut microbiota exerts a profound influence on immune and metabolic modulation by producing diverse gut microbiota-generated metabolites (GMGMs). These small molecules hold potential to impact host health via multiple pathways, which exhibit remarkable diversity, and have gained increasing attention in recent studies. Here, we elucidate the intricate implications and significant impacts of four specific metabolites, Urolithin A (UA), equol, Trimethylamine N-oxide (TMAO), and imidazole propionate, in shaping human health. Meanwhile, we also look into the advanced research on GMGMs, which demonstrate promising curative effects and hold great potential for further clinical therapies. Notably, the emergence of positive outcomes from clinical trials involving GMGMs, typified by UA, emphasizes their promising prospects in the pursuit of improved health and longevity. Collectively, the multifaceted impacts of GMGMs present intriguing avenues for future research and therapeutic interventions.

Structure of SARS-CoV-2 Spike Glycoprotein for Therapeutic and Preventive Target

  • Jaewoo Hong;Hyunjhung Jhun;Yeo-Ok Choi;Afeisha S. Taitt;Suyoung Bae;Youngmin Lee;Chang-seon Song;Su Cheong Yeom;Soohyun Kim
    • IMMUNE NETWORK
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    • 제21권1호
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    • pp.8.1-8.17
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    • 2021
  • The global crisis caused by the coronavirus disease 2019 (COVID-19) led to the most significant economic loss and human deaths after World War II. The pathogen causing this disease is a novel virus called the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). As of December 2020, there have been 80.2 million confirmed patients, and the mortality rate is known as 2.16% globally. A strategy to protect a host from SARS-CoV-2 is by suppressing intracellular viral replication or preventing viral entry. We focused on the spike glycoprotein that is responsible for the entry of SARS-CoV-2 into the host cell. Recently, the US Food and Drug Administration/EU Medicines Agency authorized a vaccine and antibody to treat COVID-19 patients by emergency use approval in the absence of long-term clinical trials. Both commercial and academic efforts to develop preventive and therapeutic agents continue all over the world. In this review, we present a perspective on current reports about the spike glycoprotein of SARS-CoV-2 as a therapeutic target.

의약품 임상시험 종사자 교육 이수자의 지식 수준, 태도, 교육 선택 요인 분석 (An Analysis on the Knowledge Levels, Attitudes, and Factors Affecting the Choices of Those Who Completed the Education of Persons Conducting Clinical Trial Workers)

  • 이윤진;장혜윤;이유미
    • 대한기관윤리심의기구협의회지
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    • 제3권2호
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    • pp.19-27
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    • 2021
  • Purpose: This study aimed to analyze the knowledge levels, attitudes, and factors affecting the choices on the education of the participants who completed their education of persons conducting clinical trial workers, and to assess the problems of the current education system for clinical trial workers, leading to improvements. Methods: Clinical trial workers (including principal investigators/subinvestigators, members of the Institutional Review Board [IRB], clinical research coordinators) who were affiliated to one of the 4 university hospitals running their own clinical trial center and IRB in Daegu and completed their education of persons conducting clinical trial workers were the subjects of this study. One hundred seven online questionnaires were answered from 2021-04-02 to 2021-04-17. Descriptive statistics and Pearson correlation analysis were used to analyze the acquired data. Independent t-test and 1-way analysis of variance were used to analyze the differences in the knowledge levels and attitudes following the characteristics of the education participants. Results: The baseline characteristics of the 107 participants were as follows: the majority of the participants were female (72.0%), were in their 30s (36.4%), had a nursing major (29.0%), were clinical research coordinators (63.6%), had never experienced a principal investigator (79.4%), had participated 3 or more educations (58.9%), had completed their maintenance course (55.1%), had 5 or more years of clinical trial experiences (34.6%). The fields on which participants had low levels of objective knowledge were "types and preparations on audits of clinical trials," "regulations on clinical trials (Pharmaceutical Affairs Act, Korea Good Clinical Practice)." The difficulties that the participants faced were on "annual educations" and "lack of information regarding the educations." Factors that showed significant differences in objective knowledge were sex (p=0.02), number of educations (p=0.004), the curriculum of 2020 (p=0.001). Age (p=0.004), having experienced a principal investigator (p=0.006), number of educations (p<0.001), the curriculum of 2020 (p<0.001), clinical trial career (p=0.001) were factors that significantly affected subjective knowledge. Attitudes toward the education were positively correlated with objective knowledge (r=0.20, p=0.04) and subjective knowledge (r=0.32, p=0.001). Major sources through which information on educations was acquired were "institutional notices," and major factors affecting the choices on the education were "when the education took place" and "where the education took place." "Within the affiliated institution," "Online classes (recorded)" and "IRB and review processes" were each the most preferred place, mode, and content of the education. Conclusion: Knowledge levels varied largely among participants who completed their education of persons conducting clinical trial workers, depending on their characteristics such as the number of educations. Participants also complained about their lack of information on educations. The quality of education may be improved if clinical trial organizations are designated as education facilities. Education programs must be developed considering the knowledge level and demand of the participants. Furthermore, as offline classes may be impossible due to pandemics such as the coronavirus disease 2019, the development of diverse and sophisticated online classes is looked forward to.

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Protein target identification of ginsenosides in skeletal muscle tissues: discovery of natural small-molecule activators of muscle-type creatine kinase

  • Chen, Feiyan;Zhu, Kexuan;Chen, Lin;Ouyang, Liufeng;Chen, Cuihua;Gu, Ling;Jiang, Yucui;Wang, Zhongli;Lin, Zixuan;Zhang, Qiang;Shao, Xiao;Dai, Jianguo;Zhao, Yunan
    • Journal of Ginseng Research
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    • 제44권3호
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    • pp.461-474
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    • 2020
  • Background: Ginseng effectively reduces fatigue in both animal models and clinical trials. However, the mechanism of action is not completely understood, and its molecular targets remain largely unknown. Methods: By screening for proteins that interact with the primary components of ginseng (ginsenosides) in an affinity chromatography assay, we have identified muscle-type creatine kinase (CK-MM) as a potential target in skeletal muscle tissues. Results: Biolayer interferometry analysis showed that ginsenoside metabolites, instead of parent ginsenosides, had direct interaction with recombinant human CK-MM. Subsequently, 20(S)-protopanaxadiol (PPD), which is a ginsenoside metabolite and displayed the strongest interaction with CK-MM in the study, was selected as a representative to confirm direct binding and its biological importance. Biolayer interferometry kinetics analysis and isothermal titration calorimetry assay demonstrated that PPD specifically bound to human CK-MM. Moreover, the mutation of key amino acids predicted by molecular docking decreased the affinity between PPD and CK-MM. The direct binding activated CK-MM activity in vitro and in vivo, which increased the levels of tissue phosphocreatine and strengthened the function of the creatine kinase/phosphocreatine system in skeletal muscle, thus buffering cellular ATP, delaying exercise-induced lactate accumulation, and improving exercise performance in mice. Conclusion: Our results suggest a cellular target and an initiating molecular event by which ginseng reduces fatigue. All these findings indicate PPD as a small molecular activator of CK-MM, which can help in further developing better CK-MM activators based on the dammarane-type triterpenoid structure.

2급 치근분지부 병소에서의 생분해성 차폐막의 효과 (Treatment of Class II Furcation Involvements in Humans with Bioabsorbable Guided Tissue Regeneration Barriers)

  • 이학철;한승민;설양조;이철우;엄흥식;장범석;정종평;한수부
    • Journal of Periodontal and Implant Science
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    • 제29권3호
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    • pp.539-553
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    • 1999
  • The purpose of this 6-months study was to compare the clinical and radiographic outcomes following guided tissue regeneration treating human mandibular Class II furcation defects with a bioabsorbable BioMesh barrier(test treatment) or a nonabsorbable ePTFE barrier(control treatment). Fourteen defects in 14 patients(mean age 44 years) were treated with BioMesh barriers and ten defects in 10 patients(mean age 48 years) with ePTFE barriers. After initial therapy, a GTR procedure was done. Following flap elevation, root planing, and removal of granulation tissue, each device was adjusted to cover the furcation defect. The flaps were repositioned and sutured to complete coverage of the barriers. A second surgical procedure was performed at control sites after 4 to 6 weeks to remove the nonresorbable barrier. Radiographic and clinical examinations(plaque index, gingival index, tooth mobility, gingival margin position, pocket depth, clinical attachment level) were carried out under standardized conditions immediately before and 6 months after surgery. Furthermore, digital subtraction radiography was carried out. All areas healed uneventfully. Surgical treatment resulted in clinically and statistically equivalent changes when comparisons were made between test and control treatments. Changes in plaque index were 0.7 for test and 0.4 for control treatments; changes in gingival index were 0.9 and 0.5. In both group gingival margin position and pocket depth reduction was 1.0mm and 3.0mm; clinical attachment level gain was 1.9mm. There were no changes in tooth mobility and the bone in radiographic evaluation. No significant(p${\leq }$0.05) difference between the two membranes could be detected with regard to plaque index, gingival index, gingival margin position, pocket depth, and clinical attachment level. In conclusion, a bioabsorbable BioMesh membrane is effective in human mandibular Class II furcation defects and a longer period study is needed to fully evaluate the outcomes.

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골육종세포에 미치는 레이저 조사의 광독성 효과 (PHOTOTOXIC EFFECTS OF LOW LEVEL LASER IRRADIATION ON HUMAN OSTEOSARCOMA CELLS)

  • 손장호;조영철;류성호;김규천;성일용;박봉수
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제30권6호
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    • pp.509-515
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    • 2004
  • 광역동치료(PDT)는 갖가지 고형 종양의 치료를 위한 임상적시도로 시작되어 화학요법 및 방사선 요법에 내성이 있는 종양의 대체 치료법의 하나로 제시되고 있다. PDT는 전신적 또는 국소적으로 투여하여 유해한 조직에 선택적으로 농축되도록 한 광증감제와 이를 활성화하는 적절한 파장과 에너지를 가진 레이저광의 조합에 기초한다. 이 연구에서는, 인체 골육종 세포(HOS)에 미치는 레이저 EIT 21의 광독성 효과에 대해 알아보았으며, 그런 광독성 효과가 세포고사를 유발하는가를 규명하고자 하였다. 본 연구는 레이저 EIT 21이 HOS 세포에 대해 광독성을 효과를 가진다는 것을 증명했다. 세포 죽음이 세포괴사에 의해 유발되는지 아니면 세포고사에 의해 유발되는지를 알아보기 위해 세포 고사를 평가 하는 여러 실험 기법을 이용하였다. TUNEL 분석은 극소수만이 응축된 핵의 양성반응을 보여주었다. Hemacolor와 AO/EB 염색 또한 대부분의 세포가 괴사로 죽는 것을 보여주었다. 레이저 EIT로 조사된 HOS 세포에서 응축되거나 분절된 핵을 발견하는 것은 어려웠다. DNA 전기영동에서, 세포고사에서 보여지는 DNA 분절의 전형적인 특징인 사다리형 절편 형태(ladder fragmentation pattern)가 나타나지 않았다. Western blotting에 의한 분석에서 p53의 발현은 일정하게 나타났고 레이저로 조사된 세포는 caspase-3과 PARP의 분열을 나타내지 않는 것으로 보아 레이저 유도 세포 죽음(laser-induced cell death)은 p53과는 관련이 없는 것 같다.

Effects of Human Chorionic Gonadotrophin, Flunixin Meglumin, Lidocane on Pregnancy Rate with Hanwoo IVF Embryo Transfer

  • Yoon, Do-Joong;Kim, Gye-Woong;Kim, Kon-Joong;Han, James-Bond;Kim, Nam-Hyung;Lee, Jong-Wan
    • 한국수정란이식학회지
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    • 제26권2호
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    • pp.97-104
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    • 2011
  • This study was carried out to confirm the effects of luteotrophin, human chorionic gonadotrophin (hCG), and an anti-luteolytic agent, flunixin meglumin (FM), on pregnancy rates in Hanwoo with in vitro produced (IVP) embryo transfers (ET), and to research the effects on the estrus cycle. Treatments included hCG and FM administration 3~10 minutes prior to ET. Also, pregnancy rates were compared with lidocane treatment and FM treatment prior to ET. The results are shown below. 30-day pregnancy rate was 76.7% in the hCG-treated group and 75.7% in the FM-treated group. Both rates were higher than the 70% rate for the control group. 42-day pregnancy rate was 76.7% in the FM-treated group. This was higher than 66.7% recorded for both the hCG-treated and control groups. The pregnancy rate of the hCG-treated group was high at Day 30 (76.7%) but low at Day 40 (66.7%), and there were no differences from the FM-treated and control groups. The recurrent estrus rate of infertile individuals at 2 weeks after ET was 36.4% in the hCG-treated group, under 71.4% in the FM-treated group and 80.0% in the control group. The non-pregnancy rate of individuals without recurrent estrus was 18.2% in the hCG-treated group, which was higher than the 0% rate in both the FM-treated and control groups. The pregnancy rates were higher in the FM-treated group than the Lidocane-treated group with 72.3% versus 67.5% in the heifers and 48.9% versus 43.6% in the cows. From the above results, the FM treatment proved more effective than the hCG treatment and no treatment whatsoever in increasing pregnancy rates after ET. In addition, hCG treatment was shown to be undesirable due to the deviations it caused in the reproductive physiology of the hCG-treated recipients. Therefore, in our study, the FM treatment resulted in a higher pregnancy rate than either lidocaine treatment or no-treatment in the trials of ET.

자궁경부 상피내종양의 환상투열요법 후 한약치료의 효과 : 체계적 문헌고찰 및 메타분석 (Herbal Medicine for Cervical Intraepithelial Neoplasia After Loop Electrosurgical Excision Procedure: A Systematic Review and Meta-Analysis)

  • 이수정;지해리;이혜정;황덕상;이창훈;장준복;이진무
    • 대한한방부인과학회지
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    • 제33권2호
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    • pp.44-62
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    • 2020
  • Objectives: The purpose of this study is to evaluate the effectiveness of herbal medicine for recovery and treatment of cervical intraepithelial neoplasia (CIN) after loop electrosurgical excision procedure (LEEP). Methods: We searched two english, one chinese and four korean database up to November 4, 2019. Randomised controlled trials (RCTs) were eligible. Primary outcome included Human papilloma virus (HPV) clearance rate and the effective ratio of treatment. And vaginal bleeding time and volume, improvement of symptoms, and recovery of wound were regarded as secondary outcomes. The risk of bias was assessed by two independent authors using the Cochrane risk of bias tool. Results: Of 47 screened, 10 RCTs were included. Number of participants per study ranged from 58 to 360. The studies which used HPV clearance rate as primary outcome were considered as low risk of bias. Most of the studies had considerable heterogeneity in terms of type of intervention, comparison and time-points for outcome measurement. Compared to LEEP alone, herbal vaginal suppository combined group showed favorable results for HPV clearance in patients (5 studies, n=627, 95% CI 1.26 to 1.55, I2=75%). And compared to LEEP alone, herbal external application also showed favorable results for HPV clearance in patients (2 studies, n=252, 95% CI 1.19 to 1.61, I2=86%). Three studies reported mild and temporary adverse events, and no serious adverse events were reported. Conclusions: The studies showed that herbal medicine can significantly effective on recovery of CIN after LEEP. However, included studies suffered from incomplete reporting, high or unclear risk of bias and substantial heterogeneity between studies. In the Future, further high-quality RCTs are needed to prove effectiveness of herbal medicine for CIN after LEEP and reduce the risk of bias.