• Title/Summary/Keyword: Preclinical research

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Analysis of Research Trends in Papers Published in the Journal of Korean Medicine for Obesity Research: Focused on 2010-2019 (최근 10년간 한방비만학회지의 연구동향 분석: 2010-2019년 한방비만학회지 게재논문을 중심으로)

  • Park, Seohyun;Song, Yun-kyung
    • Journal of Korean Medicine for Obesity Research
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    • v.20 no.2
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    • pp.149-177
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    • 2020
  • Objectives: This study performed to identify trends in research published in the Journal of Korean Medicine for Obesity Research during last one decade. Methods: All of the articles in the Journal of Korean Medicine for Obesity Research published from 2010 to 2019 were collected. Search were conducted through "http://jkomor.org." Collected articles were classified into year and type of publication. Additional data including study design, study topics, characteristics of participants and treatment, outcomes was extracted from full text of each study. Results: Total 135 articles were analyzed. The number of studies were increasing after 2015. According to classification by type of study, percentage of clinical study took 27%, preclinical study took 37%, literary study took 21%, and case report took 15%. The number of studies were grown and study topics have been diversified. However for the growth of quality, concern for subjects, study design, quality assessment according to research guidelines and ethical consideration is needed. Conclusions: The number of studies and issues each study focused on have been increasing. To improve the quality of studies, further studies should be followed.

Real-time monitoring of ultra-high dose rate electron beams using bremsstrahlung photons

  • Hyun Kim;Dong Hyeok Jeong;Sang Koo Kang;Manwoo Lee;Heuijin Lim;Sang Jin Lee;Kyoung Won Jang
    • Nuclear Engineering and Technology
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    • v.55 no.9
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    • pp.3417-3422
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    • 2023
  • Recently, as the clinically positive biological effects of ultra-high dose rate (UHDR) radiation beams have been revealed, interest in flash radiation therapy has increased. Generally, FLASH preclinical experiments are performed using UHDR electron beams generated by linear accelerators. Real-time monitoring of UHDR beams is required to deliver the correct dose to a sample. However, it is difficult to use typical transmission-type ionization chambers for primary beam monitoring because there is no suitable electrometer capable of reading high pulsed currents, and collection efficiency is drastically reduced in pulsed radiation beams with ultra-high doses. In this study, a monitoring method using bremsstrahlung photons generated by irradiation devices and a water phantom was proposed. Charges collected in an ionization chamber located at the back of a water phantom were analyzed using the bremsstrahlung tail on electron depth dose curves obtained using radiochromic films. The dose conversion factor for converting a monitored charge into a delivered dose was determined analytically for the Advanced Markus® chamber and compared with experimentally determined values. It is anticipated that the method proposed in this study can be useful for monitoring sample doses in UHDR electron beam irradiation.

Guidelines for Manufacturing and Application of Organoids: Liver

  • Hye-Ran Moon;Seon Ju Mun;Tae Hun Kim;Hyemin Kim;Dukjin Kang;Suran Kim;Ji Hyun Shin;Dongho Choi;Sun-Ju Ahn;Myung Jin Son
    • International Journal of Stem Cells
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    • v.17 no.2
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    • pp.120-129
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    • 2024
  • Recent amendments to regulatory frameworks have placed a greater emphasis on the utilization of in vitro testing platforms for preclinical drug evaluations and toxicity assessments. This requires advanced tissue models capable of accurately replicating liver functions for drug efficacy and toxicity predictions. Liver organoids, derived from human cell sources, offer promise as a reliable platform for drug evaluation. However, there is a lack of standardized quality evaluation methods, which hinders their regulatory acceptance. This paper proposes comprehensive quality standards tailored for liver organoids, addressing cell source validation, organoid generation, and functional assessment. These guidelines aim to enhance reproducibility and accuracy in toxicity testing, thereby accelerating the adoption of organoids as a reliable alternative or complementary tool to animal testing in drug development. The quality standards include criteria for size, cellular composition, gene expression, and functional assays, thus ensuring a robust hepatotoxicity testing platform.

Combined TGE-SGE Expression of Novel PAI-1-Resistant t-PA in CHO DG44 Cells Using Orbitally Shaking Disposable Bioreactors

  • Davami, Fatemeh;Barkhordari, Farzaneh;Alebouyeh, Mahmoud;Adeli, Ahmad;Mahboudi, Fereidoun
    • Journal of Microbiology and Biotechnology
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    • v.21 no.12
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    • pp.1299-1305
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    • 2011
  • An important modification of thrombolytic agents is resistance to plasminogen activator inhibitor-1 (PAI-1). In previous studies, a new truncated PAI-1-resistant variant was developed based on deletion of the first three domains in t-PA and the substitution of KHRR 128-131 amino acids with AAAA in the truncated t-PA. The novel variant expressed in a static culture system of Chinese Hamster Ovary (CHO) DG44 cells exhibited a higher resistance to PAI-1 when compared with the full-length commercial drug; Actylase. In the present study, the truncated-mutant protein was expressed in CHO DG44 cells in 50 ml orbital shaking bioreactors. The final yield of the truncated-mutant in the culture was 752 IU/ml, representing a 63% increase compared with the static culture system. Therefore, these results suggest that using the combined features of a transient and stable expression system is feasible for the production of novel recombinant proteins in the quantities needed for preclinical studies.

An integrated review on new targets in the treatment of neuropathic pain

  • Khangura, Ravneet Kaur;Sharma, Jasmine;Bali, Anjana;Singh, Nirmal;Jaggi, Amteshwar Singh
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.1
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    • pp.1-20
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    • 2019
  • Neuropathic pain is a complex chronic pain state caused by the dysfunction of somatosensory nervous system, and it affects the millions of people worldwide. At present, there are very few medical treatments available for neuropathic pain management and the intolerable side effects of medications may further worsen the symptoms. Despite the presence of profound knowledge that delineates the pathophysiology and mechanisms leading to neuropathic pain, the unmet clinical needs demand more research in this field that would ultimately assist to ameliorate the pain conditions. Efforts are being made globally to explore and understand the basic molecular mechanisms responsible for somatosensory dysfunction in preclinical pain models. The present review highlights some of the novel molecular targets like D-amino acid oxidase, endoplasmic reticulum stress receptors, sigma receptors, hyperpolarization-activated cyclic nucleotide-gated cation channels, histone deacetylase, $Wnt/{\beta}-catenin$ and Wnt/Ryk, ephrins and Eph receptor tyrosine kinase, Cdh-1 and mitochondrial ATPase that are implicated in the induction of neuropathic pain. Studies conducted on the different animal models and observed results have been summarized with an aim to facilitate the efforts made in the drug discovery. The diligent analysis and exploitation of these targets may help in the identification of some promising therapies that can better manage neuropathic pain and improve the health of patients.

Gut Microbiome as a Possible Cause of Occurrence and Therapeutic Target in Chronic Obstructive Pulmonary Disease

  • Eun Yeong Lim;Eun-Ji Song;Hee Soon Shin
    • Journal of Microbiology and Biotechnology
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    • v.33 no.9
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    • pp.1111-1118
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    • 2023
  • As a long-term condition that affects the airways and lungs, chronic obstructive pulmonary disease (COPD) is characterized by inflammation, emphysema, breathlessness, chronic cough, and sputum production. Currently, the bronchodilators and anti-inflammatory drugs prescribed for COPD are mostly off-target, warranting new disease management strategies. Accumulating research has revealed the gut-lung axis to be a bidirectional communication system. Cigarette smoke, a major exacerbating factor in COPD and lung inflammation, affects gut microbiota composition and diversity, causing gut microbiota dysbiosis, a condition that has recently been described in COPD patients and animal models. For this review, we focused on the gut-lung axis, which is influenced by gut microbial metabolites, bacterial translocation, and immune cell modulation. Further, we have summarized the findings of preclinical and clinical studies on the association between gut microbiota and COPD to provide a basis for using gut microbiota in therapeutic strategies against COPD. Our review also proposes that further research on probiotics, prebiotics, short-chain fatty acids, and fecal microbiota transplantation could assist therapeutic approaches targeting the gut microbiota to alleviate COPD.

Case Study on the Effect of IPO on the Technology Commercialization Performance of the New Drug Development Bio Venture Company (증권시장 상장이 신약개발 바이오벤처기업의 기술사업화 성과에 미치는 사례연구)

  • Kim, Ju Young;Ha, Kyu Soo
    • Asia-Pacific Journal of Business Venturing and Entrepreneurship
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    • v.14 no.1
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    • pp.151-166
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    • 2019
  • New drug development requires 10 to 15 years of long time and more than $ 1 billion in funding, ranging from basic research${\rightarrow}$preclinical medicine${\rightarrow}$clinical medicine${\rightarrow}$product approval${\rightarrow}$sales. Many new drug development bio-venture companies will continue to pursue new drug development with funds secured through listing on the securities market. This study focuses on the impact of the listing on the market of bio-venture companies in the development of new drugs. It is necessary to determine whether the increase in registered patent, preclinical, clinical and technology transfer contracts at the time of listing (D) The results of this study are as follows. We also analyzed whether the registered patent, preclinical, and clinical effects had significant effect on technology transfer contracts at two years after listing and listing. The results of the analysis are as follows. First, Korea's new drug development bio-venture firms increased their registered patents but did not increase their pre-clinical, clinical and technology transfer contracts. Second, at the time of listing and two years after listing, pre-employment has a significant effect on Korea's technology transfer contracts and has a significant effect on overseas technology transfer contracts. However, registered patents and clinics have significant influence on technology transfer contracts. Korea 's new drug development bio-venture firms showed patent increase despite the stock market listing, but pre-clinical, clinical and technology transfer contracts did not increase. In order to strengthen technological commercialization of new drug development bio-venture companies in the future, it is required to establish R & D strategy for efficient use of IPO subscription funds, open innovation through strengthening industry-academia-partnerships, and more sophisticated preclinical and clinical strategy establishment.

Effects of Coculture on Development of Biopsied Mouse Embryos as a Preclinical Model for Preimplantation Genetic Diagnosis of Human Embryos (생쥐 모델을 이용한 배아의 할구 생검법과 할구가 생검된 배아의 배양시 공배양 효과에 관한 연구: 인간에서의 착상 전 유전진단 기술 개발을 위한 동물실험 모델의 개발)

  • Kim, S.H.;Ryu, B.Y.;Jee, B.C.;Choi, S.M.;Kim, H.S.;Pang, M.G.;Oh, S.K.;Suh, C.S.;Choi, Y.M.;Kim, J.G.;Moon, S.Y.;Lee, J.Y.;Chae, H.D.;Kim, C.H.
    • Clinical and Experimental Reproductive Medicine
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    • v.26 no.1
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    • pp.9-20
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    • 1999
  • The genetic defects in human gametes and embryos can cause adverse effects on overall reproductive events. Biopsy of embryos for preimplantation genetic diagnosis (PGD) offers a new possibility of having children free of the genetic disease. In addition, advanced embryo culture method may enhance the effectiveness of embryo biopsy for the practical application of PGD. This experimental study was undertaken to evaluate the effects of coculture on the development in vitro of biopsied mouse embryos as a preclinical model for PGD of human embryos. Embryos were obtained after in vitro fertilization (IVF) from F1 hybrid mice (C57BLfemale/CBAmale). Using micromanipulation, 1, 2, 3 or 4 blastomeres of 8-cell stage embryos were aspirated through a hole made in the zona pellucida by zona drilling (ZD) with acidic Tyrode's solution (ATS). After biopsy of blastomeres, embryos were cultured in vitro for 110 hours in Ham's F-10 supplemented with 0.4% BSA or cocultured on the monolayer of Vero cells in the same medium. The frequence of blastocyst formation were recorded, and the embryos beyond blastocyst stage were stained with 10% Giemsa to count the total number of nuclei in each embryo. There was no significant difference in the blastocyst formation between the zona intact control group and the zona drilling (ZD) only, or biopsied groups. The hatching rate of all the treatment groups except 4/8 group was significantly higher than that of control group. In all the treatment groups, there was a significant reduction in the mean cell number of embryos beyond blastocyst stage ($50.2{\pm}14.0$ in control group vs. $41.2{\pm}7.9$ in ZD, $39.3{\pm}8.8$ in 7/8, $29.7{\pm}6.4$ in 6/8, $25.1{\pm}5.7$ in 5/8, and $22.1{\pm}4.3$ in 4/8 groups, p<0.05). When the same treatments were followed by coculture with Vero cells, a similar pattern was seen in the blastocyst formation and the hatching rate. However, in all the treatment groups, there was a significant increase in the mean cell number of embryos beyond blastocyst stage with coculture, compared with the parallel groups without coculture. In the cleavage rate of biopsied blastomeres cultured for 110 hours after IVF, there was no significant difference between coculture and non-coculture groups (87.2% vs. 78.7%). However, the mean cell number of embryos developed from the biopsied blastomeres was significantly higher in coculture group ($11.5{\pm}4.7\;vs.\;5.9{\pm}1.9$, p<0.05). In conclusion, biopsy of mouse embryos after ZD with ATS is a safe and highly efficient method for PGD, and coculture with Vero cells showed a positive effect on the development in vitro of biopsied mouse embryos and blastomeres as a preclinical model for PGD of human embryos.

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Effects of Stress-Induced Sterile Inflammation on the Development of Depression (스트레스로 유발된 무균 염증이 우울증 발생에 미치는 영향)

  • Mi Kyoung Seo;Jung Goo Lee;Dae-Hyun Seog;Se Young Pyo;Won Hee Lee;Sung Woo Park
    • Journal of Life Science
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    • v.33 no.12
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    • pp.1062-1073
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    • 2023
  • Although depression is a common psychiatric disorder that negatively affects individuals and societies, its exact pathogenesis is not well understood. Stress is a major risk factor for depression and is known to increase susceptibility by triggering inflammation. Indeed, many preclinical and clinical studies have suggested a strong link between depression and inflammation. Depression is associated with increased levels of pro-inflammatory cytokines, such as interleukin (IL-)1β, IL-6, IL-12, tumor necrosis factor-α, and interferon-γ, and decreased levels of the anti-inflammatory IL-4, IL-10, and transforming growth factor-β. Administering pro-inflammatory cytokines causes depression-like behaviors in rodents. Conversely, administering anti-inflammatory drugs appears to ameliorate depressive symptoms. Although the importance of inflammation as a mediator of depression has been demonstrated, the mechanisms by which inflammation is activated in depression remain unclear. To address this issue, recent studies have focused on the importance of stress-induced sterile inflammation. Sterile inflammation refers to the activation of inflammatory processes due to physical and/or psychological stress in the absence of pathogens. Stress promotes the release of endogenous factors known as damage-associated molecular patterns (DAMPs), thereby triggering sterile inflammation. In turn, DAMPs are recognized by pattern recognition receptors, leading to the production of pro-inflammatory cytokines. Here, we review the role of DAMPs in depression based on preclinical and clinical evidence on the dysregulation of sterile inflammation.

Cardiovascular Molecular Imaging (심장 분자영상)

  • Lee, Kyung-Han
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.3
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    • pp.229-239
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    • 2009
  • Molecular imaging strives to visualize processes in living subjects at the molecular level. Monitoring biochemical processes at this level will allow us to directly track biological processes and signaling events that lead to pathophysiological abnormalities, and help make personalized medicine a reality by allowing evaluation of therapeutic efficacies on an individual basis. Although most molecular imaging techniques emerged from the field of oncology, they have now gradually gained acceptance by the cardiovascular community. Hence, the availability of dedicated high-resolution small animal imaging systems and specific targeting imaging probes is now enhancing our understanding of cardiovascular diseases and expediting the development of newer therapies. Examples include imaging approaches to evaluate and track the progress of recent genetic and cellular therapies for treatment of myocardial ischemia. Other areas include in vivo monitoring of such key molecular processes as angiogenesis and apoptosis, Cardiovascular molecular imaging is already an important research tool in preclinical experiments. The challenge that lies ahead is to implement these techniques into the clinics so that they may help fulfill the promise of molecular therapies and personalized medicine, as well as to resolve disappointments and controversies surrounding the field.