• Title/Summary/Keyword: Convergence of medicine

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Direct radio-iodination of folic acid for targeting folate receptor-positive tumors

  • Huynh, Phuong Tu;Lee, Woonghee;Ha, Yeong Su;Yoo, Jeongsoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.4 no.1
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    • pp.3-10
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    • 2018
  • The folate receptor (FR) is a promising cell membrane-associated target for nuclear imaging of various cancers (via imaging $FR-{\alpha}$) and potentially also inflammatory diseases (via imaging $FR-{\beta}$), through the use of folic acid-based radioconjugates. However, there have been several drawbacks of previously reported radioconjugates, such as a short half-life of the radiolabel ($^{68}Ga\;t_{1/2}$ 68 min), a complex and time-consuming multistep radiosynthesis, and a high renal uptake of radiolabeled folate derivatives. The goal of this study was to develop an imaging probe by directly labeling folate with radioactive iodine without using an extra prosthetic group. The radiolabeling of folate was optimized using various labeling conditions and the labeled tracers were isolated by high-performance liquid chromatography. The in vitro stability of labeled folate was checked in phosphate-buffered saline and serum. The tumor-targeting efficacy of the probe was also evaluated by biodistribution studies using a murine 4T1 tumor model.

Radio-Iodinated arbutin for tumor imaging

  • Huynh, Phuong Tu;Ha, Yeong Su;Lee, Woonghee;Yoo, Jeongsoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.3 no.2
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    • pp.72-79
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    • 2017
  • Arbutin is a hydroquinone derivative with a glucose moiety. As a tyrosinase inhibitor, it is widely used as a skin-whitening cosmetic agent for the treatment of cutaneous hyperpigmentary disorders, such as melasma and freckles. In the medical field, many studies have addressed the use of arbutin in various tumors, but the mechanism for tumor uptake of arbutin is still unclear. In this paper, we radiolabeled arbutin using radioiodine and studied its pharmacokinetics and tumor uptake via biodistribution experiments and single-photon emission computed tomography (SPECT) imaging. Radiolabeled $^{131}I-arbutin$ was stable for up to 24 h in PBS and serum. Biodistribution studies and SPECT imaging indicated high uptake of the compound in the bladder and kidneys shortly after injection. Twenty-four hours post-injection, significant deiodination was observed. Apart from high thyroid uptake, selective tumor uptake was clearly observed. The tumor-to-muscle and tumor-to-blood ratios were 26 and 9, respectively.

Hypoxia-dependent mitochondrial fission regulates endothelial progenitor cell migration, invasion, and tube formation

  • Kim, Da Yeon;Jung, Seok Yun;Kim, Yeon Ju;Kang, Songhwa;Park, Ji Hye;Ji, Seung Taek;Jang, Woong Bi;Lamichane, Shreekrishna;Lamichane, Babita Dahal;Chae, Young Chan;Lee, Dongjun;Chung, Joo Seop;Kwon, Sang-Mo
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.2
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    • pp.203-213
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    • 2018
  • Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.

Atorvastatin pretreatment attenuates kainic acid-induced hippocampal neuronal death via regulation of lipocalin-2-associated neuroinflammation

  • Jin, Zhen;Jung, Yohan;Yi, Chin-ok;Lee, Jong Youl;Jeong, Eun Ae;Lee, Jung Eun;Park, Ki-Jong;Kwon, Oh-Young;Lim, Byeong Hoon;Choi, Nack-Cheon;Roh, Gu Seob
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.3
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    • pp.301-309
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    • 2018
  • Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.

Updated Primer on Generative Artificial Intelligence and Large Language Models in Medical Imaging for Medical Professionals

  • Kiduk Kim;Kyungjin Cho;Ryoungwoo Jang;Sunggu Kyung;Soyoung Lee;Sungwon Ham;Edward Choi;Gil-Sun Hong;Namkug Kim
    • Korean Journal of Radiology
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    • v.25 no.3
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    • pp.224-242
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    • 2024
  • The emergence of Chat Generative Pre-trained Transformer (ChatGPT), a chatbot developed by OpenAI, has garnered interest in the application of generative artificial intelligence (AI) models in the medical field. This review summarizes different generative AI models and their potential applications in the field of medicine and explores the evolving landscape of Generative Adversarial Networks and diffusion models since the introduction of generative AI models. These models have made valuable contributions to the field of radiology. Furthermore, this review also explores the significance of synthetic data in addressing privacy concerns and augmenting data diversity and quality within the medical domain, in addition to emphasizing the role of inversion in the investigation of generative models and outlining an approach to replicate this process. We provide an overview of Large Language Models, such as GPTs and bidirectional encoder representations (BERTs), that focus on prominent representatives and discuss recent initiatives involving language-vision models in radiology, including innovative large language and vision assistant for biomedicine (LLaVa-Med), to illustrate their practical application. This comprehensive review offers insights into the wide-ranging applications of generative AI models in clinical research and emphasizes their transformative potential.

Cereblon Deletion Ameliorates Lipopolysaccharide-induced Proinflammatory Cytokines through 5'-Adenosine Monophosphate-Activated Protein Kinase/Heme Oxygenase-1 Activation in ARPE-19 Cells

  • Yun Kyu Kim;Soo Chul Chae;Hun Ji Yang;Da Eun An;Sion Lee;Myeong Gu Yeo;Kyung Jin Lee
    • IMMUNE NETWORK
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    • v.20 no.3
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    • pp.26.1-26.9
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    • 2020
  • Cereblon (CRBN), a negative modulator of AMP-activated protein kinase (AMPK), is highly expressed in the retina. We confirmed the expression of CRBN in ARPE-19 human retinal cells by Western blotting. We also demonstrated that CRBN knock-down (KD) could effectively downregulate IL-6 and MCP-1 protein and gene expression in LPS-stimulated ARPE-19 cells. Additionally, CRBN KD increased the phosphorylation of AMPK/acetylcoenzyme A carboxylase (ACC) and the expression of heme oxygenase-1 (HO-1) in ARPE-19 cells. Furthermore, CRBN KD significantly reduced LPS-induced nuclear translocation of NF-κB p65 and activation of NF-κB promoter activity. However, these processes could be inactivated by compound C (inhibitor of AMPK) and zinc protoporphyrin-1 (ZnPP-1; inhibitor of HO-1). In conclusion, compound C and ZnPP-1 can rescue LPS-induced levels of proinflammatory cytokines (IL-6 and MCP-1) in CRBN KD ARPE-19 cells. Our data demonstrate that CRBN deficiency negatively regulates proinflammatory cytokines via the activation of AMPK/HO-1 in the retina.

A Study on the treatment of drug addiction through fusion medicine and the measures to prevent drug crime diffusion - Focused on cases of Entertainment industry drug offense -

  • NAM, SeonMo
    • International Journal of Advanced Culture Technology
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    • v.6 no.4
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    • pp.172-178
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    • 2018
  • In this paper, I tried to pursue health and social welfare together through medical convergence based on the main subject of a culture of convergence. Artists' drug accidents are never ending. Now Korea is also out of the drug cleansing country. it is impossible to get rid of them with the national public power. It is time for a treatment plan for these. They need a certain period of time and regular periods of rest and control over sports. Our humanities are researching to understand the changing human images of today. In parallel, medical convergence will also have to be transformed in various ways for human healing. Recently, we can see the case of healing with the combination of oriental medicine, natural healing and western medicine. Furthermore, the structure of medical convergence for the fight against disease can be analyzed as an example. South Korea is also preparing for various convergence programs focusing on natural sciences such as engineering, medical care, and the environment. In order to prevent drug addiction it is important to determine the department responsible for handling the problem of substance abuse. we need to improve the environment that they can be combined with Ondol therapy and natural healing therapies. Furthermore, I expect that fusion medicine will contribute to improving the quality of life of drug addicts and become a successful model to revitalize local economies in particular.

Korean Red Ginseng extract ameliorates demyelination by inhibiting infiltration and activation of immune cells in cuprizone-administrated mice

  • Min Jung Lee;Jong Hee Choi;Tae Woo Kwon;Hyo-Sung Jo;Yujeong Ha;Seung-Yeol Nah;Ik-Hyun Cho
    • Journal of Ginseng Research
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    • v.47 no.5
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    • pp.672-680
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    • 2023
  • Background: Korean Red Ginseng (KRG), the steamed root of Panax ginseng, has pharmacological activities for immunological and neurodegenerative disorders. But, the role of KRGE in multiple sclerosis (MS) remains unclear. Purpose: To determine whether KRG extract (KRGE) could inhibit demyelination in corpus callosum (CC) of cuprizone (CPZ)-induced murine model of MS Methods: Male adult mice were fed with a standard chow diet or a chow diet supplemented with 0.2% (w/w) CPZ ad libitum for six weeks to induce demyelination while were simultaneously administered with distilled water (DW) alone or KRGE-DW (0.004%, 0.02 and 0.1% of KRGE) by drinking. Results: Administration with KRGE-DW alleviated demyelination and oligodendrocyte degeneration associated with inhibition of infiltration and activation of resident microglia and monocyte-derived macrophages as well as downregulation of proinflammatory mediators in the CC of CPZ-fed mice. KRGE-DW also attenuated the level of infiltration of Th1 and Th17) cells, in line with inhibited Mrna expression of IFN-γ and IL-17, respectively, in the CC. These positive effects of KRGE-DW mitigated behavioral dysfunction based on elevated plus maze and the rotarod tests. Conclusion: The results strongly suggest that KRGE-DW may inhibit CPZ-induced demyelination due to its oligodendroglial protective and anti-inflammatory activities by inhibiting infiltration/activation of immune cells. Thus, KRGE might have potential in therapeutic intervention for MS.

Tristetraprolin Inhibits the Growth of Human Glioma Cells through Downregulation of Urokinase Plasminogen Activator/Urokinase Plasminogen Activator Receptor mRNAs

  • Ryu, Jinhyun;Yoon, Nal Ae;Lee, Yeon Kyung;Jeong, Joo Yeon;Kang, Seokmin;Seong, Hyemin;Choi, Jungil;Park, Nammi;Kim, Nayoung;Cho, Wha Ja;Paek, Sun Ha;Cho, Gyeong Jae;Choi, Wan Sung;Park, Jae-Yong;Park, Jeong Woo;Kang, Sang Soo
    • Molecules and Cells
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    • v.38 no.2
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    • pp.156-162
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    • 2015
  • Urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) play a major role in the infiltrative growth of glioblastoma. Downregulatoion of the uPA and uPAR has been reported to inhibit the growth glioblastoma. Here, we demonstrate that tristetraprolin (TTP) inhibits the growth of U87MG human glioma cells through downregulation of uPA and uPAR. Our results show that expression level of TTP is inversely correlated with those of uPA and uPAR in human glioma cells and tissues. TTP binds to the AU-rich elements within the 3' untranslated regions of uPA and uPAR and overexpression of TTP decreased the expression of uPA and uPAR through enhancing the degradation of their mRNAs. In addition, overexpression of TTP inhibited the growth and invasion of U87MG cells. Our findings implicate that TTP can be used as a promising therapeutic target to treat human glioma.

Mitochondrial genome mutations in mesenchymal stem cells derived from human dental induced pluripotent stem cells

  • Park, Jumi;Lee, Yeonmi;Shin, Joosung;Lee, Hyeon-Jeong;Son, Young-Bum;Park, Bong-Wook;Kim, Deokhoon;Rho, Gyu-Jin;Kang, Eunju
    • BMB Reports
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    • v.52 no.12
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    • pp.689-694
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    • 2019
  • Ethical and safety issues have rendered mesenchymal stem cells (MSCs) popular candidates in regenerative medicine, but their therapeutic capacity is lower than that of induced pluripotent stem cells (iPSCs). This study compared original, dental tissue-derived MSCs with re-differentiated MSCs from iPSCs (iPS-MSCs). CD marker expression in iPS-MSCs was similar to original MSCs. iPS-MSCs expressed higher in pluripotent genes, but lower levels in mesodermal genes than MSCs. In addition, iPS-MSCs did not form teratomas. All iPSCs carried mtDNA mutations; some shared with original MSCs and others not previously detected therein. Shared mutations were synonymous, while novel mutations were non-synonymous or located on RNA-encoding genes. iPS-MSCs also harbored mtDNA mutations transmitted from iPSCs. Selected iPS-MSCs displayed lower mitochondrial respiration than original MSCs. In conclusion, screening for mtDNA mutations in iPSC lines for iPS-MSCs can identify mutation-free cell lines for therapeutic applications.