• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.1
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• pp.41-49
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• 2021

Diversity and flexibility are two typical hallmarks of macrophages. Two types of macrophages, M1(classically activated macrophages) and M2(alternatively activated macrophages) exist at both ends of the commonly known macrophage polarization. M1 macrophages have inflammatory properties and are primarily responsible for defending against invading bacteria in our body. On the other hand, M2 macrophages are involved in anti-inflammatory responses and tissue remodeling. Polarized migration of macrophages is of increasing interest in regulating the initiation, generation, and resting phases of inflammatory diseases. In this review, it intend to discuss the properties and functions of tumor-associated macrophages based on polarized macrophages that affect inflammatory diseases. In addition, the purpose of this study is to investigate a molecular imaging approach that targets macrophages that affect tumor growth by controlling the polarization of macrophages that affect tumor diagnosis and treatment.

• Tuberculosis and Respiratory Diseases
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• v.86 no.3
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• pp.166-175
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• 2023

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. The lower airways contain a rich and diverse microbiome, which may play a significant regulatory role in both health and disease. In COPD, the microbiome becomes perturbed, causing dysbiosis. Increased representation of members in the Proteobacteria phylum and certain members in the Firmicutes phylum has been associated with increased risk of exacerbations and mortality. Therapies such as inhaled corticosteroids and azithromycin may modulate the airway microbiome or its metabolites in patients with COPD. This paper provides an up-to-date overview of the airway microbiome and its importance in the pathophysiology of COPD and as potential therapeutic target in the future.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.3-3
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• 2021

The ongoing global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not only influenced over 1.26 billion people but also caused 2.77 million deaths worldwide (as of March 28, 2021). The vaccination could be the most efficient strategy to prevent SARS-CoV-2 infection. However, the continuous emergence of novel variants such as VUI-202012/01 (United Kingdom) and 501.V2 (South Africa) raises huge concerns about the effectiveness of the vaccine designed to target the original virus strain. Since ancient times regardless of the East and West, the plants which refered in this presentation have been consumed not only as food but also as a natural medicine to treat diverse diseases including infectious diseases. Importantly, these plants contain secondary metabolites that display antiviral activity involved in the inhibition of viral adsorption, penetration, and replication. Also, plant-derived natural medicines are expected to have a wider range of efficacy and fewer side effects than synthetic medicine, discovering novel plant-based viral agents would be a promising strategy to fight against SARS-CoV-2.

• Biomolecules & Therapeutics
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• v.32 no.2
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• pp.171-182
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• 2024

All cells are equipped with intricate signaling networks to meet the energy demands and respond to the nutrient availability in the body. AMP-activated protein kinase (AMPK) is among the most potent regulators of cellular energy balance. Under ATP -deprived conditions, AMPK phosphorylates substrates and affects various biological processes, such as lipid/glucose metabolism and protein synthesis. These actions further affect the cell growth, death, and functions, altering the cellular outcomes in energy-restricted environments. AMPK plays vital roles in maintaining good health. AMPK dysfunction is observed in various chronic diseases, making it a promising target for preventing and alleviating such diseases. Herein, we highlight the different AMPK functions, especially in allergy, aging, and cancer, to facilitate the development of new therapeutic approaches in the future.

• International Journal of Stem Cells
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• v.16 no.4
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• pp.376-384
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• 2023

The Wnt 𝛽-catenin signaling pathway is a highly conserved mechanism that plays a critical role from embryonic development and adult stem cell homeostasis. However, dysregulation of the Wnt pathway has been implicated in various diseases, including cancer. Therefore, multiple layers of regulatory mechanisms tightly control the activation and suppression of the Wnt signal. The E3 ubiquitin ligases RNF43 and ZNRF3, which are known negative regulators of the Wnt pathway, are critical component of Wnt signaling regulation. These E3 ubiquitin ligases control Wnt signaling by targeting the Wnt receptor Frizzled to induce ubiquitination-mediated endo-lysosomal degradation, thus controlling the activation of the Wnt signaling pathway. We also discuss the regulatory mechanisms, interactors, and evolution of RNF43 and ZNRF3. This review article summarizes recent findings on RNF43 and ZNRF3 and their potential implications for the development of therapeutic strategies to target the Wnt signaling pathway in various diseases, including cancer.

• Biomolecules & Therapeutics
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• v.25 no.1
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• pp.69-79
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• 2017

Viruses continue to evolve a new strategy to take advantage of every aspect of host cells in order to maximize their survival. Due to their central roles in transducing a variety of transmembrane signals, GPCRs seem to be a prime target for viruses to pirate for their own use. Incorporation of GPCR functionality into the genome of herpesviruses has been demonstrated to be essential for pathogenesis of many herpesviruses-induced diseases. Here, we introduce US28 of human cytomegalovirus (HCMV) as the best-studied example of virally-encoded GPCRs to manipulate host GPCR signaling. In this review, we wish to summarize a number of US28-related topics including its regulation of host signaling pathways, its constitutive internalization, its structural and functional analysis, its roles in HCMV biology and pathogenesis, its proliferative activities and role in oncogenesis, and pharmacological modulation of its biological activities. This review will aid in our understanding of how pathogenic viruses usurp the host GPCR signaling for successful viral infection. This kind of knowledge will enable us to build a better strategy to control viral infection by normalizing the virally-dysregulated host GPCR signaling.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.91-96
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• 2007

The measurement of pathologically low levels of tissue $pO_2$ is an important diagnostic goal for determining the prognosis of many clinically important diseases including cardiovascular insufficiency, stroke and cancer. The target tissues nowaday have mostly been tumors or the myocardium, with less attention centered on the brain. Radiolabelled nitroimidazole or derivatives may be useful in identifying the hypoxic cells in cerebrovascular disease or traumatic brain injury, and hypoxic-ischemic encephalopathy. In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. $^{18}F-MISO$ PET and $^{99}mTc-EC-metronidazole$ SPECT in patients with acute ischemic stroke identified hypoxic tissues and ischemic penumbra, and predicted its outcome. A study using $^{123}I-IAZA$ in patient with closed head injury detected the hypoxic tissues after head injury. Up till now these radiopharmaceuticals have drawbacks due to its relatively low concentration with hypoxic tissues associated with/without low blood-brain barrier permeability and the necessity to wait a long time to achieve acceptable target to background ratios for imaging in acute ischemic stroke. It is needed to develop new hypoxic marker exhibiting more rapid localization in the hypoxic region in the brain. And then, the hypoxic brain imaging with imidazoles or non-imidazoles may be very useful in detecting the hypoxic tissues, determining therapeutic strategies and developing therapeutic drugs in several neurological disease, especially, in acute ischemic stroke.

• BMB Reports
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• v.55 no.9
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• pp.417-428
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• 2022

Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which impedes the development and application of herbal medicine. To address this, recent studies are increasingly adopting systems pharmacology, which interprets pharmacological effects of drugs from consequences of the interaction networks that drugs might have. Most conventional network-based approaches collect associations of herb-compound, compound-target, and target-disease from individual databases, respectively, and construct an integrated network of herb-compound-target-disease to study the complex mechanisms underlying herbal treatment. More recently, rapid advances in high-throughput omics technology have led numerous studies to exploring gene expression profiles induced by herbal treatments to elicit information on direct associations between herbs and genes at the genome-wide scale. In this review, we summarize key databases and computational methods utilized in systems pharmacology for studying herbal medicine. We also highlight recent studies that identify modes of action or novel indications of herbal medicine by harnessing drug-induced transcriptome data.

• Oncology Letters
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• v.17 no.3
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• pp.2576-2582
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• 2019

Gestational trophoblastic disease (GTD) is an unusual disease occurring in pregnancy that originates from abnormal trophoblastic cells and comprises a group of diseases with different properties of invasion, metastasis and recurrence. The GTD group includes hydatidiform moles and gestational trophoblastic neoplasms (GTNs), with GTNs being divided into invasive moles, choriocarcinoma, placental site trophoblastic tumors and epithelioid trophoblastic tumors. The present review focuses on current effective treatments for GTD, including conventional and novel promising direct enzyme prodrug therapies (DEPTs). Conventional therapies, such as chemotherapy and hysterectomy, are currently used in a clinical setting; however, the use of diverse DEPTs, including antibody-DEPT and gene-DEPT is also being attempted to cure GTNs. In addition, gene delivery tools using genetically engineered neural stem cells (NSCs) are presently being examined for the treatment of GTNs. The tumor-tropism of NSCs by chemoattractant factors is a unique characteristic of these cells and can serve as a vehicle to deliver anticancer agents. Previous studies have demonstrated that injection with NSC-expressing suicide genes into xenograft animal models has a significant inhibitory effect on tumor growth. Stem cells can be genetically engineered to express anticancer genes, which migrate to the metastatic sites and selectively target cancer cells, and are considered to effectively target metastatic GTNs. However, the safety issue of stem cell therapy, such as tumorigenesis, remains a challenge. Novel therapies comprising a combination of conventional and novel promising treatments are anticipated to be definitive treatments for metastasized and/or recurrent patients with GTNs.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.161-168
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• 2016

Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor effects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory effects of S109 on CRM1 is reversible. Our data demonstrated that S109 significantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the effects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy.