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한국응용약물학회> Biomolecules & Therapeutics(구 응용약물학회지)

Biomolecules & Therapeutics(구 응용약물학회지) update

  • : 한국응용약물학회
  • : 의약학분야  >  약화학
  • : KCI등재
  • : SCI,SCOPUS
  • : 연속간행물
  • : 격월
  • : 1976-9148
  • : 2005-4483
  • : 응용약물학회지(~2007)→Biomolecules & Therapeutics(2008~)

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28권1호(2020) |수록논문 수 : 12
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28권1호(2020년) 수록논문
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KCI등재 SCI SCOPUS

1Modulation of Immunosuppression by Oligonucleotide-Based Molecules and Small Molecules Targeting Myeloid-Derived Suppressor Cells

저자 : Jihyun Lim , Aram Lee , Hee Gu Lee , Jong-seok Lim

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 28권 1호 발행 연도 : 2020 페이지 : pp. 1-17 (17 pages)

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Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exert suppressive function on the immune response. MDSCs expand in tumor-bearing hosts or in the tumor microenvironment and suppress T cell responses via various mechanisms, whereas a reduction in their activities has been observed in autoimmune diseases or infections. It has been reported that the symptoms of various diseases, including malignant tumors, can be alleviated by targeting MDSCs. Moreover, MDSCs can contribute to patient resistance to therapy using immune checkpoint inhibitors. In line with these therapeutic approaches, diverse oligonucleotide-based molecules and small molecules have been evaluated for their therapeutic efficacy in several disease models via the modulation of MDSC activity. In the current review, MDSC-targeting oligonucleotides and small molecules are briefly summarized, and we highlight the immunomodulatory effects on MDSCs in a variety of disease models and the application of MDSC-targeting molecules for immuno-oncologic therapy.

KCI등재 SCI SCOPUS

2Recent Trends in Cyclic Peptides as Therapeutic Agents and Biochemical Tools

저자 : Joon-seok Choi , Sang Hoon Joo

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 28권 1호 발행 연도 : 2020 페이지 : pp. 18-24 (7 pages)

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Notable progress has been made in the therapeutic and research applications of cyclic peptides since our previous review. New drugs based on cyclic peptides are entering the market, such as plecanatide, a cyclic peptide approved by the United States Food and Drug Administration in 2017 for the treatment of chronic idiopathic constipation. In this review, we discuss recent developments in stapled peptides, prepared with the use of chemical linkers, and bicyclic/tricyclic peptides with more than two rings. These have widespread applications for clinical and research purposes: imaging, diagnostics, improvement of oral absorption, enzyme inhibition, development of receptor agonist/antagonist, and the modulation of protein-protein interaction or protein-RNA interaction. Many cyclic peptides are expected to emerge as therapeutics and biochemical tools.

KCI등재 SCI SCOPUS

3Function of NADPH Oxidases in Diabetic Nephropathy and Development of Nox Inhibitors

저자 : Sae Rom Lee , Eun Jung An , Jaesang Kim , Yun Soo Bae

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 28권 1호 발행 연도 : 2020 페이지 : pp. 25-33 (9 pages)

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Several recent studies have reported that reactive oxygen species (ROS), superoxide anion and hydrogen peroxide (H2O2), play important roles in various cellular signaling networks. NADPH oxidase (Nox) isozymes have been shown to mediate receptormediated ROS generation for physiological signaling processes involved in cell growth, differentiation, apoptosis, and fibrosis. Detectable intracellular levels of ROS can be induced by the electron leakage from mitochondrial respiratory chain as well as by activation of cytochrome p450, glucose oxidase and xanthine oxidase, leading to oxidative stress. The up-regulation and the hyper-activation of NADPH oxidases (Nox) also likely contribute to oxidative stress in pathophysiologic stages. Elevation of the renal ROS level through hyperglycemia-mediated Nox activation results in the oxidative stress which induces a damage to kidney tissues, causing to diabetic nephropathy (DN). Nox inhibitors are currently being developed as the therapeutics of DN. In this review, we summarize Nox-mediated ROS generation and development of Nox inhibitors for therapeutics of DN treatment.

KCI등재 SCI SCOPUS

4Differentiation of Human Mesenchymal Stem Cells towards Neuronal Lineage: Clinical Trials in Nervous System Disorders

저자 : Rosa Hernandez , Cristina Jimenez-luna , Jesus Perales-adan , Gloria Perazzoli , Consolacion Melguizo , Jose Prados

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 28권 1호 발행 연도 : 2020 페이지 : pp. 34-44 (11 pages)

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Mesenchymal stem cells (MSCs) have been proposed as an alternative therapy to be applied into several pathologies of the nervous system. These cells can be obtained from adipose tissue, umbilical cord blood and bone marrow, among other tissues, and have remarkable therapeutic properties. MSCs can be isolated with high yield, which adds to their ability to differentiate into non-mesodermal cell types including neuronal lineage both in vivo and in vitro. They are able to restore damaged neural tissue, thus being suitable for the treatment of neural injuries, and possess immunosuppressive activity, which may be useful for the treatment of neurological disorders of inflammatory etiology. Although the long-term safety of MSC-based therapies remains unclear, a large amount of both pre-clinical and clinical trials have shown functional improvements in animal models of nervous system diseases following transplantation of MSCs. In fact, there are several ongoing clinical trials evaluating the possible benefits this cell-based therapy could provide to patients with neurological damage, as well as their clinical limitations. In this review we focus on the potential of MSCs as a therapeutic tool to treat neurological disorders, summarizing the state of the art of this topic and the most recent clinical studies.

KCI등재 SCI SCOPUS

5The Role of a Neurovascular Signaling Pathway Involving Hypoxia-Inducible Factor and Notch in the Function of the Central Nervous System

저자 : Seunghee Kim , Minjae Lee , Yoon Kyung Choi

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 28권 1호 발행 연도 : 2020 페이지 : pp. 45-57 (13 pages)

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In the neurovascular unit, the neuronal and vascular systems communicate with each other. O2 and nutrients, reaching endothelial cells (ECs) through the blood stream, spread into neighboring cells, such as neural stem cells, and neurons. The proper function of neural circuits in adults requires sufficient O2 and glucose for their metabolic demands through angiogenesis. In a central nervous system (CNS) injury, such as glioma, Parkinson's disease, and Alzheimer's disease, damaged ECs can contribute to tissue hypoxia and to the consequent disruption of neuronal functions and accelerated neurodegeneration. This review discusses the current evidence regarding the contribution of oxygen deprivation to CNS injury, with an emphasis on hypoxia-inducible factor (HIF)-mediated pathways and Notch signaling. Additionally, it focuses on adult neurological functions and angiogenesis, as well as pathological conditions in the CNS. Furthermore, the functional interplay between HIFs and Notch is demonstrated in pathophysiological conditions.

KCI등재 SCI SCOPUS

6Impact of Sleep Disorder as a Risk Factor for Dementia in Men and Women

저자 : Hye Jin Jee , Wonseok Shin , Ho Joong Jung , Baekgyu Kim , Bo Kyung Lee , Yi-sook Jung

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 28권 1호 발행 연도 : 2020 페이지 : pp. 58-73 (16 pages)

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Sleep is an essential physiological process, especially for proper brain function through the formation of new pathways and processing information and cognition. Therefore, when sleep is insufficient, this can result in pathophysiologic conditions. Sleep deficiency is a risk factor for various conditions, including dementia, diabetes, and obesity. Recent studies have shown that there are differences in the prevalence of sleep disorders between genders. Insomnia, the most common type of sleep disorder, has been reported to have a higher incidence in females than in males. However, sex/gender differences in other sleep disorder subtypes are not thoroughly understood. Currently, increasing evidence suggests that gender issues should be considered important when prescribing medicine. Therefore, an investigation of the gender-dependent differences in sleep disorders is required. In this review, we first describe sex/gender differences not only in the prevalence of sleep disorders by category but in the efficacy of sleep medications. In addition, we summarize sex/gender differences in the impact of sleep disorders on incident dementia. This may help understand gender-dependent pathogenesis of sleep disorders and develop therapeutic strategies in men and women.

KCI등재 SCI SCOPUS

7β-Amyrin Ameliorates Alzheimer's Disease-Like Aberrant Synaptic Plasticity in the Mouse Hippocampus

저자 : Hye Jin Park , Huiyoung Kwon , Ji Hye Lee , Eunbi Cho , Young Choon Lee , Minho Moon , Mira Jun , Dong Hyun Kim , Ji Wook Jung

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 28권 1호 발행 연도 : 2020 페이지 : pp. 74-82 (9 pages)

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Alzheimer's disease (AD) is a progressive and most frequently diagnosed neurodegenerative disorder. However, there is still no drug preventing the progress of this disorder. β-Amyrin, an ingredient of the surface wax of tomato fruit and dandelion coffee, is previously reported to ameliorate memory impairment induced by cholinergic dysfunction. Therefore, we tested whether β-amyrin can prevent AD-like pathology. β-Amyrin blocked amyloid β (Aβ)-induced long-term potentiation (LTP) impairment in the hippocampal slices. Moreover, β-amyrin improved Aβ-induced suppression of phosphatidylinositol-3-kinase (PI3K)/Akt signaling. LY294002, a PI3K inhibitor, blocked the effect of β-amyrin on Aβ-induced LTP impairment. In in vivo experiments, we observed that β-amyrin ameliorated object recognition memory deficit in Aβ-injected AD mice model. Moreover, neurogenesis impairments induced by Aβ was improved by β-amyrin treatment. Taken together, β-amyrin might be a good candidate of treatment or supplement for AD patients.

KCI등재 SCI SCOPUS

8Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice

저자 : Arvie Abiero , In Soo Ryu , Chrislean Jun Botanas , Raly James Perez Custodio , Leandro Val Sayson , Mikyung Kim , Hyun Jun Lee , Hee Jin Kim , Joung-wook Seo , Min Chang Cho , Kun Won Lee , Sung Yeun Yoo ,

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 28권 1호 발행 연도 : 2020 페이지 : pp. 83-91 (9 pages)

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Tryptamines are monoamine alkaloids with hallucinogenic properties and are widely abused worldwide. To hasten the regulations of novel substances and predict their abuse potential, we designed and synthesized four novel synthetic tryptamine analogs: Pyrrolidino tryptamine hydrochloride (PYT HCl), Piperidino tryptamine hydrochloride (PIT HCl), N,N-dibutyl tryptamine hydrochloride (DBT HCl), and 2-Methyl tryptamine hydrochloride (2-MT HCl). Then, we evaluated their rewarding and reinforcing effects using the conditioned place preference (CPP) and self-administration (SA) paradigms. We conducted an open field test (OFT) to determine the effects of the novel compounds on locomotor activity. A head-twitch response (HTR) was also performed to characterize their hallucinogenic properties. Lastly, we examined the effects of the compounds on 5-HTR1a and 5-HTR2a in the prefrontal cortex using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. None of the compounds induced CPP in mice or initiated SA in rats. PYT HCl and PIT HCl reduced the locomotor activity and elevated the 5-HTR1a mRNA levels in mice. Acute and repeated treatment with the novel tryptamines elicited HTR in mice. Furthermore, a drug challenge involving a 7-day abstinence from drug use produced higher HTR than acute and repeated treatments. Both the acute treatment and drug challenge increased the 5-HTR2a mRNA levels. Ketanserin blocked the induced HTR. Taken together, the findings suggest that PYT HCl, PIT HCl, DBT HCl, and 2-MT HCl produce hallucinogenic effects via 5-HTR2a stimulation, but may have low abuse potential.

KCI등재 SCI SCOPUS

9Lodoxamide Attenuates Hepatic Fibrosis in Mice: Involvement of GPR35

저자 : Mi-jeong Kim , Soo-jin Park , So-yeon Nam , Dong-soon Im

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 28권 1호 발행 연도 : 2020 페이지 : pp. 92-97 (6 pages)

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A previous pharmacogenomic analysis identified cromolyn, an anti-allergic drug, as an effective anti-fibrotic agent that acts on hepatocytes and stellate cells. Furthermore, cromolyn was shown to be a G protein-coupled receptor 35 (GPR35) agonist. However, it has not been studied whether anti-fibrotic effects are mediated by GPR35. Therefore, in this study, the role of GPR35 in hepatic fibrosis was investigated through the use of lodoxamide, another anti-allergic drug and a potent GPR35 agonist. Longterm treatment with carbon tetrachloride induced hepatic fibrosis, which was inhibited by treatment with lodoxamide. Furthermore, CID2745687, a specific GPR35 antagonist, reversed lodoxamide-mediated anti-fibrotic effects. In addition, lodoxamide treatment showed significant effects on the mRNA expression of collagen Iα1, collagen Iα2, and TGF-β1 in the extracellular matrix. However, a transforming growth factor α (TGF-α) shedding assay revealed lodoxamide not to be a potent agonist of mouse GPR35 in vitro. Therefore, these results showed anti-fibrotic effects of lodoxamide in mice and raise concerns how lodoxamide protects against liver fibrosis in vivo and whether GPR35 is involved in the action.

KCI등재 SCI SCOPUS

10Transforming Growth Factor β Receptor Type I Inhibitor, Galunisertib, Has No Beneficial Effects on Aneurysmal Pathological Changes in Marfan Mice

저자 : Jeong-ho Park , Min-seob Kim , Seokran Ham , Eon Sub Park , Koung Li Kim , Wonhee Suh

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 28권 1호 발행 연도 : 2020 페이지 : pp. 98-103 (6 pages)

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Marfan syndrome (MFS), a connective tissue disorder caused by mutations in the fibrillin-1 (Fbn1) gene, has vascular manifestations including aortic aneurysm, dissection, and rupture. Its vascular pathogenesis is assumed to be attributed to increased transforming growth factor β (TGFβ) signaling and blockade of excessive TGFβ signaling has been thought to prevent dissection and aneurysm formation. Here, we investigated whether galunisertib, a potent small-molecule inhibitor of TGFβ receptor I (TβRI), attenuates aneurysmal disease in a murine model of MFS (Fbn1C1039G/+) and compared the impact of galuninsertib on the MFSrelated vascular pathogenesis with that of losartan, a prophylactic agent routinely used for patients with MFS. Fbn1C1039G/+ mice were administered galunisertib or losartan for 8 weeks, and their ascending aortas were assessed for histopathological changes and phosphorylation of Smad2 and extracellular signal-regulated kinase 1/2 (Erk1/2). Mice treated with galunisertib or losartan barely exhibited phosphorylated Smad2, suggesting that both drugs effectively blocked overactivated canonical TGFβ signaling in Fbn1C1039G/+ mice. However, galunisertib treatment did not attenuate disrupted medial wall architecture and only partially decreased Erk1/2 phosphorylation, whereas losartan significantly inhibited MFS-associated aortopathy and markedly decreased Erk1/2 phosphorylation in Fbn1C1039G/+ mice. These data unexpectedly revealed that galunisertib, a TβRI inhibitor, showed no benefits in aneurysmal disease in MFS mice although it completely blocked Smad2 phosphorylation. The significant losartaninduced inhibition of both aortic vascular pathogenesis and Smad2 phosphorylation implied that canonical TGFβ signaling might not prominently drive aneurysmal diseases in MFS mice.

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