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Analytical methods to manage potential impurities in drug substances (의약품 중 잠재적 불순물 관리를 위한 분석법 연구 동향)

  • Park, Kyung Min;Kim, Won Mi;Ahn, Su Hyun;Lee, Ha Lim;Hwang, Su Hyeon;Lee, Wonwoong;Hong, Jongki
    • Analytical Science and Technology
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    • v.35 no.3
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    • pp.93-115
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    • 2022
  • Potential impurities in pharmaceuticals could be produced during manufacture, distribution, and storage and affect quality and safety of pharmaceuticals. In particular, highly reactive impurities could result in carcinogenic (mutagenic) effects on human body. International Conference on Harmonisation (ICH) has provided M7(R1) guideline for "Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk" and recommended an adoption of this guideline to the authorities. ICH M7(R1) guideline provides classification, accepted intakes, and controls of potential impurities in pharmaceuticals. However, since appropriate and unified analytical methods for impurities in pharmaceuticals have not been provided in this guideline, most potential impurities in pharmaceuticals are still difficult to manage and supervise by pharmaceutical companies and regulatory authorities, respectively. In this review, we briefly described definition of unintended mutagenic impurities, basic information in ICH M7(R1) guideline, and analytical methods to determine potential impurities. This review would be helpful to manage and supervise potential impurities in pharmaceuticals by pharmaceutical companies and regulatory authorities.

Gas Sorption Analysis of Metal-organic Frameworks using Microresonators (마이크로진동자 기반 금속유기골격체의 기체 흡탈착 분석)

  • Kim, Hamin;Choi, Hyun-Kuk;Kim, Moon-Gab;Lee, Young-Sei;Yim, Changyong
    • Applied Chemistry for Engineering
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    • v.33 no.1
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    • pp.11-16
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    • 2022
  • Metal-organic frameworks (MOFs) are porous materials with nano-sized pores. The degree of gas adsorption and pore size can be controlled according to types of metal ions and organic ligands. Many studies have been conducted on MOFs in the fields of gas storage and separation, and gas sensors. For rapid and quantitative gas adsorption/desorption analyses, it is necessary to form various MOF structures in uniform films on a sensor surface. In this review, some of representative direct methods for uniformly synthesizing MOFs such as MIL-53 (Al), ZIF-8, and Cu-BDC from anodized aluminum oxide, zinc oxide nanorods, and copper thin films, respectively on the surface of a microresonator are highlighted. In addition, the operation principle of quartz crystal microbalance and microcantilever, which are representative microresonators, and the interpretation of signals that change when gas is adsorbed to MOFs are covered. This is intended to enhance the understanding of gas adsorption/desorption analysis of MOFs using microresonators.

Recent Advances in the Biotechnological Production of Natural Vanillin (생물공학에 기반한 천연 바닐린 생산에 관한 최근 연구)

  • Kim, Hyun-Song;Kim, Young-Ok;Lee, Jin-Ho
    • Journal of Life Science
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    • v.31 no.11
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    • pp.1046-1055
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    • 2021
  • Vanillin is the primary flavor and fragrance compound of natural vanilla and is extensively used in the food, beverage, perfumery, pharmaceutical industries, and other applications. Vanillin can be produced by chemical synthesis, extraction from vanilla plants, microbial bioconversion of natural precursors to vanillin, and direct fermentation using glucose. Currently, most commercially available vanillin is produced by extraction from cured vanilla pods and by chemical synthesis using guaiacol and glyoxylic acid as starting raw materials. Due to environmental issues, health complaints, preference for natural sources, and the limited supply and soaring price of natural vanilla, biotechnology-based vanillin production is regarded as a promising alternative. As many microorganisms that are able to metabolize several natural precursors, including ferulic acid, eugenol, isoeugenol, and lignin, and accumulate vanillin, have been screened and evaluated, myriad strategies and efforts have been employed for the development of commercially viable production technology. This review outlines the recent advances in the biotechnological production of natural vanillin with the use of these natural precursors. Moreover, it highlights the recent engineering approaches for the production of natural vanillin from renewable carbon sources based on the de novo biosynthetic pathway of vanillin from glucose, together with appropriate solution strategies to overcome the challenges posed to increase production titers.

Pathophysiological Functions of Deubiquitinating Enzymes in Obesity and Related Metabolic Diseases (탈유비퀴틴화 효소 DUBs의 비만 및 대사 관련 질환에서 병태생리학적 기능)

  • Lee, Seul Gi;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.32 no.6
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    • pp.476-481
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    • 2022
  • Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.

Research Trends on the Therapeutic Potential of Cordycepin, an Active Ingredient of the Insect Fungus Cordyceps spp., for the Prevention of Sarcopenia (동충하초(Cordyceps spp.)의 유효 생리활성 성분인 cordycepin의 근감소증 예방에 대한 연구 동향)

  • Kim, Sung Ok;Choi, Yung Hyun
    • Journal of Life Science
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    • v.32 no.6
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    • pp.482-490
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    • 2022
  • Sarcopenia, a geriatric and multifactorial syndrome characterized by progressive systemic skeletal muscle disorder, may be associated with many comorbidities. Sarcopenia caused by a decrease in muscle mass and muscle strength is accompanied by the aggravation of various pathological conditions, and as life expectancy increases, its prevalence will continue to increase in the future. During the aging process, chronic oxidative stress and increased inflammatory responses act as major contributors to skeletal muscle loss. In addition, disruption of autophagy and apoptosis signals associated with dysfunction of mitochondria, which are essential for energy metabolism, accelerates the loss of muscle proteins. The pharmacological effect of cordycepin, a major physiologically active substance in the genus Cordyceps, which has been widely used for the prevention and treatment of various diseases for a long time, is directly related to its antioxidant and anti-inflammatory actions. In this review, we present the correlation between apoptosis, autophagy, protein catabolism, and satellite cell activity important for muscle regeneration using cordycepin for the prevention and treatment of sarcopenia. Although there have been few studies so far on the use of cordycepin for sarcopenia, previous studies suggest that cordycepin may contribute to inhibiting the age-related weakening of mitochondrial function and blocking the breakdown of muscle proteins. In addition, the protective effect of cordycepin on muscle cell damage is considered to be closely related to its antioxidant and anti-inflammatory activities. Therefore, it is considered that more continuous basic research is needed, focusing on the molecular biological mechanism of cordycepin, which is involved in the anti-aging of muscle cells.

A Review on the Deposition/Dissolution of Lithium Metal Anodes through Analyzing Overpotential Behaviors (과전압 거동 분석을 통한 리튬 금속 음극의 전착/탈리 현상 이해)

  • Han, Jiwon;Jin, Dahee;Kim, Suhwan;Lee, Yong Min
    • Journal of the Korean Electrochemical Society
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    • v.25 no.1
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    • pp.1-12
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    • 2022
  • Lithium metal is the most promising anode for next-generation lithium-ion batteries due to its lowest reduction potential (-3.04 V vs. SHE) and high specific capacity (3860 mAh/g). However, the dendritic formation under high charging current density remains one of main technical barriers to be used for commercial rechargeable batteries. To address these issues, tremendous research to suppress lithium dendrite formation have been conducted through new electrolyte formulation, robust protection layer, shape-controlled lithium metal, separator modification, etc. However, Li/Li symmetric cell test is always a starting or essential step to demonstrate better lithium dendrite formation behavior with lower overpotential and longer cycle life without careful analysis. Thus, this review summarizes overpotential behaviors of Li/Li symmetric cells along with theoretical explanations like initial peaking or later arcing. Also, we categorize various overpotential data depending on research approaches and discuss them based on peaking and arcing behaviors. Thus, this review will be very helpful for researchers in lithium metal to analyze their overpotential behaviors.

Current Status and Necessity of Separation Technology to Secure Vanadium Mineral Resources (바나듐 광물자원 확보를 위한 선별 기술 현황 및 필요성)

  • Jeon, Hoseok;Han, Yosep;Baek, Sangho;Davaadorj, Tsogchuluun;Go, Byunghun;Jeong, Dohyun;Chu, Yeoni;Kim, Seongmin
    • Resources Recycling
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    • v.31 no.2
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    • pp.3-11
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    • 2022
  • Owing to the global development of high-strength alloys and renewable energy industries, the demand for vanadium, a key raw material in these industries, is expected to increase. Until now, vanadium has been recovered as a by-product of the industry, but interest in its direct recovery from minerals has increasing with its significantly increasing demand. In particular, the recovery of vanadium from stone coal ore and vanadium titano-magnetite (VTM) containing vanadium has been actively researched in China, which has the largest reserves and production of vanadium in the world. In Korea, a large amount of VTM also occurs in the northern part of Gyeonggi-do, and fundamental research and technical development is being conducted to recover vanadium. It is necessary to understand the current status of the separation technology used worldwide to satisfy the demand for metals such as vanadium, which currently depends on imports.

A Review on the Wet Chemical Synthesis of Sulfide Solid Electrolytes for All-Solid-State Li Batteries (전고체전지용 황화물 고체전해질 습식 합성기술 동향)

  • Ha, Yoon-Cheol
    • Journal of the Korean Electrochemical Society
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    • v.25 no.3
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    • pp.95-104
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    • 2022
  • The development of non-flammable all-solid-state batteries (ASSLBs) has become a hot topic due to the known drawbacks of commercial lithium-ion batteries. As the possibility of applying sulfide solid electrolytes (SSEs) for electric vehicle batteries increases, efforts for the low-cost mass-production are actively underway. Until now, most studies have used high-energy mechanical milling, which is easy to control composition and impurities and can reduce the process time. Through this, various SSEs that exceed the Li+ conductivity of liquid electrolytes have been reported, and expectations for the realization of ASSLBs are growing. However, the high-energy mechanical milling method has disadvantages in obtaining the same physical properties when mass-produced, and in controlling the particle size or shape, so that physical properties deteriorate during the full process. On the other hand, wet chemical synthesis technology, which has advantages in mass production and low price, is still in the initial exploration stage. In this technology, SSEs are mainly manufactured through producing a particle-type, solution-type, or mixed-type precursor, but a clear understanding of the reaction mechanism hasn't been made yet. In this review, wet chemical synthesis technologies for SSEs are summarized regarding the reaction mechanism between the raw materials in the solvent.

Diverse Mechanisms of Relaxin's Action in the Regulation of Smooth Muscles and Extracellular Matrix of Vasculature and Fibrosis (혈관과 섬유증의 평활근 및 세포외기질 조절에 대한 릴랙신의 다양한 작용기전)

  • Min, Gyesik
    • Journal of Life Science
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    • v.32 no.2
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    • pp.175-188
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    • 2022
  • Relaxin has been demonstrated to have regulatory functions on both the smooth muscle and extracellular matrix (ECM) of blood vessels and fibrotic organs. The diverse mechanisms by which relaxin acts on small resistance arteries and fibrotic organs, including the bladder, are reviewed here. Relaxin induces vasodilation by inhibiting the contractility of vascular smooth muscles and by increasing the passive compliance of vessel walls through the reduction of ECM components, such as collagen. The primary cellular mechanism whereby relaxin induces arterial vasodilation is mediated by the endothelium-dependent production of nitric oxide (NO) through the activation of RXFP1/PI3K, Akt phosphorylation, and eNOS. In addition, relaxin triggers different alternative pathways to enhance the vasodilation of renal and mesenteric arteries. In small renal arteries, relaxin stimulates the activation of the endothelial MMPs and EtB receptors and the production of VEGF and PlGF to inhibit myogenic contractility and collagen deposition, thereby bringing about vasodilation. Conversely, in small mesenteric arteries, relaxin augments bradykinin (BK)-evoked relaxation in a time-dependent manner. Whereas the rapid enhancement of the BK-mediated relaxation is dependent on IKCa channels and subsequent EDH induction, the sustained relaxation due to BK depends on COX activation and PGI2. The anti-fibrotic effects of relaxin are mediated by inhibiting the invasion of inflammatory immune cells, the endothelial-to-mesenchymal transition (EndMT), and the differentiation and activation of myofibroblasts. Relaxin also activates the NOS/NO/cGMP/PKG-1 pathways in myofibroblasts to suppress the TGF-β1-induced activation of ERK1/2 and Smad2/3 signaling and deposition of ECM collagen.

A Review on Ultrathin Ceramic-Coated Separators for Lithium Secondary Batteries using Deposition Processes (증착 기법을 이용한 리튬이차전지용 초박막 세라믹 코팅 분리막 기술)

  • Kim, Ucheol;Roh, Youngjoon;Choi, Seungyeop;Dzakpasu, Cyril Bubu;Lee, Yong Min
    • Journal of the Korean Electrochemical Society
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    • v.25 no.4
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    • pp.134-153
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    • 2022
  • Regardless of a trade-off relationship between energy density and safety, it is essential to improve both properties for future lithium secondary batteries. Especially, to improve the energy density of batteries further, not only thickness but also weight of separators including ceramic coating layers should be reduced continuously apart from the development of high-capacity electrode active materials. For this purpose, an attempt to replace conventional slurry coating methods with a deposition one has attracted much attention for securing comparable thermal stability while minimizing the thickness and weight of ceramic coating layer in the separator. This review introduces state-of-the-art technology on ceramic-coated separators (CCSs) manufactured by the deposition method. There are three representative processes to form a ceramic coating layer as follows: chemical vapor deposition (CVD), atomic layer deposition (ALD), and physical vapor deposition (PVD). Herein, we summarized the principle and advantages/disadvantages of each deposition method. Furthermore, each CCS was analyzed and compared in terms of its mechanical and thermal properties, air permeability, ionic conductivity, and electrochemical performance.