• Molecules and Cells
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• 제46권4호
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• pp.209-218
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• 2023

In induced pluripotent stem cells (iPSCs), pluripotency is induced artificially by introducing the transcription factors Oct4, Sox2, Klf4, and c-Myc. When a transgene is introduced using a viral vector, the transgene may be integrated into the host genome and cause a mutation and cancer. No integration occurs when an episomal vector is used, but this method has a limitation in that remnants of the virus or vector remain in the cell, which limits the use of such iPSCs in therapeutic applications. Chemical reprogramming, which relies on treatment with small-molecule compounds to induce pluripotency, can overcome this problem. In this method, reprogramming is induced according to the gene expression pattern of extra-embryonic endoderm (XEN) cells, which are used as an intermediate stage in pluripotency induction. Therefore, iPSCs can be induced only from established XEN cells. We induced XEN cells using small molecules that modulate a signaling pathway and affect epigenetic modifications, and devised a culture method which can produce homogeneous XEN cells. At least 4 passages were required to establish morphologically homogeneous chemically induced XEN (CiXEN) cells, whose properties were similar to those of XEN cells, as revealed through cellular and molecular characterization. Chemically iPSCs derived from CiXEN cells showed characteristics similar to those of mouse embryonic stem cells. Our results show that the homogeneity of CiXEN cells is critical for the efficient induction of pluripotency by chemicals.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.682-691
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• 2023

Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed EGF-induced cell proliferation and anchorage-independent colony growth. EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3β, and p-NFκB expression. Treatment with MK-2206, an AKT pharmacological inhibitor, suppressed EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin carcinogenesis.

• BMB Reports
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• 제56권10호
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• pp.545-550
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• 2023

Osteoporosis is a major public health concern, which requires novel therapeutic strategies to prevent or mitigate bone loss. Natural compounds have attracted attention as potential therapeutic agents due to their safety and efficacy. In this study, we investigated the regulatory activities of boeravinone B (BOB), a natural rotenoid isolated from the medicinal plant Boerhavia diffusa, on the differentiation of osteoclasts and mesenchymal stem cells (MSCs), the two main cell components responsible for bone remodeling. We found that BOB inhibited osteoclast differentiation and function, as determined by TRAP staining and pit formation assay, with no significant cytotoxicity. Furthermore, our results showing that BOB ameliorates ovariectomy-induced bone loss demonstrated that BOB is also effective in vivo. BOB exerted its inhibitory effects on osteoclastogenesis by downregulating the RANKL/RANK signaling pathways, including NF-κB, MAPK, and PI3K/Akt, resulting in the suppression of osteoclast-specific gene expression. Further experiments revealed that, at least phenomenologically, BOB promotes osteoblast differentiation of bone marrow-derived MSCs but inhibits their differentiation into adipocytes. In conclusion, our study demonstrates that BOB inhibits osteoclastogenesis and promotes osteoblastogenesis in vitro by regulating various signaling pathways. These findings suggest that BOB has potential value as a novel therapeutic agent for the prevention and treatment of osteoporosis.

• Parasites, Hosts and Diseases
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• 제61권4호
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• pp.449-454
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• 2023

Free-living amoebae (FLA) rarely cause human infections but can invoke fatal infections in the central nervous system (CNS). No consensus treatment has been established for FLA infections of the CNS, emphasizing the urgent need to discover or develop safe and effective drugs. Flavonoids, natural compounds from plants and plant-derived products, are known to have antiprotozoan activities against several pathogenic protozoa parasites. The anti-FLA activity of flavonoids has also been proposed, while their antiamoebic activity for FLA needs to be emperically determined. We herein evaluated the antiamoebic activities of 18 flavonoids against Naegleria fowleri and Acanthamoeba species which included A. castellanii and A. polyphaga. These flavonoids showed different profiles of antiamoebic activity against N. fowleri and Acanthamoeba species. Demethoxycurcumin, kaempferol, resveratrol, and silybin (A+B) showed in vitro antiamoebic activity against both N. fowleri and Acanthamoeba species. Apigenin, costunolide, (-)-epicatechin, (-)-epigallocatechin, rosmarinic acid, and (-)-trans-caryophyllene showed selective antiamoebic activity for Acanthamoeba species. Luteolin was more effective for N. fowleri. However, afzelin, berberine, (±)-catechin, chelerythrine, genistein, (+)-pinostrobin, and quercetin did not exhibit antiamoebic activity against the amoeba species. They neither showed selective antiamoebic activity with significant cytotoxicity to C6 glial cells. Our results provide a basis for the anti-FLA activity of flavonoids, which can be applied to develope alternative or supplemental therapeutic agents for FLA infections of the CNS.

• 한국식품저장유통학회지
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• 제30권3호
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• pp.369-382
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• 2023

We examined the changes in the physicochemical quality characteristics and antioxidant activity of fresh-cut Fuji apples (Malus pumila) during processing and storage after treatment with browning inhibitors. The primary aim was to elucidate processing suitability and storability. We observed that in the processing stage of slicing fresh Fuji apples, there were no significant differences in 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging ability and ferric-reducing antioxidant power (FRAP). However, after NaClO treatment, total flavonoid and total polyphenol contents decreased. When freshcut Fuji apples were treated with browning inhibitors and stored at 4℃, the L value and hardness decreased; however, the weight loss rate increased based on the storage period of all fruit groups treated with Citrus unshiu Markovich (CuM), calcium ascorbate (CA), and ascorbic acid (AA). The pH increased after 2 days of storage in 1% CuM and after 6 days of storage in 1% CA; however, no changes in pH were observed during the storage period in 1% AA. The DPPH radical scavenging activity was generally good under storage conditions of 1% AA at 4℃ and 1% CA at 20℃. Furthermore, FRAP remained relatively constant under storage conditions of 1% CA. The quality characteristics and antioxidant activity of fresh-cut fruits during processing and storage can be used as basic data for industries. Furthermore, we can gain confidence in quality improvements by improving the production and distribution environment of fresh-cut agricultural products.

• 대한한의학방제학회지
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• 제31권4호
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• pp.373-388
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• 2023

Objectives : This study aimed to provide basic data for research by investigating non-clinical experimental studies on herbal medicines and its compounds for precocious puberty. Methods : A search was conducted for all literature until October 2023 using combinations of keywords such as precocious puberty, puberty, and chinese medicine in three databases (Pubmed, OASIS, and ScienceON). Results : 1. In animal experiments, studies were mainly conducted using a model that induced precocious puberty by subcutaneously administering danazol to SD rats on the 5th day after birth, and in cell experiments, precocious puberty was induced by treating GT1-7 cells with kisspeptin 10 or estradiol. 2. Anemarrhenae Rhizoma, Phellodendri Cortex, and Prunellae Spica were mainly used as herbal medicine to evaluate their efficacy on precocious puberty in non-clinical experiments. 3. Macroscopic observation, hematological analysis, histological analysis, and genetic analysis were performed as methods to analyze the experimental results. Conclusions : In this study, the effects of herbal medicine on precocious puberty and non-clinical research methods were confirmed. Based on the results of this study, it is expected that non-clinical effectiveness and mechanism research on materials that are clinically effective in Traditional Korean Medicine will be revitalized.

• 한국재료학회지
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• 제34권3호
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• pp.170-174
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• 2024

In this study, we report the microstructural evolution and shear strength of an Sn-Sb alloy, used for die attach process as a solder layer of backside metal (BSM). The Sb content in the binary system was less than 1 at%. A chip with the Sn-Sb BSM was attached to a Ag plated Cu lead frame. The microstructure evolution was investigated after die bonding at 330 ℃, die bonding and isothermal heat treatment at 330 ℃ for 5 min and wire bonding at 260 ℃, respectively. At the interface between the chip and lead frame, Ni₃Sn₄ and Ag₃Sn intermetallic compounds (IMCs) layers and pure Sn regions were confirmed after die bonding. When the isothermal heat treatment is conducted, pure Sn regions disappear at the interface because the Sn is consumed to form Ni₃Sn₄ and Ag₃Sn IMCs. After the wire bonding process, the interface is composed of Ni₃Sn₄, Ag₃Sn and (Ag,Cu)₃Sn IMCs. The Sn-Sb BSM had a high maximum shear strength of 78.2 MPa, which is higher than the required specification of 6.2 MPa. In addition, it showed good wetting flow.

• 대한화학회지
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• 제68권4호
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• pp.191-198
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• 2024

내분비 교란 화학물질(EDCs)은 생체 외부로부터 유입되어 인체의 내분비 기관 내에서 호르몬 작용을 교란시키는 화합물이다. 파라벤, 벤조페논, 비스페놀, 프탈레이트 등이 대표적이며, 현재 광범위한 분야에서 사용되고 있다. 하지만 이들에게 지속적으로 노출되면 혈당조절, 생식, 대사, 신경계 발달, 임신, 출산, 성장 등에 부정적인 영향을 끼칠 수 있다. 본 연구에서는 EDCs의 노출정도를 파악하기 위하여 인체시료(소변)를 liquid-liquid-extraction을 사용하여 전처리한 뒤 UPLC-MS/MS로 효과적이고 빠르게 분석하였다. 이와 같이 분석조건을 확립하고, 분석법의 유효성 검증을 통해 동시분석법의 신뢰도를 평가하였다. 결과는 정확도가 75.28~122.36%, 정밀도가 2.16~22.74%의 수치를 보였다. 본 연구에서 확립된 분석법은 추후 인체시료 중 EDCs의 노출을 평가하고 모니터링할 수 있는 연구의 방법론으로 이용될 수 있을 것이다.

• 대한한의학방제학회지
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• 제32권3호
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• pp.247-261
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• 2024

Objectives : Zuojin Pill, recognized as an effective herbal remedy, has undergone investigation for its potential in alleviating symptoms like indigestion, vomiting, and abdominal distension. The purpose of this study was to investigate the mechanism of digestive function activation through network pharmacology, particularly focused on improving functional dyspepsia. Methods : The two components, Coptidis Rhizoma and Evodiae Fructus, constituting Zuojin Pill were analyzed based on broad information on chemical and pharmacological properties, confirming 40 active compounds and 115 digestive-related molecular targets. Concentration analysis revealed impacts on various pathways related to digestive functions. Results : According to network pharmacological analysis of Zuojin Pill, quercetin and beta-sitosterol were exhibited relatively numerous targets, suggesting their potential significance in the therapeutic activity of Zuojin Pill and by a Protein-Protein Interaction (PPI) network, JUN, RELA, MAPK1, HSP90AA1, TP53, TNF, AKT1, IL6, MAPK14, ESR1, FOS, MYC were identified. Also, berberine exhibited the highest contribution index (92.58%), indicating that this compound may be a major contributor to the digestive activity of Zuojin Pill. Additionally, functional interaction analysis by GeneMANIA indicated that targets of Zuojin Pill could functionally interact through various mechanisms, implying similarities in pharmacological roles. Conclusions : These findings contribute valuable insights into the digestive function activation mechanism and highlight the therapeutic potential of Zuojin Pill in improving functional dyspepsia.

• 한국환경농학회지
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• 제1권1호
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• pp.22-30
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• 1982

본 조사(本 調査)는 김해평야(金海平野)외 농업용수(農業用水)로 사용(使用)하고 있는 낙동강지류(洛東江支流)의 수질(水質)을 주요(主要) 양수장부근(揚水場附近) 6척지점(個地點)(대저, 식만, 봉림, 녹산, 마찰, 장유)에서 1981년(年) 5월(月), 7월(月) 및 10월(月)의 3회(回)에 걸쳐 채수분석(採水分析)함으로서 수질보전대책(水質保全對策)과 이 지역(地域)의 농업(農業)에 참고자료(參考資料)를 제공(提供)코자 하였다. 시기별(時期別) 각(各) 지점(地點)의 수온(水溫), 탁도(濁度), 증발잔류물(蒸發殘留物), pH, BOD, COD, DO, 경도(硬度), $Cl-,\;SO_4--,\;PO_4---,\;NH_4+,\;NO_3-,\;K+,\;Na+$, 일반세균(一般細菌), 대장균(大腸菌), 중금속(重金屬)(Cd, Pb, Cr, Fe, Zn)을 분석(分析)한 결과(結果)를 요약(要約)하면 다음과 같다. 1) 시기별(時期別) 모든 지점(地點)의 평균치(平均値)는 pH 7.8, BOD 6.3 ppm, COD 6.5 ppm, DO 6.4 ppm, 경도(硬度) 231 ppm, Cl- 582 ppm, $SO_4--\;412\;ppm,\;PO_4---\;2.32\;ppm,\;NH_4+$ 3.8 ppm, Na+ 478 ppm, 대장세균(大腸細菌) 2964개(個)/100ml, Cd 0.0040 ppm, Pb 0.006 ppm이었다. 2) 지점별(地點別) 오염도(汚染度)가 가장 높은 곳은 식만 양수장부근(揚水場附近)이었고 그 다음이 대저, 봉림, 녹산이었으며 비교적 오염도(汚染度)가 덜한 곳은 마찰, 장유양수장(揚水場) 부근(附近)이었다. 3) 오염도(汚染度)가 가장 높은 식만양수장(揚水場) 부근(附近)의 수질(水質)은 약간의 취기(臭氣)가 있을 뿐만 아니라 외관상(外觀上) 약간의 흑색(黑色)을 띄고 있었고, 분석평균치(分析平均値)는 pH가 8.0, BOD 8.1 ppm, COD 8.2ppm, DO 5.3ppm으로 농업용수기준(農業用水基準)의 한계(限界)에 도달(到達)하고 있었다. 이곳이 오염도(汚染度)가 높은 것은 김해시(金海市)의 주요(主要) 공장폐수(工場廢水)가 이곳으로 집중(集中) 배출(排出)되기 때문인 것으로 본다. 4) 시기별(時期別) 각(各) 성분(成分)의 차리(差異)는 뚜렷한 경향(傾向)이 없었으며 다만 DO가 10월(月)이 5월(月) 및 7월(月)보다 높게 나타났고 $NH_4+$는 10월(月)이 5월(月) 및 7월(月)에 비(比)해서 낮게 나타났을 뿐이다. 5) 각(各) 지점(地點)이 $NH_4+$함양(含量)이 높아 실소질비료(室素質肥料)의 시비(施肥)에 이를 고려(考慮)해야 할 것이며, Cl- 및 Na+함양(含量)은 평수시(平水時)에는 별문제(別問題)가 없을 것이나 갈수기(渴水期)에는 관개(灌漑)에 주의(注意)를 해야 할 것으로 본다.