• Molecules and Cells
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• 제47권1호
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• pp.100005.1-100005.15
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• 2024

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease with a complex genetic basis, presenting both in familial and sporadic forms. The hexanucleotide (G₄C₂) repeat expansion in the C9orf72 gene, which triggers distinct pathogenic mechanisms, has been identified as a major contributor to familial and sporadic Amyotrophic lateral sclerosis cases. Animal models have proven pivotal in understanding these mechanisms; however, discrepancies between models due to variable transgene sequence, expression levels, and toxicity profiles complicate the translation of findings. Herein, we provide a systematic comparison of 7 publicly available Drosophila transgenes modeling the G₄C₂ expansion under uniform conditions, evaluating variations in their toxicity profiles. Further, we tested 3 previously characterized disease-modifying drugs in selected lines to uncover discrepancies among the tested strains. Our study not only deepens our understanding of the C9orf72 G₄C₂ mutations but also presents a framework for comparing constructs with minute structural differences. This work may be used to inform experimental designs to better model disease mechanisms and help guide the development of targeted interventions for neurodegenerative diseases, thus bridging the gap between model-based research and therapeutic application.

• 한국어병학회지
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• 제5권2호
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• pp.143-152
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• 1992

Metallothionein은 세포내의 중금속의 농도을 조절하는 주요한 단백질로서 bacteria에서 척추동물에 이르기까지 모든 생명체에서 나타나는 공통된 단백질이다. 비록 metallothionein의 정확한 기능은 알려져 있지 않으나 독성을 나타내는 중금속에 대하여 세포내 방어기작에 관여할 뿐만 아니라 여러다른 유전자의 총괄적 조절기작 및 matalloprotein의 발현에 관여할 것으로 보고있다. 본 연구에서는 Channel Catfish의 metallothionein cDNA 유전자를 poly(A)를 갖는 mRNA로 부터 Reverse Transcriptase-Polymerase Chain Reaction(RT-PCR)에 의하여 cloning하였다. 증폭된 PCR products는 pBluescript SK+의 EcoRV site 및 pUC19의 Smal site에 dT tailing을 하여 cloning하였으며, PCR products는 multicloning site에 있는 EcoRI 및 HindIII 로 절단하여 확인하거나 신속한 PCR screening에 의하여 확인하였다. 여러 PCR clone 중 하나인 pMT150에 대한 DNA 염기서열을 조사한 결과 다른 어류의 metallothionein cDNA 유전자와 높은 유사성을 보였다.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.311-319
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• 2020

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC₅₀ values of 12.6, 21.8, and 11.12 µM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 at a concentration of 20 µM with no observed toxicity in Vero cells at 10 µM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.

• Molecular & Cellular Toxicology
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• 제2권3호
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• pp.151-158
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• 2006

Khal was a synthetic congener of halocidin, a heterodimeric peptide consisting of 19 and 15 amino acid residues detected in Halocynthia aurantium. This compound was considered a candidate for the development of a novel peptide antibiotic. The genotoxicity of Khal was subjected to high throughput toxicity screening (HTTS) because they revealed strong antibacterial effects. Mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), single cell gel electrophoresis (Comet) assay and chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. These compounds are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. Before performing the comet assay, $IC_{20}$ of Khal was determined the concentration of $25.51\;{\mu}/mL\;and\;21.99\;{\mu}g/mL$ with and without S-9, respectively. In the comet assay, Khal was not induced DNA damage in mouse lymphoma cell line. Also, the mutation frequencies in the Khal-treated cultures were similar to the vehicle controls. It is suggests that Khal is non-mutagenic in MOLY assay. And no clastogenicity was observed in Khal-treated Chinese hamster lung cells. The results of this battery of assays indicate that Khal has no genotoxic potential in bacterial or mammalian cell systems. Therefore, we suggest that Khal, as the optimal candidates with both no genotoxic potential and antibacterial effects must be chosen.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 1999년도 The 6th International Symposium on the Development of Anti-Cancer Resource from Plants
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• pp.1-45
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• 1999

To date many kinds of compounds have been obtained from plants kingdom as antineoplastic and anti-cancerous agents. However, there is no special type of compounds for ncancer therapy. Various types of substances are effective for various types of cancers and tumors: for instance, alkaloids, lignans, terpenes and steroids etc. Curcumol obtained from Curcuma aromatica was tested and noticed to be effective against cancer of the uterine cervix clinically Oridonin isolated from Rabdosia ssp.is now investigated for clinical trials in China. Moreover, camptothecine isolated from Camptotheca acuminata is also antineoplastic alkaloid, but is very toxic. Chemical modification has been tried to decrease its toxicity. This compound is now using as clinical agent. Harringtonin was investigated as an anticancerous drug in China. Taxol, a compound with a taxane ring isolated from the bark of Taxus brevifolia, has been demonstrated to have substantial anticancer activity in patients with solid tumors refractory standard chemotherapy. Supply of this drug has severely limited full exploration of its antineoplastic potential. Some efforts are continued in National Cancer Institute NCI) Washington for surveying various Taxus species for optimal taxol content, improvement in semi-synthesis from baccatin III, improvement in method of extraction, and development of alternative renewable resources. Further, there are many compounds which have been reported as antineoplastic agents. On the other hand, we have screened on higher plants collected in Japan, China, Korea, Southeast Asia and South America for antineoplastic activity, which has been done using Sarcoma 180 ascites in mice, P388 Iymphocytic leukemia in mice, Chinese hamster lung V-79 cells, P388 cells and nasopharynx carcinoma (KB) cells in our laboratory, as primary screening. In this meeting, I will present on antitumor and cytotoxic substances of the higher plants (Rubia cordifolia, Ailanfhus Vilmoriniana, Aster tataricus, Taxus cuspidata var. nana, Cephalotaxus harringtonia var drupacea, etc.) selected from above screening tests.

• 생약학회지
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• 제41권3호
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• pp.166-173
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• 2010

Oxidative stress to proteins, lipids, or DNA is higher in human autopsy tissue and in rodent models of a number of neurodegenerative conditions, including Alzheimer's and Parkinson's disease. On the basis of this information, we established a screening system using N18-RE-105 cells to identify therapeutic agents that can protect cells from glutamate toxicity. During the course of our screening program, we recently isolated the active compound 9-hydroxy-$\alpha$-tocopherone ($\alpha$-TP), which prevents glutamate-induced cell death, from Viola mandshurica. The chemical structure of $\alpha$-TP was identified using spectroscopic methods and by comparison with literature values. Antioxidant activity and protective effects of $\alpha$-TP were evaluated by DPPH radical-scavenging assay, morphological assay, MTT reduction assay, and lactate dehydrogenase (LDH) release assay. These results suggest that $\alpha$-TP could be a new potential chemotherapeutic agent against neuronal diseases.

• Plant Resources
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• 제3권1호
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• pp.1-45
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• 2000

To date many kinds of compounds have been obtained from plants kingdom as antineoplastic and anti-cancerous agents. However, there is no special type of compounds for cancer therapy. Various types of substances are effective for various types of cancers and tumors: for instance, alkaloids. lignans, terpenes and steroids etc. Curcumol obtained from Curcuma aromatica was tested and noticed to be effective against cancer of the uterine cervix clinically. Oridonin isolated from Rabdosia ssp. is now investigate for clinical trials in China. Moreover camptothecine isolated from Camptotheca acuminata is also antineoplastic alkaloid, but is very toxic. Chemical modification has been tried to decrease its toxicity This compound is now using as clinical agent. Harringtonin was investigated as an anticancerous drug in China. Taxol, a compound with a taxane ring isolated from the bark of Taxus brevifotia. has been demonstrated to have substantial anticancer activity in patients with solid tumors refractory standard chemotherapy. Supply of this drug has severely limited full exploration of its antineoplastic potential Some efforts are continued in National Cancer Institute(NCI) Washington for surveying various Taxus species for optimal taxol content, improvement in semi-synthesis from baccatin 111, improvement in method of extraction, and development of alternative renewable resources. Further, there are many compounds which have been reported as antineoplastic agents. On the other hand, we have screened on higher plants collected In Japan, China, Korea. Southeast Asia and South America for antineoplastic activity, which has been done using Sarcoma 180 ascites in mice, P388 Iymphocytic leukemia In mice, Chinese hamster lung V-79 cells, P388 cells and nasopharynx carcinoma(KB) cells in our laboratory, as primary screening. In this meeting, 1 will present on antitumor and cytotoxic substances of the higher plants(Rubis cordifolia, Ailanthus vilmoriniana, Aster tataricus, Taxus cuspidata var. nana, Cephalotaxus harringtonia var. drupacea, etc.) selected from above screening tests.

• 한국환경보건학회지
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• 제48권5호
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• pp.272-281
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• 2022

Background: The constant consumption of chemical products owing to expanding industrialization has led to an increase in public interest in chemical substances. As the production and disposal processes for these chemical products cause environmental problems, regional information on the hazard level of chemical substances is required considering their effects on humans and in order to ensure environmental safety. Objectives: This study aimed to identify hazard contribution and spatiotemporal characteristics by region and chemical by calculating a hazard-based result score using pollutant release and transfer register (PRTR) data. Methods: This study calculated the chemical discharge and hazard-based result score from the Risk-Screening Environmental Indicators (RSEI) model, analyzed their spatiotemporal patterns, and identified hotspot areas where chemical discharges and high hazard-based scores were concentrated. The amount of chemical discharge and hazard-based risk scores for 250 cities and counties across South Korea were calculated using PRTR data from 2011 to 2018. Results: The chemical discharge (high densities in Incheon, Daegu, and Busan) and hazard-based result scores (high densities in Incheon, Chungcheongnam-do, and some areas of Gyeongsangnam-do Province) showed varying spatial patterns. The chemical discharge (A, B) and hazard-based result score (C, D) hotspots were identified. Additionally, identification of the hazard-based result scores revealed differences in the type of chemicals contributing to the discharge. Ethylbenzene accounted for ≥80% of the discharged chemicals in the discharge hotspots, while chromium accounted for >90% of the discharged chemicals in the hazard-based result score hotspots. Conclusions: The RSEI hazard-based result score is a quantitative indicator that considers the degree of impact on human health as a toxicity-weighted value. It can be used for the management of industries discharging chemical substances as well as local environmental health management.

• 한국수산과학회지
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• 제54권6호
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• pp.927-937
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• 2021

This study was performed to screen the antimicrobial activities of the extract from the Pacific oyster Crassostrea gigas against skin pathogens and to purify the relevant antibacterial peptide. The acidified extract showed potent antibacterial activities against gram-positive and gram-negative bacteria but showed no activity against Candida albicans and no significant cell toxicity. Among acne-causing pathogens, the acidified extract showed potent antibacterial activity only against Staphylococcus aureus, and its antibacterial activity was completely abolished by treatment with trypsin or chymotrypsin, and was inhibited by salt treatment. The acidified extract showed strong DNA-binding ability but did not show bacterial membrane permeabilizing ability. Based on antimicrobial activity screening and cytotoxic effects, a novel antibacterial peptide was purified from the acidified gill extract using solid-phase extraction, cation-exchange, and reversed-phase HPLC. The resulting peptide had a molecular weight of 4800.8 Da and showed partial sequence homology with the carbonic anhydrase 4 (CA4) protein in the hard-shelled mussel. Overall, we purified a novel antibacterial peptide, named cgCAFLP, which is related to carbonic anhydrase 4 (CA4) protein, against skin pathogens. Our results suggest that the Pacific oyster extract could be used as an additive to control some acne-related skin pathogens (S. aureus).

• International Journal of Industrial Entomology and Biomaterials
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• 제47권1호
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• pp.12-24
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• 2023

Sitophilus oryzae L. (Rice Weevil) is a stored pest of rice that causes extensive loss throughout the world. We tested the leaf powders of 12 plant species viz., Chrysanthemum sp., Cinnamomum zeylanicum, Citrus grandis, Citrus limon, Gliricidia sepium, Gymnema sylvestre, Hemigraphis colorata, Michelia champaca, Moringa oleifera, Murraya koenigii, Polyalthia longifolia, and Sauropus androgynus at dosages of 1.00, 1.50, 2.00 and 3.00g against the adult rice weevil and mortality was recorded at 1, 2, 3, 5, 7, 12 and 2l days after treatment (DAT) by direct contact toxicity for their adulticidal effect. We observed 100 percent adult mortality in C. zevlanicum and M. koenigii among the tested leaf powders. In addition, the first-time tested H. colorata and S. androgynus also caused high mortality compared to other plants. All the plant powders caused moderate to high adult mortality. Hence, these plants could be effective botanical insecticides against S. oryzae as they comprise a potential source of bioactive chemicals and are generally free from toxicants. Applications of these natural derivatives in S. oryzae control could reduce the cost of control methods and storage of rice contamination. Therefore, the present study indicates that some plant extracts can be used as an alternative to toxic synthetic chemicals in the management of rice weevils.