• Journal of Ginseng Research
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• 제47권2호
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• pp.183-192
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• 2023

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H₂S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2489-2493
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• 2015

Background: Loss of heterozygosity (LOH) on chromosomal regions is crucial in tumor progression and this study aimed to identify genome-wide LOH in pancreatic cancer. Materials and Methods: Single-nucleotide polymorphism (SNP) profiling data GSE32682 of human pancreatic samples snap-frozen during surgery were downloaded from Gene Expression Omnibus database. Genotype console software was used to perform data processing. Candidate genes with LOH were screened based on the genotype calls, SNP loci of LOH and dbSNP database. Gene annotation was performed to identify the functions of candidate genes using NCBI (the National Center for Biotechnology Information) database, followed by Gene Ontology, INTERPRO, PFAM and SMART annotation and UCSC Genome Browser track to the unannotated genes using DAVID (the Database for Annotation, Visualization and Integration Discovery). Results: The candidate genes with LOH identified in this study were MCU, MICU1 and OIT3 on chromosome 10. MCU was found to encode a calcium transporter and MICU1 could encode an essential regulator of mitochondrial $Ca^{2+}$ uptake. OIT3 possibly correlated with calcium binding revealed by the annotation analyses and was regulated by a large number of transcription factors including STAT, SOX9, CREB, NF-kB, PPARG and p53. Conclusions: Global genomic analysis of SNPs identified MICU1, MCU and OIT3 with LOH on chromosome 10, implying involvement of these genes in progression of pancreatic cancer.

• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.354-363
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• 2009

Cytotoxic Nitric oxide (NO) overproduced by inducible NO Synthase (iNOS or NOS2), which was induced in inflammatory reactions and immune responses directly or indirectly affects the functions as host defense and can cause normal tissue damage. Microarray analysis was performed to identify gene profiles of both NO-dependent and -independent transcripts in RAW 264.7 macrophages that use selective NOS2 inhibitors aminoguanidine ($100\;{\mu}M$) and L-canavanine (1 mM). A total of 3,297 genes were identified that were up- or down-regulated significantly over 2-fold in lipopolysaccharide (LPS)-treated macrophages. NO-dependency was determined in the expressed total gene profiles and also within inflammatory conditions-related functional categories. Out of all the gene profiles, 1711 genes affected NO-dependently and -independently in 567 genes. In the categories of inflammatory conditions, transcripts of 16 genes (Pomp, C8a, Ifih1, Irak1, Txnrd1, Ptafr, Scube1, Cd8a, Gpx4, Ltb, Fasl, Igk-V21-9, Vac14, Mbl1, C1r and Tlr6) and 29 geneas (IL-1beta, Mpa2l, IFN activated genes and Chemokine ligands) affected NO-dependently and -independently, respectively. This NO dependency can be applied to inflammatory reaction-related functional classifications, such as cell migration, chemotaxis, cytokine, Jak/STAT signaling pathway, and MAPK signaling pathway. Our results suggest that LPS-induced gene transcripts in inflammation or infection can be classified into physiological and toxic effects by their dependency on the NOS2-mediated NO release.

• Journal of Microbiology and Biotechnology
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• 제9권6호
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• pp.751-756
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• 1999

For mass production of poly(3-hydroxybutyrate) (PHB), high cell density cultures of Ralstonia eutropha were carried out in 2.5-1 and 60-1 fermentors by two fed-batch culture techniques of nitrogen and phosphate limitation. When the nitrogen limitation technique was employed using both an on-line glucose monitoring and control system, a high concentration level of PHB (121g/l) was obtained in the small-scale fermentor of 2.5 1. However, the PHB concentration obtained in a large-scale fermentor of 60 1 only turned out to be 60g/l. In contrast, when another fed-batch culture technique of the phosphate-limitation employing dissolved oxygen (DO) stat glucose feeding was used, a large amount of PHB was successfully produced in both 60-1 and 2.5-1 fermentors. In a 2.5-1 fermentor, concentrations of PHB and cells obtained in 58 h were 175 and 210 g/l, respectively, which corresponded to the PHB productivity level of 3.02 g/l/h. In a 60-1 fermentor, a final cell concentration of 221 g/l and a PHB concentration of 180 g/l with PHB productivity level of 3.75 g/l/h were obtained in 48h. PHB content and yield from glucose were 81% and 0.38g PHB/g glucose, respectively. These data suggest that the phosphate limitation technique is more effective compared to nitrogen limitation in the mass production of PHB by R. eutropha of a large scale.

• Toxicological Research
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• 제33권4호
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• pp.325-332
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• 2017

3-Bromo-4,5-dihydroxybenzaldehyde (BDB) is a natural bromophenol compound that is most commonly isolated from red algae. The present study was designed to investigate the anti-inflammatory properties of BDB on atopic dermatitis (AD) in mice induced by 2,4-dinitrochlorobenzene (DNCB) and on lipopolysaccharide (LPS)-stimulated murine macrophages. BDB treatment (100 mg/kg) resulted in suppression of the development of AD symptoms compared with the control treatment (induction-only), as demonstrated by reduced immunoglobulin E levels in serum, smaller lymph nodes with reduced thickness and length, a decrease in ear edema, and reduced levels of inflammatory cell infiltration in the ears. In RAW 264.7 murine macrophages, BDB (12.5, 25, 50, and $100{\mu}M$) suppressed the production of interleukin-6, a proinflammatory cytokine, in a dose-dependent manner. BDB also had an inhibitory effect on the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) and signal transducer and activator of transcription 1 (STAT1; Tyr 701), two major signaling molecules involved in cellular inflammation. Taken together, the results show that BDB treatment alleviates inflammatory responses in an atopic dermatitis mouse model and RAW 264.7 macrophages. These results suggest that BDB may be a useful therapeutic strategy for treating conditions involving allergic inflammation such as atopic dermatitis.

• Journal of Applied Biological Chemistry
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• 제63권1호
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• pp.95-101
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• 2020

건선(psoriasis)은 인체 피부조직 중 표피의 과증식 및 다양한 크기의 홍반, 인설 등이 동반되는 난치성 자가면역 피부질환이다. 건선 피부염 발병 기작은 명확히 규명되지 않았으나 각질 형성세포의 과분화 과정에 관여하는 염증성 cytokine과 Th17 세포를 포함한 면역세포를 염증부위로 유인하는 chemokine (C-C motif) ligand 20 (CCL20)이 발병과정에 관여하는 것으로 알려진다. 따라서 건선치료에 효과적인 천연 소재를 발굴하기 위해 예로부터 항염증 활성이 알려진 익지인(Alpiniaoxyphylla Miquel)의 유효성분인 yakuchinone-A의 건선 피부염 개선효과를 연구하였다. 먼저 CCK-8 assay 통해 human keratinocyte (HaCaT) 세포에 tumor necrosis factor-alpha (TNF-α)와 yakuchinone-A를 동시 처리하여 세포독성을 관찰한 결과, yakuchinone-A는 10 ㎍/mL까지 세포독성이 관찰되지 않았다. TNF-α를 HaCaT 세포에 처리하여 염증을 유발한 후 yakuchinone-A를 농도별로 처리한 결과 IL-6, IL-8, TNF-α 등 건선 피부염 유발 cytokine의 mRNA 발현이 각각 61.4±7.5, 23.6±1.5, 46.0±4.8% 수준으로 감소하였고, Th17 세포를 유인하는 chemokine인 CCL20 또한 yakuchinone-A에 의해 유의적으로 억제되었다. 또한 CCL20 발현에 관여하는 NF-κB/IκB pathway에서 IκB 인산화 및 STAT3 인산화가 yakuchinone-A에 의해 79.1±5.0, 80.8±2.3% 수준만큼 농도 의존적으로 억제되었다. 마지막으로 Th17 세포에 의해 분비되는 IL-17A에 의해 활성화된 HaCaT 세포에 yakuchinone-A를 처리한 결과, CCL20 mRNA발현이 농도의존적으로 감소하였다. 이러한 결과들을 토대로 yakuchinone-A는 건선 피부염 개선 활성을 가지며, 향후 새로운 건선 피부염 개선 소재로 개발될 수 있을 것으로 기대된다.

• Journal of Ginseng Research
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• 제39권1호
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• pp.54-60
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• 2015

Background: The present study was designed to prepare and find the optimum active preparation or fraction from Korea Red Ginseng inhibiting matrix metalloproteinase-13 (MMP-13) expression, because MMP-13 is a pivotal enzyme to degrade the collagen matrix of the joint cartilage. Methods: From total red ginseng ethanol extract, n-BuOH fraction (total ginsenoside-enriched fraction), ginsenoside diol-type-enriched fraction (GDF), and ginsenoside triol-type-enriched fraction (GTF) were prepared, and ginsenoside diol type-/F4-enriched fraction (GDF/F4) was obtained from Panax ginseng leaf extract. Results: The n-BuOH fraction, GDF, and GDF/F4 clearly inhibited MMP-13 expression compared to interleukin-$1{\beta}$-treated SW1353 cells (human chondrosarcoma), whereas the total extract and ginsenoside diol-type-enriched fraction did not. In particular, GDF/F4, the most effective inhibitor, blocked the activation of p38 mitogen-activated protein kinase (p38 MAPK), c-Jun-activated protein kinase (JNK), and signal transducer and activator of transcription-1/2 (STAT-1/2) among the signal transcription pathways involved. Further, GDF/F4 also inhibited the glycosaminoglycan release from interleukin-$1{\alpha}$-treated rabbit cartilage culture (30.6% inhibition at $30{\mu}g/mL$). Conclusion: Some preparations from Korean Red Ginseng and ginseng leaves, particularly GDF/F4, may possess the protective activity against cartilage degradation in joint disorders, and may have potential as new therapeutic agents.

• KSBB Journal
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• 제29권1호
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• pp.50-57
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• 2014

NF-${\kappa}B$ is a transcriptional factor which is involved in many biological processes including immunity, inflammation, and cell survival. Many investigators studied on the mechanism involved in activation of NF-${\kappa}B$ signalling pathway via ubiquitination and degradation of $I{\kappa}B$ regarding skin disease. Some specific molecules including Akt, MEK, p38 MAP Kinase, Stat3, et al. represent convergence points and key regulatory proteins in signaling pathways controlling cellular events such as growth and differentiation, energy homeostasis, and the response to stress and inflammation. Ultraviolet (UV) irradiation has many adverse effects on skin, including inflammation, alteration in the extracellular matrix, cellular senescence, apoptosis and skin cancer. Prunus mume, a naturally derived plant extract, has beneficial biological activities as blood fluidity improvement, anti-fatigue action, antioxidative and free radical scavenging activities, inhibiting the motility of Helicobacter pyolri. Previous reports on various beneficial function prompted us to investigate UVB-induced or other immunostimulated biological marker regarding P. mume extract. P. mume extract suppresses UVB-induced cyclooxygenase-2 (COX-2) expression in mouse skin epidermal JB6 P+ cells. The activation of activator protein-1 and nuclear factor-${\kappa}B$ induced by UVB was dose-dependently inhibited by P. mume extract treatment. This results suggest that P. mume extracts might be used as a potential agents for protection of inflammation or UVB induced skin damage.

• 한국미생물·생명공학회지
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• 제17권4호
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• pp.392-396
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• 1989

Facultative methylotroph인 Methylobacterium organophilum을 유일한 탄소원으로 메탄올을 0.5% (v/v) 함유한 최소 합성배지를 이용하여 pH 6.8과 3$0^{\circ}C$에서 배양하였다. 세포의 증식은 배지 내의 여러 성분들에 의해 영향을 받았으며 이로부터 최대증식속도를 얻을 수 있는 최적 합성배지 조성을 확립하였다. 배지조성 중 질소원이 결핍되면 세포의 증식이 감소하며 Fe$^{+2}$ 또는 Mn$^{+2}$ 이온의 결핍은 세포의 비증식속도를 감소시켰다. 탄소원인 메탄올은 농도를 증가시킬수록 세포의 비증식속도가 감소하는 메탄올의 기질 저해성을 확인하였으며, 4%(v/v) 이상의 메탄을 농도에서는 세포의 증식이 완전히 저해되었다. 이러한 메탄올의 기질 저해성은 간헐식 유가배양법을 이용하여 극복하고 PHB의 축적을 촉진하는 영양분 제한(nutrient-deficiency) 실험을 수행하였다. 합성배지의 영양분 중 NH$_{4}^{+}$, SO$_{4}^{-2}$, $K^+$ 또는 PO$_{4}^{-3}$ 이온을 결핍시켰을 때 M. organophilum의 PHB 생산이 증가하였으며 칼륨이온을 결핍시켰을때 세포의 건조 중량에 대한 PHB 함량은 최대 58%를 얻었다.

• 한국발생생물학회지:발생과생식
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• 제12권2호
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• pp.159-168
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• 2008

Nanog is a newly identified member of the homeobox family of DNA binding transcription factors that functions to maintain the undifferentiated state of stem cells. However, molecular mechanisms underlying the function of Nanog remain largely unknown. To elucidate the regulatory roles of Nanog involved in maintenance of P19 embryonal carcinoma (EC) stem cells, we transfected three small interfering RNA (siRNA) duplexes targeted against different regions of the Nanog gene into P19 cells. The Nanog siRNA-100 duplexes effectively decreased the expression of Nanog up to 30.7% compared to other two Nanog siRNAs, the Nanog siRNA-400 (67.9 %) and -793 (53.0%). When examined by RT-PCR and real-time PCR, the expression of markers for pluripotency such as Fgf4, Oct3/4, Rex1, Sox1 and Yes was downregulated at 48 h after transfection with Nanog siRNA-100. Furthermore, expression of the ectodermal markers, Fgf5 and Isl1 was reduced by Nanog knockdown. By contrast, the expression of other markers for pluripotency such as Cripto, Sox2 and Zfp57 was not affected by Nanog knockdown at this time. On the other hand, the expression of Lif/Stat3 pathway molecules and of the endoderm markers including Dab2, Gata4, Gata6 and the germ cell nuclear factor was not changed by Nanog knockdown. The results of this study demonstrated that the knockdown of Nanog expression by RNA interference in P19 cells was sufficient to modulate the expression of pluripotent markers involved in the self-renewal of EC stem cells. These results provide the valuable information on potential downstream targets of Nanog and add to our understanding of the function of Nanog in P19 EC stem cells.