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Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation

  • TaeKyung Nam;Wonku Kang;Sangtaek Oh
    • Journal of Microbiology and Biotechnology
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    • v.33 no.9
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    • pp.1206-1212
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    • 2023
  • The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N6-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

Pheno- and genotyping of Streptococcus iniae isolated from cultured rockfish, Sebastes schlegelii at Korean coastal sites (국내 조피볼락(Sebastes sclegelii) 양식장에서 분리한 Streptococcus iniae의 표현형 및 유전형 특성)

  • Tae-Ho Kim;Hyun-Ja Han;Myoung Sug Kim;Miyoung Cho;Soo-Jin Kim
    • Journal of fish pathology
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    • v.36 no.2
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    • pp.277-286
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    • 2023
  • Korean rockfish, Sebastes schlegelii, is a representative bony fish that belongs to the family Scorpaenidae and the order Scorpaeniformes. It has high ecological and economic value and is widely cultivated in many East Asian countries, including South Korea, Japan and China. One of streptococci, Streptococcus iniae, is Gram-positive cocci with a negative reaction for catalase and oxidase. The Korean rockfish shows clinical signs when infected with S. iniae, such as body darkening, bleeding, enlarged kidneys, blurred eyes, abdominal distension, etc., ultimately leading to death. The Korean rockfish causes significant economic losses every year in South Korea due to streptococcosis. In this study, we identified bacteria from the fish using polymerase chain reaction and conducted analyses of hemolytic activity and biochemical tests using API 20 STREP and API ZYM systems. Results of confirming the hemolytic activity (n=4) observed in alpha-type hemolysis (25%), beta-type hemol- ysis (50%), and gamma-type hemolysis (25%) of isolates. The biochemical test results exhibited sig- nificant variation among S. iniae. Additionally, we performed intraperitoneal injection with S. iniae in the fish and analyzed the phylogenetic tree using housekeeping genes of S. iniae, including cpsD, arcC, glnA, groEL, gyrB, mutS, pheT, prkC, rpoB, and tkt, via multilocus sequence typing (MLST). The lethal dose (LD50) showed strong pathogenicity, such as 3.34 × 10 colony-forming unit (CFU)/ml for 23FBStr0601 strain and 7.16 × 10 CFU/ml for 23FBStr0602 strain. 23FBStr0603 strain showed relatively low pathogenicity at 1.73 × 105 CFU/ml. The strains 23FBStr0601 and 23FBStr0602, which showed strong pathogenicity, clustered into one monophyletic group. The 23FBStr0603 strain showed weak pathogenicity and formed a monophyletic group with KCTC 3657.

Validation of Analytical Methods for Unriped Rubus crataegifolius, Gardenia jasminoides and Ulmus macrocarpa Marker Compounds for Standardization of Natural Complex LS-RUG-com Preparation as Functional Ingredient (천연복합소재 LS-RUG-com의 기능성원료 표준화를 위한 산딸기 미숙과, 치자 및 유백피 지표성분의 분석법 검증)

  • Young Ik Lee;Su Jin Pyo;Hee Jin Lee;Hye Jung Yoon;Ho Yong Sohn;Jin Sook Cho
    • Journal of Life Science
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    • v.34 no.1
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    • pp.59-67
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    • 2024
  • LS-RUG-com preparation in a complex extract from mixture of three natural plants. Rubus crataegifolius/unriped, Gardenia jasminoides and Ulmus marcrocarpa that have been widely used in traditional functional health food. This study was conducted to establish the HPLC analysis methods that can be used to establish quantitative analysis of R. crataegifolius, G. jasminoides and U. macrocarpa for standardization of LS-RUG-com preparations. HPLC analysis methods for simultaneous determination of ellagic acid and geniposide and single determination of catechin-7-O-β-D-apiofuranoside were established for the quality control of natural plants complex (LS-RUG-com). Validation of HPLC analysis were performed by checking specificity, accuracy, precision, limit of detection and quantitation, and linearity following ICH (International Council for Harmonisation) guideline. As the result of quantitative analysis, the contents of ellagic acid, geniposide and catechin-7-O-β-D-apiofuranoside in each plant extracts were 11.2 mg/g (ellagic acid) and 72 mg/g (geniposide) and 10.2 mg/g (catechin-7-O-β-D-apiofuranoside). The contents of ellagic acid, geniposide and catechin-7-O-β-D-apiofuranoside in LS-RUG-com were 4.62~6.82 mg/g (ellagic acid), 19.2~28.8 mg/g (geniposide) and 1.36~2.04 mg/g (catechin-7-O-β-D-apiofuranoside) respectively.

Interactions between NCR+ILC3s and the Microbiome in the Airways Shape Asthma Severity

  • Jongho Ham;Jihyun Kim;Sungmi Choi;Jaehyun Park;Min-gyung Baek;Young-Chan Kim;Kyoung-Hee Sohn;Sang-Heon Cho;Siyoung Yang;Yong-Soo Bae;Doo Hyun Chung;Sungho Won;Hana Yi;Hye Ryun Kang;Hye Young Kim
    • IMMUNE NETWORK
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    • v.21 no.4
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    • pp.25.1-25.16
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    • 2021
  • Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR)+ILC3s in the lung. Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR+ILC3 frequencies and microbial diversity in the lung. Sputum NCR+ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR+ILC3s may contribute to a healthy commensal diversity and normal lung function.

Induction of Unique STAT Heterodimers by IL-21 Provokes IL-1RI Expression on CD8+ T Cells, Resulting in Enhanced IL-1β Dependent Effector Function

  • Dong Hyun Kim;Hee Young Kim;Won-Woo Lee
    • IMMUNE NETWORK
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    • v.21 no.5
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    • pp.33.1-33.19
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    • 2021
  • IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8+ T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8+ T cells and features of IL-1R+ CD8+ T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8+ T cells. Further, IL-1β enhances the effector function of CD8+ T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8+ T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8+ T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8+ T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.

Comparison of Molecular Characterization and Antimicrobial Resistance in Carbapenem-Resistant Klebsiella pneumoniae ST307 and Non-ST307 (Carbapenem 내성 Klebsiella pneumoniae ST307과 Non-ST307의 분자 특성 및 항균제 내성 비교)

  • Hye Hyun Cho
    • Microbiology and Biotechnology Letters
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    • v.51 no.4
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    • pp.500-506
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    • 2023
  • Carbapenem-resistant Klebsiella pneumoniae (CRKP) is emerging as a worldwide public health threat. Recently, Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing sequence type (ST) 307 was identified main clone of CRKP, and dissemination of ST307 was reported in South Korea. This study examined the molecular characteristic and antimicrobial resistance pattern of 50 CRKP isolated from a tertiary hospital in Daejeon, from March 2020 to December 2021. Epidemiological relationship was analyzed by Multilocus sequence typing (MLST) and antimicrobial susceptibility test was determined using disk-diffusion method. PCR and DNA sequence analysis were performed to identify carbapenemase genes. CRKP infections were significantly more frequent in males and the patients aged ≥ 60 years. Among the 50 CRKP isolates, 46 isolates (92.0%) were multidrug-resistant (MDR), and 44 isolates (88.0%) were carbapenemase-producing K. pneumoniae (CPKP). The major carbapenemase type was KPC-2 (36 isolates, 72.0%) and New Delhi metalloenzyme-1 (NDM-1) and NDM-5 were identified in 7 isolates (14.0%) and 1 isolate (2.0%), respectively. In particular, 88.9% (32/36) of KPC-2-producing K. pneumoniae belonged to ST307, whereas 87.5% (7/8) of NDM-1,-5-producing K. pneumoniae belonged to non-ST307. These results suggest that proper infection control and effective surveillance network need to prevent not olny the spread of ST307, but also the development of non-ST307.

Influence of β-carotene enhanced transgenic soybean cultivation on the diversity of non-target arthropods in Korea for three years

  • Sung-Dug Oh;Eunji Bae;Soo-Yun Park;Seong-Kon Lee;Doh-Won Yun;Kihun Ha;Minwook Kim;Yeongjin Son;Chang Uk Eun;Young-Kun Kim;Junho Lee;Dongmin Kim;Donguk Kim;Jongwon Kim;Sang Jae Suh
    • Korean Journal of Agricultural Science
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    • v.49 no.4
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    • pp.719-736
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    • 2022
  • Environmental risk assessment of living modified (LM) crops is essential for their cultivation. In this study, we cultivated β-carotene enhanced transgenic soybean (LM soybean) and non-LM soybean (Gwangan) in living modified organism (LMO) isolated fields, and investigated changes in the insect fauna using three types of collection methods for three years. In total, 331,483 individual insects and arachnids, representing 82 families in 14 orders, were captured during the study. Totals of 166,518 and 164,965 individual insects and arachnids were collected from LM soybean and Gwangan, respectively. Throughout the study, although there were differences between the investigation year, region, and methods, there were no significant differences between the population densities of insect pests, natural enemies, and other insects on LM soybean and non-LM soybean. Also, there were no statistically significant differences between varieties in the results of the species diversity analysis. The data on insect species population densities were subjected to multidimensional scaling (MDS), which did not distinguish between the two varieties, LM soybean and the non-LM soybean, in all cultivated fields. However, the results of the MDS analysis were completely divided into six groups based on the yearly survey areas. These results provided the insect diversity for an environmental risk assessment of LM soybean and suggested that the guideline could be useful to detect LM crops.

Rationale, Design, and Interim Observations of the Steady Movement With Innovating Leadership for Heart Failure (SMILE HF) Registry: A Multicenter Prospective Cohort Registry for Patients With Acute Heart Failure

  • Jah Yeon Choi;Mi-Na Kim;Seongwoo Han;Sunki Lee;Myung Soo Park;Min Gyu Kong;Sung-Hea Kim;Yong-Hyun Kim;Sang-Ho Jo;Sungeun Kim;Seonghoon Choi;Jinsung Jeon;Jieun Lee;Byambakhand Battumur;Seong-Mi Park;Eung Ju Kim;SMILE HF Investigators
    • International Journal of Heart Failure
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    • v.6 no.3
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    • pp.129-136
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    • 2024
  • Background and Objectives: Heart failure (HF) is a leading cause of hospitalization and death worldwide. The Steady Movement with Innovating Leadership for Heart Failure (SMILE HF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute HF in South Korea. Methods: This prospective, observational multicenter cohort study was conducted on consecutive patients hospitalized for acute HF in nine university hospitals since September 2019. Enrolment of 2000 patients should be completed in 2024, and follow-up is planned through 2025. Results: Interim analysis of 1,052 consecutive patients was performed to understand the baseline characteristics. The mean age was 69±15 years; 57.6% were male. The mean left ventricular ejection fraction was 39±15%. The prevalences of HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction were 50.9%, 15.3%, and 29.2%. Ischemic cardiomyopathy (CMP) was the most common etiology (32%), followed by tachycardia-induced CMP (12.8%) and idiopathic dilated CMP (9.5%). The prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers/angiotensin receptor/neprilysin inhibitor, beta-blockers, spironolactone, and sodium-glucose cotransporter-2 inhibitors at discharge were 76.8%, 66.5%, 50.0%, and 17.5%, respectively. The post-discharge 90-day mortality and readmission rates due to HF aggravation were 2.0% and 6.4%, respectively. Our analysis reveals the current state of acute HF in South Korea. Conclusions: Our interim analysis provides valuable insights into the clinical characteristics, management, and early outcomes of acute HF patients in South Korea, highlighting the current state and treatment patterns in this population.

Effect of Air Temperature on Growth and Phytochemical Content of Beet and Ssamchoo (온도처리가 비트와 쌈추의 생육과 생리활성 물질 함량에 미치는 영향)

  • Lee, Sang Gyu;Choi, Chang Sun;Lee, Hee Ju;Jang, Yoon Ah;Lee, Jun Gu
    • Horticultural Science & Technology
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    • v.33 no.3
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    • pp.303-308
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    • 2015
  • The consumption of leaf vegetables has been steadily increasing in Korea. Leaf vegetables are used for "Ssam (vegetable wrap-up), eaf vegetables has been steadily increasing in Korea. Leaf vegetables are used for asoned condiments inside several layers of young vegetable leaves. This study investigated the effect of air temperature on the growth and phytochemical contents of beet (Beta vulgaris L.) and Ssamchoo (Brassica lee L. ssp. namai) grown in a closed-type plant factory system where fluorescent lamps were used as an artificial light source. Seeds of beet and Ssamchoo were sown in a peat-lite germination mix. The roots of 20-day-old seedlings were washed, and the seedlings were planted on a styrofoam board and grown in hydroponic beds for 25 days under fluorescent light. Plants were exposed to one of three different air temperature regimes (20, 25 and $30^{\circ}C$ during the day combined with $18^{\circ}C$ during the night), which were monitored with a sensor at 30 cm above the plant canopy. Increased plant height and leaf area were observed in beet at $25^{\circ}C$ and $30^{\circ}C$ compared to $20^{\circ}C$. For Ssamchoo, the greatest plant height, leaf area, fresh weight and dry weight were obtained at $20^{\circ}C$. Ascorbic acid content of beet and Ssamchoo leaves were highest at $30^{\circ}C$. In beet, total polyphenol and flavonoid contents were higher at $20^{\circ}C$ (42.4, $197.0mg{\cdot}g^{-1}DW$) and $25^{\circ}C$ (46.9, $217.0mg{\cdot}g^{-1}DW$) than $30^{\circ}C$ (22.4, $88.0mg{\cdot}g^{-1}DW$). In Ssamchoo, total polyphenol and flavonoid contents were also higher at $20^{\circ}C$ (79.2, $268.2mg{\cdot}g^{-1}DW$) and $25^{\circ}C$ (66.3, $258.3mg{\cdot}g^{-1}DW$), respectively, than $30^{\circ}C$ (53.7, $134.7mg{\cdot}g^{-1}DW$). Hence, the optimum temperature appears to be $20^{\circ}C$ for growing both beet and Ssamchoo in a closed-type plant factory system with fluorescent light.

A Case Study of Environmental Design from a Viewpoint of Hybrid and Features of User Experience (하이브리드와 이용자체험 특성으로 본 환경설계의 사례연구)

  • Jang, Il-Young;Kim, Jin-Seon
    • Archives of design research
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    • v.19 no.1 s.63
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    • pp.201-214
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    • 2006
  • Modern society is an age of vagueness and confusion. In addition, vagueness, complexity and variety are seen throughout art including modern philosophy, literature, and environmental design. A phenomenon like this shows that modern society has integrated different components as an organic relationship frequently crossing the boundary of fields. This feature can be regarded as hybrid related with accepting contradictory components and binding them into one under relationship between part and whole. As new design concept, presented are attitude to accept the two instead of attitude to select one of the alternatives, abundance instead of dearness, and ambiguity instead of simplicity. This principle has a crucial influence on creative design providing opposing contradiction and several alternative plans as non-deterministic form not completed one and, above all, useful information in mutual dependence and mutual relationship. When it comes to hybrid, therefore, a strategy is needed to consider layer of several fields getting out of standardizing space into a single space. As an event of this situation and concept, space experience means behaving freely based on experience of users' body. It can be known that this experience brings about users' more dynamic experience in comparison with the experience of seeing environmental design from a viewpoint of visual ism on the existing simplicity. Such a practical experience is subjective, synesthetic, and non-observational one. Therefore, hybrid has brought active users to the stage, which is distinguished from synesthesia felt through body's experience, not through observational attitude and visual space which achieve former balance and harmony with non-determination. That's because hybrid creatures are turning to a product resulted from creative imagination instead of from reappearance which makes text visualized. Such experience performed by user's active participation collapses the boundary between special elite-centered art and daily life and it is the present progressive form showing creation process of future events and new esthetic experience.

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