• Animal cells and systems
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• v.2 no.2
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• pp.153-164
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• 1998

Cytokines regulate proliferation, differentiation and functions of haemotopoietic cells. Each cytokine possesses a variety of activities on various target cells (pleiotropy) and various cytokines have similar and overlapping activities on the same target cells (redundancy). The nature of these cytokine activities predicts unique feature of cytokine receptors, namely, cytokine has multiple receptors, different cytokines share a common receptor, and different cytokine receptors are linked to common signaling pathways. cDNA cloning of genes for cytokine receptors revealed distinct sets of receptor family with different structural features. The cytokine receptor superfamily consists of a largest family, and contains more than twenty cytokine receptor subunits. This receptor has common structural features in both extracellular and intracellular regions without tyrosine kinase domain. Another striking feature of the receptor is to share common subunit of multiple cytokines, which partly explains the redundancy of activities of some cytokines. Recent studies revealed detailed signaling events of the cytokine receptor, the primary activation of JAK and subsequent phosphorylation of tyrosine residues of receptor, and various cellular proteins. Many SH2 containing adapter proteins play an important role in cytokine signals, and this system has similarities with tyrosine kinase receptor signal transduction. STAT may mainly account for cytokine specific functions as suggested by knockout mice studies. It is of importance to note that cytokine activates multiple signaling pathways and the balance and combination of related signaling events may determine the specificity of functions of cytokines.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6803-6812
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• 2015

Caveolin-1 is a 22-kD trans-membrane protein enriched in particular plasma membrane invaginations known as caveolae. Cav-1 expression is often dysregulated in human breast cancers, being commonly upregulated in cancer cells and downregulated in stromal cells. As an intracellular scaffolding protein, Cav-1, is involved in several vital biological regulations including endocytosis, transcytosis, vesicular transport, and signaling pathways. Several pathways are modulated by Cav-1 including estrogen receptor, EGFR, Her2/neu, $TGF{\beta}$, and mTOR and represent as major drivers in mammary carcinogenesis. Expression and role of Cav-1 in breast carcinogenesis is highly variable depending on the stage of tumor development as well as context of the cell. However, recent data have shown that downregulation of Cav-1 expression in stromal breast tumors is associated with frequent relapse, resistance to therapy, and poor outcome. Modification of Cav-1 expression for translational cancer therapy is particularly challenging since numerous signaling pathways might be affected. This review focuses on present understanding of Cav-1 in breast carcinogenesis and its potential role as a new biomarker for predicting therapeutic response and prognosis as well as new target for therapeutic manipulation.

• Korean Journal of Exercise Nutrition
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• v.24 no.3
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• pp.32-38
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• 2020

[Purpose] Sarcopenia is considered one of the major causes of disability in the elderly population and is highly associated with aging. Exercise is an essential strategy for improving muscle health while aging and involves multiple metabolic and transcriptional adaptations. Although the beneficial effects of exercise modalities on skeletal muscle structure and function in aging are well recognized, the exact cellular and molecular mechanisms underlying the influence of exercise have not been fully elucidated. [Methods] We summarize the biochemical pathways involved in the progression and pathogenesis of sarcopenia and describe the beneficial effects of exercise training on the relevant signaling pathways associated with sarcopenia. [Results] This study briefly introduces current knowledge on the signaling pathways involved in the development of sarcopenia, effects of aerobic exercise on mitochondria-related parameters and mitochondrial function, and role of resistance exercise in the regulation of muscle protein synthesis against sarcopenia. [Conclusion] This review suggested that the beneficial effects of exercise are still under-explored, and accelerated research will help develop better modalities for the prevention, management, and treatment of sarcopenia.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.113-121
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• 2024

Since its outbreak in late 2019, the Coronavirus disease 2019 (COVID-19) pandemic has profoundly caused global morbidity and deaths. The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has major complications in cardiovascular and pulmonary system. The increased rate of mortality is due to delayed detection of certain biomarkers that are crucial in the development of disease. Furthermore, certain proteins and enzymes in cellular signaling pathways play an important role in replication of SARS-CoV-2. Most cases are mild to moderate symptoms, however severe cases of COVID-19 leads to death. Detecting the level of biomarkers such as C-reactive protein, cardiac troponin, creatine kinase, creatine kinaseMB, procalcitonin and Matrix metalloproteinases helps in early detection of the severity of disease. Similarly, through downregulating Renin-angiotensin system, interleukin, Mitogen-activated protein kinases and Phosphoinositide 3-kinases pathways, COVID-19 can be effectively controlled and mortality could be prevented. Ginseng and ginsenosides possess therapeutic potential in cardiac and pulmonary complications, there are several studies performed in which they have suppressed these biomarkers and downregulated the pathways, thereby inhibiting the further spread of disease. Supplementation with ginseng or ginsenoside could act on multiple pathways to reduce the level of biomarkers significantly and alleviate cardiac and pulmonary damage. Therefore, this review summarizes the potential of ginseng extract and ginsenosides in controlling the cardiovascular and pulmonary diseases by COVID-19.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.371-383
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• 2014

The nematode Caenorhabditis elegans (C. elegans) offers a unique opportunity for biological and basic medical researches due to its genetic tractability and well-defined developmental lineage. It also provides an exceptional model for genetic, molecular, and cellular analysis of human disease-related genes. Recently, C. elegans has been used as an ideal model for the identification and functional analysis of drugs (or small-molecules) in vivo. In this review, we describe conserved oncogenic signaling pathways (Wnt, Notch, and Ras) and their potential roles in the development of cancer stem cells. During C. elegans germline development, these signaling pathways regulate multiple cellular processes such as germline stem cell niche specification, germline stem cell maintenance, and germ cell fate specification. Therefore, the aberrant regulations of these signaling pathways can cause either loss of germline stem cells or overproliferation of a specific cell type, resulting in sterility. This sterility phenotype allows us to identify drugs that can modulate the oncogenic signaling pathways directly or indirectly through a high-throughput screening. Current in vivo or in vitro screening methods are largely focused on the specific core signaling components. However, this phenotype-based screening will identify drugs that possibly target upstream or downstream of core signaling pathways as well as exclude toxic effects. Although phenotype-based drug screening is ideal, the identification of drug targets is a major challenge. We here introduce a new technique, called Drug Affinity Responsive Target Stability (DARTS). This innovative method is able to identify the target of the identified drug. Importantly, signaling pathways and their regulators in C. elegans are highly conserved in most vertebrates, including humans. Therefore, C. elegans will provide a great opportunity to identify therapeutic drugs and their targets, as well as to understand mechanisms underlying the formation of cancer.

• Animal Bioscience
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• v.37 no.3
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• pp.428-436
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• 2024

Objective: This study compared five distinct sets of biological pathways and associated genes related to semen volume (VOL), number of sperm (NS), and sperm motility (MOT) in the Thai multibreed dairy population. Methods: The phenotypic data included 13,533 VOL records, 12,773 NS records, and 12,660 MOT records from 131 bulls. The genotypic data consisted of 76,519 imputed and actual single nucleotide polymorphisms (SNPs) from 72 animals. The SNP additive genetic variances for VOL, NS, and MOT were estimated for SNP windows of one SNP (SW1), ten SNP (SW10), 30 SNP (SW30), 50 SNP (SW50), and 100 SNP (SW100) using a single-step genomic best linear unbiased prediction approach. The fixed effects in the model were contemporary group, ejaculate order, bull age, ambient temperature, and heterosis. The random effects accounted for animal additive genetic effects, permanent environment effects, and residual. The SNPs explaining at least 0.001% of the additive genetic variance in SW1, 0.01% in SW10, 0.03% in SW30, 0.05% in SW50, and 0.1% in SW100 were selected for gene identification through the NCBI database. The pathway analysis utilized genes associated with the identified SNP windows. Results: Comparison of overlapping and non-overlapping SNP windows revealed notable differences among the identified pathways and genes associated with the studied traits. Overlapping windows consistently yielded a larger number of shared biological pathways and genes than non-overlapping windows. In particular, overlapping SW30 and SW50 identified the largest number of shared pathways and genes in the Thai multibreed dairy population. Conclusion: This study yielded valuable insights into the genetic architecture of VOL, NS, and MOT. It also highlighted the importance of assessing overlapping and non-overlapping SNP windows of various sizes for their effectiveness to identify shared pathways and genes influencing multiple traits.

• Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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• v.11 no.4
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• pp.281-291
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• 2013

A hypothetical repository was assumed to be located at the KURT (KAERI Underground Research Tunnel) site, and the travel times of radionuclides released from three source positions were calculated. The groundwater flow around the KURT site was simulated and the groundwater pathways from the hypothetical source positions to the shallow groundwater were identified. Of the pathways, three pathways were selected because they had highly water-conductive features. The transport travel times of the radionuclides were calculated by a TDRW (Time-Domain Random Walk) method. Diffusion and sorption mechanisms in a host rock matrix as well as advection-dispersion mechanisms under the KURT field condition were considered. To reflect the radioactive decay, four decay chains with the radionuclides included in the high-level radioactive wastes were selected. From the simulation results, the half-life and distribution coefficient in the rock matrix, as well as multiple pathways, had an influence on the mass flux of the radionuclides. For enhancing the reliability of safety assessment, this reveals that identifying the history of the radionuclides contained in the high-level wastes and investigating the sorption processes between the radionuclides and the rock matrix in the field condition are preferentially necessary.

• Proceedings of the Zoological Society Korea Conference
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• 2000.10a
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• pp.187-188
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• 2000

No Abstract, See Full Text

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.549-555
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• 2015

We attempted to investigate molecular mechanisms underlying phenotypic change of vascular smooth muscle cells (VSMCs) by determining signaling molecules involved in chemokine production. Treatment of human aortic smooth muscle cells (HAoSMCs) with thrombin resulted not only in elevated transcription of the (C-C motif) ligand 11 (CCL11) gene but also in enhanced secretion of CCL11 protein. Co-treatment of HAoSMCs with GF109230X, an inhibitor of protein kinase C, or GW5074, an inhibitor of Raf-1 kinase, caused inhibition of ERK1/2 phosphorylation and significantly attenuated expression of CCL11 at transcriptional and protein levels induced by thrombin. Both Akt phosphorylation and CCL11 expression induced by thrombin were attenuated in the presence of pertussis toxin (PTX), an inhibitor of Gi protein-coupled receptor, or LY294002, a PI3K inhibitor. In addition, thrombin-induced production of CCL11 was significantly attenuated by pharmacological inhibition of Akt or MEK which phosphorylates ERK1/2. These results indicate that thrombin is likely to promote expression of CCL11 via PKC/Raf-1/ERK1/2 and PTX-sensitive protease-activated receptors /PI3K/Akt pathways in HAoSMCs. We propose that multiple signaling pathways are involved in change of VSMCs to a secretory phenotype.

• Proceedings of the Korean Society of Crop Science Conference
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• 2022.10a
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• pp.287-287
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• 2022

In this study, we analyze RNA-seq data from OxF3Hand WT at several points (Oh, 3 h, 12 h, and 24 h) after WBPH infection. A number of the genes were further validated by RT-qPCR. Results revealed that highest number of DEGs (4,735) between the two genotypes detected after 24 h of infection. Interestingly, many of the DEGs between the WT and OsF3H under control conditions were also found to be differentially expressed in OsF3H in response to WBPH infestation. These results indicate that significant differences in gene expression between the "OxF3H" and "WT" exist as the infection time increases. Many of these DEGs were related to oxidoreductase activity, response to stress, salicylic acid biosynthesis, metabolic process, defense response to pathogen, cellular response to toxic substance, and regulation of hormones level. Moreover, genes involved in salicylic acid (SA) and Ethylene (Et) biosynthesis were upregulated in OxF3H plants while jasmonic acid (JA), Brassinosteroid (Br), and abscisic acid (ABA) signaling pathways were found downregulated in OxF3H plant during WBPH infestation. Interestingly, many DEGs related to pathogenesis such as OsPR1, OsPR1b, NPR1, OsNPR3 and OsNPR5 were found significantly upregulated in OxF3H plants. Additionally, genes related to MAPKs pathway, and about 30 WRKY genes involved in different pathways were found upregulated in OxF3H plants after WBPH infestation. This suggests that overexpression of the OxF3H gene leads to multiple transcriptomic changes and impact plant hormones, pathogenic related and secondary metabolites related genes and enhancing the plant resistance to WBPH infestation.