• Molecules and Cells
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• v.38 no.1
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• pp.20-25
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• 2015

TGF-${\beta}$ regulates pleiotropic cellular responses including cell growth, differentiation, migration, apoptosis, extracellular matrix production, and many other biological processes. Although non-Smad signaling pathways are being increasingly reported to play many roles in TGF-${\beta}$-mediated biological processes, Smads, especially receptor-regulated Smads (R-Smads), still play a central mediatory role in TGF-${\beta}$ signaling for epithelial-mesenchymal transition. Thus, the biological activities of R-Smads are tightly regulated at multiple points. Inhibitory Smad (I-Smad also called Smad7) acts as a critical endogenous negative feedback regulator of Smad-signaling pathways by inhibiting R-Smad phosphorylation and by inducing activated type I TGF-${\beta}$ receptor degradation. Roles played by Smad7 in health and disease are being increasingly reported, but the molecular mechanisms that regulate Smad7 are not well understood. In this study, we show that E3 ubiquitin ligase Itch acts as a positive regulator of TGF-${\beta}$ signaling and of subsequent EMT-related gene expression. Interestingly, the Itch-mediated positive regulation of TGF-${\beta}$ signaling was found to be dependent on Smad7 ubiquitination and its subsequent degradation. Further study revealed Itch acts as an E3 ubiquitin ligase for Smad7 polyubiquitination, and thus, that Itch is an important regulator of Smad7 activity and a positive regulator of TGF-${\beta}$ signaling and of TGF-${\beta}$-mediated biological processes. Accordingly, the study uncovers a novel regulatory mechanism whereby Smad7 is controlled by Itch.

• Journal of Veterinary Science
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• v.23 no.4
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• pp.47.1-47.11
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• 2022

Background: In lipopolysaccharide-induced RAW264.7 cells, Aster tataricus (AT) inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells and MAPKs pathways and critical pathways of osteoclast development and bone resorption. Objectives: This study examined how aster saponin A2 (AS-A2) isolated from AT affects the processes and function of osteoclastogenesis induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264.7 cells and bone marrow macrophages (BMMs). Methods: The cell viability, tartrate-resistant acid phosphatase staining, pit formation assay, polymerase chain reaction, and western blot were carried out to determine the effects of AS-A2 on osteoclastogenesis. Results: In RAW264.7 and BMMs, AS-A2 decreased RANKL-initiated osteoclast differentiation in a concentration-dependent manner. In AS-A2-treated cells, the phosphorylation of ERK1/2, JNK, and p38 protein expression were reduced considerably compared to the control cells. In RAW264.7 cells, AS-A2 suppressed the RANKL-induced activation of osteoclast-related genes. During osteoclast differentiation, AS-A2 suppressed the transcriptional and translational expression of NFATc1 and c-Fos. AS-A2 inhibited osteoclast development, reducing the size of the bone resorption pit area. Conclusion: AS-A2 isolated from AT appears to be a viable therapeutic therapy for osteolytic illnesses, such as osteoporosis, Paget's disease, and osteogenesis imperfecta.

• Journal of Veterinary Science
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• v.21 no.3
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• pp.50.1-50.16
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• 2020

Background: Porcine parvovirus (PPV) is a single-stranded DNA virus that causes porcine reproductive failure. It is of critical importance to study PPV pathogenesis for the prevention and control of the disease. NS1, a PPV non-structural protein, is participated in viral DNA replication, transcriptional regulation, and cytotoxicity. Our previous research showed that PPV can activate nuclear factor kappa B (NF-κB) signaling pathway and then up-regulate the expression of interleukin (IL)-6. Objectives: Herein, the purpose of this study is to determine whether the non-structural protein NS1 of PPV also has the same function. Methods: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay, western blot, immunofluorescence assay and small interfering RNA (siRNA) were used. Results: Our findings demonstrated that PPV NS1 protein can up-regulate the expression levels of IL-6 and tumor necrosis factor-alpha in a dose-dependent manner. Moreover, PPV NS1 protein was found to induce the phosphorylation of IκBα, then leading to the phosphorylation and nuclear translocation of NF-κB. In addition, the NS1 protein activated the upstream pathways of NF-κB. Meanwhile, TLR2-siRNA assay showed TLR2 plays an important role in the activation of NF-κB signaling pathway induced by PPV-NS1. Conclusions: These findings indicated that PPV NS1 protein induced the up-regulated of IL-6 expression through activating the TLR2 and NF-κB signaling pathways. In conclusion, these findings provide a new avenue to study the innate immune mechanism of PPV infection.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.2
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• pp.57-76
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• 2023

Objectives This study aims to develop Korean Medicine Clinical Pathway (CP) based on Clinical Practice Guideline of carpal tunnel syndrome to improve quality of treatment and reduce medical cost to maximize the quality of patient management. Methods A draft version of CP for carpal tunnel syndrome is developed by expert agreement and a prospective case study was carried out based on the draft CP. Twenty experts working at various medical institution answered validity verification survey of developed CP. Fifteen patients enrolled in the prospective case study answered survey on demand and satisfaction. Qualification and adjustment process of the draft CP was conducted based on results of both surveys. Results Final version of CP for carpal tunnel syndrome is confirmed after qualification and adjustment on the draft version. Conclusions CP for carpal tunnel syndrome will provide patients with standardized, high-quality Korean medicine treatment and also reduce financial burden of health insurance by reducing medical cost.

• Genomics & Informatics
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• v.21 no.1
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• pp.8.1-8.19
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• 2023

Cancer of the stomach is the second most frequent cancer-related death worldwide. The survival rate of patients with gastric cancer (GC) remains fragile. There is a requirement to discover biomarkers for prognosis approaches. Helicobacter pylori in the stomach is closely associated with the progression of GC. We identified the genes associated with poor/favorable prognosis in H. pylori-induced GC. Multivariate statistical analysis was applied on the Gene Expression Omnibus (GEO) dataset GSE54397 to identify differentially expressed miRNAs (DEMs) in gastric tissues with H. pylori-induced cancer compared with the H. pylori-positive with non-cancerous tissue. A protein interaction map (PIM) was built and subjected to DEMs targets. The enriched pathways and biological processes within the PIM were identified based on substantial clusters. Thereafter, the most critical genes in the PIM were illustrated, and their prognostic impact in GC was investigated. Considering p-value less than 0.01 and |Log2 fold change| as >1, five microRNAs demonstrated significant changes among the two groups. Gene functional analysis revealed that the ubiquitination system, neddylation pathway, and ciliary process are primarily involved in H. pylori-induced GC. Survival analysis illustrated that the overexpression of DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, and TXNIP was associated with poor prognosis, while increased MRPS5 expression was related to a favorable prognosis in GC patients. DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, TXNIP, and MRPS5 may be considered prognostic biomarkers for H. pylori-induced GC. However, experimental validation is necessary in the future.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.267-280
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• 2024

Apoptosis, programmed cell death pathway, is a vital physiological mechanism that ensures cellular homeostasis and overall cellular well-being. In the context of cancer, where evasion of apoptosis is a hallmark, the overexpression of anti-apoptotic proteins like Bcl2, Bcl-xL and Mcl-1 has been documented. Consequently, these proteins have emerged as promising targets for therapeutic interventions. The BCL-2 protein family is central to apoptosis and plays a significant importance in determining cellular fate serving as a critical determinant in this biological process. This review offers a comprehensive exploration of the BCL-2 protein family, emphasizing its dual nature. Specifically, certain members of this family promote cell survival (known as anti-apoptotic proteins), while others are involved in facilitating cell death (referred to as pro-apoptotic and BH3-only proteins). The potential of directly targeting these proteins is examined, particularly due to their involvement in conferring resistance to traditional cancer therapies. The effectiveness of such targeting strategies is also discussed, considering the tumor's propensity for anti-apoptotic pathways. Furthermore, the review highlights emerging research on combination therapies, where BCL-2 inhibitors are used synergistically with other treatments to enhance therapeutic outcomes. By understanding and manipulating the BCL-2 family and its associated pathways, we open doors to innovative and more effective cancer treatments, offering hope for resistant and aggressive cases.

• Journal of Korean Academy of Nursing
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• v.28 no.1
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• pp.117-131
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• 1998

The purpose of this study was to develop a critical pathway for case management for patients who have received Coronary Artery Bypass Graft (CABG) because of Ischemic Heart Disease(IHD) which is a factor of rising medical expenses. For this study. a conceptual framework was developed through a review of the literature including six critical pathways which are currently being used in USA. In order to identify the overall service contents required by these patients and to draw up a preliminary critical pathway, 30 cases of medical records of patients who had CABG because of IHD between January, 1995 to June. 1996 at the Cardiovascular Center of Yonsei Medical Center in Seoul were analyzed. An expert validity test was done for the preliminary critical pathway and clinical validity test was also done using seven IHD patients with CABG between November 11 and 23, 1996. After these processes. the final critical pathway was developed. The results of this study are summarized as follows : 1. The vertical axis of the critical pathway includes the following eight items : tests, nutrition, medications, consultations, activity, assessments, treatments, education discharge planning and the horizontal axis includes the time from the start of hospitalization to discharge. 2. Analysis of the 30 medical records indicated that the average length of stay was 20.2days with the average length of stay from hospitalization day to operation day being 6.2 days, and the average length of stay from operation day to discharge day was 13. 9 days. Analysis of the service contents showed that the horizontal axis of the preliminary critical pathway was set from hospitalization to the 14th post operation day and the vertical axis was set to include eight items, the contents which ought to have occurred, according to the time frames of the horizontal axis. 3. As a result of the experts validity, it was found that among the total of 571 items. there was over 83% agreement for 482 items, less than 83% for 89 items, which were then deleted and a revision of the critical pathway was done. 4. A clinical validity test was done using seven IHD patients with CABG. During the process, three patients were deleted because they were out of the criteria the investigator set. Finally, four patients were used. The result of study indicated that only one patient was discharged on the tenth post operation day, which was one day later than the expected day. Three patients were discharged later than the expected day from three days to nine days. All the cases progressed on schedule until the operation day and the first post operation day, but from the second post operation days, there were differences between the critical pathway and the actual practice. The differences came from tests, assessments, and treatments. 5. On the basis of the results of the clinical validity test. the following revisions in the final critical pathway were made : the transfer from ICU to step down ward would be the second post operation day, and the transfer to a general ward, the fifth post operation day, for patients who complained of lack of sleep from the fifth post operation day to discharge, a sleeping pill would be prescribed, skin observations would be performed routinely from immediately after the operation until the third post operation day, and would continue if there was a sign of skin injury on the fourth post operation day, and assessment of chest pain would be done from the third post operation day, and the “stairs climbing” item, expected to be done on the ninth post operation day would be deleted. In conclusion, this critical pathway is partially applicable to the care of patients with CABG but there are some parts needed to be further investigated.

• 한국사회정책
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• v.25 no.2
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• pp.191-217
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• 2018

At the turn of the century, social policy in both developed and developing countries confronts new challenges and risks caused by the multiple crises in finance, food, energy and climate change. Changes in the structures of risks are particularly significant. In addition, the global economic crisis starting in 2008 has provided a new context of the global political economy. Both developed and developing countries have responded to these new challenges and risks differently. What risks do these responses aim to address? How can these responses address these risks? Can these diverse responses offer lessons for lower income economies attempting to address social development challenges alongside economic growth in the globalised and increasingly uncertain 21st century context? This paper aims to provide a critical review of the new trends, phenomena or directions of social policy discourse and practice to respond to the new risks in the context of development. Explaining the nature and forms of new challenges and risks and pointing out the potentials and limitations of social policy discourse, it introduces the key points of the previous research we have to keep in mind in formulating alternative social policy approaches. General principles and core elements of social policy in addressing new challenges and risks in the $21^{st}$ century, which are particularly visible in social policy reforms in emerging economies, are highlighted as a conclusion.

• Development and Reproduction
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• v.12 no.3
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• pp.267-274
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• 2008

Differentiation of blastocyst is critical step for implantation and is under the control of regulation factors originated from embryo or reproductive tracts. The sequential communication with those factors is suspected as critical events for differentiation. It has been suggested that intracellular signaling pathways activated by calcium is essential in differentiation of blastocyst. Previously, it was known that concanavalin A (Con A) increase the levels of free calcium in blastocyst stage. However, Con A can not accelerate the hatching, although heparin-binding epidermal growth factor-like growth factor (HB-EGF), a modulator of calcium level, accelerate the hatching of blastocyst. In this study, it was investigated whether Con A or prostaglandin $E_2$ ($PGE_2$) can modulate the differentiation of blastocyst. Con A accelerated the expansion of blastocyst in both 1 hr pulse treatment group and continuous treatment group. However, Con A significantly suppressed the hatching in both groups. The inhibition was significantly strong in continuous treatment group compared with 1 hr pulse treatment group. On the other hand, $PGE_2$ induced the increase the free calcium level, but did not accelerate the expansion. In addition $10{\mu}m\;PGE_2$ inhibited hatching. However, $PGE_2$ could accelerate hatching in Con A pretreated blastocyst. $PGE_2$ also caused the increase of free calcium level in Con A pretreated blastocyst. From these results, it is suggested that changes of the free calcium level induce a different calcium-mediated signaling pathways. In addition, sequential stimulation by signal molecules may triggers the cellular mechanisms for the differentiation of blastocyst.

• Molecules and Cells
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• v.47 no.3
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• pp.100033.1-100033.13
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• 2024

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.