• 제목/요약/키워드: Critical Pathways

검색결과 268건 처리시간 0.027초

Porcine parvovirus nonstructural protein NS1 activates NF-κB and it involves TLR2 signaling pathway

  • Jin, Xiaohui;Yuan, Yixin;Zhang, Chi;Zhou, Yong;Song, Yue;Wei, Zhanyong;Zhang, Gaiping
    • Journal of Veterinary Science
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    • 제21권3호
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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.

손목터널증후군의 한의표준임상경로 개발 (Development of Korean Medicine Clinical Pathways for Carpal Tunnel Syndrome)

  • 박혜진;김현태;박선영;허인;황만석;신병철;황의형
    • 한방재활의학과학회지
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    • 제33권2호
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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.

Prognostic biomarkers and molecular pathways mediating Helicobacter pylori-induced gastric cancer: a network-biology approach

  • Farideh Kamarehei;Massoud Saidijam;Amir Taherkhani
    • Genomics & Informatics
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    • 제21권1호
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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.

Unlocking the Therapeutic Potential of BCL-2 Associated Protein Family: Exploring BCL-2 Inhibitors in Cancer Therapy

  • Bisan El Dakkak;Jalal Taneera;Waseem El-Huneidi;Eman Abu-Gharbieh;Rifat Hamoudi;Mohammad H. Semreen;Nelson C. Soares;Eman Y. Abu-Rish;Mahmoud Y. Alkawareek;Alaaldin M. Alkilany;Yasser Bustanji
    • Biomolecules & Therapeutics
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    • 제32권3호
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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.

관상동맥 우회술 환자를 위한 Critical Pathway개발 (Development of a Critical Pathway for Patients with Coronary Artery Bypass Graft)

  • 김기연
    • 대한간호학회지
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    • 제28권1호
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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.

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개발 맥락에서 신사회정책에 대한 대안적 접근의 비판적 고찰 (A Critical Review of Alternative Pathways to New Social Policy in Development Context)

  • 이일청;손혁상;김태균
    • 한국사회정책
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    • 제25권2호
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    • pp.191-217
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    • 2018
  • 세기말 개발도상국과 선진국의 사회정책은 금융, 식량, 에너지, 기후분야 등의 복합적인 위기로 인해 새로운 도전에 직면하면서, 대응해야할 위기 구조의 변화가 명확해졌다. 2008년부터 시작된 전세계적금융, 경제 위기로 인해 세계정치경제 구조의 새로운 조건이 만들어지기도 했다. 이에 많은 발전도상국과 선진국들은 새로운 위기와 도전에 응하기 위해 사회정책의 개혁을 다양한 방식으로 추구하기 시작했다. 이들 개혁들은 어떤 특정한 위기와 도전에 대응하였는가? 이러한 다양한 개혁방안들은 사회정책 개혁을 추구하는 국가들, 특히 세계화와 불확실성 시대인 21세기에 경제성장과 사회개발을 동시에 추구해야하는 개발도상국에 어떤 교훈을 주는가? 본 논문은 새로운 도전과 위기에 대응하기 위한 사회정책 개혁 담론과 정책에서 발견되는 새로운 동향을 비판적으로 평가하는 것을 그 목적으로 한다. 이를 위해 본 논문은 첫째, 사회정책이 대응해야 할 새로운 위기와 도전의 본질과 다양한 형태를 분석한다. 둘째, 개혁담론과 정책의 한계점을 논의한 후, 신흥부국의 사회정책 개혁이 주는 긍정적인 측면과 그 정책적 시사점을 밝힌다. 이를 토대로 새로운 위기와 도전에 대응할 수 있는 사회정책의 근간이 되는 원칙과 핵심요소를 제시한다.

Concanavalin A와 $PGE_2$의 순차적 노출에 의한 포배의 분화 조절 (Regulation of Blastocyst Differentiation by the Serial Exposure of Conconavalin A and $PGE_2$)

  • 전용필
    • 한국발생생물학회지:발생과생식
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    • 제12권3호
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    • pp.267-274
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    • 2008
  • 포배의 분화는 배아의 착상에 있어 핵심적인 단계로 배아 자체 또는 생식수관에서 유래하는 조절요인의 조절을 받는다. 이들 조절요인과 포배와의 순차적인 신호의 주고 받음은 분화의 중요한 단계로 인식되고 있다. 한편, 포배기 때 자유 칼슘을 통한 신호전달경로가 포배의 분화에 중요한 축의 하나로 제안되어 왔다. Concanavalin A(Con A)가 포배의 자유 칼슘 농도 증감을 유도한다는 것을 밝혀졌으나, 포배 내 자유 칼슘 농도를 변형시켜 부화와 그 이후의 발생을 촉진하는 것으로 알려진 heparin-binding epidermal growth factor-like growth factor(HB-EGF)와는 달리 팽창 이후의 부화를 억제하였다. 따라서 본 연구에서는 착상과정에서 중요한 역할을 하는 것으로 알려진 prostaglandin $E_2(PGE_2)$가 포배의 분화에 관여하는지를 Con A와 연계하여 알아보았다. Con A는 그 처리 시간에 관계없이 1시간 처리군 그리고 계속처리군에서 팽창은 촉진하고 부화는 유의하게 억제하였다. 특히 계속처리군에서 부화율이 1시간 처리군에 비하여 유의하게 감소하였다. 또한, $PGE_2$도 포배 내 자율 칼슘 농도를 증가시켰으나 팽창과 부화를 촉진하지 않았다. 또한, $10{\mu}m\;PGE_2$ 농도에서는 부화가 억제되는 경향을 보였다. 그러나 흥미롭게도 $PGE_2$는 Con A가 처리된 포배의 부화를 촉진하였다. Con A를 전처리한 포배에 $PGE_2$를 처리할 경우 포배 내 자유 칼슘의 농도 증감이 진행됨을 공촛점현미경을 이용하여 분석할 수 있었다. 이러한 결과는 신호물질에 의해 유도된 자유 칼슘 농도의 증감이 신호물질에 따른 각기 다른 칼슘 매개로 활성화되는 신호경로를 조절하는 것을 추정할 수 있다. 또한, 순차적 신호물질 조절에 의한 자유 칼슘의 농도 증감이 포배의 분화에 있어 중요함을 제안한다.

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Comprehensive RNA-sequencing analysis of colorectal cancer in a Korean cohort

  • Jaeim Lee;Jong-Hwan Kim;Hoang Bao Khanh Chu;Seong-Taek Oh;Sung-Bum Kang;Sejoon Lee;Duck-Woo Kim;Heung-Kwon Oh;Ji-Hwan Park;Jisu Kim;Jisun Kang;Jin-Young Lee;Sheehyun Cho;Hyeran Shim;Hong Seok Lee;Seon-Young Kim;Young-Joon Kim;Jin Ok Yang;Kil-yong Lee
    • Molecules and Cells
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    • 제47권3호
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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.

리포다당질로 인한 직접성 급성폐손상에서 Nuclear Factor-κB Decoy Oligodeoxynucleotide의 효과 (The Effects of Nuclear Factor-κB Decoy Oligodeoxynucleotide on Lipopolysaccharide-Induced Direct Acute Lung Injury)

  • 김제형;윤대위;정기환;김혜옥;하은실;이경주;허규영;이승룡;이상엽;신철;심재정;인광호;유세화;강경호
    • Tuberculosis and Respiratory Diseases
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    • 제67권2호
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    • pp.95-104
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    • 2009
  • Background: The pathophysiologic mechanisms of early acute lung injury (ALI) differ according to the type of primary insult. It is important to differentiate between direct and indirect pathophysiologic pathways, and this may influence the approach to treatment strategies. NF-$\kappa$B decoy oligodeoxynucleotide (ODN) is a useful tool for the blockade of the expression of NF-$\kappa$B-dependent proinflammatory mediators and has been reported to be effective in indirect ALI. The purpose of this study was to investigate the effect of NF-$\kappa$B decoy ODN in the lipopolysaccharide (LPS)-induced direct ALI model. Methods: Five-week-old specific pathogen-free male BALB/c mice were used for the experiment. In the preliminary studies, tumor necrosis factor (TNF)-$\alpha$, interleukine (IL)-6 and NF-$\kappa$B activity peaked at 6 hours after LPS administration. Myeloperoxidase (MPO) activity and ALI score were highest at 36 and 48 hours, respectively. Therefore, it was decided to measure each parameter at the time of its highest level. The study mice were randomly divided into three experimental groups: (1) control group which was administered 50 ${\mu}L$ of saline and treated with intratracheal administration of 200 ${\mu}L$ DW containing only hemagglutinating virus of Japan (HVJ) vector (n=24); (2) LPS group in which LPS-induced ALI mice were treated with intratracheal administration of 200 ${\mu}L$ DW containing only HVJ vector (n=24); (3) LPS+ODN group in which LPS-induced ALI mice were treated with intratracheal administration of 200 ${\mu}L$ DW containing 160 ${\mu}g$ of NF-$\kappa$B decoy ODN and HVJ vector (n=24). Each group was subdivided into four experimental subgroups: (1) tissue subgroup for histopathological examination for ALI at 48 hours (n=6); (2) 6-hour bronchoalveolar lavage (BAL) subgroup for measurement of TNF-$\alpha$ and IL-6 in BAL fluid (BALF) (n=6); (3) 36-hour BAL subgroup for MPO activity assays in BALF (n=6); and (4) tissue homogenate subgroup for measurement of NF-$\kappa$B activity in lung tissue homogenates at 6 hours (n=6). Results: NF-$\kappa$B decoy ODN treatment significantly decreased NF-$\kappa$B activity in lung tissues. However, it failed to improve the parameters of LPS-induced direct ALI, including the concentrations of tumor necrosis factor-$\alpha$ and interleukin-6 in BALF, myeloperoxidase activity in BALF and histopathologic changes measured by the ALI score. Conclusion: NF-$\kappa$B decoy ODN, which has been proven to be effective in indirect models, had no effect in the direct ALI model.

Outcomes of Critical Pathway in Laparoscopic and Open Surgical Treatments for Gastric Cancer Patients: Patients Selection for Fast-Track Program through Retrospective Analysis

  • Choi, Ji Woo;Xuan, Yi;Hur, Hoon;Byun, Cheul Su;Han, Sang-Uk;Cho, Yong Kwan
    • Journal of Gastric Cancer
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    • 제13권2호
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    • pp.98-105
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    • 2013
  • Purpose: The aim of this study is to investigate the clinical factors affecting on the cure rate by invasive and open surgery for gastric cancer and to establish a subgroup of patients who can be applied by the early recovery after surgery program through this retrospective analysis. Materials and Methods: In this retrospective study, we analyzed 425 patients who underwent gastric cancer surgery between January 2011 and December 2011 and were managed with conventional clinical therapies. This clinical algorithm was made when the patient was in minimally invasive surgery group and discharged from hospital one day faster than them in open surgery group. Results: The completion rate of the clinical pathway was 62.4%. Despite the different applications of clinical pathway, completion rate in minimally invasive surgery group was significantly higher than that of open group (P<0.001). In multivariate analysis, the surgical procedure of minimally invasive surgery (odds ratio=4.281) was the most predictable factor to complete clinical pathway. Additionally, younger patients (odds ratio=1.933) who underwent distal gastrectomy (odds ratio=1.999) without combined resection (odds ratio=3.069) were predicted to accomplish the clinical pathway without any modifications. Conclusions: We concluded that high efficacy of the clinical pathway for gastric cancer surgery was expected to selected patients through retrospective analysis (expected completion rate=85.4%). In addition, these patients would become enrolled criteria for early recovery program in gastric cancer surgery.