• The Korean Journal of Physiology and Pharmacology
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• v.26 no.4
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• pp.239-253
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• 2022

Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.

• The Journal of Internal Korean Medicine
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• v.38 no.6
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• pp.917-929
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• 2017

Objectives: The objective of this study was to investigate the validity of the preliminary critical pathway of integrative medicine to improve the quality of life of lung cancer patients who received chemotherapy. Methods: The vertical axis of the preliminary critical pathway of integrated medicine consisted of nine domains: assessment, treatment, activity, consult, diet, medication, Korean medical examination, education, and others. The frame of the horizontal axis was the date from hospitalization to discharge. A total of 105 items in this preliminary critical pathway were validated by an expert group from October 28, 2016 to November 4, 2016. A total of ten experts from two different medical institutions participated in the validity test, using the four-point Content Validity Index (CVI) scale. The items with validity of greater than 80% were considered as significant. Results: The analysis of the content validity of 105 items showed 102 items with greater than 80% agreement. Assessment, treatment, consult, diet, medication, and education showed 100% agreement. Only three items showed a low validity (62.5%). Based on additional comments, the preliminary critical pathway of integrative medicine has been supplemented. Conclusions: This study suggests the possibility of using the integrated medical critical pathway for patients with lung cancer who received chemotherapy.

• Clinical and Experimental Reproductive Medicine
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• v.39 no.2
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• pp.58-67
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• 2012

Objective: Previously, we identified that transketolase (Tkt), an important enzyme in the pentose phosphate pathway, is highly expressed at 2 hours of spontaneous maturation in oocytes. Therefore, this study was performed to determine the function of Tkt in meiotic cell cycle regulation, especially at the point of germinal vesicle breakdown (GVBD). Methods: We evaluated the loss-of-function of Tkt by microinjecting Tkt double-stranded RNAs (dsRNAs) into germinal vesicle-stage oocytes, and the oocytes were cultured in vitro to evaluate phenotypic changes during oocyte maturation. In addition to maturation rates, meiotic spindle and chromosome rearrangements, and changes in expression of other enzymes in the pentose phosphate pathway were determined after Tkt RNA interference (RNAi). Results: Despite the complete and specific knockdown of Tkt expression, GVBD occurred and meiosis was arrested at the metaphase I (MI) stage. The arrested oocytes exhibited spindle loss, chromosomal aggregation, and declined maturation promoting factor and mitogen-activated protein kinase activities. The modified expression of two enzymes in the pentose phosphate pathway, Prps1 and Rbks, after Tkt RNAi and decreased maturation rates were amended when ribose-5-phosphate was supplemented in the culture medium, suggesting that the Tkt and pentose phosphate pathway are important for the maturation process. Conclusion: We concluded that Tkt and its associated pentose phosphate pathway play an important role in the MI-MII transition of the oocytes' meiotic cell cycle, but not in the process of GVBD.

• Clinical and Experimental Pediatrics
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• v.54 no.6
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• pp.241-245
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• 2011

Tuberous sclerosis complex (TSC) is a genetic multisystem disorder that results from mutations in the TSC1 or TSC2 genes, and is associated with hamartomas in several organs, including subependymal giant cell tumors. The neurological manifestations of TSC are particularly challenging and include infantile spasms, intractable epilepsy, cognitive disabilities, and autism. The TSC1- and TSC2-encoded proteins modulate cell function via the mammalian target of rapamycin (mTOR) signaling cascade, and are key factors in the regulation of cell growth and proliferation. The mTOR pathway provides an intersection for an intricate network of protein cascades that respond to cellular nutrition, energy levels, and growth factor stimulation. In the brain, TSC1 and TSC2 have been implicated in cell body size, dendritic arborization, axonal outgrowth and targeting, neuronal migration, cortical lamination, and spine formation. The mTOR pathway represents a logical candidate for drug targeting, because mTOR regulates multiple cellular functions that may contribute to epileptogenesis, including protein synthesis, cell growth and proliferation, and synaptic plasticity. Antagonism of the mTOR pathway with rapamycin and related compounds may provide new therapeutic options for TSC patients.

• Genomics & Informatics
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• v.17 no.1
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• pp.3.1-3.4
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• 2019

Intratumor heterogeneity within a single tumor mass is one of the hallmarks of malignancy and has been reported in various tumor types. The molecular characterization of intratumor heterogeneity in breast cancer is a significant challenge for effective treatment. Using single-cell RNA sequencing (RNA-seq) data from a public resource, an ERBB pathway activated triple-negative cell population was identified. The differential expression of three subtyping marker genes (ERBB2, ESR1, and PGR) was not changed in the bulk RNA-seq data, but the single-cell transcriptomes showed intratumor heterogeneity. This result shows that ERBB signaling is activated using an indirect route and that the molecular subtype is changed on a single-cell level. Our data propose a different view on breast cancer subtypes, clarifying much confusion in this field and contributing to precision medicine.

• Journal of Microbiology and Biotechnology
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• v.31 no.8
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• pp.1109-1114
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• 2021

Chlamydia pneumoniae is a type of pathogenic gram-negative bacteria that causes various respiratory tract infections including asthma. Chlamydia species infect humans and cause respiratory infection by rupturing the lining of the respiratory which includes the throat, lungs and windpipe. Meanwhile, the function of interleukin-4 (IL-4) in Ch. pneumoniae respiratory infection and its association with the development of airway hyperresponsiveness (AHR) in adulthood and causing allergic airway disease (AAD) are not understood properly. We therefore investigated the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. In this study, Ch. pneumonia strain was propagated and cultured in HEp-2 cells according to standard protocol and infant C57BL/6 mice around 3-4 weeks old were infected to study the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. We observed that IL-4 is linked with Chlamydia respiratory infection and its absence lowers respiratory infection. IL-4R α2 is also responsible for controlling the IL-4 signaling pathway and averts the progression of infection and inflammation. Furthermore, the IL-4 signaling pathway also influences infection-induced AHR and aids in increasing AAD severity. STAT6 also promotes respiratory infection caused by Ch. pneumoniae and further enhanced its downstream process. Our study concluded that IL-4 is a potential target for preventing infection-induced AHR and severe asthma.

• Journal of Acupuncture Research
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• v.40 no.4
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• pp.368-376
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• 2023

Background: Although bee venom (BV) has clinical benefits in osteoarthritis and rheumatoid arthritis, it has not been tested as treatment for gouty arthritis. Moreover, in vitro, BV has been proven to exhibit anti-inflammatory and positive effects on osteoarthritis, but only limited evidence can confirm its beneficial effects on gout. Thus, this study aims to assess the anti-inflammatory effects of BV on monosodium urate (MSU)-induced THP-1 monocytes. Methods: THP-1 monocytes were differentiated into mature macrophages using phorbol 12-myristate 13-acetate (PMA) and pretreated for 6 hours with BV and a Caspase-1 inhibitor in a physiologically achievable range of concentrations (BV, 0.1-1 ㎍/mL; Caspase-1 inhibitor, 1-10 μM), followed by MSU crystal stimulation for 24 hours. The secretions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, IL-8, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) were increased in the MSU crystal-stimulated THP-1 cells. Results: Caspase-1 inhibitors suppressed the production of all mediators in a dose-dependent manner. BV worked on equal terms with Caspase-1 inhibitors and showed more satisfactory effects on TNF-α, PGE2, COX-2, and inducible nitric oxide synthase (iNOS). Moreover, the western blot analysis revealed that BV regulated the transcriptional levels of these mediators via the suppression of extracellular signal-regulated kinase (ERK) pathway activation. Conclusion: The results of the present study clearly suggest that BV inhibits MSU-induced inflammation in vitro, suggesting a possible role for BV in gout treatment.

• Women's Health Nursing
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• v.6 no.2
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• pp.234-257
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• 2000

At present in the medical care, the study and effort for producing health service to consider efficiency, effectiveness, and quality are urgently called for because of the difficulty in the keen competition according to the inter- nationalization and opening, the operation in the medical institution service testing system, the change in the medical policy of KDRGs, and the lack of the health care cost increasing rate. As an alternative, the case management for the new management system is introduced in the U.S., and the Critical Pathway that is the method designing the contents of activity and its result has been developed and applied in order to anticipate and manage the patient-outcome for the realization of the cost-effective case-management. Thus, this study intended to analyze the effectiveness to obtain by developing the Critical Pathway presented as the method to improve the quality-betterment and cost effectiveness through the continuous and consistent patient management for the hysterectomy patient and applying it to the real practice. As a study method, this author formed a conceptual framework through considering five Critical Pathway used in the current U.S. and three Critical Pathway presented in the literature to develop the Critical Pathway for the hysterectomy patient, and made out the preliminary Critical Pathway through reviewing the old chart. This author made the verified the validity of the expert group about the developed Critical Pathway, and to confirm the possibility of practice application, completed and settled the final Critical Pathway after using the Critical Pathway to the hysterectomy patient from March 1st to 15th, 1997. Finally, to analyze the application-effect of the developed Critical Pathway, this author offered health care service applying the Critical Pathway to the hysterectomy patient from April 15th to August 31th, 1997. The guide for the Critical Pathway was carried out in advance by outpatient setting nurse for outpatient setting visit before the operation, and after hospitalization the primary nurse monitored the execution degree on the every duty. After discharge this author surveyed the complication through phone visiting, and one month after discharge surveyed the patient's reaction about the offered service when outpatient setting visit and analyzed the result. The source for health care cost was obtained by the statistics about the hospital charge which was offered by the General Business Department. The results were as follows. 1. It was decided that the vertical line of the Critical Pathway was made up of eight items such as monitoring/assessment, treatment, line/drains, activity, medication, lab test, diet, patient teaching, and the horizontal line of the Critical Pathway was made up of from hospitalization to discharge. 2. After the analysis of service contents through reviewing the old chart, it was decided that the horizontal line of the preliminary Critical Pathway was made up of from hopitalization to fourth postoperative day, and the vertical line of it was divided into eight items which were the contents to occur with the time frame of the horizontal line. 3. After the verifying the validity of the expert group about the preliminary Critical Pathway, the horizontal line was amended from hopitalization to third postoperative day, and taking their consensus, some contents of the horizontal line was amended and deleted. 4. From March 1st to 15th, 1997, to confirm the clinical suitability, this author offered eight hysterectomy patients the medical service through the Critical Pathway. The result was that three of them could be discharged at the expected discharge day, and the others later than that day. Supplementing the preliminary Critical Pathway through analyzing the cause of that delay- case, this author developed the final Critical Pathway. 5. There were no significant differences between the experimental and the control group in the incidence of complication(P > 0.05). 6. The 92.4% of experimental group was satisfied with the Critical Pathway service. 7. The length of hospital stay of the experimental group offered with the Critical Pathway service was 4.6 days and there was a significant difference that it was 1.3 days shorter than that of the control group(t=-29.514, P=0.000). 8. There wsa a significant difference that the mean medical charge per one patient of the experimental group offered the Critical Pathway service was cheaper \124,150 than that of the control group(t=-9.826, P=0.000). 9. The result that the author assumed and analyzed hospital income with the rate of turning bed was assumed that the increase of hospital income was \63,245,072 for that study, and the income increase was expected with \68,704,864 for a year. The result that this author applied the Critical Pathway to the hysterectomy patient have no differences in the incidence of complication, high satisfaction with that service, and the length of hospital stay decreased in the experimental group, and the mean hospital charge per one patient decreased, but hospital income increased. Suggestions for further study and nursing practice are as follows. 1. The study to apply the Critical Pathway for a year, verify the validity, and measure the effect repeatedly is needed. 2. To apply and manage the Critical Pathway effectively, the study to computerize it is needed. 3. The study to develop hospital-based Critical Pathway about other diseases or procedure, and measure the effect is needed.

• Korean Journal of Adult Nursing
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• v.12 no.4
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• pp.727-740
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• 2000

It is well recognized that case management is required to survive in the rapidly changing medical environment. One of the case management is the critical pathway(CP) which is assumed to increase the quality of care and at the same time to decrease the length of stay in hospital. The purpose of the study was to develop a CP for the management of patients with postero-lateral fusion for lumbar spinal stenosis. Through review of literature and medical records of patients with spinal stenosis, a pilot CP was designed, including 8 different care components such as medication, laboratory tests, assessment etc., from one day before surgery to 6 days of postoperative care. Every item of the pilot CP was evaluated by a panel of experts to test the content validity. The items not agreed on by more than 4 out of 6 experts were deleted or modified to be integrated in the CP. To apply the modified CP to a clinical environment, the items reflecting treatment, medication and lab work were entered into an order communication system(OCS), and doctors and nurses were taught to use the CP. Finally, the development of CP for the patients with posterolateral lumbar fusion was completed after the application and variance analysis of the CP.

• BMB Reports
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• v.51 no.3
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• pp.119-125
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• 2018

The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy. The analysis of YAP expressions can facilitate the identification of patients who respond better to an anti-cancer drug treatment comprising RAF-, MEK-, and EGFR-targeted inhibitors. The prominence of YAP for those aspects of cancer biology denotes that these factors are ideal targets for the development of anti-cancer medications. Therefore, our report strongly indicates that the YAP is of potential prognostic utility and druggability in various human cancers.