• Title/Summary/Keyword: Therapeutic Target

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Tissue Distribution of HuR Protein in Crohn's Disease and IBD Experimental Model (염증성 장질환 모델 및 크론병 환자에서의 점막상피 HuR 단백질의 변화 분석)

  • Choi, Hye Jin;Park, Jae-Hong;Park, Jiyeon;Kim, Juil;Park, Seong-Hwan;Oh, Chang Gyu;Do, Kee Hun;Song, Bo Gyoung;Lee, Seung Joon;Moon, Yuseok
    • Journal of Life Science
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    • v.24 no.12
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    • pp.1339-1344
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    • 2014
  • Inflammatory bowel disease is an immune disorder associated with chronic mucosal inflammation and severe ulceration in the gastrointestinal tract. Antibodies against proinflammatory cytokines, including TNF${\alpha}$, are currently used as promising therapeutic agents against the disease. Stabilization of the transcript is a crucial post-transcriptional process in the expression of proinflammatory cytokines. In the present study, we assessed the expression and histological distribution of the HuR protein, an important transcript stabilizer, in tissues from experimental animals and patients with Crohn's disease. The total and cytosolic levels of the HuR protein were enhanced in the intestinal epithelia from dextran sodium sulfate (DSS)-treated mice compared to those in control tissues from normal mice. Moreover, the expression of HuR was very high only in the mucosal and glandular epithelium, and the relative localization of the protein was sequestered in the lower parts of the villus during the DSS insult. The expression of HuR was significantly higher in mucosal lesions than in normal-looking areas. Consistent with the data from the animal model, the expression of HuR was confined to the mucosal and glandular epithelium. These results suggest that HuR may contribute to the post-transcriptional regulation of proinflammatory genes during early mucosal insults. More mechanistic investigations are warranted to determine the potential use of HuR as a predictive biomarker or a promising target against IBD.

Clinical Report of 46 Intracranial Tumors with LINAC Based Stereotactic Radiosurgery (선형가속기를 이용한 뇌종양 46예의 뇌정위다방향방사선치료 성적)

  • Yoon Sei C;Suh Tge S;Kim Sung W;Kang Ki M;Kim Yun S;Choi Byung O;Jang Hong S;Choi Kyo H;Kim Moon C;Shinn Kyung S
    • Radiation Oncology Journal
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    • v.11 no.2
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    • pp.241-247
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    • 1993
  • Between July 1988 and December 1992, we treated 45 patients who had deep seated inoperable or residual and/or recurrent intracranial tumors using LINAC based stereotactic radiosurgery at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. Treated intracranial tumors included pituitary tumors (n=15), acoustic neurinomas (n=8), meningiomas (n=7), gliomas (n=6), craniopharyngiomas (n=4), pinealomas (n=3), hemangioblastomas (n=2), and solitary metastatic tumor from lung cancer (n=1). The dimension of treatment field varied from 0.23 to 42.88 $cm^3\;(mean;\;7.26\;cm^3)$. The maximum tumor doses ranging from 5 to 35.5 Gy (mean; 29.9 Gy) were given, and depended on patients' age, target volume, location of lesion and previous history of irradiation. There were 22 male and 23 female patients. The age was varied from 5 to 74 years of age (a median age; 43 years). The mean duration of follow-up was 35 months (2~55 months). To date, 18 $(39.1\%)$ of 46 intracranial tumors treated with SRS showed absent or decrease of the tumor by serial follow-up CT and/or MRI and 16 $(34.8\%)$ were stationary, e.g. growth arrest. From the view point of the clinical aspects, 34 $(73.9\%)$ of 46 tumors were considered improved status, that is, alive with no evidence of active tumor and 8 $(17.4\%)$ of them were stable, alive with disease but no deterioration as compared with before SRS. Although there showed slight increase of the tumor in size according to follow-up imagings of 4 cases (pituitary tumor 1, acoustic neurinomas 2, pinealoma 1), they still represented clinically stable status. Clinically, two $(4.4\%)$ Patients who were anaplastic astrocytoma (n=1) and metastatic brain tumor (n=1) were worsened following SRS treatment. So far, no serious complications were found after treatment. The minor degree headache which could be relieved by steroid or analgesics and transient focal hair loss were observed in a few cases. There should be meticulous long term follow-up inall cases.

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Deterimination of an Optimal Time Point for Analyzing Transcriptional Activity and Analysis of Transcripts of Avian Influenza Virus H9N2 in Cultured Cell (배양세포에서 Semi-quantitative RT-PCR에 의한 조류인플루엔자 H9N2의 전사활성 분석 최적 시기 결정 및 전사체 분석)

  • Na, Gi-Youn;Lee, Young-Min;Byun, Sung-June;Jeon, Ik-Soo;Park, Jong-Hyeon;Cho, In-Soo;Joo, Yi-Seok;Lee, Yun-Jung;Kwon, Jun-Hun;Koo, Yong-Bum
    • Korean Journal of Microbiology
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    • v.45 no.3
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    • pp.286-290
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    • 2009
  • The transcription of mRNA of avian influenza virus is regulated temporally during infection. Therefore, the measurement of transcript level in host cells should be performed before viral release from host cells because errors can occur in the analysis of the transcript levels if the viruses released from the infected cells re-infect cells. In this study, the timing of viral release was determined by measuring the level of viral RNA from viruses released from H9N2-infected chicken fibroblast cell line UMNSAH/DF-1 by semi-quantitative RT-PCR. The viral genomic RNA was isolated together with mouse total RNA which was added to the collected medium as carrier to monitor the viral RNA recovery and to use its GAPDH as an internal control for normalizing reverse transcription reaction as well as PCR reaction. It was found that viral release of H9N2 in the chicken fibroblast cell line UMNSAH/DF-1 took between 16 and 20 h after infection. We measured all 8 viral mRNA levels. Of the 8 transcripts, 7 species of viral mRNAs (each encoding HA, NA, PB1, PB2, NP, M, NS, respectively) except PA mRNA showed robust amplification, indicating these mRNA can be used as targets for amplification to measure transcript levels. These results altogether suggest that the method in this study can be used for screening antiviral materials against viral RNA polymerase as a therapeutic target.

The Anti-angiogenic Potential of a Phellodendron amurense Hot Water Extract in Vitro and ex Vivo (in Vitro와 ex vivo에서 황백 온수추출물의 신생혈관 억제효과)

  • Kim, Eok-Cheon;Kim, Seo Ho;Bae, Kiho;Kim, Han Sung;Gelinsky, Michael;Kim, Tack-Joong
    • Journal of Life Science
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    • v.25 no.6
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    • pp.693-702
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    • 2015
  • Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE’s anti-angiogenic properties, this study’s authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE’s anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.

Anti-neuroinflammatory Effect of Teleogryllus emma Derived Teleogryllusine in LPS-stimulated BV-2 Microglia (BV-2 미세아교세포에서 왕귀뚜라미 유래 Teleogryllusine의 신경염증 억제 효과)

  • Seo, Minchul;Shin, Yong Pyo;Lee, Hwa Jeong;Baek, Minhee;Lee, Joon Ha;Kim, In-Woo;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.30 no.11
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    • pp.999-1006
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    • 2020
  • The suppression of neuroinflammatory responses in microglial cells, well known as the main immune cells in the central nervous system (CNS), are considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Teleogryllus emma is widely consumed around the world for its broad-spectrum therapeutic effect. In a previous work, we performed transcriptome analysis on T. emma in order to obtain the diversity and activity of its antimicrobial peptides (AMPs). AMPs are found in a variety of species, from microorganisms to mammals. They have received much attention as candidates oftherapeutic drugs for the treatment of inflammation-associated diseases. In this study, we investigated the anti-neuroinflammatory effect of Teleogryllusine (VKWKRLNNNKVLQKIYFVKI-NH2) derived from T. emma on lipopolysaccharide (LPS) induced BV-2 microglia cells. Teleogryllusine significantly inhibited nitric oxide (NO) production without cytotoxicity, and reducing pro-inflammatory enzymes expression such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Telegryllusine also inhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) through down-regulation of the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathway. These results suggest that T. emma-derived Teleogryllusine could be a good source of functional substances that prevent neuroinflammation and neurodegenerative diseases.

Recent Advancement in the Stem Cell Biology (Stem Cell Biology, 최근의 진보)

  • Harn, Chang-Yawl
    • Journal of Plant Biotechnology
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    • v.33 no.3
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    • pp.195-207
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    • 2006
  • Stem cells are the primordial, initial cells which usually divide asymmetrically giving rise to on the one hand self-renewals and on the other hand progenitor cells with potential for differentiation. Zygote (fertilized egg), with totipotency, deserves the top-ranking stem cell - he totipotent stem cell (TSC). Both the ICM (inner cell mass) taken from the 6 days-old human blastocyst and ESC (embryonic stem cell) derived from the in vitro cultured ICM have slightly less potency for differentiation than the zygote, and are termed pluripotent stem cells. Stem cells in the tissues and organs of fetus, infant, and adult have highly reduced potency and committed to produce only progenitor cells for particular tissues. These tissue-specific stem cells are called multipotent stem cells. These tissue-specific/committed multipotent stem cells, when placed in altered environment other than their original niche, can yield cells characteristic of the altered environment. These findings are certainly of potential interest from the clinical, therapeutic perspective. The controversial terminology 'somatic stem cell plasticity' coined by the stem cell community seems to have been proved true. Followings are some of the recent knowledges related to the stem cell. Just as the tissues of our body have their own multipotent stem cells, cancerous tumor has undifferentiated cells known as cancer stem cell (CSC). Each time CSC cleaves, it makes two daughter cells with different fate. One is endowed with immortality, the remarkable ability to divide indefinitely, while the other progeny cell divides occasionally but lives forever. In the cancer tumor, CSC is minority being as few as 3-5% of the tumor mass but it is the culprit behind the tumor-malignancy, metastasis, and recurrence of cancer. CSC is like a master print. As long as the original exists, copies can be made and the disease can persist. If the CSC is destroyed, cancer tumor can't grow. In the decades-long cancer therapy, efforts were focused on the reducing of the bulk of cancerous growth. How cancer therapy is changing to destroy the origin of tumor, the CSC. The next generation of treatments should be to recognize and target the root cause of cancerous growth, the CSC, rather than the reducing of the bulk of tumor, Now the strategy is to find a way to identify and isolate the stem cells. The surfaces of normal as well as the cancer stem cells are studded with proteins. In leukaemia stem cell, for example, protein CD 34 is identified. In the new treatment of cancer disease it is needed to look for protein unique to the CSC. Blocking the stem cell's source of nutrients might be another effective strategy. The mystery of sternness of stem cells has begun to be deciphered. ESC can replicate indefinitely and yet retains the potential to turn into any kind of differentiated cells. Polycomb group protein such as Suz 12 repress most of the regulatory genes which, activated, are turned to be developmental genes. These protein molecules keep the ESC in an undifferentiated state. Many of the regulator genes silenced by polycomb proteins are also occupied by such ESC transcription factors as Oct 4, Sox 2, and Nanog. Both polycomb and transcription factor proteins seem to cooperate to keep the ESC in an undifferentiated state, pluripotent, and self-renewable. A normal prion protein (PrP) is found throughout the body from blood to the brain. Prion diseases such as mad cow disease (bovine spongiform encephalopathy) are caused when a normal prion protein misfolds to give rise to PrP$^{SC}$ and assault brain tissue. Why has human body kept such a deadly and enigmatic protein? Although our body has preserved the prion protein, prion diseases are of rare occurrence. Deadly prion diseases have been intensively studied, but normal prion problems are not. Very few facts on the benefit of prion proteins have been known so far. It was found that PrP was hugely expressed on the stem cell surface of bone marrow and on the cells of neural progenitor, PrP seems to have some function in cell maturation and facilitate the division of stem cells and their self-renewal. PrP also might help guide the decision of neural progenitor cell to become a neuron.

The Risk Factors Related to Constipation in High School Students (고등학생 변비의 위험요인에 관한 연구)

  • Yoon, Yoon-Soo;Lee, Sok-Goo;Kim, Jeong-Yeon
    • Journal of agricultural medicine and community health
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    • v.30 no.1
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    • pp.15-28
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    • 2005
  • Objectives: The purpose of this cross-sectional study was aimed to investigate the status of bowel health behaviors, prevalence of constipation and risk factors related to self-reported constipation in high school students. Methods: The study subjects were 1,882 students of six high schools located in a metropolitan city, who were selected by the accidental sampling from June to August, 2002. We analyzed the data by frequency analysis, chi-square test, and multivariate logistic regression using SPSS ver. 10.0. Results: The result of this study were summarized as follows: 1. A prevalence rate of self-reported constipation was 25.2%. A rate in male students was 13.4% and in female students 36.5%. 2. In regard to therapeutic behavior, 52.1% of study student with change in bowel habit had not find particular counsellor, 38.9% of the student had counselling with parents. 16.3% of students in constipation group had taken laxative medicine for treating the constipation. 73.5% of the student in constipation group had suffered from anal pain during defecation, but 48.0% in normal group. 41.6% of the student in constipation group had a experience of rectal bleeding after defecation, but 23.7% in normal group. So constipation related symptoms distribution had showed statistically significant difference between two group. 3. From the multivariate analysis by self-reported method, the risk factors related to the constipation were sex(female), experience of diet for weight reduction, absence of the breakfast and intake of vegetable more than 3 times per weeks. Conclusions: we had reconfirmed that we should improve eating habits to prevent and treat the constipation in a result of this study. Intervention that is target to girl students, abstain from weight reduction diet, regularity of taking meals, intake more vegetables, stress management should be provided to prevent the constipation especially in Korean high school students. Further prospective designed study are needed to establish the causal-effect relationship between so many risk factors with constipation.

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Effect of Bronchial Artery Embolization in the Treatment of Massive Hemoptysis (대량객혈의 치료에 있어서 기관지동맥색전술의 효과)

  • Lee, Sang-Kyeong;Chun, Ho-Kee;Yoon, Ki-Heon;Yoo, Jee-Hong;Kang, Hong-Mo;Yoon, Yup
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.6
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    • pp.677-682
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    • 1993
  • Background: Massive hemoptysis is a major clinical problem with high mortality. Bronchial artery embolization is well accepted and widely used for treatment of massive and recurrent hemoptysis, especially in patients with chronic diffuse pulmonary disease who are poor candidates for surgery. We evaluated the therapeutic effect of transcatheter arterial embolization for immediate control and prevention of recurrent hemoptysis. Method: We reviewed 20 cases(M:F=13:7) of bronchial artery embolization for the management of massive hemoptysis from Jun 1989 to Aug 1992 retrospectively. Results: Underlying causes of hemoptysis were pulmonary tuberculosis(n=14), bronchiectasis(n=3), aspergilloma(n=2) and paragonimiasis(n=1). Embolization material was choosed randomly gelfoam(n=7) or Ivalon(n=11) and in 2 cases both were used simultaneously. Target arteries of embolization were bronchial artery only in 15 cases, non-bronchial systemic arteries with or without bronchial artery in 5 cases. After the arterial embolization, immediate cessation of hemoptysis was achieved in 17 cases(85%) and total recurrence rate including 3 cases of immediate treatment failure was 50%. Among recurrences 3 cases were achieved lobectomy, 1 case was expired by asphyxia due to massive hemoptysis and remained 6 were managed by medical conservative treatment with no further recurrence of hemoptysis during follow up periods. Conclusion: Bronchial artery embolization for treatment of massive or recurrent hemoptysis was effective in immediate bleeding control. Despite high recurrence rate the rebleeding after embolization was less severe and controllable by conservative management. Bronchial artery embolization is valuable as primary trial to massive hemoptysis.

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Adrenomedullin Deficiency Increases the Susceptibility of Liver Fibrosis Induced by CCl4 (아드레노메둘린 결핍은 사염화탄소로 유도된 간경화 감수성을 상승시킴)

  • Ji, Ae-Ri;Hwang, Meeyul;Kim, Ah-Young;Lee, Eun-Mi;Lee, Eun-Joo;Lee, Myeong-Mi;Sung, Soo-Eun;Kim, Sang-Hyeob;Park, Jin-Kyu;Jeong, Kyu-Shik
    • Journal of Life Science
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    • v.25 no.4
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    • pp.463-472
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    • 2015
  • Adrenomedullin (AM) is a peptide expressed in all body tissues, and its related receptors are increased in liver fibrosis. In this study, we evaluated the effect of AM deficiency on liver fibrogenesis induced by $CCl_4$ using AM heterozygous (HT) mice. The animals received a single injection of $CCl_4$ or olive oil for the acute experiment, and received $CCl_4$ or olive oil three times a week for 6 weeks for the chronic experiment. Fibrosis was accessed using histopathological analysis and the western blot. The AM HT mice showed mild pericentrilobular degeneration when compared to the AM wild type (WT) mice. In the acute experiment, there was no significant difference between the AM WT and AM HT mice. However, in the chronic experiment, the $CCl_4$-treated AM HT mice showed more severe liver fibrosis than that of the CCl4-treated AM WT mice. The AST and ALT levels of the AM HT $CCl_4$ group were higher than those of the AM WT CCl4 group. Additionally, the collagen deposition, $\alpha$- SMA protein and TGF-$\beta$ protein were increased in the AM HT $CCl_4$ group when compared to the AM WT $CCl_4$ group. The AM HT mice also exhibited severe lipid peroxidation through the GSH decrement. Taken together, our data suggest that AM deficiency increases the susceptibility to liver fibrosis induced by $CCl_4$, indicating a novel therapeutic target for patients with liver fibrosis.

Incidence and Procedure-Related Risk Factors of Delirium in Patients Admitted to an Intensive Care Unit (중환자실 입원 환자의 섬망 발생과 처치 관련 위험인자)

  • Ahn, Jee Seon;Oh, Jooyoung;Park, Jaesub;Kim, Jae-Jin;Park, Jin Young
    • Korean Journal of Psychosomatic Medicine
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    • v.27 no.1
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    • pp.35-41
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    • 2019
  • Objectives : Although delirium is a common complication among patients hospitalized in intensive care units(ICUs), little is known about the roles that diagnostic and therapeutic procedures play in its development. This study investigates the procedure-related risk factors of delirium in ICU patients. Methods : All the consecutive patients admitted to the ICU between June 2016 and May 2017 were routinely evaluated for delirium by psychiatrists. In total, 1156 patients met the inclusion criteria and were retrospectively analyzed. A multiple logistic regression analysis was conducted to investigate independent risk factors of delirium development while adjusting for other characteristics. Results : The age, Acute Physiology and Chronic Health Evaluation (APACHE II) score, proportion of patients who had undergone an operation, and proportion of patients who were foley catheterized, mechanically ventilated, and physically restrained were higher in the delirium group. The multiple logistic regression analysis confirmed that the use of restraint was an independent risk factor of delirium (odds ratio : 10.006 ; 95% confidence interval : 6.120-16.360 ; p<0.001). The patient factors independently associated with delirium were an advanced age and a higher APACHE II score. The incidence of delirium was 15.3%. Conclusions : There is a high prevalence of delirium influenced by potentially harmful procedures in patients in ICU settings. The use of physical restraint had the strongest association with the development of delirium. These findings advocate the need to target procedure-related risk factors such as the use of restraints as preventive intervention measures for ICU delirium.