• 제목/요약/키워드: therapeutic evidence

검색결과 636건 처리시간 0.03초

Aequorin Based Functional Assessment of the Melanin Concentrating Hormone Receptor by Intracellular Calcium Mobilization

  • Lee, Sung-Hou
    • Biomolecules & Therapeutics
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    • 제18권2호
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    • pp.152-158
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    • 2010
  • Melanin concentrating hormone is a neuropeptide highly expressed in the brain that regulates several physiological functions mediated by receptors in the G-protein coupled receptor family, especially plays an important role in the complex regulation of energy balance and body weight mediated by the melanin concentrating hormone receptor subtype 1 (MCH1). Compelling pharmacological evidence implicating MCH1 signaling in the regulation of food intake and energy expenditure has generated a great deal of interest by pharmaceutical companies as MCH1 antagonists may have potential therapeutic benefit in the treatment of obesity and metabolic syndrome. Although fluorescence-based calcium mobilization assay platform has been one of the most widely accepted tools for receptor research and drug discovery, fluorescence interference and shallow assay window limit their application in high throughput screening and have led to a growing interest in alternative, luminescence-based technologies. Herein, a luminescence-based functional assay system for the MCH1 receptor was developed and validated with the mitochondrial targeted aequorin. Aequorin based functional assay system for MCH1 presented excellent Z' factor (0.8983) and high signal-to-noise ratio (141.9). The nonpeptide MCH1 receptor antagonist, SNAP 7941 and GSK 803430, exhibited $IC_{50}$ values of 0.62 ${\pm}$ 0.11 and 12.29 ${\pm}$ 2.31 nM with excellent correlation coefficient. These results suggest that the aequorin based assay system for MCH1 is a strong alternative to the traditional GPCR related tools such as radioligand binding experiments and fluorescence functional determinations for the compound screening and receptor research.

Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis

  • Kim, Ju-Young;Cheon, Yoon-Hee;Yoon, Kwon-Ha;Lee, Myeung Su;Oh, Jaemin
    • BMB Reports
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    • 제47권8호
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    • pp.451-456
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    • 2014
  • Parthenolide, a natural product derived from Feverfew, prevents septic shock and inflammation. We aimed to identify the effects of parthenolide on the RANKL (receptor activator of $NF-{\kappa}B$ ligand)-induced differentiation and bone resorbing activity of osteoclasts. In this study, parthenolide dose-dependently inhibited RANKL-mediated osteoclast differentiation in BMMs, without any evidence of cytotoxicity and the phosphorylation of p38, ERK, and $I{\kappa}B$, as well as $I{\kappa}B$ degradation by RANKL treatment. Parthenolide suppressed the expression of NFATc1, OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treated BMMs. Furthermore, parthenolide down-regulated the stability of c-Fos protein, but could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in BMMs reversed the inhibitory effect of parthenolide on RANKL-mediated osteoclast differentiation. Parthenolide also inhibited the bone resorbing activity of mature osteoclasts. Parthenolide inhibits the differentiation and bone-resolving activity of osteoclast by RANKL, suggesting its potential therapeutic value for bone destructive disorders associated with osteoclast-mediated bone resorption.

Prostate Cancer and Metabolic Syndrome: Is there a link?

  • McGrowder, Donovan A.;Jackson, Lennox Anderson;Crawford, Tazhmoye V.
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권1호
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    • pp.1-13
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    • 2012
  • Metabolic syndrome has become quite prevalent within our society. Over the past two decades, the prevalence of metabolic syndrome has sharply increased worldwide and it has become a major public health problem in several countries. It is associated with the global epidemic of obesity and diabetes mellitus and imposes numerous cardiovascular risks. Prostate cancer is the second most common cancer among men, surpassed only by non-melanoma skin cancer. A considerable body of evidence exists suggesting that some components of the metabolic syndrome have been associated with the risk of prostate cancer. These components include obesity, an abdominal fat distribution, and hyperinsulinemia. Androgen deprivation therapy (ADT) is the most widely used therapeutic modality in prostate cancer. It changed the body composition and lipid profile of men with prostate cancer. Androgen deficiency is associated with increased levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, increased production of proinflammatory factors, and increased thickness of the arterial wall and contributes to endothelial dysfunction. The aim of this review is to evaluate the association between metabolic syndrome and prostate cancer and to discuss the implications of androgen deficiency in men with cardiovascular risk factors. A comprehensive literature search was carried out with the use of PubMed from 1980 through 2011, and relevant articles pertinent to metabolic syndrome and prostate cancer are evaluated and discussed.

Hsa-miR-181a-5p Expression and Effects on Cell Proliferation in Gastric Cancer

  • Chen, Gang;Shen, Zhi-Li;Wang, Ling;Lv, Chun-Ye;Huang, Xin-En;Zhou, Rong-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권6호
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    • pp.3871-3875
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    • 2013
  • Purpose: MicroRNAs (miRNAs) are small endogenous, non-coding, single-stranded RNAs (approximately 22 nt). Accumulating evidence has shown that aberrant miRNA expression is pronounced and correlated with gastric cancer genesis and progression. Materials and Methods: Expression levels of miR-181a-5p in GC tissues and cell lines were assessed by qRT-PCR and tested for correlation with clinical features. In addition, effects of miR-181a-5p on GC cell growth were investigated. Results: Our findings indicate that miR-181a-5p is upregulated in GC, in correlation with lymph node invasion, nerve invasion and vascular invasion (P<0.05). Enforced expression of miR-181a -5p promoted cell proliferation ability. Conclusions: This study suggested that increased miR-181a-5p is related to GC progression. MiR-181a-5p may represent a potential therapeutic target for GC.

Asthma and the Risk of Rheumatoid Arthritis: An Insight into the Heterogeneity and Phenotypes of Asthma

  • Rolfes, Mary Claire;Juhn, Young Jun;Wi, Chung-Il;Sheen, Youn Ho
    • Tuberculosis and Respiratory Diseases
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    • 제80권2호
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    • pp.113-135
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    • 2017
  • Asthma is traditionally regarded as a chronic airway disease, and recent literature proves its heterogeneity, based on distinctive clusters or phenotypes of asthma. In defining such asthma clusters, the nature of comorbidity among patients with asthma is poorly understood, by assuming no causal relationship between asthma and other comorbid conditions, including both communicable and noncommunicable diseases. However, emerging evidence suggests that the status of asthma significantly affects the increased susceptibility of the patient to both communicable and noncommunicable diseases. Specifically, the impact of asthma on susceptibility to noncommunicable diseases such as chronic systemic inflammatory diseases (e.g., rheumatoid arthritis), may provide an important insight into asthma as a disease with systemic inflammatory features, a conceptual understanding between asthma and asthma-related comorbidity, and the potential implications on the therapeutic and preventive interventions for patients with asthma. This review discusses the currently under-recognized clinical and immunological phenotypes of asthma; specifically, a higher risk of developing a systemic inflammatory disease such as rheumatoid arthritis and their implications, on the conceptual understanding and management of asthma. Our discussion is divided into three parts: literature summary on the relationship between asthma and the risk of rheumatoid arthritis; potential mechanisms underlying the association; and implications on asthma management and research.

Anti-inflammatory Effects of Abeliophyllum distichum Flower Extract and Associated MAPKs and NF-κB Pathway in Raw264.7 Cells

  • Lee, Jin-Wook;Kang, Yoon-Joong
    • 한국자원식물학회지
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    • 제31권3호
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    • pp.202-210
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    • 2018
  • Abeliophyllum distichum is a medicinal plant used in regional traditional medicine to relieve pain in inflammatory processes. In this study, anti-inflammatory effects of Abeliophyllum distichum flower (ADF) extract were examined. Furthermore, possible molecular mechanisms of the anti-inflammatory effects were dissected. The anti-inflammatory activity was investigated by inhibition of lipopolysaccharide (LPS) induced pro-inflammatory cytokine production in murine macrophage-like cell line Raw264.7 cells. The measurement of the induced pro-inflammatory cytokine levels were carried out by ELISA. The phosphorylation of ERK1/2, JNK, and MAPK, and the nuclear expression of nuclear factor NF-${\kappa}B$ p65 were investigated by Western blot analysis. The extract of ADF significantly decreased the production of pro-inflammatory cytokines. In addition, the extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of NF-${\kappa}B$ p65 in activated cells. Our findings provide evidence for the popular use of Abeliophylli distichum in inflammation around Goesan region and also suggest that the flower extract has potential therapeutic benefits against various inflammatory diseases.

만성 뇌졸중 환자의 마비측 중간볼기근 테이핑이 균형과 보행에 미치는 영향 (The Effect of Gluteus Medius Taping on Balance and Walking in Chronic Stroke Patients)

  • 이양진;조남정
    • 대한통합의학회지
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    • 제6권3호
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    • pp.17-24
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    • 2018
  • Purpose : Kinesio taping is a therapeutic method used in the treatment of various musculoskeletal and neuromuscular deficits limited evidence the effects of gluteus medius kinesio taping in neurologic patients. Therefore, this study aimed to determine the effects of gluteus medius kinesio taping on balance ability and gait function in after a stroke. Methods : Twenty-four post-stroke patients were included in this study. Gluteus medius taping group and sham gluteus medius taping group were divided into intervention. Kinesio tape was applied the gluteus medius muscles. In all the subjects, the balance ability was measured using the force plate and timed up & go test (TUG) and gait function was assessed using the 10-meter walking test at time points of both before and after the taping. Result : There was a significant difference in balance ability and gait function between the two groups before and after gluteus medius taping group (p<.05). The gluteus medius taping group showed a significant difference between the groups (p<.05). Conclusion : The results suggest that taping may be a useful method during rehabilitation programs for stroke patients. Application of Kinesio taping to the gluteus medius muscles was found to be useful especially in improving balance ability.

비인강암(鼻咽腔癌) 방사선치료성적(放射線治療成績) (The Radiotherapy Result of the Nasopharyngeal Carcinoma)

  • 박찬일;고경환;김종선;김노경
    • Radiation Oncology Journal
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    • 제1권1호
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    • pp.85-94
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    • 1983
  • A total of 47 patients with a diagnosis of nasopharyngeal carcinoma was treated in Department of Therapeutic Radiology, Seoul National University Hospital during last 4 years. Of the 47 patients, 23(49%) had undifferentiated carcinoma, 20(43%) had squamous cell carcinoma, while 4(8%) had lymphoepithelioma. Most of the patients(71%) has Stage IV disease, cervical lymph node metastases were found in 36(77%) and distant metastasis was found in 1 at the time of diagnosis. Complete response rate after radiotherapy for 47 patients of nasopharyngeal carcinoma was 85.1%. The overall actuarial 3 year survival rates was 0.718 and the disease free actuarial 3 year survival rates was 0.468. Nodal involvement and symptom duration were statistically significiant influencing factors for actuarial survival rate. Treatment failures were found in 20 patients (42.6%), local recurrence only in 6(30%), local and neck recurrence in 3(15%), local recurrence with metastasis in 4(20%) and distant metastasis only in 7(35%). Local failures were more frequent in the patients with cranial nerve symptoms (P=0.032). Distant metastases were more frequent with T4 lesions (P=0.047), and with nodal involvement (P<0.01). Retreatment after the tumor recurrence was chemotherapy and/or radiotherapy, two pationts refreated for local recurrence were alive without evidence of disease for more than 19 and 44 months after retreatment.

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간호실무현장에서 요구하는 간호대학 졸업생들의 간호핵심역량 (Nursing Core Competencies Needed in the Fields of Nursing Practice for Graduates in Nursing)

  • 이선경;박선남;정석희
    • 간호행정학회지
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    • 제18권4호
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    • pp.460-473
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    • 2012
  • Purpose: This study was done to provide information on issues of nursing core competencies needed in the fields of nursing practice for graduates in nursing, from the perspective of nursing managers, and to make suggestion for improving nursing education programs. Methods: Ten nursing managers participated in this study. They were in charge of clinical nursing education in the fields of nursing practice. Data were collected using focus group interviews and analyzed with the content analysis methodology of Downe - Wamboldt's. Results: Six types of nursing core competency - therapeutic nursing competency, professional nursing competency, administrative nursing competency, humanistic nursing competency, relational nursing competency, and personal nursing competency - were identified as nursing core competencies needed in the fields of nursing practice for graduates in nursing. Conclusion: Results of the study show important evidence for decision-making about nursing curriculum revision based on nursing core competency, both in the classroom and in nursing practice areas. These results should contribute to the development of evaluation indicators for nursing students or new nurses. Further research is required to measure degree of nursing core competency in graduates of nursing and to identify the effect of competency-based education for improving nursing core competency.

Recent insights into the role of ChREBP in intestinal fructose absorption and metabolism

  • Lee, Ho-Jae;Cha, Ji-Young
    • BMB Reports
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    • 제51권9호
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    • pp.429-436
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    • 2018
  • Fructose in the form of sucrose and high fructose corn syrup is absorbed by the intestinal transporter and mainly metabolized in the small intestine. However, excess intake of fructose overwhelms the absorptive capacity of the small intestine, leading to fructose malabsorption. Carbohydrate response element-binding protein (ChREBP) is a basic helix-loop-helix leucine zipper transcription factor that plays a key role in glycolytic and lipogenic gene expression in response to carbohydrate consumption. While ChREBP was initially identified as a glucose-responsive factor in the liver, recent evidence suggests that ChREBP is essential for fructose-induced lipogenesis and gluconeogenesis in the small intestine as well as in the liver. We recently identified that the loss of ChREBP leads to fructose intolerance via insufficient induction of genes involved in fructose transport and metabolism in the intestine. As fructose consumption is increasing and closely associated with metabolic and gastrointestinal diseases, a comprehensive understanding of cellular fructose sensing and metabolism via ChREBP may uncover new therapeutic opportunities. In this mini review, we briefly summarize recent progress in intestinal fructose metabolism, regulation and function of ChREBP by fructose, and delineate the potential mechanisms by which excessive fructose consumption may lead to irritable bowel syndrome.