• Title/Summary/Keyword: Drug-associated

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Nuclear localization signal domain of HDAC3 is necessary and sufficient for the expression regulation of MDR1

  • Park, Hyunmi;Kim, Youngmi;Park, Deokbum;Jeoung, Dooil
    • BMB Reports
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    • v.47 no.6
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    • pp.342-347
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    • 2014
  • Histone acetylation/deacetylation has been known to be associated with the transcriptional regulation of various genes. The role of histone deacetylase-3 in the expression regulation of MDR1 was investigated. The expression level of HDAC3 showed an inverse relationship with the expression level of MDR1. Wild-type HDAC3, but not catalytic mutant $HDAC3^{S424A}$, negatively regulated the expression of MDR1. Wild-type HDAC3, but not catalytic mutant $HDAC3^{S424A}$, showed binding to the promoter sequences of HDAC3. HDAC3 regulated the expression level, and the binding of Ac-$H3^{K9/14}$ and Ac-$H4^{K16}$ around the MDR1 promoter sequences. The nuclear localization signal domain of HDAC3 was necessary, and sufficient for the binding of HDAC3 to the MDR1 promoter sequences and for conferring sensitivity to microtubule-targeting drugs.

Downregulated microRNAs in the colorectal cancer: diagnostic and therapeutic perspectives

  • Hernandez, Rosa;Sanchez-Jimenez, Ester;Melguizo, Consolacion;Prados, Jose;Rama, Ana Rosa
    • BMB Reports
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    • v.51 no.11
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    • pp.563-571
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    • 2018
  • Colorectal cancer (CRC), the third most common cancer in the world, has no specific biomarkers that facilitate its diagnosis and subsequent treatment. The miRNAs, small single-stranded RNAs that repress the mRNA translation and trigger the mRNA degradation, show aberrant levels in the CRC, by which these molecules have been related with the initiation, progression, and drug-resistance of this cancer type. Numerous studies show the microRNAs influence the cellular mechanisms related to the cell cycle, differentiation, apoptosis, and migration of the cancer cells through the post-transcriptionally regulated gene expression. Specific patterns of the upregulated and down-regulated miRNA have been associated with the CRC diagnosis, prognosis, and therapeutic response. Concretely, the downregulated miRNAs represent attractive candidates, not only for the CRC diagnosis, but for the targeted therapies via the tumor-suppressing microRNA replacement. This review shows a general overview of the potential uses of the miRNAs in the CRC diagnosis, prognosis, and treatment with a special focus on the downregulated ones.

Functional Imaging of the Multidrug Resistance In Vivo (기능적 영상술을 이용한 다약제 내성의 체내 진단)

  • Lee, Jea-Tae
    • 대한핵의학회:학술대회논문집
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    • 2001.05a
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    • pp.66-75
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    • 2001
  • Although diverse mechanisms are involved in multidrug resistance for chemotherapeutic drugs, the development of cellular P-glycoprotein(Pgp) and multidrug-resistance associated protein (MRP) are important factors in the chemotherapy failure to cancer. Various detection assays provide information about the presence of drug efflux pumps at the mRNA and protein levels. However these methods do not yield information about dynamic function of Pgp and MRP un vivo. Single photon emission tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transport. $^{99m}Tc$-sestaMIBl and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of Pgp-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and N-$[^{11}C]$acetyl-leukotriene E4 provides an opportunity to study MRP function non-invasively in vivo. Results obtained from recent publications are reviewed to confirm the feasibility of using SPECT and PET to study the functionality of MDR transporters in vivo.

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The Factors Associated Depression and Suicidal Ideation in Adolescents (남녀 청소년의 우울 및 자살 생각과의 관련 요인)

  • Kim, Chae-Bong;Jung, Tae-Young;Hwang, Sung-Wan;Kim, Jae-Haeng
    • The Korean Journal of Health Service Management
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    • v.7 no.2
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    • pp.161-177
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    • 2013
  • This study aims to provide basic evidence for establishing prevention programs of school' mental health by identifying the factors of middle and high school student's depression and suicidal ideation related to stress of peer-relationship. For this purpose, we analyzed the data of 6,924 (who Experienced stress related to peer-relationship) among the 2012 Korean Youth Health Risk Behavior Online Survey(8th). In demographic characteristics, subjective academic achievement affects depression in the case of girls. In health-related characteristics, medical treatment by violence, drinking experience, smoking experience have an effect on depression in the case of boys. Subjective health, drinking experience, smoking experience, drug experience are the factors affecting suicidal ideation both boys and girls. In order to promote mental health of youth, school-based prevention education complementing existing realistic problems needs to be implemented.

Rheumatiod Arthritis: An Updated Overview of Latest Therapy and Drug Delivery

  • Kesharwani, Disha;Paliwal, Rishi;Satapathy, Trilochan;Paul, Swarnali Das
    • Journal of Pharmacopuncture
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    • v.22 no.4
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    • pp.210-224
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    • 2019
  • Rheumatoid arthritis is a severe autoimmune disorder, related to joints. It is associated with serious cartilage destruction. This causes disability and reduces the excellence of life. Numerous treatments are existed to combat this disease, however, they are not very efficient and possess severe side effects, higher doses, and frequent administration. Therefore, newer therapies are developed to overcome all these limitations. These include different monoclonal antibodies, immunoglobulins, small molecules used for immunotherapy and transgenes for gene therapy. One of the main goals of these new generation therapeutics is to address the underlying distressing biological processes by specifically targeting the causative agents with fewer systemic side effects and greater patient console. It is very fortuitous that loads of progressive investigations are going on in this field and many of them have entered into the successful clinical trial. But till date, a limited molecule has got FDA clearance and entered the market for treating this devastating disease. This review highlights the overview of conventional therapy and advancements in newer therapeutics including immunotherapy and gene therapy for rheumatoid arthritis. Further, different novel techniques for the delivery of these therapeutics of active and passive targeting are also described.

Protective Effect of Pterocarpus santalinus on Galactosamine Induced Liver Damage

  • Dhanabal, S.P.;Syamala, G.;Elango, K.;Suresh, B.
    • Natural Product Sciences
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    • v.12 no.1
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    • pp.8-13
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    • 2006
  • The present study was carried out to investigate the hepatoprotective effect of the extract of Pterocarpus santalinus Linn on acute hepatotoxicity induced in Wistar albino rats by a single dose of Galactosamine (400 mg/kg). Suspensions of methanolic extract of heartwood of P. santalinus (200 and 400 mg/kg) in 0.3% Carboxy Methyl Cellulose (CMC) were administered p.o. to experimental animals and hepatoprotective activity was monitored by estimating aspartate amino transferase (ASAT, GOT), alanine amino transferase (ALAT, GPT), alkaline phosphatase (ALP), total bilirubin (TB), lactate dehydrogenase (LDH), total cholesterol (TC), triglycerides (TGL), albumin, total protein (TP) levels. The methanolic extract significantly reduced the elevation of serum transaminases and alterations of biochemical parameters induced by hepatotoxin, and alleviated the degree of liver damage. The results were supported by histopathological studies of liver samples showing regeneration of hepatocytes in treated animals. Silymarin (25 mg/kg), a known hepatoprotective drug was used for comparison. Based on the results obtained, it can be concluded that P. santalinus exerts hepatoprotective activity and may serve as a useful adjuvant in several clinical conditions associated with liver damage.

Toxoplasmosis in piglets (자돈의 톡소플라즈마증 발생)

  • Roh, In-soon;Han, Jeong-hee;Kim, Jae-hoon;Ahn, Byeong-woo
    • Korean Journal of Veterinary Research
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    • v.37 no.4
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    • pp.817-823
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    • 1997
  • Suckling piglets and weaned pigs showed anorexia, dehydration, severe abdominal breathing, emaciation and paresis from Oct. 1993. to Nov. 1993. Five 2-week-old piglets were submitted for diagnosis in Kangwon National University. At necropsy, the pin-point well demarcated yellowish white foci were scattered on the surface of the lung, heart, liver, spleen and kidney. Histologically, multifocal areas of necrosis with mononuclear cells infiltration were found in the lung, heart, liver, lymph node, spleen, kidney and small intestine. These lesions tended to be associated with blood vessels. Variable round to ovoid tachyzoites were located at the periphery of the lesions. The organisms were demonstrated as Toxoplasma gondii by immunohistochemical staining method. Ultrastructurally, this parasite was surrounded with parasitophorous vacuole in alveolar macrophage. The parasite was crescent-shaped and $6{\sim}8{\times}1{\sim}2{\mu}m$ in size. It was enclosed by an thick outer membrane and an underlying thin inner membrane. Several club-shaped paired organelles and conoids lay in the cytoplasm at the anterior. Numerous round body and one to several mitochondria were presented in the cytoplasm. Based on the gross findings, histopathology, immunohistochemical and electron microscopic findings, this case was diagnosed as toxoplasmosis in piglets.

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Molecular characterization of Acanthamoeba isolated from amebic keratitis related to orthokeratology lens overnight wear

  • Lee, Jun-Joo;Jeong, Hae-Jin;Lee, Ji-Eun;Lee, Jong-Soo;Xuan, Ying-Hua;Kong, Hyun-Hee;Chung, Dong-Il;Ock, Mee-Sun;Yu, Hak-Sun
    • Parasites, Hosts and Diseases
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    • v.44 no.4 s.140
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    • pp.313-320
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    • 2006
  • In an effort to characterize, on the molecular scale, the Acanthamoeba initially isolated from the cornea of an amoebic keratitis patient associated with overnight-wear orthokeratology lens in Korea, we conducted mitochondrial DNA restriction fragment length polymorphism, 18S rDNA sequencing, and drug sensitivity analyses on the isolate (KA/PE1). The patient was treated with polyhexamethylene biguanide, chlorhexidine and oral itraconazole, which resulted in resolution of the patient's ocular inflammation. The majority of the molecular characteristics of the KA/PE1 were determined to be identical, or quite similar, to those of A. castellanii Ma strain, which had been isolated also from amoebic keratitis. The risk of Acanthamoeba keratitis as a potential complication of overnight orthokeratology is briefly discussed.

Lung Perfusion Imaging and $Tc^{99m}-Macroaggregated$ Human Serum Albumin

  • Haider, Kh.H.;Ilyas, M.;Hyder, Q.;Kim, Chong-Kook
    • Journal of Pharmaceutical Investigation
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    • v.31 no.2
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    • pp.73-80
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    • 2001
  • Lung perfusion scanning, invariably combined with ventilation studies provides a reliable and non-invasive mean to diagnose lung related pathologies despite the availability of modern techniques such as angiography, magnetic resonance imaging, magnetic resonance angiography, and helical (spiral) computed tomography. The technique involves the generation of images by radiations emitted from radioisotopes introduced in to the lungs. Various radiopharmaceuticals have been proposed and designed to incorporate $Tc^{99m}$ in to macroparticulate form for lung perfusion imaging. However, most of these have associated difficulties such as reproducibility of the product with regards to particle size distribution and poor elimination from the lung capillary bed. $Tc^{99m}$ macroaggregated albumin $(Tc^{99m}-MAA)$ is used extensively for clinical lung perfusion imaging and is considered as the radiopharmaceutical of choice. It is non-toxic, safe, and being biodegradable, is easily eliminated from the lung capillary bed by proteolytic enzyme metabolism and by mechanical forces due to lung movement.

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Apoptotic effect of formaldehyde in cultured human hepatocyte cell lines (인간 간세포주 에서 포름알데히드에 의한 세포 사멸 효과)

  • Park, Soo-Hyun
    • Korean Journal of Environmental Agriculture
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    • v.28 no.4
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    • pp.462-467
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    • 2009
  • Exposure of formaldehyde (FA), one of the major compounds in pesticides and in the onset of sick house syndrome, has been implicated in the development of diverse diseases. Liver is a very important organ to body metabolism and drug detoxification. Apotosis of hepatocytes is associated with the onset of liver diseases such as hepatitis. However, the apoptotic effect of FA in hepatocytes is not clear. Therefore, this study was conducted to investigate the effect of FA on the apoptosis in HepG2 cells, a human hepatocyte cell line. As a result, FA (> $500\;{\mu}M$) decreased cell viability and increased lactate dehydrogenase activity in HepG2 cells, which was blocked by the treatment of vitamin E and N-acetylcysteine (NAC). In addition, FA decreased glutathione (GSH) contents and Bcl-2 levels, while increasing lipid peroxide formation and Bax levels. It also cleaved caspase-3 form, which was blocked by the treatment of vitamin E and NAC. It is insisted that FA induced apoptosis via oxidative stress in human hepatocytes.