• Title/Summary/Keyword: Models, animal

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Adenosine monophosphate-activated protein kinase in diabetic nephropathy

  • Kim, Yaeni;Park, Cheol Whee
    • Kidney Research and Clinical Practice
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    • v.35 no.2
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    • pp.69-77
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    • 2016
  • Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 50 adenosine monophosphate-activated protein kinase (AMPK), an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder.

Anti-cancer Mechanism of Docosahexaenoic Acid in Pancreatic Carcinogenesis: A Mini-review

  • Park, Mirae;Kim, Hyeyoung
    • Journal of Cancer Prevention
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    • v.22 no.1
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    • pp.1-5
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    • 2017
  • Pancreatic cancer is a highly aggressive malignant tumor of the digestive system and radical resection, which is available to very few patients, might be the only possibility for cure. Since therapeutic choices are limited at the advanced stage, prevention is more important for reducing incidence in high-risk individuals with family history of pancreatic cancer. Epidemiological studies have shown that a high consumption of fish oil or ${\omega}3-polyunsaturated$ fatty acids reduces the risk of pancreatic cancers. Dietary fish oil supplementation has shown to suppress pancreatic cancer development in animal models. Previous experimental studies revealed that several hallmarks of cancer involved in the pathogenesis of pancreatic cancer, such as the resistance to apoptosis, hyper-proliferation with abnormal $Wnt/{\beta}-catenin$ signaling, expression of pro-angiogenic growth factors, and invasion. Docosahexaenoic acid (DHA) is a ${\omega}3-polyunsaturated$ fatty acid and rich in cold oceanic fish oil. DHA shows anti-cancer activity by inducing oxidative stress and apoptosis, inhibiting $Wnt/{\beta}-catenin$ signaling, and decreasing extracellular matrix degradation and expression of pro-angiogenic factors in pancreatic cancer cells. This review will summarize anti-cancer mechanism of DHA in pancreatic carcinogenesis based on the recent studies.

Role of nociceptin/orphanin FQ and nociceptin opioid peptide receptor in depression and antidepressant effects of nociceptin opioid peptide receptor antagonists

  • Park, Jong Yung;Chae, Suji;Kim, Chang Seop;Kim, Yoon Jae;Yi, Hyun Joo;Han, Eunjoo;Joo, Youngshin;Hong, Surim;Yun, Jae Won;Kim, Hyojung;Shin, Kyung Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.6
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    • pp.427-448
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    • 2019
  • Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying $K^+$ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.

Pharmacokinetic Changes in Drugs during Protein-Calorie Malnutrition: Correlation between Drug Metabolism and Hepatic Microsomal Cytochrome P450 Isozymes

  • Lee, Joo-Hyun;Suh, Ok-Kyung;Lee, Myung-Gull
    • Archives of Pharmacal Research
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    • v.27 no.7
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    • pp.693-712
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    • 2004
  • The rats with protein-calorie malnutrition (PCM, 5% casein diet for a period of 4-week) were reported to exhibit 60 and 80% suppression in the hepatic microsomal cytochrome P450 (CYP) 1 A2 and CYP2C11 levels, respectively, and 40-50% decreases in CYP2E1 and CYP3A 1/2 levels compared to control (23% casein diet for a period of 4-week) based on Western blot analysis. In addition, Northern blot analysis showed that CYP1 A2, CYP2E1, CYP2C11, and CYP3A1/2 mRNAs decreased in the state of PCM as well. Hence, pharmacokinetic changes of the drugs in rats with PCM [especially the area under the plasma concentration-time curve from time zero to time infinity (AUC) changes of metabolite(s)] reported from literatures were tried to explain in terms of CYP isozyme changes in the rats. Otherwise, the time-averaged nonrenal clearance ($CL_{NR}$) of parent drug was compared. Pharmacokinetic changes of the drugs in other types of malnutritional state, such as kwashiorkor and marasmus, in both human and animal models were also compared. The drugs reviewed are as follows: diuretics, antibiotics, anticancer agents, antiepileptics, antiarrythmics, analgesics, xanthines, antimalarials, and miscellaneous.

Decorin: a multifunctional proteoglycan involved in oocyte maturation and trophoblast migration

  • Park, Beom Seok;Lee, Jaewang;Jun, Jin Hyun
    • Clinical and Experimental Reproductive Medicine
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    • v.48 no.4
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    • pp.303-310
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    • 2021
  • Decorin (DCN) is a proteoglycan belonging to the small leucine-rich proteoglycan family. It is composed of a protein core containing leucine repeats with a glycosaminoglycan chain consisting of either chondroitin sulfate or dermatan sulfate. DCN is a structural component of connective tissues that can bind to type I collagen. It plays a role in the assembly of the extracellular matrix (ECM), and it is related to fibrillogenesis. It can interact with fibronectin, thrombospondin, complement component C1, transforming growth factor (TGF), and epidermal growth factor receptor. Normal DCN expression regulates a wide range of cellular processes, including proliferation, migration, apoptosis, and autophagy, through interactions with various molecules. However, its aberrant expression is associated with oocyte maturation, oocyte quality, and poor extravillous trophoblast invasion of the uterus, which underlies the occurrence of preeclampsia and intrauterine growth restriction. Spatiotemporal hormonal control of successful pregnancy should regulate the concentration and activity of specific proteins such as proteoglycan participating in the ECM remodeling of trophoblastic and uterine cells in fetal membranes and uterus. At the human feto-maternal interface, TGF-β and DCN play crucial roles in the regulation of trophoblast invasion of the uterus. This review summarizes the role of the proteoglycan DCN as an important and multifunctional molecule in the physiological regulation of oocyte maturation and trophoblast migration. This review also shows that recombinant DCN proteins might be useful for substantiating diverse functions in both animal and in vitro models of oogenesis and implantation.

Draft Genome Sequence of Xylaria grammica EL000614, a Strain Producing Grammicin, a Potent Nematicidal Compound

  • Park, Sook-Young;Jeon, Jongbum;Kim, Jung A;Jeon, Mi Jin;Yu, Nan Hee;Kim, Seulbi;Park, Ae Ran;Kim, Jin-Cheol;Lee, Yerim;Kim, Youngmin;Choi, Eu Ddeum;Jeong, Min-Hye;Lee, Yong-Hwan;Kim, Soonok
    • Mycobiology
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    • v.49 no.3
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    • pp.294-296
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    • 2021
  • An endolichenic fungus, Xylaria grammica strain EL000614, showed strong nematicidal effects against plant pathogenic nematode, Meloidogyne incognita by producing grammicin. We report genome assembly of X. grammica EL000614 comprised of 25 scaffolds with a total length of 54.73 Mb, N50 of 4.60 Mb, and 99.8% of BUSCO completeness. GC contents of this genome were 44.02%. Gene families associated with biosynthesis of secondary metabolites or regulatory proteins were identified out of 13,730 gene models predicted.

Target/non-target classification using active sonar spectrogram image and CNN (능동소나 스펙트로그램 이미지와 CNN을 사용한 표적/비표적 식별)

  • Kim, Dong-Wook;Seok, Jong-Won;Bae, Keun-Sung
    • Journal of IKEEE
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    • v.22 no.4
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    • pp.1044-1049
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    • 2018
  • CNN (Convolutional Neural Networks) is a neural network that models animal visual information processing. And it shows good performance in various fields. In this paper, we use CNN to classify target and non-target data by analyzing the spectrogram of active sonar signal. The data were divided into 8 classes according to the ratios containing the targets and used for learning CNN. The spectrogram of the signal is divided into frames and used as inputs. As a result, it was possible to classify the target and non-target using the characteristic that the classification results of the seven classes corresponding to the target signal sequentially appear only at the position of the target signal.

Analysis of Ingredients and biological activities confirm Process for Personalized Diet Offering Service: Basic ingredients Analysis and biological Activities of Grifola frondosa

  • Hong, Seok Chan;Hwang, You Jin;Kang, Un Gu
    • Journal of the Korea Society of Computer and Information
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    • v.24 no.8
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    • pp.113-121
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    • 2019
  • The personalized meal service is being developed to prevent and alleviate illnesses according to the individual's health condition. However, the current meal does not provide a fully customized service to individuals and a diet that meets the consumer's information needs. The cause is the lack of information on the ingredients and the difficulty of comparative analysis between the materials. Therefore, in this study, we propose basic analysis process for basic information acquisition and database construction for food composition before providing personalized food. In this study, we investigated the content of carbohydrate, reducing sugar and protein as basic components of Grifola frondosa and investigate the content of polyphenol as a biological active ingredients. Respectively. Studies on the hypoglycemic effect of the diabetic rat model have been carried out in relation to the prevention of diseases. Based on the results of this study, it is also possible to obtain information on the basic ingredients of the food and to analyze the information on the content and activity of the biological active ingredients. Using animal models, information on disease prevention and mitigation was also available. The process introduced in this study is applied to various food materials, accumulating data, and utilizing Database, this results will be an excellent tool for providing more efficient service by providing a proper dietary composition for consumers.

Dose-Dependent Inhibition of Melanoma Differentiation-Associated Gene 5-Mediated Activation of Type I Interferon Responses by Methyltransferase of Hepatitis E Virus

  • Myoung, Jinjong;Min, Kang Sang
    • Journal of Microbiology and Biotechnology
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    • v.29 no.7
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    • pp.1137-1143
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    • 2019
  • Hepatitis E virus (HEV) accounts for 20 million infections in humans worldwide. In most cases, the infections are self-limiting while HEV genotype 1 infection cases may lead to lethal infections in pregnant women (~ 20% fatality). The lack of small animal models has hampered detailed analysis of virus-host interactions and HEV-induced pathology. Here, by employing a recently developed culture-adapted HEV, we demonstrated that methyltransferase, a non-structural protein, strongly inhibits melanoma differentiation-associated gene 5 (MDA5)-mediated activation of type I interferon responses. Compared to uninfected controls, HEV-infected cells display significantly lower levels of $IFN-{\beta}$ promoter activation when assessed by luciferase assay and RT-PCR. HEV genome-wide screening showed that HEV-encoded methyltransferase (MeT) strongly inhibits MDA5-mediated transcriptional activation of $IFN-{\beta}$ and $NF-{\kappa}B$ in a dose-responsive manner whether or not it is expressed in the presence/absence of a tag fused to it. Taken together, current studies clearly demonstrated that HEV MeT is a novel antagonist of MDA5-mediated induction of $IFN-{\beta}$ signaling.

Characterization of Plasmodium berghei Homologues of T-cell Immunomodulatory Protein as a New Potential Candidate for Protecting against Experimental Cerebral Malaria

  • Cui, Ai;Li, Yucen;Zhou, Xia;Wang, Lin;Luo, Enjie
    • Parasites, Hosts and Diseases
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    • v.57 no.2
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    • pp.101-115
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    • 2019
  • The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.