• Title/Summary/Keyword: Endogenous Development

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Human Immunodeficiency Virus-l Tat Positively Regulates the Human CD99 Gene via DNA Demethylation (Human Immunodeficiency Virus-1 Tat 단백에 의한 인간 CD99유전자의 조절기전에 대한 연구)

  • Lee, Eu-Gene;Kim, Ye-Ri;Lee, Mi-Kyung;Lee, Im-Soon
    • Korean Journal of Microbiology
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    • v.44 no.4
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    • pp.277-281
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    • 2008
  • HIV affects many organ systems. Patients with HIV infection have substantially increased risk of developing various cancers, primarily by opportunistic infection with oncogenic viruses due to their immunocompromised status. However, extensive evidence also indicates that the viral protein, Tat itself, may playas a major factor in the development of AIDS-related neoplasms. The molecular mechanism underlying Tat's oncogenic activity may include deregulation of cellular genes. Therefore, in this study, we examined the effect of HIV-l Tat on CD99 as one of the target cellular genes, which is a well-known tumor marker in several cancers. By using established HeLa clones that are stably expressing Tat, we found that CD99 is upregulated by endogenous Tat, whereas STAT3 is down regulated. Upon the screening of genes differentially expressed between Tat-stable cells and the control cells by using the gene fishing technique, DEG, we detected 3 genes which expression is affected by the presence of Tat. Furthermore, the methylation specific PCR analysis of the stably Tat expressing cell lines revealed that the CD99 promoter is de methylated in the presence of Tat. Taken together, these results open a potential role of CD99 in AIDS-related oncogenesis via epigenetic regulation by HIV-1 Tat.

Infection kinetics and developmental biology of Cryptosporidiam muris (strain MCR) in Korean native kids and Corriedale lambs (재래산양 및 면양에 있어서 쥐와포자충 (MCR주)의 감염 동태)

  • Lee, Jae-Gu;Kim, Hyeon-Cheol;Eun, Gil-Su
    • Parasites, Hosts and Diseases
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    • v.36 no.3
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    • pp.171-182
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    • 1998
  • A total of nine Korean native kids and two Corriedale lambs, 1-20 days old, were each inoculated per os with a single dose of 2 × 107 oocysts of Cwptospori,mum muris (strain MCR) originated from mice to elucidate the kinetics and developmental stages of the coccidium in small ruminants. Irrespective of host's age, the prepatent period for both animals ranged from 19 to 35 days (28.1 days, on the average) and the patent period 16-85 days (47.8 days), and the total oocyst outputs showed enormous differences. Infection with greater numbers of oocyst outputs was not ordinarily established by transmission experiments. Oocysts discharged from the kids retained their infectivity by the mouse titration method. The immunogenicity of the coccidium and oocyst reproduction were proven by challenge infection and administration of prednisolone acetate. respectively. All the developmental stages of the coccidium in parasitophorous vacuoles were found by transmission electron microscopy in the pits of the gastric glands of a kid inoculated with oocysts and then necropsied on day 44 postinoculation. It indicated the full course of the host-parasite relationship in kids and lambs as well as mice.

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Gaseous signal molecule SO2 regulates autophagy through PI3K/AKT pathway inhibits cardiomyocyte apoptosis and improves myocardial fibrosis in rats with type II diabetes

  • Zhao, Junxiong;Wu, Qian;Yang, Ting;Nie, Liangui;Liu, Shengquan;Zhou, Jia;Chen, Jian;Jiang, Zhentao;Xiao, Ting;Yang, Jun;Chu, Chun
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.6
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    • pp.541-556
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    • 2022
  • Myocardial fibrosis is a key link in the occurrence and development of diabetic cardiomyopathy. Its etiology is complex, and the effect of drugs is not good. Cardiomyocyte apoptosis is an important cause of myocardial fibrosis. The purpose of this study was to investigate the effect of gaseous signal molecule sulfur dioxide (SO2) on diabetic myocardial fibrosis and its internal regulatory mechanism. Masson and TUNEL staining, Western-blot, transmission electron microscopy, RT-qPCR, immunofluorescence staining, and flow cytometry were used in the study, and the interstitial collagen deposition, autophagy, apoptosis, and changes in phosphatidylinositol 3-kinase (PI3K)/AKT pathways were evaluated from in vivo and in vitro experiments. The results showed that diabetic myocardial fibrosis was accompanied by cardiomyocyte apoptosis and down-regulation of endogenous SO2-producing enzyme aspartate aminotransferase (AAT)1/2. However, exogenous SO2 donors could up-regulate AAT1/2, reduce apoptosis of cardiomyocytes induced by diabetic rats or high glucose, inhibit phosphorylation of PI3K/AKT protein, up-regulate autophagy, and reduce interstitial collagen deposition. In conclusion, the results of this study suggest that the gaseous signal molecule SO2 can inhibit the PI3K/AKT pathway to promote cytoprotective autophagy and inhibit cardiomyocyte apoptosis to improve myocardial fibrosis in diabetic rats. The results of this study are expected to provide new targets and intervention strategies for the prevention and treatment of diabetic cardiomyopathy.

Development of a real-time polymerase chain reaction assay for reliable detection of a novel porcine circovirus 4 with an endogenous internal positive control

  • Kim, Hye-Ryung;Park, Jonghyun;Park, Ji-Hoon;Kim, Jong-Min;Baek, Ji-Su;Kim, Da-Young;Lyoo, Young S.;Park, Choi-Kyu
    • Korean Journal of Veterinary Service
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    • v.45 no.1
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    • pp.1-11
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    • 2022
  • A novel porcine circovirus 4 (PCV4) was recently identified in Chinese and Korean pig herds. Although several conventional polymerase chain reaction (cPCR) and real-time PCR (qPCR) assays were used for PCV4 detection, more sensitive and reliable qPCR assay is needed that can simultaneously detect PCV4 and internal positive control (IPC) to avoid false-negative results. In the present study, a duplex qPCR (dqPCR) assay was developed using primers/probe sets targeting the PCV4 Cap gene and pig (glyceraldehyde-3-phosphate dehydrogenase) GAPDH gene as an IPC. The developed dqPCR assay was specifically detected PCV4 but not other PCVs and porcine pathogens, indicating that the newly designed primers/probe set is specific to the PCV4 Cap gene. Furthermore, GAPDH was stably amplified by the dqPCR in all tested viral and clinical samples containing pig cellular materials, indicating the high reliability of the dqPCR assay. The limit of detection of the assay 5 copies of the target PCV4 genes, but the sensitivity of the assay was higher than that of the previously described assays. The assay demonstrated high repeatability and reproducibility, with coefficients of intra-assay and inter-assay variation of less than 1.0%. Clinical evaluation using 102 diseased pig samples from 18 pig farms showed that PCV4 circulated in the Korean pig population. The detection rate of PCV4 obtained using the newly developed dqPCR was 26.5% (27/102), which was higher than that obtained using the previously described cPCR and TaqMan probe-based qPCR and similar to that obtained using the previously described SYBR Green-based qPCR. The dqPCR assay with IPC is highly specific, sensitive, and reliable for detecting PCV4 from clinical samples, and it will be useful for etiological diagnosis, epidemiological study, and control of the PCV4 infections.

Three sesquiterpene lactones suppress lung adenocarcinoma by blocking TMEM16A-mediated Ca2+-activated Cl- channels

  • Ruilian Xiu;Jie Jia;Qing Zhang;Fengjiao Liu;Yaxin Jia;Yuanyuan Zhang;Beibei Song;Xiaodan Liu;Jingwei Chen;Dongyang Huang;Fan Zhang;Juanjuan Ma;Honglin Li;Xuan Zhang;Yunyun Geng
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.6
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    • pp.521-531
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    • 2023
  • Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (Emax) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

Effects of Stress-Induced Sterile Inflammation on the Development of Depression (스트레스로 유발된 무균 염증이 우울증 발생에 미치는 영향)

  • Mi Kyoung Seo;Jung Goo Lee;Dae-Hyun Seog;Se Young Pyo;Won Hee Lee;Sung Woo Park
    • Journal of Life Science
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    • v.33 no.12
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    • pp.1062-1073
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    • 2023
  • Although depression is a common psychiatric disorder that negatively affects individuals and societies, its exact pathogenesis is not well understood. Stress is a major risk factor for depression and is known to increase susceptibility by triggering inflammation. Indeed, many preclinical and clinical studies have suggested a strong link between depression and inflammation. Depression is associated with increased levels of pro-inflammatory cytokines, such as interleukin (IL-)1β, IL-6, IL-12, tumor necrosis factor-α, and interferon-γ, and decreased levels of the anti-inflammatory IL-4, IL-10, and transforming growth factor-β. Administering pro-inflammatory cytokines causes depression-like behaviors in rodents. Conversely, administering anti-inflammatory drugs appears to ameliorate depressive symptoms. Although the importance of inflammation as a mediator of depression has been demonstrated, the mechanisms by which inflammation is activated in depression remain unclear. To address this issue, recent studies have focused on the importance of stress-induced sterile inflammation. Sterile inflammation refers to the activation of inflammatory processes due to physical and/or psychological stress in the absence of pathogens. Stress promotes the release of endogenous factors known as damage-associated molecular patterns (DAMPs), thereby triggering sterile inflammation. In turn, DAMPs are recognized by pattern recognition receptors, leading to the production of pro-inflammatory cytokines. Here, we review the role of DAMPs in depression based on preclinical and clinical evidence on the dysregulation of sterile inflammation.

Bta-miR-365-3p-targeted FK506-binding protein 5 participates in the AMPK/mTOR signaling pathway in the regulation of preadipocyte differentiation in cattle

  • Mengdi Chen;Congcong Zhang;Zewen Wu;Siwei Guo;Wenfa Lv;Jixuan Song;Beibei Hao;Jinhui Bai;Xinxin Zhang;Hongyan Xu;Guangjun Xia
    • Animal Bioscience
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    • v.37 no.7
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    • pp.1156-1167
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    • 2024
  • Objective: MicroRNAs (miRNAs) are endogenous non-coding RNAs that can play a role in the post-transcriptional regulation of mammalian preadipocyte differentiation. However, the precise functional mechanism of its regulation of fat metabolism is not fully understood. Methods: We identified bta-miR-365-3p, which specifically targets the 3' untranslated region (3'UTR) of the FK506-binding protein 5 (FKBP5), and verified its mechanisms for regulating expression and involvement in adipogenesis. Results: In this study, we found that the overexpression of bta-miR-365-3p significantly decreased the lipid accumulation and triglyceride content in the adipocytes. Compared to inhibiting bta-miR-36 5-3p group, overexpression of bta-miR-365-3p can inhibit the expression of adipocyte differentiation-related genes C/EBPα and PPARγ. The dual-luciferase reporter system further validated the targeting relationship between bta-miR-365-3p and FKBP5. FKBP5 mRNA and protein expression were detected by quantitative real-time polymerase chain reaction and Western blot. Overexpression of bta-miR-365-3p significantly down-regulated FKBP5 expression, while inhibition of bta-miR-365-3p showed the opposite, indicating that bta-miR-365-3p negatively regulates FKBP5. Adenosine 5'-monophosphate (AMP)-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway is closely related to the regulation of cell growth and is involved in the development of bovine adipocytes. In this study, overexpression of bta-miR-365-3p significantly inhibited mRNA and protein expression of AMPK, mTOR, and SREBP1 genes, while the inhibition of bta-miR-365-3p expression was contrary to these results. Overexpression of FKBP5 significantly upregulated AMPK, mTOR, and SREBP1 gene expression, while inhibition of FKBP5 expression was contrary to the above experimental results. Conclusion: In conclusion, these results indicate that bta-miR-365-3p may be involved in the AMPK/mTOR signaling pathway in regulating Yanbian yellow cattle preadipocytes differentiation by targeting the FKBP5 gene.

Transcriptome sequencing reveals non-coding RNAs respond to porcine reproductive and respiratory syndrome virus and Haemophilus parasuis co-infection in Kele piglets

  • Jing Zhang;Chunping Zhao;Min Yao;Jing Qi;Ya Tan;Kaizhi Shi;Jing Wang;Sixuan Zhou;Zhixin Li
    • Journal of Animal Science and Technology
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    • v.66 no.4
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    • pp.663-681
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    • 2024
  • Co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (HPS) has severely restricted the healthy development of pig breeding. Exploring disease resistance of non-coding RNAs in pigs co-infected with PRRSV and HPS is therefore critical to complement and elucidate the molecular mechanisms of disease resistance in Kele piglets and to innovate the use of local pig germplasm resources in China. RNA-seq of lungs from Kele piglets with single-infection of PRRSV or HPS and co-infection of both pathogens was performed. Two hundred and twenty-five differentially expressed long non-coding RNAs (DElncRNAs) and 30 DEmicroRNAs (DEmiRNAs) were identified and characterized in the PRRSV and HPS co-infection (PRRSV-HPS) group. Compared with the single-infection groups, 146 unique DElncRNAs, 17 unique DEmiRNAs, and 206 target differentially expressed genes (DEGs) were identified in the PRRSV-HPS group. The expression patterns of 20 DEmiRNAs and DElncRNAs confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) were consistent with those determined by high-throughput sequencing. In the PRRSV-HPS group, the target DEGs were enriched in eight immune Gene Ontology terms relating to two unique DEmiRNAs and 16 DElncRNAs, and the unique target DEGs participated the host immune response to pathogens infection by affecting 15 immune-related Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Notably, competitive endogenous RNA (ceRNA) networks of different groups were constructed, and the ssc-miR-671-5p miRNA was validated as a potential regulatory factor to regulate DTX4 and AEBP1 genes to achieve innate antiviral effects and inhibit pulmonary fibrosis by dual-luciferase reporter assays. These results provided insight into further study on the molecular mechanisms of resistance to PRRSV and HPS co-infection in Kele piglets.

A Theory on the Scope of Financial Activity (금융(金融)의 전업(專業) 및 겸업화(兼業化) 이론(理論): 금융산업조직론(金融産業組織論)의 모색(摸索))

  • Jwa, Sung-hee
    • KDI Journal of Economic Policy
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    • v.13 no.1
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    • pp.167-197
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    • 1991
  • This paper is intended as an introductory essay to explain endogenous changes in the scope of firm activities in the competitive structure of a deregulated, multi-product financial industry. Recently, the global financial industry has been experiencing a widespread reshuffling in its activities, reflecting both consolidation and specialization. The spread of the universal banking system, which involves the integration of various kinds of financial activities, has resulted in the so-called financial supermarket. At the same time, the traditional set of banking activities has been unbundled into so-called financial boutiques. A relevant question is where the current reshuffling process of integration and disintegration in financial activities might lead the financial industry. However, presently popular theories of the financial industry are not really appropriate for the analysis of this issue. This paper attempts to integrate the theory of specialization [George J. Stigler, "The Division of Labor is Limited by the Extent of the Market," Journal of Political Economy, Vol. LIX, No.3, June 1951] and the theory of the multi-product firm [William J. Baumol, John C. Panzar, and Robert D. Willig, Contestable Markets and the Theory of Industry Structure, Harcourt Brace Jovanovich, Inc., New York, 1982] and to apply the resulting hybrid theory, a theory on the scope of financial activity, to the financial industry. The implications of this theory for the issues raised above are formalized under five hypotheses on the reshuffling of financial activities as listed below: Hypothesis I: The differences in the organization of financial industries among countries are determined by differences in the size of the financial markets, other things being equal. Hypothesis II: A financial firm will separate those financial activities simultaneously having relatively strong economies of scale and relatively weak economies of scope (alternatively, diseconomies of scope) from other activities. Conversely, the firm will integrate those activities simultaneously having relatively weak economies of scale (alternatively, diseconomies of scale) and relatively strong economies of scope with incumbent activities. Hypothesis III: A competitive equilibrium in the deregulated financial industry will consist of both specialized and multi-product financial firms, resulting in a mixed form of specialized and universal banking systems. Hypothesis IV: As world financial markets fully integrate and all countries consequently face this single, common world market, the financial structures of individual countries will become increasingly similar. Hypothesis V: A more universal banking system will dominate the deregulated financial industry in countries with relatively small financial markets, while a more specialized banking system will dominate in countries with relatively large financial markets. However, equilibrium will ultimately be mixed, with specialized and universal banks coexisting, as stated in Hypothesis III. Based on these hypotheses, this paper interprets the historical development of specialized vs. universal banking systems in major industrial countries as a process driven by the evolution of the financial market in each country - i.e. the change in the size of the financial market over time. In addition, this paper anticipates that the final equilibrium of the world financial industry, which is currently under the pressure of financial innovations and deregulation, will be a mixed equilibrium with both specialized boutiques and universal supermarket-type financial firms, instead of an exclusively specialized or universal banking system. Future research should seek continued theoretical elaboration and empirical verification of this paper's hypotheses.

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Immunohistochemical Identification of the Two Forms of Gonadotropin Releasing Hormones (sGnRH, cGnRH-II) in Spotted Sea Bass (Lateolabrax sp.) Brain (면역조직화학법을 이용한 점농어 (Lateolabrax sp.) 뇌에서 두 종류 (sGnRH, cGnRH-II) 의 생식소자극호르몬 분비호르몬의 동정)

  • KIM Jung-Woo;LEE Won-Kyo;YANG Seok-Woo;JEONG Kwan-Sik;CHO Yong-Chul;RHO Yong-Gil;BANG In-Chul;KIM Kwang-Soo;KIM Sang-Koo;YOO Myung-Sik;KWON Hyuk-Bang
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.32 no.3
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    • pp.266-270
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    • 1999
  • Two forms of gonadotropin releasing hormone (GnRH) are identified in the brain of adult mature spotted sea bass (Lateolabrax sp.) by immunohistochemical methods. Salmon GnRH immunoreactive (sGnRH-ir) cell bodies were distributed in the olfactory bulb, ventral telencephalon and preoptic region. Immunoreactive fibers were observed in the vicinity of the brain including the olfactory bulbs, the telencephalon, the optic nerve, the optic tectum, the cerebellum, the medulla oblongata and rostral spinal cord. In most cases, these fibers did not form well defined bundles. However, there was a clear continuum of immunoreactive fibers, extending from the olfactory bulbs to the pituitary. cGnRH-II-ir cell bodies were only found in olfactory bulbs. However, the distribution of cGnRH-II-ir fibers was basically similar to that of sGnRH-ir fibers except for the absence of their continuity between the olfactory bulbs and the pituitary. These data suggest that sGnRH and cGnRH-II are endogenous peptides and indicate the presence of multiple neuroendocrine functions in the brain of the spotted sea bass. It seems that sGnRH not only regulates GTH secretion but also functions as a neurotransmitter, whereas cGnRH-II functions only as a neurotransmitter.

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