• Title/Summary/Keyword: Aberrant

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Aberrant Expression of Cx Isoforms in the Adult Caput Epididymis exposed to Estradiol Benzoate or Flutamide at the Weaning

  • Lee, Ki-Ho
    • Development and Reproduction
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    • v.21 no.4
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    • pp.379-389
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    • 2017
  • Connexin (Cx) involves in the regulation of various physiological functions of tissue by forming a channel, a gap junction which allows direct cell-cell communication, between adjacent cells. The effect of a single subcutaneous treatment of estradiol benzoate (EB) or flutamide (Flu) at the weaning age on the expression of Cx isoforms in the adult caput epididymis was evaluated in this research. Using quantitative real-time PCR analysis, a low-dose of EB [$0.015{\mu}g/kg$ body weight (BW)] caused significant decreases of Cx30.3, Cx32, Cx40, Cx43, and Cx45 mRNA levels and no change of Cx26, Cx31, Cx31.1, Cx37 transcript levels. The treatment of a high-dose EB ($1.5{\mu}g/kg\;BW$) resulted in reduced expression of Cx30.3, Cx31, Cx43, and Cx45 but increased expression of Cx37 and Cx40. Expression of all Cx isoforms examined, except Cx31, was significantly increased by the treatment of a low-dose Flu ($500{\mu}g/kg\;BW$). However, the treatment of a high-dose Flu (5 mg/kg BW) led significant expressional suppression of Cx30.3, Cx31, Cx31.1, Cx32, Cx40, Cx43, and Cx45 but an increase of Cx37 transcript level. With the comparison of previous findings, the expression of Cx isoforms in the adult epididymis after the exposure to EB or Flu is likely differentially regulated in regional-specific and/or exposed postnatal age-specific manner.

Transcriptional Analysis of 10 Selected Genes in a Model of Penicillin G Induced Persistence of Chlamydophila psittaci in HeLa Cells

  • Hu, Yanqun;Chen, Lili;Wang, Chuan;Xie, Yafeng;Chen, Zhixi;Liu, Liangzhuan;Su, Zehong;Wu, Yimou
    • Journal of Microbiology and Biotechnology
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    • v.25 no.8
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    • pp.1246-1256
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    • 2015
  • Chlamydophila psittaci is an important intracellular pathogen. Persistent infection is an important state of the host-parasite interaction in this chlamydial infection, which plays a significant role in spreading the organism within animal populations and in causing chronic chlamydiosis and serious sequelae. In this study, a C. psittaci persistent infection cell model was induced by penicillin G, and real-time quantitative PCR was used to study the transcriptional levels of 10 C. psittaci genes (dnaA, dnaK, ftsW, ftsY, grpE, rpsD, incC, omcB, CPSIT_0846, and CPSIT_0042) in acute and penicillin-G-induced persistent infection cultures. Compared with the acute cultures, the penicillin-G-treated cultures showed a reduced chlamydial inclusion size and a significantly decreased number of elementary body particles. Additionally, some enlarged aberrant reticulate body particles were present in the penicillin-G-treated cultures but not the acute ones. The expression levels of genes encoding products for cell division (FtsW, FtsY) and outer membrane protein E encoding gene (CPSIT_0042) were downregulated (p < 0.05) from 6 h post-infection onward in the persistent infection cultures. Also from 6 h post-infection, the expression levels of DnaA, DnaK, IncC, RpsD, GrpE, and CPSIT_0846 were upregulated (p < 0.05); however, the expression level of OmcB in the persistent infection was< almost the same as that in the acute infection (p > 0.05). These results provide new insight regarding molecular activities that accompany persistence of C. psittaci, which may play important roles in the pathogenesis of C. psittaci infection.

Orobol, A Derivative of Genistein, Inhibits Heat-Killed Propionibacterium acnes-Induced Inflammation in HaCaT Keratinocytes

  • Oh, Yunsil;Hwang, Hwan Ju;Yang, Hee;Kim, Jong Hun;Yoon Park, Jung Han;Kim, Jong-Eun;Lee, Ki Won
    • Journal of Microbiology and Biotechnology
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    • v.30 no.9
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    • pp.1379-1386
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    • 2020
  • Acne is a chronic skin disease that typically occurs in the teens and twenties, and its symptoms vary according to age, sex, diet, and lifestyle. The condition is characterized by hyperproliferation of keratinocytes in the epidermis, sebum overproduction, excessive growth of Propionibacterium acnes, and P. acnes-induced skin inflammation. Interleukin (IL)-1α and IL-6 are predominant in the inflammatory lesions of acne vulgaris. These cytokines induce an inflammatory reaction in the skin in the presence of pathogens or stresses. Moreover, IL-1α accelerates the production of keratin 16, which is typically expressed in wounded or aberrant skin, leading to abnormalities in architecture and hyperkeratinization. Orobol (3',4',5,7-tetrahydroxyisoflavone) is a metabolite of genistein that inhibited the P. acnes-induced increases in IL-6 and IL-1α levels in human keratinocytes (HaCaTs) more effectively compared with salicylic acid. In addition, orobol decreased the IL-1α and IL-6 mRNA levels and inhibited the phosphorylation of inhibitor of kappa-B kinase, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, and mitogen-activated protein kinase induced by P. acnes. Finally, the expression of Ki67 was decreased by orobol. Thus, orobol ameliorated the inflammation and hyperkeratinization induced by heat-killed P. acnes and thus has potential for use in functional foods and cosmetics.

Treatment of Systemic Arterial Supply to Lower Lobe of Left Lung (Operation vs. Embolotherapy): Comparison of Two Cases and Literature Review (좌측 하폐엽에 공급하는 비정상적인 체동맥의 치료 (수술과 색전술의 비교))

  • Jeon Eui-Yong;Rhee Gwang-Woo;Goo Dong-Erk;Kim Eung-Soo
    • Journal of Chest Surgery
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    • v.39 no.3 s.260
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    • pp.230-235
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    • 2006
  • Systemic arterialization of lung with/without sequestration (Sequestration/Anomalous Origin of Left Pulmonary Artery, AOLPA) is a rare form of congenital anomalous systemic arterial supply to the lungs. In this anomaly, the arterial supply of one or more arteries of the basal segments of the lower lobe derives from an aberrant vessel arising from the aorta. We report two adult cases of systemic arterialization of normal basal segments of left lower lobe lung with/without sequestration. The one (AOLPA) was treated by left lower basal segmentectomy and the other (Sequestration) by therapeutic angiographic embolization. Based on the favorable follow-up result in our patients, although lobectomy (segmentectomy) is the basic treatment modality, embolotherapy could also be a mode of treatment that could be selectively applied to elderly, infirm patients or high risk patients with poor pulmonary function.

A Case of Canine Ectopic Parasitism of Heartworm in the Systemic Circulation (개에서 발생한 전신 순환계의 심장사상충 이소기생 증례)

  • Jang, Hyo-Mi;Lee, Hee-Chun;Jung, Dong-In
    • Journal of Veterinary Clinics
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    • v.32 no.4
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    • pp.347-351
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    • 2015
  • A 3-year-old intact female Dachshund was referred due to paraplegia and cool extremities. History taking, physical examination, neurological examination, and blood profiling studies were evaluated to determine the diagnosis. Based on abdominal ultrasound and echocardiograph, features suggestive of adult heartworm were detected in aberrant places. The result of enzyme-linked immunosorbent assay (ELISA) testing with a commercial heartworm antigen kit was positive. The dog fell into a comatose state, and the client requested the dog be euthanized. On post-mortem examination, the patient was diagnosed with ectopic parasitism of heartworm in the left side of heart, aorta, aorta abdominalis, and iliac arteries, a circumstance that induced systemic thromboembolism. This case report describes the clinical, diagnostic imaging, and necropsy findings of canine ectopic parasitism of heartworm.

Immunological Activity and Immunotoxicity of Pine Tree Pollen in Mice (마우스를 이용한 송화분 섭취의 면역원성 및 안전성 탐색)

  • Kim, Young-Ok;Kim, Kwang-Ho;Park, Hyun-Ji;Park, Yeong-Chul;Park, Sung-Wook;Heo, Yong
    • Toxicological Research
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    • v.21 no.3
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    • pp.235-240
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    • 2005
  • Pollen has been used for prevention or treatment of certain diseases such as diabetes arthritis or cancer in traditional medicine. Among various pollens, pine tree pollen is known to relieve hypertension, suppress fatty liver progression, and facilitate the digestion, but its immunological activities are less known. To evaluate immunological reactivities and immunotoxicities of pine tree pollen, BALB/c mice were administered to the poller through oral route. Pine tree pollen suspended in distilled water or extracted with methanol has been administered at the concentration of 0, 10, or 100 mg/kg five days per week for four weeks. Polyclonal activation of splenic T cells with phytohemagglutinins did not induce a significant difference in IL-4 and $IFN_{\gamma}$ production between the pollen-administered mice groups and the control mice. Furthermore, polyclonal activation of splenic B cells with lipopolysaccharides did not result a significant difference in IgG1 and IgG2a production among the groups. These findings imply that the intake of pine tree pollen does not bring any humoral and cellular immune-dysrequlation. Whereas, viability of Listeria monocytogenes was suppressed in the mice administered with 100 mg/kg bw methanol extract, indicating the potential ability of pine tree pollen to enhance cell-mediated immunity mediated by type-1 helper T cells. In addition, aberrant upregulation of plasma IgG1 level was observed in the pollen-administered mice, which suggests a possibility of allergic response induction through the pine tree pollen uptake. Overall, pine tree pollen-mediated modulation of humoral or cellular immunity is worthy of further systematic investigation.

Genotoxicity Study of HM10411, Recombinant Human Granulocyte Colony Stimulating Factor (재조합 인과립구 콜로니 자극인자 HM10411의 유전독성 연구)

  • 권정;이미가엘;홍미영;조지희;정문구;권세창;이관순
    • Biomolecules & Therapeutics
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    • v.10 no.4
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    • pp.268-273
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    • 2002
  • Mutagenic potential of HM10411 (recombinant human granulocyte colony stimulating factor) was evaluated by bacterial reverse mutation test, in vitro chromosome aberration test and in vivo micronucleus test. The bacterial reverse mutation test was performed using the histidine auxotroph strains of Salmonella typhimurium TA100, TA1535, TA98, TA1537 and tryptophan auxotroph strain of Escherichia coli WP2 uvrA. The negative results of the bacterial reverse mutation test suggest that HM10411 does not induce mutation, in the genome of Salmonella typhimurium and E. coli under the conditions used. In addition, it has little clastogenicity either in vitro chromosome aberration test or in vivo micronucleus test. For in vitro chromosomal aberration test, Chinese hamster lung(CHL) cells were exposed to HM10411 of 23, 46 or 92 $\mu\textrm{g}$/ml for 6 or 24 hours in the absence and for 6 hours in the presence of metabolic activation system. There was no significant increase in the number of aberrant metaphase in HM 10411-treated groups at any dose levels both in the presence and absence of metabolic activation system. The micronucleus test was carried out using specific pathogen free(SPF) 7-week old male ICR mice, The test item, HM10411 was intraperitoneally administered at 1150, 2300 or 4600 $\mu\textrm{g}$/kg once a day for 2 consecutive days. There was no significant increase in the frequencies of micronucleated polychromatic erythrocytes(PCEs) at any treated groups compared with negative control group. Therefore, these results demonstrate that the test item, HM10411, was not mutagenic under the condition of these studies.

Anti-Cancer Effect of IN-2001 in MDA-MB-231 Human Breast Cancer

  • Min, Kyung-Nan;Joung, Ki-Eun;Kim, Dae-Kee;Sheen, Yhun-Yhong
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.313-319
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    • 2012
  • In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity ($IC_{50}$ = 0.585 nM) inMDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231human breast cancer cells. Cell cycle analysis revealed that the growth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at $G_0/G_1$ and/or $G_2$/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors $p21^{WAF1}$ and $p27^{KIP1}$ cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

Enforced Expression of CXCR5 Drives T Follicular Regulatory-Like Features in Foxp3+ T Cells

  • Kim, Young Uk;Kim, Byung-Seok;Lim, Hoyong;Wetsel, Rick A.;Chung, Yeonseok
    • Biomolecules & Therapeutics
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    • v.25 no.2
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    • pp.130-139
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    • 2017
  • $CXCR5^+$ T follicular helper (Tfh) cells are associated with aberrant autoantibody production in patients with antibody-mediated autoimmune diseases including lupus. Follicular regulatory T (Tfr) cells expressing CXCR5 and Bcl6 have been recently identified as a specialized subset of $Foxp3^+$ regulatory T (Treg) cells that control germinal center reactions. In this study, we show that retroviral transduction of CXCR5 gene in $Foxp3^+$ Treg cells induced a stable expression of functional CXCR5 on their surface. The Cxcr5-transduced Treg cells maintained the expression of Treg cell signature genes and the suppressive activity. The expression of CXCR5 as well as Foxp3 in the transduced Treg cells appeared to be stable in vivo in an adoptive transfer experiment. Moreover, Cxcr5-transduced Treg cells preferentially migrated toward the CXCL13 gradient, leading to an effective suppression of antibody production from B cells stimulated with Tfh cells. Therefore, our results demonstrate that enforced expression of CXCR5 onto Treg cells efficiently induces Tfr cell-like properties, which might be a promising cellular therapeutic approach for the treatment of antibody-mediated autoimmune diseases.

β-Amyrin Ameliorates Alzheimer's Disease-Like Aberrant Synaptic Plasticity in the Mouse Hippocampus

  • Park, Hye Jin;Kwon, Huiyoung;Lee, Ji Hye;Cho, Eunbi;Lee, Young Choon;Moon, Minho;Jun, Mira;Kim, Dong Hyun;Jung, Ji Wook
    • Biomolecules & Therapeutics
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    • v.28 no.1
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    • pp.74-82
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    • 2020
  • Alzheimer's disease (AD) is a progressive and most frequently diagnosed neurodegenerative disorder. However, there is still no drug preventing the progress of this disorder. β-Amyrin, an ingredient of the surface wax of tomato fruit and dandelion coffee, is previously reported to ameliorate memory impairment induced by cholinergic dysfunction. Therefore, we tested whether β-amyrin can prevent AD-like pathology. β-Amyrin blocked amyloid β (Aβ)-induced long-term potentiation (LTP) impairment in the hippocampal slices. Moreover, β-amyrin improved Aβ-induced suppression of phosphatidylinositol-3-kinase (PI3K)/Akt signaling. LY294002, a PI3K inhibitor, blocked the effect of β-amyrin on Aβ-induced LTP impairment. In in vivo experiments, we observed that β-amyrin ameliorated object recognition memory deficit in Aβ-injected AD mice model. Moreover, neurogenesis impairments induced by Aβ was improved by β-amyrin treatment. Taken together, β-amyrin might be a good candidate of treatment or supplement for AD patients.