• Korean Journal of Poultry Science
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• 제47권1호
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• pp.9-19
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• 2020

Avian influenza (AI) viruses are highly contagious viruses that infect many bird species and are zoonotic. Ducks are resistant to the deadly and highly pathogenic avian influenza virus (HPAIV) and remain asymptomatic to the low pathogenic avian influenza virus (LPAIV). In this study, we identified common differentially expressed genes (DEGs) after a reanalysis of previous transcriptomic data for the HPAIV and LPAIV infected duck lung cells. Microarray datasets from a previous study were reanalyzed to identify common target genes from DEGs and their biological functions. A total of 731 and 439 DEGs were identified in HPAIV- and LPAIV-infected duck lung cells, respectively. Of these, 227 genes were common to cells infected with both viruses, in which 193 genes were upregulated and 34 genes were downregulated. Functional annotation of common DEGs revealed that translation related gene ontology (GO) terms were enriched, including ribosome, protein metabolism, and gene expression. REACTOME analyses also identified pathways for protein and RNA metabolism as well as for tissue repair, including collagen biosynthesis and modification, suggesting that AIVs may evade the host defense system by suppressing host translation machinery or may be suppressed before being exported to the cytosol for translation. AIV infection also increased collagen synthesis, showing that tissue lesions by virus infection may be mediated by this pathway. Further studies should focus on these genes to clarify their roles in AIV pathogenesis and their possible use in AIV therapeutics.

• Journal of Life Science
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• 제32권6호
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• pp.476-481
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• 2022

Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.

• Tuberculosis and Respiratory Diseases
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• 제45권2호
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• pp.369-379
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• 1998

Background: Platelet-activating factor(PAF) might play an important role in the development of acute respiratory distress syndrome. Since PAF induced lung injury is similar to changes of acute respiratory distress gyndrome, and abnormalities in surfactant function have been described in acute respiratory distress syndrome, the authors investigated the effects of PAF on the regulation of surfactant protein A, B and C mRNA accumulation Method: The effects of PAF on gene expression of surfactant protein A, B and C in 24 hours after intratracheal injection of PAF in rats. Surfactant protein A, B and C mRNAs were measured by filter hybridization. Results: The accumulation of SP-A mRNA in PAF treated group was significantly decreased by 37.1 % and 41.6%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.025, p<0.01). The accumulation of SP-B mRNA in PAF treated group was decreased by 18.7% and 32.2 %, respectively compared to the control group and the group treated with Lyso-PAF but statistically not significant. The accumulation of SP-C mRNA in PAF treated group was significantly decreased by 30.7% and 38.5%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.l, p<0.01). Conclusion: These findings represent a marked inhibitory effects of platelet-activating factor on surfactant proteins expression in vivo. This supports, in turn, 'platelet-activating factor might be related to pathogenesis of acute respiratory distress syndrome.

• Journal of Plant Biotechnology
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• 제47권2호
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• pp.157-163
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• 2020

Calmodulin (CaM) mediates cellular Ca²⁺ signals in the defense responses of plants. We previously reported that GmCaM-4 and 5 are involved in salicylic acid-independent activation of disease resistance responses in soybean (Glycine max). Here, we generated a GmCaM-4 cDNA construct under the control of the cauliflower mosaic virus (CaMV) 35S promoter and transformed this construct into potato (Solanum tuberosum L.). The constitutive over-expression of GmCaM-4 in potato induced high-level expression of pathogenesis-related (PR) genes, such as PR-2, PR-3, PR-5, phenylalanine ammonia-lyase (PAL), and proteinase inhibitorII (pinII). In addition, the transgenic potato plants exhibited enhanced resistance against a bacterial pathogen, Erwinia carotovora ssp. Carotovora (ECC), that causes soft rot disease and showed spontaneous lesion phenotypes on their leaves. These results strongly suggest that a CaM protein in soybean, GmCaM-4, plays an important role in the response of potato plants to pathogen defense signaling.

• Biomolecules & Therapeutics
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• 제22권6호
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• pp.532-539
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• 2014

Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (> $25{\mu}m$), whereas ddC mainly affected small diameter DRG neurons (${\leq}25{\mu}m$). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1321-1326
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• 2014

Background/Aim: Toll-like receptor 4 (TLR4) and B7-H1, both normally expressed restricted to immune cells, are found to be aberrantly expressed in a majority of human tumors and may play important roles in regulation of tumor immunity. It has been shown that urothelial bladder cancer (UBC) patients can manifest tumoral immune escape which may be a potential critical factor in tumor pathogenesis and progression. However, so far, the mechanisms of UBC-related immune escape have not been clarified. The aim of this study was to investigate the effect of TLR4 and B7-H1 on immune escape of UBC. Methods: Bladder cancer T24 cells were pre-incubated with LPS and co-cultured with tumor specific CTLs. CTL cytotoxicity and apoptosis rates were measured by MTT assay and flow cytometry, respectively. The effects of an ERK inhibitor on B7-H1 expression and CTL cytotoxicity against T24 cells were also evaluated. In addition, TLR4, B7-H1 and PD-1 protein expression was analyzed by immunohistochemistry in 60 UBC specimens and 10 normal urothelia. Results: TLR4 activation protected T24 cells from CTL killing via B7-H1 overexpression. However PD98059, an inhibitor of ERK, enhanced CTL killing of T24 cells by reducing B7-H1 expression. TLR4 expression was generally decreased in UBC specimens, while B7-H1 and PD-1 were greatly overexpressed. Moreover, expression of both B7-H1 and PD-1 was significantly associated with UICC stage and WHO grade classification. Conclusions: TLR4 and B7-H1 may contribute to immune escape of UBC. Targeting B7-H1 or the ERK pathway may offer new immunotherapy strategies for bladder cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• 제23권2호
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• pp.397-404
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• 2009

For standardization of LMK02 quality, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelica gigas Nakai in the constituents of LMK02 were estimated as indicative components. From LMK02 water extract, has been used in vitro test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease (AD). $A{\beta}$ oligomer derived from proteolytic processing of the ${\beta}$-amyloid precursor protein (APP), including the amyloid-${\beta}$ peptide ($A{\beta}$), play a critical role in the pathogenesis of Alzheimer's dementia. We determined that oligomer amyloid-${\beta}$ ($A{\beta}$) have a profound attenuation in the increase in rat hippocampus H19-7 cells from. Experimental evidence indicates that LMK02 protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a hippocampus cell line on $A{\beta}$ oligomer-induced neuronal cytotoxicity, we demonstrated that LMK02 inhibits formation of $A{\beta}$ oligomer, which are the behavior, and possibly causative, feature of AD. In the Red Ginseng, the average amounts of Ginsenoside Rg3 were $47.04{\mu}g/g$ and $42.3{\mu}g/g$, 90 % of its weight were set as a standard value. And, in the Angelica gigas Nakai, the average amounts of Decursin were 2.71 mg/g and 2.44mg/g, 90 % of its weight were also set as a standard value. The attenuated $A{\beta}$ oligomer in the presence of LMK02 was observed in the conditioned medium of this $A{\beta}$ oligomer-induced cells under in vitro. In the cells, LMK02 significantly activated antiapoptosis and decreased the production of ROS. These results suggest that neuronal damage in AD might be due to two factors: a direct $A{\beta}$ oligomer toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of $A{\beta}$ oligomer, underlie the neuroprotective effects of LMK02 treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2185-2193
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• 2016

Background: The pathogenesis of sporadic colorectal cancer (CRC) is influenced by the patient genetic background and environmental factors. Based on prior understanding, these are classified in two major pathways of genetic instability. Microsatellite instability (MSI) and CPG island methylator phenotype (CIMP) are categorized as features of the hypermethylated prototype, and chromosomal instability (CIN) is known to be indicative of the non-hypermethylated category. Secreted frizzled related protein 2 (SFRP2), APC1A in WNT signaling pathway and the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), are frequently hypermethylated in colorectal cancer. Detection of methylated DNA as a biomarker by easy and inexpensive methods might improve the quality of life of patients with CRC via early detection of cancer or a precancerous condition. Aim: To evaluate the rate of SFRP2 and MGMT hypermethylation in both polyp tissue and serum of patients in south Iran as compared with matched control normal population corresponding samples. Materials and Methods: Methylation-specific PCR was used to detect hypermethylation in DNA extracted from 48 polypoid tissue samples and 25 healthy individuals. Results: Of total polyp samples, 89.5% had at least one promoter gene hypermethylation. The most frequent methylated locus was SFRP2 followed by MGMT-B (81.2 and 66.6 percent respectively). Serologic detection of hypermethylation was 95% sensitive as compared with polyp tissue. No hypermethylation was detected in normal tissue and serum and its detection in patients with polyps, especially of serrated type, was specific. Conclusions: Serologic investigation for detection of MGMT-B, SFRP2 hypermethylation could facilitate prioritization of high risk patients for colonoscopic polyp detection and excision.

• The Korean Journal of Nuclear Medicine
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• 제26권2호
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• pp.318-326
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• 1992

Ga-67 citrate scan has been requested for detection or follow-up of inflammatory or neoplastic disease. Visualization of Ga-67 citrate in the kidneys at 48 and 72 hr post injection is usually interpreted as evidence of renal pathology. But precise mechanisms of abnormal Ga-67 uptake in kidneys were unknown. We undertook a study to determine the clinical value of Ga-67 citrate imaging of the kidneys in 68 patients with primary or secondary nephropathy confirmed by renal biopsy and 66 control patients without renal disease. Renal uptake in 48 to 72 hr images was graded as follows: Grade 0=back-ground activity:1=faint uptake greater than background;2=definite uptake, but less than lumbar vertebrae; 3=same uptake as lumbar vertebrae, but less than liver; 4=same or higher uptake than liver. The results were as follows. 1) 42 of 65 (62%) patients with noninfectious nephritis showed grade 2 or higher Ga-67 renal uptake but only 10 percent of control patients showed similar uptake. 2) In 14 patients with systemic lupus erythematosus, 8 of 9 (89%) patients with lupus nephritis exhibited marked renal uptake 3) 36 of 41 patients (88%) with combined nephrotic syndrome showed Grade 2 or higher renal uptake. 4) Renal Ga-67 uptake was correlated with clinical severity of nephrotic syndrome determined by serum albumin level, 24 hr urine protein excretion and serum lipid levels. 5) After complete remission of nephrotic syndrome, renal uptake in all 8 patients who were initially Grade 3 or 4, decreased to Grade 1 or 0. In conclusion, we think that the mechanism of renal Ga-67 uptake in nephrotic syndrome might be related to the pathogenesis of nephrotic syndrome. In systemic lupus erythematosus, Ga-67 citrate scan is useful in predicting renal involvement.

• Korean Journal of Clinical Laboratory Science
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• 제50권2호
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• pp.118-125
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• 2018

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), but the genes associated with the host immune system can be attributed to the development of TB. The ITGB2 gene encodes the integrin beta 2 chain CD18 protein and is present on chromosome 21. The integrin beta 2 chain is an integrin expressed in leukocytes and plays a very important role in leukocyte maturation and attachment. ITGB2 plays an important role in the phagocytosis of MTB and the aggregation of leukocytes in MTB infections. This study examined the genetic polymorphisms of the ITGB2 gene between the TB case and normal control using Korean genomic and epidemiologic data. As a result, a statistically significant correlation was confirmed in 10 SNPs. The most significant SNP was rs113421921 (OR=0.69, CI: 0.53~0.90, $P=5.8{\times}10^{-3}$). In addition, rs173098, one of the significant 10 SNPs, is possibly located in a binding motif with the transcription factor cofactor p300, and can affect ITGB2 gene expression. These findings suggest that the pathogenesis of TB may be influenced by a range of genetic factors related to the immune function of the host, e.g., the reactions associated with the recruitment and attachment of leukocytes. The results of this study could be used to predict the infection control for tuberculosis in a patient-tailored manner.