• 대한의생명과학회지
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• 제26권3호
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• pp.230-237
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• 2020

Staphylococcus aureus (S. aureus) is known as a bacterium that can cause skin infections, respiratory system infections, and sinusitis; however, it can exist as a normal flora rather than a pathogen. Recently, methicillin-resistant S. aureus (MRSA) infections have emerged in the community as a new variant of community-associated (CA)-MRSA. In the present study, S. aureus and MRSA were isolated and cultured by collecting samples from facilities and environments where students and educational personnel have multiple contacts on university campuses; specifically, the nostrils and hands of college students were tested from July to September of 2019. The molecular properties of the isolated MRSA were analyzed, and the one MRSA strain was isolated from the university campuses. One MRSA that was isolated and cultured on campus was the mec complex group A and staphylococcal cassette chromosome (SCC) mec type II, which is a characteristic of healthcare-associated (HA)-MRSA, and SCCmec type V, which is a characteristic of CA-MRSA. This result was similar to other studies wherein the SCCmec type II was detected in SCCmec typing analysis in CA-MRSA. To confirm whether there is a new variant of CA-MRSA in the Republic of Korea, additional follow-up studies on the analysis of virulence factors of MRSA are needed by additionally separating CA-MRSA from the body parts of university students and educational personnel.

• Molecular & Cellular Toxicology
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• 제2권1호
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• pp.29-34
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• 2006

Immunoglobulin E (IgE) plays an important role in the development of allergic disorders including asthma. Cigarette smoking was reported to elevate serum IgE level and air pollutants such as $NO_{2}$ have been reported to modulate the immune system including inflammation. Moreover, genetic polymorphisms of glutathione S-transferases (GSTs) were reported to affect inflammatory diseases including asthma. Therefore, in the present study we tried to investigate whether tobacco smoke or $NO_{2}$ exposure increases the level of IgE and the GST gene polymorphisms are associated with change of IgE level due to tobacco smoke or $NO_{2}$ exposure. We measured urinary cotinine, personal $NO_{2}$ exposure, and serum IgE levels in 300 healthy university students without allergic disorders. Allelic loss of the GSTM1 and GSTT1 and the GSTP1 (lle105Val) polymorphism were determined by PCR and RFLP. Total serum IgE levels were significantly different according to urinary cotinine levels (P=0.046), while $NO_{2}$ passive dosimeter level and genetic polymorphisms of three GSTs were not associated with total IgE level. Moreover, subjects with cotinine $500\;{\mu}g/g$ creatinine or more showed the highest level of total IgE when they had null type of GSTM1, null type of GSTT1, or variant type of GSTP1 (P<0.05). When we considered IgE level according to urinary cotinine levels in strata with the combinations of GSTM1, GSTT1, and GSTP1 genetic polymorphisms, the subjects with GSTM1 null, GSTT1 null, and GSTP1 variant types showed the largest difference between IgE levels of subpopulations according to cotinine levels (P=0.030). However, there was no significant difference between IgE levels of subpopulations according to $NO_{2}$ passive dosimeter levels in any group with combinations of GSTM1, GSTT1, and GSTP1 polymorphisms. This result suggests that smoking increases allergic response measured as IgE level and combinations of the GSTM1, GSTT1, and GSTP1 polymorph isms modify the effect of smoking on serum IgE level.

• 미생물학회지
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• 제54권4호
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• pp.420-427
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• 2018

효모균 타이로실-tRNA 합성효소(Sc YRS)와 엠버 멈춤코돈을 인식하는 대장균 시작tRNA 변이체(fMam $tRNA_{CUA}$)쌍은 대장균에서 단백질 생합성시 원하는 특정 위치에 비천연아미노산을 도입하는데 활용된다. Sc YRS/fMam $tRNA_{CUA}$쌍의 엠버써프레션 활성을 높이기 위해 fMam $tRNA_{CUA}$의 첫번째 안티코돈 염기를 인식하는 Sc YRS의 320번, 321번 아미노산 잔기를 암호화하는 염기서열을 무작위로 돌연변이시킨 라이브러리를 제작하였다. 엠버써프레션에 의한 클로람페니콜 저항성을 이용해 라이브러리를 탐색하여 활성이 향상된 2개의 돌연변이주를 선별하였다. 이들의 클로람페니콜 저항성 성장의 $IC_{50}$값은 야생형 YRS보다 1.7~2.3배 높았으며, in vivo 엠버써프레션 활성을 비교한 결과 3~6.5배의 활성 증가가 나타났다. 높은 활성을 보인 mYRS-3 (P320A/D321A) 단백질의 fMam $tRNA_{CUA}$에 대한 in vitro aminoacylation kinetics 분석은 야생형보다 약 7배 높은 효소활성을 보였으며, 이는 주로 기질인 fMam $tRNA_{CUA}$에 대한 결합 친화도가 증가하여 나타났다. 이런 접근법을 이용하여 다양한 종류의 비천연 아미노산 도입에 활용되는 aminoacyl-tRNA 합성효소의 엠버써프레션 활성을 높임으로써 엠버 멈춤코돈을 이용한 비천연 아미노산 도입 효율성을 높일 수 있을 것이다.

• Journal of Microbiology
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• 제37권3호
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• pp.168-174
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• 1999

Escherichia coli O157 is an important pathogenic organism which causes diarrhea, haemorrhagic colitis, and haemolytic ureamic syndrome (HUS) in human. E. coli O157 KNIH317 was isolated form patients suffering with HUS in Korea. We designed a primer set for cloning shiga-like toxin (slt) gene. The amplified PCR product was used to Southern and colony hybridization as a probe. As a result, we cloned 4.5-kb KpnI fragment containing the slt gene encoding shiga-like toxin from chromosomal DNA of E. coli O157 KNIH317. This recombinant plasmid was named pOVT45. E. coli XL1-Blue harboring pOVT45 showed cytotoxicity in Vero cells. We sequenced the slt gene of this strain. The A-subunit gene of the slt was composed of 960 base pairs with ATG initiation codon and TAA terminationcodon. The B-subunit was composed of 270 base paris with ATG initiation codon and TGA termination codon. Nucleotide sequence comparison of the slt gene exhibited 100%, 98.4%, 93.7%, and 93.7% identity with that of shiga-like toxin type II (sltII) of E. coli bacteriophage 933W, variant slt of E. coli, slt of E. coli, and variant sltII of E. coli, respectively. From these results, it was concluded that the cloned slt gene belongs to SltII family and that the strain used in this study may be a lysogeny of E. coli bcteriphage 933W.

• BMB Reports
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• 제39권1호
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• pp.55-60
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• 2006

We describe a phage display strategy, based on the differential resistance of proteins to denaturant-induced unfolding, that can be used to select protein variants with improved conformational stability. To test the efficiency of this strategy, wild-type and two stable variants of ${\alpha}_1$-antitrypsin (${\alpha}_1AT$) were fused to the gene III protein of M13 phage. These phages were incubated in unfolding solution containing denaturant (urea or guanidinium chloride), and then subjected to an unfavorable refolding procedure (dialysis at $37^{\circ}C$). Once the ${\alpha}_1AT$ moiety of the fusion protein had unfolded in the unfolding solution, in which the denaturant concentration was higher than the unfolding transition midpoint ($C_m$) of the ${\alpha}_1AT$ variant, around 20% of the phage retained binding affinity to anti-${\alpha}_1AT$ antibody due to a low refolding efficiency. Moreover, this affinity reduced to less than 5% when 10 mg/mL skimmed milk (a misfolding-promoting additive) was included during the unfolding/refolding procedure. In contrast, most binding affinity (>95%) remained if the ${\alpha}_1AT$ variant was stable enough to resist unfolding. Because this selection procedure does not affect the infectivity of M13, the method is expected to be generally applicable to the high-throughput screening of stable protein variants, when activity-based screening is not possible.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2307-2309
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• 2016

Background: Acute lymphoblastic leukemia (ALL) is a malignant disease in which early lymphoid precursors proliferate and replace the normal hematopoiesis. It has distinctive clinical and biological features. In respect to adult ALL, available data from Pakistan are limited. Therefore we reviewed the demographical and clinicohematological profiles along with FAB stratification of adult patients with ALL presented at our hospital. Materials and Methods: In this cross sectional study, 51 adults (${\geq}15years$) patients with ALL were enrolled from January 2010 to December 2014. Results: The mean age was $23.8{\pm}12.9years$ with the median age of 18.0 years. The male to female ratio was 2:1. The major complaints were fever (60.7%), generalized weakness (47.0%), overt bleeding (19.6%) and weight loss (13.7%). Physical examination revealed lymphodenopathy as a predominant finding detected in 43.1% followed by splenomegaly and hepatomegaly in 23.5% and 21.5%, respectively. The mean hemoglobin level was $9.0{\pm}2.75g/dl$ with a mean MCV of $82.2{\pm}15.4fl$, a mean total leukocyte count of $31.1{\pm}64.0{\times}10^9/l$, a mean ANC of $2.1{\pm}3.0{\times}10^9/l$ and a mean platelet count of $71.7{\pm}85.7{\times}10^9/l$. According to FAB classification, 47.1% were L1 type, 45.1% L2 and 7.8% L3 variant. Conclusions: Clinico-pathological features appeared comparable to published data. Febrile illness associated with lymphodenopathy was the commonest presentation. FAB classification revealed a predominance of ALL-L1 variant in Pakistani adult patients with ALL.

• Journal of Genetic Medicine
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• 제8권2호
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• pp.125-129
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• 2011

저자들은 고도근시, 망막이상, 납작한콧등, 구개열, 하악후퇴, 소하악증, 저신장, 양쪽 손가락의 관절구축증(arthrogryposis)이 있고, 방사선 검사상 불규칙한 대퇴골과 경골의 골단면, 척추골단이형성증이 보이는 Stickler 증후군 환자 1례에서 COL2A1 유전자의 새로운 돌연변이를 국내 최초로 증명하였기에 문헌고찰과 함께 보고하는 바이다.

• Journal of Preventive Medicine and Public Health
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• 제56권3호
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• pp.221-230
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• 2023

Objectives: The second wave of coronavirus disease 2019 (COVID-19) cases in Indonesia, during which the Delta variant predominated, took place after a vaccination program had been initiated in the country. This study was conducted to assess the impact of COVID-19 vaccination on unfavorable clinical outcomes including hospitalization, severe COVID-19, intensive care unit (ICU) admission, and death using a real-world model. Methods: This single-center retrospective cohort study involved patients with COVID-19 aged ≥18 years who presented to the COVID-19 emergency room at a secondary referral teaching hospital between June 1, 2021 and August 31, 2021. We used a binary logistic regression model to assess the effect of COVID-19 vaccination on unfavorable clinical outcomes, with age, sex, and comorbidities as confounding variables. Results: A total of 716 patients were included, 32.1% of whom were vaccinated. The elderly participants (≥65 years) had the lowest vaccine coverage among age groups. Vaccination had an effectiveness of 50% (95% confidence interval [CI], 25 to 66) for preventing hospitalization, 97% (95% CI, 77 to 99) for preventing severe COVID-19, 95% (95% CI, 56 to 99) for preventing ICU admission, and 90% (95% CI, 22 to 99) for preventing death. Interestingly, patients with type 2 diabetes had a 2-fold to 4-fold elevated risk of unfavorable outcomes. Conclusions: Among adults, COVID-19 vaccination has a moderate preventive impact on hospitalization but a high preventive impact on severe COVID-19, ICU admission, and death. The authors suggest that relevant parties increase COVID-19 vaccination coverage, especially in the elderly population.

• Genomics & Informatics
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• 제21권4호
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• pp.48.1-48.8
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• 2023

Liver cancer is the fourth leading cause of death worldwide. Well-known risk factors include hepatitis B virus and hepatitis C virus, along with exposure to aflatoxins, excessive alcohol consumption, obesity, and type 2 diabetes. Genomic variants play a crucial role in mediating the associations between these risk factors and liver cancer. However, the specific variants involved in this process remain under-explored. This study utilized a bioinformatics approach to identify genetic variants associated with liver cancer from various continents. Single-nucleotide polymorphisms associated with liver cancer were retrieved from the genome-wide association studies catalog. Prioritization was then performed using functional annotation with HaploReg v4.1 and the Ensembl database. The prevalence and allele frequencies of each variant were evaluated using Pearson correlation coefficients. Two variants, rs2294915 and rs2896019, encoded by the PNPLA3 gene, were found to be highly expressed in the liver tissue, as well as in the skin, cell-cultured fibroblasts, and adipose-subcutaneous tissue, all of which contribute to the risk of liver cancer. We further found that these two SNPs (rs2294915 and rs2896019) were positively correlated with the prevalence rate. Positive associations with the prevalence rate were more frequent in East Asian and African populations. We highlight the utility of this population-specific PNPLA3 genetic variant for genetic association studies and for the early prognosis and treatment of liver cancer. This study highlights the potential of integrating genomic databases with bioinformatic analysis to identify genetic variations involved in the pathogenesis of liver cancer. The genetic variants investigated in this study are likely to predispose to liver cancer and could affect its progression and aggressiveness. We recommend future research prioritizing the validation of these variations in clinical settings.

• The Korean Journal of Physiology and Pharmacology
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• 제28권2호
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• pp.113-120
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• 2024

Solute carrier 40A1 (SLC40A1) encodes ferroportin, which is the only known transmembrane protein that exports elemental iron from mammalian cells and is essential for iron homeostasis. Mutations in SLC40A1 are associated with iron-overload disorders. In addition to ferroportin diseases, SLC40A1 expression is downregulated in various cancer types. Despite the clinical significance of the SLC40A1 transporter, only a few studies have investigated genetic variants in SLC40A1. The present study was performed to identify genetic variations in the SLC40A1 promoter and functionally characterize each variant using in vitro assays. We investigated four haplotypes and five variants in the SLC40A1 promoter. We observed that haplotype 3 (H3) had significantly lower promoter activity than H1, whereas the activity of H4 was significantly higher than that of H1. Luciferase activity of H2 was comparable to that of H1. In addition, four variants of SLC40A1, c.-1355G>C, c.-662C>T, c.-98G>C, and c.-8C>G, showed significantly increased luciferase activity compared to the wild type (WT), whereas c.-750G>A showed significantly decreased luciferase activity compared to the WT. Three transcription factors, cAMP response element-binding protein-1 (CREB-1), chicken ovalbumin upstream promoter transcription factor 1, and hepatic leukemia factor (HLF), were predicted to bind to the promoter regions of SLC40A1 near c.-662C>T, c.-98G>C, and c.-8C>G, respectively. Among these, CREB1 and HLF bound more strongly to the variant sequences than to the WT and functioned as activators of SLC40A1 transcription. Collectively, our findings indicate that the two SLC40A1 promoter haplotypes affect SLC40A1 transcription, which is regulated by CREB-1 and HLF.