• Journal of Veterinary Science
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• v.21 no.1
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• pp.2.1-2.14
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• 2020

The emergence of livestock-associated (LA)-methicillin-resistant Staphylococcus aureus (MRSA) in livestock animal has become a significant zoonotic concern. In the present study, we investigated nationwide prevalence of LA-MRSA across pork production chain including pig farms, slaughterhouses, and retail markets. A total of 40 MRSA strains were isolated during the investigation and the overall prevalence of MRSA was 3.4% (n = 37), 0.6% (n = 2), and 0.4% (n = 1) in pig farms, slaughterhouses, and retail markets, respectively. Multilocus sequence typing analyses revealed that the 2 most significant clonal lineages in pork production chain in Korea were ST398 (n = 25) and ST541 (n = 6). All of the 40 MRSA isolates were further characterized to investigate key genotypic and phenotypic correlates associated with the emergence and spread of clonal complex 398 (CC398; ST398, and ST541) LA-MRSA. Although the prevalence of swine-associated MRSA was still relatively low and mostly restricted to pig farms, multidrug-resistant CC398 LA-MRSA isolates with new spa types (t18102 and t18103) were identified as a major clonal lineage. The CC398 LA-MRSA strains tended to exhibit increased levels of multiple drug resistance (MDR) phenotype compared with non-CC398 MRSA strains. Of note, in comparison with non-CC398 MRSA isolates, CC398 LA-MRSA isolates exhibited significantly enhanced tetracycline (TET) and zinc resistance. These findings suggested that co-selection pressure associated with MDR phenotype, especially TET resistance, and zinc resistance may have played a significant role in the emergence and persistence of CC398 LA-MRSA in pig farms in Korea.

• Korean Journal of Veterinary Service
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• v.45 no.3
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• pp.171-180
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• 2022

The aim of this study was to investigate the prevalence of antimicrobial resistance and virulence factors in staphylococci isolated from canine otitis externa. A total 295 causative microorganisms were isolated. The most common isolated species were Staphylococcus (S) pseudintermedius (94 isolates) followed by Pseudomonas aeruginosa (60 isolates), S. schleiferi (25 isolates), Escherichia coli (23 isolates) and Proteus mirabilis (20 isolates). Staphylococci isolates were showed high resistance to penicillin (78.6%), erythromycin (55.9%), tetracycline (52.4%), clindamycin (51.7%) and ciprofloxacin (42.8%). Of the 145 staphylococci isolates, 49 (33.8%) methicillin-resistant staphylococci (MRS) were observed, distributed among S. pseudintermedius (n=34), S. schleiferi (n=6), S. epidermis (n=4), S. hominis (n=2), S. aureus, S. caprae and S. saprophyticus (n=1, respectively). Forty-three (87.8%) of 49 MRS and 10 (10.4%) of 96 methicillin-susceptibility staphylococci harbored mecA gene. About 80% of MRS were multidrug-resistant with resistance to at least one antibiotic in three or more antibiotic classes. Resistance genes blaZ (93/114, 81.5%), ermB (35/81, 43.2%), ermC (3/81, 3.7%), aacA-aphD (50/54, 92.5%), tetM (69/76, 90.7%) and tetK (6/76, 7.8%) were detected among resistant isolates. Virulence factors genes lukF and lukS were found in 100%(145/145) and 43.4%(63/145), respectively. Genes encoding ermA, eta, etb and tsst were not detected. To the best of our knowledge, this is the first study which investigated for the presence of genes encoding antimicrobial resistance and staphylococcal toxins in staphylococci isolated from canine otitis externa. A continuous monitoring and surveillance program to prevent antimicrobial resistance in companion animals is demanded.

• Journal of Pharmacopuncture
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• v.26 no.3
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• pp.265-275
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• 2023

Objectives: The aim of this study was to evaluate the effect of fruit juices on Multi-Drug Resistant (MDR) bacterial pathogens involved in Urinary Tract Infections (UTIs) and Sexually Transmitted Infections (STIs) among tribal women in the district Anuppur, Madhya Pradesh, India. Methods: Fresh juices of lemon (Citrus limon), amla/Indian gooseberry (Phyllanthus emblica), pineapple (Ananas comosus), mosambi/sweet lime (Citrus limetta), orange (Citrus sinensis), kiwi (Actinidia deliciosa), and pomegranate (Punica granatum) fruits were evaluated for in vitro antibacterial activity against bacterial pathogens involved in UITs and STIs among tribal women. Physico-chemical analysis of fresh fruits was also carried out by measuring the pH, moisture, protein, fat, crude fibre, carbohydrate, and ascorbic acid content. Results: Lemon and amla juice showed better antibacterial activity against the pathogens as compared to other juices. MIC results fruit juices against UTIs and STIs pathogens vary depending on the specific pathogen and juice chemical constituents. The physico-chemical analysis showed that the moisture content was highest in mosambi (90%), followed by orange (87%). Ascorbic acid content was found highest in amla (540 mg/100 g), followed by kiwi (90.3 mg/100 g). Pomegranate showed highest concentration of carbohydrate (15.28 g/100 g), fat (1.28 g/100 g), and protein (1.65 g/100 g). Lemon juice had lowest pH of 2.20, followed by amla 2.67. Conclusion: The lemon juice showed highest antibacterial activity against MDR bacterial pathogens involved in UTIs and STIs among tribal women in district Anuppur, Madhya Pradesh, India. The low pH of lemon may be responsible for its high antibacterial activity as compared to other juices.

• Journal of Oral Medicine and Pain
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• v.47 no.1
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• pp.52-61
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• 2022

Purpose: Most cases of oral and maxillofacial infections are usually easily treated by proper diagnosis, elimination of causative factors, and antibiotic therapy. However, the emergence and the increase of multidrug-resistant bacteria make treatment challenging. "ESKAPE" pathogens are the most common opportunistic organisms in nosocomial infections and have resistant to commonly used antibiotics. There are many medical reviews of ESKAPE pathogens, but few in dentistry. This study focuses on oral and maxillofacial infection especially with ESKAPE pathogens. The purpose of this study is to prepare feasible data about tracing and treatment of infection related to pathogens that may be beneficial to clinicians. Methods: A total of 154 patients with oral and maxillofacial infections were reviewed by analyzing retrospectively hospitalized data in the Department of Oral and Maxillofacial surgery, Chosun University Hospital, Korea, past 5 years from January 2014 to December 2018. Based on the medical records and microbiological tests, the results were divided into two groups: infections with ESKAPE pathogens and other bacteria. Results: A total of 22 species were isolated from 154 patients. The proportion of ESKAPE pathogens among all bacterial isolates collected from infected patients was 39.6%. Causative factors, especially in post-operative infection, showed a statistically significant correlation to ESKAPE infections (29 cases). And average of treatment period in ESKAPE group was longer than non-ESKAPE groups. Overall, Klebsiella pneumoniae (60.7%) was the most frequently isolated ESKAPE pathogen. And high antibiotic resistance rates had been detected in the ESKAPE during the five-year period. Conclusions: Infections with ESKAPE pathogens are now a problem that can no longer be overlooked in Dentistry. Based on results of this study, ESKAPE pathogens were highly associated with post-operative or opportunistic infections. Clinicians should be careful about these antibiotic resistant pathogens and use appropriate antibiotics to patients while having dental treatments.

• Genomics & Informatics
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• v.21 no.3
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• pp.42.1-42.23
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• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.286-291
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• 1996

Phenolic compounds are prevalent as toxins or environmental pollutants, but they are also widely used as drugs for various purpose including anticancer agent. A novel biphenolic compound, bis(2-hydroxy-3-tert-butyl-5-methylphenyl)methane (GERI-BPO02-A) was isolated from the fermentation broth of Aspergillus fumigatus F93 previously, and it has revealed cytotoxicity against human solid tumor cells. Its effective doses that cause 50% inhibition of cell growth in vitro against non-small cell lung cancer cell A549, ovarian cancer cell SK-OV-3, skin cancer cell SK-MEL-2 and central nerve system cancer cell XF498 were 8.24, 10.60, 8.83, $9.85\mug/ml$ respectively. GERI-BPO02-A has also revealed cytotoxicity against P-glycoproteinexpressed human colon cancer cell HCT15 and its multidrug-resistant subline HCT15/CL02, and its cytotoxicity was not affected by P-glycoprotein. We have also tested cytotoxicities of structurally related compounds of GERI-BPO02-A such as diphenylmethane, 1,1-bis(3,4dimethylphenyl)ethane, 2,2-diphenylpropane, 2-benzylpyridine, 3-benzylpyridine, $4,4^I-di-tert-butylphenyl$, bibenzyl, $2,2^I-dimethylbibenzyl$, cis-stilbene, trans-stilbene, 3-tert-butyl-4-hydroxy-5-methylphenyisulfide, sulfadiazine and sulfisomidine for studying of structure and activity relationship, and from these data we could suppose that hydroxyl group of GERI-BPO02A conducted important role in its cytotoxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.143-148
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• 2008

Caveolin-1 (CAV1) is an integral membrane protein that may function as a scaffold for plasma membrane proteins and acts as a tumor suppressor protein. One causative factor of chemotherapy-resistant cancers is P-plycoprotein (P-gp), the product of the multidrug resistance-1 gene (MDR1), which is localized in the caveolar structure. Currently, the interactive roles of CAV1 and MDR1 expression in the death of cancer cells remain controversial. In this study, we investigated the effects of indomethacin on the cell viability and the expression levels of MDR1 mRNA and protein in a CAV1-siRNA-mediated gene knockdown hepatoma cell line (SK-Hep1). Cell viability was significantly decreased in CAV1-siRNA-transfected cells compared with that of control-siRNA-transfected cells. Furthermore, the viability of cells pretreated with CAV1 siRNA was markedly decreased by treatment with indomethacin (400${\mu}$M for 24 h). However, the protein and mRNA levels of MDR1 were unchanged in CAV1-siRNA-transfected cells. These results suggest that CAV1 plays an important role as a major survival enzyme in cancer cells, and indomethacin can sensitively induce cell death under conditions of reduced CAV1 expression, independent of MDR1 expression.

• Korean Journal of Microbiology
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• v.54 no.3
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• pp.286-288
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• 2018

Moraxella osloensis NP7 was isolated from human skin of a collage male and showed resistance to ${\beta}-lactam$ and aminoglycoside antibiotics. Herein, we report the complete whole-genome sequence and gene annotations of M. osloensis NP7. It possesses single circular chromosome and seven plasmids. Chromosome is 2,389,582 bp in length with the G + C content of 43.9% and encodes 2,065 protein-coding genes. The combined seven plasmids are 654,202 bp in size with the average G + C content of 40.5% and code for a total of 667 protein-coding genes. The chromosome of NP7 strain contains four ribosomal RNA operon copies, one transfer-messenger RNA gene, forty-seven tRNA genes, three riboswitch genes and three CRISPR arrays. Additional CRISPR array is found in the plasmid pNP7-1. The genes conferring resistance to ${\beta}-lactam$ and aminoglycoside antibiotics were predicted to reside in the plasmid pNP7-1.

• Journal of Korean Neurosurgical Society
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• v.41 no.6
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• pp.397-402
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• 2007

Objective : Balloon cells and dysplastic neurons are histopathological hallmarks of the cortical tubers of tuberous sclerosis complex [TSC] and focal cortical dysplasia [FCD] of the Taylor type. They are believed to be the epileptogenic substrate and cause therapeutic drug resistant epilepsy in man. P-glycoprotein [P-gp] is the product of multidrug resistance gene [MDR1], and it maintains intracellular drug concentration at a relatively low level. The authors investigated expression of P-gp in balloon cells and dysplastic neurons of cortical tubers in patients with TSC. Methods : An immunohistochemical study using the primary antibody for P-gp, as an indicative of drug resistance, was performed in the cortical tuber tissues in two patients of surgical resection for epilepsy and six autopsy cases. Results : Balloon cells of each lesion showed different intensity and number in P-gp immunopositivity. P-gp immunopositivity in balloon cells were 28.2%, and dysplastic neurons were 22.7%. These immunoreactivities were more prominent in balloon cells distributed in the subpial region than deeper region of the cortical tubers. Capillary endothelial cells within the cortical tubers also showed P-gp immunopositivity. Conclusion : In this study, the drug resistance protein P-glycoprotein in balloon cells and dysplastic neurons might explain medically refractory epilepsy in TSC.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.2
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• pp.119-124
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• 2022

Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are typical opportunistic pathogens. Moreover, these bacteria are known to possess multidrug-resistant (MDR) properties. This study investigates the antimicrobial activity of six fermented products, which have varying efficacies against P. aeruginosa, E. coli, and S. aureus. To identify novel candidate genes, differential expression analysis was performed using an annealing control primer. In the disk diffusion method, Fig vinegar (FV) and Diospyros kaki Thunb vinegar (DTV) showed the greatest increase in inhibition compared to other fermented products, whereas fermented Korean traditional nature herb (FKTNH) had no antibacterial effect. This study identified down-regulation of Escherichia coli O157:H7 ompW gene for outer membrane protein W, whereas gene for synthetic construct Lao1 gene for L-amino acid oxidase were up-regulated in E. coli treated with 5% FV. Consuming fermented vinegar helps prevent bacterial infections. Especially, FV and DTV are potentially useful alternative natural products for multidrug resistance. Furthermore, both are expected to be used as effective natural antimicrobial agents, such as disinfectants.