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Choi, Hyeon Jin,Kil, Min Cheol,Choi, Ji-Young,Kim, Sun Ju,Park, Ki-Sup,Kim, Yae-Jean,Ko, Kwan Soo Elsevier 2017 International journal of antimicrobial agents Vol.49 No.1
<P><B>Abstract</B></P> <P>In this study, 38 <I>Acinetobacter baumannii</I> isolates successively isolated from blood, skin swabs and tracheal aspirates from a single patient who died from haemophagocytic lymphohistiocytosis were investigated. The isolates were collected between March 2012 and August 2012. <I>A. baumannii</I> genotypes were determined by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). In vitro antimicrobial susceptibility testing was performed and colistin heteroresistance and persistence were evaluated. The structure of AbaR resistance islands was explored, and serum sensitivity was determined. Based on MLST analysis, all 38 <I>A. baumannii</I> isolates showed the same sequence type (ST138). However, PFGE analysis showed that isolates from blood samples belonged to different genotypes depending on the isolation time: whilst blood isolates obtained at the early stages showed restriction patterns similar to those of isolates from other sources, isolates obtained at later stages exhibited a distinct pattern. All isolates were resistant to imipenem, cefepime, ciprofloxacin and piperacillin/tazobactam. Five isolates from tracheal aspirates and one from a skin swab were resistant to polymyxins, and two isolates from skin swabs and one from another source were non-susceptible to tigecycline. All colistin-susceptible isolates showed heteroresistance to colistin, and four were persisters. Isolates from blood showed higher survival rates against human serum than those from other sources. This study shows that the patient was infected with more than one <I>A. baumannii</I> strain. Heteroresistance, persistence or evasion of the innate immune response may explain the failure of antimicrobial treatments in this patient.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 38 <I>Acinetobacter baumannii</I> isolates successively isolated from a single patient. </LI> <LI> By PFGE, isolates from blood belonged to different genotypes depending on the isolation time. </LI> <LI> Isolates from blood showed higher survival rates against human serum. </LI> <LI> Heteroresistance, persistence or immune evasion may explain the treatment failures in this patient. </LI> </UL> </P>
Choi Yae Jin,Shin Seon-Hee,Shin Hea Soon 한국미생물·생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.9
The intake of probiotic lactic acid bacteria not only promotes digestion through the microbiome regulated host intestinal metabolism but also improves diseases such as irritable bowel syndrome and inflammatory bowel disease, and suppresses pathogenic harmful bacteria. This investigation aimed to evaluate the immunomodulatory effects in intestinal epithelial cells and to study the clinical efficacy of the selected the Bifidobacterium breve and Bifidobacterium longum groups. The physiological and biochemical properties were characterized, and immunomodulatory activity was measured against pathogenic bacteria. In order to find out the mechanism of inflammatory action of the eight viable and sonicated Bifidobacterium spp., we tried to confirm the changes in the proinflammatory cytokines (TNF-α, interleukin (IL)-6, IL-12) and anti-inflammatory cytokine (IL-10), and chemokines, (monocyte chemoattractant protein-1, IL-8) and inflammatory enzymatic mediator (nitric oxide) against Enterococcus faecalis ATCC 29212 infection in Caco-2 cells and RAW 264.7 cells. The clinical efficacy of the selected B. breve and B. longum group was studied as a probiotic adjuvant for acute diarrhea in children by oral administration. The results showed significant immunomodulatory effects on the expression levels of TNF-α, IL-6, IL-12, MCP-1, IL-8 and NO, in sonicated Bifidobacterium extracts and viable bifidobacteria. Moreover, each of the Bifidobacterium strains was found to react more specifically to different cytokines. However, treatment with sonicated Bifidobacterium extracts showed a more significant effect compared to treatment with the viable bacteria. We suggest that probiotics functions should be subdivided according to individual characteristics, and that personalized probiotics should be designed to address individual applications.
Jin, Yena,Yoon, Yae Jin,Jeon, Yoon Jung,Choi, Jiyeon,Lee, Yu-Jin,Lee, Joonku,Choi, Sangho,Nash, Oyekanmi,Han, Dong Cho,Kwon, Byoung-Mog Pergamon Press 2017 Biochemical pharmacology Vol.142 No.-
<P><B>Abstract</B></P> <P>The roles and significance of signal transducer and activator of transcription 3 (STAT3) in human cancers have been extensively studied and STAT3 is a promising therapeutic target for cancer drug discovery. During the screening of natural products to identify STAT3 inhibitors, we identified geranylnaringenin (CG902), which decreased luciferase activity in a dose-dependent manner. CG902 specifically inhibited STAT3 phosphorylation at Tyr-705 in DU145 prostate cancer cells and decreased the expression levels of STAT3 target genes, such as cyclin D1, cyclin A, and survivin. Notably, the knockdown of the SHP-2 gene by small interfering RNA suppressed the ability of CG902 to inhibit STAT3 activation and CG902 activated the phosphatase activity of SHP-2 through direct interaction with SHP-2 and induced the phosphorylation of SHP-2. The interactions between CG902 and SHP-2 were confirmed by pull-down assay using biotinylated CG902. The interactions were also further validated by the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA). The inhibitory effect of CG902 on cell growth was confirmed using the DU145 mouse xenograft model. We propose that CG902 inhibits STAT3 activity through a mechanism that involves the interactions between CG902 and SHP-2, and the phosphorylation of SHP-2, which leads to SHP-2 activation in DU145 cells. CG902 is the first compound to regulate STAT3 activity via the modulation of SHP-2 activity, and our results suggest that CG902 is a novel inhibitor of the STAT3 pathway and an activator of SHP-2, and may be a useful lead molecule for the development of a therapeutic STAT3 inhibitor.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Benproperine, an ARPC2 inhibitor, suppresses cancer cell migration and tumor metastasis
Yoon, Yae Jin,Han, Young-Min,Choi, Jiyeon,Lee, Yu-Jin,Yun, Jieun,Lee, Su-Kyung,Lee, Chang Woo,Kang, Jong Soon,Chi, Seung-Wook,Moon, Jeong Hee,Lee, Sangku,Han, Dong Cho,Kwon, Byoung-Mog Elsevier 2019 Biochemical pharmacology Vol.163 No.-
<P><B>Abstract</B></P> <P>Metastasis is the leading cause of cancer mortality and cancer cell migration is an essential stage of metastasis. We identified benproperine (Benp, a clinically used antitussive drug) as an inhibitor of cancer cell migration and an anti-metastatic agent. Benp selectively inhibited cancer cell migration and invasion, which also suppressed metastasis of cancer cells in animal models. Actin-related protein 2/3 complex subunit 2 (ARPC2) was identified as a molecular target of Benp by affinity column chromatography with Benp-tagged Sepharose beads. Benp bound directly to ARPC2 in cells, which was validated by pull-down assay using Benp-biotin and label-free biochemical methods such as the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA). Benp inhibited Arp2/3 function, showing disruption of lamellipodial structure and inhibition of actin polymerization. Unlike Arp2/3 inhibitors, Benp selectively inhibited the migration of cancer cells but not normal cells. ARPC2-knockdown cancer cells showed defective cell migration and suppressed metastasis in an animal model. Therefore, ARPC2 is a potential target for anti-metastatic therapy, and Benp has the clinical potential to block metastasis. Furthermore, Benp is a useful agent for studying the functions of the Arp2/3 complex in cancer cell migration and metastasis.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Yoon, Yae Jin,Kim, Young‐,Hwan,Lee, Yu‐,Jin,Choi, Jiyeon,Kim, Cheol‐,Hee,Han, Dong Cho,Kwon, Byoung‐,Mog John Wiley and Sons Inc. 2019 CANCER SCIENCE Vol.110 No.1
<P>Inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling pathway is a novel therapeutic strategy to treat human cancers with constitutively active STAT3. During the screening of natural products to find STAT3 inhibitors, we identified 2′‐hydroxycinnamaldehyde (HCA) as a STAT3 inhibitor, which was isolated from the stem bark of <I>Cinnamomum cassia</I>. In this study, we found that HCA inhibited constitutive and inducible STAT3 activation in STAT3‐activated DU145 prostate cancer cells. HCA selectively inhibited the STAT3 activity by direct binding to STAT3, which was confirmed by biochemical methods, including a pull‐down assay with biotin‐conjugated HCA, a drug affinity responsive target stability (DARTS) experiment and a cellular thermal shift assay (CETSA). HCA inhibited STAT3 phosphorylation at the tyrosine 705 residue, dimer formation, and nuclear translocation in DU145 cells, which led to a downregulation of STAT3 target genes. The downregulation of cell cycle progression and antiapoptosis‐related gene expression by HCA induced the accumulation of cells in the G0/G1 phase of the cell cycle and then induced apoptosis. We also found that reactive oxygen species (ROS) were involved in the HCA‐induced inhibition of STAT3 activation and cell proliferation because the suppressed p‐STAT3 level was rescued by glutathione or N‐acetyl‐L‐cysteine treatment, which are general ROS inhibitors. These results suggest that HCA could be a potent anticancer agent targeting STAT3‐activated tumor cells.</P>
Recommendation for the use of newly introduced Tdap vaccine in Korea
Choi, Kyong-Min,Kim, Kyung-Hyo,Kim, Yae-Jean,Kim, Jong-Hyun,Park, Su-Eun,Lee, Hoan-Jong,Eun, Byung-Wook,Jo, Dae-Sun,Choi, Eun-Hwa,Hong, Young-Jin The Korean Pediatric Society 2011 Clinical and Experimental Pediatrics (CEP) Vol.54 No.4
Pertussis is an acute respiratory infection characterized by paroxysmal cough and inspiratory whoop for over 2 weeks. The incidence of pertussis has decreased markedly after the introduction of DTwP/DTaP vaccine, but the incidence of pertussis has increased steadily among young infant and among adolescents and adults in many countries. Td vaccine was used in this age group but the increase in pertussis has lead to the development of a Tdap vaccine. The Tdap vaccine is a Td vaccine with a pertussis vaccine added and is thought to decrease the incidence and transmission of pertussis in the respective age group. In Korea, two products are approved by the KOREA FOOD & DRUG ADMINISTRATION, which are ADACEL$^{TM}$ (Sanofi-Pasteur, Totonto, Ontario, Canada) and BOOSTRIX$^{(R)}$ (GlaxoSmithKline Biologicals, Rixensart, Belgium) for those aged between 11-64. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society.
Choi, Eun Hwa,Park, Su Eun,Kim, Yae-Jean,Jo, Dae Sun,Kim, Yun-Kyung,Eun, Byung-Wook,Lee, Taek-Jin,Lee, Jina,Lee, Hyunju,Kim, Ki Hwan,Cho, Hye-Kyung,Cho, Eun Young,Kim, Jong-Hyun The Korean Pediatric Society 2019 Clinical and Experimental Pediatrics (CEP) Vol.62 No.7
The Committee on Infectious Diseases of the Korean Pediatric Society recommended immunization schedule for children and adolescents aged 18 years or younger in the 9th (2018) edition of Immunization guideline. This report provides the revised recommendations made by the committee and summarizes several changes from the 2015 guideline. National immunization program (NIP) launched a human papillomavirus (HPV) immunization for girls aged 12 years in 2016. NIP has also expanded age indication for inactivated influenza vaccine (IIV) to 12 years of age in the 2018-2019 season. Quadrivalent IIVs with a full dose (0.5 mL) are approved for all children of 6 months or older. Recommendations of live attenuated influenza vaccine were removed. For inactivated Japanese encephalitis vaccine, first 2 doses are considered as the primary series. Recommendations for use of newly introduced vaccines (diphtheria-tetanus-acellular pertussis/inactivated poliovirus/Haemophilus influenzae type b, 9-valent HPV, new varicella vaccine, new quadrivalent IIV, and attenuated oral typhoid vaccine) were added. Lastly, monitoring system for adverse events following immunization was updated. Other changes can be found in the 9th edition of Immunization guideline in detail.