• Title/Summary/Keyword: OXA-10

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Combination of oxaliplatin and β-carotene suppresses colorectal cancer by regulating cell cycle, apoptosis, and cancer stemness in vitro

  • Junghyeun Lee;Seung Chul Heo;Yuri Kim
    • Nutrition Research and Practice
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    • 제18권1호
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    • pp.62-77
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    • 2024
  • BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide with a high recurrence rate. Oxaliplatin (OXA) resistance is one of the major reasons hindering CRC therapy. β-Carotene (BC) is a provitamin A and is known to have antioxidant and anticancer effects. However, the combined effect of OXA and BC has not been investigated. Therefore, this study investigated the anticancer effects and mechanism of the combination of OXA and BC on CRC. MATERIALS/METHODS: In the present study, the effects of the combination of OXA and BC on cell viability, cell cycle arrest, and cancer stemness were investigated using HCT116, HT29, OXA-resistant cells, and human CRC organoids. RESULTS: The combination of OXA and BC enhanced apoptosis, G2/M phase cell cycle arrest, and inhibited cancer cell survival in human CRC resistant cells and CRC organoids without toxicity in normal organoids. Cancer stem cell marker expression and self-replicating capacity were suppressed by combined treatment with OXA and BC. Moreover, this combined treatment upregulated apoptosis and the stem cell-related JAK/STAT signaling pathway. CONCLUSIONS: Our results suggest a novel potential role of BC in reducing resistance to OXA, thereby enhances the anticancer effects of OXA. This enhancement is achieved through the regulation of cell cycle, apoptosis, and stemness in CRC.

Genotyping and Molecular Characterization of Carbapenem-resistant Acinetobacter baumannii Strains Isolated from Intensive Care Unit Patients

  • Abozahra, Rania;Abdelhamid, Sarah M.;Elsheredy, Amel G.;Abdulwahab, Kawther E.;Baraka, Kholoud
    • 한국미생물·생명공학회지
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    • 제49권2호
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    • pp.239-248
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    • 2021
  • The emergence of multidrug-resistant Acinetobacter baumannii has partly increased treatment failure and patient mortality. Class D β-lactamases is an important mechanism of resistance to beta-lactam antibiotics in this species. This study aimed to investigate the relationship between the presence oxacillinase gene and genetic fingerprints of A. baumannii isolates from the intensive care unit of an Egyptian tertiary care hospital. One hundred and twenty A. baumannii clinical isolates were collected. Multiplex PCR was performed to detect genes encoding oxacillinases (OXA-23, OXA-24, OXA-51, OXA-58 and OXA-143). Molecular typing of all collected isolates was performed using random amplified polymorphic DNA (RAPD)-PCR assay. Out of 120 examined isolates, 92, 88 and 84% were resistant to ertapenem, imipenem and meropenem, respectively. The species-specific, commonly present OXA-51 gene was found in all isolates while OXA-23 showed a high prevalence of 88% of isolates. OXA-24 and OXA-143 genes were detected in 3% and 1% of isolates, respectively. No OXA-58 gene was detected. Five clusters consisting of 19 genotypes were detected using RAPD-PCR. Genotype A was the most prevalent, it was observed in 62% of the isolates followed by genotype B (12%). These results revealed that genotypes A and B are common in the hospital. Results also demonstrate that RAPD-PCR is a rapid and reliable method for studying the clonal similarity among A. baumannii isolated from different clinical specimens.

Association between Beta-lactam Antibiotic Resistance and Virulence Factors in AmpC Producing Clinical Strains of P. aeruginosa

  • Dehbashi, Sanaz;Tahmasebi, Hamed;Arabestani, Mohammad Reza
    • Osong Public Health and Research Perspectives
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    • 제9권6호
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    • pp.325-333
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    • 2018
  • Objectives: The purpose of this study was to determine the presence of IMP and OXA genes in clinical strains of Pseudomonas aeruginosa (P. aeruginosa) that are carriers of the ampC gene. Methods: In this study, 105 clinical isolates of P. aeruginosa were collected. Antibiotic resistance patterns were determined using the disk diffusion method. The strains carrying AmpC enzymes were characterized by a combination disk method. Multiplex-PCR was used to identify resistance and virulence genes, chi-square test was used to determine the relationship between variables. Results: Among 105 isolates of P. aeruginosa, the highest antibiotic resistance was to cefotaxime and aztreonam, and the least resistance was to colictin and ceftazidime. There were 49 isolates (46.66%) that showed an AmpC phenotype. In addition, the frequencies of the resistance genes were; OXA48 gene 85.2%, OXA199, 139 3.8%, OXA23 3.8%, OXA2 66.6%, OXA10 3.8%, OXA51 85.2% and OXA58 3.8%. The IMP27 gene was detected in 9 isolates (8.57%) and the IMP3.34 was detected in 11 isolates (10.47%). Other genes detected included; lasR (17.1%), lasB (18%) and lasA (26.6%). There was a significant relationship between virulence factors and the OX and IMP genes ($p{\leq}0.05$). Conclusion: The relationship between antibiotic resistance and virulence factors observed in this study could play an important role in outbreaks associated with P. aeruginosa infections.

대전지역 소재 대학병원에 blaOXA-23 유전자를 가지고 있는 다제내성 Acinetobacter baumannii의 확산 (Clonal Dissemination of Multidrug Resistant Acinetobacter baumannii Isolates Harboring blaOXA-23 at One University Hospital in Daejeon, Korea)

  • 성지연
    • 대한임상검사과학회지
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    • 제48권2호
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    • pp.94-101
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    • 2016
  • Acinetobacter species는 중요한 기회감염균으로 빈번하게 원내감염을 일으킨다. 뿐만 아니라 다제내성을 보이는 경우가 많아 치료를 위한 항균제 선택이 매우 제한적이다. 본 연구에서는 Acinetobacter species 68균주를 대상으로 하여 다양한 carbapenemase 유전자를 조사했다. 디스크확산법으로 항균제 감수성 양상을 조사했으며 다중 중합효소연쇄반응을 통해 carbapenemase 유전자를 포함하고 있는 균주를 선별하였고 PCR과 염기서열분석을 통해 최종적으로 carbapenemase 유전형을 확인했다. 한편 REP-PCR 방법으로 균주간의 clonality를 분석했다. 본 연구에서 A. baumannii 균주는 분석된 모든 항균제에 대해 높은 내성을 나타냈으나 non-A. baumannii 균주는 분석된 항균제 중 aztreonam과 cefotaxime을 제외한 항균제에 모두 감수성을 보였다. A. baumannii 51 균주는 $bla_{OXA-51}$ 유전자를 가지고 있었으며 그 중 37(72.5%)균주는 $bla_{OXA-23}$ 유전자도 동시에 가지고 있었다. 본 연구에서 39 균주의 다제내성 A. baumannii 가 분리되었는데 그 중 37균주가 $bla_{OXA-23}$ 유전자를 가지고 있었다. $bla_{OXA-23}$ 유전자를 포함하고 있는 균주들은 I (n=22) 형 또는 II (n=15) 형의 REP-PCR band 패턴을 보였는데 이는 대전에 위치한 일개의 대학병원에 $bla_{OXA-23}$ 유전자를 포함하고 있는 다제내성 균주들이 수평 확산 되어 있음을 의미한다. 다제내성 A. baumannii 균주에 의한 감염 및 집락화를 막기 위해서는 지속적으로 내성을 유발하는 인자를 조사하고 MDR균주의 출현 및 확산을 감시할 필요가 있을 것으로 사료된다.

Development of a Novel Immunochromatographic Assay for Rapid Detection of OXA-23 β-lactamase-producing Acinetobacter baumannii

  • Ji, Gil Young;Song, Hyung Geun;Jo, Mi Young;Hong, Seung Bok;Shin, Kyeong Seob
    • 대한의생명과학회지
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    • 제22권2호
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    • pp.29-36
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    • 2016
  • Among the several agents causing carbapenem resistance of Acinetobacter baumannii, the most common cause is OXA-23 ${\beta}$-lactamase, which is known to hydrolyze carbapenem. To effectively control dissemination of carbapenem-resistant Acinetobacter baumannii (CRAB), development of both rapid and easy-to-use detection methods are required. The aim of this study is to develop a novel immunochromatographic assay (ICA) for rapid detection of OXA-23 ${\beta}$-lactamase. Of the seven monoclonal antibodies (mAbs) screened by ELISA, four mAbs (4G6, 4H6, 6G4, 9A4) exhibited high reactivity. Of these four specific antibodies, the combination of 6G4/4G6 showed the greatest reactivity and this combination of mAbs (6G4/4G6 mAbs) was used to develop the OXA-23 ${\beta}$-lactamase ICA. Of 102 A. baumannii isolates tested, the OXA-23 ${\beta}$-lactamase ICA results were consistent with PCR analysis except one false positive and one false negative isolate. The overall sensitivity and specificity were 98.36% and 97.56%, respectively. In conclusion, to the best of our knowledge, we have developed the first specific antibody set to detect OXA-23 ${\beta}$-lactamase using an ICA kit. This novel ICA can be used as a reliable and easy-to-use immunological assay for detection of OXA-23 ${\beta}$-lactamase producing CRAB in clinical laboratories.

In vitro Evaluation of New Acetylcholinesterase Reactivators as Casual Antidotes against Tabun and Cyclosarin

  • Kuca, Kamil;Jun, Daniel;Kim, Tae-Hyuk;Cabal, Jiri;Jung, Young-Sik
    • Bulletin of the Korean Chemical Society
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    • 제27권3호
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    • pp.395-398
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    • 2006
  • Nerve agents (sarin, tabun, soman and VX) are class of military important substances able to cause many severe intoxications during few minutes. Currently, the threat of misuse of these agents is daily discussed. Unfortunately, there is no single antidote able to treat intoxication caused by all of these agents. Owing to this fact, new generation of antidotes, especially acetylcholinesterase (AChE; EC 3.1.1.7) reactivators, is still developed. In this study, we have tested four newly developed AChE reactivators: 1-(4-hydroxyiminomethylpyridinium)- 5-(4-carbamoylpyridinium)-3-oxa-pentane dibromide (1), 1-(3-hydroxyiminomethylpyridinium)-5-(4-carbamoylpyridinium)-3-oxa-pentane dibromide (2), 1,5-bis(2-hydroxyiminomethylpyridinium)-3-oxa-pentane dichloride (3) and 1,5-bis(4-hydroxyiminomethylpyridinium)-3-oxa-pentane dibromide (4) for their potency to reactivate in vitro tabun and cyclosarin-inhibited AChE. Their reactivation efficacy was compared with currently the most promising oxime HI-6 (1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxa-propane dichloride). According to obtained results, two AChE reactivators 1 and 4 were able to reactivate tabun-inhibited AChE. On the contrary, there was no better AChE reactivator than HI-6 able to reactivate cyclosarin-inhibited AChE.

임상검체에서 분리된 그람음성막대균으로부터 카바페넴 내성 유전자 검출 (Detection of the Carbapenem Resistance Gene in Gram-negative Rod Bacteria Isolated from Clinical Specimens)

  • 양병선
    • 대한임상검사과학회지
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    • 제54권3호
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    • pp.179-191
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    • 2022
  • 본 연구는 공중보건에 위협이 되고 있는 carbapenemase 유전자형 중 blaKPC, blaNDM, blaIMP, blaVIM, blaOXA-48-like 유전자의 표현형적 검사 및 분자진단으로 검출하고 관련 유전자 분포 양상에 대해 알아보았다. 표현형적 검사결과 MHT는 41균주 모두에서 양성을 확인하고, CIT는 meropenem+PBA는 18균주 및 meropenem+EDTA에서 8균주의 양성을 확인하였다. PCR 결과 blaKPC 28균주, blaNDM 25균주, blaIMP 5균주, blaVIM 1균주, blaOXA-48-like 13균주에서 증폭 산물을 확인하였다. 또한 blaKPC+blaNDM 7균주, blaKPC+blaIMP 1균주, blaNDM+blaOXA-48-like 1균주, blaNDM+blaVIM 1균주, blaKPC+blaNDM+blaIMP 4균주, blaKPC+blaNDM+blaOXA-48-like 4균주를 확인하였다. 실시간 중합효소 연쇄반응을 이용한 융해 곡선 분석결과는 PCR 결과와 100% 일치함을 확인하였다. 결론적으로 real-time PCR을 이용한 신속하고 특이성이 높은 CRE 조기진단을 통한 유전자 확인은 제한된 치료 옵션과 높은 사망률로 공중 보건 위협을 고조하는 CRE의 감시, 진단 및 치료를 개선할 수 있으며 전염을 방지하기 위한 효과적인 항균 치료 및 시기적절한 감염 통제가 가능할 것으로 사료된다.

Facile Syntheses of Modified Tripyrranes and Their Application to the Syntheses fo Regioisomerically Pure Porphyrin Derivatives

  • 허필연;이창희
    • Bulletin of the Korean Chemical Society
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    • 제17권6호
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    • pp.515-520
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    • 1996
  • Simple conditions were discovered to afford tripyrranes by reaction of 2,5-bis(α-hydroxymethyl)furan or 2,5-bis(α-hydroxy-α-phenylmethyl)thiophene with excess pyrrole in the presence of acid catalyst. Stepwise synthesis of porphyrins with core-ligand modification and synthesis of meso-tetraarylporphyrins bearing two different substituents in cis orientation have developed as building blocks for the various porphyrin-based model systems. Consequently, 21-thia-23-oxa-10,15-diphenylporphyrin (28), 21-oxa-10,15-diphenylporphyrin (29) and 21-oxa-23-carba-12-aza-10,15-diphenylporphyrin (30) were synthesized by acid-catalyzed [3+1] condensation between tripyrranes and 2,5-bis(α-hydroxymethyl)pyrrole or 2,5-bis(α-hydroxy-α-phenylmethyl)thiophene. The synthetic pathway described here gave regioisomerically pure porphyrins and thus overcame the synthetic problems associated with separation and purification of regioisomeric mixture.

주변 수계에서 미생물유래 extended-spectrum beta-lactamase 유전자의 분포 (Distribution of the extended-spectrum beta-lactamase genes derived from microorganisms in the waterfront environments)

  • 배영민
    • 한국응용과학기술학회지
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    • 제39권6호
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    • pp.916-923
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    • 2022
  • 창원시의 3개 지점(남천, 창원천, 청운지)에서 물 시료를 채취하고, 채취한 시료로부터 genomic DNA를 분리하였다. 분리된 DNA와 class A extended-spectrum beta-lactamase(ESBL) 유전자 5가지(blaOXA-1, blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9)를 target으로 하는 primers를 사용하여 quantitative PCR을 수행하였다. 시료를 채취한 지점별로 ESBL 유전자들의 수와 비율에서 확연한 차이가 있음을 알 수 있었다. 남천의 경우 DNA 30ng당 ESBL 유전자가 1.93×106 copy나 존재하는 데에 반해 창원천의 경우에는 1.47×105 copy 그리고 청운지에는 9.5×103 copy 밖에 존재하지 않았다. 흐르는 하천인 남천과 창원천에서는 각 ESBL 유전자들의 비율에서 큰 차이가 없었다. 즉, 남천에서는 blaOXA-1 유전자가 65.3%, blaCTX-M-1 유전자가 33.6%를 차지하여서 이 두 유전자가 전체 ESBL 유전자의 99% 가까이를 차지하고 있었다. 창원천에서도 blaOXA-1 유전자가 64.1%, blaCTX-M-1 유전자가 19.1%를 차지하므로 이 두 유전자가 전체의 83% 이상을 차지하고 있었다. 하천과 다르게 폐쇄된 환경인 청운지 연못에서는 내성세균들의 총량 자체가 다른 두 하천에 비해서 월등하게 적었다. 또한 내성 세균의 비율도 달라서 blaCTX-M-1 유전자가 전체의 87.5%, 그리고 blaCTX-M-9 유전자가 9.8%를 차지하고 있었다.