Contribution of EmrAB efflux pumps to colistin resistance in Acinetobacter baumannii

Ming-Feng Lin,Yun-You Lin,Chung-Yu Lan 한국미생물학회 2017 The journal of microbiology Vol.55 No.2

Efflux pumps play an important role in antimicrobial resistance for Acinetobacter baumannii. However, the function of the Emr pump system and the relationship between Emr and drug resistance has not been characterized in A. baumannii. In this study, four possible groups of emr-like genes were found by searching a genome database. Among them, A1S_ 1772 (emrB) and A1S_1773 (emrA) were demonstrated to be co-transcribed as a single operon. Moreover, during osmotic stress, A1S_1772 showed the largest change in gene expression compared to the other emrB-like genes, and deletion of A1S_1772 (AB ΔemrB) significantly slowed cell growth in 20% sucrose. Using a phenotypic microarray analysis, the AB ΔemrB mutant was more susceptible to colistin and nafcillin, paromomycin, spiramycin, and D,L-serine hydroxmate than the wild type. The spot assay, time kill assay and minimal inhibition concentration determination also indicated that the wild type could tolerate colistin better than the AB ΔemrB mutant. Finally, the increased expression levels of all emrBlike genes, including A1S_0775, A1S_0909, A1S_1772, and A1S_1799, in colistin resistance-induced A. baumannii further supported the possible involvement of the emrB genes in A. baumannii colistin resistance. Together, the Emr pump systems in A. baumannii contribute to adaptation to osmotic stress and resistance to colistin.

Molecular Epidemiology of Integron-Associated Antimicrobial Gene Cassettes in the Clinical Isolates of Acinetobacter baumannii from Northern Taiwan

Ming-Feng Lin,Ming- Li Liou,Chi-Chao Tu,Hui-Wen Yeh,Chung-YuLan 대한진단검사의학회 2013 Annals of Laboratory Medicine Vol.33 No.4

Background: The aims of this study were to understand the molecular epidemiology of integron-associated gene cassettes in Acinetobacter baumannii across four hospitals in northern Taiwan and to clarify the relationship between the presence of integrons and antibiotic-resistant phenotypes. Methods: Sixty-five A. baumannii isolates, collected from the patients of four regional hospitals in northern Taiwan in 2009, were tested for the presence of integrons and their associated gene cassettes. The susceptibility difference between integron-positive and integron-negative A. baumannii strains was analyzed. Antibiotic-resistant phenotypes among A. baumannii with different types of gene cassette array combinations were also compared. Results: Around 72% of the A. baumannii isolates carried class 1 integrase genes. Despite this, only three gene cassette arrays were found in the integrons. Integron-positive strains were significantly more resistant to all the tested antibiotics than the integrase-negative strains. All the four types of A. baumannii with different gene cassette array combinations were multidrug-resistant in nature. Gene cassette array aacA4-catB8-aadA1 existed in all the integron-positive A. baumannii isolates. Repetitive-sequence-based PCR (rep-PCR)results revealed the prevalence of one major cluster of imipenem-resistant A. baumannii strains (84%) in the four regional hospitals. Conclusions: The presence of integrons with associated antimicrobial resistance gene cassettes can be used as a representative marker of multidrug resistance in A. baumannii. Some prevalent gene cassette arrays may exist among epidemiologically unrelated A. baumannii strains.

Investigation of Planar Optical Waveguide Formed by MeV He+ Ion - Implantation into NaEr(WO₄)₂ Crystal

Feng Chen,Xue-Lin Wang,Ke-Ming Wang,Zhen-Xiang Cheng,Huan-Chu Chen,Ding-Yu Shen 한국진공학회(ASCT) 2002 Journal of Korean Vacuum Science & Technology Vol.6 No.2

NaEr(WO₄)₂ is a new laser material. The planar optical waveguide was formed in NaEr(WO₄)₂ crystal by 2.6 MeV He^+ ion implantation at doses of 1.0-1.5×10^(16) ions/㎤ at room temperature. The effective refractive indices of the dark modes were measured using the prism coupling method. Four TE modes and five TM modes were observed in the waveguide. The refractive index profiles were analyzed using the reflectivity calculation method (RCM). The influence of heat treatment at moderate temperature on the refractive index profiles of the waveguide was also investigated. We used the TRIM’98 (Transport of Ions in Matter) code to simulate the damage profile in the NaEr(WO₄)₂ crystal by 2.6 MeV He^+ ion implantation which is helpful for a better understanding of the waveguide formation.

Efficacy and Safety of 12 Weeks of Daclatasvir, Asunaprevir Plus Ribavirin for the Treatment of HCV Genotype 1b Infection without Baseline NS5A Resistance-Associated Variants (DARING)-Interim Report

( Ming-lung Yu ),( Chao-hung Hung ),( Yi-hsiang Huang ),( Cheng-yuan Peng ),( Chun-yen Lin ),( Pin-nan Cheng ),( Rong-nan Chien ),( Shih-jer Hsu ),( Chen-hua Liu ),( Jee-fu Huang ),( Chung-feng Huang 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The current study aims to elucidate the treatment efficacy (defined as undetectable HCV RNA throughout 12 weeks of post-treatment follow-up, SVR12) and safety DCV/ASV plus ribavirin for 12 weeks in HCV-1b patients without NS5A RAS. Methods: This is a single-arm, open-label phase 2 study. Seventy directly acting antivirals (DAA)-naïve HCV-1b patients without L31/Y93 RAS are planned to receive daclatasvir (60 mg/ day) and asunaprevir (100 mg twice daily) plus weight-based ribavirin (1000-1200 mg/day) for 12 weeks. After treatment they were followed up for 12 weeks. Results: As of 31 Oct 2017, 58 eligible patients are allocated to treatment, with a mean age of 59.3 years and female predominance (67.2%, 39/58). The mean HCV RNA was 5.87+0.77 log10 IU/mL; 23 patients (39.7 %) had significant hepatic fibrosis (>F2). In the modified intention-to-treat analysis, the rate of undetectable HCV at week 1, week 2, week 4, week 8 and endof- treatment was 25 % (14/56), 84.8 % (39/46), 100 % (46/46), 100 % (38/38) and 100 % (27/27), respectively. Undetectable HCV RNA were observed in all of the patients with HCV RNA assessable 4 weeks (SVR4, 18/18) and 12 weeks (SVR12, 12/12) post treatment. None of the 18 patients who completed the 12-week treatment experienced relapse during post-treatment follow-up. The most common adverse event was fatigue (78.3 %), followed by pruritus (65.2 %) and dizziness (52.2 %), of which were considered as ribavirin related. None of the participating subjects withdrew treatment or follow-up throughout the trial peroid. Three serious adverse events were reported which included urosepsis, appendicitis and left ureteral stone. All were unrelated to the investigating drugs. Conclusions: 12 weeks of DCV/ASV plus ribavirin was highly effective and safe in HCV-1b patients without NS5A RAS in the interim analysis. The satisfactory results would be anticipated in the full patient set.

Choledochoduodenal fistula in Mainland China

Ming-Bing Wu,Wen-Feng Zhang,Ying-Lin Zhang,Di Mu,Jian-Ping Gong 대한외과학회 2015 Annals of Surgical Treatment and Research(ASRT) Vol.89 No.5

Purpose: Choledochoduodenal fistula (CDF) is an extremely rare condition even in the most populous nations. However, diagnostic tools are inadequate for the young surgeon to be made aware of such a rare condition before surgery. Hence, basic understanding of the epidemiology, etiology, and management for this unusual but discoverable condition are necessary and essential. Methods: The exclusive case reports of CDF, which were published from 1983 to 2014 concerning mainland Chinese people, were performed to review the epidemiology, etiology, and management. Results: A total of 728 cases were incorporated into this review among 48 papers. More than half of the CDF cases were female (416) with an average age of 57.3 years. CDF was usually caused by cholelithiasis (573 of 728). Epigastric pain (589 of 728) and cholangitis (395 of 728) were the most common symptoms of CDF. CDF was usually detected and confirmed by endoscopic retrograde cholangiopancreatography (ERCP) (475 of 728) in Mainland China. The fistulas larger than 1 cm (82 of 654) were recommended for surgical biliary reconstruction. Fistulas between 0.5 cm and 1.0 cm (467 of 654) which were followed frequently by cholangitis attacks also required surgery; the rest were recommended to have stone removal and/or the application of an effective biliary drainage. Fistulas less than 0.5 cm (105 of 654) were usually received conservative therapy. Conclusion: CDF should be considered in differential diagnosis of recurrent epigastric pain and cholangitis. A possible ERCP should be arranged to investigate carefully. Depending on the size of fistula and clinical presentation, different programs for CDF are indicated, ranging from drug therapy to choledochojejunostomy.

The high Curie temperature and long-range ferromagnetism in Mn-doped 3C-SiC: a study using first-principles calculation

Lin Xue-ling,Zhang He-xiang,Yang Wei-xia,Chen Huan-ming,Pan Feng-chun 한국물리학회 2021 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.79 No.6

Magnetic semiconductors with high Curie temper (TC) and inherent ferromagnetism, which not only provide a data-processing function via semiconductors’ properties, but also offer a data-storage function through intrinsic ferromagnetism, have become key materials in the field of spintronics. We studied the electronic structures and magnetic properties of Mn-doped cubic (3C) SiC using first-principles calculation. The calculated results revealed that MnSi and MnC substitutions can introduce 3 μB and 1 μB magnetic moments into SiC, respectively, which are both localized and extended. The extended tails of the moments indicate a significant spatial extension of the spin-polarized electron states. The interaction between the long tails, which can mediate long-range ferromagnetic (FM) coupling up to 8.55 Å, and is very different from common exchange, in which the ferromagnetism decreases sharply with increasing distance between the moments, and is hard to maintain to the next-neighbor order due to the limited spatial spin-electrons distribution. The distributions of magnetic moments become more and more localized or extended as compressive or tensile strains are increased, but FM interactions under compressive and tensile strains are weaker than those in undeformed structure. The FM coupling mechanism is explained and discussed in detail using p–d electron exchange. These results can provide a routine for engineering FM semiconductor of 3C-SiC.

Influence of Preparation Conditions on the Formation of Copper (II) Architectures with Pyrazine-2,3,5-tricarboxylic Acid

Feng-Qin Wang,Shu Lin,Ming-Lin Guo,Jun-Jian Xu,Xiao-Qing Wang,Yong-Nan Zhao 대한화학회 2011 Bulletin of the Korean Chemical Society Vol.32 No.7

Three new metal-organic copper(II) complexes, [Cu(H_2PZTC)_2]_n·2nH_2O (1), [Cu(HPZTC)·2H_2O]_n·2nH_2O (2),and Cu_2[(PZHD)(OH)(H_2O)_2]_n (3) (H_3PZTC = pyrazine-2,3,5-tricarboxylic acid, PZHD^3− = 2-hydroxypyrazine-3,5-dicarboxylate), have been synthesized from Cu(II)/H3PZTC system under different synthetic conditions, and characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopy and thermogravimetric analysis. In complexes 1 and 2, H_3PZTC ligands loose one and two protons, which were transformed into H_2PZTC− anion and HPZTC^2− dianion under different preparation condition, respectively. Furthermore, two ligands coordinate with Cu(II) cations in different modes, leading to the formation of the different chain structures. In complex 3, H_3PZTC ligand was converted into a new ligand-PZHD by in situ decarboxylation and hydroxylation under a higher pH value than that for complexes 1 and 2. PZHD ligands link the Cu(II) cations to form a 2D layer structure. These results demonstrate that the preparation conditions,including pH value and reaction temperature etc, play an important role in the construction of complexes based on H_3PZTC ligand.

EGF Reverses Multi-drug Resistance via the p-ERK Pathway in HepG2/ADM and SMMC7721/ADM Hepatocellular Carcinoma Models

Yan, Feng,Bai, Li-Ping,Gao, Hua,Zhu, Chang-Ming,Lin, Li,Kang, Xiang-Peng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

Isolation, Characterization, and Application of Chitosan-Degrading Fungus from Soil

( Xin Lin Wei ),( Wei Chen ),( Ming Xiao ),( Jian Bo Xiao ),( Yuan Feng Wang ) 한국미생물 · 생명공학회 2010 Journal of microbiology and biotechnology Vol.20 No.7

ppGalNAc T1 as a Potential Novel Marker for Human Bladder Cancer

Ding, Ming-Xia,Wang, Hai-Feng,Wang, Jian-Song,Zhan, Hui,Zuo, Yi-Gang,Yang, De-Lin,Liu, Jing-Yu,Wang, Wei,Ke, Chang-Xing,Yan, Ru-Ping Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Objectives: To investigate the effect of glycopeptide-preferring polypeptide GalNAc transferase 1 (ppGalNAc T1 ) targeted RNA interference (RNAi) on the growth and migration of human bladder carcinoma EJ cells in vitro and in vivo. Methods: DNA microarray assays were performed to determine ppGalNAc Ts(ppGalNAc T1-9) expression in human bladder cancer and normal bladder tissues. We transfected the EJ bladder cancer cell line with well-designed ppGalNAc T1 siRNA. Boyden chamber and Wound healing assays were used to investigate changes of shppGalNAc T1-EJ cell migration. Proliferation of shppGalNAc T1-EJ cells in vitro was assessed using [3H]-thymidine incorporation assay and soft agar colony formation assays. Subcutaneous bladder tumors in BALB/c nude mice were induced by inoculation of shppGalNAc T1-EJ cells and after inoculation diameters of tumors were measured every 5 days to determine gross tumor volumes. Results: ppGalNAc T1 mRNA in bladder cancer tissues was 11.2-fold higher than in normal bladder tissues. When ppGalNAc T1 expression in EJ cells was knocked down through transfection by pSUPER-shppGalNAc T1 vector, markedly reduced incorporation of [3H]-thymidine into DNA of EJ cells was observed at all time points compared with the empty vector transfected control cells. However, ppGalNAc T1 knockdown did not significantly inhibited cell migration (only 12.3%). Silenced ppGalNAc T1 expression significantly inhibited subcutaneous tumor growth compared with the control groups injected with empty vector transfected control cells. At the end of observation course (40 days), the inhibitory rate of cancerous growth for ppGalNAc T1 knockdown was 52.5%. Conclusion: ppGalNAc T1 might be a potential novel marker for human bladder cancer. Although ppGalNAc T1 knockdown caused no remarkable change in cell migration, silenced expression significantly inhibited proliferation and tumor growth of the bladder cancer EJ cell line.