EXPRESSION DIFFERENCES OF VASCULAR GROWTH FACTORS IN HUMAN LUNG ADENOCARCINOMA CELL LINE A549 AND CISPLATIN-RESISTANT HUMAN LUNG ADENOCARCINOMA CELL LINE A_(549)^(DDP)

Objective:To elucidate the expression differences of vascular growth factors in human lung adenocarcinoma cell line A549 and cisplatin-resistant human lung adenocarcinoma cell line A549^DDP.Methods:RT-PCR and immunohistochemistry was used to detect the mRNA and protein expressions of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor (bFGF) in A549 and A549^DDP.Results:VEGF and bFGF mRNA were expressed in A549 and in A549^DDP.VEGF and bFGF mRNA expression levels in A549^DDP were signifi-cant higher than those in A549(P<0.025).VEGF and bFGF protein expressions were all strong positive in A549 and A549^DDP.Conclusion:There are certain differences between VEGF and bFGF expressions in A549 and A549^DDP.Drug-resistance of lung cancer is associated with those above genes over-expressions.Over-expression of vascular growth factors are related to drug resistance of lung cancer.

Carbapenemases: A worldwide threat to antimicrobial therapy

Carbapenems are potent β-lactams with activity against extended-spectrum cephalosporinases and β-lactamases. These antibiotics, derived from thienamycn, a carbapenem produced by the environmental bacterium Streptomyces cattleya, were initially used as last-resort treatments forsevere Gram-negative bacterial infections presenting resistance to most β-lactams but have become an empirical option in countries with high prevalence of Extended Spectrum β-lactamase-producing bacterial infections. Imipenem, the first commercially available carbapenem, was approved for clinical use in 1985. Since then, a wide variety of carbapenem-resistant bacteria has appeared, primarily Enterobacteriaceae such as Escherichia coli or Klebsiella pneumoniae(K. pneumoniae), Pseudomonas aeruginosa and Acinetobacter baumannii, presenting different resistance mechanisms. The most relevant mechanism is the production of carbapenem-hydrolyzing β-lactamases, also known as carbapenemases. These enzymes also inactivate all known β-lactams, and some of these enzymes can be acquired through horizontal gene transfer. Moreover, plasmids, transposons and integrons harboring these genes typically carry other resistance determinants, rendering the recipient bacteria resistant to almost all currently used antimicrobials, as is the case for K. pneumoniae carbapenemase- or New Delhi metallo-β-lactamases-type enzymes. The recent advent of these enzymes in the health landscape presents a serious challenge. First, the emergence of carbapenemases limits the currently available treatment options; second, these enzymes pose a risk to patients, as some studies have demonstrated high mortality associated with carbapenemase-producing bacterial infections; and third, these circumstances require an extra cost to sanitary systems, which are particularly cumbersome in developing countries. Therefore, emphasis should be placed on the early detection of these enzymes, the prevention of the spread of carbapenemase-producing bacteria and the development of new drugs resistant to carbapenemase hydrolysis.

Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances

Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.

Community-acquired serious bacterial infections in the first 90 days of life:a revisit in the era of multi-drug-resistant organisms

Background Infants in the first 90 days of life are more prone to develop serious bacterial infections(SBIs).Multi-drug-resistant organisms(MDROs)are emerging as important pathogens causing SBIs.We reviewed the epidemiology of SBIs in infants 0-90 days old and compared the clinical features,laboratory values and final outcome for SBIs due to MDROs vs.non-MDROs.Methods Episodes of culture-proven SBIs(bacteremia,urinary tract infections,or meningitis)with age at onset of 0-90 days during a 7-year period were retrospectively reviewed.Health care-associated infections were excluded.We collected demo-graphics,clinical features,and laboratory and microbiology data.We compared clinical characteristics,laboratory data,microbiologic results and final outcome for SBIs due to MDROs vs.non-MDROs.Results Ninety-four episodes(88 patients)including bacteremia(42.6%),urinary tract infections(54.3%)and meningi-tis(3.1%)were caused by Gram-negative bacteria(67%),and Gram-positive bacteria(33%).Escherichia coli,Klebsiella pneumoniae and GBS were the most common causes.MDROs caused SBIs in 39 patients(44.3%).SBIs due to MDROs were associated with more delay in providing targeted antimicrobial therapy compared to non-MDROs(74.4%vs.0%,P≤0.001,but no difference in case-fatality rate(12.8%vs.12.2%,P=1.0).Clinical features or basic laboratory values were not statistically different between the two groups.Conclusions The bacteriology of SBIs in the first 90 days of life is changing to include more MDROs,which causes more delay in providing targeted antimicrobial therapy.Awareness of the local epidemiology is crucial to ensure appropriate antibiotics are provided in a timely manner.

Emerging trends and future challenges of advanced 2D nanomaterials for combating bacterial resistance

The number of multi-drug-resistant bacteria has increased over the last few decades,which has caused a detrimental impact on public health worldwide.In resolving antibiotic resistance development among different bacterial communities,new antimicrobial agents and nanoparticle-based strategies need to be designed foreseeing the slow discovery of new functioning antibiotics.Advanced research studies have revealed the significant disinfection potential of two-dimensional nanomaterials(2D NMs)to be severed as effective antibacterial agents due to their unique physicochemical properties.This review covers the current research progress of 2D NMs-based antibacterial strategies based on an inclusive explanation of 2D NMs’impact as antibacterial agents,including a detailed introduction to each possible well-known antibacterial mechanism.The impact of the physicochemical properties of 2D NMs on their antibacterial activities has been deliberated while explaining the toxic effects of 2D NMs and discussing their biomedical significance,dysbiosis,and cellular nanotoxicity.Adding to the challenges,we also discussed the major issues regarding the current quality and availability of nanotoxicity data.However,smart advancements are required to fabricate biocompatible 2D antibacterial NMs and exploit their potential to combat bacterial resistance clinically.