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51.
Ardeshir Rineh John B. Bremner Michael R. Hamblin Anthony R. Ball George P. Tegos Michael J. Kelso 《Bioorganic & medicinal chemistry letters》2018,28(16):2736-2740
Resistance of bacteria to antibiotics is a public health concern worldwide due to the increasing failure of standard antibiotic therapies. Antimicrobial photodynamic inactivation (aPDI) is a promising non-antibiotic alternative for treating localized bacterial infections that uses non-toxic photosensitizers and harmless visible light to produce reactive oxygen species and kill microbes. Phenothiazinium photosensitizers like methylene blue (MB) and toluidine blue O are hydrophobic cations that are naturally expelled from bacterial cells by multidrug efflux pumps, which reduces their effectiveness. We recently reported the discovery of a NorA efflux pump inhibitor-methylene blue (EPI-MB) hybrid compound INF55-(Ac)en–MB that shows enhanced photodynamic inactivation of the Gram-positive bacterium methicillin-resistant Staphylococcus aureus (MRSA) relative to MB, both in vitro and in vivo. Here, we report the surprising observation that INF55-(Ac)en–MB and two related hybrids bearing the NorA efflux pump inhibitors INF55 and INF271 also show enhanced aPDI activity in vitro (relative to MB) against the Gram-negative bacteria Escherichia coli and Acinetobacter baumannii, despite neither species expressing the NorA pump. Two of the hybrids showed superior effects to MB in murine aPDI infection models. The findings motivate wider exploration of aPDI with EPI-MB hybrids against Gram-negative pathogens and more detailed studies into the molecular mechanisms underpinning their activity. 相似文献
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Rostam Abdollahi-Arpanahi Abbas Pakdel Ardeshir Nejati-Javaremi Mohammad Moradi Shahrbabak Farhad Ghafouri-Kesbi 《Journal of applied genetics》2014,55(3):373-381
The genetic architecture of a quantitative trait refers to the number of genetic variants, allele frequencies, and effect sizes of variants that affect a trait and their mode of gene action. This study was conducted to investigate the effect of four shapes of allelic frequency distributions (constant, uniform, L-shaped and U-shaped) and different number of trait-affecting loci (50, 100, 200, 500) on allelic frequency changes, long term genetic response, and maintaining genetic variance. To this end, a population of 440 individuals composed of 40 males and 400 females as well as a genome of 200 cM consisting of two chromosomes and with a mutation rate of 2.5?×?10?5 per locus was simulated. Selection of superior animals was done using best linear unbiased prediction (BLUP) with assumption of infinitesimal model. Selection intensity was constant over 30 generations of selection. The highest genetic progress obtained when the allelic frequency had L-shaped distribution and number of trait-affecting loci was high (500). Although quantitative genetic theories predict the extinction of genetic variance due to artificial selection in long time, our results showed that under L- and U-shapped allelic frequency distributions, the additive genetic variance is persistent after 30 generations of selection. Further, presence or absence of selection limit can be an indication of low (<50) or high (>100) number of trait-affecting loci, respectively. It was concluded that the genetic architecture of complex traits is an important subject which should be considered in studies concerning long-term response to selection. 相似文献
53.
Keloid disease (KD) is an abnormal cutaneous fibroproliferative disorder of unknown aetiopathogenesis. Keloid fibroblasts (KF) are implicated as mediators of elevated extracellular matrix deposition. Aberrant secretory behaviour by KF relative to normal skin fibroblasts (NF) may influence the disease state. To date, no previous reports exist on the ability of site-specific KF to induce fibrotic-like phenotypic changes in NF or normal scar fibroblasts (NS) by paracrine mechanisms. Therefore, the aim of this study was to investigate the influence of conditioned media from site-specific KF on the cellular and molecular behaviour of both NF and NS enabled by paracrine mechanisms. Conditioned media was collected from cultured primary fibroblasts during a proliferative log phase of growth including: NF, NS, peri-lesional keloid fibroblasts (PKF) and intra-lesional keloid fibroblasts (IKF). Conditioned media was used to grow NF, NS, PKF and IKF cells over 240 hrs. Cellular behavior was monitored through real time cell analysis (RTCA), proliferation rates and migration in a scratch wound assay. Fibrosis-associated marker expression was determined at both protein and gene level. PKF conditioned media treatment of both NF and NS elicited enhanced cell proliferation, spreading and viability as measured in real time over 240 hrs versus control conditioned media. Following PKF and IKF media treatments up to 240 hrs, both NF and NS showed significantly elevated proliferation rates (p<0.03) and migration in a scratch wound assay (p<0.04). Concomitant up-regulation of collagen I, fibronectin, α-SMA, PAI-1, TGF-β and CTGF (p<0.03) protein expression were also observed. Corresponding qRT-PCR analysis supported these findings (P<0.03). In all cases, conditioned media from growing marginal PKF elicited the strongest effects. In conclusion, primary NF and NS cells treated with PKF or IKF conditioned media exhibit enhanced expression of fibrosis-associated molecular markers and increased cellular activity as a result of keloid fibroblast-derived paracrine factors. 相似文献
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This research was conducted to evaluate acaricidal effects of some plant essences on Varroa mites and the possibility of their usage for Varroa control. First, live Varroa mites were obtained from adult honeybees with CO2 in a newly designed apparatus. Thyme, savory, rosemary, marjoram, dillsun and lavender essences at concentrations of 2 and
1g/100g (w/w), caused a mite mortality rate of more than 97% and 95%, respectively. Also spearmint at 2g/100g was able to
kill more than 97% of Varroa mites. When sprayed on worker honeybees infected with mites, thyme, savory, spearmint and dillsun essences at 2g/100g (w/w)
caused 43–58% Varroa mortality. Toxicity of thyme, savory and spearmint essences for worker honeybees was not significantly different from that
of controls (acetone and water), but dillsun essence caused 12% honeybee mortality. These results showed that essences of
thyme, savory and spearmint have acaricidal properties that could be used for controlling Varroa in honeybee colonies.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
58.
Amirkhani A Heldin E Markides KE Bergquist J 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2002,780(2):381-387
Concentrations of tryptophan and its metabolites in plasma are of great interest in determining proper diagnosis and medication of several neurological diseases like, for example, Alzheimer's disease. A method of standard addition was developed to determine total level of tryptophan and two of its metabolites, kynurenine and kynurenic acid, in human plasma by capillary liquid chromatography-electrospray ionization tandem mass spectrometry. Plasma samples were simply deproteinized by addition of diluted perchloric acid. Samples were then mixed with trichloroacetic acid and injected onto a capillary column. Analytes were separated by a fast gradient elution of the injected samples. Detection was performed by sheathless electrospray tandem mass spectrometry in the multiple reaction monitoring mode. Linear calibration curves were obtained for spiked plasma sample with up to 100% of the expected analytes concentrations. The determined concentrations were well within ranges previously reported (i.e., 6 nM-95 microM) and limit of detections were around 3 nM for each analyte. 相似文献
59.
Hashmi AZ Hakim W Kruglov EA Watanabe A Watkins W Dranoff JA Mehal WZ 《American journal of physiology. Gastrointestinal and liver physiology》2007,292(1):G395-G401
Adenosine is produced during cellular hypoxia and apoptosis, resulting in elevated tissue levels at sites of injury. Adenosine is also known to regulate a number of cellular responses to injury, but its role in hepatic stellate cell (HSC) biology and liver fibrosis is poorly understood. We tested the effect of adenosine on the cytosolic Ca2+ concentration, chemotaxis, and upregulation of activation markers in HSCs. We showed that adenosine did not induce an increase in the cytosolic Ca2+ concentration in LX-2 cells and, in addition, inhibited increases in the cytosolic Ca2+ concentration in response to ATP and PDGF. Using a Transwell system, we showed that adenosine strongly inhibited PDGF-induced HSC chemotaxis in a dose-dependent manner. This inhibition was mediated via the A(2a) receptor, was reversible, was reproduced by forskolin, and was blocked by the adenylate cyclase inhibitor 2,5-dideoxyadenosine. Adenosine also upregulated the production of TGF-beta and collagen I mRNA. In conclusion, adenosine reversibly inhibits Ca2+ fluxes and chemotaxis of HSCs and upregulates TGF-beta and collagen I mRNA. We propose that adenosine provides 1) a "stop" signal to HSCs when they reach sites of tissue injury with high adenosine concentrations and 2) stimulates transdifferentiation of HSCs by upregulating collagen and TGF-beta production. 相似文献
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Ardeshir R. Rastinehad Nikhil Waingankar Baris Turkbey Oksana Yaskiv Anna M. Sonstegard Mathew Fakhoury Carl A. Olsson David N. Siegel Peter L. Choyke Eran Ben-Levi Robert Villani 《PloS one》2015,10(11)