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171.
Victoria Magrioti Aikaterini Nikolaou Annetta Smyrniotou Ishita Shah Violetta Constantinou-Kokotou Edward A. Dennis George Kokotos 《Bioorganic & medicinal chemistry》2013,21(18):5823-5829
Group VIA calcium-independent phospholipase A2 (GVIA iPLA2) has recently emerged as an important pharmaceutical target. Selective and potent GVIA iPLA2 inhibitors can be used to study its role in various neurological disorders. In the current work, we explore the significance of the introduction of a substituent in previously reported potent GVIA iPLA2 inhibitors. 1,1,1,2,2-Pentafluoro-7-(4-methoxyphenyl)heptan-3-one (GK187) is the most potent and selective GVIA iPLA2 inhibitor ever reported with a XI(50) value of 0.0001, and with no significant inhibition against GIVA cPLA2 or GV sPLA2. We also compare the inhibition of two difluoromethyl ketones on GVIA iPLA2, GIVA cPLA2, and GV sPLA2. 相似文献
172.
173.
Mahim Khan Muhammad Qasim Usman Ali Ashfaq Sobia Idrees Masoud Shah 《Bioinformation》2013,9(14):710-714
Background:
HCV has become a leading cause of liver cirrhosis and hepatocellular carcinoma and is a major health concern worldwide. To date,
there is no vaccine available in the market to tackle this disease, therefore there is a strong need to develop antiviral compounds
that can target all genotypes of HCV with the same efficiency. Medicinal plants have low cost and are less toxic therefore, extracts
of medicinal plants can serve as important antiviral agents against HCV. This study was designed to screen phytochemicals of
Accacia nilotica to find a potent drug candidate that can inhibit HCV infection effectively.Results:
Docking of NS3/4A protease and Flavonoids of Accacia nilotica revealed that most of the flavonoids bound deeply with the active
site of NS3/4A protease. Compound 01 showed a high ranking on docking score. All other compounds also showed reliable
docking scores and had interactions with the binding cavity of NS3/4A protease, suggesting them as a potent drug candidate to
block HCV replication.Conclusion:
To recognize binding interactions of Accacia nilotica phytochemicals with NS3/4A protease, molecular docking was performed to
find potential inhibitor against NS3/4A protease of HCV. After post docking analysis, important interactions were found between
active compounds and active site of NS3/4A protease. It can be concluded from the study that phytochemicals of Accacia nilotica
may serve as a potential drug candidate with relatively simple structural changes against HCV NS3/4A protease. 相似文献
174.
175.
Isolation of microorganisms capable of synthesising amino acids, utilizing hydrocarbons, has been reported. These microorganisms were isolated from soil samples by selective culture techniques. 91 strains were found capable of producing amino acids in the broth. Different amino acids and their maximum yield obtained were glutamic acid 160 mg/1; leucine 90.0 mg/1; isoleucine 40.0 mg/1; valine 105.0 mg/1; methionine 25.0 mg/1; tryptophan 2.5 mg/1; arginine 70.0 mg/1; and histidine 10.0 mg/1. 相似文献
176.
HIV-1 glycoprotein 120 (gp120) is known to cause neurotoxicity via several mechanisms including production of proinflammatory cytokines/chemokines and oxidative stress. Likewise, drug abuse is thought to have a direct impact on the pathology of HIV-associated neuroinflammation through the induction of proinflammatory cytokines/chemokines and oxidative stress. In the present study, we demonstrate that gp120 and methamphetamine (MA) causes apoptotic cell death by inducing oxidative stress through the cytochrome P450 (CYP) and NADPH oxidase (NOX) pathways. The results showed that both MA and gp120 induced reactive oxygen species (ROS) production in concentration- and time-dependent manners. The combination of gp120 and MA also induced CYP2E1 expression at both mRNA (1.7±0.2- and 2.8±0.3-fold in SVGA and primary astrocytes, respectively) and protein (1.3±0.1-fold in SVGA and 1.4±0.03-fold in primary astrocytes) levels, suggesting the involvement of CYP2E1 in ROS production. This was further confirmed by using a selective inhibitor of CYP2E1, diallylsulfide (DAS), and CYP2E1 knockdown using siRNA, which significantly reduced ROS production (30–60%). As the CYP pathway is known to be coupled with the NOX pathway, including Fenton–Weiss–Haber (FWH) reaction, we examined whether the NOX pathway is also involved in ROS production induced by either gp120 or MA. Our results showed that selective inhibitors of NOX, diphenyleneiodonium (DPI), and FWH reaction, deferoxamine (DFO), also significantly reduced ROS production. These findings were further confirmed using specific siRNAs against NOX2 and NOX4 (NADPH oxidase family). We then showed that gp120 and MA both induced apoptosis (caspase-3 activity and DNA lesion using TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling) assay) and cell death. Furthermore, we showed that DAS, DPI, and DFO completely abolished apoptosis and cell death, suggesting the involvement of CYP and NOX pathways in ROS-mediated apoptotic cell death. In conclusion, this is the first report on the involvement of CYP and NOX pathways in gp120/MA-induced oxidative stress and apoptotic cell death in astrocytes, which has clinical implications in neurodegenerative diseases, including neuroAIDS. 相似文献
177.
Noah M Ivers Jacqueline Young Jill J Francis Jan Barnsley Baiju R Shah Ross E Upshur Jeremy M Grimshaw Merrick Zwarenstein 《Implementation science : IS》2013,8(1):142
Background
Audit and feedback to physicians is a commonly used quality improvement strategy, but its optimal design is unknown. This trial tested the effects of a theory-informed worksheet to facilitate goal setting and action planning, appended to feedback reports on chronic disease management, compared to feedback reports provided without these worksheets.Methods
A two-arm pragmatic cluster randomized trial was conducted, with allocation at the level of primary care clinics. Participants were family physicians who contributed data from their electronic medical records. The ‘usual feedback’ arm received feedback every six months for two years regarding the proportion of their patients meeting quality targets for diabetes and/or ischemic heart disease. The intervention arm received these same reports plus a worksheet designed to facilitate goal setting and action plan development in response to the feedback reports. Blood pressure (BP) and low-density lipoprotein cholesterol (LDL) values were compared after two years as the primary outcomes. Process outcomes measured the proportion of guideline-recommended actions (e.g., testing and prescribing) conducted within the appropriate timeframe. Intention-to-treat analysis was performed.Results
Outcomes were similar across groups at baseline. Final analysis included 20 physicians from seven clinics and 1,832 patients in the intervention arm (15% loss to follow up) and 29 physicians from seven clinics and 2,223 patients in the usual feedback arm (10% loss to follow up). Ten of 20 physicians completed the worksheet at least once during the study. Mean BP was 128/72 in the feedback plus worksheet arm and 128/73 in the feedback alone arm, while LDL was 2.1 and 2.0, respectively. Thus, no significant differences were observed across groups in the primary outcomes, but mean haemoglobin A1c was lower in the feedback plus worksheet arm (7.2% versus 7.4%, p<0.001). Improvements in both arms were noted over time for one-half of the process outcomes.Discussion
Appending a theory-informed goal setting and action planning worksheet to an externally produced audit and feedback intervention did not lead to improvements in patient outcomes. The results may be explained in part by passive dissemination of the worksheet leading to inadequate engagement with the intervention.Trial registration
ClinicalTrials.gov NCT00996645178.
179.
Kim M Handley Nathan C VerBerkmoes Carl I Steefel Kenneth H Williams Itai Sharon Christopher S Miller Kyle R Frischkorn Karuna Chourey Brian C Thomas Manesh B Shah Philip E Long Robert L Hettich Jillian F Banfield 《The ISME journal》2013,7(4):800-816
Stimulation of subsurface microorganisms to induce reductive immobilization of metals is
a promising approach for bioremediation, yet the overall microbial community response is
typically poorly understood. Here we used proteogenomics to test the hypothesis that
excess input of acetate activates complex community functioning and syntrophic
interactions among autotrophs and heterotrophs. A flow-through sediment column was
incubated in a groundwater well of an acetate-amended aquifer and recovered during
microbial sulfate reduction. De novo reconstruction of community sequences
yielded near-complete genomes of Desulfobacter (Deltaproteobacteria),
Sulfurovum- and Sulfurimonas-like Epsilonproteobacteria and
Bacteroidetes. Partial genomes were obtained for Clostridiales
(Firmicutes) and Desulfuromonadales-like Deltaproteobacteria.
The majority of proteins identified by mass spectrometry corresponded to
Desulfobacter-like species, and demonstrate the role of this organism in
sulfate reduction (Dsr and APS), nitrogen fixation and acetate oxidation to CO2
during amendment. Results indicate less abundant Desulfuromonadales, and possibly
Bacteroidetes, also actively contributed to CO2 production via the
tricarboxylic acid (TCA) cycle. Proteomic data indicate that sulfide was partially
re-oxidized by Epsilonproteobacteria through nitrate-dependent sulfide oxidation
(using Nap, Nir, Nos, SQR and Sox), with CO2 fixed using the reverse TCA cycle.
We infer that high acetate concentrations, aimed at stimulating anaerobic heterotrophy,
led to the co-enrichment of, and carbon fixation in Epsilonproteobacteria.
Results give an insight into ecosystem behavior following addition of simple organic
carbon to the subsurface, and demonstrate a range of biological processes and community
interactions were stimulated. 相似文献
180.
Plants have evolved complex biochemical mechanisms to counter threats from insect herbivory. Recent research has revealed an important role of roots in plant responses to above ground herbivory (AGH). The involvement of roots is integral to plant resistance and tolerance mechanisms. Roots not only play an active role in plant defenses by acting as sites for biosynthesis of various toxins and but also contribute to tolerance by storing photoassimilates to enable future regrowth. The interaction of roots with beneficial soil‐borne microorganisms also influences the outcome of the interaction between plant and insect herbivores. Shoot‐to‐root communication signals are critical for plant response to AGH. A better understanding of the role of roots in plant response to AGH is essential in order to develop a comprehensive picture of plant‐insect interactions. Here, we summarize the current status of research on the role of roots in plant response to AGH and also discuss possible signals involved in shoot‐to‐root communication. 相似文献