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Articles 1 - 8 of 8
Full-Text Articles in Chemicals and Drugs
Lipopolysaccharide Biosynthesis Without The Lipids: Substrate Recognition For Escherichia Coli Heptosyltransferasei, Daniel J. Czyzyk, Cassie Liu, Erika A. Taylor
Lipopolysaccharide Biosynthesis Without The Lipids: Substrate Recognition For Escherichia Coli Heptosyltransferasei, Daniel J. Czyzyk, Cassie Liu, Erika A. Taylor
Erika A. Taylor, Ph.D.
Heptosyltransferase I (HepI) is responsible for the transfer of l-glycero-d-manno-heptose to a 3-deoxy-α-D-oct-2-ulopyranosonic acid (Kdo) of the growing core region of lipopolysaccharide (LPS). The catalytic efficiency of HepI with the fully deacylated analogue of Escherichia coli HepI LipidA is 12-fold greater than with the fully acylated substrate, with a k(cat)/K(m) of 2.7 × 10(6) M(-1) s(-1), compared to a value of 2.2 × 10(5) M(-1) s(-1) for the Kdo(2)-LipidA substrate. Not only is this is the first demonstration that an LPS biosynthetic enzyme is catalytically enhanced by the absence of lipids, this result has significant implications for downstream enzymes that …
The Growth Suppressing Effects Of Girinimbine On Hepg2 Involve Induction Of Apoptosis And Cell Cycle Arrest, Syam Mohan
The Growth Suppressing Effects Of Girinimbine On Hepg2 Involve Induction Of Apoptosis And Cell Cycle Arrest, Syam Mohan
Syam Mohan
Murraya koenigii is an edible herb widely used in folk medicine. Here we report that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The MTT and LDH assay results showed that girinimbine decreased cell viability and increased cytotoxicity in a dose-and time-dependent manner selectively. Girinimbine-treated HepG2 cells showed typical morphological features of apoptosis, as observed from normal inverted microscopy and Hoechst 33342 assay. Furthermore, girinimbine treatment resulted in DNA fragmentation and elevated levels of caspase-3 in HepG2 cells. Girinimbine treatment also displayed a time-dependent accumulation of the Sub-G(0)/G(1) …
Does Inorganic Mercury Play A Role In Alzheimer's Disease? A Systematic Review And An Integrated Molecular Mechanism, Joachim Mutter, Annika Curth, Johannes Naumann, Richard Deth, Harald Walach
Does Inorganic Mercury Play A Role In Alzheimer's Disease? A Systematic Review And An Integrated Molecular Mechanism, Joachim Mutter, Annika Curth, Johannes Naumann, Richard Deth, Harald Walach
Richard Deth
Mercury is one of the most toxic substances known to humans. It has been introduced into the human environment and has also been widely used in medicine. Since circumstantial evidence exists that the pathology of Alzheimer’s disease (AD) might be in part caused or exacerbated by inorganic mercury, we conducted a systematic review using a comprehensive search strategy. Studies were screened according to a predefined protocol. Two reviewers extracted relevant data independent of each other. One thousand and forty one references were scrutinized, and 106 studies fulfilled the inclusion criteria. Most studies were case control or comparative cohort studies. Thirty-two …
Cost-Effectiveness Of Lowering Blood Pressure With A Fixed Combination Of Perindopril And Indapamide In Type 2 Diabetes Mellitus: An Advance Trial-Based Analysis, Paul Glasziou, Philip Clarke, Jan Alexander, Mohana Rajmokan, Elaine Beller, Mark Woodward, John Chalmers, Neil Poulter, Anushka Patel
Cost-Effectiveness Of Lowering Blood Pressure With A Fixed Combination Of Perindopril And Indapamide In Type 2 Diabetes Mellitus: An Advance Trial-Based Analysis, Paul Glasziou, Philip Clarke, Jan Alexander, Mohana Rajmokan, Elaine Beller, Mark Woodward, John Chalmers, Neil Poulter, Anushka Patel
Elaine Beller
Objective: To determine the cost-effectiveness of routine administration, irrespective of blood pressure (BP), of a fixed-dose combination of perindopril and indapamide to patients with type 2 diabetes mellitus.
Design, setting and participants: Prospective cost-effectiveness analysis within the Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trial, an international, multicentre, randomised controlled trial of 11 140 participants with type 2 diabetes randomly allocated to receive perindopril plus indapamide (4mg-1.25mg/day) or placebo.
Main outcome measures: Health-related quality-of-life measured by the EuroQol-5D, resource utilisation, and cost-effectiveness (cost per death averted at 4.3 years' average follow-up, and …
Spatiotemporal Effects Of A Controlled-Release Anti-Inflammatory Drug On The Cellular Dynamics Of Host Response, Tram T. Dang, Kaitlin M. Bratlie, Said R. Bogatyrev, Xiao Chen, Robert Langer, Daniel G. Anderson
Spatiotemporal Effects Of A Controlled-Release Anti-Inflammatory Drug On The Cellular Dynamics Of Host Response, Tram T. Dang, Kaitlin M. Bratlie, Said R. Bogatyrev, Xiao Chen, Robert Langer, Daniel G. Anderson
Kaitlin M. Bratlie
In general, biomaterials induce a non-specific host response when implanted in the body. This reaction has the potential to interfere with the function of the implanted materials. One method for controlling the host response is through local, controlled-release of anti-inflammatory agents. Herein, we investigate the spatial and temporal effects of an anti-inflammatory drug on the cellular dynamics of the innate immune response to subcutaneously implanted poly(lactic-co-glycolic) microparticles. Noninvasive fluorescence imaging was used to investigate the influence of dexamethasone drug loading and release kinetics on the local and systemic inhibition of inflammatory cellular activities. Temporal monitoring of host response showed that …
Automated Sequence- And Stereo-Specific Assignment Of Methyl-Labeled Proteins By Paramagnetic Relaxation And Methyl–Methyl Nuclear Overhauser Enhancement Spectroscopy, Vincenzo Venditti, Nicolas L. Fawzi, G. Marius Clore
Automated Sequence- And Stereo-Specific Assignment Of Methyl-Labeled Proteins By Paramagnetic Relaxation And Methyl–Methyl Nuclear Overhauser Enhancement Spectroscopy, Vincenzo Venditti, Nicolas L. Fawzi, G. Marius Clore
Vincenzo Venditti
Methyl-transverse relaxation optimized spectroscopy is rapidly becoming the preferred NMR technique for probing structure and dynamics of very large proteins up to ~1 MDa in molecular size. Data interpretation, however, necessitates assignment of methyl groups which still presents a very challenging and time-consuming process. Here we demonstrate that, in combination with a known 3D structure, paramagnetic relaxation enhancement (PRE), induced by nitroxide spin-labels incorporated at only a few surface-exposed engineered cysteines, provides fast, straightforward and robust access to methyl group resonance assignments, including stereoassignments for the methyl groups of leucine and valine. Neither prior assignments, including backbone assignments, for the …
A Structurally Driven Analysis Of Thiol Reactivity In Mammalian Albumins, Ottavia Spiga, Domenico Summa, Simone Cirri, Andrea Bernini, Vincenzo Venditti, Matteo De Chiara, Raffaella Priora, Simona Frosail, Antonios Margaritis, Danila Di Giuseppe, Paolo Di Simplicio, Neri Niccolai
A Structurally Driven Analysis Of Thiol Reactivity In Mammalian Albumins, Ottavia Spiga, Domenico Summa, Simone Cirri, Andrea Bernini, Vincenzo Venditti, Matteo De Chiara, Raffaella Priora, Simona Frosail, Antonios Margaritis, Danila Di Giuseppe, Paolo Di Simplicio, Neri Niccolai
Vincenzo Venditti
Understanding the structural basis of protein redox activity is still an open question. Hence, by using a structural genomics approach, different albumins have been chosen to correlate protein structural features with the corresponding reaction rates of thiol exchange between albumin and disulfide DTNB. Predicted structures of rat, porcine, and bovine albumins have been compared with the experimentally derived human albumin. High structural similarity among these four albumins can be observed, in spite of their markedly different reactivity with DTNB. Sequence alignments offered preliminary hints on the contributions of sequence-specific local environments modulating albumin reactivity. Molecular dynamics simulations performed on experimental …
Real-Time In Vivo Detection Of Biomaterial-Induced Reactive Oxygen Species, Minglin Ma, Wendy F. Liu, Kaitlin M. Bratlie, Tram Dang, Robert Langer, Daniel G. Anderson
Real-Time In Vivo Detection Of Biomaterial-Induced Reactive Oxygen Species, Minglin Ma, Wendy F. Liu, Kaitlin M. Bratlie, Tram Dang, Robert Langer, Daniel G. Anderson
Kaitlin M. Bratlie
The non-specific host response to implanted biomaterials is often a key challenge of medical device design. To evaluate biocompatibility, measuring the release of reactive oxygen species (ROS) produced by inflammatory cells in response to biomaterial surfaces is a well-established method. However, the detection of ROS in response to materials implanted in vivo has not yet been demonstrated. Here, we develop a bioluminescence whole animal imaging approach to observe ROS released in response to subcutaneously-implanted materials in live animals. We compared the real-time generation of ROS in response to two representative materials, polystyrene and alginate, over the course of 28 days. …