189 research outputs found
Microfluidic Devices for Drug Delivery Systems and Drug Screening
Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase fluids, microfluidic technology enables the generation of highly stable, uniform, monodispersed particles with higher encapsulation efficiency. Since the existing preclinical models are inefficient drug screens for predicting clinical outcomes, microfluidic platforms might offer a more rapid and cost-effective alternative. Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D platforms mimic the in vivo cell systems in a simple, inexpensive manner, which allows high throughput and multiplexed drug screening at the cell, organ, and whole-body levels. In this review, the generation of appropriate drug or gene carriers including different particle types using different configurations of microfluidic devices is highlighted. Additionally, this paper discusses the emergence of fabricated microfluidic cell-free protein synthesis systems for potential use at point of care as well as cell-, organ-, and human-on-a-chip models as smart, sensitive, and reproducible platforms, allowing the investigation of the effects of drugs under conditions imitating the biological system
Polyaromatic hydrocarbons in pollution: a heart-breaking matter
Air pollution is associated with detrimental effects on human health, including decreased cardiovascular function. However, the causative mechanisms behind these effects have yet to be fully elucidated. Here we review the current epidemiological, clinical and experimental evidence linking pollution with cardiovascular dysfunction. Our focus is on particulate matter (PM) and the associated low molecular weight polycyclic aromatic hydrocarbons (PAHs) as key mediators of cardiotoxicity. We begin by reviewing the growing epidemiological evidence linking air pollution to cardiovascular dysfunction in humans. We next address the pollution‐based cardiotoxic mechanisms first identified in fish following the release of large quantities of PAHs into the marine environment from point oil spills (e.g. Deepwater Horizon). We finish by discussing the current state of mechanistic knowledge linking PM and PAH exposure to mammalian cardiovascular patho‐physiologies such as atherosclerosis, cardiac hypertrophy, arrhythmias, contractile dysfunction and the underlying alterations in gene regulation. Our aim is to show conservation of toxicant pathways and cellular targets across vertebrate hearts to allow a broad framework of the global problem of cardiotoxic pollution to be established. AhR; Aryl hydrocarbon receptor. Dark lines indicate topics discussed in this review. Grey lines indicate topics reviewed elsewhere.publishedVersio
Nanoparticle-Mediated Expression of an Angiogenic Inhibitor Ameliorates Ischemia-Induced Retinal Neovascularization and Diabetes-Induced Retinal Vascular Leakage
LEDGF1-326 Decreases P23H and Wild Type Rhodopsin Aggregates and P23H Rhodopsin Mediated Cell Damage in Human Retinal Pigment Epithelial Cells
P23H rhodopsin, a mutant rhodopsin, is known to aggregate and cause retinal degeneration. However, its effects on retinal pigment epithelial (RPE) cells are unknown. The purpose of this study was to determine the effect of P23H rhodopsin in RPE cells and further assess whether LEDGF(1-326), a protein devoid of heat shock elements of LEDGF, a cell survival factor, reduces P23H rhodopsin aggregates and any associated cellular damage.ARPE-19 cells were transiently transfected/cotransfected with pLEDGF(1-326) and/or pWT-Rho (wild type)/pP23H-Rho. Rhodopsin mediated cellular damage and rescue by LEDGF(1-326) was assessed using cell viability, cell proliferation, and confocal microscopy assays. Rhodopsin monomers, oligomers, and their reduction in the presence of LEDGF(1-326) were quantified by western blot analysis. P23H rhodopsin mRNA levels in the presence and absence of LEDGF(1-326) was determined by real time quantitative PCR.P23H rhodopsin reduced RPE cell viability and cell proliferation in a dose dependent manner, and disrupted the nuclear material. LEDGF(1-326) did not alter P23H rhodopsin mRNA levels, reduced its oligomers, and significantly increased RPE cell viability as well as proliferation, while reducing nuclear damage. WT rhodopsin formed oligomers, although to a smaller extent than P23H rhodopsin. Further, LEDGF(1-326) decreased WT rhodopsin aggregates.P23H rhodopsin as well as WT rhodopsin form aggregates in RPE cells and LEDGF(1-326) decreases these aggregates. Further, LEDGF(1-326) reduces the RPE cell damage caused by P23H rhodopsin. LEDGF(1-326) might be useful in treating cellular damage associated with protein aggregation diseases such as retinitis pigmentosa
A simulated annealing based genetic local search algorithm for multi-objective multicast routing problems
This paper presents a new hybrid evolutionary algorithm to solve multi-objective multicast routing problems in telecommunication networks. The algorithm combines simulated annealing based strategies and a genetic local search, aiming at a more flexible and effective exploration and exploitation in the search space of the complex problem to find more non-dominated solutions in the Pareto Front. Due to the complex structure of the multicast tree, crossover and mutation operators have been specifically devised concerning the features and constraints in the problem. A new adaptive mutation probability based on simulated annealing is proposed in the hybrid algorithm to adaptively adjust the mutation rate according to the fitness of the new solution against the average quality of the current population during the evolution procedure. Two simulated annealing based search direction tuning strategies are applied to improve the efficiency and effectiveness of the hybrid evolutionary algorithm. Simulations have been carried out on some benchmark multi-objective multicast routing instances and a large amount of random networks with five real world objectives including cost, delay, link utilisations, average delay and delay variation in telecommunication networks. Experimental results demonstrate that both the simulated annealing based strategies and the genetic local search within the proposed multi-objective algorithm, compared with other multi-objective evolutionary algorithms, can efficiently identify high quality non-dominated solution set for multi-objective multicast routing problems and outperform other conventional multi-objective evolutionary algorithms in the literature
Gantrez AN Nanoparticles for Ocular Delivery of Memantine: In vitro Release Evaluation in Albino Rabbits
Particle swarm optimization for the Steiner tree in graph and delay-constrained multicast routing problems
This paper presents the first investigation on applying a particle swarm optimization (PSO) algorithm to both the Steiner tree problem and the delay constrained multicast routing problem. Steiner tree problems, being the underlining models of many applications, have received significant research attention within the meta-heuristics community. The literature on the application of meta-heuristics to multicast routing problems is less extensive but includes several promising approaches. Many interesting research issues still remain to be investigated, for example, the inclusion of different constraints, such as delay bounds, when finding multicast trees with minimum cost. In this paper, we develop a novel PSO algorithm based on the jumping PSO (JPSO) algorithm recently developed by Moreno-Perez et al. (Proc. of the 7th Metaheuristics International Conference, 2007), and also propose two novel local search heuristics within our JPSO framework. A path replacement operator has been used in particle moves to improve the positions of the particle with regard to the structure of the tree. We test the performance of our JPSO algorithm, and the effect of the integrated local search heuristics by an extensive set of experiments on multicast routing benchmark problems and Steiner tree problems from the OR library. The experimental results show the superior performance of the proposed JPSO algorithm over a number of other state-of-the-art approaches
Rescue of Photoreceptor Degeneration by Curcumin in Transgenic Rats with P23H Rhodopsin Mutation
The P23H mutation in the rhodopsin gene causes rhodopsin misfolding, altered trafficking and formation of insoluble aggregates leading to photoreceptor degeneration and autosomal dominant retinitis pigmentosa (RP). There are no effective therapies to treat this condition. Compounds that enhance dissociation of protein aggregates may be of value in developing new treatments for such diseases. Anti-protein aggregating activity of curcumin has been reported earlier. In this study we present that treatment of COS-7 cells expressing mutant rhodopsin with curcumin results in dissociation of mutant protein aggregates and decreases endoplasmic reticulum stress. Furthermore we demonstrate that administration of curcumin to P23H-rhodopsin transgenic rats improves retinal morphology, physiology, gene expression and localization of rhodopsin. Our findings indicate that supplementation of curcumin improves retinal structure and function in P23H-rhodopsin transgenic rats. This data also suggest that curcumin may serve as a potential therapeutic agent in treating RP due to the P23H rhodopsin mutation and perhaps other degenerative diseases caused by protein trafficking defects
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