780 research outputs found
Furanone quorum-sensing inhibitors with potential as novel therapeutics against <i>Pseudomonas aeruginosa</i>
Kirigami Actuators
Thin elastic sheets bend easily and, if they are patterned with cuts, can
deform in sophisticated ways. Here we show that carefully tuning the location
and arrangement of cuts within thin sheets enables the design of mechanical
actuators that scale down to atomically-thin 2D materials. We first show that
by understanding the mechanics of a single, non-propagating crack in a sheet we
can generate four fundamental forms of linear actuation: roll, pitch, yaw, and
lift. Our analytical model shows that these deformations are only weakly
dependent on thickness, which we confirm with experiments at centimeter scale
objects and molecular dynamics simulations of graphene and MoS nanoscale
sheets. We show how the interactions between non-propagating cracks can enable
either lift or rotation, and we use a combination of experiments, theory,
continuum computational analysis, and molecular dynamics simulations to provide
mechanistic insights into the geometric and topological design of kirigami
actuators.Comment: Soft Matter, 201
The Role of Insulin in Wound Healing Process: Mechanism of Action and Pharmaceutical Applications
Albumin nano-encapsulation of caffeic acid phenethyl ester and piceatannol potentiated its ability to modulate HIF and NF-kB pathways and improves therapeutic outcome in experimental colitis
Mechanisms of Electrical Conductivity in Y(1-x)CaxBa2Cu3O6.1 System
Systematic studies of transport properties in deoxygenated
Y(1-x)CaxBa2Cu3O6.1 series allowed to propose a diagram of conductivity
mechanisms for this system. At intermediate temperature a variable range
hopping (VRH) in 2 dimensions prevails. At lower temperature VRH in the
presence of a Coulomb gap for smaller x and VRH in 2 dimensions for larger x
are found. In a vicinity of superconductivity we observe conductivity
proportional to \sqrt{T}. Thermally activated conductivity dominates at higher
temperature. This diagram may be universal for the whole family of undoped high
Tc related cuprates.Comment: 5 page
Effect of poly(ethylene glycol) on insulin stability and cutaneous cell proliferation in vitro following cytoplasmic delivery of insulin-loaded nanoparticulate carriers – A potential topical wound management approach
We describe the development of a nanoparticulate system, with variation of poly(ethylene glycol) (PEG) content, capable of releasing therapeutic levels of bioactive insulin for extended periods of time. Recombinant human insulin was encapsulated in poly(d,l-lactide-co-glycolide) nanoparticles, manufactured with variation in poly(ethylene glycol) content, and shown to be stable for 6days using SDS-PAGE, western blot and MALDI MS. To determine if insulin released from this sustained release matrix could stimulate migration of cell types normally active in dermal repair, a model wound was simulated by scratching confluent cultures of human keratinocytes (HaCaT) and fibroblasts (Hs27). Although free insulin was shown to have proliferative effect, closure of in vitro scratch fissures was significantly faster following administration of nano-encapsulated insulin. This effect was more pronounced in HaCaT cells when compared to Hs27 cells. Variation in PEG content had the greatest effect on NP size, with a lesser influence on scratch closure times. Our work supports a particulate uptake mechanism that provides for intracellular insulin delivery, leading to enhanced cell proliferation. When placed into an appropriate topical delivery vehicle, such as a hydrogel, the extended and sustained topical administration of active insulin delivered from a nanoparticulate vehicle shows promise in promoting tissue healing
Diffusive Release of Photosensitizing Agents (PS) from Novel PVA-Borate Semi-Solid Drug Carriers Through In Vitro Oral Streptococcus mutans Biofilm
Background: Streptococcus mutans, one of the agent of human dental caries, is particularly effective at forming biofilms on the hard tissues of the human oral cavity; the purpose of this study was to investigate and quantify the diffusional release of photosentising agents (PS): methylene blue (MB), toludine blue (TB), rose bengal (RB) and methyl orange (MO) from Polyvinyl alcohol (PVA)-borate semi-solid gels in the presence of in vitro oral Streptococcus mutans biofilm. Methods: S. mutans biofilm growths were ascertained to ensure proper dental plaque formation and were characterized using confocal microscopy. Release profiles for MB, TB, RB and MO-loaded PVA-borate semi-solids in the absence of biofilms were directly compared to their counterparts in the presence of S. mutans biofilms. In addition, their diffusion coefficients and resistances were determined. Results: The confocal imaging results showed that biofilms grown over a 5-day period had a generally uninterrupted film of colonies occupying the entire surface area of growth surface of a nylon mesh support with approximately 60 µm biofilm size. The overall diffusion resistance of all PVA-borate semi-solids in the presence of S. mutans biofilms was about 1.2 times lower than the diffusion resistance for PVAborate semi-solids in the absence of biofilms. The diffusion resistances for all studied PS, indicate that electrostatic forces and molecular size play an important part in controlled and sustained drug release from PVA-borate semi-solids. Conclusions: PVA-borate semi-solids as novel PSs carriers might offer an innovative delivery system in the treatment against Streptococcus mutans
Novel Ran-RCC1 inhibitory peptide-loaded nanoparticles have anti-cancer efficacy in vitro and in vivo
YesThe delivery of anticancer agents to their subcellular sites of action is a significant challenge
for effective cancer therapy. Peptides, which are integral to several oncogenic pathways, have
significant potential to be utilised as cancer therapeutics due to their selectivity, high potency
and lack of normal cell toxicity. Novel Ras protein-Regulator of chromosome condensation 1
(Ran-RCC1) inhibitory peptides designed to interact with Ran, a novel therapeutic target in
breast cancer, were delivered by entrapment into polyethylene glycol-poly (lactic-co-glycolic acid)
PEG-PLGA polymeric nanoparticles (NPs). A modified double emulsion solvent evaporation
technique was used to optimise the physicochemical properties of these peptide-loaded biodegradable
NPs. The anti-cancer activity of peptide-loaded NPs was studied in vitro using Ran-expressing
metastatic breast (MDA-MB-231) and lung cancer (A549) cell lines, and in vivo using Solid Ehrlich
Carcinoma-bearing mice. The anti-metastatic activity of peptide-loaded NPs was investigated using
migration, invasion and colony formation assays in vitro. A PEG-PLGA-nanoparticle encapsulating
N-terminal peptide showed a pronounced antitumor and anti-metastatic action in lung and breast
cancer cells in vitro and caused a significant reduction of tumor volume and associated tumor growth
inhibition of breast cancer model in vivo. These findings suggest that the novel inhibitory peptides
encapsulated into PEGylated PLGA NPs are delivered effectively to interact and deactivate Ran.
This novel Ran-targeting peptide construct shows significant potential for therapy of breast cancer
and other cancers mediated by Ran overexpression
The Biomechanical Role of Scaffolds in Augmented Rotator Cuff Tendon Repairs
Background
Scaffolds continue to be developed and used for rotator cuff repair augmentation; however, the appropriate scaffold material properties and/or surgical application techniques for achieving optimal biomechanical performance remains unknown. The objectives of the study were to simulate a previously validated spring-network model for clinically relevant scenarios to predict: (1) the manner in which changes to components of the repair influence the biomechanical performance of the repair and (2) the percent load carried by the scaffold augmentation component.
Materials and methods
The models were parametrically varied to simulate clinically relevant scenarios, namely, changes in tendon quality, altered surgical technique(s), and different scaffold designs. The biomechanical performance of the repair constructs and the percent load carried by the scaffold component were evaluated for each of the simulated scenarios.
Results
The model predicts that the biomechanical performance of a rotator cuff repair can be modestly increased by augmenting the repair with a scaffold that has tendon-like properties. However, engineering a scaffold with supraphysiologic stiffness may not translate into yet stiffer or stronger repairs. Importantly, the mechanical properties of a repair construct appear to be most influenced by the properties of the tendon-to-bone repair. The model suggests that in the clinical setting of a weak tendon-to-bone repair, scaffold augmentation may significantly off-load the repair and largely mitigate the poor construct properties.
Conclusions
The model suggests that future efforts in the field of rotator cuff repair augmentation may be directed toward strategies that strengthen the tendon-to-bone repair and/or toward engineering scaffolds with tendon-like mechanical properties
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