Inhibition of 11β-HSD1 Expression by Insulin in Skin: Impact for Diabetic Wound Healing.

Chronic, non-healing wounds impose a great burden on patients, professionals and health care systems worldwide. Diabetes mellitus (DM) and obesity are globally highly prevalent metabolic disorders and increase the risk for developing chronic wounds. Glucocorticoids (GCs) are endogenous stress hormones that exert profound effects on inflammation and repair systems.

Influence of hyaluronic acid binding on the actin cortex measured by optical forces.

Melanoma cells are often surrounded by hyaluronic acid (HA) rich environments, which are considered to promote tumor progression and metastasis. Induced effects in compound materials consisting of cells embedded in an extracellular matrix have been studied, however, alterations of the single cells have never been addressed. Here, we explicitly addressed single cell properties and measured HA-induced biomechanical changes via deformations induced solely by optical forces.

Evaluating the toxicity of bDtBPP on CHO-K1 cells for testing of single-use bioprocessing systems considering media selection, cell culture volume, mixing, and exposure duration.

Single-use bioprocessing bags are gaining popularity due to ease of use, lower risk of contamination, and ease of process scale-up. Bis(2,4-di-tert-butylphenyl)phosphate (bDtBPP), a degradant of tris(2,4-di-tert-butylphenyl)phosphite, marketed as Irgafos 168®, which is an antioxidant stabilizer added to resins, has been identified as a potentially toxic leachate which may impact the performance of single-use, multilayer bioprocessing bags. In this study, the toxicity of bDtBPP was tested on CHO-K1 cells grown as adherent or suspended cells.

Determining iron oxide nanoparticle heating efficiency and elucidating local nanoparticle temperature for application in agarose gel-based tumor model.

Magnetic iron oxide nanoparticles (MNPs) have been developed for magnetic fluid hyperthermia (MFH) cancer therapy, where cancer cells are treated through the heat generated by application of a high frequency magnetic field. This heat has also been proposed as a mechanism to trigger release of chemotherapy agents. In each of these cases, MNPs with optimal heating performance can be used to maximize therapeutic effect while minimizing the required dosage of MNPs.

Potentially inappropriate medications (PIMs) in older hospital in-patients: Prevalence, contribution to hospital admission and documentation of rationale for continuation.

Aim: To establish prevalence, sequelae and documentation of potentially inappropriate medication (PIM) use in older hospital in-patients.

Methods: Notes of all patients ≥65 years old, admitted to our tertiary teaching hospital (January 2013), were retrospectively reviewed, and the Screening Tool of Older Persons' potentially inappropriate Prescriptions applied.

Results: Amongst 534 patients, 54.

A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity.

Keratin intermediate filaments (KIFs) protect the epidermis against mechanical force, support strong adhesion, help barrier formation, and regulate growth. The mechanisms by which type I and II keratins contribute to these functions remain incompletely understood. Here, we report that mice lacking all type I or type II keratins display severe barrier defects and fragile skin, leading to perinatal mortality with full penetrance.

Impact of magnetic field parameters and iron oxide nanoparticle properties on heat generation for use in magnetic hyperthermia.

Heating of nanoparticles (NPs) using an AC magnetic field depends on several factors, and optimization of these parameters can improve the efficiency of heat generation for effective cancer therapy while administering a low NP treatment dose. This study investigated magnetic field strength and frequency, NP size, NP concentration, and solution viscosity as important parameters that impact the heating efficiency of iron oxide NPs with magnetite (FeO) and maghemite (γ-FeO) crystal structures. Heating efficiencies were determined for each experimental setting, with specific absorption rates (SARs) ranging from 3.

Intramolecular anion effect in polyoxometalate-based organocatalysts: reactivity enhancement and chirality transfer by a metal oxide-organic cation interaction.

An α1 -Dawson polyanion bearing a lateral side chain with a 4-aminopyridine end group was synthesized. This organopolyoxometalate catalyzes the addition of indenyl allyl silanes to cinnamoyl fluorides. The polyanionic framework influences the organocatalyst activity and selectivity.

Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases.

Isolating a pure population of neural stem cells (NSCs) has been difficult since no exclusive surface markers have been identified for panning or FACS purification. Moreover, additional refinements for maintaining NSCs in culture are required, since NSCs generate a variety of neural precursors (NPs) as they proliferate. Here, we demonstrate that post-natal rat NPs express low levels of pro-apoptotic molecules and resist phosphatidylinositol 3'OH kinase and extracellular regulated kinase 1/2 inhibition as compared to late oligodendrocyte progenitors.

Magnetic Heating of Iron Oxide Nanoparticles and Magnetic Micelles for Cancer Therapy.

The inclusion of magnetic nanoparticles into block copolymer micelles was studied towards the development of a targeted, magnetically triggered drug delivery system for cancer therapy. Herein, we report the synthesis of magnetic nanoparticles and poly(ethylene glycol-b-caprolactone) block copolymers, and experimental verification of magnetic heating of the nanoparticles, self-assembly of the block copolymers to form magnetic micelles, and thermally-enhanced drug release. The semicrystalline core of the micelles melted at temperatures just above physiological conditions, indicating that they could be used to release a chemotherapy agent from a thermo-responsive polymer system.

Interactions of iron oxide nanoparticles with the immune system: challenges and opportunities for their use in nano-oncology.

Iron oxide (IO) nanoparticles hold great promise as diagnostic and therapeutic agents in oncology. Their intrinsic physical properties make IO nanoparticles particularly interesting for simultaneous drug delivery, molecular imaging, and applications such as localized hyperthermia. Multiple non-targeted IO nanoparticle preparations have entered clinical trials, but more exciting, new tumortargeted IO nanoparticle preparations are currently being tested in preclinical settings.

Self-buffering hybrid gold-polyoxometalate catalysts for the catalytic cyclization of acid-sensitive substrates.

Grafting of a gold complex to an organo-polyoxometalate delivers catalytically active bitopic hybrids. The gold end activates allenes, while the metal-oxide surface can capture protons (see scheme). The scope of the gold-catalyzed oxacyclization of allenols is expanded to highly sensitive tertiary benzylic alcohols.

Polymer micelles with crystalline cores for thermally triggered release.

Interest in the use of poly(ethylene glycol)-b-polycaprolactone diblock copolymers in a targeted, magnetically triggered drug delivery system has led to this study of the phase behavior of the polycaprolactone core. Four different diblock copolymers were prepared by the ring-opening polymerization of caprolactone from the alcohol terminus of poly(ethylene glycol) monomethylether, M(n) ≈ 2000. The critical micelle concentration depended on the degree of polymerization for the polycaprolactone block and was in the range of 2.

Synthesis and Characterization of Multifunctional Chitosan- MnFe₂O Nanoparticles for Magnetic Hyperthermia and Drug Delivery.

Multifunctional nanoparticles composed of MnFe₂O₄ were encapsulated in chitosan for investigation of system to combine magnetically-triggered drug delivery and localized hyperthermia for cancer treatment with the previously published capacity of MnFe₂O₄ to be used as an efficient MRI contrast agent for cancer diagnosis. This paper focuses on the synthesis and characterization of magnetic MnFe₂O₄ nanoparticles, their dispersion in water and their incorporation in chitosan, which serves as a drug carrier. The surface of the MnFe₂O₄ nanoparticles was modified with meso-2,3-di-mercaptosuccinic acid (DMSA) to develop stable aqueous dispersions.

Numerical study on the multi-region bio-heat equation to model magnetic fluid hyperthermia (MFH) using low Curie temperature nanoparticles.

This study develops and solves two-dimensional convective-conductive coupled partial differential equations based on Pennes' bio-heat transfer model using low Curie temperature nanoparticles (LCTNPs) to illustrate thermal behavior quantitatively within tumor-normal composite tissue by establishing a multi-region finite difference algorithm. The model combines NEel relaxation and temperature-variant saturation magnetization derived from Brillouin Equation and Curie-Weiss Law. The numerical results indicate that different deposition patterns of LCTNP and boundary conditions directly effect the steady state temperature distribution.

The domino multicomponent allylation reaction for the stereoselective synthesis of homoallylic alcohols.

Stereoselective allylations of carbonyl compounds such as aldehydes and ketones are useful but challenging reactions in organic chemistry. The resulting chiral secondary and tertiary homoallylic alcohols or ethers are valuable building blocks in the synthesis of biologically active natural compounds and pharmaceuticals. Although researchers have developed several methods for the facially selective allylation of aldehydes, the stereoselective allylation of ketones still poses a severe problem.

Magnetothermally-responsive nanomaterials: combining magnetic nanostructures and thermally-sensitive polymers for triggered drug release.

This paper reviews the design and development of magnetothermally-triggered drug delivery systems, whereby magnetic nanoparticles are combined with thermally-activated materials. By combining superparamagnetic nanoparticles with lower critical solution temperature (LCST) polymers, an alternating current (AC) magnetic field can be used to trigger localized heating in vivo, which in turn causes a phase change in the host polymer to allow diffusion and release of drugs. The use of magnetic nanoparticles for biomedical applications is reviewed, as well as the design of thermally-activated polymeric systems.

Developmental toxicity assessment of thermoresponsive poly(N-isopropylacrylamide-co-acrylamide) oligomers in CD-1 mice.

Background: Although polymers and hydrogels are used successfully in biomedical applications, including implants and drug delivery devices, smaller molecular weight oligomers, such as those investigated here, have not been extensively studied in vivo. Poly(N-isopropylacrylamide-co-acrylamide), or P(NIPAAm-co-AAm), has a unique thermoresponsive behavior and is under investigation as a novel drug delivery system for metastatic cancer treatment. To date, no studies have been published regarding the safety of P(NIPAAm-co-AAm) to the conceptus.

Modifying the release of proxyphylline from PVA hydrogels using surface crosslinking.

Drug release profiles were altered to prevent the initial burst effect or introduce a lag phase by creating surface crosslinked layers in poly(vinyl alcohol) (PVA) hydrogels. Confocal laser scanning microscopy (CLSM) confirmed the successful introduction of these surface crosslinked layers. The thickness and crosslinking density of the surface crosslinked layer were highly dependent on the surface crosslinking conditions (i.

Surface crosslinking for delayed release of proxyphylline from PHEMA hydrogels.

Delayed release systems find applications in chronotherapeutics and colon-specific delivery. They have also been considered suitable carriers for the oral delivery of peptides and proteins. In prior work, our research group has reported surface crosslinking as an effective technique to modify drug release profiles for poly(vinyl alcohol) (PVA) hydrogels, reducing the early burst effect in particular.

Combination of viral biology and nanotechnology: new applications in nanomedicine.

Viruses are well known for their ability to cause disease, but their beneficial usefulness as vectors for gene therapy have been noted as well. As an extension of their use in a gene therapy context, their combination with nanotechnology is starting to benefit many areas of science and medicine. These include nanofabrication and medical diagnostics, to name a few, as well as viro-nanotherapy, here defined as the combination of viral biology with nanotechnology to create new therapeutic avenues to treat disease.

Synthesis and characterization of grafted thermosensitive hydrogels for heating activated controlled release.

Poly(N-isopropylacrylamide), PNIPAAm, hydrogels are negatively thermosensitive which means that they have an expanded hydrogel structure at low temperatures and a shrunken structure at high temperatures. Based on this negative thermosensitivity of PNIPAAm, a drug delivery system with PNIPAAm oligomers grafted onto poly(hydroxyethyl methacrylate) PHEMA, a thermally nonresponsive polymer was designed. Poly(hydroxyethyl methacrylate-g-N-isopropylacrylamide), P(HEMA-g-NIPAAm) hydrogels were synthesized to control the release of an imbedded drug.