Mathematical model for promotion of wound closure with ATP release.

To computationally investigate the recent experimental finding such that extracellular ATP release caused by exogeneous mechanical forces promote wound closure, we introduce a mathematical model, the Cellular Potts Model (CPM), which is a popular discretized model on a lattice, where the movement of a "cell" is determined by a Monte Carlo procedure. In the experiment, it was observed that there is mechanosensitive ATP release from the leading cells facing the wound gap and the subsequent extracellular Ca influx. To model these phenomena, the Reaction-Diffusion equations for extracellular ATP and intracellular Ca concentrations are adopted and combined with CPM, where we also add a polarity term because the cell migration is enhanced in the case of ATP release.

Role of Skin Stretch on Local Vascular Permeability in Murine and Cell Culture Models.

Unlabelled: Excessive mechanical forces, particularly skin stretch, have been implicated in pathological cutaneous scarring. We hypothesize that this reflects, in part, stretch-induced vessel leakage that provokes prolonged wound/scar inflammation. However, this has never been observed directly.

A New Model for Specific Visualization of Skin Graft Neoangiogenesis Using Flt1-tdsRed BAC Transgenic Mice.

Background: Neovascularization plays a critical role in skin graft survival. Up to date, the lack of specificity to solely track the newly sprouting blood vessels has remained a limiting factor in skin graft transplantation models. Therefore, the authors developed a new model by using Flt1-tdsRed BAC transgenic mice.

Photodynamic Therapy Delays Cutaneous Wound Healing in Mice.

Background: Cutaneous wound healing is a complex, dynamic physiological process. Traditional methods of promoting wound healing are not always effective. Consequently, alternative modalities, such as photodynamic therapy (PDT), are needed.

Noncontact Phased-Array Ultrasound Facilitates Acute Wound Healing in Mice.

Background: The authors developed a noncontact low-frequency ultrasound device that delivers high-intensity mechanical force based on phased-array technology. It may aid wound healing because it is likely to be associated with lower risks of infection and heat-induced pain compared with conventional ultrasound methods. The authors hypothesized that the microdeformation it induces accelerates wound epithelialization.

Hyperforin/HP--Cyclodextrin Enhances Mechanosensitive Ca Signaling in HaCaT Keratinocytes and in Atopic Skin Ex Vivo Which Accelerates Wound Healing.

Cutaneous wound healing is accelerated by mechanical stretching, and treatment with hyperforin, a major component of a traditional herbal medicine and a known TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of ATP-Ca signaling in keratinocytes by hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of hyperforin for therapeutic purposes.

Mechanosensitive ATP release from hemichannels and Ca²⁺ influx through TRPC6 accelerate wound closure in keratinocytes.

Cutaneous wound healing is accelerated by exogenous mechanical forces and is impaired in TRPC6-knockout mice. Therefore, we designed experiments to determine how mechanical force and TRPC6 channels contribute to wound healing using HaCaT keratinocytes. HaCaT cells were pretreated with hyperforin, a major component of a traditional herbal medicine for wound healing and also a TRPC6 activator, and cultured in an elastic chamber.

Facile synthesis of highly water-soluble fullerenes more than half-covered by hydroxyl groups.

Using a novel hydrogen peroxide heating method, we synthesized milky white, water-soluble polyhydroxylated fullerenes (fullerenols) with 36-40 hydroxyl groups (estimated average) along with 8-9 secondary bound water molecules. The fullerenols exhibited high water solubility up to 58.9 mg/mL in a neutral (pH = 7) condition.

Water-soluble C60 fullerene prevents degeneration of articular cartilage in osteoarthritis via down-regulation of chondrocyte catabolic activity and inhibition of cartilage degeneration during disease development.

Objective: Studies have shown the roles of oxidative stress in the pathogenesis of osteoarthritis (OA) and induction of chondrocyte senescence during OA progression. The aim of this study was to examine the potential of a strong free-radical scavenger, water-soluble fullerene (C60), as a protective agent against catabolic stress-induced degeneration of articular cartilage in OA, both in vitro and in vivo.

Methods: In the presence or absence of C60 (100 microM), human chondrocytes were incubated with interleukin-1beta (10 ng/ml) or H2O2 (100 microM), and chondrocyte activity was analyzed.

Antioxidant activity of supramolecular water-soluble fullerenes evaluated by beta-carotene bleaching assay.

We investigated the antioxidant activity of supramolecular water-soluble fullerenes, polyvinylpyrrolidone (PVP)-entrapped C(60), and gamma-cyclodextrin (CD)-bi-capped C(60), based on comparable beta-carotene bleaching assay. Antioxidant activity against reactive oxygen species (ROS) generated by three different methods, (i) autoxidation of linoleic acid, (ii) hydrogen peroxide promoter, and (iii) photoirradiation, was evaluated as percent of inhibition relative to a control experiment in view of the bleaching rate constant (k(obs)) as well as the persistent absorbency of beta-carotene. Water-soluble fullerenes exhibit significant inhibitory effects on the oxidative discoloration of beta-carotene in any system.

Preclinical studies on safety of fullerene upon acute oral administration and evaluation for no mutagenesis.

Fullerenes characterized as an antioxidant are believed to reduce various reactive chemical species, such as free radicals, and their characteristic features have been disclosed to furnish many useful medical technologies. Despite the numerous applications for the biological efficacy of fullerenes, less is known about the toxicity of fullerenes in mammals. Hence, the protocol was designed to determine the acute oral median lethal dose and evaluate the acute toxicity of fullerenes when administrated as a single dose to Sprague-Dawley rats.

The water-soluble fullerene derivative "Radical Sponge" exerts cytoprotective action against UVA irradiation but not visible-light-catalyzed cytotoxicity in human skin keratinocytes.

Fullerene was entrapped in polyvinylpyrrolidone of 60-80 kDa at a molar ratio range of 0.42-0.67:1, resulting in a water-soluble derivative with a mean particle diameter of about 688 nm, named "Radical Sponge" because of its ROS-scavenging ability as previously demonstrated, and examined in the present study for its photo-biological actions toward human skin keratinocytes HaCaT.

Antioxidant effects of water-soluble fullerene derivatives against ultraviolet ray or peroxylipid through their action of scavenging the reactive oxygen species in human skin keratinocytes.

Chemically generated hydroxyl radicals were scavenged by PEG-modified fullerene, hydroxy-fullerene and isostearate-mixed fullerene as efficiently as ascorbic acid (Asc) or its 2-O-phosphorylated derivative (A2P) as shown by the DMPO-spin trap/ESR method. Enzymatically generated superoxide anion radicals were also scavenged by PEG-modified or PVP-entrapped fullerene similarly as done by Asc or A2P. Some reactive oxygen species (ROS) such as hydroperoxides and hydrogen peroxides were generated preferably in the nuclei of UVB-irradiated human skin keratinocytes HaCaT, and repressed by PVP- or gamma-cyclodextrin-fullerene.

Amination of ethers using chloramine-T hydrate and a copper(I) catalyst.

Amination of C-H bonds activated by ether oxygen atoms is facile with chloramine-T as nitrene source and copper(I) chloride in acetonitrile as catalyst. For cyclic ethers the hemiaminal products are generally stable and can be isolated pure. For acyclic ethers, the hemiaminal products, as expected, fragment with elimination of alcohol to yield imines.

Catalytic Diastereoselective Imidation of Diaryl Sulfides Bearing a Chiral Oxazolinyl Moiety with Chloramine T Trihydrate.

Up to 99 % de is obtained in the imidation of diaryl sulfides bearing a chiral oxazolinyl moiety at the ortho position. The corresponding N-p-tosylsulfimides are produced upon use of chloramine T trihydrate in the presence of Cu(OTf) as catalyst [Eq. (1)].