Organic ultraviolet filters regulate hyaluronan metabolism in human epidermal keratinocytes through the phosphatidylinositol 3-kinase pathway.

Chronic exposure of skin to ultraviolet (UV) radiation is responsible for skin ageing, which includes degradation of the epidermal and dermal layers. Filtering UV light is key in the sunscreen industry. We studied the effects of organic UV filters on hyaluronan (HA) metabolism and skin hydration in human HaCaT keratinocytes. The gene expression of HA receptors, HA synthase (HAS), hyaluronidase (HYAL), and water channel aquaporin 3 (AQP3) was evaluated by quantitative RT-PCR. The state of oxidative stress was determined by measuring the intracellular levels of reactive oxygen species (ROS). The results showed that five organic UV filters reduced the extracellular contents of HA, and a phosphatidylinositol 3-kinase (PI3K) inhibitor partially restored the decreased HA levels after octinoxate, octocrylene, and oxybenzone treatment. The expression levels of HA receptors, including cluster of differentiation 44 (CD44), receptor for hyaluronic acid-mediated motility (RHAMM), and toll-like receptors (TLRs), were determined. Avobenzone, octinoxate, oxybenzone, and padimate O exerted inhibitory effects on RHAMM expression. Oxybenzone led to a significant increase in CD44 and AQP3 expression. Both octinoxate and octocrylene increased TLR4 expression but decreased ROS accumulation by activating the PI3K pathway. However, the organic UV filters differentially regulated the mRNA expression of HAS and HYAL. Taken together, these results suggest that certain organic UV filters regulate HA metabolism in human keratinocytes in a PI3K pathway-dependent manner.

Detecting Effects of Low Levels of FCCP on Stem Cell Micromotion and Wound-Healing Migration by Time-Series Capacitance Measurement.

Electric cell-substrate impedance sensing (ECIS) has been used as a real-time impedance-based method to quantify cell behavior in tissue culture. The method is capable of measuring both the resistance and capacitance of a cell-covered microelectrode at various AC frequencies. In this study, we demonstrate the application of high-frequency capacitance measurement (f = 40 or 64 kHz) for the sensitive detection of both the micromotion and wound-healing migration of human mesenchymal stem cells (hMSCs). Impedance measurements of cell-covered electrodes upon the challenge of various concentrations of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), from 0.1 to 30 µM, were conducted using ECIS. FCCP is an uncoupler of mitochondrial oxidative phosphorylation (OXPHOS), thereby reducing mitochondrial ATP production. By numerically analyzing the time-series capacitance data, a dose-dependent decrease in hMSC micromotion and wound-healing migration was observed, and the effect was significantly detected at levels as low as 0.1 µM. While most reported works with ECIS use the resistance/impedance time series, our results suggest the potential use of high-frequency capacitance time series for assessing migratory cell behavior such as micromotion and wound-healing migration.

In vivo investigation of temporal effects and drug delivery induced by transdermal microneedles with optical coherence tomography.

Transdermal drug-delivery systems (TDDS) have been a growing field in drug delivery because of their advantages over parenteral and oral administration. Recent studies illustrate that microneedles (MNs) can effectively penetrate through the stratum corneum barrier to facilitate drug delivery. However, the temporal effects on skin and drug diffusion are difficult to investigate in vivo. In this study, we used optical coherence tomography (OCT) to observe the process by which MNs dissolve and to investigate the temporal effects on mouse skin induced by MNs, including the morphological and vascular changes. Moreover, the recovery process of the skin was observed with OCT. Additionally, we proposed a method to observe drug delivery by estimation of cross-correlation relationship between sequential 2D OCT images obtained at the same location, reflecting the variation in the backscattered intensity due to the diffusion of the rhodamine molecules encapsulated in MNs. Our observations supported the hypothesis that the temporal effects on skin due to MNs, the dissolution of MNs, and the drug diffusion process can be quantitatively evaluated with OCT. The results showed that OCT can be a potential tool for in vivo monitoring of effects and outcomes when MNs are used as a TDDS.

Enhanced Therapeutic Epidermal Growth Factor Receptor (EGFR) Antibody Delivery via Pulsed Ultrasound with Targeting Microbubbles for Glioma Treatment.

Pulsed-mode ultrasound (pUS) in combination with intravenously (IV) administered microbubbles (MBs) can enhance local drug delivery by temporarily enhancing capillary permeability. This study evaluates the use of epidermal growth factor receptor (EGFR)-targeting MBs after pUS treatment to enhance the effects of therapeutic-EGFR antibody delivery to glioma tumor cells in mice. Three animal groups were compared: (1) IV-injected non-targeting MBs, (2) IV-injected targeting MBs, and (3) IV-injected targeting MBs combined with pUS treatment. All animals were analyzed using high-frequency small-animal US imaging. The mean halftime of circulating targeting MBs was significantly increased from 3.13 min of targeting bubble alone to 5.86 min by targeting MBs combined with pUS treatment, compared to 2.34 min for non-targeting MBs. Compared to targeting bubble administration alone, pUS exposure prior to injection of targeting MBs was also significantly better at suppressing tumor growth when monitored for up to 35 days (p < 0.05). The final relative tumor volumes were 2664, 700, and 188 mm3 for non-targeting MBs, targeting MBs, and targeting MBs combined with pUS treatment, respectively. pUS treatment prolonged the mean circulatory halftime of targeting MBs and enhanced the anti-tumor effect of EGFR antibodies in a human glioma model in mice. Targeting MBs combined with pUS treatment thus has potential for enhanced therapeutic antibody delivery for facilitating anti-glioma treatment.

Magnetic gold-nanorod/ PNIPAAmMA nanoparticles for dual magnetic resonance and photoacoustic imaging and targeted photothermal therapy.

Nanomedicine can provide a multi-functional platform for image-guided diagnosis and treatment of cancer. Although gold nanorods (GNRs) have been developed for photoacoustic (PA) imaging and near infra-red (NIR) photothermal applications, their efficiency has remained limited by low thermal stability. Here we present the synthesis, characterization, and functional evaluation of non-cytotoxic magnetic polymer-modified gold nanorods (MPGNRs), designed to act as dual magnetic resonance imaging (MRI) and PA imaging contrast agents. In addition, their high magnetization allowed MPGNRs to be actively localized and concentrated by targeting with an external magnet. Finally, MPGNRs significantly enhanced the NIR-laser-induced photothermal effect due to their increased thermal stability. MPGNRs thus provide a promising new theranostic platform for cancer diagnosis and treatment by combining dual MR/PA imaging with highly effective targeted photothermal therapy.

Fabrication of patterned superbydrophobic polybenzoxazine hybrid surfaces.

The hydrophilicity of bis(3-allyl-3,4-dihydro-2H-1,3-benzoxazinyl)isopropane(B-ala) polybenzoxazine film and superhydrophobic polybenzoxazine-hybrid surface can be controlled through UV exposure to change the ratio of intra- to intermolecular hydrogen bonds. A fraction of the intramolecular hydrogen bonding of the as-cured sample will convert into intermolecular hydrogen bonding upon UV exposure and thus results in an increase of hydrophilicity. This simple method allows for manipulating the hydrophilicity at selected regions on a superhydrophobic polybenzoxazine hybrid surface to create a patterned surface with superhydrophobic and superhydrophilic regions. Additionally, we have found that the superhydrophobic polybenzoxazine-silica hybrid surface exhibits good adhesion of water droplets after UV exposure, which can be served as a "mechanical hand" to transfer water droplets from a superhydrophobic surface to a hydrophilic one.

Long-term prognostic effects of plasma epstein-barr virus DNA by minor groove binder-probe real-time quantitative PCR on nasopharyngeal carcinoma patients receiving concurrent chemoradiotherapy.

PURPOSE: To evaluate the long-term prognostic impact of plasma Epstein-Barr virus (EBV) DNA concentration measured by real-time quantitative polymerase chain reaction (RTQ-PCR) in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT). METHODS AND MATERIALS: Epstein-Barr virus DNA was retrospectively measured from stock plasma of 152 biopsy-proven NPC patients with Stage II-IV (M0) disease with a RTQ-PCR using the minor groove binder-probe. All patients received CCRT with a median follow-up of 78 months. We divided patients into three subgroups: (1) low pretreatment EBV DNA (<1,500 copies/mL) and undetectable posttreatment EBV DNA (pre-L/post-U), (2) high pretreatment EBV DNA (> or =1,500 copies/mL) and undetectable posttreatment EBV DNA (pre-H/post-U), and (3) low or high pretreatment EBV DNA and detectable posttreatment EBV DNA (pre-L or H/post-D) for prognostic analyses. RESULTS: Epstein-Barr virus DNA (median concentration, 573 copies/mL; interquartile range, 197-3,074) was detected in the pretreatment plasma of 94.1% (143/152) of patients. After treatment, plasma EBV DNA decreased or remained 0 for all patients and was detectable in 31 patients (20.4%) with a median concentration 0 copy/mL (interquartile range, 0-0). The 5-year overall survival rates of the pre-L/post-U, pre-H/post-U, and pre-L or H/post-D subgroups were 87.2%, 71.0%, and 38.7%, respectively (p < 0.0001). The relapse-free survival showed similar results with corresponding rates of 85.6%, 75.9%, and 26.9%, respectively (p < 0.0001). Multivariate Cox analysis confirmed the superior effects of plasma EBV DNA compared to other clinical parameters in prognosis prediction. CONCLUSION: Plasma EBV DNA is the most valuable prognostic factor for NPC. More chemotherapy should be considered for patients with persistently detectable EBV DNA after CCRT.