Travelling Surface Acoustic Waves Microfluidics

AbstractIn this paper, we demonstrate the working principle of travelling surface acoustic waves (TSAWs) in a microfluidic system. The TSAWs were incorporated to separate polystyrene (PS) particles of variable diameters and perform controlled mixing of different chemicals for concentration gradient generation, both inside a polydimethylsiloxane (PDMS) microfluidic channel. The TSAWs generated an acoustic streaming flow (ASF) upon coupling with a liquid and exerted an acoustic radiation force (ARF) on the suspended particles. The ARF was theoretically estimated for PS microspheres suspended in water, and conditions for ARF dominance over ASF or vice versa were identified. Recently reported TSAW-based PS particles separation and gradient generation results by our group are summarized here

Establishment of an experimental model of ovalbumin-induced atopic dermatitis in canines

IntroductionA reliable standard model is required to evaluate the efficacy of new drugs for companion animals, especially dogs. Canine atopic dermatitis (cAD), also known as allergic inflammatory skin disease, is a common condition. Currently, the house dust mite animal model is used in the research of cAD; however, this model exhibits significant individual variation and is difficult to standardize. In this study, we used ovalbumin as an antigen to sensitize and stimulate dogs, thereby establishing a stable model mimicking the T-helper 2 (Th2) response seen in cAD. Our objective was to create a cAD model that could be employed to evaluate the efficacy of novel drugs and mimic the Th2 dominant allergic response observed in the pathogenesis of atopic dermatitis of dogs.MethodsIn this study, six beagles were used. Normal saline was applied to two animals, and ovalbumin to four, on their dorsal skin.ResultsThe ovalbumin-treated groups exhibited clinical cAD symptoms, such as pruritus and erythema. Moreover, plasma levels of the cAD markers immunoglobulin E and CCL17 chemokine were higher in the ovalbumin-treated group than in the vehicle control group. The skin thickness of the epidermis was significantly increased in the ovalbumin-treated group, with infiltration of inflammatory cells observed in the thickened dermis region. In conclusion, treatment of canine skin with an optimal concentration of ovalbumin induced typical cAD-like symptoms, and histological and molecular analyses confirmed an enhanced Th2-related immune response.ConclusionTherefore, we successfully established a suitable Th2-dominant response mimicking cAD, which will facilitate targeted research of atopic dermatitis in dogs

Chemical Targeting of GAPDH Moonlighting Function in Cancer Cells Reveals Its Role in Tubulin Regulation

SummaryGlycolytic enzymes are attractive anticancer targets. They also carry out numerous, nonglycolytic “moonlighting” functions in cells. In this study, we investigated the anticancer activity of the triazine small molecule, GAPDS, that targets the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDS showed greater toxicity against cancer cells compared to a known GAPDH enzyme inhibitor. GAPDS also selectively inhibited cell migration and invasion. Our analysis showed that GAPDS treatment reduced GAPDH levels in the cytoplasm, which would modulate the secondary, moonlighting functions of this enzyme. We then used GAPDS as a probe to demonstrate that a moonlighting function of GAPDH is tubulin regulation, which may explain its anti-invasive properties. We also observed that GAPDS has potent anticancer activity in vivo. Our study indicates that strategies to target the secondary functions of anticancer candidates may yield potent therapeutics and useful chemical probes

Mitochondria are physiologically maintained at close to 50 degrees C

In endothermic species, heat released as a product of metabolism ensures stable internal temperature throughout the organism, despite varying environmental conditions. Mitochondria are major actors in this thermogenic process. Part of the energy released by the oxidation of respiratory substrates drives ATP synthesis and metabolite transport, but a substantial proportion is released as heat. Using a temperature-sensitive fluorescent probe targeted to mitochondria, we measured mitochondrial temperature in situ under different physiological conditions. At a constant external temperature of 38 degrees C, mitochondria were more than 10 degrees C warmer when the respiratory chain (RC) was fully functional, both in human embryonic kidney (HEK) 293 cells and primary skin fibroblasts. This differential was abolished in cells depleted of mitochondrial DNA or treated with respiratory inhibitors but preserved or enhanced by expressing thermogenic enzymes, such as the alternative oxidase or the uncoupling protein 1. The activity of various RC enzymes was maximal at or slightly above 50 degrees C. In view of their potential consequences, these observations need to be further validated and explored by independent methods. Our study prompts a critical re-examination of the literature on mitochondria.Peer reviewe

Antitumor activity of sorafenib-incorporated nanoparticles of dextran/poly(dl-lactide-co-glycolide) block copolymer

Sorafenib-incoporated nanoparticles were prepared using a block copolymer that is composed of dextran and poly(DL-lactide-co-glycolide) [DexbLG] for antitumor drug delivery. Sorafenib-incorporated nanoparticles were prepared by a nanoprecipitation-dialysis method. Sorafenib-incorporated DexbLG nanoparticles were uniformly distributed in an aqueous solution regardless of the content of sorafenib. Transmission electron microscopy of the sorafenib-incorporated DexbLG nanoparticles revealed a spherical shape with a diameter < 300 nm. Sorafenib-incorporated DexbLG nanoparticles at a polymer/drug weight ratio of 40:5 showed a relatively uniform size and morphology. Higher initial drug feeding was associated with increased drug content in nanoparticles and in nanoparticle size. A drug release study revealed a decreased drug release rate with increasing drug content. In an in vitro anti-proliferation assay using human cholangiocarcinoma cells, sorafenib-incorporated DexbLG nanoparticles showed a similar antitumor activity as sorafenib. Sorafenib-incorporated DexbLG nanoparticles are promising candidates as vehicles for antitumor drug targeting

Large Oncocytic Adrenocortical Tumor with Uncertain Malignant Potential

Oncocytoma is a neoplasm consisting of oncocytes that is found in the salivary gland, kidney, and thyroid. Adrenocortical oncocytoma is particularly uncommon, and most cases reported are benign and nonfunctioning. Here, we report a 20 cm adrenal mass associated with necrosis that was identified as an oncocytic adrenocortical tumor with uncertain malignant potential through histopathological evaluation after its resection

Optical Shaping of Plasma Cavity for Controlled Laser Wakefield Acceleration

Laser wakefield accelerators rely on relativistically moving micron-sized plasma cavities that provide extremely high electric field >100GV/m. Here, we demonstrate transverse shaping of the plasma cavity to produce controlled sub-GeV electron beams, adopting laser pulses with an axially rotatable ellipse-shaped focal spot. We showed the control capability on electron self-injection, charge, and transverse profile of the electron beam by rotating the focal spot. We observed that the effect of the elliptical focal spot was imprinted in the profiles of the electron beams and the electron energy increased, as compared to the case of a circular focal spot. We performed 3D particle-in-cell (PIC) simulations which reproduced the experimental results and revealed dynamics of a new asymmetric self-injection process. This simple scheme offers a novel control method on laser wakefield acceleration to produce tailored electron beams and x-rays for various applications.Comment: 5 pages, 5 figure

4-O-Carboxymethylascochlorin Inhibits Expression Levels of on Inflammation-Related Cytokines and Matrix Metalloproteinase-9 Through NF–κB/MAPK/TLR4 Signaling Pathway in LPS-Activated RAW264.7 Cells

Toll-like receptor 4 (TLR4) and matrix metalloproteinase-9 (MMP-9) are known to play important roles in inflammatory diseases such as arteriosclerosis and plaque instability. The purpose of this study was to perform the effect of 4-O-carboxymethylascochlorin (AS-6) on MMP-9 expression in lipopolysaccharide (LPS)-induced murine macrophages and signaling pathway involved in its anti-inflammatory effect. Effect of AS-6 on MAPK/NF-κB/TLR4 signaling pathway in LPS-activated murine macrophages was examined using ELISA, Western blotting, reverse transcription polymerase chain reaction (RT-PCR) and fluorescence immunoassay. MMP-9 enzyme activity was examined by gelatin zymography. AS-6 significantly suppressed MMP-9 and MAPK/NF-κB expression levels in LPS-stimulated murine macrophages. Expression levels of inducible nitric oxide synthase (iNOS), COX2, MMP-9, JNK, ERK, p38 phosphorylation, and NF-κB stimulated by LPS were also decreased by AS-6. Moreover, AS-6 suppressed TLR4 expression and dysregulated LPS-induced activators of transcription signaling pathway. The results of this study showed that AS-6 can inhibit LPS-stimulated inflammatory response by suppressing TLR4/MAPK/NF-κB signals, suggesting that AS-6 can be used to induce the stability of atherosclerotic plaque and prevent inflammatory diseases in an in vitro model