Fabrication and Evaluation of Magnetic Micro actuators for Implantable Self-Clearing Glaucoma Drainage Devices

According to the World Health Organization, glaucoma is the second leading cause of blindness in the world. It currently affects more than 2.7 million people in the United States alone and over 79.6 million people worldwide are estimated to be inflicted by this debilitating disease by 2020. Glaucoma patients are often characterized with elevated intraocular pressure (IOP) and are treated with implantation of glaucoma drainage devices (GDD) to maintain optimum IOP. Although initially effective at delaying glaucoma progression, contemporary GDD often lead to numerous complications and only 50% of implanted devices remain functional after 5 years. Biofouling is seen to be one of the leading cause for the failure of GDDs. In order to overcome biological blockage, we propose a self-clearing glaucoma drainage device using integrated magnetic microactuators. Here we report on the maskless photolithographic fabrication results of magnetic microactuators to be integrated into a bespoke GDD. The maskless photography enabled rapid prototyping of microdevices using low-cost materials in contrast to conventional lithographic methods. The fabricated devices were able to produce maximum deflection of 57.9 degree at magnetic field strength of 32.6 kA/m. The static response of the fabricated devices was compared with the theoretical data

Intense ultraviolet emission from needle-like WO3 nanostructures synthesized by noncatalytic thermal evaporation

Photoluminescence measurements showed that needle-like tungsten oxide nanostructures synthesized at 590°C to 750°C by the thermal evaporation of WO3 nanopowders without the use of a catalyst had an intense near-ultraviolet (NUV) emission band that was different from that of the tungsten oxide nanostructures obtained in other temperature ranges. The intense NUV emission might be due to the localized states associated with oxygen vacancies and surface states

Improved application of the electrophoretic tissue clearing technology, CLARITY, to intact solid organs including brain, pancreas, liver, kidney, lung, and intestine

Background: Mapping of tissue structure at the cellular, circuit, and organ-wide scale is important for understanding physiological and biological functions. A bio-electrochemical technique known as CLARITY used for three-dimensional anatomical and phenotypical mapping within transparent intact tissues has been recently developed. This method provided a major advance in understanding the structure-function relationships in circuits of the nervous system and organs by using whole-body clearing. Thus, in the present study, we aimed to improve the original CLARITY procedure and developed specific CLARITY protocols for various intact organs. Results: We determined the optimal conditions for reducing bubble formation, discoloration, and depositing of black particles on the surface of tissue, which allowed production of clearer organ images. We also determined the appropriate replacement cycles of clearing solution for each type of organ, and convincingly demonstrated that 250–280 mA is the ideal range of electrical current for tissue clearing. We then acquired each type of cleared organs including brain, pancreas, liver, lung, kidney, and intestine. Additionally, we determined the images of axon fibers of hippocampal region, the Purkinje layer of cerebellum, and vessels and cellular nuclei of pancreas. Conclusions: CLARITY is an innovative biochemical technology for the structural and molecular analysis of various types of tissue. We developed improved CLARITY methods for clearing of the brain, pancreas, lung, intestine, liver, and kidney, and identified the appropriate experimental conditions for clearing of each specific tissue type. These optimized methods will be useful for the application of CLARITY to various types of organs. Electronic supplementary material The online version of this article (doi:10.1186/s12861-014-0048-3) contains supplementary material, which is available to authorized users

Magnetically Actuated Cell Stretching Platform to Induce Phenotypic Changes in Metastatic Cells

Although metastasis is responsible for about 90% of cancer deaths, only few in vitro models can be used to evaluate dynamic behaviors of metastatic cancer cells. Many studies have shown that mechanical stimuli can trigger various cellular responses such as gene and protein expression, which could lead to changes in cellular phenotype. Similarly, metastasized breast cancer cells in the lung tissue are constantly stretched by cyclic mechanical stress due to breathing, which alters cellular morphology and proliferation state. Such transitions can make the secondary tumors resistant to the chemotherapy used to effectively treat the primary tumors. In this work, we developed an in vitro tumor microenvironment that simulates in vivo respiration to investigate the mechanism of the phenotypic changes of metastatic breast cancer cells due to mechanical stimulation. We designed and fabricated magnetic microactuators using maskless photolithography technique to stretch tumor cells. Next, we coated fibronectin fibrils over the gaps of microactuators to mimic natural ECM environment and seeded tumor cells on the fibronectin mesh to generate a tumor microenvironment. As a result, the amount of strain that our microdevice could apply on the fibronectin mesh corresponded to the amount of strain experienced during normal respiration. In conclusion, the magnetically actuated in vitro cell stretching platform can provide precise strain control over a large actuation range to mimic mechanical stimulation in the lung. In the future, we will evaluate potential changes in metastatic cell phenotype and provide additional insights on the mechanism of secondary tumor drug resistance

Towards smart self-clearing glaucoma drainage device.

For patients who are unresponsive to pharmacological treatments of glaucoma, an implantable glaucoma drainage devices (GDD) are often used to manage the intraocular pressure. However, the microscale channel that removes excess aqueous humor from the anterior chamber often gets obstructed due to biofouling, which necessitates additional surgical intervention. Here we demonstrate the proof-of-concept for smart self-clearing GDD by integrating magnetic microactuators inside the drainage tube of GDD. The magnetic microactuators can be controlled using externally applied magnetic fields to mechanically clear biofouling-based obstruction, thereby eliminating the need for surgical intervention. In this work, our prototype magnetic microactuators were fabricated using low-cost maskless photolithography to expedite design iteration. The fabricated devices were evaluated for their static and dynamic mechanical responses. Using transient numerical analysis, the fluid–structure interaction of our microactuator inside a microtube was characterized to better understand the amount of shear force generated by the device motion. Finally, the anti-biofouling performance of our device was evaluated using fluorescein isothiocyanate labeled bovine serum albumin. The microactuators were effective in removing proteinaceous film deposited on device surface as well as on the inner surface of the microchannel, which supports our hypothesis that a smart self-clearing GDD may be possible by integrating microfabricated magnetic actuators in chronically implanted microtubes

Effect of Achyranthes bidentata

The present study investigated the antiobesity effect of Achyranthes bidentata Blume root water extract in a 3T3-L1 adipocyte differentiation model and rats fed with a high-fat diet. To investigate the effect of Achyranthes bidentata Blume on adipogenesis in vitro, differentiating 3T3-L1 cells in adipocyte-induction media were treated every two days with Achyranthes bidentata Blume at various concentrations (1 to 25 μg/mL) for eight days. We found that Achyranthes bidentata Blume root inhibited 3T3-L1 adipocyte differentiation without affecting cell viability, and Western blot analysis revealed that phospho-Akt expression was markedly decreased, whereas there was no significant change in perilipin expression. Furthermore, administration of Achyranthes bidentata Blume root (0.5 g/kg body weight for six weeks) to rats fed with a high-fat diet significantly reduced body weight gain without affecting food intake, and the level of triglyceride was significantly decreased when compared to those in rats fed with only a high-fat diet. These results suggest that Achyranthes bidentata Blume root water extract could have a beneficial effect on inhibition of adipogenesis and controlling body weight in rats fed with a high-fat diet

Anti-biofouling implantable catheter using thin-film magnetic microactuators

Here we report on the development of polyimide-based flexible magnetic actuators for actively combating biofouling that occurs in many chronically implanted devices. The thin-film flexible devices are microfabricated and integrated into a single-pore silicone catheter to demonstrate a proof-of-concept for a self-clearing smart catheter. The static and dynamic mechanical responses of the thin-film magnetic microdevices were quantitatively measured and compared to theoretical values. The mechanical fatigue properties of these polyimide-based microdevices were also characterized up to 300 million cycles. Finally, the biofouling removal capabilities of magnetically powered microdevices were demonstrated using bovine serum albumin and bioconjugated microbeads. Our results indicate that these thin-film microdevices are capable of significantly reducing the amount of biofouling. At the same time, we demonstrated that these microdevices are mechanically robust enough to withstand a large number of actuation cycles during its chronic implantation

Bee Venom Mitigates Cisplatin-Induced Nephrotoxicity by Regulating CD4 +

Cisplatin is used as a potent anticancer drug, but it often causes nephrotoxicity. Bee venom (BV) has been used for the treatment of various inflammatory diseases, and its renoprotective action was shown in NZB/W mice. However, little is known about whether BV has beneficial effects on cisplatin-induced nephrotoxicity and how such effects might be mediated. In the present study, the BV-injected group showed a significant increase in the population of Tregs in spleen. Although there was no significant difference in the numbers of Tregs 3 days after cisplatin injection between the BV- and PBS-injected groups, more migration of Tregs into the kidney was observed 6 hours after cisplatin administration in BV group than in PBS group. In addition, BV-injected mice showed reduced levels of serum creatinine, blood urea nitrogen, renal tissue damage, proinflammatory cytokines, and macrophage infiltration into the kidney 3 days after cisplatin administration. These renoprotective effects were abolished by the depletion of Tregs. The anticancer effect of repeated administrations of cisplatin was not affected by BV injection. These results suggest that BV has protective effects on cisplatin-induced nephrotoxicity in mice, at least in part, through the regulation of Tregs without a big influence on the antitumor effects of cisplatin

The Effects of Maekmoondong-Tang on Cockroach Extract-Induced Allergic Asthma

Maekmoondong-tang (MMDT) has long been used in Asian countries to treat respiratory diseases. However, the precise mechanisms underlying its effects on asthma are unknown. This study was conducted to evaluate the protective effects of MMDT in a cockroach allergen (CKA-)induced animal model of allergic asthma. After being challenged with CKA, the number of macrophages, eosinophils, neutrophils, lymphocytes, and total cells in the bronchoalveolar lavage fluid (BALF) was evaluated. The Th2 specific cytokines IL-4, IL-5, and IL-13 were also analyzed in BALF along with IgE levels in serum. For histological analysis, hematoxylin and eosin (H&E) staining, periodic acid-Schiff (PAS) staining, and immunohistochemical staining were performed. In addition, airway hyperresponsiveness was assessed by noninvasive plethysmography. The cellular profiles and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly decreased in the MMDT-treated groups compared with the cockroach extract-injected (CKA) groups. In addition, the IgE, IL-4, IL-5, and IL-13 levels were significantly decreased in the MMDT group. MMDT treatment also significantly attenuated airway hyperresponsiveness. These results demonstrated that MMDT significantly reduced the hallmark signs of asthma: elevated serum IgE, airway eosinophilia, airway remodeling, mucus hypersecretion, and airway hyperresponsiveness. The remarkable antiasthmatic effects of MMDT suggest its therapeutic potential in allergic asthma treatment