Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.     

Magnetically Guidable Proteinaceous Adhesive Microbots for Targeted Locoregional Therapeutics Delivery in the Highly Dynamic Environment of the Esophagus

The esophagus is a tubular-shaped muscular organ where swallowed fluids and muscular contractions constitute a highly dynamic environment. The turbulent, coordinated processes that occur through the oropharyngeal conduit can often compromise targeted administration of therapeutic drugs to a lesion, significantly reducing therapeutic efficacy. Here, magnetically guidable drug vehicles capable of strongly adhering to target sites using a bioengineered mussel adhesive protein (MAP) to achieve localized delivery of therapeutic drugs against the hydrodynamic physiological conditions are proposed. A suite of highly uniform microparticles embedded with iron oxide (IO) nanoparticles (MAP@IO MPs) is microfluidically fabricated using the genipin-mediated covalent cross-linking of bioengineered MAP. The MAP@IO MPs are successfully targeted to a specific region and prolongedly retained in the tubular-structured passageway. In particular, orally administered MAP@IO MPs are effectively captured in the esophagus in vivo in a magnetically guidable manner. Moreover, doxorubicin (DOX)-loaded MAP@IO MPs exhibit a sustainable DOX release profile, effective anticancer therapeutic activity, and excellent biocompatibility. Thus, the magnetically guidable locomotion and robust underwater adhesive properties of the proteinaceous soft microbots can provide an intelligent modular approach for targeted locoregional therapeutics delivery to a specific lesion site in dynamic fluid-associated tubular organs such as the esophagus.     

Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h⁻¹. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (c_e), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications.     

Solid phase crystallization of amorphous silicon on glass by thin film heater for thin film transistor (TFT) application

A new process for solid phase crystallization (SPC) of amorphous silicon (a-Si) using thin film heater is reported. With this localized Ti silicide thin film heater, we successfully crystallized 500 Å-thick a-Si in a few minutes without any thermal deformation of glass substrate. The size of crystallized silicon grain was abnormally big (30-40 μm). Polycrystalline thin film transistors (TFT) fabricated using this unique thin film heater showed better mobility than those of conventional ones by furnace annealing.     

NO emission characteristics in counterflow diffusion flame of blended fuel of H2/CO2/Ar

Flame structure and NO emission characteristics in counterflow diffusion flame of blended fuel of H₂/CO₂/Ar have been numerically simulated with detailed chemistry. The combination of H₂, CO₂ and Ar as fuel is selected to clearly display the contribution of hydrocarbon products to flame structure and NO emission characteristics due to the breakdown of CO₂. A radiative heat loss term is involved to correctly describe the flame dynamics especially at low strain rates. The detailed chemistry adopts the reaction mechanism of GRI 2.11, which consists of 49 species and 279 elementary reactions. All mechanisms including thermal, NO₂, N₂O and Fenimore are taken into account to separately evaluate the effects of CO₂ addition on NO emission characteristics. The increase of added CO₂ quantity causes flame temperature to fall since at high strain rates a diluent effect is prevailing and at low strain rates the breakdown of CO₂ produces relatively populous hydrocarbon products and thus the existence of hydrocarbon products inhibits chain branching. It is also found that the contribution of NO production by N₂O and NO₂ mechanisms are negligible and that thermal mechanism is concentrated on only the reaction zone. As strain rate and CO₂ quantity increase, NO production is remarkably augmented. Copyright © 2002 John Wiley & Sons, Ltd.