Oxidative stress mediated by lipid metabolism contributes to high glucose-induced senescence in retinal pigment epithelium.

Retinal pigment epithelium (RPE) dysfunction is thought to increase the risk of the development and progression of diabetic retinopathy (DR), the leading cause of blindness. However, the molecular mechanism behind high glucose-induced RPE cell damage is still blurred. We reported that ARPE-19 exposed to 25 mM glucose for 48 h did not induce apoptosis, but senescence validated by SA-ß-Gal staining, p21 expression and cell cycle distribution. High glucose also increased oxidant species that exerted a pivotal role in senescence, which could be relieved by the treatment with antioxidant N-acetylcysteine (NAC). The accumulation of lipid droplets and the increase of lipid oxidation were also observed in ARPE-19 treated with high glucose. And the supplementation of free fatty acids (FFAs) indicated that lipid metabolism was associated with the generation of hydrogen peroxide (H2O2) and subsequent senescence in ARPE-19. PI3K/Akt/mTOR signaling pathway was shown to be responsible for the accumulation of intracellular lipids by regulating fatty acid synthesis, which in turn controlled senescence. Furthermore, high glucose induced autophagy in ARPE-19 with the treatment of glucose for 48 h, and autophagy inhibitor hydroxychloroquine (HCQ) or bafilomycin further aggravated the senescence, accompanying by an increase in oxidant species. Whereas, prolonged high glucose exposure inhibited autophagy and increased apoptotic cells. Experiments above provide evidence that lipid metabolism plays an important role in oxidative stressed senescence of RPE.

Dihydrodiosgenin protects against experimental acute pancreatitis and associated lung injury through mitochondrial protection and PI3Kγ/Akt inhibition.

BACKGROUND AND PURPOSE: Acute pancreatitis (AP) is a painful and distressing disorder of the exocrine pancreas with no specific treatment. Diosgenyl saponins extracted from from Dioscorea zingiberensis C. H. Wright have been reported to protect against experimental models of AP. Diosgenin, or its derivatives are anti-inflammatory in various conditions. However, the effects of diosgenin and its spiroacetal ring opened analogue, dihydrodiosgenin (Dydio), on AP have not been determined. EXPERIMENTAL APPROACH: Effects of diosgenin and Dydio on sodium taurocholate hydrate (Tauro)-induced necrosis were tested, using freshly isolated murine pancreatic acinar cells. Effects of Dydio on mitochondrial dysfunction in response to Tauro, cholecystokinin-8 and palmitoleic acid ethyl ester were also assessed. Dydio (5 or 10 mg·kg-1 ) was administered after the induction in vivo of Tauro-induced AP (Wistar rats), caerulein-induced AP and palmitoleic acid plus ethanol-induced AP (Balb/c mice). Pancreatitis was assessed biochemically and histologically. Activation of pancreatic PI3Kγ/Akt was measured by immunoblotting. KEY RESULTS: Dydio inhibited Tauro-induced activation of the necrotic cell death pathway and prevented pancreatitis stimuli-induced mitochondrial dysfunction. Therapeutic administration of Dydio ameliorated biochemical and histopathological responses in all three models of AP through pancreatic mitochondrial protection and PI3Kγ/Akt inactivation. Moreover, Dydio improved pancreatitis-associated acute lung injury through preventing excessive inflammatory responses. CONCLUSION AND IMPLICATIONS: These data provide in vitro and in vivo mechanistic evidence that the diosgenin analogue, Dydio could be potential treatment for AP. Further medicinal optimization of diosgenin and its analogue might be a useful strategy for identifying lead candidates for inflammatory diseases.

Observation of localized surface plasmons and hybridized surface plasmon polaritons on self-assembled two-dimensional nanocavities.

Large-area patterning of periodic nanostructures using self-assembled nanospheres is of interest for fabricating low-cost plasmonic substrates, such as two-dimensional (2D) metallic gratings. Surface plasmon polaritons (SPPs) excited on metallic gratings have applications in biosensors, thin-film photovoltaics, photoelectrochemical cells, and photodetectors. Here we fabricated large-area metallic gratings using nanosphere lithography, and the geometry of gratings was controlled by the sphere size and distance between nanospheres. Both forward and backward propagating SPPs were observed using the grating coupling geometry. Furthermore, we reported the first observation of localized surface plasmons (LSPs) on this large-area metallic grating by both simulation and experimental studies. Such an LSP mode was confined in the 2D nanocavities and was not supported by dielectric gratings with the same 2D geometry.

Numerical Study of Complementary Nanostructures for Light Trapping in Colloidal Quantum Dot Solar Cells.

We have investigated two complementary nanostructures, nanocavity and nanopillar arrays, for light absorption enhancement in depleted heterojunction colloidal quantum dot (CQD) solar cells. A facile complementary fabrication process is demonstrated for patterning these nanostructures over the large area required for light trapping in photovoltaic devices. The simulation results show that both proposed periodic nanostructures can effectively increase the light absorption in CQD layer of the solar cell throughout the near-infrared region where CQD solar cells typically exhibit weak light absorption. The complementary fabrication process for implementation of these nanostructures can pave the way for large-area, inexpensive light trapping implementation in nanostructured solar cells.

Resonance-induced absorption enhancement in colloidal quantum dot solar cells using nanostructured electrodes.

The application of nanostructured indium-doped tin oxide (ITO) electrodes as diffraction gratings for light absorption enhancement in colloidal quantum dot solar cells is numerically investigated using finite-difference time-domain (FDTD) simulation. Resonant coupling of the incident diffracted light with supported waveguide modes in light absorbing layer at particular wavelengths predicted by grating far-field projection analysis is shown to provide superior near-infrared light trapping for nanostructured devices as compared to the planar structure. Among various technologically feasible nanostructures, the two-dimensional nano-branch array is demonstrated as the most promising polarization-independent structure and proved to be able to maintain its performance despite structural imperfections common in fabrication.

Practicability and safety of laser-assisted reduction surgery.

We have presented an innovative laser-assisted reduction surgery (LARS) based on plasma-induced ablation and photodisruption effects. In addition, we developed a laser operation system. Fetuses of mice from the Institute for Cancer Research that were immersed in physiological saline were irradiated by convergent-pulsed laser with a wavelength of 1064 nm, pulse width of 6 ns, and pulse energy of 50 mJ. The hearts of the postirradiated fetuses were significantly damaged, which resulted in rapid fetal death. We also substantiated the safety of LARS by analyzing the heat distribution of the induced laser pulse with thermal distribution equations. The results demonstrate that this innovative method for pregnancy reduction is feasible.