Disintegrable inorganic nanoclusters (GIONs) with gold seed (GS) coating of an iron oxide core with a primary nanoparticle size less than 6 nm were prepared for theranostic applications. The GIONs possessed a broad near-infrared (NIR) absorbance at ∼750 nm because of plasmon coupling between closely positioned GSs on the iron oxide nanoclusters (ION) surface, in addition to the ∼513 nm peak corresponding to the isolated GS. The NIR laser-triggered photothermal response of GIONs was found to be concentration-dependent with a temperature rise of ∼8.5 and ∼4.5 °C from physiological temperature for 0.5 and 0.25 mg/mL, respectively. The nanoclusters were nonhemolytic and showed compatibility with human umbilical vein endothelial cells up to a concentration of 0.7 mg/mL under physiological conditions. The nanoclusters completely disintegrated at a lysosomal pH of 5.2 within 1 month. With an acute increase of over 400% intracellular reactive oxygen species soon after γ-irradiation and assistance from Fenton reaction-mediated supplemental oxidative stress, GION treatment in conjunction with radiation killed ∼50% of PLC/PRF/5 hepatoma cells. Confocal microscopy images of these cells showed significant cytoskeletal and nuclear damage from radiosensitization with GIONs. The cell viability further decreased to ∼10% when they were sequentially exposed to the NIR laser followed by γ-irradiation. The magnetic and optical properties of the nanoclusters enabled GIONs to possess a T 2 relaxivity of ∼223 mM −1 s −1 and a concentration-dependent strong photoacoustic signal toward magnetic resonance and optical imaging. GIONs did not incur any organ damage or evoke an acute inflammatory response in healthy C57BL/6 mice. Elemental analysis of various organs indicated differential clearance of gold and iron via both renal and hepatobiliary routes.
Background: Human stomach is a highly specialised organ with distinct types of glands and microscopic features for its physiological activity. This study aimed to assess the chronological order in the development of different layers and the cyto-differentiation of various glandular cells in 50 fetuses from 12 weeks of gestation till term.Methods: Tissue was taken from cardiac, body and pylorus to investigate with light and confocal microscopy.Results: The gastric gland formation began as an indentation of the surface epithelium, gastric pit and simultaneous development of glandular buds in the mucosa. The pyloric glands preceded the development of cardiac and gastric glands showing retro cranial sequence of development. In contrast, the muscularis externa showed the classical craniocaudal model of development with oblique layer in the cardiac region by 14 weeks and body region by 16 weeks of gestation. The parietal cells were well developed by 12 weeks and the chief cells by 16 weeks with prominent secretory granules. In addition, the pyloric sphincter was a clearly defined anatomical sphincter developed by whorling of the inner circular layer at the pyloric end of the stomach evident from 12 weeks of gestation.Conclusions: The results showed that the significant cellular morphogenesis occurred between 12-20 weeks of gestation. This aggregated data will serve as a catalyst in the understanding intricacy of embryogenesis, pathogenesis tracing of congenital anomalies and invention of new drugs.
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