State-of-the-art microscopy to understand islets of Langerhans:what to expect next?

The discovery of Langerhans and microscopic description of islets in the pancreas were crucial steps in the discovery of insulin. Over the past 150 years, many discoveries in islet biology and type 1 diabetes have been made using powerful microscopic techniques. In the past decade, combination of new probes, animal and tissue models, application of new biosensors and automation of light and electron microscopic methods and other (sub)cellular imaging modalities have proven their potential in understanding the beta cell under (patho)physiological conditions. The imaging evolution, from fluorescent jellyfish to real-time intravital functional imaging, the revolution in automation and data handling and the increased resolving power of analytical imaging techniques are now converging. Here, we review innovative approaches that address islet biology from new angles by studying cells and molecules at high spatiotemporal resolution and in live models. Broad implementation of these cellular imaging techniques will shed new light on cause/consequence of (mal)function in islets of Langerhans in the years to come

Pegylated and nanoparticle-conjugated sulfonium salt photo triggers necrotic cell death

Alaa A Fadhel,1 Xiling Yue,1 Ebrahim H Ghazvini Zadeh,1 Mykhailo V Bondar,2 Kevin D Belfield3 1Department of Chemistry, University of Central Florida, Orlando, FL, USA; 2Institute of Physics NASU, Kiev, Ukraine; 3Department of Chemistry and Environmental Science, College of Science and Liberal Arts, New Jersey Institute of Technology, University Heights, Newark, NJ, USA Abstract: Photodynamic therapy (PDT) processes involving the production of singlet oxygen face the issue of oxygen concentration dependency. Despite high oxygen delivery, a variety of properties related to metabolism and vascular morphology in cancer cells result in hypoxic environments, resulting in limited effectiveness of such therapies. An alternative oxygen-independent agent whose cell cytotoxicity can be remotely controlled by light may allow access to treatment of hypoxic tumors. Toward that end, we developed and tested both polyethylene glycol (PEG)-functionalized and hydrophilic silica nanoparticle (SiNP)-enriched photoacid generator (PAG) as a nontraditional PDT agent to effectively induce necrotic cell death in HCT-116 cells. Already known for applications in lithography and cationic polymerization, our developed oxygen-independent PDT, whether free or highly monodispersed on SiNPs, generates acid when a one-photon (1P) or two-photon (2P) excitation source is used, thus potentially permitting deep tissue treatment. Our study shows that when conjugated to SiNPs with protruding amine functionalities (SiNP–PAG9), such atypical PDT agents can be effectively delivered into HCT-116 cells and compartmentalize exclusively in lysosomes and endosomes. Loss of cell adhesion and cell swelling are detected when an excitation source is applied, suggesting that SiNP–PAG9, when excited via near-infrared 2P absorption (a subject of future investigation), can be used as a delivery system to selectively induce cell death in oxygen-deprived optically thick tissue. Keywords: oxygen-independent photodynamic therapy, photoacid generator, silica nanoparticles, stimuli-responsive, sulfonium sal

Total synthesis of teixobactin

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