Prognostic Significance of Somatostatin Receptor Heterogeneity in Progressive Neuroendocrine Tumor Treated with Lu-177 DOTATOC or Lu-177 DOTATATE

European Journal of Nuclear Medicine and Molecular Imaging - One of the primary prerequisites for peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine tumors (NET) is the...     

Molecular alterations in the hippocampus after experimental subarachnoid hemorrhage

Patients with aneurysmal subarachnoid hemorrhage (SAH) frequently have deficits in learning and memory that may or may not be associated with detectable brain lesions. We examined mediators of long-term potentiation after SAH in rats to determine what processes might be involved. There was a reduction in synapses in the dendritic layer of the CA1 region on transmission electron microscopy as well as reduced colocalization of microtubule-associated protein 2 (MAP2) and synaptophysin. Immunohistochemistry showed reduced staining for GluR1 and calmodulin kinase 2 and increased staining for GluR2. Myelin basic protein staining was decreased as well. There was no detectable neuronal injury by Fluoro-Jade B, TUNEL, or activated caspase-3 staining. Vasospasm of the large arteries of the circle of Willis was mild to moderate in severity. Nitric oxide was increased and superoxide anion radical was decreased in hippocampal tissue. Cerebral blood flow, measured by magnetic resonance imaging, and cerebral glucose metabolism, measured by positron emission tomography, were no different in SAH compared with control groups. The results suggest that the etiology of loss of LTP after SAH is not cerebral ischemia but may be mediated by effects of subarachnoid blood such as oxidative stress and inflammation.     

Bilirubin and its oxidation products damage brain white matter

Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke.     

Metabolic determinants of lupus pathogenesis

The metabolism of healthy murine and more recently human immune cells has been investigated with an increasing amount of details. These studies have revealed the challenges presented by immune cells to respond rapidly to a wide variety of triggers by adjusting the amount, type, and utilization of the nutrients they import. A concept has emerged that cellular metabolic programs regulate the size of the immune response and the plasticity of its effector functions. This has generated a lot of enthusiasm with the prediction that cellular metabolism could be manipulated to either enhance or limit an immune response. In support of this hypothesis, studies in animal models as well as human subjects have shown that the dysregulation of the immune system in autoimmune diseases is associated with a skewing of the immunometabolic programs. These studies have been mostly conducted on autoimmune CD4⁺ T cells, with the metabolism of other immune cells in autoimmune settings still being understudied. Here we discuss systemic metabolism as well as cellular immunometabolism as novel tools to decipher fundamental mechanisms of autoimmunity. We review the contribution of each major metabolic pathway to autoimmune diseases, with a focus on systemic lupus erythematosus (SLE), with the relevant translational opportunities, existing or predicted from results obtained with healthy immune cells. Finally, we review how targeting metabolic programs may present novel therapeutic venues.     

The synergetic effect of hydrogel stiffness and growth factor on osteogenic differentiation

Cells respond to various chemical signals as well as environmental aspects of the extracellular matrix (ECM) that may alter cellular structures and functions. Hence, better understanding of the mechanical stimuli of the matrix is essential for creating an adjuvant material that mimics the physiological environment to support cell growth and differentiation, and control the release of the growth factor. In this study, we utilized the property of transglutaminase cross-linked gelatin (TG-Gel), where modification of the mechanical properties of TG-Gel can be easily achieved by tuning the concentration of gelatin. Modifying one or more of the material parameters will result in changes of the cellular responses, including different phenotype-specific gene expressions and functional differentiations. In this study, stiffer TG-Gels itself facilitated focal contact formation and osteogenic differentiation while soft TG-Gel promoted cell proliferation. We also evaluated the interactions between a stimulating factor (i.e. BMP-2) and matrix rigidity on osteogenesis both in vitro and in vivo. The results presented in this study suggest that the interactions of chemical and physical factors in ECM scaffolds may work synergistically to enhance bone regeneration.     

Large refractive index changes in ZIF-8 thin films of optical quality

ZIF-8 (zeolitic imidazolate framework-8) is a member of the growing family of metal–organic frameworks (MOFs). Homogeneous and crack-free ZIF-8 thin films of optical quality were crystallized on silicon and glass substrates. The refractive index of such ZIF-8 thin films in the complete visible light spectrum was directly determined for the first time. By incubating the porous films in different substances, the refractive index could be modulated over a wide range, two times larger than previously reported for MOF thin films. Reversible refractive index switching in ZIF-8 thin films was performed via the liquid and the gas phase. The ability to adjust the refractive index over a broad range enables the use of ZIF-8 films for applications in optical devices such as sensors, coatings for mirrors and lenses, or as an optical medium in more complex optical devices.

The refractive index (RI) of ZIF-8 thin films with optical quality was determined over the whole visible spectrum. The RI can be fine-tuned over a wide range by loading with different organic guest molecules for various optical applications.