SIRT7 Deficiency Protects against Aß42-Induced Apoptosis through the Regulation of NOX4-Derived Reactive Oxygen Species Production in SH-SY5Y Cells.

Alzheimer's disease (AD) is an age-related neurodegenerative disease that is characterized by irreversible memory loss and cognitive decline. The deposition of amyloid-ß (Aß), especially aggregation-prone Aß42, is considered to be an early event preceding neurodegeneration in AD. Sirtuins (SIRT1-7 in mammals) are nicotinamide adenine dinucleotide-dependent lysine deacetylases/deacylases, and several sirtuins play important roles in AD. However, the involvement of SIRT7 in AD pathogenesis is not known. Here, we demonstrate that SIRT7 mRNA expression is increased in the cortex, entorhinal cortex, and prefrontal cortex of AD patients. We also found that Aß42 treatment rapidly increased NADPH oxidase 4 (NOX4) expression at the post-transcriptional level, and induced reactive oxygen species (ROS) production and apoptosis in neuronal SH-SY5Y cells. In contrast, SIRT7 knockdown inhibited Aß42-induced ROS production and apoptosis by suppressing the upregulation of NOX4. Collectively, these findings suggest that the inhibition of SIRT7 may play a beneficial role in AD pathogenesis through the regulation of ROS production.

Delayed cerebral complications associated with endovascular catheter coil embolization for pulmonary venous shunts mimicking cerebral inflammatory diseases.

Introduction: Hydrophilic polymer embolism in the brain is a delayed complication of cerebral angiography or endovascular therapy. Herein, we report a rare case of a hydrophilic polymer embolism in the brain due to endovascular catheter coil embolization of pulmonary venous shunts. Case report: A 16-year-old female presented with headache, dizziness, nausea, and dysesthesia in the left upper limb. Brain magnetic resonance imaging (MRI) revealed multiple bilateral subcortical white matter lesions with nodular gadolinium enhancement lesions surrounded with edema. Two weeks before onset, the patient underwent endovascular catheter coil embolization with two coils for two systemic-to-pulmonary venous shunts. We suspected that her multiple cerebral lesions were delayed allergic complications due to a catheter hydrophilic polymer-coating embolism after endovascular catheter coil embolization. Corticosteroid treatment rapidly improved neurological symptoms and MRI findings. Conclusion: To avoid unnecessary brain biopsy, careful history taking of previous catheterization is essential among patients presenting with focal deficits and punctate-enhancing brain lesions for the diagnosis of hydrophilic polymer embolism.

Serum levels of leptin receptor in patients with malignant melanoma as a new tumor marker.

Leptin is known to be abnormally expressed in a variety of cancers, and leptin receptors have been reported to be expressed on human melanoma cells. In this study, we evaluated the possibility that the serum levels of leptin receptor could be a tumor marker of malignant melanoma (MM). Serum samples were obtained from 71 patients with MM, and the serum levels of leptin receptor were measured by double-determinant ELISA. Interestingly, serum levels of leptin receptor decreased gradually with the stages of MM, being highest at in situ and lowest at stage IV. There was also a trend of reverse correlation between tumor thickness and serum levels of leptin receptor. To our knowledge, this is the first report investigating the serum levels of leptin receptor in MM, and serum leptin receptor levels may be used as a useful tumor marker of MM.

Patterns of Reacted Adatoms in Adsorption of Acetonitrile on Si{111}-(7 × 7).

We report on the covalent binding of acetonitrile (CH3CN) on Si{111}-(7 × 7) at ∼300 K studied by scanning tunneling microscopy, thermal desorption spectroscopy, and first-principles theoretical calculations. The site-specific study makes it possible to unravel the site-by-site and step-by-step kinetics. A polarized CH3CN prefers to adsorb on the faulted half more frequently compared to on the unfaulted half. Moreover, a molecular CH3CN adsorbs four-times more preferably on the center adatom-rest atom (CEA-REA) pair than on the corner adatom-rest atom (COA-REA) pair. Such site selectivity, the number ratio of reacted-CEA/reacted-COA, depends on the number of reacted adatoms in the half-unit cell. The site selectivity and the resulting reacted-adatom patterns are understood well by considering a simple model. In this simple model, the molecular adsorption probability changes step-by-step and site-by-site with increasing reacted adatoms. Furthermore, our theoretical calculations are overall consistent with the experimental results. The site-selectivity of the adsorption of CH3CN on Si{111}-(7 × 7) is explained well by the chemical reactivity depending on the local conformation, the local density of states, and the interaction between polarized adsorbates.

Adsorption of Acetonitrile on Si(111)-(7 × 7).

The adsorption of acetonitrile (CH3CN) on Si(111)-(7 × 7) at a room temperature has been investigated using scanning tunneling microscopy (STM) and first-principles calculations. The site-specific information on adsorption enables us to understand the site-by-site and step-by-step adsorption mechanism. From theoretical simulations, the most stable configuration of CH3CN on Si(111)-(7 × 7) is found to be a molecularly chemisorbed CH3CN with the carbon and nitrogen atoms of CN bonded to the rest atom and adatom on the Si surface, respectively. Some chemisorption-induced features in the STM topographic image are assigned based on the theoretical calculations.

[Embolic stroke immediately after initial administration of intravitreal aflibercept].

A 72-year-old man was admitted to our hospital because of right upper limb monoplegia 8 hours after the initial intravitreal injection of aflibercept, which is an inhibitor of vascular endothelial growth factor. Magnetic resonance diffusion-weighted images showed recent ischemic lesions in the left corona radiata and the right superior frontal gyrus. Laboratory findings showed mild hyperfibrinolysis. A patent foramen ovale was diagnosed on transesophageal echocardiography; however, lower-extremity ultrasonography did not detect deep vein thrombosis. The source of embolism remained unknown. A possible mechanism of cerebral emboli in the present case was a rapidly induced hypercoagulative state due to transfer of aflibercept from the vitreous body to the systemic circulation.

CSF TACI and BAFF levels in patients with primary CNS lymphoma as novel diagnostic biomarkers.

We used an enzyme-linked immunosorbent assay to measure pretreatment B cell-activating factor belonging to the tumour necrosis factor family (BAFF) and transmembrane activator and CAML-interactor (TACI) levels in CSF and serum collected from patients with primary central nervous system lymphoma (PCNSL) and control groups. The decision tree analysis of CSF TACI and BAFF levels for patients with a PCNSL diagnosis showed 100% sensitivity and 100% specificity when we attempted to differentiate PCNSL from glioblastoma and CNS inflammatory diseases. The combination of CSF TACI and BAFF levels may thus be a novel and useful diagnostic biomarker of PCNSL.