Primary deep cutaneous opportunistic mycoses in OTR occur mainly in the first two yr after transplantation, in renal transplant recipients, and in older patients.

Glioblastoma (GBM) is a particularly challenging brain tumor characterized by a heterogeneous, complex, and multicellular microenvironment, which represents a strategic network for treatment escape. Furthermore, the presence of GBM stem cells (GSCs) seems to contribute to GBM recurrence after surgery, and chemo- and/or radiotherapy. In this context, intercellular communication modalities play key roles in driving GBM therapy resistance. The presence of tunneling nanotubes (TNTs), long membranous open-ended channels connecting distant cells, has been observed in several types of cancer, where they emerge to steer a more malignant phenotype. Here, we discuss the current knowledge about the formation of TNTs between different cellular types in the GBM microenvironment and their potential role in tumor progression and recurrence. Particularly, we highlight two prospective strategies targeting TNTs as possible therapeutics: (i) the inhibition of TNT formation and (ii) a boost in drug delivery between cells through these channels. The latter may require future studies to design drug delivery systems that are exchangeable through TNTs, thus allowing for access to distant tumor niches that are involved in tumor immune escape, maintenance of GSC plasticity, and increases in metastatic potential.

The cerebral synthesis of cholesterol is mainly handled by astrocytes, which are also responsible for apoproteins’ synthesis and lipoproteins’ assembly required for the cholesterol transport in the brain parenchyma. In Alzheimer disease (AD), these processes are impaired, likely because of the astrogliosis, a process characterized by morphological and functional changes in astrocytes. Several ATP-binding cassette transporters expressed by brain cells are involved in the formation of nascent discoidal lipoproteins, but the effect of beta-amyloid (Aβ) assemblies on this process is not fully understood. In this study, we investigated how of Aβ1-42-induced astrogliosis affects the metabolism of cholesterol in vitro. We detected an impairment in the cholesterol efflux of reactive astrocytes attributable to reduced levels of ABCA1 transporters that could explain the decreased lipoproteins’ levels detected in AD patients. To approach this issue, we designed biomimetic HDLs and evaluated their performance as cholesterol acceptors. The results demonstrated the ability of apoA-I nanodiscs to cross the blood–brain barrier in vitro and to promote the cholesterol efflux from astrocytes, making them suitable as a potential supportive treatment for AD to compensate the depletion of cerebral HDLs.

Vascular oxidative stress is considered a worsening factor in the progression of Alzheimer’s disease (AD). Increased reactive oxygen species (ROS) levels promote the accumulation of amyloid-β peptide (Aβ), one of the main hallmarks of AD. In turn, Aβ is a potent inducer of oxidative stress. In early stages of AD, the concomitant action of oxidative stress and Aβ on brain capillary endothelial cells was observed to compromise the blood–brain barrier functionality. In this context, antioxidant compounds might provide therapeutic benefits. To this aim, we investigated the antioxidant activity of cerium oxide nanoparticles (CNP) in human cerebral microvascular endothelial cells (hCMEC/D3) exposed to Aβ oligomers. Treatment with CNP (13.9 ± 0.7 nm in diameter) restored basal ROS levels in hCMEC/D3 cells, both after acute or prolonged exposure to Aβ. Moreover, we found that the extent of CNP uptake by hCMEC/D3 was +43% higher in the presence of Aβ. Scanning electron microscopy and western blot analysis suggested that changes in microvilli structures on the cell surface, under pro-oxidant stimuli (Aβ or H2O2), might be involved in the enhancement of CNP uptake. This finding opens the possibility to exploit the modulation of endothelial microvilli pattern to improve the uptake of anti-oxidant particles designed to counteract ROS-mediated cerebrovascular dysfunctions.