In Vivo Efficacy of a Nanoconjugated Glycopeptide Antibiotic in Silkworm Larvae Infected by .

To contrast the rapid spread of antibiotic resistance in bacteria, new alternative therapeutic options are urgently needed. The use of nanoparticles as carriers for clinically relevant antibiotics represents a promising solution to potentiate their efficacy. In this study, we used larvae for the first time as an animal model for testing a nanoconjugated glycopeptide antibiotic (teicoplanin) against infection.

Dental pulp mesenchymal stem cell (DPSCs)-derived soluble factors, produced under hypoxic conditions, support angiogenesis via endothelial cell activation and generation of M2-like macrophages.

Background: Cell therapy has emerged as a revolutionary tool to repair damaged tissues by restoration of an adequate vasculature. Dental Pulp stem cells (DPSC), due to their easy biological access, ex vivo properties, and ability to support angiogenesis have been largely explored in regenerative medicine.

Methods: Here, we tested the capability of Dental Pulp Stem Cell-Conditioned medium (DPSC-CM), produced in normoxic (DPSC-CM Normox) or hypoxic (DPSC-CM Hypox) conditions, to support angiogenesis via their soluble factors.

Notch3-regulated microRNAs impair CXCR4-dependent maturation of thymocytes allowing maintenance and progression of T-ALL.

Malignant transformation of T-cell progenitors causes T-cell acute lymphoblastic leukemia (T-ALL), an aggressive childhood lymphoproliferative disorder. Activating mutations of Notch, Notch1 and Notch3, have been detected in T-ALL patients. In this study, we aimed to deeply characterize hyperactive Notch3-related pathways involved in T-cell dynamics within the thymus and bone marrow to propose these processes as an important step in facilitating the progression of T-ALL.

Cardiac Aging Is Promoted by Pseudohypoxia Increasing p300-Induced Glycolysis.

Background: Heart failure is typical in the elderly. Metabolic remodeling of cardiomyocytes underlies inexorable deterioration of cardiac function with aging: glycolysis increases at the expense of oxidative phosphorylation, causing an energy deficit contributing to impaired contractility. Better understanding of the mechanisms of this metabolic switching could be critical for reversing the condition.

Energy Transfer from Magnetic Iron Oxide Nanoparticles: Implications for Magnetic Hyperthermia.

Magnetic iron oxide nanoparticles (IONPs) have gained momentum in the field of biomedical applications. They can be remotely heated via alternating magnetic fields, and such heat can be transferred from the IONPs to the local environment. However, the microscopic mechanism of heat transfer is still debated.

Iron Oxide Nanoparticles with and without Cobalt Functionalization Provoke Changes in the Transcription Profile via Epigenetic Modulation of Enhancer Activity.

Despite the progress in the field of nanotoxicology, much about the cellular mechanisms that mediate the adverse effects of nanoparticles (NPs) and, in particular, the possible role of epigenetics in nanotoxicity, remains to be clarified. Therefore, we studied the changes occurring in the genome-wide distribution of H3K27ac, H3K4me1, H3K9me2, and H3K27me3 histone modifications and compared them with the transcriptome after exposing NIH3T3 cells to iron-based magnetic NPs (i.e.

A chromEM-staining protocol optimized for cardiac tissue.

Three-dimensional (3D) chromatin organization has a key role in defining the transcription program of cells during development. Its alteration is the cause of gene expression changes responsible for several diseases. Thus, we need new tools to study this aspect of gene expression regulation.

CCRL2 Expression by Specialized Lung Capillary Endothelial Cells Controls NK-cell Homing in Lung Cancer.

Patterns of receptors for chemotactic factors regulate the homing of leukocytes to tissues. Here we report that the CCRL2/chemerin/CMKLR1 axis represents a selective pathway for the homing of natural killer (NK) cells to the lung. C-C motif chemokine receptor-like 2 (CCRL2) is a nonsignaling seven-transmembrane domain receptor able to control lung tumor growth.

Adipose mesenchymal stem cell-derived soluble factors, produced under hypoxic condition, efficiently support in vivo angiogenesis.

Tissue regeneration or healing both require efficient vascularization within a tissue-damaged area. Based on this concept, a remarkable number of strategies, aimed at developing new tools to support re-vascularization of damaged tissue have emerged. Among the strategies proposed, the use of pro-angiogenic soluble factors, as a cell-free tool, appears as a promising approach, able to overcome the issues concerning the direct use of cells for regenerative medicine therapy.

Blocking immune cell infiltration of the central nervous system to tame Neuroinflammation in Amyotrophic lateral sclerosis.

Neuroinflammation is one of the main hallmarks of amyotrophic lateral sclerosis (ALS). Recently, peripheral immune cells were discovered as pivotal players that promptly participate in this process, speeding up neurodegeneration during progression of the disease. In particular, infiltrating T cells and natural killer cells release inflammatory cytokines that switch glial cells toward a pro-inflammatory/detrimental phenotype, and directly attack motor neurons with specific ligand-receptor signals.

Human Adipose-Derived Stem Cell-Conditioned Medium Promotes Vascularization of Nanostructured Scaffold Transplanted into Nude Mice.

Several studies have been conducted on the interaction between three-dimensional scaffolds and mesenchymal stem cells for the regeneration of damaged tissues. Considering that stem cells do not survive for sufficient time to directly sustain tissue regeneration, it is essential to develop cell-free systems to be applied in regenerative medicine. In this work, by in vivo experiments, we established that a collagen-nanostructured scaffold, loaded with a culture medium conditioned with mesenchymal stem cells derived from adipose tissue (hASC-CM), exerts a synergic positive effect on angiogenesis, fundamental in tissue regeneration.

Copper oxide nanoparticles trigger macrophage cell death with misfolding of Cu/Zn superoxide dismutase 1 (SOD1).

Background: Copper oxide (CuO) nanoparticles (NPs) are known to trigger cytotoxicity in a variety of cell models, but the mechanism of cell death remains unknown. Here we addressed the mechanism of cytotoxicity in macrophages exposed to CuO NPs versus copper chloride (CuCl).

Methods: The mouse macrophage cell line RAW264.

Nanoantibiotics to fight multidrug resistant infections by Gram-positive bacteria: hope or reality?

The spread of antimicrobial resistance in Gram-positive pathogens represents a threat to human health. To counteract the current lack of novel antibiotics, alternative antibacterial treatments have been increasingly investigated. This review covers the last decade's developments in using nanoparticles as carriers for the two classes of frontline antibiotics active on multidrug-resistant Gram-positive pathogens, i.

NK Cell Anti-Tumor Surveillance in a Myeloid Cell-Shaped Environment.

NK cells are innate lymphoid cells endowed with cytotoxic capacity that play key roles in the immune surveillance of tumors. Increasing evidence indicates that NK cell anti-tumor response is shaped by bidirectional interactions with myeloid cell subsets such as dendritic cells (DCs) and macrophages. DC-NK cell crosstalk in the tumor microenvironment (TME) strongly impacts on the overall NK cell anti-tumor response as DCs can affect NK cell survival and optimal activation while, in turn, NK cells can stimulate DCs survival, maturation and tumor infiltration through the release of soluble factors.

Impact on NK cell functions of acute versus chronic exposure to extracellular vesicle-associated MICA: Dual role in cancer immunosurveillance.

Natural killer (NK) cells are innate cytotoxic lymphocytes that play a key role in cancer immunosurveillance thanks to their ability to recognize and kill cancer cells. NKG2D is an activating receptor that binds to MIC and ULBP molecules typically induced on damaged, transformed or infected cells. The release of NKG2D ligands (NKG2DLs) in the extracellular milieu through protease-mediated cleavage or by extracellular vesicle (EV) secretion allows cancer cells to evade NKG2D-mediated immunosurveillance.

Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Biofilm.

In the era of antimicrobial resistance, the use of nanoconjugated antibiotics is regarded as a promising approach for preventing and fighting infections caused by resistant bacteria, including those exacerbated by the formation of difficult-to-treat bacterial biofilms. Thanks to their biocompatibility and magnetic properties, iron oxide nanoparticles (IONPs) are particularly attractive as antibiotic carriers for the targeting therapy. IONPs can direct conjugated antibiotics to infection sites by the use of an external magnet, facilitating tissue penetration and disturbing biofilm formation.

Enriched Environment Cues Suggest a New Strategy to Counteract Glioma: Engineered rAAV2-IL-15 Microglia Modulate the Tumor Microenvironment.

Several types of cancer grow differently depending on the environmental stimuli they receive. In glioma, exposure to an enriched environment (EE) increases the overall survival rate of tumor-bearing mice, acting on the cells that participate to define the tumor microenvironment. In particular, environmental cues increase the microglial production of interleukin (IL)-15 which promotes a pro-inflammatory (antitumor) phenotype of microglia and the cytotoxic activity of natural killer (NK) cells, counteracting glioma growth, thus representing a virtuous mechanism of interaction between NK cells and microglia.

Microglia modulate hippocampal synaptic transmission and sleep duration along the light/dark cycle.

Microglia, the brain's resident macrophages, actively contribute to the homeostasis of cerebral parenchyma by sensing neuronal activity and supporting synaptic remodeling and plasticity. While several studies demonstrated different roles for astrocytes in sleep, the contribution of microglia in the regulation of sleep/wake cycle and in the modulation of synaptic activity in the different day phases has not been deeply investigated. Using light as a zeitgeber cue, we studied the effects of microglial depletion with the colony stimulating factor-1 receptor antagonist PLX5622 on the sleep/wake cycle and on hippocampal synaptic transmission in male mice.