Functional Activity of Cytokine-Induced Killer Cells Enhanced by CAR-CD19 Modification or by Soluble Bispecific Antibody Blinatumomab.

Strategies to increase the anti-tumor efficacy of cytokine-induced killer cells (CIKs) include genetic modification with chimeric antigen receptors (CARs) or the addition of soluble T-cell engaging bispecific antibodies (BsAbs). Here, CIKs were modified using a transposon system integrating two distinct anti-CD19 CARs (CAR-MNZ and CAR-BG2) or combined with soluble CD3xCD19 BsAb blinatumomab (CIK + Blina). CAR-MNZ bearing the CD28-OX40-CD3ζ signaling modules, and CAR-BG2, designed on the Tisagenlecleucel CAR sequence (Kymriah), carrying the 4-1BB and CD3ζ signaling elements, were employed.

Loss of interleukin 1 signaling causes impairment of microglia- mediated synapse elimination and autistic-like behaviour in mice.

In the last years, the hypothesis that elevated levels of proinflammatory cytokines contribute to the pathogenesis of neurodevelopmental diseases has gained popularity. IL-1 is one of the main cytokines found to be elevated in Autism spectrum disorder (ASD), a complex neurodevelopmental condition characterized by defects in social communication and cognitive impairments. In this study, we demonstrate that mice lacking IL-1 signaling display autistic-like defects associated with an excessive number of synapses.

Cholangiocarcinoma-on-a-chip: A human 3D platform for personalised medicine.

Background & Aims: Cholangiocarcinoma (CCA) is a primary liver tumour characterised by a poor prognosis and limited therapeutic options. Available 3D human CCA models fail to faithfully recapitulate the tumour niche. We aimed to develop an innovative patient-specific CCA-on-chip platform.

Size-advantage of monovalent nanobodies against the macrophage mannose receptor for deep tumor penetration and tumor-associated macrophage targeting.

Nanobodies (Nbs) have emerged as an elegant alternative to the use of conventional monoclonal antibodies in cancer therapy, but a detailed microscopic insight into the pharmacokinetics of different Nb formats in tumor-bearers is lacking. This is especially relevant for the recognition and targeting of pro-tumoral tumor-associated macrophages (TAMs), which may be located in less penetrable tumor regions. We employed anti-Macrophage Mannose Receptor (MMR) Nbs, in a monovalent (m) or bivalent (biv) format, to assess TAM targeting.

Measuring Molecular Diffusion in Dynamic Subcellular Nanostructures by Fast Raster Image Correlation Spectroscopy and 3D Orbital Tracking.

Here we provide demonstration that fast fluorescence fluctuation spectroscopy is a fast and robust approach to extract information on the dynamics of molecules enclosed within subcellular nanostructures (e.g., organelles or vesicles) which are also moving in the complex cellular environment.

Synthetic recovery of impulse propagation in myocardial infarction via silicon carbide semiconductive nanowires.

Myocardial infarction causes 7.3 million deaths worldwide, mostly for fibrillation that electrically originates from the damaged areas of the left ventricle. Conventional cardiac bypass graft and percutaneous coronary interventions allow reperfusion of the downstream tissue but do not counteract the bioelectrical alteration originated from the infarct area.

Probing Liquid-Ordered and Disordered Phases in Lipid Model Membranes: A Combined Theoretical and Spectroscopic Study of a Fluorescent Molecular Rotor.

An integrated theoretical/experimental strategy has been applied to the study of environmental effects on the spectroscopic parameters of 4-(diphenylamino)phtalonitrile (DPAP), a fluorescent molecular rotor. The computational part starts from the development of an effective force field for the first excited electronic state of DPAP and proceeds through molecular dynamics simulations in solvents of different polarities toward the evaluation of Stokes shifts by quantum mechanics/molecular mechanics (QM/MM) approaches. The trends of the computed results closely parallel the available experimental results thus giving confidence to the interpretation of new experimental studies of the photophysics of DPAP in lipid bilayers.

Complementary Roles of Short and Long Pentraxins in the Complement-Mediated Immune Response to Infections.

The ubiquitous mold is the major etiologic agent of invasive aspergillosis, a life-threatening infection amongst immune compromised individuals. An increasing body of evidence indicates that effective disposal of requires the coordinate action of both cellular and humoral components of the innate immune system. Early recognition of the fungal pathogen, in particular, is mediated by a set of diverse soluble pattern recognition molecules (PRMs) that act as "ancestral antibodies" inasmuch as they are endowed with opsonic, pro-phagocytic and killing properties.

Myopalladin knockout mice develop cardiac dilation and show a maladaptive response to mechanical pressure overload.

Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band. gene mutations are causative for dilated (DCM), hypertrophic, and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis.

Probing Structural and Dynamic Properties of Trafficking Subcellular Nanostructures by Spatiotemporal Fluctuation Spectroscopy.

Imaging-derived mean square displacement (iMSD) is used to address the structural and dynamic properties of subcellular nanostructures, such as vesicles involved in the endo/exocytotic trafficking of solutes and biomolecules. iMSD relies on standard time-lapse imaging, is compatible with any optical setup, and does not need to dwell on single objects to extract trajectories. From each iMSD trace, a unique triplet of average structural and dynamic parameters (i.

Nanobodies as Versatile Tool for Multiscale Imaging Modalities.

Molecular imaging is constantly growing in different areas of preclinical biomedical research. Several imaging methods have been developed and are continuously updated for both in vivo and in vitro applications, in order to increase the information about the structure, localization and function of molecules involved in physiology and disease. Along with these progresses, there is a continuous need for improving labeling strategies.

Author Correction: Evaluation of cell metabolic adaptation in wound and tumour by Fluorescence Lifetime Imaging Microscopy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evaluation of cell metabolic adaptation in wound and tumour by Fluorescence Lifetime Imaging Microscopy.

Acidic pH occurs in acute wounds progressing to healing as consequence of a cell metabolic adaptation in response to injury-induced tissue hypoperfusion. In tumours, high metabolic rate leads to acidosis affecting cancer progression. Acidic pH affects activities of remodelling cells in vitro.

Interplay between lipid lateral diffusion, dye concentration and membrane permeability unveiled by a combined spectroscopic and computational study of a model lipid bilayer.

Lipid lateral diffusion in membrane bilayers is a fundamental process exploited by cells to enable complex protein structural and dynamic reorganizations. For its importance, lipid mobility in both cellular and model bilayers has been extensively investigated in recent years, especially through the application of time-resolved, fluorescence-based, optical microscopy techniques. However, one caveat of fluorescence techniques is the need to use dye-labeled variants of the lipid of interest, thus potentially perturbing the structural and dynamic properties of the native species.

Capturing Metabolism-Dependent Solvent Dynamics in the Lumen of a Trafficking Lysosome.

The eukaryotic cell compartmentalizes into spatially confined, membrane-enclosed, intracellular structures ( e. g., organelles, endosomes, and vesicles).

Time-lapse confocal imaging datasets to assess structural and dynamic properties of subcellular nanostructures.

Time-lapse optical microscopy datasets from living cells can potentially afford an enormous amount of quantitative information on the relevant structural and dynamic properties of sub-cellular organelles/structures, provided that both the spatial and temporal dimensions are properly sampled during the experiment. Here we provide exemplary live-cell, time-lapse confocal imaging datasets corresponding to three sub-cellular structures of the endo-lysosomal pathway, i.e.

Probing labeling-induced lysosome alterations in living cells by imaging-derived mean squared displacement analysis.

Lysosomes are not merely degradative organelles but play a central role in nutrient sensing, metabolism and cell-growth regulation. Our ability to study their function in living cells strictly relies on the use of lysosome-specific fluorescent probes tailored to optical microscopy applications. Still, no report thus far quantitatively analyzed the effect of labeling strategies/procedures on lysosome properties in live cells.

Image-Based Tracking of Anticancer Drug-Loaded Nanoengineered Polyelectrolyte Capsules in Cellular Environments Using a Fast Benchtop Mid-Infrared (MIR) Microscope.

Drug delivery monitoring and tracking in the human body are two of the biggest challenges in targeted therapy to be addressed by nanomedicine. The ability of imaging drugs and micro-/nanoengineered drug carriers and of visualizing their interactions at the cellular interface in a label-free manner is crucial in providing the ability of tracking their cellular pathways and will help understand their biological impact, allowing thus to improve the therapeutic efficacy. We present a fast, label-free technique to achieve high-resolution imaging at the mid-infrared (MIR) spectrum that provides chemical information.

Dynamic fingerprinting of sub-cellular nanostructures by image mean square displacement analysis.

Here we provide demonstration that image mean square displacement (iMSD) analysis is a fast and robust platform to address living matter dynamic organization at the level of sub-cellular nanostructures (e.g. endocytic vesicles, early/late endosomes, lysosomes), with no a-priori knowledge of the system, and no need to extract single trajectories.

Self-aggregation propensity of the Tat peptide revealed by UV-Vis, NMR and MD analyses.

By a combination of UV-Vis analyses, NMR-based diffusion measurements and MD simulations we have demonstrated for the first time that the HIV-1 Tat arginine-rich peptide (Tat) is able to self-aggregate in both its fluorescently labeled and unlabeled variants. We propose Tat dimerization as the dominant aggregation process and show that the associated equilibrium constant increases ten-fold by labeling with the standard TAMRA dye. Also, we extend similar conclusions to other cationic cell penetrating peptides (CPPs), such as Antennapedia (Ant) and nona-arginine (R9).

Polylactic Acid-Lemongrass Essential Oil Nanocapsules with Antimicrobial Properties.

Polylactic acid was combined with lemongrass essential oil (EO) to produce functional nanocapsules (NCs). The obtained polylactic acid nanoparticles showed antimicrobial activity both with and without the presence of lemongrass oil; however, the presence of EO improved the activity of the NCs. The presence of lemongrass assisted the formation of well-separated NCs and also provided enhanced antimicrobial properties, since lemongrass is known for its antimicrobial character.

Ultrastable Liquid-Liquid Interface as Viable Route for Controlled Deposition of Biodegradable Polymer Nanocapsules.

Liquid-liquid interfaces are highly dynamic and characterized by an elevated interfacial tension as compared to solid-liquid interfaces. Therefore, they are gaining an increasing interest as viable templates for ordered assembly of molecules and nanoparticles. However, liquid-liquid interfaces are more difficult to handle compared to solid-liquid interfaces; their intrinsic instability may affect the assembly process, especially in the case of multiple deposition.

All natural cellulose acetate-Lemongrass essential oil antimicrobial nanocapsules.

Nanocapsules and nanoparticles play an essential role in the delivery of pharmaceutical agents in modern era, since they can be delivered in specific tissues and cells. Natural polymers, such as cellulose acetate, are becoming very important due to their availability, biocompatibility, absence of toxicity and biodegradability. In parallel, essential oils are having continuous growth in biomedical applications due to the inherent active compounds that they contain.

Multilayered polyelectrolyte microcapsules: interaction with the enzyme cytochrome C oxidase.

Cell-sized polyelectrolyte capsules functionalized with a redox-driven proton pump protein were assembled for the first time. The interaction of polyelectrolyte microcapsules, fabricated by electrostatic layer-by-layer assembly, with cytochrome c oxidase molecules was investigated. We found that the cytochrome c oxidase retained its functionality, that the functionalized microcapsules interacting with cytochrome c oxidase were permeable and that the permeability characteristics of the microcapsule shell depend on the shell components.

Chitosan gel containing polymeric nanocapsules: a new formulation for vaginal drug delivery.

The vaginal route of administration is an alternative for several treatments for either local or systemic pharmacological effects. However, the permanence of a drug in this route represents a challenge for formulation development that can be overcome by using nanoencapsulation and chitosan gel. Thus, this work aimed to evaluate the performance of chitosan hydrogels containing cationic and anionic acrylic-based nanocapsules (Eudragit RS 100 and Eudragit S 100, respectively) with Nile red as a model of lipophilic substance in the vaginal route of administration, as measured by increases in the residence time and the penetration of these formulations.