Production of reactive species in alginate hydrogels for cold atmospheric plasma-based therapies.

In the last years, great advances have been made in therapies based in cold atmospheric plasmas (CAP). CAP generate reactive oxygen and nitrogen species (RONS) which can be transferred to liquids. These CAP activated liquids display the same biological efficacy (i.

Epigenetic Repression in Tumor-Associated Fibroblasts Impairs Fibrosis and Response to the Antifibrotic Drug Nintedanib in Lung Squamous Cell Carcinoma.

The tumor-promoting fibrotic stroma rich in tumor-associated fibroblasts (TAF) is drawing increased therapeutic attention. Intriguingly, a trial with the antifibrotic drug nintedanib in non-small cell lung cancer reported clinical benefits in adenocarcinoma (ADC) but not squamous cell carcinoma (SCC), even though the stroma is fibrotic in both histotypes. Likewise, we reported that nintedanib inhibited the tumor-promoting fibrotic phenotype of TAFs selectively in ADC.

Cultivar-Dependent Anticancer and Antibacterial Properties of Silver Nanoparticles Synthesized Using Leaves of Different Trees.

The green synthesis of nanoparticles (NPs) is currently under worldwide investigation as an eco-friendly alternative to traditional routes (NPs): the absence of toxic solvents and catalysts make it suitable in the design of promising nanomaterials for nanomedicine applications. In this work, we used the extracts collected from leaves of two cultivars ( and ) belonging to the species , to synthesize silver NPs (AgNPs) in different pH conditions and low temperature. NPs underwent full morphological characterization with the aim to define a suitable protocol to obtain a monodispersed population of AgNPs.

Electrically Polarized Hydroxyapatite: Influence of the Polarization Process on the Microstructure and Properties.

Semipermanently polarized hydroxyapatite, named SP/HAp(w), is obtained by applying a constant dc electric field of 1-10 kV/cm at 300-850 °C to the samples previously sintered in water vapor, while permanently polarized hydroxyapatite, PP/HAp(a), is produced by applying a dc electric field of 3 kV/cm at 1000 °C to the samples sintered in air. SP/HAp(w) has been used for biomedical applications, while PP/HAp(a) has been proved to be a valuable catalyst for N and CO fixation. In this work, structural differences between SP/HAp(w) and PP/HAp(a) have been ascertained using Raman microscopy, wide-angle X-ray diffraction, scanning electronic microscopy, high-resolution transmission electron microscopy, and grazing incidence X-ray diffraction.

Modeling the Distribution of Diprotic Basic Drugs in Liposomal Systems: Perspectives on Malaria Nanotherapy.

Understanding how polyprotic compounds distribute within liposome (LP) suspensions is of major importance to design effective drug delivery strategies. Advances in this research field led to the definition of LP-based active drug encapsulation methods driven by transmembrane pH gradients with evidenced efficacy in the management of cancer and infectious diseases. An accurate modeling of membrane-solution drug partitioning is also fundamental when designing drug delivery systems for poorly endocytic cells, such as red blood cells (RBCs), in which the delivered payloads rely mostly on the passive diffusion of drug molecules across the cell membrane.

Enzyme-Powered Gated Mesoporous Silica Nanomotors for On-Command Intracellular Payload Delivery.

The introduction of stimuli-responsive cargo release capabilities on self-propelled micro- and nanomotors holds enormous potential in a number of applications in the biomedical field. Herein, we report the preparation of mesoporous silica nanoparticles gated with pH-responsive supramolecular nanovalves and equipped with urease enzymes which act as chemical engines to power the nanomotors. The nanoparticles are loaded with different cargo molecules ([Ru(bpy)]Cl (bpy = 2,2'-bipyridine) or doxorubicin), grafted with benzimidazole groups on the outer surface, and capped by the formation of inclusion complexes between benzimidazole and cyclodextrin-modified urease.

Sizing single nanoscale objects from polarization forces.

Sizing natural or engineered single nanoscale objects is fundamental in many areas of science and technology. To achieve it several advanced microscopic techniques have been developed, mostly based on electron and scanning probe microscopies. Still for soft and poorly adhered samples the existing techniques face important challenges.

Fast Measurements with MOX Sensors: A Least-Squares Approach to Blind Deconvolution.

Metal oxide (MOX) sensors are widely used for chemical sensing due to their low cost, miniaturization, low power consumption and durability. Yet, getting instantaneous measurements of fluctuating gas concentration in turbulent plumes is not possible due to their slow response time. In this paper, we show that the slow response of MOX sensors can be compensated by deconvolution, provided that an invertible, parametrized, sensor model is available.

Protrusion membrane pearling emerges during 3D cell division.

Cell division is accompanied by dramatic changes in shape that ultimately lead to the physical separation of one cell into two. In 2D microenvironments, cells round up and remain adhered onto the substrate by thin retraction fibers during division. In contrast, in 3D environments, cells divide exhibiting long protrusions that guide the orientation of the division axis.

Antimicrobial activity of poly(3,4-ethylenedioxythiophene) n-doped with a pyridinium-containing polyelectrolyte.

In spite of p-doped conducting polymers having been widely studied in the last decades and many applications having been developed, studies based on n-doped conducting polymers are extremely scarce. This fact is even more evident when it comes to conducting polymers n-doped with polycations, even though polyanions, such as poly(styrenesulfonate), are often used to obtain p-doped conducting polymers. In this work poly(pyridinium-1,4-diyliminocarbonyl-1,4-phenylene-methylene chloride), abbreviated as P(Py-1,4-P), has been used to prepare n-doped poly(3,4-ethylenedioxythiophene) (PEDOT) electrodes by applying a reduction potential to a de-doped PEDOT film in a P(Py-1,4-P) water solution.

The mechanical stability of proteins regulates their translocation rate into the cell nucleus.

The translocation of mechanosensitive transcription factors (TFs) across the nuclear envelope is a crucial step in cellular mechanotransduction. Yet the molecular mechanisms by which external mechanical cues control the nuclear shuttling dynamics of TFs through the nuclear pore complex (NPC) to activate gene expression are poorly understood. Here, we show that the nuclear import rate of myocardin-related transcription factor A (MRTFA) - a protein that regulates cytoskeletal dynamics via the activation of the TF serum response factor (SRF) - inversely correlates with the protein's nanomechanical stability and does not relate to its thermodynamic stability.

Self-Propelled Micro/Nanomotors for On-Demand Biomedical Cargo Transportation.

Micro/nanomotors (MNMs) are miniaturized machines that can perform assigned tasks at the micro/nanoscale. Over the past decade, significant progress has been made in the design, preparation, and applications of MNMs that are powered by converting different sources of energy into mechanical force, to realize active movement and fulfill on-demand tasks. MNMs can be navigated to desired locations with precise controllability based on different guidance mechanisms.

Hydroxylamine Derivatives as a New Paradigm in the Search of Antibacterial Agents.

Serious infections caused by bacteria that are resistant to commonly used antibiotics have become a major global healthcare problem in the 21st century. Multidrug-resistant bacteria causing severe infections mainly grow in complex bacterial communities known as biofilms, in which bacterial resistance to antibacterial agents and to the host immune system is strengthened. As drug resistance is becoming a threatening problem, it is necessary to develop new antimicrobial agents with novel mechanisms of action.

Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer.

Objectives: Tumor associated fibroblasts (TAFs) are essential contributors of the progression of non-small cell lung cancer (NSCLC). Most lung TAFs exhibit an activated phenotype characterized by the expression of α-SMA and fibrillar collagens. However, the prognostic value of these activation markers in NSCLC remains unclear.

The plasma membrane as a mechanochemical transducer.

Cells are constantly submitted to external mechanical stresses, which they must withstand and respond to. By forming a physical boundary between cells and their environment that is also a biochemical platform, the plasma membrane (PM) is a key interface mediating both cellular response to mechanical stimuli, and subsequent biochemical responses. Here, we review the role of the PM as a mechanosensing structure.

Super-resolution Microscopy for Nanomedicine Research.

Super-resolution microscopy, or nanoscopy, revolutionized the field of cell biology, enabling researchers to visualize cellular structures with nanometric resolution, single-molecule sensitivity, and in multiple colors. However, the impact of these techniques goes beyond biology as the fields of nanotechnology and nanomedicine can greatly benefit from them, as well. Nanoscopy can visualize nanostructures and in cells and can contribute to the characterization of their structures and nano-bio interactions.

3D sub-diffraction imaging in a conventional confocal configuration by exploiting super-linear emitters.

Sub-diffraction microscopy enables bio-imaging with unprecedented clarity. However, most super-resolution methods require complex, costly purpose-built systems, involve image post-processing and struggle with sub-diffraction imaging in 3D. Here, we realize a conceptually different super-resolution approach which circumvents these limitations and enables 3D sub-diffraction imaging on conventional confocal microscopes.

Modulating grid cell scale and intrinsic frequencies via slow high-threshold conductances: A simplified model.

Grid cells in the medial entorhinal cortex (MEC) have known spatial periodic firing fields which provide a metric for the representation of self-location and path planning. The hexagonal tessellation pattern of grid cells scales up progressively along the MEC's layer II dorsal-to-ventral axis. This scaling gradient has been hypothesized to originate either from inter-population synaptic dynamics as postulated by attractor networks, or from projected theta frequency waves to different axis levels, as in oscillatory models.

Biominerals Formed by DNA and Calcium Oxalate or Hydroxyapatite: A Comparative Study.

Biominerals formed by DNA and calcium oxalate (CaOx) or hydroxyapatite (HAp), the most important and stable phase of calcium phosphate) have been examined and compared using a synergistic combination of computer simulation and experimental studies. The interest of this comparison stems from the medical observation that HAp- and CaOx-based microcalcifications are frequently observed in breast cancer tissues, and some of their features are used as part of the diagnosis. Molecular dynamics simulations show that (1) the DNA double helix remains stable when it is adsorbed onto the most stable facet of HAp, whereas it undergoes significant structural distortions when it is adsorbed onto CaOx; (2) DNA acts as a template for the nucleation and growth of HAp but not for the mineralization of CaOx; and (3) the DNA double helix remains stable when it is encapsulated inside HAp nanopores, but it becomes destabilized when the encapsulation occurs into CaOx nanopores.

Enhanced photosensitizing properties of protein bound curcumin.

Aims: The naturally occurring compound curcumin has been proposed for a number of pharmacological applications. In spite of the promising chemotherapeutic properties of the molecule, the use of curcumin has been largely limited by its chemical instability in water. In this work, we propose the use of water soluble proteins to overcome this issue in perspective applications to photodynamic therapy of tumors.

Guidance of active particles at liquid-liquid interfaces near surfaces.

Artificial microswimmers have the potential for applications in many fields, ranging from targeted cargo delivery and mobile sensing to environmental remediation. In many of these applications, the artificial swimmers will operate in complex media necessarily involving liquid-liquid interfaces. Here, we experimentally study the motion of chemically powered phoretic active colloids close to liquid-liquid interfaces while swimming next to a solid substrate.

Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative process characterized by the accumulation of extracellular deposits of amyloid β-peptide (Aβ), which induces neuronal death. Monomeric Aβ is not toxic but tends to aggregate into β-sheets that are neurotoxic. Therefore to prevent or delay AD onset and progression one of the main therapeutic approaches would be to impair Aβ assembly into oligomers and fibrils and to promote disaggregation of the preformed aggregate.

Amorphous binary dispersions of chloramphenicol in enantiomeric pure and racemic poly-lactic acid: Morphology, molecular relaxations, and controlled drug release.

We characterize amorphous solid dispersions (ASDs) of the Chloramphenicol antibiotic in two biodegradable polylactic acid polymers, namely a commercial sample of enantiomeric pure PLLA and a home-synthesized PDLLA copolymer, investigating in particular the effect of polylactic acid in stabilizing the amorphous form of the drug and controlling its release (e.g. for antitumoral purposes).

Drug delivery systems based on intrinsically conducting polymers.

This work provides an overview of the up to date research related to intrinsically conducting polymers (ICPs) and their function as novel drug delivery systems (DDSs). Drugs administrated to patients do not always reach the targeted organ, which may affect other tissues leading to undesired side-effects. To overcome these problems, DDSs are under development.