Association with TFIIIC limits MYCN localisation in hubs of active promoters and chromatin accumulation of non-phosphorylated RNA polymerase II.

MYC family oncoproteins regulate the expression of a large number of genes and broadly stimulate elongation by RNA polymerase II (RNAPII). While the factors that control the chromatin association of MYC proteins are well understood, much less is known about how interacting proteins mediate MYC's effects on transcription. Here, we show that TFIIIC, an architectural protein complex that controls the three-dimensional chromatin organisation at its target sites, binds directly to the amino-terminal transcriptional regulatory domain of MYCN.

Photodynamic Eradication of with Ru-Photosensitizers Encapsulated in Enzyme Degradable Nanocarriers.

The development of new approaches for the treatment of the increasingly antibiotic-resistant pathogen was targeted by enhancing the effect of local antimicrobial photodynamic therapy (aPDT) using poly(ethylene glycol)--poly(lactic acid) (PEG--PLA) nanocarriers that were loaded with a ruthenium-based photosensitizer (PS). The action of tris(1,10-phenanthroline) ruthenium (II) bis(hexafluorophosphate) (RuPhen3) encapsulated in PEG--PLA micelles and vesicles was shown to result in an appreciable aPDT inactivation efficiency against planktonic . In particular, the encapsulation of the PS, its release, and the efficiency of singlet oxygen (O) generation upon irradiation with blue light were studied spectroscopically.

Monitoring Growth and Removal of Biofilms on Cellulose-Based Fabrics.

Biofilms are often tolerant towards routine cleaning and disinfection processes. As they can grow on fabrics in household or healthcare settings, resulting in odors and serious health problems, it is necessary to contain biofilms through eradication strategies. The current study proposes a novel test model for the growth and removal of biofilms on textiles with and the opportunistic nosocomial pathogen as model organisms.

Bare Eye Detection of Bacterial Enzymes of with Polymer Modified Nanoporous Silicon Rugate Filters.

The fabrication, characterization and application of a nanoporous Silicon Rugate Filter (pSiRF) loaded with an enzymatically degradable polymer is reported as a bare eye detection optical sensor for enzymes of pathogenic bacteria, which is devoid of any dyes. The nanopores of pSiRF were filled with poly(lactic acid) (PLA), which, upon enzymatic degradation, resulted in a change in the effective refractive index of the pSiRF film, leading to a readily discernible color change of the sensor. The shifts in the characteristic fringe patterns before and after the enzymatic reaction were analyzed quantitatively by Reflectometric Interference Spectroscopy (RIfS) to estimate the apparent kinetics and its dependence on enzyme concentration.

Ruthenium(II) Polypyridyl Complexes for Antimicrobial Photodynamic Therapy: Prospects for Application in Cystic Fibrosis Lung Airways.

Antimicrobial photodynamic therapy (aPDT) depends on a variety of parameters notably related to the photosensitizers used, the pathogens to target and the environment to operate. In a previous study using a series of Ruthenium(II) polypyridyl ([Ru(II)]) complexes, we reported the importance of the chemical structure on both their photo-physical/physico-chemical properties and their efficacy for aPDT. By employing standard in vitro conditions, effective [Ru(II)]-mediated aPDT was demonstrated against planktonic cultures of and strains notably isolated from the airways of Cystic Fibrosis (CF) patients.

Effects of the Sex Steroid Hormone Estradiol on Biofilm Growth of Cystic Fibrosis Isolates.

Women with cystic fibrosis (CF) have a significantly lower life expectancy compared to men, which is indicated by an earlier impairment of lung function due to chronic colonization with biofilm formed by . There is growing evidence that blood serum concentrations of the steroid sex hormone estradiol (E) correlate with the occurrence of pulmonary exacerbations in CF but also play a role in the mucoid switch of . This study aims to shed light on possible microbiological reasons for sexual dimorphism in CF by investigating the influence of E on biofilm formation of .

Nanomedicine-based strategies to improve treatment of cutaneous leishmaniasis.

Nanomedicine strategies were first adapted and successfully translated to clinical application for diseases, such as cancer and diabetes. These strategies would no doubt benefit unmet diseases needs as in the case of leishmaniasis. The latter causes skin sores in the cutaneous form and affects internal organs in the visceral form.

Antimicrobial Photodynamic Therapy: Latest Developments with a Focus on Combinatory Strategies.

Antimicrobial photodynamic therapy (aPDT) has become a fundamental tool in modern therapeutics, notably due to the expanding versatility of photosensitizers (PSs) and the numerous possibilities to combine aPDT with other antimicrobial treatments to combat localized infections. After revisiting the basic principles of aPDT, this review first highlights the current state of the art of curative or preventive aPDT applications with relevant clinical trials. In addition, the most recent developments in photochemistry and photophysics as well as advanced carrier systems in the context of aPDT are provided, with a focus on the latest generations of efficient and versatile PSs and the progress towards hybrid-multicomponent systems.

Does positive MGMT methylation outbalance the limitation of subtotal resection in glioblastoma IDH-wildtype patients?

Background: The impact on survival of complete resection (CR) in patients with malignant glioma and MGMT promoter methylation on adjuvant therapy strategies has been proven in the past. However, it is not known whether a MGMT promoter methylation can compensate a subtotal resection. Therefore, we analyzed the progress of postoperative residual tumor tissue depending on the molecular tumor status.

Multiplexed detection and differentiation of bacterial enzymes and bacteria by color-encoded sensor hydrogels.

We report on the fabrication and characterization of color-encoded chitosan hydrogels for the rapid, sensitive and specific detection of bacterial enzymes as well as the selective detection of a set of tested bacteria through characteristic enzyme reactions. These patterned sensor hydrogels are functionalized with three different colorimetric enzyme substrates affording the multiplexed detection and differentiation of α-glucosidase, β-galactosidase and β-glucuronidase. The limits of detection of the hydrogels for an observation time of 60 min using a conventional microplate reader correspond to concentrations of 0.

Drug Release from Thermo-Responsive Polymer Brush Coatings to Control Bacterial Colonization and Biofilm Growth on Titanium Implants.

Despite decades of biomedical advances, the colonization of implant devices with bacterial biofilms is still a leading cause of implant failure. Clearly, new strategies and materials that suppress both initial and later stage bacterial colonization are required in this context. Ideal would be the implementation of a bactericidal functionality in the implants that is temporally and spatially triggered in an autonomous fashion at the infection site.

Quantitative Enzyme Detection in Reporter Hydrogel-Coated Paper Using a Smartphone Camera.

There is a growing demand for rapid and sensitive detection approaches for pathogenic bacteria that can be applied by non-specialists in non-laboratory field settings. Here, the detection of the typical enzyme β-glucuronidase using a chitosan-based sensing hydrogel-coated paper sensor and the detailed analysis of the reaction kinetics, as detected by a smartphone camera, is reported. The chromogenic reporter unit affords an intense blue color in a two-step reaction, which was analyzed using a modified Michaelis-Menten approach.

Enhanced Colorimetric Differentiation between and Using a Shape-Encoded Sensor Hydrogel.

Herein, we demonstrate a combined fluorescent probe/shape-encoded hydrogel strategy for the fast, sensitive, and selective detection of bacterial species via their characteristic enzymes. A poly(vinyl alcohol) (PVA) hydrogel loaded with the fluorescent probe ,'-(3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-3',6'-diyl)bis(2,2,3,3,3-pentafluoropropanamide) (ACS-HNE) was designed for the detection of elastase, an enzyme produced by . Likewise, a chitosan-derived hydrogel was loaded with the fluorescent probe 4-methylumbelliferyl-α-d-glucopyranoside (MUD) by entrapment for the selective detection of α-glucosidase, an enzyme produced by .

Targeting non-apoptotic cell death in cancer treatment by nanomaterials: Recent advances and future outlook.

Many tumors develop resistance to most of the apoptosis-based cancer therapies. In this sense targeting non-apoptotic forms of cell death including necroptosis, autophagy and ferroptosis may have therapeutic benefits in apoptosis-defective cancer cells. Nanomaterials have shown great advantages in cancer treatment owing to their unique characteristics.

Alterations in inflammatory markers and clinical outcome after spontaneous intracerebral hemorrhage - Preliminary results.

Objective: After an intracerebral hemorrhage, there is an immunological reaction, the specific mechanism of which is not fully understood, that seems to contribute to secondary brain injury. In this study, we investigated alterations of inflammatory markers in the blood and clinical outcome after an intracerebral hemorrhage.

Methods: Between July 2013 and February 2016, we performed a prospective study for which we recruited patients who had suffered an intracerebral hemorrhage.

Novel therapeutic strategies for Alzheimer's disease: Implications from cell-based therapy and nanotherapy.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease which leads to progressive dysfunction of cognition, memory and learning in elderly people. Common therapeutic agents are not only inadequate to suppress the progression of AD pathogenesis but also produce deleterious side effects; hence, development of alternative therapies is required to specifically suppress complications of AD. The current review provides a commentary on conventional as well as novel therapeutic approaches with an emphasis on stem cell and nano-based therapies for improvement and management of AD pathogenesis.

The Role of Stabilization-Free Microsurgical Decompression in the Surgical Treatment of Spinal Metastases.

Objective: Symptomatic spine metastases are found in about 10% of patients with cancer. As the long-term survival of patients with carcinoma rises, the number of patients with symptomatic spine metastases is also increasing. In our tertiary referral center, patients usually present rapidly progressive neurologic disorders, which require an urgent treatment decision.

Colorimetric and Fluorimetric DNA Detection with a Hydroxystyryl-Quinolizinium Photoacid and Its Application for Cell Imaging.

The combination of styryl dye properties with the acidity and strong photoacidity of the 2,2'-[(1''-hydroxy-4''-methyl-(E)-2'',6''-phenylene)]-bisquinolizinium enables the detection of DNA by distinct absorption and emission color changes and the fluorimetric detection of DNA in cells with epifluorescence and confocal fluorescence microscopy.

Toward Label-Free Selective Cell Separation of Different Eukaryotic Cell Lines Using Thermoresponsive Homopolymer Layers.

Ultrathin thermoresponsive poly(di(ethylene glycol) methyl ether methacrylate) (PDEGMA) homopolymer layers are reported as a novel platform for label-free temperature-stimulated cell separation from a coculture of eukaryotic cell lines. Pancreatic tumor cells (PaTu 8988t) and fibroblasts (NIH 3T3) were shown to attach and proliferate on PDEGMA layers with a dry thickness of 5 ± 1 nm at 37 °C. After the cell medium cooled to below the lower critical solution temperature (LCST), PaTu 8988t cells showed a significantly decreased cell area.

Propagation and Purification of Human Induced Pluripotent Stem Cells with Selective Homopolymer Release Surfaces.

The selective detachment of undifferentiated human induced pluripotent stem (iPS) cells from a thermal release coating, fabricated from a tailored poly(di(ethylene glycol) methyl ether methacrylate) (PDEGMA) homopolymer layer on gold, is reported. By exploiting the mild, thermally triggered release of iPS cell colonies in the absence of any releasing reagent, pluripotent iPS cells are shown to be selectively separated from spontaneously differentiated cells. The maintained pluripotency and high cell viability of detached and reseeded iPS cell colonies were confirmed and suggest the feasibility of a generally applicable platform approach for cell separation and purification in the context of iPS cell culture, differentiation of pathologically altered cells and normal cells, as well as isolation of different cell types derived from certain tissues, for example, from biopsies.

Thickness-Encoded Micropatterns in One-Component Thermoresponsive Polymer Brushes for Culture and Triggered Release of Pancreatic Tumor Cell Monolayers and Spheroids.

Fabrication, characterization, and application of micropatterned one-component poly(di(ethylene glycol)methyl ether methacrylate) (PDEGMA) brushes for monolayer cell and spheroid culture and temperature-triggered release are reported. Micropatterns of various shapes and sizes were designed to possess a unique functionality imparted by thermoresponsive thin PDEGMA patches, which are cell adhesive at 37 °C, embedded in a much thicker cell-resistant PDEGMA matrix that does not exhibit measurable thermoresponsive properties. Depending on the cell seeding density, PaTu 8988t human pancreatic tumor cells or spheroids were cultured area-selectively, confined by the 40 ± 4 nm thick passivating PDEGMA matrix, and could be released on demand by a mild thermally triggered brush swelling in the 5 ± 1 nm thin regions.

Selective Discrimination of Key Enzymes of Pathogenic and Nonpathogenic Bacteria on Autonomously Reporting Shape-Encoded Hydrogel Patterns.

This work reports on a new approach to rapidly and selectively detect and discriminate enzymes of pathogenic from those of nonpathogenic bacteria using a patterned autonomously reporting hydrogel on a transparent support, in which the selectivity has been encoded by the pattern shape to enable facile detection by a color change at one single wavelength. In particular, enzyme-responsive chitosan hydrogel layers that report the presence of the enzymes β-glucuronidase (β-Gus) and β-galactosidase (β-Gal), produced by the nonvirulent Escherichia coli K12 and the food-borne biosafety level 3 pathogen enterohemorrhagic E. coli, respectively, via the blue color of an indigo dye were patterned by two complementary strategies.