Effect of Chitosan and Amphiphilic Polymers on the Photosensitizing and Spectral Properties of Rose Bengal.

The influence of chitosan (CS) and amphiphilic polymers (AP: pluronic F108 and polyvinylpyrrolidone (PVP)) on the photocatalytic activity of rose bengal (RB) in a model reaction of tryptophan photo-oxidation in phosphate-buffered saline (PBS) was studied. It was shown that in the presence of CS, the effective rate constant keff of tryptophan photo-oxidation catalyzed by RB in PBS solution decreases by a factor of two. This is due to the ionic interaction of the RB with the chitosan. Rose bengal in a slightly acidic environment (pH 4.5) passes into a neutral lactone form, which sharply reduces the photosensitizing properties of the dye. It was demonstrated that the introduction of AP into a solution containing RB and CS prevents direct interaction between RB and CS. This is evidenced by the presence of photocatalytic activity of the dye in the RB-AP-CS systems, as well as bathochromic shifts of the main absorption bands of the dye, and an increase in the optical density and luminescence intensity of the RB when AP is introduced into a buffer solution containing RB and chitosan. The presence of RB-CS and RB-AP interaction in aqueous and PBS media is confirmed by the increase in the degree of fluorescence anisotropy (r) of these binary systems. In an aqueous solution, the value of r for the RB-F108-CS system decreases by a factor of 3.5 (compared to the value of r for the RB-CS system), which is associated with the localization of the dye in pluronic micelles. In PBS, the fluorescence anisotropy is practically the same for all systems, which is related to the stability of the dye structure in this medium. The presence of interaction between RB and AP in aqueous solutions was confirmed by the proton NMR method. In addition, the formation of RB-F108 macromolecular complexes, which form associates during solution concentration (in particular, during evaporation), was shown by AFM. Such RB-AP-CS systems may be promising for practical application in the treatment of local foci of infections by aPDT.

Isoforms of autophagy-related proteins: role in glioma progression and therapy resistance.

Autophagy is the process of recycling and utilization of degraded organelles and macromolecules in the cell compartments formed during the fusion of autophagosomes with lysosomes. During autophagy induction the healthy and tumor cells adapt themselves to harsh conditions such as cellular stress or insufficient supply of nutrients in the cell environment to maintain their homeostasis. Autophagy is currently seen as a form of programmed cell death along with apoptosis and necroptosis. In recent years multiple studies have considered the autophagy as a potential mechanism of anticancer therapy in malignant glioma. Although, subsequent steps in autophagy development are known and well-described, on molecular level the mechanism of autophagosome initiation and maturation using autophagy-related proteins is under investigation. This article reviews current state about the mechanism of autophagy, its molecular pathways and the most recent studies on roles of autophagy-related proteins and their isoforms in glioma progression and its treatment.

Amianthoid transformation of costal cartilage matrix in children with pectus excavatum and pectus carinatum.

BACKGROUND: It is unclear if amianthoid transformation (AT) of costal cartilage extracellular matrix (ECM) has an impact on the development of pectus excavatum (PE) and pectus carinatum (PC). METHODS: AT foci were examined in intrasurgical biopsy specimens of costal cartilages of children (8-17 years old) with PE (n = 12) and PC (n = 12) and in age-matching autopsy control samples (n = 10) using histological and immunohistochemical staining, atomic force and nonlinear optical microscopy, transmission and scanning electron microscopy, morphometry and statistics. RESULTS: AT areas were identified in the costal cartilage ECM in children with normal chest, PE and PC. Each type of the AT areas ("canonical", "intertwined", "fine-fibred" and "intralacunary") had a unique morphological pattern of thickness and alignment of amianthoid fibers (AFs). AFs were formed via lateral aggregation of collagen type II fibrils in the intact ECM. Foci of the AT were observed significantly more frequently in the PE and PC groups. The AT areas had unique quantitative features in each study group. CONCLUSION: AT is a structurally diverse form of ECM alteration present in healthy and pathological costal cartilage. PE and PC are associated with specific AT disorders.

Therapeutic Potential of Mesenchymal Stem Cells for Postmastectomy Lymphedema: A Literature Review.

Upper limb lymphedema is one of the most common complications after breast cancer surgery and radiotherapy. Despite various physical therapy and surgical options available, the impaired lymph fluid drainage may be progressive due to lymphatic vascular insufficiency making treatment more difficulty. Stem cell therapy provides a promising alternative in the treatment of various chronic diseases. The wide applicability of cell therapy has been reviewed throughout literature. This review provides an overview of recent progress in the therapeutic effect of adult stem cells for primary and secondary lymphedema after breast surgery in preclinical studies and clinical cases. We start with a brief introduction about the pathophysiological mechanisms of postmastectomy lymphedema. Regarding existing treatments, we systematically summarize the benefits and limitations of recent progress. Because of their multidirectional differentiation potential and growth factor secretion, stem cell therapy shows promising results in the management of light to severe lymphedema. Increasing evidences have demonstrated a noticeable reduction in postmastectomy lymphedema and increased lymph-angiogenesis after specific stem cell therapy. Current data suggests that stem cell therapy in lymphedema treatment provides reversal of pathological reorganization associated with lymphedema progression. Finally, we propose potential strategies for overcoming the challenges in the development of multipotent progenitor cells for the treatment and prevention of lymphedema in clinical practice.

TMZ regulates GBM stemness via MMP14-DLL4-Notch3 pathway.

Glioblastoma (GBM) is one of the most aggressive primary brain tumors with frequent recurrences following the standard methods of treatment-temozolomide (TMZ), ionizing radiation and surgical resection. The objective of our study was to investigate GBM resistance mediated via MMP14 (matrix metalloproteinase 14). We used multiple PDX GBM models and established glioma cell lines to characterize expression and subcellular localization of MMP14 after TMZ treatment. We performed a Kiloplex ELISA-based array to evaluate changes in cellular proteins induced by MMP14 expression and translocation. Lastly, we conducted functional and mechanistic studies to elucidate the role of DLL4 (delta-like canonical notch ligand 4) in regulation of glioma stemness, particularly in the context of its relationship to MMP14. We detected that TMZ treatment promotes nuclear translocation of MMP14 followed by extracellular release of DLL4. DLL4 in turn stimulates cleavage of Notch3, its nuclear translocation and induction of sphering capacity and stemness.

Editing Cytoprotective Autophagy in Glioma: An Unfulfilled Potential for Therapy.

Glioblastoma (GBM) resistance to the standard of care is prompting scientists to develop better targeted therapeutic strategies. Autophagy is one of the many signaling mechanisms that regulate tumor regrowth. Despite the extensive in vitro and in vivo studies published, knowledge on autophagic modulation remains scarce. This hinders the development of novel treatment modalities that employ autophagic mechanisms for the clinical benefit of patients with GBM. Clinical trials for GBM continue to fall short of showing significant survival or clinical benefit, with the complex glioma heterogeneity often being the reason to blame. Here, we propose that a combination therapy of current antiglioma regimens and autophagic mediators or suppressors can allow us to overcome GBM regrowth in the context of tumor heterogeneity.

Flexible Polycaprolactone and Polycaprolactone/Graphene Scaffolds for Tissue Engineering.

Developing bone scaffolds can greatly improve the patient's quality of life by accelerating the rehabilitation process. In this paper, we studied the process of composite polycaprolactone supercritical foaming for tissue engineering. The influence of graphene oxide and reduced graphene oxide on the foaming parameters was studied. The structural and mechanical properties were studied. The scaffolds demonstrated mechanical flexibility and endurance. The co-culturing and live/dead tests demonstrated that the obtained scaffolds are biocompatible. Different composite scaffolds induced various surface cell behaviors. The experimental data demonstrate that composite foams are promising candidates for in vivo medical trials.

Solvent-free synthesis and characterization of allyl chitosan derivatives.

The solvent-free synthesis of allyl-substituted chitosan derivatives through reactive co-extrusion of chitosan powder with allyl bromide at shear deformation was performed. For the structural characterization, FTIR and NMR methods were employed. The results were confirmed by chemical analysis. The total content of allyl substituents from 5 to 50 per 100 chitosan units as a function of the component ratio in the reactive mixtures was revealed. Carrying out the reaction without any additives leads to the selective formation of N-alkylated derivatives, whereas in the presence of alkali the ethers of chitosan were preferentially formed. The results suggest that the proposed approach allows significantly higher yield of products to be obtained at high process speeds and significantly lower reagent consumption as compared with the liquid-phase synthesis in organic medium. The synthesized unsaturated derivatives are promising photosensitive components for use in laser stereolithography for fabrication of three-dimensional biocompatible structures with well-defined architectonics.

Publisher Correction: Carbon nanowalls as a platform for biological SERS studies.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Carbon nanowalls as a platform for biological SERS studies.

Herein we report about developing new type of Surface Enhanced Raman Scattering (SERS) substrates based on Au-decorated carbon nanowalls. The designed substrates possess high specific surface area and high sensitivity. Chemical stability of Au perfectly blends with electrical properties and high value of specific surface area of carbon nanowalls. Created structures were applied to detect signals of a typical molecule used for SERS substrates testing, rhodamine 6G, which exhibits electronic absorption in the visible area of spectrum, and biomacromolecules such as tryptophan, guanine, bovine serum albumin and keratin hydrolysates, whose electronic absorption is in the ultraviolet region of spectrum and lies far from the Au plasmonic resonance. The obtained signals for these compounds suggest that the developed substrate is a prominent platform for the detection of biological macromolecules. The properties of the substrate, including its morphology and Au film thickness, as well as the analyte deposition method, were optimized to achieve the optimum Raman signal enhancement. Electric field distribution in the designed structures was calculated to describe the observed dependence of SERS activity on the substrate morphology.