Features of Remyelination after Transplantation of Olfactory Ensheathing Cells with Neurotrophic Factors into Spinal Cord Cysts.

This paper shows for the first time that co-transplantation of human olfactory ensheathing cells with neurotrophin-3 into spinal cord cysts is more effective for activation of remyelination than transplantation of cells with brain-derived neurotrophic factor and a combination of these two factors. The studied neurotrophic factors do not affect proliferation and migration of ensheathing cells in vitro. It can be concluded that the maximum improvement of motor function in rats receiving ensheathing cells with neurotrophin-3 is largely determined by activation of remyelination.

Neurotrophin-3 Enhances the Effectiveness of Cell Therapy in Chronic Spinal Cord Injuries.

Neurotrophin-3 enhances the effectiveness of human olfactory ensheathing cells in improving hind limb mobility in rats with post-traumatic cysts of the spinal cord. Transplantation of olfactory ensheathing cells into spinal cord cysts reduced their size; neurotrophin-3 did not modulate this effect. Combined preparation of human olfactory ensheathing cells and neurotrophin- 3 can be used in neurosurgery for the treatment of patients with spinal cord injuries.

Application of a New Gene-Cell Construct Based on the Olfactory Mucosa Escheating Cells Transduced with an Adenoviral Vector Encoding Mature BDNF in the Therapy of Spinal Cord Cysts.

A gene-cell construct based on rat olfactory mucosa ensheathing cells transduced with an adenoviral vector encoding a mature form of brain neurotrophic factor (mBDNF) was transplanted into post-traumatic cysts of rat spinal cord. Transplantation of the gene-cell construct improved motor activity of the hind limbs and reduced the size of cysts in some animals. However, comparison of the effects of transduced and non-transduced ensheathing cells revealed no significant differences. In parallel in vitro experiments, a decrease in the proliferation of transduced cells compared to non-transduced cells was observed. It is likely that mBDNF reduces proliferation of transduced cells, which can affect their efficiency. The therapeutic efficacy of the new gene-cell construct is most likely provided by the cellular component.

Combined Preparation of Human Olfactory Ensheathing Cells in the Therapy of Post-Traumatic Cysts of the Spinal Cord.

In experiments on rats, co-transplantation of olfactory ensheathing cells of the human olfactory mucosa and neural stem/progenitor cells from the same source into post-traumatic cysts of the spinal cord led to improvement of the motor activity of the hind limbs and reduced the size of the cysts in some animals by 4-12%. The transplantation of a combination of the olfactory mucosa cells is effective and can be used in preclinical trials for the treatment of spinal cord injuries.

Neural Stem/Progenitor Cells of Human Olfactory Mucosa for the Treatment of Chronic Spinal Cord Injuries.

We studied the efficiency of transplantation of neural stem/progenitor cells from human olfactory mucosa in chronic spinal cord injury. Neural stem/progenitor cells were obtained by a protocol modified by us and transplanted to rats with spinal post-traumatic cysts. It was shown that transplantation of neural stem/progenitor cells from human olfactory lining improved motor activity of hind limbs in the recipient rat with spinal post-traumatic cysts (according to BBB scale).

[Brain-derived neurotrophic factor in multiple sclerosis]. / Mozgovoi neirotroficheskii faktor pri rasseiannom skleroze.

The review presents data on brain-derived neurotrophic factor (BDNF), its structure and functions, the effect on the pathogenesis of experimental autoimmune encephalomyelitis and multiple sclerosis (MS). The correlation of BDNF level with clinical manifestations of MS and the changes of its level during disease-modifying therapy is considered.

Synthesis and characterization of bacteriochlorin loaded magnetic nanoparticles (MNP) for personalized MRI guided photosensitizers delivery to tumor.

HYPOTHESIS: Hydrophobic bacteriochlorin based photosensitizer (PS) can be effectively immobilized on MNP covered by human serum albumin (HSA). PS loading into MNP protein shell allows solubilizing PS in water solution without altering its photodynamic activity. MNP@PS can serve as diagnostic tool for tracking PS delivery to tumor tissues by MRI. EXPERIMENTS: Immobilization on MNP-HSA-PEG was performed by adding PS solution in organic solvents with further purification. MNP@PS were characterized by DLS, HAADF STEM and AFM. Absorbance and fluorescence measurements were used to assess PS photophysical properties before and after immobilization. MNP@PS internalization into CT26 cells was investigated by confocal microscopy in vitro and MRI/IVIS were used for tracking MNP@PS delivery to tumors in vivo. FINDINGS: MNP@PS complexes were stable in water solution and retained PS photophysical activity. The length of side chain affected MNP@PS size, loading capacity and cell internalization. In vitro testing demonstrated MNP@PS delivery to cancer cells followed by photoinduced toxicity. In vivo studies confirmed that as-synthetized complexes can be used for MRI tracking over drug accumulation in tumors.

Correction: New ferrocene-based 2-thio-imidazol-4-ones and their copper complexes. Synthesis and cytotoxicity.

Correction for 'New ferrocene-based 2-thio-imidazol-4-ones and their copper complexes. Synthesis and cytotoxicity' by D. A. Guk et al., Dalton Trans., 2018, DOI: 10.1039/c8dt03164a.

New ferrocene-based 2-thio-imidazol-4-ones and their copper complexes. Synthesis and cytotoxicity.

Synthesis, characterization (HRMS, NMR, EPR, XANES, UV-Vis spectroscopy, and electrochemistry), DNA and BSA binding and in vitro biological screening of two new ferrocene-incorporated thiohydantoin derivatives (5 and 6) and their copper coordination compounds are reported. The ferrocene-based thiohydantoin derivatives were prepared by copper-catalyzed azide alkyne cycloaddition reactions between alkynyl ferrocenes and 5-(Z)-3-(2-azidoethyl)-2-(methylthio)-5-(pyridin-2-ylmethylene)-1H-imidazol-4H-one. Alkynyl ferrocenes necessary for these syntheses were prepared by new procedures. Intermolecular redox reactions between the ferrocene fragment and copper(+2) coordinated ions were studied by different methods to determine the mechanism and kinetic constants of redox processes. Ferrocene-containing imidazolones (5 and 6) and their copper complexes were also tested for their in vitro cytotoxic activity against MCF-7 and A-549 carcinoma cells, and also against the noncancerous cell line Hek-293. The results showed modest cytotoxicity against the subjected cancer cell line compared with cisplatin. The ability of the obtained compounds to cause DNA degradation and cell apoptosis was investigated, and the distribution of cytosol/pellets was studied by AAS.

Survival and Migration of Rat Olfactory Ensheathing Cells after Transplantation into Posttraumatic Cysts in the Spinal Cord.

We studied survival of rat ensheathing cells after transplantation into experimental posttraumatic cysts. These cells were prepared according to our original protocol, labeled with intravital membrane dye PKH26, and transplanted into posttraumatic cysts of the spinal cord. The presence of cysts was verified by magnetic resonance imaging. Olfactory ensheathing cells were detected in the spinal cord by the immunofluorescence method. It was shown that rat olfactory ensheathing cells survived in the spinal cord over 4 weeks and their migration was observed. High survival rate and the possibility of obtaining olfactory ensheathing cells from the olfactory mucosa of patients for creation of an autologous preparation allow considering them as very promising material for the treatment of patients with posttraumatic cysts of the spinal cord.

Biodistribution and Tumors MRI Contrast Enhancement of Magnetic Nanocubes, Nanoclusters, and Nanorods in Multiple Mice Models.

Magnetic resonance imaging (MRI) is a powerful technique for tumor diagnostics. Iron oxide nanoparticles (IONPs) are safe and biocompatible tools that can be used for further enhancing MR tumor contrasting. Although numerous IONPs have been proposed as MRI contrast agents, low delivery rates to tumor site limit its application. IONPs accumulation in malignancies depends on both IONPs characteristics and tumor properties. In the current paper, three differently shaped Pluronic F-127-modified IONPs (nanocubes, nanoclusters, and nanorods) were compared side by side in three murine tumor models (4T1 breast cancer, B16 melanoma, and CT26 colon cancer). Orthotopic B16 tumors demonstrated more efficient IONPs uptake than heterotopic implants. Magnetic nanocubes (MNCb) had the highest r2-relaxivity in vitro (300 mM-1·s-1) compared with magnetic nanoclusters (MNCl, 104 mM-1·s-1) and magnetic nanorods (MNRd, 51 mM-1·s-1). As measured by atomic emission spectroscopy, MNCb also demonstrated better delivery efficiency to tumors (3.79% ID) than MNCl (2.94% ID) and MNRd (1.21% ID). Nevertheless, MNCl overperformed its counterparts in tumor imaging, providing contrast enhancement in 96% of studied malignancies, whereas MNCb and MNRd were detected by MRI in 73% and 63% of tumors, respectively. Maximum MR contrasting efficiency for MNCb and MNCl was around 6-24 hours after systemic administration, whereas for MNRd maximum contrast enhancement was found within first 30 minutes upon treatment. Presumably, MNRd poor MRI performance was due to low r2-relaxivity and rapid clearance by lungs (17.3% ID) immediately after injection. MNCb and MNCl were mainly captured by the liver and spleen without significant accumulation in the lungs, kidneys, and heart. High biocompatibility and profound accumulation in tumor tissues make MNCb and MNCl the promising platforms for MRI-based tumor diagnostics and drug delivery.

Magnetic Resonance Imaging of Tumors with the Use of Iron Oxide Magnetic Nanoparticles as a Contrast Agent.

We studied the possibility of using BSA-coated magnetic iron oxide nanoparticles for magnetic resonance imaging diagnosis of C6 glioblastoma, 4T1 mammary adenocarcinoma, and RS-1 hepatic mucous carcinoma. In all three cases, magnetic nanoparticles accumulated in the tumor and its large vessels. Magnetic resonance imaging with contrast agent allows visualization of the tumor tissue and its vascularization.

Relationship between the Size of Magnetic Nanoparticles and Efficiency of MRT Imaging of Cerebral Glioma in Rats.

BSA-coated Fe3O4 nanoparticles with different hydrodynamic diameters (36±4 and 85±10 nm) were synthesized, zeta potential and T2 relaxivity were determined, and their morphology was studied by transmission electron microscopy. Studies on rats with experimental glioma C6 showed that smaller nanoparticles more effectively accumulated in the tumor and circulated longer in brain vessels. Optimization of the hydrodynamic diameter improves the efficiency of MRT contrast agent.

Core-shell-corona doxorubicin-loaded superparamagnetic Fe3O4 nanoparticles for cancer theranostics.

Superparamagnetic iron oxide magnetic nanoparticles (MNPs) are successfully used as contrast agents in magnetic-resonance imaging. They can be easily functionalized for drug delivery functions, demonstrating great potential for both imaging and therapeutic applications. Here we developed new pH-responsive theranostic core-shell-corona nanoparticles consisting of superparamagentic Fe3O4 core that displays high T2 relaxivity, bovine serum albumin (BSA) shell that binds anticancer drug, doxorubicin (Dox) and poly(ethylene glycol) (PEG) corona that increases stability and biocompatibility. The nanoparticles were produced by adsorption of the BSA shell onto the Fe3O4 core followed by crosslinking of the protein layer and subsequent grafting of the PEG corona using monoamino-terminated PEG via carbodiimide chemistry. The hydrodynamic diameter, zeta-potential, composition and T2 relaxivity of the resulting nanoparticles were characterized using transmission electron microscopy, dynamic light scattering, thermogravimetric analysis and T2-relaxometry. Nanoparticles were shown to absorb Dox molecules, possibly through a combination of electrostatic and hydrophobic interactions. The loading capacity (LC) of the nanoparticles was 8 wt.%. The Dox loaded nanoparticles release the drug at a higher rate at pH 5.5 compared to pH 7.4 and display similar cytotoxicity against C6 and HEK293 cells as the free Dox.

[Induction of apoptosis in murine myeloma cells NS0/1, transfected with the gene for the basic heat shock protein HSP70i]. / Induktsiia apoptoza v kletkakh myshinoi mielomy NS0/1, transfitsirovannoi genom osnovnogo belka teplovogo shoka BTSh70i.

Murine myelomas are rare cell variants deficient in inducible isoform of Hsp70 that protects cells from injury. In these cells Hsp70 is absent and is not induced under stress conditions. In this study myeloma cells NS0/1 were transfected with hsp70, and their susceptibility to apoptosis was challenged by serum deprivation or hydrogen peroxide. Expression of Hsp70 in NS0/1 cells made them more resistant to apoptosis in serum-free medium but did not affect their response to hydrogen peroxide. Hsp70 involvement in the protection of myeloma cells from apoptosis caused by different agents is discussed.