Mesenchymal stem cell (MSC) therapy represents an alternative approach for tissue regeneration and inflammation control. In spite of a huge amount of preclinical data that has been accumulated on the ...therapeutic properties of MSCs, there are many conflicting results, possibly due to differences in the properties of MSCs obtained from different sources or underestimated mechanisms of MSC in vivo behavior. This review consolidates the in vivo effects of MSC therapy, discusses the fate of MSCs after intravascular and local delivery and proposes possible trends in MSC therapy.
We studied the effect of intranasal administration of exosomes obtained by culturing of multipotent mesenchymal stromal cells (MMSC) isolated from the Wharton’s jelly of the human umbilical cord on ...spatial memory of olfactory bulbectomized mice demonstrating the basic signs of a sporadic form of Alzheimer’s disease. Intranasal administration of isolated exosomes expressing typical markers CD9, CD63 and CD81 improved spatial memory in bulbectomized animals, which manifested in a significant increase in the number of visits to the target sector and the time spent there in comparison with indifferent sectors. After administration, labeled exosomes were found in the hippocampus and neocortex, the structures playing an important role in learning and memory processes and affected by Alzheimer’s disease. The advantages of exosomes in comparison with MMSC are their small size, low immunogenicity, and inability to cause cell transformation together with high therapeutic efficacy.
Chitosan (Chi) is a biodegradable nontoxic polycation with multiple reactive groups that is easily used to obtain derivatives with a desired charge and hydrophobic properties. The aim of this work ...was to study the intracellular traffic of positively charged hexanoyl-chitosan (HC) or HC-based nanoparticles (HCNPs) and negatively charged succinoyl-chitosan (SC) and SCNPs in epithelial and macrophage cell lines. By using flow cytometry we demonstrated that positively charged HC adhered to cell membranes quicker and more efficiently than negatively charged SC or NPs. However confocal studies showed that SC and SCNPs penetrated cells much more efficiently than HC while HCNPs did not enter the epithelial cells. Macrophages also phagocyted better negatively charged material but were able to engulf both HC and HCNPs. Upon entering the cells, SC and SCNPs were co-localized with endosomes and lysosomes while HC was found in mitochondria and, to a lesser extent, in lysosomes of epithelial cells. Macrophages, RAW264.7, more efficiently transported all Chi samples to the lysosomal compartment while some positively charged material was still found in mitochondria. Incubation of Chi derivatives and ChiNPs at pH specific to mitochondria (8.0) and lysosomes (4.5) demonstrated the neutralization of Chi charge. We concluded that epithelial cells and, to a lesser extent, macrophages sort charged material to the organelles neutralizing Chi charge.
Chitosan (Chi) is a biodegradable nontoxic polycation with multiple reactive groups that is easily used to obtain derivatives with a desired charge and hydrophobic properties.
According to WHO, cancer is the cause of ~5 million deaths annually. To date, there is no universal solution to fight cancer despite outstanding achievements of radiotherapy, chemotherapy, and ...immunotherapy. In this regard, there is a need to develop new approaches to antitumor therapy, in particular based on the search and use of targeted molecules that allow killing tumor cells of various types with high efficiency without significant toxic effects on healthy organs and tissues. This review presents the characteristics of the main proteins of the heat shock proteins (HSP) family, the features of their expression in tumor cells, and the possibility of using monoclonal antibodies against these proteins as a guiding vector for antitumor immunotherapy.
Signaling proteins involved in the TGF-β (transforming growth factor beta) pathway regulate cellular processes such as cell growth, division, differentiation, migration, invasion, and apoptosis. Due ...to the large contribution of the TGB-β signaling pathway to carcinogenesis, these proteins are promising oncotargets. Based on the literature data, we propose a new structural type of TGF-β receptor inhibitors that are 2-aminopyrimidine derivatives. Two general approaches to their synthesis have been proposed, where the key step is the three-component Biginelli condensation producing the pyrimidine fragment. Sixteen new compounds have been synthesized, and their in vitro antiproliferative activity has been evaluated against a panel of tumor cell lines.
Alzheimer’s disease (AD) remains one of the socially significant pathologies still lacking effective therapy. The purpose of this work was to analyze the efficacy of the intravenous (i.v.) ...administration of exosomes obtained from human umbilical cord Wharton jelly multipotent mesenchymal stromal cell culture supernatant. Exosomes were isolated by column filtration and characterized by the expression of specific markers and in vitro binding to mouse fibroblast cells L929. Using a model of the sporadic form of AD, it was shown that i.v. administration of exosomes prevented the deterioration of spatial memory in olfactory bulbectomized mice (OBE). The therapeutic effect was possibly due to the ability of exosomes to penetrate the brain–blood barrier of OBE animals, which was confirmed by visualization of fluorescently labeled exosomes in the cortex and hippocampus after i.v. administration of exosomes.
A series of colchicine and thiocolchicine derivatives bearing a Michael acceptor moiety in ring
A
were synthesized. Some of these compounds exhibit cytotoxic activity in the nanomolar range, ...efficiently disrupt the mitotic spindle, and cause the accumulation of G2/M-phase cells resulting in the development of apoptosis. These derivatives can be covalently bound to the cysteine residues at the colchicine-binding site of tubulin.
Conjugates of the natural alkaloid (a
R
,7
S
)-colchicine with bicyclic monoterpenoids and their derivatives were synthesized for the first time. Molecular docking of the synthesized agents in the ...active site of the main viral protease of the SARS-CoV-2 virus was carried out. The cytotoxic properties of the agents against different cell lines and the ability to inhibit the main viral protease 3CLPro were studied.
Smooth skin mycoses are common all over the world and occur in 20-30% of the population. Currently, with climate change, the distribution areas of pathogenic fungi are changing, which is observed all ...over the world. In this paper, the analysis of changes in the epidemiological regions of the spread of mycoses of the feet and hands, microsporia, trichophytia and onychomycosis in Russia is carried out. The most disadvantaged federal districts have been identified. The incidence of mycoses of the feet and hands, as well as onychomycosis, is increased in the Northwestern, Central, Ural and Far Eastern districts. At the same time, infections in the Far Eastern District are localized mainly in the Khabarovsk Territory, but not in the Yamalo-Nenets District. Microsporia is common in the Volga and North Caucasian districts. The incidence of trichophytia is increased in the Siberian, Far Eastern and, especially, in the North Caucasus (10 times higher than the national average) districts. In recent years, the incidence of microsporia has significantly decreased in the Southern and Far Eastern districts. At the moment, the Southern District is the most prosperous in terms of epidemiology of all types of superficial skin mycoses. In the North Caucasian district, it is necessary to find out the cause of highly increased trichophytia. First of all, this may be due to aquaphilic pathogens. The article provides recommendations for the treatment and prevention of mycoses of smooth skin. The main drug in the treatment of superficial skin mycoses is sertaconazole. The hydrophobic nature of the drug makes it possible to obtain effective topical products based on it (creams, gels, shampoos, candles). Several sertaconazole-based drugs have been developed in Russia, for example, Acrimicol cream, recommended for the treatment and prevention of mycoses of smooth skin and multicolored lichen.
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The synthesis of a lipid conjugate of immunostimulatory oligodeoxyribonucleotide CpG-ODN (PD-CpG-DOPE) is described. Liposomes loaded with a composition of T-cell epitopes of the SARS-CoV-2 virus ...(7 peptides) and carrying the PD-CpG-DOPE conjugate in the membrane, including lyophilized liposomes suitable for long-term storage, were prepared. In vitro experiments on mouse peritoneal exudate cells showed a tendency to increase the immunogenicity of liposomes with peptides when the PD-CpG-DOPE conjugate was introduced into the lipid bilayer, compared with the addition of the (commercial) phosphorothioate derivative of CpG-ODN in solution.
