A criterion of colorectal cancer diagnosis using exosome fluorescence-lifetime imaging

This study was aimed to investigate the applicability of the exosome fluorescence-lifetime imaging microscopy (FLIM) for colorectal cancer (CRC) diagnosis. Differential ultra-centrifugation was used to extract exosomes from the blood plasma of 11 patients with colon polyps (CPs) and 13 patients with CRC at the T2-4, N0-3, and M0-1 stages. Analysis was performed using a two-photon FLIM device. In total, 165 and 195 FLIM images were recorded for the CP and CCR patient groups, respectively. Two classes of exosomes differentiated by autofluorescence average lifetime tm were discovered in the samples. The first class of exosomes with tm = (0.21 0.06) ns was mostly found in samples from CRC patients. The second class with tm = (0.43 0.19) ns was mostly found in samples from CP patients. The relative number of “CRC-associated” exosomes Nch in the FLIM dataset was shown to be very small for the CP patient group and large for the CRC patient group. This difference was statistically significant. Therefore, the suggested CRS diagnostics criterion can be as follows. If Nch > 0.5, the probability of CRC is high. If Nch < 0.3, the probability of CRC is low

Features of Chronic Bronchitis in Different Age Groups

Background: Lung diseases are assuming greater relevance and importance today. Chronic bronchitis is a self-nosology, which may precede the development of COPD, the importance of which can hardly be overestimated. The main problem in this disease is caused by late diagnosis and treatment due to the delay by patients in seeking medical help. The aim of the work was to study the distribution and exposure to tobacco smoke, especially chronic bronchitis, depending on various factors, including age. Methods: We examined 1779 persons, including 855 men and 924 women. The mean age of the population was 35.83±8.3 years. We conducted surveys and spirometry. The outcome was assessed after a bronchodilation test was performed with salbutamol 400 mcg. We performed all statistical analysis using software package Statistica 10. Results: We identified chronic bronchitis in 9.2% of the cases in the group of younger individuals and in 14.9% of the cases in the group of older individuals, during the active detection of chronic bronchitis using questionnaires. The prevalence of cigarette smoking was slightly higher among the younger (39.5%) than the older persons (33.6%); the frequency of smoking in a group of chronic bronchitis was reliably higher. Also, in this group, the performance spirometry reliably decreased. Conclusions: Outpatient survey is an effective method of identifying chronic bronchitis. Smoking is a major risk factor in the group of young respondents and the prevalence of smoking is inversely related to the education level of the respondents, regardless of age. As the decline in the Forced Expiratory Volume (FEV1 and FEV1/FVC) is the main criterion diagnosis of COPD, it revealed significant declines in the FEV1 of the younger smoking individuals, which may help to predict the development of COPD in the older age group

Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice

Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals. We have applied the mitochondria-targeted antioxidant 10-(6′-plastoquinonyl)decyltriphenylphosphonium (SkQ1) to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice. Healing of full-thickness excisional dermal wounds in diabetic C57BL/KsJ-db−/db− mice was significantly enhanced after long-term (12 weeks) administration of SkQ1. SkQ1 accelerated wound closure and stimulated epithelization, granulation tissue formation, and vascularization. On the 7th day after wounding, SkQ1 treatment increased the number of α-smooth muscle actin-positive cells (myofibroblasts), reduced the number of neutrophils, and increased macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change the level of the circulatory IL-6 and TNF. SkQ1 pretreatment also stimulated cell migration in a scratch-wound assay in vitro under hyperglycemic condition. Thus, a mitochondria-targeted antioxidant normalized both inflammatory and regenerative phases of wound healing in diabetic mice. Our results pointed to nearly all the major steps of wound healing as the target of excessive mitochondrial reactive oxygen species production in type II diabetes

Small-angle X-ray characterization of the nucleoprotein complexes resulting from DNA-induced oligomerization of HIV-1 integrase

HIV-1 integrase (IN) catalyses integration of a DNA copy of the viral genome into the host genome. Specific interactions between retroviral IN and long terminal repeats (LTR) are required for this insertion. To characterize quantitatively the influence of the determinants of DNA substrate specificity on the oligomerization status of IN, we used the small-angle X-ray scattering (SAXS) technique. Under certain conditions in the absence of ODNs IN existed only as monomers. IN preincubation with specific ODNs led mainly to formation of dimers, the relative amount of which correlated well with the increase in the enzyme activity in the 3′-processing reaction. Under these conditions, tetramers were scarce. Non-specific ODNs stimulated formation of catalytically inactive dimers and tetramers. Complexes of monomeric, dimeric and tetrameric forms of IN with specific and non-specific ODNs had varying radii of gyration (R(g)), suggesting that the specific sequence-dependent formation of IN tetramers can probably occur by dimerization of two dimers of different structure. From our data we can conclude that the DNA-induced oligomerization of HIV-1 IN is probably of importance to provide substrate specificity and to increase the enzyme activity

Medium-Dependent Antibacterial Properties and Bacterial Filtration Ability of Reduced Graphene Oxide

Toxicity of reduced graphene oxide (rGO) has been a topic of multiple studies and was shown to depend on a variety of characteristics of rGO and biological objects of interest. In this paper, we demonstrate that when studying the same dispersions of rGO and fluorescent Escherichia coli (E. coli) bacteria, the outcome of nanotoxicity experiments also depends on the type of culture medium. We show that rGO inhibits the growth of bacteria in a nutrition medium but shows little effect on the behavior of E. coli in a physiological saline solution. The observed effects of rGO on E. coli in different media could be at least partially rationalized through the adsorption of bacteria and nutrients on the dispersed rGO sheets, which is likely mediated via hydrogen bonding. We also found that the interaction between rGO and E. coli is medium-dependent, and in physiological saline solutions they form stable flocculate structures that were not observed in nutrition media. Furthermore, the aggregation of rGO and E. coli in saline media was observed regardless of whether the bacteria were alive or dead. Filtration of the aggregate suspensions led to nearly complete removal of bacteria from filtered liquids, which highlights the potential of rGO for the filtration and separation of biological contaminants, regardless of whether they include live or dead microorganisms

Medium-Dependent Antibacterial Properties and Bacterial Filtration Ability of Reduced Graphene Oxide

Toxicity of reduced graphene oxide (rGO) has been a topic of multiple studies and was shown to depend on a variety of characteristics of rGO and biological objects of interest. In this paper, we demonstrate that when studying the same dispersions of rGO and fluorescent Escherichia coli (E. coli) bacteria, the outcome of nanotoxicity experiments also depends on the type of culture medium. We show that rGO inhibits the growth of bacteria in a nutrition medium but shows little eect on the behavior of E. coli in a physiological saline solution. The observed eects of rGO on E. coli in dierent media could be at least partially rationalized through the adsorption of bacteria and nutrients on the dispersed rGO sheets, which is likely mediated via hydrogen bonding. We also found that the interaction between rGO and E. coli is medium-dependent, and in physiological saline solutions they form stable flocculate structures that were not observed in nutrition media. Furthermore, the aggregation of rGO and E. coli in saline media was observed regardless of whether the bacteria were alive or dead. Filtration of the aggregate suspensions led to nearly complete removal of bacteria from filtered liquids, which highlights the potential of rGO for the filtration and separation of biological contaminants, regardless of whether they include live or dead microorganisms

C9ORF72 hexanucleotide repeat expansion in ALS patients from the Central European Russia population

Cohorts of amyotrophic lateral sclerosis (ALS) patients and control individuals of Caucasian origin from the Central European Russia (Moscow city and region) were analyzed for the presence of hexanucleotide repeat GGGGCC expansion within the first intron of the C9ORF72 gene. The presence of a large (>40) repeat expansion was found in 15% of familial ALS cases (3 of 20 unrelated familial cases) and 2.5% of sporadic ALS cases (6 of 238) but in none of control cases. These results suggest that the frequency of C9ORF72 hexanucleotide repeats expansions in the Central Europea

THE PROBLEM OF THE PLOT AND THE GENRE IN N. A. RADISHCHEV’S “CHURILA PLENKOVICH, BOGATYR SONGWRITING”

In the 18th–19th centuries, attempts to appropriate folklore heroes and genres in literature were made. One of such literary works was N. A. Radishchev’s poem (1801) where the epic hero Churila Plenkovich became a character. Imitating the folkloric and literary tradition (Homer, Virgil, Ariosto, Voltaire, Wieland, V. A. Levshin, I. P. Bogdanovich), the author combined the images and motives of such genres as bylina (Russian epic song), fairy and literary tale, heroic and comic poem in his work. Using the storyline and retaining the main motives of Levshin’s tale, the poet added mythological and fairy images (Zmey Gorynych (dragon), Yaga, Lel’ (Lel’o), Lada) to his writing, supplemented the narrative with new motives, and gave justifications for the heroes’ actions. Radishchev created literary heroes using fairytale types; he showed their sufferings, emotions and feelings. Radishchev’s Churila lost all features of the bogatyr. He is a literary hero — a handsome, good-looking, ardent and sensitive young man. Prelepa and Yaga have fallen in love with him. His feats represent a plot of romance and adventure novel; his heroic deeds are inspired by Lel’o, a god of love who gives the bogatyr strength. As a result of these transformations, an original fabulous plot and genre of the literary work appeared. The writer is precise in his defining: his Churila is a character of the epic story in verse based on folkloric and literary tale

Graphene Nanoribbons: Prospects of Application in Biomedicine and Toxicity

Graphene nanoribbons are a type of graphene characterized by remarkable electrical and mechanical properties. This review considers the prospects for the application of graphene ribbons in biomedicine, taking into account safety aspects. According to the analysis of the recent studies, the topical areas of using graphene nanoribbons include mechanical, chemical, photo- and acoustic sensors, devices for the direct sequencing of biological macromolecules, including DNA, gene and drug delivery vehicles, and tissue engineering. There is evidence of good biocompatibility of graphene nanoribbons with human cell lines, but a number of researchers have revealed toxic effects, including cytotoxicity and genotoxicity. Moreover, the damaging effects of nanoribbons are often higher than those of chemical analogs, for instance, graphene oxide nanoplates. The possible mechanism of toxicity is the ability of graphene nanoribbons to damage the cell membrane mechanically, stimulate reactive oxidative stress (ROS) production, autophagy, and inhibition of proliferation, as well as apoptosis induction, DNA fragmentation, and the formation of chromosomal aberrations. At the same time, the biodegradability of graphene nanoribbons under the environmental factors has been proven. In general, this review allows us to conclude that graphene nanoribbons, as components of high-precision nanodevices and therapeutic agents, have significant potential for biomedical applications; however, additional studies of their safety are needed. Particular emphasis should be placed on the lack of information about the effect of graphene nanoribbons on the organism as a whole obtained from in vivo experiments, as well as about their ecological toxicity, accumulation, migration, and destruction within ecosystems

BYLINA AS A LITERARY GENRE

The bylina is a Russian epic song about the bogatyrs. Diff erent genre transformations of bylinas are known in folklore: prosaic narrations [pobyval’shchiny], bogatyr tales, legends about the bogatyrs, lubok tales about the feats of the bogatyrs and knights. In the early 19th  century, Russian literature was actively absorbing epic images and motives: the bogatyrs were turning into characters of novellas, literary tales, poems, novels, operas. Some poets and writers were attempting to develop the bylina as a literary genre. Their genre search was a  creative imitation of Th e Tale of Igor’s Campaign [“Slovo o polku Igoreve”] published in 1800 and in some cases of the Collection of Kirsha Danilov (1804). One of the first attempts was Gavrila R. Derzhavin’s work Dobrynya, Dramatic Musical Performance in Five Acts [“Dobrynya, teatral’noe predstavlenie s muzykoyu, v pyati deystviyakh”, 1804]. Glorifying the idea of the state, the poet composes a work where epic and literary characters act and the plot is derived not only from bylinas and tales, but also from chivalric novels. In Stepan S. Andreev’s poem Levsil, a Russian Bogatyr [“Levsil, russkiy bogatyr’”, 1807] the hero is not only a folkloric (epic and fabulous) character, but also a literary one. Alexander F. Veltman’s novel Koshchei the Immortal. A Bylina of the Old Times [“Koshchey bessmertnyy. Bylina starogo vremeni”, 1833] was an ingenious genre experiment. The word ‘bylina’ was used in its title in  the literary genre meaning for the fi rst time ever. The genre of Easter novella Ilya Muromets. A Tale from the Rus’ of the Bogatyrs [“Il’ya Muromets. Skazka Rusi bogatyrskyi”, 1836] by Vladimir I. Dahl emerged from a complicated interaction of the tale, the bylina, the Old Russian novella and the hagiography. The literary transformations of folkloric genre stemmed from the authors’ imaginative need to create a national and historical myth, conjecture the ‘fabulous’ history and imagine what happened in the old preliterate times