Issue 2 | June 2022
Prenatal hypoxia remains the leading cause of infant mortality and severe disability in newborns. Disturbances in the development of fetal brain structures and functions due to hypoxic damage are the main trigger for the development of severe neurological disorders and accelerated neurodegeneration processes and can also be the cause of epileptiform activity in the postnatal period. Herein, the role of chronic prenatal hypoxia on the functional state of C3H+C57Bl6 hybrid mice during the first three weeks of postnatal development and the risks of developing epileptiform activity when provoking audiogenic seizures were assessed. Exposure to chronic prenatal hypoxia was found to increase the risk of neonatal mortality and developmental delay in the surviving individuals in the first two weeks of the postnatal period. It was shown that one of the causes of the failure of adaptation might be the disruption of the functional activity of the mitochondrial apparatus of brain cells mediated by the disruption of the first and second respiratory chain complexes. Exposure to chronic prenatal hypoxia has no significant effect on the increased risk of seizure activity in mice during audiogenic stimulation in late postnatal development, does not activate the development of persistent neurological deficit, and does not significantly affect the cognitive functions and learning ability of animals.
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The study was performed at the Gomel Regional Clinic of Sports Medicine (Belarus). Two hundred thirty-six healthy athletes (134 men and 102 women) were examined. The mean age of the examined athletes was 20 years. Features of blood biochemical parameters in athletes of cyclic sports, strength sports, and team game sports have been evaluated.
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The study of mitochondrial DNA (mtDNA), particularly the hypervariable segment (HVS1) region, is widely used to reconstruct a population's history, structure, and origin. The origin of the Sakha people living in the north-east of Russia has been discussed for more than 300 years, but up to the present time many aspects of their ethnogenesis remain unclear. In order to clarify the migration routes of the ancient ancestors of the Sakha, we analyzed the mitotypes of 69 unrelated representatives of this ethnic group, whose belonging to the ethnic group was traced to the third generation. In the studied Sakha group, we identified 33 mitotypes, the distribution of which by haplogroups approximately coincides with the data of other studies. The results of a comparative study of Sakha mitotypes according to EMPOP data and literature sources revealed a wide distribution of the identified mtDNA HVS1 haplotypes in many populations of Eurasia. A comparison of the obtained mitotypes with the results of mtDNA sequencing of ancient samples shows that most of the mtDNA lines of modern Sakha have long been located on the territory of Yakutia. West Eurasian and East Asian mtDNA lines were incorporated into the Sakha genome at different times in different ways. The results obtained contribute to a better understanding of the routes of ancient migrations of the ancestors of the Sakha population.
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The energy shortage, as well as the lack of antioxidant micronutrients that occur with severe thermal lesions, lead to poor clinical outcomes. It is important to carry out timely and effective therapy that helps maintain the redox and energy balance of the burned body. The aim of this work was to evaluate the energy status of red blood cells in severely burned patients with the use of antioxidant therapy and hyperbaric oxygenation on different days of therapy. The study involved 60 practically healthy people (norm) and patients with burns of I-II-III degree with different localization over 25% of the body surface. The age of patients is from 20 to 87 years. The data obtained suggested the effectiveness of the use of antioxidant therapy in burn patients due to the activation of oxidoreductases that support energy metabolism. The combined use of HBO and antioxidant nutrients in addition to standard therapy presumably contributed to maintaining the energy and redox balance of the body in patients with burns.
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The aim of the work was established as to study the effect of low-intensity laser therapy (LILT) on the morphology of neutrophils by the method of interference microscopy in correlation with metabolic parameters in the use of modulators which permits to assess the contribution of various structures of neutrophils to the realization of LILT effect. There was in vitro research. The neutrophils of rats served as the object of research. The neutrophils were incubated with adrenalin, cortisol, and β-blockers of adrenoreceptors. The effect of LILT in combination with a preliminary incubation of these substances was studied. Autonomous laser shower MarsiK (R&D company “Petrolaizer,” Saint Petersbourg), a laser therapeutic complex for animals, was used as a laser irradiation source. The wavelength of the irradiation was 830 nm, and the total power was 90 MW. The phasometry of neutrophils was studied by the laser modulation interference microscopy method, the processes of lipid peroxidation were analyzed by the malondialdehyde concentration, and the ATP concentration was defined by spectrophotometry. LILT provoked unidirectional changes in indices in the groups where the neutrophils were incubated with adrenalin, cortisol, and adrenoreceptor blockers. It manifested in the intensification of lipid peroxidation, increase in ATP concentration, and on the other hand, an increase in phase diameter of neutrophils regarding indicators without the impact of LILT. It is shown that the LILT effect intensity may be modified depending on stress realizing hormones (adrenalin and cortisol), β-blocker of adrenoreceptors. It permits us to suppose that the LILT effects may be realized in different ways depending on the state of the cells.
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The methods of scanning microscopy were used to study blood cells (neutrophil granulocytes, lymphocytes, and erythrocytes) morphology and rigidity. Differences between morphology and adhesion properties of fixed and living cells were shown. The Young’s modulus in various lymphocytes and erythrocytes populations was obtained. Scanning ion-conductance microscopy was compared to the most widespread biological scanning probe methods: atomic force microscopy and scanning electron microscopy. It was established that scanning ion-conductance microscopy is capable of obtaining the morphology and stiffness of living cells at one scan.
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Issue 1 | March 2022
At present, it can be noted that COVID-19 is the most serious challenge to the international health care system in its recent history. Extremely high rates of morbidity and mortality dictate the need for a more detailed study of the pathogenetic aspects of the developing infectious catastrophe. Besides respiratory distress syndrome, systemic inflammatory response syndrome, COVID-19 is characterized by polyvalent disorders of the mechanisms of systemic hemostasis, which has reflected in an increase in the number of venous thromboembolic complications in the overall structure of morbidity and mortality. The given literature summarizes the information on COVID-associated coagulopathy and its effect on changes in the clinical and epidemiological characteristics of venous thromboembolic complications.
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Cisplatin, as an antineoplastic drug belonging to the platinum family, has severely nephrotoxic and neurotoxic side effects. L-carnitine (LC) is an antioxidant-rich natural substance. The notion that LC may play a protective function in Cisplatin-induced nephropathy and neuropathy was investigated in this study. Nephropathy was created by a single intraperitoneal injection of Cisplatin at 20 mg/kg body weight, while neuropathy was induced by daily intraperitoneal injections of Cisplatin at 2.3 mg/kg body weight over two rounds of five days, with five days break in between. The rats were subsequently given LC at a dose of 250 mg/kg body weight, followed by estimation of serum urea and creatinine with histological examination of renal tissue for the nephropathy group and evaluation of nerve conduction velocity for the neuropathy group. In comparison to the nephropathy group, blood urea and creatinine levels were significantly lower after treatment with LC. Furthermore, LC therapy improved the physiological characteristics of the sciatic nerve significantly. In conclusion, the significant impairment of renal function and the decrease in sciatic nerve conduction velocity induced by Cisplatin may be avoided if L-carnitine is administered as a preventative medication.
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Conditions were determined for the identification of cholesterol in erythrocyte membranes by the fluorescent method using amphotericin B as a probe. We performed a comparative analysis of electronic absorption and fluorescence spectra of cholesterol, amphotericin B, and the products of their interaction, and determined the optimal wavelengths for excitation (328 nm) and recording (468 nm) of fluorescence. Amphotericin B stained cholesterol in membranes was visualized by fluorescence microscopy. It was shown that the registration of emission band at 468 nm on fluorescence spectra of free and membrane-bound cholesterol can serve as a marker of the presence of this lipid in the samples.
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The search for new molecular targets to protect brain cells from ischemic damage has remained one of the most urgent tasks of neurobiology and medicine over the past decades. The modern concept of the glucose-lactate shuttle, the main mechanism for providing energy support to neurons under conditions of increased physiological activity, implies a functional fusion of neuron and astrocyte metabolism, which becomes particularly important under energy or oxygen starvation conditions. The transfer of energy substrates in response to increased glutamate release by the presynaptic terminal occurs through monocarboxylate transporters (MCTs) and depends on a large number of endogenous mechanisms of homeostasis. Our work examined the role of MCTs in the implementation of the neuroprotective effect of glial cell-derived neurotrophic factor (GDNF), one of the key participants in the regulatory system capable of maintaining the viability and functional activity of neurons under conditions of energy starvation. It has been shown that the application of the MCT1 transporter inhibitor, even under normal conditions, significantly affects the parameters of spontaneous bioelectrical activity of neural networks and cell viability of primary dissociated hippocampal cultures. However, the authors’ data on the role of this type of transporters in glucose deprivation and the effect of MCT blockade on the neuroprotective effects of GDNF are of the greatest interest.
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Pseudomonas syringae is a widely distributed bacterial epiphyte of plants. When the temperature of the environment drops below zero, P. syringae can serve as biological ice nuclei due to the presence of specialized ice-nucleating proteins. This property has found application in various fields, but despite its evident importance, the molecular mechanisms behind protein-induced freezing have remained largely elusive. One of the problems in the study of the ice-nucleating process is the difficulty of carrying out experiments with freezing/melting solutions at near-zero temperatures. The experimental design implies special requirements for the equipment used and measurement technique. In this work, we used an experimental setup assembled from a dry thermostat that maintains a constant temperature and an accurate digital thermometer. We experimentally tested the possible sources of errors of the setup. As a result, we have shown that the accuracy of determining the freezing temperature of liquids and the coexistence of ice and water is mainly determined by the accuracy of the thermometer. The accuracy of determining the melting point of ice depends on the volume of the sample and is systematically underestimated in our setup. Using the proposed experimental technique, we performed a comparative study of P. syringae and E. coli cells, which revealed that P. syringae cells affect not only the freezing point of the solution but also the temperature of the coexistence of ice and water. The observed effect can be explained by the binding of P. syringae cells to the ice surface.
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In this study, we investigated the toxic properties of synthesized immunomagnetoliposomes of the following composition: phosphatidylcholine - cholesterol - disteroylphosphoethanolamine-polyethylene glycol (2000) - magnetite - antibodies to histone H3. Their dimensional characteristics were studied by the dynamic light scattering method. It was revealed that liposomal nanoparticles have dimensions of 176.4 ± 12.9 nm. Data on the toxicity of the synthesized nanoparticles in relation to human blood cells: liposomes in cells to liposomes ratio from 1/1 to 1/1000 have no toxic effect on lymphocytes; lactate dehydrogenase (LDH) release from human blood erythrocytes has been observed in the case of cells/liposomes ratio 1/100-1/1000 after the incubation with liposomes containing sodium azide (0.03%).
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The widespread occurrence of drug-resistant urogenital mycoplasmas and the high rate of their genetic variability make it possible to consider Mycoplasma hominis as a natural reservoir of antibiotic resistance determinants. Multiple drug resistance of many bacterial types is due to the active elimination of the antibiotic from the cell through various efflux systems. The genome structure of ten clinical isolates Mycoplasma hominis was studied using next-generation sequencing. The molecular genetic characterization family MATE proteins of Russian isolates M. hominis genes using bioinformatics analysis was obtained in the first. It has been established that proteins of the transport systems (ABC-transporters) and MATE play an important role in the formation of antibiotic resistance in urogenital mycoplasmas. The activity and functioning of transport systems are associated with the presence of mutations in the genes encoding regulatory proteins. Efflux systems should be considered as promising potential targets in the creation of new generation antibacterial drugs.
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Issue 4 | December 2021
The methodology of digital psychophysiological mapping was used in a group of 18 stroke patients and a matched group of healthy controls to reveal possible markers of acute cerebrovascular accident. The patients were found to have a number of indicators that were significantly different from the norm and could claim the role of stroke biomarkers. Among them there are lowered values of the power and peak frequency of the EEG alpha rhythm, significantly lowered HRV indices, as well as a significantly higher levels of emotional disadaptation. Stroke patients participated in a treatment session, in which they were exposed to EEG-based bimodal (light-musical) adaptive neurostimulation, in which some EEG characteristics (EEG oscillators) control sound (musical) stimulation, and other EEG characteristics (native EEG) simultaneously control light stimulation. As a result of the treatment, patients demonstrated a normalization of all the described indicators of the functional state: the values of a power and frequency of the EEG alpha rhythm significantly increased and approached the norm, as well as the parameters of the cardiovascular system and the cognitive-emotional sphere of stroke patients. The method of EEG-guided adaptive neurostimulation used in this work demonstrates the possibility of effective cognitive rehabilitation of stroke patients even with a single application.
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Purpose of the study: substantiation of indications and assessment of results X-ray endovascular treatment of "critical" PE in patients with acute hemorrhagic cerebrovascular accident. Material and methods: the study included 47 patients with acute violation of cerebral circulation for hemorrhagic and mixed types complicated by massive pulmonary thromboembolism of high risk, with "critical" manifestations of right ventricular failure. Depending on the method of PE treatment used, the patients were divided into 2 groups: the study group (17 people), in which endovascular mechanical fragmentation of thromboembols was performed, and the control group (30 people), in which only basic intensive therapy was used. Results: patients of the study group underwent thromboembolic fragmentation in order to transfer embolism of the trunk and the main branches into embolism of smaller branches of the pulmonary artery. Technical success of the procedure (destruction of the central thromboembolus) was achieved in 100% of the cases. 14 patients (82.4%) showed positive clinical dynamics in the form of an improvement in the general condition, a decrease in pressure in the pulmonary artery, and a decrease in the volume of the lesion of the pulmonary bed according to CT angiography. Three patients (17.6%) died in the early postoperative period. In the control group of 30 patients, 25 patients died, hospital mortality was 83.3%. Conclusion: the method of catheter endovascular fragmentation of thrombi for the treatment of "critical" pulmonary embolism in patients with acute hemorrhagic cerebrovascular accident leads to a rapid and safe decrease in pulmonary artery pressure.
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Objectives: to evaluate the efficacy and safety of circular radiofrequency ablation of the pulmonary trunk and main pulmonary arteries in patients with severe pulmonary hypertension using a histological study. Materials and methods: for the analysis of autopsy material from non-operated patients, three study groups were identified. Experimental – with chronic pulmonary hypertension with mitral disease and radiofrequency ablation. Comparisons – with severe pulmonary hypertension and without radiofrequency ablation. Control – without pulmonary hypertension and radiofrequency ablation, who died from causes not associated with cardiovascular diseases. Hematoxylin and eosin staining according to Van Gieson was used to visualize the damage to the tissue samples of the vascular wall. The technique of impregnation with silver staining was used to determine the damage to the nerve plexuses and endings. Results: analysis of the results of optical density and the relative average area of argentophilic fibers revealed a decrease in these parameters in the ablation group. In patients of the comparison group, where a high level of pulmonary hypertension was also observed, there was a significant accumulation of argentophilic fibers. Conclusion: histological examination showed an increase in the formation of sympathetic nerves in the adventitia of the pulmonary arteries in severe pulmonary hypertension. The same pulmonary arteries denervation procedure is an effective and safe way of denervation of the sympathetic plexuses located in the adventitia layer of the pulmonary arteries, which is confirmed by histological studies.
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The actuality of the problem of thermal trauma is determined by its high prevalence. Severe disorders of central, regional and peripheral hemodynamics are developing with a predominant violation of microcirculation and metabolic processes in the body during burn disease. Promising NO donors suitable for biomedical use are dinitrosyl iron complexes (DNIC). The aim of the study was to evaluate the effect of DNIC on the state of microcirculation in normal conditions and on the model of combined thermal trauma (CTT). The experiments were carried out on white male rats of the Wistar line. CTT (contact burn on the area of 20% of the body surface and thermal inhalation exposure to hot air and combustion products for 20-30 seconds) was applied under anesthesia. Animals with CTT were treated daily with intraperitoneal injections of a 10% DNIC solution (1 ml; 0.3 micromol/l). Laser Doppler flowmetry was used to assess the dynamics of the microcirculation state. The physiological and biochemical mechanisms of microcirculation disorders in CTT are revealed in the work. There was an increase in the endothelial, neurogenic and respiratory components of microcirculation, microhemodynamics of the border area of the burn, and the index of the microcirculation bypass. It was shown that when using 0.3 micromol/l of DNIC in rats under normal conditions, there is a decrease in the neurogenic and respiratory components, an increase in perfusion and the myogenic component of the microcirculatory channel. The role of 0.3 micromol/l of DNIC in the normalization of microcirculation in CTT was established.
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Currently, we continue to actively develop a high-tech rehabilitation method of microwave therapy using sub- and millimeter-wave radiation sources. However, the question of the feasibility of its use in the rehabilitation of patients with burn injuries is not sufficiently studied. In this connection, the works analyzing the effectiveness of the influence of different micro-wave ranges on the nature and degree of development of adaptive metabolic and vascular reactions in the early period of trauma, which affect the outcome of the burn, become particularly relevant. The study was carried out on male rats of the Wistar line under conditions of experimental contact thermal burn of the IIIА degree on an area of 20% of the dorsal surface of the body. A 7-day course of point non-contact exposure to broadband microwave emitters of various ranges with a radiation power of 10 µW on the occipital protuberance area was started after the rats were released from anesthesia when the contact burn was applied. The vascular status, the state of oxidative stress and energy homeostasis were assessed by the intensity of oxidative processes, antioxidant protection, and the total microcirculation index with a wavelet analysis. The obtained data reliably revealed a more pronounced favorable effect on the level of adaptive reactions in the range of 150,179-150.664 GHz, which contains the frequencies of radiation and absorption of nitric oxide. This should be taken into account when choosing frequency-energy parameters and developing a potential method of rehabilitation in the acute period of burn injury.
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The work aimed to study the protein spectrum, morpho-functional state of erythrocyte membranes under stress and correction by low-intensity laser radiation. The experiments were carried out in vitro. Low-intensity laser radiation with a wavelength of 830 nm and a power of 90 mw was used for irradiation. Laser therapy was performed using an autonomous laser shower "MarsIK" (NPO "Petrolaser", St. Petersburg). The protein fractions of red blood cells were analyzed by electrophoresis, the morphology of red blood cells by laser interference microscopy, the еletrophoretic mobility of erythrocytes was measured by microelectrophoresis in our modification and the concentration of malondialdehyde in red blood cells by reaction with thiobarbituric acid spectrophotometrically. It is proved that the change of protein fractions in the erythrocyte membrane under stress, a decrease in the amount of spectrin, band 3 protein, glycophorin and ankirin. The stress is characterized by an increase in the number of echinocytes, stomatocytes and degenerative-altered red blood cells. Exposure to LLLT on blood samples determined the recovery of the studied parameters to the control group values (physiological norm). The role of the discovered metabolic changes in RBC in stress and their correction by LLLT is under discussion.
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The article focuses on identifying specific eye movement parameters during reading unfamiliar words to study the formation of epistemic evaluation. The sample consisted of 40 students. 240 eye-tracking records were registered while the participants were reading 6 texts in Russian. The study revealed that the speed of saccades decreased, and the duration of fixations increased while reading an unknown word. Eye movements at first encounter of a new term may be an indicator of epistemic evaluation formation.
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Increase in the life expectancy of the population is associated with a tendency of aging in patients with chronic heart failure (CHF). Gender, age and genetic differences of the individual risk factors are still discussed in the aspect of influence on the heart failure clinical phenotype. The study aimed to identify the gender and age differences of chronic heart failure clinical characteristics in terms of the ZBTB17 gene (rs10927875) polymorphism. Materials and methods. A total of 351 patients with CHF of ischemic etiology of both genders were examined. The average age of men was 65.3±9.9, women ̶ 69.7±9.61 years. Results and conclusions: CHF of ischemic etiology in the absence of differences in the burdened family history, previous myocardial infarction (MI) observed mainly in middle-aged and elderly men and elderly and senile women. Significant gender differences in comorbidities were revealed: in 40% of men, CHF was associated with chronic obstructive pulmonary disease (COPD), in 47.3% of women ‒ with chronic kidney disease (CKD) and in 32.2% - with diabetes mellitus (DM). The distribution of rs10927875 polymorphism ZBTB17 genotypes were corresponded to the Hardy-Weinberg equilibrium (χ2 = 0.272, p = 0.873). CC genotype in men was associated with reduced left ventricular ejection fraction (LVEF). CT genotype in women associated with CHF FC III and IV due to the frequent indications in the past on myocardial infarction, concomitant DM, obesity and hypercholesterolemia. The CT genotype rs10927875 was characterized by a frequent combination of CHF with COPD in men and CKD and DM in women.
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SELENOM is a highly conserved protein, presented in different species and classes of animals, belongs to the family of thioredoxin–like folding proteins. It is known that SELENOM is more expressed in the brain and is very sensitive to selenium deficiency in this organ; it is involved in the regulation of calcium signaling, redox homeostasis, and apoptosis in brain cells. This study showed that SELENOM–knockdown in human glioblastoma cells (A–172 cell line) contributed to a decrease in the number of apoptotic A–172 cells after 24 or 48 h treatment with the known apoptosis inducer staurosporine, as well as a significant decrease in the number of necrotic cells after 48 h treatment with this inductor. A decrease in SELENOM activity also led to a decrease in the Ca2+ ER–buffer capacity and influenced the level of mRNA expression of key ER–stress markers in glioblastoma cells.
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The aim of the work was to study the effects of photobiomodulation (PBM) in the red spectrum (640 nm) with fluences from 3 mJ/cm2 to 2 J/cm2 in combination with ionizing radiation (IR) at doses of 2-6 Gy against human BJ-5ta-hTERT - postnatal fibroblasts. The cells were exposed to low-intensity red light before or after their exposure to IR, the viability of the cells was determined by MTT 24 hours after the last exposure. It is shown that the effects of PBM depend on the fluence of PBM, the dose of IR and the sequence of the actions of these physical factors on cells. The adaptive effect of PBM was observed only for high fluences-1 and 2 J/cm2 when exposed to PBM and subsequent (after 1 hour) irradiation of IR. At the same time, the stimulating effect of PBM was observed only for low fluences from 3 to 300 mJ/cm2 under IR irradiation and subsequent (after 1 hour) exposure to PBM. These data should be taken into account when using PBM for the correction of adverse events of radiation therapy in an oncological clinic.
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Pulp diseases treatment may lead to complications, such as the development of apical periodontitis registered with the help of X-ray examination. At the same time, a dentist might provide endodontic treatment associated with apical periodontitis in case there are relevant X-ray changes. In both cases, the periapical status follow-up is required for causality assessment. CBCT data of 2915 endodontically treated teeth were studied assessing the distance from the X-ray root apex to the root filling, as well as assessing the periapical status and tracing the relation between those. It is least probable to detect periapical changes if the length of the root canal filling is 0-1 mm from the X-ray apex, more probable within the length of 1-2 mm, and most probable within the level of over 1 mm and 2 mm, correspondingly. An individual approach excludes the strategy of ‘indication — contra-indication’ related to the length of the root canal filling showing no ground to assess it as a success criterion for endodontic treatment or as an indication for retreatment regardless of the clinical case. In many situations, if there are no clinical signs of unsuccessful endodontic treatment, the periapical tissues follow-up strategy is well-grounded.
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Issue 3 | September 2021
Mitochondria-endoplasmic reticulum contacts (MERC) are known as one of the key regulators of many cell functions. In particular, MERC effects on the mobility and morphology of mitochondria, exchange of calcium and lipids between organelles, and participates in the processes of autophagy and apoptosis that are crucial for neuronal development. MERC can influence the functioning of the neurotrophic factor BDNF through the activation of the Sigma-1 receptor. That points to the presence of feedback i.e. itself BDNF influence on the structural characteristics of MERC. At the same time, the effect of chronic stimulation of BDNF or blockade of TrkB receptors on an ability to form contacts between mitochondria and ER is different and depends on cellular compartment.
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In probabilistic conditions, people choose low-payoff alternatives on some trials, thus failing to maximize their payoffs. We suggest that such behavior implicates exploration of task rules by choosing risky options instead of exploiting more rewarding alternatives. We hypothesized that exploration would affect brain responses to feedback. Further, a shift to exploration develops gradually and, therefore, a decision to make an exploratory choice may be observed on trials preceding risky choices. We investigated beta power (16–30 Hz) in the magnetoencephalographic data from 62 healthy participants performing a two-choice probabilistic gambling with monetary gains and losses. The effects were found at 600–800 ms after feedback onset in frontal, central and occipital brain regions. On trials preceding risky choices we identified a decrease in beta power which implies a change in decision-making strategy and a shift towards cognitive flexibility and exploration. An increase in beta power during risky decisions indicates that reward learning mechanisms are implicated. Increases in beta power following losses in risky choices indicates at the process of updating the internal representation of the task. In summary, current findings reveal that the outcomes of exploratory trials are processed differentially, while there is no evidence of such processing on exploitatory trials. This corroborates the hypothesis that exploratory choices represent active probing into the surmised task rules. Current findings also suggest that the processing of outcomes preceding the exploratory trials is altered in such a way that subjects override their intention to use the utility model and reset their behavioral strategy.
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Plastic changes in the neurons of the amygdala during learning in fear conditioning and their contribution to the modifications of behavior are well known, but the impact of hippocampal neurons in this behavioral task is not well studied to date. Recently a novel technique for simultaneous recording of calcium signal in multiple neurons in the brain of awake freely moving animals by miniature fluorescent microscope (miniscope) was developed. With the use of the miniscope, we have investigated neuronal activity in the CA1 area of hippocampus during memory formation and a recall in the task of contextual fear conditioning and correlated it with recorded mice behavior. Three epochs during learning were analyzed in mice behavior and brain activity: 120 s before, 2 s during, and 30 s after the electric shock. Memory retrieval was induced by placement of the animals for 180 s in the same context 24 h and 48 h after learning. The total amount of the neurons recorded in three mice was 507 during learning and 401 during memory retrieval. The patterns of neuronal activity were analyzed and discussed.
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Cognitive status and EEG in the theta, alpha, and beta ranges were studied using cluster analysis by discrete optimization in patients with cardiovascular disease in the preoperative period of coronary artery bypass grafting. The cognitive status was measured by Mini-Mental State Examination (MMSE) scale, and an integral indicator of cognitive status (IICS) formed on the basis of complex testing the indices of visual-motor responses, attention, and memory. The new method of clustering the EEG power and the cognitive status made it possible to distinguish groups of patients differenced by cognitive reserves. The IICS better differentiates groups than MMSE. The factors of age and education were decisive only in specific groups. The clusters characterized by the most represented cognitive reserves according to the higher both MMSE and IICS indicators included less pronounced activation of the cortex according to more power of the theta, alpha, and less beta rhythm. Patients with supposedly minimal reserves are differed by a low level of cognitive status, as well as education level together with higher activation state of the cortex. The third type of clusters was distinguished by an unstable composition due to the variability of EEG indicators in it, mostly cortical activity at the alpha1 frequencies. The EEG neurophysiological approach, together with cognitive screening and proposed clustering analysis, could be helpful in understanding mechanisms of cognitive reserves and identify the risk factors of postoperative cognitive dysfunction in patients with brain cardiovascular damage.
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The information influence in the modern globalizing world is a serious challenge to the security of any state. This article presents the results of an experimental study of the way the modern Internet media affect the cognitive attitudes of individuals on the example of two leading international TV channels – RT and BBC. In order to conduct this study our team developed an experimental plan for the psychophysiological recording of deformation of cognitive attitudes under the external informational influence. The study was conducted at the Department of Psychophysiology of the Lobachevsky State University of Nizhny Novgorod from March to May 2018. The experiment was conducted on twenty-one (21) volunteers aged from nineteen to thirty-six, the average age of the group being twenty-four. Since the largest audience of modern communication networks is the younger generation, they became the focus of the study. The authors analyzed the deformations of the cognitive attitudes of individuals to identify distinctive features of these processes.
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The extracellular matrix plays an important role in brain function. Recent findings suggest that disruption of hyaluronan-based extracellular matrix can cause seizure-like activity (Vedunova et al., 2013). Epilepsy can be characterized by an excessive influx of Ca2+ ions through (Ca2+) – permeable AMPA receptors, which may, in certain circumstances, contribute to seizures. Ca2+ – permeability of these receptors is dependent on RNA-editing of pre-mRNA transcript of GluA2 subunit at the Q/R site. Regulation of this process is carried out by a special nuclear enzyme, ADAR2 (Adenosine Deaminase Acting on RNA-2). Thus, the study of the principle of operation of this enzyme can contribute to understanding the mechanism of epileptogenesis.
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Gamma band oscillations (25 - 70 Hz) play an important role in processing of information by neocortical neurons. In simple cells of the cat's visual cortex, it was previously shown that strength of gamma oscillations is modulated by the membrane potential oscillations at the temporal frequency of the stimulus. More recently, theoretical studies using a conductance-based neuronal model have shown that this coupling significantly improves visual stimulus encoding. Due to the availability of a broad range of genetic tools, mice had recently become an important experimental subject for research in various fields of neuroscience, including visual physiology. It has been suggested that gamma oscillations in the mouse visual cortex play a minor role in visual processing due to the lack of specialized neurons that take part in generating gamma oscillations. Here we show, using patch clamp recording from simple cells in the visual cortex of anesthetized mice, that the strength of gamma oscillations is modulated by the phase of stimulus-induced oscillations during visual stimulation with moving gratings. In addition, using patch clamp recording from mouse visual cortex neurons in slices, we demonstrated benefits of gamma activity modulation for encoding of slow sinusoidal signals into sequences of action potentials. Thus, the phenomenon of amplitude modulation of gamma oscillations by temporal frequency of stimulus, originally described in the visual system of cats, may represent a universal mechanism that improves encoding of visual information which is present even in animals with a relatively poorly developed visual system, such as mice.
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Emotion regulation is a popular research topic in social, clinical, cognitive psychology, and neurophysiology. Event-related potentials (ERPs) studies have high temporal resolution and are therefore conventionally used in emotion research to study the patterns of emotion processing. Advances in digital technologies are promoting neuro-psychological research of emotion and attention in virtual reality (VR). In this work, for the first time, we investigated how the presented emotional facial expressions in VR modulate ERP components in conditions of different combinations of passive or active attention and random or linear presentation sequence. We found the higher amplitude of the C1, N170, P2, P3, P4 ERP components in the condition of active attention compared to passive attention during the random presentation of emotional 3D facial expression. During the linear presentation of emotional 3D facial expressions, a statistically significant difference was found only for the C1 ERP component in conditions of both passive and active attention. We proved that the P2 ERP component represents the perception of positive and negative 3D facial expressions encoding the emotional valence of the stimuli. We also found no statistically significant difference in latency of ERP components between passive and active attention to emotional 3D facial expressions.
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Spontaneous activity is known to be a characteristic feature of the vast majority of the neocortical principal cells including neurons of the primary sensory areas. The question of how spontaneous activity interacts with perception and encoding of sensory information remains open. In the present study, pyramidal neurons of the mouse primary visual cortex were recorded extracellularly under urethane anesthesia and simultaneous single-channel EEG recording was performed. To evaluate orientation and direction selectivity of the recorded neurons, mice were presented with visual stimuli consisting of moving sinusoidal gratings of different orientations displayed on a monitor. We noted quite regular bursts of generalized brain activity that were manifested in the recorded neuron as bundles of action potentials accompanied with a distinctive EEG pattern. Clearly, whenever such spontaneous activity shows up during visual stimulation, it is considered as noise, which significantly compromises the characteristics of the neuron’s measured visual response. To eliminate this effect, we developed a machine learning-based algorithm that enables to identify EEG predictors of generalized spontaneous activity and then to exclude spontaneous (i.e. not evoked by visual stimulation) action potentials from the recording. Our algorithm was shown to reliably detect action potentials that have been caused by generalized brain activity. Removal of action potentials of this origin from extracellular recordings obtained during visual stimulation allows for a more adequate estimation of parameters of neuronal receptive fields, in particular their orientation selectivity.
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Issue 2 | June 2021
This work shows the in vivo effect of the bioactive triterpenoid betulonic acid on the liver of C57BL/10 mice and the functioning of the mitochondria of this organ. We have found that betulonic acid has no significant effect on the histological parameters of the mouse liver, as well as on the biochemical parameters of the blood serum of the studied animals. At the same time, betulonic acid has demonstrated mitochondrial targeting. Betulonic acid has shown a decrease in the functional activity of mitochondria, especially in the case of their energization with succinate, a substrate of complex II of the respiratory chain of organelles. Treatment with betulonic acid has no effect on the resistance of mouse liver mitochondria to the induction of a calcium-dependent MPT pore. On the other hand, we have revealed the antioxidant effect of betulonic acid associated with a decrease in the rate of H2O2 generation in the mouse liver mitochondria. The paper discusses the possible use of betulonic acid as a mitochondria-targeting agent.
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The study aimed to evaluate the effectiveness of previously developed methods of adaptive neurostimulation in correcting stress-induced states in specialists who demonstrate signs of post-traumatic stress disorder (PTSD) and professional burnout syndrome (PBS). Materials and methods. Each of the 17 stressed subjects participated in three examinations, alternated in random order. In the control experiment (control), simple listening to classical music was used. In two other examinations, musical or light-musical stimulation was used, automatically modulated by feedback signals from the rhythmic components of the subject's electroencephalogram (EEG). In the first case (musical feedback), the subjects were presented with music-like stimuli formed on the basis of the subject's alpha EEG oscillator. In the second case (double feedback), such musical stimulation was supplemented by rhythmic light stimuli generated by online transformations of the native EEG of the subject. Results. Comparison of the effects of both experimental conditions with the control one allowed us to establish that only in the presence of feedback from the EEG, there is a significant increase in the power of alpha EEG rhythm, accompanied by positive emotional reactions, a decrease in the level of disadaptation and stress, as well as a significant increase in the assessments of health and mood of the subjects. The most pronounced psychophysiological effects were recorded under light-music stimulation with double feedback from the EEG. Conclusion. The obtained results make it possible to suggest the described methods of adaptive neurostimulation as a means of psychotherapeutic correction of PTSD and PBS, especially during the COVID-19 pandemic.
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Using the methods of fluorescence microscopy, Tirf microscopy, inhibitory analysis, immunocytochemistry and PCR, it has been shown that in response to an increase in [Ca2+]o or a CaSR agonist – protamine in the minor population of white adipocytes, Ca2+ signals are rapidly generated – a short-term Ca2+ increase and Ca2+-oscillations, while in most cells the generation of Ca2+ responses occurs after a lag period of varying duration. White adipocyte signals for CaSR activation were completely suppressed in the presence of the selective CaSR antagonist, NPS2143, in both cell populations. When CaSR is activated, a calcium-dependent process of secretion of ATP-containing vesicles occurs, which was also suppressed by NPS2143 and a calcium-dependent secretion blocker tetanus toxin. After a 24- hour exposure to the CaSR activator protamine on white adipocytes, an increase in the level of expression of genes – Lipe, Atgl, Sirt1 and Sirt3, encoding hormone-sensitive lipase, triglyceride lipase, sirtuins 1 and 3, respectively. At the same time, an increase in the expression of these genes was not observed with the selective CaSR antagonist, NPS2143. Thus, one of the new mechanisms of activation of genes regulating white adipose tissue lipolysis can be assumed through an increase in [Ca2+]i in the minor population of CaSR-expressing adipocytes, followed by calcium-dependent ATP secretion and paracrine activation of the entire cell network, which will help play an important role in the regulation of the balance of lipogenesis/lipolysis processes.
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The three-dimensional structure of tumor tissue and particularly cell-cell and cell-extracellular matrix adhesion is an important factor that can determine the phenotype of tumor cells. In this work, we have investigated the abundance profile of actin-binding adhesion proteins in human ovarian adenocarcinoma cell lines SKOV-3 and SKOV-3.ip. We have investigated levels of total and superficially localized adherens junctions proteins E- and N-cadherin, gap junction protein сonnexin-43 and cell-extracellular matrix contacting integrin beta-1. Our results indicate a complete absence of epithelial marker E-cadherin, a low level of mesenchymal N-cadherin and high levels of connexin-43 and integrin beta-1. Modest superficial localization of the represented proteins was observed, indicating their mislocalization. SKOV-3 cell line was characterized by higher levels of the total content of studied cell-cell contacts proteins and a lower level of superficially localized integrin beta-1, which is both considered to be associated with lower tumor aggressiveness. The revealed differences in the profile of adhesion proteins are in line with the accepted view on SKOV-3.ip cell line having a more aggressive phenotype than that of SKOV-3. The revealed features of the total abundance of the adhesion proteins and their superficially localized pool made it possible to supplement the information on the nature of phenotypic differences between the studied cell lines.
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Relevance. The risk factors for urolithiasis include an increase in the daily excretion of lithogenic metabolites. These factors have not been sufficiently studied in childhood. Methods. We conducted a study of the 24-hour urinary excretion of calcium, oxalate and phosphorus in 196 patients (median age was 9.0 [6.0; 14.0] years, boys 23.5% (46/196)) with the urinary syndrome. Results. We found a statistically significantly higher daily urinary excretion of oxalates in boys compared to girls, 18.1 [11.2; 25.6] mg/day and 14.1 [9.6; 21.3] mg/day, respectively, p = 0.012. However, these differences manifest themselves only at the age of 10 years and older, amounting to 23.85 [11.2; 25.5] mg/day in boys and 13.91 [8.02; 18.9] mg/day in girls, p = 0.005. We did not establish gender differences in daily calcium excretion, p = 0.45. At the same time, we revealed gender differences in daily phosphorus excretion in boys compared with girls 23.25 [15.0; 38.0] mmol/day and 18.9 [10.6; 29.2] mmol/day, respectively, p = 0.013. These patterns were also typical only for the age older than 10 years – in boys 31.7 [21.1; 43.0] mmol/day, in girls 17.9 [11.6; 30.9] mmol/day, p = 0.003. Conclusions. Boys aged 10 years and older have a statistically significantly higher 24-hour urinary excretion of oxalate and phosphorus than girls. This may indicate the gender dependence of some lithogenic factors and the need for increased attention to the prevention of nephrolithiasis during early puberty.
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Type 2 diabetes mellitus (T2D) is one of the most common endocrine diseases in the world. It is characterized by dysfunction of pancreatic β-cells, insulin resistance, and hyperglycemia. Despite numerous studies on the pathogenesis and risk factors of diabetes, there is still no consensus on how best to diagnose, classify, and treat the disease. Accumulating evidence suggests that antidiabetic drugs can course unwanted side effects. S-15176 difumarate salt, a novel derivative of trimetazidine, inhibits the rate-limiting enzyme of fatty acid β-oxidation carnitine palmitoyltransferase I and has anti-ischemic properties, which makes it useful as an antidiabetic agent. Here, the effect of chronic treatment with S-15176 difumarate salt on the leukocyte formula and cytochemical indices of the peripheral blood neutrophils (myeloperoxidase activity, free phospholipids, and lysosomal cationic proteins) of C57Bl/6 mice in control and experimental T2D was studied. It was found that in the control group, S-15176 difumarate salt decreased the number of neutrophils containing lysosomal cationic proteins and the cytochemical coefficient of the cells. The treatment of diabetic mice with S-15176 had no significant effect on the activity of myeloperoxidase and free phospholipids in neutrophils. The results obtained suggest that the use of S-15176 difumarate salt as an antidiabetic drug does not induce changes in peripheral blood markers associated with immune-related adverse effects.
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Photodynamic therapy is a minimally invasive cancer treatment modality based on the production of the reactive oxygen species by photoactive dye under light irradiation in the presence of molecular oxygen. During the development of the photodynamic reaction, various types of reactive oxygen species are formed, among which hydrogen peroxide is of the greatest interest since it can act as an extracellular and intracellular signaling molecule. Using a genetically encoded sensor of hydrogen peroxide, we have registered the development of oxidative stress in non-irradiated cells in response to local photodynamic exposure of a single cell using Photosens as a photosensitizer. The effect manifested when the cells were closely contacted to each other; if the irradiated cell was at some distance from the bulk of the population, the response of non-target cells was not observed. The oxidative stress in the irradiated cell is assumed to be the initiator of the signal transmission and triggering the response of non-target cells. That this response is more likely mediated by gap junction intercellular signaling. Нowever, the mechanisms involved in the propagation of damaging effects to cells outside the area of photodynamic exposure have to be further investigated.
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This work is devoted to the study of the individual characteristics of cerebral circulation, galvanic skin response and heart rate during mental, sensorimotor and sensory activity. In two groups, differing in the level of behavior control (precise and imprecise), a comparative analysis of behavioral and physiological indicators was carried out. Imprecise subjects before the test (readiness state) GO/NOGO showed higher indices of the tone of the arterioles and venules of the cerebral vessels in the basin of the carotid arteries. During the GO/NOGO trial, a more reactive increase in vascular tone was observed in the precise group, more pronounced in the right hemisphere. In the imprecise group, a higher level of mental stress was registered in terms of GSR and heart rate during mental counting. GSR was also more pronounced in this group when viewing images. The optimal and non-optimal types of information load portability are discussed.
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Issue 1 | March 2021
Photodynamic therapy (PDT) is a promising approach in the treatment of various tumors. The presence of three essential components: a photosensitizer, a light source and oxygen is required for generating reactive oxygen species and subsequent tumor destruction. In this study, we investigated the cell death pathway induced by Photodithazine (PD) mediated photodynamic therapy (PD-PDT). We found that PD localizes in the endoplasmic reticulum and Golgi apparatus of cancer cells. Upon irradiation at 20 J/cm2, PD induced death of tumor cells at concentrations exceeding 100 nM. Based on dying cell morphology, exposure of phosphatidylserine to the cell surface, presence of phosphorylated form of mixed lineage kinase domain like pseudokinase (pMLKL) and protective action of pan-caspase inhibitor and inhibitor of receptor-interacting protein kinase 1 (RIPK1), we hypothesize that Photodithazine forces cells to enter mixed-type cell death with features of apoptosis and necroptosis.
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We have explored the features of PPARγ2 gene alleles expression in elderly patients with comorbid conditions such as obesity and coronary artery disease. 140 patients of both sexes (54.3% men and 45.7% women) aged 60-89 were examined. The main group included 70 pts with CHD; the control group included 70 pts without CHD. Pro12 allele carrier state in the main group was 85%, and Ala12 allele carrier state – 15%. Pro12Ala and Ala12Ala genotypes, Ala12 allele were detected more often in patients with coronary artery disease than in the control group (p = 0.0008 and p = 0.0003, respectively). Pro12Ala genotypes (OR = 2.02, CI = 1.28–3.19, p = 0.003) and Ala12Ala (OR = 2.002, CI = 1.32–3.04, p = 0.0006) of Ala12 gene PPARγ2 carrier state increases the risk of CHD developing by 2 times. It was confirmed that nuclear PPARs are capable of controlling development, differentiation, metabolic homeostasis and reproduction. The role of various genotypes of the PPARγ2 gene in the regulation of lipid metabolism and angiogenesis in comorbid conditions in elderly patients may help to identify new methods of their treatment.
Currently, radionuclide therapy of tumors using sources of alpha and beta radiation is actively developing. However, the radiosensitivity of tumor cells has been studied mainly using acute gamma radiation. In this regard, studies aimed at determining the ranges of radiosensitivity of cells of various origins in relation to beta-emission radionuclides are gaining relevance. The study was carried out on A431, CHO and SK-BR-3 cell lines using beta-emission sealed sources Sr-90+Y-90. Cell viability was assessed via MTT-assay. Dose dependences were obtained for irradiating cells with a beta source: the LD50 range was from 17 to 19 Gy, and LD37 was from 24 to 36 Gy. It was shown that at the same dose of radiation, the percentage of viable cells relative to the control of 72 hours after irradiation is significantly less than after 24 hours. The revealed LD50 values for tumor cells under chronic beta-irradiation are higher than with acute gamma-irradiation, which should be considered when selecting doses during the development of potential radiopharmaceutical treatment. Decreased cell viability in response to beta radiation is due to both cytotoxic and cytostatic manifestations.
CuO in the form of micro- and nano-sized colloidal particles enters the human body from environment. The aim of the study is the identification of morphological changes in rat liver tissues during chronic oral intake of micro- and nanosized CuO by image analysis. The experiments were performed on 45 male Wistar rats (3 groups: experimental (nanosized CuO); comparison (micro-sized CuO); control (water without CuO)). Suspensions CuO were administered to the rats orally once a day. Quantitative morphological parameters were determined by pathomorphological examination and image analysis using the method of constructing Voronoi diagrams (the ratio of cells of various shapes); average cell area; the average size of the cell perimeter and the number of cells per unit area. As a result of the analysis by the constructing Voronoi diagrams, was found that the main part of the model cells corresponding to hepatocytes has the shape of a hexagon. In the control group, their share is 35.89%, in the experience group – 29.09%, and in the comparison group – 30.59%. The density of cells’ distribution in the comparison group is 7 times higher than in the control group; in the experimental group the same indicator is 4 times higher than in the control group. Collectively, the characteristics of morphological changes in liver tissue indicate greater toxicity of nano-sized copper oxide compared to its micro-sized analogue.
The world’s biggest killer is ischemic heart disease, responsible for 16% of the world’s total deaths. Since 2000, the largest increase in deaths has been for this disease, rising by more than 2 million to 8.9 million deaths in 2019. In recent years, many studies have shown that hydrogen has therapeutic and preventive effects in various human and animal disease models. In this study, we investigated the possible antioxidant effects of molecular hydrogen in erythrocytes and blood plasma in rats with the experimentally simulated chronic heart failure. We estimated the intensity of lipid peroxidation processes by the contents of diene and triene conjugates, Schiff bases, malonic dialdehyde, catalase activity. The results from this study suggest that inhalation of 2% molecular hydrogen leads to a decrease in pro-oxidant and an increase in antioxidant parameters. The results of this study provide the basic data for the mechanism research and application of molecular hydrogen in the future.
Achieving both deep penetration of photons into biological tissue and highly sensitive recording of optical probes' response are the key goals of non-invasive optical imaging. In comparison with the traditional fluorescence imaging in the visible (400–700 nm) and near-infrared (700–900 nm) regions, optical fluorescence imaging in the second optical tissue transparency window (1000–2300 nm) demonstrates low photon scattering, deeper penetration into the tissues and lower autofluorescence. In the present study, biocompatible upconversion nanoparticles with different contents of doping lanthanides, capable of luminescence in the visible and short-wave IR regions, were obtained and characterized. Also, targeted complexes based on Gd-containing nanophosphors were obtained as potential contrast agents for magnetic resonance imaging. Selective binding of targeted complexes to the surface of tumor cells expressing the HER2 receptor was shown.
Epilepsy affects around 1% of the population in the world. Thus, it is imperative that new more effective and safe treatments be found. In order to understand the nature of epilepsy, new and better animal models are needed in that they offer valuable resources for researchers. Such models provide an opportunity to characterize seizures in the whole organism, to understand the molecular basis of these processes and to test the effectiveness of treatments and therapies. In this study, we have shown that screening after chemical mutagenesis can be used as a tool to identify new genes that may be involved in the mechanism of epilepsy formation.
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Issue 4 | December 2020
Over the past two decades, developments in the field of nanobiomedicine have come a long way despite the unresolved hindrances. The creation and development of effective theranostic agents based on nanomaterials are urgent needs of modern medicine. Upconversion nanoparticles (UCNP) appear to be the most promising agents for developing theranostics due to their unique optical properties. There has been extensive research on new approaches to obtain stable colloids capable of prolonged circulation in the bloodstream, particularly with bovine serum albumin (BSA). The present work contributes to solving the problem of obtaining stable agents based on UCNP by coating water-soluble UCNPNOBF4 with a stable protein corona layer of BSA. The assembled nanocomplex is promising for usage as a diagnostic agent and is set for further investigation.
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Methylation of DNA cytosine bases is a key epigenetic modification that plays an important role in the regulation of gene expression and the formation of the epigenome. Numerous studies of the human genome show that there is a close relationship between DNA methylation, age and sex of a person. Until now, the popular model has been the linear change in the methylation level with age. Here we find a fundamentally different DNA methylation behavior, namely the nonlinear dependence of the methylation level on age. We identify CpG probes whose methylation changes exponentially with age or according to a power law, and perform Gene Ontology enrichment analysis of the latter. Our results are relevant to understanding how DNA methylation changes with age and the found nonlinear CpG sites can be used to construct new epigenetic clocks.
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