Search Results (12)

In order to combat resistance, it is necessary to develop antimicrobial agents that act differently from conventional antibiotics. Fluorothiazinone, 300 mg tablet (The Gamaleya National Research Center), is an original antibacterial drug based on a new small molecule T3SS and flagellum inhibitor. A total of 357 patients with complicated urinary tract infections (UTIs) were divided into two groups and given Fluorothiazinone 1200 mg/day or a placebo for 7 days to evaluate the efficacy and safety of the drug. Additionally, all patients were given Cefepime 2000 mg/day. Fluorothiazinone with Cefepime showed superiority over placebo/Cefepime based on the assessment of the proportion of patients with an overall outcome in the form of a cure after 21 days post-therapy (primary outcome), overall outcome in cure rates, clinical cure rates, and microbiological efficacy at the end of therapy and after 21 days post-therapy (secondary outcomes). In patients who received Fluorothiazinone, the rate of infection recurrences 53 and 83 days after the end of the therapy was lower by 18.9%, compared with patients who received placebo. Fluorothiazinone demonstrated a favorable safety profile with no serious unexpected adverse events reported. The results showed superiority of the therapy with Fluorothiazinone in combination with Cefepime compared with placebo/Cefepime in patients with cUTIs. Full article

Understanding the rate and direction of pyrogenic succession in arid ecosystems, which depends on many factors, including the intensity of grazing and the frequency of pyrogenic expo-sure, will allow for more accurate predictions of the consequences of fire onplant communities, and will assist with better fire management. We studied the vegetation on 55 sites in and near the “Chernye Zemli” Natural Biosphere Reserve that burned at different times or were not affected by fires over the past 35 years and characterized the changes in vegetation cover associated with the impact of wildfire and grazing. The descriptions were grouped into chronological stages according to the time elapsed since the last fire, or into groups according to the frequency of fires. In pairwise comparison of the projective cover of plant species between chronological stages, it correlated most strongly between successive initial stages (for stages 1 and 2, p = 0.003, r = 0.73; for stages 2 and 3, p < 0.001, r = 0.78). Species with an initially higher projective cover were more likely to grow on plots in the first year after the fire: p < 0.03. Plots with rare and frequent fires had similar projective cover of individual species (r = 0.64, p < 0.001). We conclude that in the course of pyrogenic succession, communities are gradually replaced over at least ten years. At the same time, the composition of a plant community at the initial point of succession depends on the prevalence of species in the community before the fire. No fundamental effect of the frequency of fires on the composition of plant communities has been revealed. Full article

The potato is one of the most important food crops in the world. Improving the efficiency of potato breeding is of great importance for solving the global food problem. Today, researchers distinguish between six potato cytoplasm types: A, M, P, T, W, D. In the current study, the complete chloroplast genomes of Solanum tuberosum accessions with five out of the six major cytoplasmic genome types were sequenced (T-, W-, D-, A-, and P-genomes). A comparative analysis of the plastomes in potato accessions with different cytoplasm types was carried out for the first time. The time of origin of the different cytoplasm types was estimated. The presence of two main groups of chloroplast genomes among cultivated potato was confirmed. Based on the phylogenetic analysis of the complete plastome sequences, five main evolutionary branches of chloroplast genomes can be distinguished within the Petota section. Samples with A- and P- cytoplasm formed isolated and distant groups within a large and polymorphic group of samples with M-type cytoplasm, suggesting that A and P genomes arose independently. The findings suggest that the diversity of the T-genome in S. tuberosum Group Tuberosum could be initially low due to a bottle neck already existing at the origin of the Chilean clade. Differences in the rbcL gene sequence may be one of the factors causing differences in economically important traits in species with A and T-type cytoplasm. The data obtained will contribute to the development of methods for molecular marking of cytoplasm types and increase knowledge about the evolution and diversity of potato. Full article

The declaration of the conclusion of the COVID-19 pandemic notwithstanding, coronavirus remains prevalent in circulation, and the potential emergence of novel variants of concern introduces the possibility of new outbreaks. Moreover, it is not clear how quickly and to what extent the effectiveness of vaccination will decline as the virus continues to mutate. One possible solution to combat the rapidly mutating coronavirus is the creation of safe vaccine platforms that can be rapidly adapted to deliver new, specific antigens in response to viral mutations. Recombinant probiotic microorganisms that can produce viral antigens by inserting specific viral DNA fragments into their genome show promise as a platform and vector for mucosal vaccine antigen delivery. The authors of this study have developed a convenient and universal technique for inserting the DNA sequences of pathogenic bacteria and viruses into the gene that encodes the pili protein of the probiotic strain E. faecium L3. The paper presents data on the immunogenic properties of two E. faecium L3 vaccine strains, which produce two different fragments of the coronavirus S1 protein, and provides an assessment of the protective efficacy of these oral vaccines against coronavirus infection in Syrian hamsters. Full article

Many previous studies have demonstrated that transcutaneous vagus nerve stimulation (VNS) has the potential to exhibit therapeutic effects similar to its invasive counterpart. An objective assessment of VNS requires a reliable biomarker of successful vagal activation. Although many potential biomarkers have been proposed, most studies have focused on heart rate variability (HRV). Despite the physiological rationale for HRV as a biomarker for assessing vagal stimulation, data on its effects on HRV are equivocal. To further advance this field, future studies investigating VNS should contain adequate methodological specifics that make it possible to compare the results between studies, to replicate studies, and to enhance the safety of study participants. This article describes the design and methodology of a randomized study evaluating the effect of short-term noninvasive stimulation of the auricular branch of the vagus nerve on parameters of HRV. Primary records of rhythmograms of all the subjects, as well as a dataset with clinical, instrumental, and laboratory data of all the current study subjects are in the public domain for possible secondary analysis to all interested researchers. The physiological interpretation of the obtained data is not considered in the article. Full article

Nitric oxide is one of the endogenous molecules that play a key role in migraine. However, the interaction between NO and the main players in the nociceptive activity of the meningeal trigeminal afferents—TRPV1 and P2X3 receptors—remains unstudied. In the current project, the effects of acute and chronic NO administration on the activity of TRPV1 and P2X3 receptors in the peripheral afferents were studied using electrophysiological recording of action potentials of the trigeminal nerve in the rat hemiskull preparations. The data obtained indicate that exogenous and endogenous NO increased the activity of the trigeminal nerve independent on the inhibition of the TRPV1 and P2X3 receptors. The activity of the trigeminal nerve triggered by ATP changed neither in acute incubation in the NO donor—sodium nitroprusside (SNP) nor in the chronic nitroglycerine (NG)-induced migraine model. Moreover, the chronic NG administration did not increase in the number of degranulated mast cells in the rat meninges. At the same time, the capsaicin-induced activity of the trigeminal nerve was higher with chronic NO administration or after acute NO application, and these effects were prevented by N-ethylmaleimide. In conclusion, we suggested that NO positively modulates the activity of TRPV1 receptors by S-nitrosylation, which may contribute to the pro-nociceptive action of NO and underlie the sensitization of meningeal afferents in chronic migraine. Full article

Background: Motor recovery after stroke is based on neuronal plasticity and the structural reorganization of the brain. Questions are debated about the proper moment to start rehabilitation in the acute period of stroke, the significance of rehabilitation interventions during the so-called “plastic window”, and the advantages of modern and traditional programs. The aims of this study were to evaluate the role of different rehabilitation strategies and their combinations for motor recovery and the impact on functional disability by way of neurological and functional outcomes 3 months after ischemic stroke. Methods: We used three rehabilitation approaches: early rehabilitation from the first day of stroke (Phase I), traditional exercise programs (Phase II), and an author’s new method of biofeedback rehabilitation using motion sensors and augmented reality (AR) rehabilitation (Phase III). Clinical and functional outcomes were measured on the 90th day after stroke. We developed algorithms for quantifying the quality of movements during the execution of tasks in the motor domains of the AR rehabilitation program. Results: Phase I of rehabilitation led to an improvement in functional independence, and the recovery of motor functions of the extremities with an absence of mortality and clinical deterioration. AR rehabilitation led to significant improvement both with respect to clinical and functional scores on scales and to variables reflecting the quality of movements. Patients who were actively treated during Phases II and III achieved the same final level of motor recovery and functional outcomes as that of participants who had only received AR rehabilitation during Phase III. Patients who underwent outpatient observation after Phase I showed a deficit of spontaneous motor recovery on the 90th day after stroke. Conclusions: Early rehabilitation was successful but was not enough; rehabilitation programs should be carried out throughout the entire “sensitive period” of poststroke plasticity. The newly developed AR biofeedback motion training is effective and safe as a separate rehabilitation method in the early recovery period of moderately severe, hemiparalytic, and ischemic stroke. These two rehabilitation approaches must be applied together or after each other, not instead of each other, as shown in clinical practice. Full article

Potatoes contain antioxidants such as flavonoids, carotenoids and ascorbic acid. High level consumption worldwide makes potato a valuable source of phytonutrients. Developing new potato varieties with high nutritional value in combination with resistance to pathogens is an important task. In this study, 25 interspecific potato hybrids with resistance to Synchytrium endobioticum, common scab, silver scab, rhizoctonia, nematodes and PVY were evaluated for total phenolics, total flavonoids, total carotenoids, ascorbic acid contents and antioxidant activity. The identification of the dominant allele related with yellow flesh color at the Chy locus was also performed by the specific CAPS marker. Total protein content was detected and ranged from 8.19 ± 0.59 to 30.17 ± 4.56 mg/g dry weight (DW). Total starch and total carbohydrate contents were in the range of 9.0–21.0% and 73.21 ± 20.94–676.36 ± 195.28, respectively. Total phenolic content of hybrids varied from 8.45 to 82.75 mg/100 g, and total flavonoids content—from 0.64 to 9.67 mg/100 g DW. It is possible to distinguish samples with high protein and carbohydrate contents, high level of substances with antioxidant activity and characterized by resistance to pathogens. Quality evaluation has shown that some of the samples have a high potential for processing and chip production in combination with high eating qualities. These samples can be used in breeding programs to develope varieties resistant to pathogens and with high nutritional value. Full article

Chitosan, the product of chitin deacetylation, is an excellent candidate for enzyme immobilization purposes. Here we demonstrate that papain, an endolytic cysteine protease (EC: 3.4.22.2) from Carica papaya latex immobilized on the matrixes of medium molecular (200 kDa) and high molecular (350 kDa) weight chitosans exhibits anti-biofilm activity and increases the antimicrobials efficiency against biofilm-embedded bacteria. Immobilization in glycine buffer (pH 9.0) allowed adsorption up to 30% of the total protein (mg g chitosan⁻¹) and specific activity (U mg protein⁻¹), leading to the preservation of more than 90% of the initial total activity (U mL⁻¹). While optimal pH and temperature of the immobilized papain did not change, the immobilized enzyme exhibited elevated thermal stability and 6–7-fold longer half-life time in comparison with the soluble papain. While one-half of the total enzyme dissociates from both carriers in 24 h, this property could be used for wound-dressing materials design with dosed release of the enzyme to overcome the relatively high cytotoxicity of soluble papain. Our results indicate that both soluble and immobilized papain efficiently destroy biofilms formed by Staphylococcus aureus and Staphylococcus epidermidis. As a consequence, papain, both soluble and immobilized on medium molecular weight chitosan, is capable of potentiating the efficacy of antimicrobials against biofilm-embedded Staphylococci. Thus, papain immobilized on medium molecular weight chitosan appears a presumably beneficial agent for outer wound treatment for biofilms destruction, increasing antimicrobial treatment effectiveness. Full article

Plant enzymes such as ficin (EC 3.4.22.3), papain (EC 3.4.22.2) and bromelain (EC 3.4.22.4) are obtained from tropical plants. These biocatalysts belong to thiol proteases, in the active center of which cysteine is contained. Ficin, papain and bromelain have a wide substrate specificity, which provides a demand for their use in various industries. Enzymes in the free state are less commonly used; immobilized biocatalysts are the preferred form. The aim of this work was to determine the optimal concentration of a crosslinking agent in the covalent immobilization of ficin, papain and bromelain on a chitosan matrix. Ficin, papain and bromelain (Sigma) were chosen as objects of study. An acid-soluble chitosan (350 kDa, Bioprogress CJSC) was used as an immobilization carrier. The concentration range of glutaraldehyde (crosslinking agent) ranged from 1 to 25%. Suitable concentrations of glutaraldehyde for covalent immobilization were identified by the optimal ratio of protein content (mg per g of carrier), total activity (in units per ml of solution) and specific activity (in units per mg of protein). It was shown that for covalent immobilization of ficin and bromelain on a chitosan matrix, it is most promising to use 10% glutaraldehyde. For immobilization of papain on chitosan by covalent means, the concentration of glutaraldehyde equal to 20% is optimal. Full article

Immobilized enzymes are the most sought-after preparations in the global market. They are used in medicine, veterinary medicine, the food industry, winemaking and brewing. The simplest method for immobilizing biocatalysts on insoluble carriers is the simple adsorption method. Its advantage is that it preserves the natural conformation of the enzyme, which slightly reduces its catalytic ability compared to the native form. In our study, we carried out the selection of optimal conditions for adsorption immobilization of acid-soluble chitosan (Mr = 350 kDa) enzymes of plant origin (ficin, papain and bromelain) on a matrix. Ficin (EC 3.4.22.3), papain (EC 3.4.22.2) and bromelain (EC 3.4.22.4) (Sigma) were chosen as the objects of study, azocasein (Sigma) was used as a substrate for hydrolysis and an acid-soluble high-molecular-weight chitosan (350 kDa) was used as an immobilization matrix, synthesized by Bioprogress CJSC. Suitable buffer systems for immobilization were identified by the optimal ratio of protein content and total and specific activity. Ficin is immobilized on a chitosan matrix using glycine buffer with a pH of 8.6. Glycine buffer with a pH of 8.6–10.5 is an optimal medium for sorption of papain on chitosan. Bromelain is immobilized on a chitosan matrix under Tris-glycine buffer with pH 8.5 conditions. Full article

Background: brain-derived neurotrophic factor (BDNF) may play a role during neurorehabilitation following ischemic stroke. This study aimed to elucidate the possible role of BDNF during early recovery from ischemic stroke assisted by motor training. Methods: fifty patients were included after acute recovery from ischemic stroke: 21 first received classical rehabilitation followed by ‘motor rehabilitation using motion sensors and augmented reality’ (AR-rehabilitation), 14 only received AR-rehabilitation, and 15 were only observed. Serum BDNF levels were measured on the first day of stroke, on the 14th day, before AR-based rehabilitation (median, 45th day), and after the AR-based rehabilitation (median, 82nd day). Motor impairment was quantified clinically using the Fugl–Meyer scale (FMA); functional disability and activities of daily living (ADL) were measured using the Modified Rankin Scale (mRS). For comparison, serum BDNF was measured in 50 healthy individuals. Results: BDNF levels were found to significantly increase during the phase with AR-based rehabilitation. The pattern of the sequentially measured BDNF levels was similar in the treated patients. Untreated patients had significantly lower BDNF levels at the endpoint. Conclusions: the fluctuations of BDNF levels are not consistently related to motor improvement but seem to react to active treatment. Without active rehabilitation treatment, BDNF tends to decrease. Full article