Search

This article is devoted to the study of issues of cooperation between the USSR and the PRC in the field of personnel training for the healthcare sector in the 1949-1960-ies. Based on the analysis of archival data, sources and literature on this topic, the authors came to the conclusion that after the establishment of diplomatic relations between the countries in 1949, intensive interaction began in various sectors of the economy and public life. The research focuses on the features of building the healthcare system as a whole, as well as training personnel for this area at the initial stage of development of the Chinese state and its healthcare system. It is revealed that despite the short historical period of active cooperation, China, with the help of the USSR, was able to integrate the Soviet model into the national health system, which allowed solving one of the acute social problems in the specified historical period. In addition, the Soviet model of public health made it possible to deal in a timely manner with the threats of the spread of diseases, including those of a mass nature, up to the present time. The authors concluded that the development of cooperation in the field of healthcare between our countries can be divided into five main stages. The period 1949-1960 is the most effective, since it was at this time that comprehensive assistance was provided by the USSR.

The spread of Mycobacterium tuberculosis drug resistance accentuates the demand for anti-tuberculosis drugs with a fundamentally new mechanism of action without conferring cross-resistance. G-quadruplexes (G4, non-canonical DNA structures) are plausible new drug targets. Although G4-stabilizing ligands have been shown to inhibit mycobacterial growth, the exact mechanism of their action is uncertain. The aim of this study was to assess a possible correlation between putative G4 elements in a model mycobacterial strain M. smegmatis MC2155 and transcriptomic changes under the action of subinhibitory concentrations of G4 ligands BRACO-19 and TMPyP4. We also planned to compare the results with corresponding data previously obtained by us using higher, inhibitory concentrations of these ligands. For BRACO-19, we identified 589 (316↑; 273↓) and 865 (555↑; 310↓) differentially expressed genes at 5 µМ and 10 µМ, respectively. For TMPyP4, we observed the opposite trend, the number of differentially expressed genes decreased at higher concentration of the ligand: 754 (337↑; 417↓) and 702 (359↑; 343↓) for 2 µМ and 4 µМ, respectively. Statistical analysis revealed no correlation between ligand-induced transcriptomic changes and genomic localization of the putative quadruplex-forming sequences. At the same time, the data indicate certain functional specificity of the ligand-mediated transcriptomic effects, with TMPyP4 significantly affecting expression levels of transcription factors and arginine biosynthesis genes and BRACO-19 significantly affecting expression levels of iron metabolism and replication and reparation system genes.

G-quadruplexes (G4s) are non-canonical DNA structures that could be considered as potential therapeutic targets for antimicrobial compounds, also known as G4-stabilizing ligands. While some of these ligands are shown

There is growing concern about the emergence and spread of multidrug-resistant Neisseria gonorrhoeae. To effectively control antibiotic-resistant bacterial pathogens, it is necessary to develop new antimicrobials and to understand the resistance mechanisms to existing antibiotics. In this study, we discovered the unexpected onset of drug resistance in N. gonorrhoeae caused by amino acid substitutions in the periplasmic chaperone SurA and the β-barrel assembly machinery component BamA. Here, we investigated the i19.05 clinical isolate with mutations in corresponding genes along with reduced susceptibility to penicillin, tetracycline, and azithromycin. The mutant strain NG05 (surAmut bamAmut, and penAmut) was obtained using the pan-susceptible n01.08 clinical isolate as a recipient in the transformation procedure. Comparative proteomic analysis of NG05 and n01.08 strains revealed significantly increased levels of other chaperones, Skp and FkpA, and some transport proteins. Efflux pump inhibition experiments demonstrated that the reduction in sensitivity was achieved due to the activity of efflux pumps. We hypothesize that the described mutations in the surA and bamA genes cause the qualitative and quantitative changes of periplasmic chaperones, which in turn alters the function of synthesized cell envelope proteins.

Antibiotic resistance is a major public health concern in many countries worldwide. The rapid spread of multidrug-resistant (MDR) bacteria is the main driving force for the development of novel non-antibiotic antimicrobials as a therapeutic alternative. Here, we isolated and characterized three virulent bacteriophages that specifically infect and lyse MDR Klebsiella pneumoniae with K23 capsule type. The phages belonged to the Autographiviridae (vB_KpnP_Dlv622) and Myoviridae (vB_KpnM_Seu621, KpS8) families and contained highly similar receptor-binding proteins (RBPs) with polysaccharide depolymerase enzymatic activity. Based on phylogenetic analysis, a similar pattern was also noted for five other groups of depolymerases, specific against capsule types K1, K30/K69, K57, K63, and KN2. The resulting recombinant depolymerases Dep622 (phage vB_KpnP_Dlv622) and DepS8 (phage KpS8) demonstrated narrow specificity against K. pneumoniae with capsule type K23 and were able to protect Galleria mellonella larvae in a model infection with a K. pneumoniae multidrug-resistant strain. These findings expand our knowledge of the diversity of phage depolymerases and provide further evidence that bacteriophages and phage polysaccharide depolymerases represent a promising tool for antimicrobial therapy.

Antibiotic resistance is a major public health concern in many countries worldwide. The rapid spread of multidrug-resistant (MDR) bacteria is the main driving force for the development of novel non-antibiotic antimicrobials as a therapeutic alternative. Here, we isolated and characterized three virulent bacteriophages that specifically infect and lyse MDR Klebsiella pneumoniae with K23 capsule type. The phages belonged to the Autographiviridae (vB_KpnP_Dlv622) and Myoviridae (vB_KpnM_Seu621, KpS8) families and contained highly similar receptor-binding proteins (RBPs) with polysaccharide depolymerase enzymatic activity. Based on phylogenetic analysis, a similar pattern was also noted for five other groups of depolymerases, specific against capsule types K1, K30/K69, K57, K63, and KN2. The resulting recombinant depolymerases Dep622 (phage vB_KpnP_Dlv622) and DepS8 (phage KpS8) demonstrated narrow specificity against K. pneumoniae with capsule type K23 and were able to protect Galleria mellonella larvae in a model infection with a K. pneumoniae multidrug-resistant strain. These findings expand our knowledge of the diversity of phage depolymerases and provide further evidence that bacteriophages and phage polysaccharide depolymerases represent a promising tool for antimicrobial therapy.

Juvenile common carp were treated with Cd

The programmed death-1 receptor, PD-1, is a negative regulator of T-cell activation. The PD-1.3 polymorphism of the PD-1 gene (PDCD1) has been previously shown to be associated with several autoimmune and inflammatory disorders including systemic lupus erythematosus and multiple sclerosis. We examined for the first time PD-1.3 association with another inflammatory disease with strong immune component, IgE-mediated bronchial asthma, its severity and its biochemical markers (total serum IgE and IL-4).PD-1.3 G/A was genotyped by PCR-RFLP analysis using two different populations: Caucasian (492 Russian individuals) and Asian (276 Buryat individuals).We found a significant association of the PD-1.3 polymorphism with IgE-mediated bronchial asthma and total serum IgE level in the Russian population. Combined genotype AA+AG was correlated with risk of developing allergic bronchial asthma (OR = 1.78, 95% CI 1.13-2.78, p = 0.011) and lower concentrations of total serum IgE (p = 0.001) compared with the wild-type genotype GG. However, PD-1.3 was not polymorphic in the Buryat population.PD-1.3 polymorphism of the PD-1 gene (PDCD1) may contribute to the development of allergic asthma in the Russians but not in the Buryats. Our results could be helpful for a better understanding of the effect of this polymorphism on the development of diseases with strong immune components.

Alzheimer's disease is the most prevalent neurodegenerative pathology. According to the amyloid cascade hypothesis, a key event of the Alzheimer's disease pathogenesis is a transition of the β-amyloid peptide (Аβ) from the monomeric form to the aggregated state. The mechanism of Аβ aggregation is intensively studied in vitro, by means of synthetic peptides and various physico-chemical methods allowing evaluation of size, molecular structure, and morphology of the formed aggregates. The paper reviews both the well-known and recently introduced physico-chemical methods for analysis of Аβ aggregation, including microscopу, optical and fluorescent methods, method of electron paramagnetic resonance, electrochemical and electrophoretic methods, gel-filtration, and mass spectrometric methods. Merits and drawbacks of the methods are discussed. The unique possibility to simultaneously observe Аβ monomers as well oligomers and large aggregates by means of atomic force microscopy or fluorescence correlation spectroscopy is emphasized. The high detection sensitivity of the latter method, monitoring the aggregation process in Аβ solutions at low peptide concentrations is underlined. Among mass spectrometric methods, the ion mobility mass spectrometry is marked out as a method enabling to obtain information about both the spectrum of Аβ oligomers and their structure. It is pointed out that the use of several methods giving the complementary data about Аβ aggregates is the best experimental approach to studying the process of b-amyloid peptide aggregation in vitro.Bolezn' Al'tsgeĭmera iavliaetsia naibolee rasprostranennym neĭrodegenerativnym zabolevaniem. Soglasno gipoteze “amiloidnogo kaskada”, kliuchevym sobytiem patogeneza bolezni Al'tsgeĭmera iavliaetsia perekhod b-amiloidnogo peptida (Ab) iz monomernogo sostoianiia v agregirovannoe. Mekhanizm agregatsii Ab intensivno izuchaetsia in vitro s ispol'zovaniem sinteticheskikh peptidov s pomoshch'iu fiziko-khimicheskikh metodov, pozvoliaiushchikh otsenivat' razmer, molekuliarnuiu strukturu i morfologiiu obrazuiushchikhsia agregatov. V obzore rassmotreny kak khorosho izvestnye, tak i nedavno poiavivshiesia fiziko-khimicheskie metody issledovaniia agregatsii Ab, vkliuchaia metody mikroskopii, opticheskie i fluorestsentnye metody, metod élektronnogo paramagnitnogo rezonansa, élektrokhimicheskiĭ i élektroforeticheskiĭ metody, gel'-fil'tratsiiu i mass-spektrometricheskie metody. Obsuzhdaiutsia dostoinstv a i nedostatki metodov. Otmechena unikal'naia vozmozhnost' odnovremenno nabliudat' kak monomery Ab, tak i ego oligomery i krupnye agregaty s pomoshch'iu metodov atomno-silovoĭ mikroskopii i fluorestsentnoĭ korreliatsionnoĭ spektroskopii, a takzhe vysokaia chuvstvitel'nost' poslednego, pozvoliaiushchaia sledit' za protsessom agregatsii v nizkokontsentrirovannykh rastvorakh Ab. Sredi mass-spektrometricheskikh metodov vydelen metod spektrometrii ionnoĭ podvizhnosti/mass-spektrometrii, kotoryĭ, nariadu s opredeleniem spektra oligomerov Ab, pozvoliaet poluchat' informatsiiu ob ikh strukture. Odnovremennoe ispol'zovanie neskol'kikh metodov, pozvoliaiushchikh poluchit' vzaimodopolniaiushchie dannye ob agregatakh Ab, iavliaetsia naibolee optimal'nym éksperimental'nym podkhodom k issledovaniiu protsessa agregatsii b-amiloidnykh peptidov in vitro.

A novel label-free electrochemical method for protein detection based on redox properties of silver was developed. As recognition elements, thrombin-binding aptamers were used. Screen printed electrodes modified with silver nanoparticles (AgNP) were employed as a sensing platform for aptasensor devices. The oxidation of silver upon polarization served as a basis for analytical response. Three different thrombin binding aptamers with various surface concentrations were studied. Linear range of aptasensor response corresponded to the 10−9 M to 10−7 M thrombin concentration range and the detection limit was 10−9 M.

Aptamers interacting selectively with the anion-binding exosites 1 and 2 of thrombin were merged into dimeric oligonucleotide constructs with use of a poly-(dT)-linker of 35 nucleotides (nt) long. Complexes of thrombin with the aptamers and their hetero- and homodimeric constructs were measured using the optical biosensor Biacore-3000. KD values measured for the hetero- and homodimeric constructs were correspondingly 25-30- and 2-3-fold lower than those for the primary aptamers. Analysis of temperature dependencies of KD values within the temperature interval of 10°C-40°C has shown that the values of enthalpy change ΔH upon formation of complexes of thrombin with the aptamers and the hetrodimeric construct are close. The value of the entropy change ΔS upon complex formation of thrombin with the aptamer heterodimeric construct was 1.5-2-fold higher than ΔS values for the complexes with the aptamers. The complex formation and dissociation rates increased with the elevation of temperature from 10°С to 37°С. However, the dissociation rate for the complex of thrombin with the heterodimeric construct was evidently lower that that for the complexes with the aptamers.