Bulletin of Experimental Biology and Medicine最新文献

Escherichia phage Ec1-7 was characterized and its efficacy on food products, as well as on stainless-steel surfaces, was evaluated. The bacteriophage with high adsorption rate and short latency period remained stable when exposed to various aggressive factors and demonstrated lytic activity against STEC strains. In addition, the phage did not contain antibiotic resistance, virulence, and toxin genes. In 24 h after application of the bacteriophage, E. coli concentration on lettuce leaves and on stainless-steel surfaces decreased by 98.2 and 90.5%, respectively. In the experiment with artificially contaminated beef, an 81% decrease in bacterial concentration was recorded on day 3 in comparison with the control samples treated with 0.9% NaCl solution. The bacteriophage Ec1-7 exhibited stability and efficacy as a biocontrol agent across diverse test materials.

The study examined implication of miRNA-19b carried by endothelial microparticles (EMPs) in phenotypic switching of vascular smooth muscle cells (VSMCs) and the mechanisms underlying this transformation. The functions of miRNA-19b were assessed by phenotypic switching, proliferation, and migration of VSMCs. The target genes of miR-19b associated with proliferation and migration were revealed by analysis of TargetScan and miRanda databases and verified with luciferase assay. Experiments showed that EMPs could transfer miRNA-19b into VSMCs. Elevated content of miRNA-19b increased expression of contractile phenotypic markers SMA and SM22α and inhibited proliferation and migration of VSMCs. The direct target gene of miRNA-19b turned out to be the mitogen-activated protein kinase 6 (MAPK6). Thus, miRNA-19b in EMPs could inhibit phenotypic transformation of VSMCs from the contractile phenotype to synthetic one and reduce proliferation and migration by down-regulating MAPK6 expression, which can potentially inhibit the development of atherosclerosis.

Coiled-coil domain-containing protein 86 (CCDC86) expression is correlated with the occurrence of lymphoma. However, the expression of CCDC86 in solid tumors such as nasopharyngeal carcinoma (NPC) and the effects of CCDC86 on tumorigenesis remains unclear. Here we studied both problems using tumor tissue samples from NPC patients, NPC cell lines (in vivo), and a model of transplanted tumor in BALB/c nude mice (in vitro). We found that CCDC86 protein was expressed in all studied cell lines, but its expression in CNE1, CNE2, CNE-2Z, 5-8F, and 6-10B cell lines was higher than in nasopharyngeal epithelium cell lines NP69 and NP460. In tumor tissues obtained from patients with NPC, CCDC86 expression was higher than in normal (adjacent) tissues. Knockdown of CCDC86 gene inhibited colony formation and cell proliferation, but increased apoptosis. In BALB/c nude mice transplanted with CCDC86-knockdown CNE-2Z cells, tumors barely grew in comparison with the controls transplanted with CNE-2Z cells transfected with an empty vector lentivirus. In conclusion, CCDC86 is expressed in NPC tissues and NPC cell lines and is closely associated with NPC tumorigenesis. Our study may provide insights into exploring the novel therapeutic targets for NPC.

We studied the participation of the brain dopaminergic system in cognitive processes in rats on the model of spatial learning in the Morris water maze. Administration of the dopamine D1/5-receptor agonist dihydrexidine hydrochloride during repeated training in the Morris water maze resulted in improvement of early memory consolidation by the platform search time index selectively in animals with low abilities to perform the task at this stage of training, but not in individuals with high abilities to early memory consolidation. The agonist was also ineffective in rats with low memory consolidation abilities at all stages of memory formation. In the retrieval phase after repeated training, the agonist improved the retrieval of the skill in rats with low abilities to perform the task. The results illustrate the involvement of the brain dopaminergic system in rats not only in the processes of early spatial memory consolidation, but also in the retrieval of the memory trace after learning.

The autophagy-related structures, the size of the rough endoplasmic reticulum (ER) cisterns, and the expression of apoptosis-related proteins were assessed by transmission electron microscopy and immunohistochemistry in tumor samples from mice with B16 skin melanoma after administration of autophagy inducer (rapamycin) or ER stress inducer (brefeldin A). Brefeldin A stimulated significant ER stress in mouse skin melanoma cells, but rapamycin contributed to the maintenance of cell homeostasis by inducing autophagy, which was confirmed by the presence of autophagy-related structures and significantly smaller sizes of the rough ER cisterns in the group of mice receiving both rapamycin and brefeldin A. Brefeldin A-induced ER stress triggered apoptosis of tumor cells. Moreover, simultaneous stimulation of autophagy and ER stress in tumor cells promoted cytoprotective selective autophagy (reticulophagy) aimed at resolving ER stress, which may be a mechanism underlying the development of chemoresistance in skin melanoma.

We evaluated the response of Mycobacterium tuberculosis to exposure to a new aroylhydrazone derivative using the in vitro mutagenesis followed by genomic analysis of a resistant variant. The compound N'-[(E)-(5-methoxy-1H-indol-3-yl)methylidene]furan-2-carbohydrazide showed minimal inhibitory concentration (MIC) of 0.4412 μM for the reference strain M. tuberculosis H37Rv. An H37Rv clone resistant to elevated (4 × MIC) concentration of this compound recovered on a solid medium was further analyzed by whole genome sequencing and bioinformatics tools. A non-synonymous mutation was detected in the Rv3755c gene at position 302A>G (codon 101H>R, CAC-CGC). The gene-gene interaction analysis showed that this gene belongs to a network that also includes several ABC transporter genes. The identified mutation in Rv3755c may be associated with bacterial adaptation to the selective pressure of the studied aroylhydrazone derivative and reflect a non-specific drug tolerance mechanism. The conserved M. tuberculosis protein Rv3755c, whose function is unknown, may be related to the ABC transporter efflux system.

Tuberculous meningitis (TBM) is the most prevalent and severe manifestation of tuberculosis in CNS. The mechanisms of neurological injury caused by TBM are not well understood. Our study showed that overexpression of WTAP (Wilms tumor 1 associated protein) reduced inflammatory factors and Iba-1 expression induced in BV-2 by H37Rv. It also increased proliferation of neural stem/progenitor cells (NSPCs) and expression of the neuronal marker DCX in these cells. WTAP enhanced expression of high mobility group nucleosome-binding domain-containing protein 3 (HMGN3) by promoting m⁶A methylation of its mRNA. Reducing HMGN3 expression negated WTAP-induced anti-inflammatory and neuroprotective effects in TBM cell model. WTAP inhibited inflammation and microglia activation while promoting NSPC differentiation into neurons via elevation of HMGN3 expression. WTAP/HMGN3 proteins and the corresponding mRNA could be potential targets in the treatment of TBM.

It is known that the senescence-associated secretory phenotype (SASP) can promote senescence of surrounding normal cells. However, SASP signaling during senescence of mesenchymal stromal cells (MSCs) has not yet been fully studied. We determined the pattern of secreted proteins specific to MSCs under stress-induced senescence. Using chromatography-mass spectrometry, proteins specific to the secretome of senescent or "young" cells were identified. The secretome of senescent cells contains proteins both associated with senescence (LOXL2, CCL2, PLAT, SERPINE2, etc.) and important for reducing the impact of these processes, in particular, proteins responsible for inhibition of oxidative stress (MIF, PRDX5, GSTM2), detoxification of methylglyoxal (GLO1), and suppression of inflammatory reactions (GAS6, GSTM2). The obtained results indicate the complex etiology of aging and the ambiguity of the function of SASP within the paracrine induction of aging of neighboring cells.

Among the species belonging to the genus Lysobacter, known as micropredators, there are valuable strains-producers of antibiotics that can be effective in the fight against pathogenic microorganisms. The morphological features (pigments and cell sizes) of a new strain Lysobacter sp. Hz25 were studied during cultivation on different media. It was found that the size of Lysobacter sp. Hz25 cells depends on the number of CFU per unit area of solid medium and the location relative to the center of the colony. At low CFU number and at the periphery of the colony, the cells are longer, which indicates their possible transition to a mobile state. The color of the colonies depended on the medium composition. The presence of a complex of yellow hydrophobic pigments in the cells and a complex of hydrophilic pigments secreted into the medium and coloring it pink and yellow was found. Understanding of the effect of the medium composition on the morphology of Lysobacter sp. Hz25 cells and colonies and, consequently, on its interaction with pathogenic microorganisms will allow more complete use of its properties for combating human infections.

The sizes of intracerebral high-grade gliomas 101.8 and C6 in Wistar and Long-Evans rats and their relationship with survival were determined; changes in the thickness of the cerebral cortex were evaluated and morphological features of glioma models were studied. Median glioma volumes measured on MRI of brain slices in Wistar rats with glioblastoma 101.8 and glioma C6 were 169 (148-252) mm³ and 114 (47-154) mm³, respectively; in Long-Evans rats with glioma C6, the median volume of the tumor was 159 (85-223) mm³ without significant differences. The mean survival time of Wistar rats with glioblastoma 101.8 and glioma C6 were 16 ± 1 (SE = 0.3) days and 33 ± 6 (SE = 2) days; in Long-Evans rats with glioma C6, the mean survival time was 30 ± 2 (SE = 4) days. Survival in rats with glioblastoma 101.8 was significantly lower than in animals with C6 glioma. A negative correlation of tumor size and survival was revealed in Wistar and Long-Evans rats with glioma C6: r = -0.80 (p = 0.006) and r = -0.70 (p = 0.03), respectively. The mean thickness of the cortex of the contralateral hemisphere in tumor-bearing rats was significantly lower than in sham-operated animals. Glioma models vary in the growth rate. At the late stages of 101.8 and C6 gliomas, the thickness of the cerebral cortex of the contralateral hemisphere decreases. The volume of C6 glioma can be used as a predictor of Wistar and Long-Evans rat survival.