Восстановление дрожжевых клеток от лучевых повреждений с помощью магнитных изотопов: Новый подход к созданию противолучевых средств для биомедицины

Once atomic power engineering has become a part of our everyday life; the special precautions should be taken to defend the people in case of chronic radiation. Novel anti-radiation protectors are required which would be non-toxic and suited to long-time applications. Of special interest, can be stable magnetic isotopes of some chemical elements which normally present in living nature. The so-called magnetic isotope effects (MIEs) have long been known in physics of liquid matter. Not long ago, MIEs were discovered in the experiments with living cells. In this review, I present the experimental results of our research group on searching in this direction. The striking effect of the magnetic isotope of magnesium, 25Mg, has been revealed in the studies of post-radiation recovery of yeast cells irradiated by short UV light or ionizing radiation. The post-radiation recovery of the cells enriched with 25Mg proceeds two times faster than the post-radiation recovery of the cells enriched with the nonmagnetic magnesium isotope. Furthermore, the striking beneficial effects of the magnetic 25Mg were found in experiments with the isolated enzymes, muscle myosin and mitochondrial H+-ATPase, the most important biomolecular motors of cell bioenergetics. A similar effect, i.e., the acceleration of chemo-mechanical cycle of myosin by the nuclear spin, has been discovered in experiments with the magnetic isotope of zinc, 67Zn. Although physical mechanisms of the nuclear spin catalysis in molecular liquids and biomolecular nanoreactors require further investigations, there are the grounds to believe that pharmaceutical agents enriched with the magnetic isotopes will find use for creating novel anti-radiation protectors.

Abstract— A method is presented for analyzing data on the kinetics of photoreactivation and liquid‐holding recovery in microorganisms. The method extracts, from measurements on survival, the number of repairable lethal hits per cell remaining after a period of photoreactivation or liquid‐holding recovery. A semilogarithmic plot of this quantity as a function of the duration of the survival‐enhancing treatment reveals the nature of the kinetics of inactivation of the lethal hits.The method has been applied to photoreactivation and liquid‐holding recovery in yeast cells with wild‐type radiation resistance. In the case of photoreactivation of ultraviolet‐damaged cells, the number of lethal hits per cell is found to decrease exponentially with the length of exposure to a continuous source of photoreactivating light. Liquid‐holding recovery in cells exposed to ultraviolet light or X‐rays also results in exponential decrease of lethal hits with increasing time.The method is compared with the fluence‐decrement method and Dulbecco's treatment of photoreactivation data.

In this study, three novel flavonoid composite materials, created by combining an aglycone [quercetin (QUE), hesperetin (HES) or naringenin (NAR)] with monoglucosyl rutin (MGR), were designed to test for improved radioprotectivity compared with that provided by administration of MGR alone. Aglycone in the MGR-composite state was highly soluble in water, compared with aglycone alone dissolved in dimethyl sulfoxide or distilled water. The antioxidant activity of the three flavonoid composites was as high as that of MGR only. Next, the cytotoxicity test after 30 min treatment of an MGR composite showed a clear reduction in cell viability and suggested that a rapid introduction of aglycone into cells had taken place. In addition, QUE/MGR and HES/MGR composites strongly scavenged intracellular reactive oxygen species (ROS) induced by X-ray irradiation as well as MGR alone did. However, in the colony-formation assay using irradiated Chinese hamster ovary (CHO) cells, the HES/MGR composite showed a stronger radioprotective effect than MGR alone did, but the QUE/MGR composite showed no additional protective effect compared with the control. Furthermore, it was revealed that QUE and QUE/MGR composite treatment had the effect of reducing the glutathione (GSH) content in cells, and that QUE showed a stronger inhibition of PARP activity compared that of HES and NAR. Our data demonstrated that when designing a flavonoid composite as a radioprotective agent, it was necessary to select an appropriate aglycone, considering not only its antioxidant ability but also its inhibitory effect on cell recovery or DNA repair after radiation injury.

Matrix-assisted pulsed-laser evaporation direct-write (MAPLE DW) has been emerging as a promising biological construct fabrication technique. The post-transfer cell viability in MAPLE DW depends on various operation conditions such as the applied laser fluence; unfortunately, the effect of laser fluence on the post-transfer cell viability has not been well elucidated. This work aims to study the effect of laser fluence on the post-transfer cell viability and the cell recovery ability in MAPLE DW of yeast cells (Saccharomyces cerevisiae). It has been observed that (1) yeast cell viability decreases as the laser fluence increases from 85 to around 1500mJ∕cm2 and (2) some of the MAPLE DW process-induced cell damage is reversible. The post-transfer yeast cell recovery is a function of laser fluence; however, this dependence relationship is not monotonic. Future work is needed to better understand the physical and chemical mechanisms of the above observations.

Severe acute radiation injuries are both very lethal and exceptionally difficult to treat. Though the radioresistant bacterium D. radiodurans was first characterized in 1956, genes and proteins key to its radioprotection have not yet to be applied in radiation injury therapy for humans. In this work, we express the D. radiodurans protein PprI in Pichia pastoris yeast cells transfected with the designed vector plasmid pHBM905A-pprI. We then treat human umbilical endothelial vein cells and BALB/c mouse cells with the yeast-derived PprI and elucidate the radioprotective effects the protein provides upon gamma irradiation. We see that PprI significantly increases the survival rate, antioxidant viability, and DNA-repair capacity in irradiated cells and decreases concomitant apoptosis rates and counts of damage-indicative γH2AX foci. Furthermore, we find that PprI reduces mortality and enhances bone marrow cell clone formation and white blood cell and platelet counts in irradiated mice. PprI also seems to alleviate pathological injuries to multiple organs and improve antioxidant viability in some tissues. Our results thus suggest that PprI has crucial radioprotective effects on irradiated human and mouse cells.

Indole-3-carboxaldehyde (I3A), one of tryptophan metabolites derived from gut microbiota, extends the lifespan of mice after high-dose ionizing radiation exposure. Persistent myelosuppression is the most common and fatal complication for victims of nuclear accidents and patients undergoing radiotherapy, with few therapeutic options available. However, whether and how I3A protects ionizing radiation-induced hematopoietic toxicity remain unknown. In this study, we demonstrated that I3A treatment effectively ameliorated radiation-induced hematopoietic injury through accelerating peripheral blood cells recovery, promoting bone marrow cellularity restoration and enhancing functional HSPC regeneration. Additionally, I3A also suppressed intracellular reactive oxygen species production and inhibited apoptosis in irradiated HSPCs. Mechanistically, I3A treatment significantly increased HSPC quiescence, thus conferring HSPCs with resistance against radiation injury. Finally, I3A treatment could improve survival of lethally irradiated mice. Taken together, our data suggest that I3A acts as a gut microbiota-derived paracrine factor that regulates HSPC regeneration and may serve as a promising therapeutic agent for ionizing radiation-induced myelosuppression.

It is now well established for a wide variety of biological systems that the amount of dissolved present in cells during X-irradiation is a crucial parameter in determining what fraction of the initial molecular changes produced by the ionizations is ultimately expressed in detectable form.l-3 The shape of the survival curves for various cells and microorganisms, using inhibition of colony formation as an assay for lethality, is often found to be independent of whether the radiation is delivered in the presence or absence of oxygen;2, 3 that is, the curves obtained under different tensions can be made to superimpose by a suitable linear adjustment of the dose axis, and so it is convenient to describe the increased effectiveness of the radiation in the presence of in terms of an oxygen enhancement ratio. The enhancement ratio for cellular inactivation has been found to depend on certain details of the biological assay such as the type and richness of the plating media, even for a given organism.4 However, for a given assay procedure, a fundamental question in any theory of radiation injury is whether or not there are any differences in the nature or pattern of the lesions relevant to this end point produced in cells following exposure to X rays under aerobic as opposed to anaerobic conditions. In a search for further criteria of ionizing radiation damage, especially any which might distinguish between effects produced in the presence and absence of oxygen, we have recently found that yeast cells which survive anaerobic X-irradiation are more sensitive to subsequent dye-sensitized photoinactivation than are the survivors of comparable aerobic X-irradiation.5 The results show that, under anaerobic conditions, X rays inflict latent or unexpressed damage that can be detected by subsequent photoinactivation, but which is not present after X-irradiation under aerobic conditions. There is no such sensitization by preliminary anaerobic X-irradiation to subsequent ultraviolet inactivation. Thus, conditions which appear to protect cells from the effects of X rays (e.g., anoxia) may, at the same time, serve to promote the formation of X-ray induced lesions that sensztize them to other agents. Materials and Methods.-The results reported in this paper were all derived from radiation interaction experiments on starved suspensions of the haploid and diploid yeasts, Saccharomyces cerevisiae (SC-7, SC-6). The use of such experiments to determine the extent to which X rays and ultraviolet light exert their lethal effects on these cells through common sensitive sites has already been described.6 In the present experiments, both fully oxygenated and anoxic suspensions of cells were inactivated with X rays down to a given survival level (usually 10%), and then further inactivated either by visible light in the presence of acridine orange' or by ultraviolet light. The percentage of cells surviving any given radiation dose was determined from visible

This report illustrates that the β-androstenes are indeed able to upregulate the host immune response to a level that enables the host to resist lethal infection by viruses or bacteria. These agents consist of a subgroup of steroids, which also mediates a rapid recovery of hematopoietic precursor cells after whole-body lethal radiation injury. In vivo, the androstenes increase the levels of the Th1 cytokines such as IL-2, IL-3, and IFN. Similar to hydrocortisone, they suppress inflammation, but without immune suppression, and have a role in the maintenance of the Th1/Th2 balance and immune homeostasis.

Lignocellulosic sugar management for xylitol and ethanol fermentation with multiple cell recycling by Kluyveromyces marxianus IIPE453

The study of post-irradiation recovery of yeast: the ‘opremolecular period’

As hematopoietic stem cells can differentiate into all hematopoietic lineages, mitigating the damage to hematopoietic stem cells is important for recovery from overdose radiation injury. Cells in bone marrow microenvironment are essential for hematopoietic stem cells maintenance and protection, and many of the paracrine mediators have been discovered in shaping hematopoietic function. Several recent reports support exosomes as effective regulators of hematopoietic stem cells, but the role of osteoblast derived exosomes in hematopoietic stem cells protection is less understood. Here, we investigated that osteoblast derived exosomes could alleviate radiation damage to hematopoietic stem cells. We show that intravenous injection of osteoblast derived exosomes promoted WBC, lymphocyte, monocyte and hematopoietic stem cells recovery after irradiation significantly. By sequencing osteoblast derived exosomes derived miRNAs and verified in vitro, we identified miR-21 is involved in hematopoietic stem cells protection via targeting PDCD4. Collectively, our data demonstrate that osteoblast derived exosomes derived miR-21 is a resultful regulator to radio-protection of hematopoietic stem cells and provide a new strategy for reducing radiation induced hematopoietic injury.

In 1966, Pohl and Hawk [Science 152, 647-649 (1966)] published the first demonstration of dielectrophoresis of living and dead yeast cells; their paper described how the different ways in which the cells responded to an applied nonuniform electric field could form the basis of a cell separation method. Fifty years later, the field of dielectrophoretic (DEP) cell separation has expanded, with myriad demonstrations of its ability to sort cells on the basis of differences in electrical properties without the need for chemical labelling. As DEP separation enters its second half-century, new approaches are being found to move the technique from laboratory prototypes to functional commercial devices; to gain widespread acceptance beyond the DEP community, it will be necessary to develop ways of separating cells with throughputs, purities, and cell recovery comparable to gold-standard techniques in life sciences, such as fluorescence- and magnetically activated cell sorting. In this paper, the history of DEP separation is charted, from a description of the work leading up to the first paper, to the current dual approaches of electrode-based and electrodeless DEP separation, and the path to future acceptance outside the DEP mainstream is considered.