Rescue Effect Research Articles

Analysis of Emergency Care Pathway for Effects in Rescue of Patients with Rhabdomyolysis Syndrome

Analysis of Emergency Care Pathway for Effects in Rescue of Patients with Rhabdomyolysis Syndrome

TNF Signaling Acts Downstream of MiR-322/-503 in Regulating DM1 Myogenesis

Myotonic dystrophy type 1 (DM1) is caused by the expanded CUG repeats and usually displays defective myogenesis. Although we previously reported that ectopic miR-322/-503 expression improved myogenesis in DM1 by targeting the toxic RNA, the underlying pathways regulating myogenesis that were aberrantly altered in DM1 and rescued by miR-322/-503 were still unknown. Here, we constructed DM1 and miR-322/-503 overexpressing DM1 myoblast models, which were subjected to in vitro myoblast differentiation along with their corresponding controls. Agreeing with previous findings, DM1 myoblast showed remarkable myogenesis defects, while miR-322/-503 overexpression successfully rescued the defects. By RNA sequencing, we noticed that Tumor necrosis factor (TNF) signaling was the only pathway that was significantly and oppositely altered in these two experimental sets, with it upregulated in DM1 and inhibited by miR-322/-503 overexpression. Consistently, hyperactivity of TNF signaling was detected in two DM1 mouse models. Blocking TNF signaling significantly rescued the myogenesis defects in DM1. On the contrary, TNF-α treatment abolished the rescue effect of miR-322/-503 on DM1 myogenesis. Taking together, these results implied that TNF signaling mediated the myogenesis defects in DM1 and might act downstream of miR-322/-503 in regulating the myogenesis in DM1. Moreover, the inhibition of TNF signaling benefiting myogenesis in DM1 provided us with a novel therapeutic strategy for DM1.

Saving migrants’ lives at sea: Improving search and rescue operations

The present study focuses on the Mediterranean Sea migration crisis and investigates the effectiveness of search and rescue (SAR) operations alongside measures to reduce the number of deaths of migrants at sea. It also describes the stakeholders involved in SAR activities. The paper first analyzes secondary data and the results of 24 in‐depth interviews in order to develop an analytical framework, which is then complemented by a system dynamics model to explore the complexity and interactions among stakeholders in SAR operations. The study shows that the death toll at sea can be reduced by enhancing cooperation among stakeholders by providing legal migration pathways under certain conditions and by engaging in more effective migrant detection and interception at sea. Lastly, raising potential migrants’ awareness about the risk of death during the sea crossing should be seen as an additional measure, while SAR activities should be maintained to prevent loss of life at sea.

Chromosome-length genome assembly and linkage map of a critically endangered Australian bird: the helmeted honeyeater.

BackgroundThe helmeted honeyeater (Lichenostomus melanops cassidix) is a Critically Endangered bird endemic to Victoria, Australia. To aid its conservation, the population is the subject of genetic rescue. To understand, monitor, and modulate the effects of genetic rescue on the helmeted honeyeater genome, a chromosome-length genome and a high-density linkage map are required.ResultsWe used a combination of Illumina, Oxford Nanopore, and Hi-C sequencing technologies to assemble a chromosome-length genome of the helmeted honeyeater, comprising 906 scaffolds, with length of 1.1 Gb and scaffold N50 of 63.8 Mb. Annotation comprised 57,181 gene models. Using a pedigree of 257 birds and 53,111 single-nucleotide polymorphisms, we obtained high-density linkage and recombination maps for 25 autosomes and Z chromosome. The total sex-averaged linkage map was 1,347 cM long, with the male map being 6.7% longer than the female map. Recombination maps revealed sexually dimorphic recombination rates (overall higher in males), with average recombination rate of 1.8 cM/Mb. Comparative analyses revealed high synteny of the helmeted honeyeater genome with that of 3 passerine species (e.g., 32 Hi-C scaffolds mapped to 30 zebra finch autosomes and Z chromosome). The genome assembly and linkage map suggest that the helmeted honeyeater exhibits a fission of chromosome 1A into 2 chromosomes relative to zebra finch. PSMC analysis showed a ∼15-fold decline in effective population size to ∼60,000 from mid- to late Pleistocene.ConclusionsThe annotated chromosome-length genome and high-density linkage map provide rich resources for evolutionary studies and will be fundamental in guiding conservation efforts for the helmeted honeyeater.

High turnover and rescue effect of XRCC1 in response to heavy charged particle radiation

The DNA damage response is a highly orchestrated process. The involvement of the DNA damage response factors in DNA damage response depends on their biochemical reactions with each other and with chromatin. Using online live-cell imaging combined with heavy ion microbeam irradiation, we studied the response of the scaffold protein X-ray repair cross-complementary protein 1 (XRCC1) at the localized DNA damage in charged particle irradiated HT1080 cells expressing XRCC1-tagged RFP. The results showed that XRCC1 was recruited to the DNA damage with ultrafast kinetics in a poly ADP-ribose polymerase-dependent manner. The consecutive reaction model well explained the response of XRCC1 at ion hits, and we found that the XRCC1 recruitment was faster and dissociation was slower in the G2 phase than those in the G1 phase. The fractionated irradiation of the same cells resulted in accelerated dissociation at the previous damage sites, and the dissociated XRCC1 immediately recycled with a higher recruitment efficiency. Our data revealed XRCC1’s new rescue mechanism and its high turnover in DNA damage response, which benefits our understanding of the biochemical mechanism in DNA damage response.

Osteopontin aggravates acute lung injury in influenza virus infection by promoting macrophages necroptosis

Infection with influenza A virus (IAV) can trigger pulmonary inflammation and lung damage. Osteopontin (OPN) is an essential regulator of cell death and immunity. However, the role and underlying mechanism of OPN in cell death in IAV-induced pulmonary injury remain poorly understood. Here, we demonstrated that OPN-deficient (OPN−/−) mice were insensitive to IAV, exhibiting decreased viral loads and attenuated lung injury after IAV infection compared to those in wild-type (WT) mice. Moreover, macrophage necroptosis was significantly reduced in OPN−/− mice infected with IAV compared to that in infected WT mice. OPN increased the expression of necroptosis-related genes and exacerbated macrophage necroptosis in IAV-infected THP1 cells. Notably, adoptive transfer of WT bone marrow-derived macrophages (BMDMs) or OPN−/− BMDMs into mice restored resistance to influenza infection, and the rescue effect of OPN−/− BMDMs was better than that of WT BMDMs. Collectively, these results suggest that OPN deficiency in macrophages reduces necroptosis, which leads to a decrease in viral titers and protects against IAV infection. Therefore, OPN is a potential target for the treatment of IAV infection.

Augmentation of progestin signaling rescues testis organization and spermatogenesis in zebrafish with the depletion of androgen signaling.

Disruption of androgen signaling is known to cause testicular malformation and defective spermatogenesis in zebrafish. However, knockout of cyp17a1, a key enzyme responsible for the androgen synthesis, in ar-/- male zebrafish paradoxically causes testicular hypertrophy and enhanced spermatogenesis. Because Cyp17a1 plays key roles in hydroxylation of pregnenolone and progesterone (P4), and converts 17α-hydroxypregnenolone to dehydroepiandrosterone and 17α-hydroxyprogesterone to androstenedione, we hypothesize that the unexpected phenotype in cyp17a1-/-;androgen receptor (ar)-/- zebrafish may be mediated through an augmentation of progestin/nuclear progestin receptor (nPgr) signaling. In support of this hypothesis, we show that knockout of cyp17a1 leads to accumulation of 17α,20β-dihydroxy-4-pregnen-3-one (DHP) and P4. Further, administration of progestin, a synthetic DHP mimetic, is sufficient to rescue testicular development and spermatogenesis in ar-/- zebrafish, whereas knockout of npgr abolishes the rescue effect of cyp17a1-/- in the cyp17a1-/-;ar-/- double mutant. Analyses of the transcriptomes among the mutants with defective testicular organization and spermatogenesis (ar-/-, ar-/-;npgr-/- and cyp17a-/-;ar-/-;npgr-/-), those with normal phenotype (control and cyp17a1-/-), and rescued phenotype (cyp17a1-/-;ar-/-) reveal a common link between a downregulated expression of insl3 and its related downstream genes in cyp17a-/-;ar-/-;npgr-/- zebrafish. Taken together, our data suggest that genetic or pharmacological augmentation of the progestin/nPgr pathway is sufficient to restore testis organization and spermatogenesis in zebrafish with the depletion of androgen signaling.

Saving species in a snap: On the feasibility and efficacy of augmented reality-based wildlife interactions for conservation

Interactions with wildlife can contribute to biodiversity conservation outcomes, though safety and accessibility considerations limit animal encounters from being a viable strategy. This investigation explores the feasibility of mobile augmented reality to facilitate interactions with wildlife and encourage biodversity conservation. A mobile augmented reality experience (Snapchat lens), titled “Penguin Rescue!”, was created to allow users to rehabilitate an oil-slicked virtual penguin. Study 1 distributed the lens globally to Snapchat users (N = 63,605) who spent an average of 47 s rehabilitating the penguin; psychographic data showed pro-environmental interests were not associated with the lens’ use. Study 2 employed a within-subjects experimental design (N = 80) to examine the effects of Penguin Rescue! on conservation outcomes. Results showed that the interaction increased connectedness with the species. Moreover, social presence and plausibility served as key mechanisms contributing to environmental concern and behavioral intentions. Overall, results clarify how biophilic interactions via augmented reality can benefit biodiversity conservation.

Drosophila ZIP13 over-expression or transferrin1 RNAi influences the muscle degeneration of Pink1 RNAi by elevating iron levels in mitochondria.

Disruption of iron homeostasis in the brain of Parkinson's disease (PD) patients has been reported for many years, but the underlying mechanisms remain unclear. To investigate iron metabolism genes related to PTEN-induced kinase 1 (Pink1) and parkin (E3 ubiquitin ligase), two PD-associated proteins that function to coordinate mitochondrial turnover via induction of selective mitophagy, we conducted a genetic screen in Drosophila and found that altered expression of genes involved in iron metabolism, such as Drosophila ZIP13 (dZIP13) or transferrin1 (Tsf1), significantly influences the disease progression related to Pink1 but not parkin. Several phenotypes of Pink1 mutant and Pink1 RNAi but not parkin mutant were significantly rescued by over-expression (OE) of dZIP13 (dZIP13 OE) or silencing of Tsf1 (Tsf1 RNAi) in the flight muscles. The rescue effects of dZIP13 OE or Tsf1 RNAi were not exerted through mitochondrial disruption or mitophagy; instead, the iron levels in mitochondira were significantly increased, resulting in enhanced activities of enzymes participating in respiration and increased ATP synthesis. Consistently, the rescue effects of dZIP13 OE or Tsf1 RNAi on Pink1 RNAi can be inhibited by decreasing the iron levels in mitochondria through mitoferrin (dmfrn) RNAi. This study suggests that dZIP13, Tsf1, and dmfrn might act independently of parkin in a parallel pathway downstream of Pink1 by modulating respiration and indicates that manipulation of iron levels in mitochondria may provide a novel therapeutic strategy for PD associated with Pink1.

Effects of rescue inhaled nitric oxide on right ventricle and pulmonary circulation in severe COVID-related acute respiratory distress syndrome.

PurposesTo assess the effects of inhaled Nitric Oxide (iNO) on right ventricle dimension and function and systolic pulmonary arterial pressures in severe Acute Respiratory Distress (ARDS) due to Sars-Cov2 (COVID) infection.Materials and methodsWe assessed the effects of iNO on right ventricle dimension and function and systolic pulmonary arterial pressures in 12 consecutive COVID-related ARDS patients by means of serial echocardiographic exams (baseline, 12 and 24 h since iNO start).ResultsInhaled NO administration did not influence systolic pulmonary arterial pressures nor RV dimension and function. No changes were detectable in ventilatory data with iNO administration. Considering the negligible effect on oxygenation, iNO use was discontinued in all cases.ConclusionsIn COVID-related severe ARDS iNO administrated as rescue therapy is not able to ameliorate oxygenation nor pulmonary hypertension, as assessed by serial echocardiograms. This finding may be explained by the diffuse loss of hypoxic pulmonary vasoconstriction with increased perfusion around alveolar consolidations which characterizes COVID-related severe ARDS.

Scaling of population resilience with dispersal length and habitat size

Environmental fluctuations can create population-depleted areas and even extinct areas for the population. This effect is more severe in the presence of the Allee effect (decreasing growth rate at low population densities). Dispersal inside the habitat provides a rescue effect on population-depleted areas, enhancing the population resilience to environmental fluctuations. Habitat reduction decreases the effectiveness of the dispersal rescue mechanism. We report here how the population resilience to environmental fluctuations decreases when the dispersal length or the habitat size are reduced. The resilience reduction is characterized by a decrease of the extinction threshold for environmental fluctuations. The extinction threshold is shown to scale with the ratio between the dispersal length and the scale of environmental synchrony, i.e. it is the dispersal connection between non-environmentally-correlated regions that provides resilience to environmental fluctuations. Habitat reduction also decreases the resilience to environmental fluctuations, when the habitat size is similar to or smaller than the characteristic dispersal distances. The power laws of these scaling behaviors are characterized here. Alternative scaling functions with spatial scales of population synchrony are found to fit the simulations worse. These results support the dispersal length as the critical scale for extinction induced by habitat reduction.

Deciphering the Complex Molecular Pathogenesis of Myotonic Dystrophy Type 1 through Omics Studies

Omics studies are crucial to improve our understanding of myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults. Employing tissue samples and cell lines derived from patients and animal models, omics approaches have revealed the myriad alterations in gene and microRNA expression, alternative splicing, 3′ polyadenylation, CpG methylation, and proteins levels, among others, that contribute to this complex multisystem disease. In addition, omics characterization of drug candidate treatment experiments provides crucial insight into the degree of therapeutic rescue and off-target effects that can be achieved. Finally, several innovative technologies such as single-cell sequencing and artificial intelligence will have a significant impact on future DM1 research.

Functional Rescue of a Nephrogenic Diabetes Insipidus Causing Mutation in the V2 Vasopressin Receptor by Specific Antagonist and Agonist Pharmacochaperones.

The urine concentrating function of the kidney is essential to maintain the water homeostasis of the human body. It is mainly regulated by the arginine-vasopressin (AVP), which targets the type 2 vasopressin receptor (V2R) in the kidney. The inability of V2R to respond to AVP stimulation leads to decreased urine concentration and congenital nephrogenic diabetes insipidus (NDI). NDI is characterized by polyuria, polydipsia, and hyposthenuria. In this study, we identified a point mutation (S127F) in the AVPR2 gene of an NDI patient, and we characterized the impaired function of the V2R mutant in HEK293 cells. Based on our data, the S127F-V2R mutant is almost exclusively located intracellularly in the endoplasmic reticulum (ER), and very few receptors were detected at the cell surface, where the receptor can bind to AVP. The overexpressed S127F-V2R mutant receptor has negligible cAMP generation capability compared to the wild-type receptor in response to AVP stimulation. Since certain misfolded mutant proteins, that are retained in the ER, can be rescued by pharmacological chaperones, we examined the potential rescue effects of two pharmacochaperones on the S127F-V2R. We found that pretreatment with both tolvaptan (an established V2R inverse agonist) and MCF14 compound (a cell-permeable high-affinity agonist for the V2R) were capable of partially restoring the cAMP generating function of the receptor in response to vasopressin stimulation. According to our data, both cell permeant agonists and antagonists can function as pharmacochaperones, and serve as the starting compounds to develop medicines for patients carrying the S127F mutation.

Effects of delta-opioid receptor agonist pretreatment on the cardiotoxicity of bupivacaine in rats

BackgroundDelta-opioid receptor is widely expressed in human and rodent hearts, and has been proved to protect cardiomyocytes against ischemia/reperfusion and heart failure. The antagonist of delta-opioid receptor could block the rescue effect of lipid emulsion against local anesthetic cardiotoxicity. However, no evidence is available for the direct effect of delta-opioid-receptor agonists on the cardiotoxicity of local anesthetics.MethodsAnesthetized Sprague Dawley rats were divided into five groups. Group NS received 2 ml·kg−1·min−1 normal saline, group LE received 2 ml·kg−1·min−1 30% lipid emulsion and group BW received 0.1, 1.0, or 5.0 mg/kg BW373U86, a delta-opioid-receptor agonist, for 5 min. Then 0.5% bupivacaine was infused intravenously at a rate of 3.0 mg·kg−1·min−1 until asystole. The time of arrhythmia, 50% mean arterial pressure-, 50% heart rate-reduction and asystole were recorded, and the dose of bupivacaine at each time point was calculated.ResultsAll three different doses of BW373U86 did not affect the arrhythmia, 50% mean arterial pressure-reduction, 50% heart rate-reduction and asystole dose of bupivacaine compared with group NS. 30% LE significantly increased the bupivacaine threshold of 50% mean arterial pressure-reduction (17.9 [15.4–20.7] versus 7.2 [5.9–8.7], p = 0.018), 50% heart rate-reduction (18.7 ± 4.2 versus 8.8 ± 1.7, p < 0.001) and asystole (26.5 [21.0–29.1] versus 11.3 [10.7–13.4], p = 0.008) compared with group NS. There was no difference between group LE and group NS in the arrhythmia dose of bupivacaine (9.9 [8.9–11.7] versus 5.6 [4.5–7.0], p = 0.060).ConclusionsOur data show that BW373U86 does not affect the cardiotoxicity of bupivacaine compared with NS control in rats. 30% LE pretreatment protects the myocardium against bupivacaine-induced cardiotoxicity.

Pharmacological activation of the Sonic hedgehog pathway with a Smoothened small molecule agonist ameliorates the severity of alcohol-induced morphological and behavioral birth defects in a zebrafish model of fetal alcohol spectrum disorder.

Ethanol exposure during the early stages of embryonic development can lead to a range of morphological and behavioral differences termed fetal alcohol spectrum disorders (FASDs). In a zebrafish model, we have shown that acute ethanol exposure at 8-10hr postfertilization (hpf), a critical time of development, produces birth defects similar to those clinically characterized in FASD. Dysregulation of the Sonic hedgehog (Shh) pathway has been implicated as a molecular basis for many of the birth defects caused by prenatal alcohol exposure. We observed in zebrafish embryos that shh expression was significantly decreased by ethanol exposure at 8-10 hpf, while smo expression was much less affected. Treatment of zebrafish embryos with SAG or purmorphamine, small molecule Smoothened agonists that activate Shh signaling, ameliorated the severity of ethanol-induced developmental malformations including altered eye size and midline brain development. Furthermore, this rescue effect of Smo activation was dose dependent and occurred primarily when treatment was given after ethanol exposure. Markers of Shh signaling (gli1/2) and eye development (pax6a) were restored in embryos treated with SAG post-ethanol exposure. Since embryonic ethanol exposure has been shown to produce later-life neurobehavioral impairments, juvenile zebrafish were examined in the novel tank diving test. Our results further demonstrated that in zebrafish embryos exposed to ethanol, SAG treatment was able to mitigate long-term neurodevelopmental impairments related to anxiety and risk-taking behavior. Our results indicate that pharmacological activation of the Shh pathway at specific developmental timing markedly diminishes the severity of alcohol-induced birth defects.

The Value of Emergency Nursing Mode in the Treatment of Patients with Traumatic Shock.

Objective To study the value of emergency nursing mode in patients with traumatic shock. Methods 76 patients with traumatic shock in our hospital from March 2019 to February 2021 were selected and divided into study group and control group according to different rescue modes, 38 cases in each group. The study group adopted emergency nursing mode for rescue, while the control group adopted routine nursing mode for rescue. The rescue intervention, emergency stay and preoperative preparation time, rescue success rate, emergency rescue effect, complications, and satisfaction rate of patients and their families for rescue were compared between the two groups. Results The rescue intervention, emergency stay and preoperative preparation time of the study group were significantly shorter than those of the control group, and the difference was statistically significant (P < 0.05). The rescue success rate of the study group was 97.37%, which was significantly higher than 84.21% of the control group, and the difference was statistically significant (P < 0.05). The improvement rate of the study group was significantly higher than that of the control group, the disability rate was significantly lower than that of the control group, the overall emergency rescue effect was better than that of the control group, and the difference was statistically significant (P < 0.05). The incidence of complications in the study group was 2.63%, which was significantly lower than 23.68% in the control group (P < 0.05). The satisfaction rate of patients and their families in the study group was 97.37%, which was significantly higher than 84.21% in the control group (P < 0.05). Conclusion Emergency nursing mode in patients with traumatic shock owns higher rescue value, can buy time for the operation, improve the success rate and effect of rescue, make safety and satisfaction higher. Overall, for patients with traumatic shock, emergency nursing mode is better than conventional rescue nursing.

Circulatory GSK-3β: Blood-Based Biomarker and Therapeutic Target for Alzheimer's Disease.

Alzheimer's disease (AD) is the progressive brain disorder which degenerates brain cells connection and causes memory loss. Although AD is irreversible, it is not impossible to arrest or slow down the progression of the disease. However, this would only be possible if the disease is diagnosed at an early stage, and early diagnosis requires clear understanding of the pathogenesis at molecular level. Overactivity of GSK-3β and p53 accounts for tau hyperphosphorylation and the formation of amyloid-β plaques. Here, we explored GSK-3β and p53 as blood-based biomarkers for early detection of AD. The levels of GSK-3β, p53, and their phosphorylated states were measured using surface plasmon resonance and verified using western blot in serum from AD, mild cognitive impairment (MCI), and geriatric-control (GC) subjects. The neurotoxic SH-SY5Y cell line was treated with antioxidant Emblica Officinalis (EO) for rescue effect. GSK-3β, p53, and their phosphorylated states were significantly over expressed (p > 0.001) in AD and MCI compared to GC and can differentiate AD and MCI from GC. The expression level of GSK-3β and p53 proteins were found to be downregulated in a dose-dependent manner after the treatment with EO in amyloid-b-induced neurotoxic cells. These proteins can serve as potential blood markers for the diagnosis of AD and EO can suppress their level. This work has translational value and clinical utility in the future.

Decreased Cardiac NOX4 and SIRT-1 Protein Levels Contribute to Decreased Angiogenesis in the Heart of Diabetic Rats: Rescue Effects of IGF-1 and Exercise.

Purpose: Reduced angiogenesis in the heart tissue is a primary risk factor for heart disease in the diabetes condition. This study was aimed to evaluate the changes of two main angiogenesis mediators, NADPH oxidase 4 (NOX4) and sirtuin 1 (SIRT-1) protein levels in the heart of diabetic rats and the impact of Insulin-like growth factor 1 (IGF-1) and exercise on these proteins. Methods: Injection of 60 mg/kg of streptozotocin in 40 male Wistar rats led to the induction of type 1 diabetes. Angiogenesis was detected in the hearts by immunostaining for PECAM-1/ CD31 after 30 days of treatment with IGF-1 (2 mg/kg/day) and exercise. ELISA technique was utilized to establish the expression levels of NOX4 and SIRT-1 within the heart. Results: The results revealed a significant increase in HbA1c and a significant decrease in SIRT1, NOX4 levels and angiogenesis grade in the heart of diabetes group compared to control group. Meanwhile, IGF-1 and exercise alone or in combination completely masked these effects. Additionally, synergistic effect on SIRT-1, HbA1c levels and angiogenesis grade is evident when IGF-1 and exercise are applied simultaneously. Conclusion: Our findings suggest that reduction in angiogenesis in the heart of diabetic rats may be mediated by down expression of NOX4 and SIRT-1 protein levels. It was also displayed that IGF-1 and exercise as novel therapies increase NOX4 and SIRT-1 protein levels within the hearts of diabetic rats.

DNA Polymerase Gamma Recovers Mitochondrial Function and Inhibits Vascular Calcification by Interacted with p53.

DNA polymerase gamma (PolG) is the major polymerase of mitochondrial DNA (mtDNA) and essential for stabilizing mitochondrial function. Vascular calcification (VC) is common senescence related degenerative pathology phenomenon in the end-stage of multiple chronic diseases. Mitochondrial dysfunction was often observed in calcified vessels, but the function and mechanism of PolG in the calcification process was still unknown. The present study found PolGD257A/D257A mice presented more severe calcification of aortas than wild type (WT) mice with vitamin D3 (Vit D3) treatment, and this phenomenon was also confirmed in vitro. Mechanistically, PolG could enhance the recruitment and interaction of p53 in calcification condition to recover mitochondrial function and eventually to resist calcification. Meanwhile, we found the mutant PolG (D257A) failed to achieve the same rescue effects, suggesting the 3'-5' exonuclease activity guarantee the enhanced interaction of p53 and PolG in response to calcification stimulation. Thus, we believed that it was PolG, not mutant PolG, could maintain mitochondrial function and attenuate calcification in vitro and in vivo. And PolG could be a novel potential therapeutic target against calcification, providing a novel insight to clinical treatment.

CYTOGENETIC STUDY OF MANIFESTATIONS OF THE UNIVERSAL PHENOMENON OF THE BYSTANDER RESPONSE.

to establish the level of chromosomal instability in peripheral blood lymphocytes (PBL) from healthyindividuals and cells from patients with B-cell chronic lymphocytic leukemia (CLL) under co-cultivation conditions and to determine the possibility of inducing manifestations of the universal phenomenon of bystander response in them. Cytogenetic analysis of uniformly stained chromosomes from human PBL, which differed by cytogenetic markers of sex; the presence of oncological transformation and in vitro irradiation of 137Cs in a dose of 0.50 Gy under the conditions of their joint cultivation was performed. The frequency of chromosome aberrations in PBL from healthy individuals when co-cultured with the blood from CLL patients was 3.35 per 100 cells, exceeded the control (1.48 per 100 cells, р < 0.01), did not significantly differ from the rate in non-irradiated blood T-lymphocytes from patients with B-cell CLL (3.18 per 100 cells, р > 0.05) and was lower than when co-cultivated with irradiated blood from CLL patients (5.00 per 100 cells, р < 0.01). In irradiated in vitro blood lymphocytes from CLL patients, the mean group level of chromosome aberrations under separate cultivation was 12.36 per 100 cells and exceeded the indicator during their co-cultivation with lymphocytes from healthy individuals (8.35 per 100 cells, р < 0.05). A tumor-induced bystander effect (TIBE) develops in PBL from healthy individuals when co-cultured with the blood from CLL patients and in T lymphocytes of B-cell CLL patients, the cytogenetic manifestation of which is an increase in the frequency of single chromatid fragments. The interaction of irradiated blood cells from CLL patients with lymphocytes from healthy individuals causes an increase in chromosomal instability in the latter due to the development of a radiation-induced bystander effect (RIBE) and leads to a decrease in the level of chromosomal instability in irradiated lymphocytes from CLL patients (rescue effect). An increase in the level of chromatid-type aberrations in T-lymphocytes of CLL patients during in vitro irradiation is a consequence of the development of RIBE against the background of TIBE.