Radiation Syndrome Research Articles

Investigate the impact of laser dosages on the regeneration of peripheral blood leukocytes after gamma radiation exposure

This research aims to examine how treatment with lasers affects the regeneration of peripheral blood leukocytes following ionizing radiation exposure. Furthermore, how may laser treatment be administered to people who have inadvertently come into contact with ionizing radiation? After being subjected to one dose of five Gy, non-lethal (1.5 Gy/min) from gamma radiation (cobalt-60), the mice developed radiation-induced sickness, as evidenced by a drop in white blood cell count and hematological symptoms. The mice were subsequently subjected to non-ionizing radiation using a 20 W power laser (Nd: YAG 1064 nm). Within the first two weeks after the application of gamma rays for 30 min, there were a total of five laser treatments. Laser energy yielded a total of 60,000 J/cm2. The energy density in each treatment was 12,000 J/cm2. Based on the peripheral blood examination, the study establishes that the use of lasers had an important influence on the number of lymphocytes two weeks after irradiation. Furthermore, following laser treatment, the lymphocyte lineage of white blood cells recovered more quickly. In gamma-irradiated mice, the study showed that the treatment laser under examination increased the overall counts of several types of white blood cells, indicating an indefinite effect. The investigation's findings may have an impact on how radiation illness is treated for specific patients. The results of this investigation may have a substantial influence on the treatment of radiation sickness in people.

Role of Neurotransmitters in Steady State Hematopoiesis, Aging, and Leukemia.

Haematopoiesis within the bone marrow (BM) represents a complex and dynamic process intricately regulated by neural signaling pathways. This delicate orchestration is susceptible to disruption by factors such as aging, diabetes, and obesity, which can impair the BM niche and consequently affect haematopoiesis. Genetic mutations in Tet2, Dnmt3a, Asxl1, and Jak2 are known to give rise to clonal haematopoiesis of intermediate potential (CHIP), a condition linked to age-related haematological malignancies. Despite these insights, the exact roles of circadian rhythms, sphingosine-1-phosphate (S1P), stromal cell-derived factor-1 (SDF-1), sterile inflammation, and the complement cascade on various BM niche cells remain inadequately understood. Further research is needed to elucidate how BM niche cells contribute to these malignancies through neural regulation and their potential in the development of gene-corrected stem cells. This literature review describes the updated functional aspects of BM niche cells in haematopoiesis within the context of haematological malignancies, with a particular focus on neural signaling and the potential of radiomitigators in acute radiation syndrome. Additionally, it underscores the pressing need for technological advancements in stem cell-based therapies to alleviate the impacts of immunological stressors. Recent studies have illuminated the microheterogeneity and temporal stochasticity of niche cells within the BM during haematopoiesis, emphasizing the updated roles of neural signaling and immunosurveillance. The development of gene-corrected stem cells capable of producing blood, immune cells, and tissue-resident progeny is essential for combating age-related haematological malignancies and overcoming immunological challenges. This review aims to provide a comprehensive overview of these evolving insights and their implications for future therapeutic strategies.

An Overview of Radiation Countermeasure Development in Radiation Research from 1954 to 2024.

Preparation for medical responses to major radiation accidents, further driven by increases in the threat of nuclear warfare, has led to a pressing need to understand the underlying mechanisms of radiation injury (RI) alone or in combination with other trauma (combined injury, CI). The identification of these mechanisms suggests molecules and signaling pathways that can be targeted to develop radiation medical countermeasures. Thus far, the United States Food and Drug Administration (U.S. FDA) has approved seven countermeasures to mitigate hematopoietic acute radiation syndrome (H-ARS), but no drugs are available for prophylaxis and no agents have been approved to combat the other sub-syndromes of ARS, let alone delayed effects of acute radiation exposure or the effects of combined injury. From its inception, Radiation Research has significantly contributed to the understanding of the underlying mechanisms of radiation injury and combined injury, and to the development of radiation medical countermeasures for these indications through the publication of peer-reviewed research and review articles.

Radioprotective activity of the liposomal composition of quercetin in acute radiation syndrome (experimental study)

Background. The targeted search for new effective radioprotective agents, especially among compounds with antioxidant properties, remains relevant. Among them, quercetin which has a high specific activity against oxidative stress (cited as a «universal antioxidant») deserves attention. The transport liposomal composition of quercetin, which significantly improves its bioavailability and is the basis of the licensed drug «Lipoflavon®» (LF), is known, but the radioprotective properties of this drug have not been studied. The purpose of the work is to position Lipoflavon as a radioprotector for the first time based on the study of radioprotective activity in an acute experiment with total irradiation of rats. Materials and methods. The rat model of acute radiation syndrome (ARS) was carried out by short-term bilateral total body irradiation (TBI) on a CLINAC (6 MeV) linear accelerator at doses of 5.5 and 7.0 Gy. The control rats were sham-irradiated. The test sample of LF was used for the studies. LF (1.5 mg/mL) was administered to rats 30 min before TBI through the tail vein. The control TBI rats were injected with physiological saline. Experimental rats were randomly assigned into groups as follows: group 1 – non-irradiated control (intact animals); group 2 – irradiated control at a dose of 5.5 Gy (TBI5.5); group 3 – irradiation at a dose of 5.5 Gy with administration of LF (LF + TBI5.5); group 4 – irradiated control at a dose of 7.0 Gy (TBI7.0); group 5 – irradiation at a dose of 7.0 Gy with administration of LF (LF + TBI7.0). Clinical characteristics of ARS, overall survival, and the mean survival time of the dead animals were determined. The profiles of lethality («peaks of death») were calculated as total rat lethality (%) in certain time periods of the ARS. In hematological studies, LF was administered 24 h prior to TBI and twice a week the next 4 weeks after TBI. The hematological parameters were monitored on days 3, 7, 14 and 21 after TBI. Results. It was established that prophylactic LF administered 30 min before TBI at doses of 5.5 and 7.0 Gy, which were LD20/30 and DL73.3/30, increased the 30-day survival rate of the irradiated rats to 90 and 40% respectively, compared to 80 and 26.7% in irradiated control, and changed the radiation lethality profile of the rats in the model of ARS. The radioprotective activity of LF manifested in the form of the absence of early and late peaks of death of the irradiated rats and the survival time of more than 30 days after the treatment in 40% of rats with LD73,3/30. Prophylactic and therapeutic administration of LF prevented development of severe leukopenia and thrombocytopenia and contributed to a more rapid and sustained recovery of erythrocytes during the period of ARS. The most efficient radioprotective therapeutic effect of LF was observed in rats with a dose of LD73.3/30. Conclusions. The results of the study substantiate the radioprotective activity of Lipoflavon in ARS and help develop the new approaches to using the licensed drug «Lipoflavon®» as an effective pharmacological therapeutic agent for radiation protection in acute radiation.

Butyrate promotes visceral hypersensitivity in IBS model via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway.

Emerging evidence indicates that gut dysbiosis is involved in the pathogenesis of visceral hypersensitivity (VH). However, how gut microbiota contributes to the development of VH is unknown. Here, we sought to examine the signal transduction pathways from gut to dorsal root ganglion (DRG) responsible for this. Therefore, abdominal withdrawal reflex (AWR) scores, fecal output, fecal water content, and total gastrointestinal transit time (TGITT) were assessed in Con rats, VH rats, rats treated with NaB, and VH rats treated with VSL#3. Fecal microbiota and its metabolite (short-chain fatty acids, SCFAs), mast cell degranulation in colon, lincRNA-01028, miR-143, and protease kinase C (PKC) and TRPV1 expression in DRGs were further detected. VH rats showed an increased fecal water content, a shortened TGITT, an increased abundance of Clostridium sensu stricto 1 and increased butyrate in fecal samples, an increased mast cell degranulation, an increased expression of lincRNA-01028, PKC, and TRPV1, and a decreased expression of miR-143 in DRGs compared with control rats, which could be restored by the application of probiotic VSL#3. The above-mentioned detection in rats treated with butyrate was similar to that of VH rats. We further confirm whether butyrate sensitized DRG neurons by a lincRNA-01028, miR-143, and PKC-dependent mechanism via mast cell in vitro. In co-cultures, MCs treated with butyrate elicited a higher TRPV1 current, a higher expression of lincRNA-01028, PKC, and a lower expression of miR-143 in DRG neurons, which could be inhibited by a lincRNA-01028 inhibitor. These findings indicate that butyrate promotes visceral hypersensitivity via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway.IMPORTANCEIrritable bowel syndrome (IBS), characterized by visceral hypersensitivity, is a common gastrointestinal dysfunction syndrome. Although the gut microbiota plays a role in the pathogenesis and treatment of irritable bowel syndrome (IBS), the possible underlying mechanisms are unclear. Therefore, it is of critical importance to determine the signal transduction pathways from gut to DRG responsible for this in vitro and in vivo assay. This study demonstrated that butyrate sensitized TRPV1 in DRG neurons via mast cells in vivo and in vitro by a lincRNA-01028, miR-143, and PKC-dependent mechanism. VH rats similarly showed an increased abundance of Clostridium sensu stricto 1, an increased fecal butyrate, an increased mast cell degranulation, and increased expression of TRPV1 compared with control rats, which could be restored by the application of VSL#3. In conclusion, butyrate produced by the altered intestinal microbiota is associated with increased VH.

Future Perspectives of Wharton's Jelly Mesenchymal Stem Cells and their Soluble Factors in Radioprotection.

Acute radiation syndrome (ARS) is also known as triple syndrome, which develops after whole-body radiation exposure. During unforeseen exposures, these syndromes are set in depending on the dose of radiation. Cell-based therapy, especially using stem cells and their soluble factors, is gaining wide attention in the field of regenerative medicine to treat various diseases, including degenerative diseases. Stem cells attract prime attention because of their profound inherent tissue repair capability and regeneration potential. Further, stem cell therapy can be one of the promising strategies for the amelioration of ARS because of its ability to lodge in damaged tissue and release regenerative cytokines by sensing the local injury. In this regard, human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) have gained substantial attention for their applications in the treatment of various human diseases due to several advantages offered by them. This article is intended to provide future perspective on the use of WJ-MSCs for the management of accidental radiation injury in pre-clinical models, and finally, their utility in regeneration of damaged tissues and organs.

Cell Therapies for Acute Radiation Syndrome.

The risks of severe ionizing radiation exposure are increasing due to the involvement of nuclear powers in combat operations, the increasing use of nuclear power, and the existence of terrorist threats. Exposure to a whole-body radiation dose above about 0.7 Gy results in H-ARS (hematopoietic acute radiation syndrome), which is characterized by damage to the hematopoietic system; higher doses result in further damage to the gastrointestinal and nervous systems. Only a few medical countermeasures for ARS are currently available and approved for use, although others are in development. Cell therapies (cells or products produced by cells) are complex therapeutics that show promise for the treatment of radiation injury and have been shown to reduce mortality and morbidity in animal models. Since clinical trials for ARS cannot be ethically conducted, animal testing is extremely important. Here, we describe cell therapies that have been tested in animal models. Both cells and cell products appear to promote survival and lessen tissue damage after whole-body irradiation, although the mechanisms are not clear. Because radiation exposure often occurs in conjunction with other traumatic injuries, animal models of combined injury involving radiation and future countermeasure testing for these complex medical problems are also discussed.

Fitting the Crab Supernova with a Gamma-Ray Burst

Here, we reconsider the historical data, assuming a gamma-ray burst (GRB) as its source. A Supernova correlated with the GRB explains well the fading time observed by the ancient Chinese astronomers in the daytime and the nighttime, while the GRB power law explains the present X-rays and GeV emission of the Crab. On the grounds of a recent understanding of the first episode of binary-driven hypernova GRB (BDHN GRB) in terms of the collapse of a ten solar masses core, we propose the possible identification of the real Supernova event at an earlier time than Chinese chronicles. This work allows a new understanding of the significance of historical astronomical observations, including a fireball due to gamma-ray air shower observation and a plague of acute radiation syndrome, documented with several thousands of victims in the Eurasian area (Egypt, Iraq, and Syria).

Proteomic analysis of plasma at the preterminal stage of rhesus nonhuman primates exposed to a lethal total-body dose of gamma-radiation

The identification and validation of radiation biomarkers is critical for assessing the radiation dose received in exposed individuals and for developing radiation medical countermeasures that can be used to treat acute radiation syndrome (ARS). Additionally, a fundamental understanding of the effects of radiation injury could further aid in the identification and development of therapeutic targets for mitigating radiation damage. In this study, blood samples were collected from fourteen male nonhuman primates (NHPs) that were exposed to 7.2 Gy ionizing radiation at various time points (seven days prior to irradiation; 1, 13, and 25 days post-irradiation; and immediately prior to the euthanasia of moribund (preterminal) animals). Plasma was isolated from these samples and was analyzed using a liquid chromatography tandem mass spectrometry approach in an effort to determine the effects of radiation on plasma proteomic profiles. The primary objective was to determine if the radiation-induced expression of specific proteins could serve as an early predictor for health decline leading to a preterminal phenotype. Our results suggest that radiation induced a complex temporal response in which some features exhibit upregulation while others trend downward. These statistically significantly altered features varied from pre-irradiation levels by as much as tenfold. Specifically, we found the expression of integrin alpha and thrombospondin correlated in peripheral blood with the preterminal stage. The differential expression of these proteins implicates dysregulation of biological processes such as hemostasis, inflammation, and immune response that could be leveraged for mitigating radiation-induced adverse effects.

Germline Predisposition to Hematopoietic Malignancies: An Overview

Deleterious germline variants are now recognized as common drivers of hematopoietic malignancies (HMs) and bone marrow failure syndromes. With the increasing use of personalized medicine and the application of tumor-based profiling via next-generation sequencing, diagnosis of HM predisposition occurs with increasing frequency. Although deleterious germline variants can be readily identified by comprehensive clinical testing, numerous barriers exist for many clinicians. Observations regarding particular germline predisposition disorders challenge widely held assumptions about these conditions. Here, we review approaches to germline genetic testing, highlighting key points in a typical patient's course that present challenges for testing and interpreting results. Increasing awareness by health care providers of these conditions and improvements in testing platforms are crucial for enabling a proactive approach to tailoring a suitable treatment plan and surveillance program for the patient and their family members.

Machine-learning-based models assist the prediction of pulmonary embolism in autoimmune diseases: A retrospective, multicenter study.

Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. Chictr.org.cn : ChiCTR2200059599.

Effectiveness of cell therapy of acute radiation syndrome in mice with intravenous and intraperitoneal administration of a cellular product

The therapeutic effect of fibroblast-like cells obtained from the stromal vascular fraction of subcutaneous adipose tissue of mice and cultured for the treatment of bone marrow form of acute radiation syndrome was studied on a mouse experimental model. The cells were identified as multipotent mesenchymal stem (stromal) cells, owing to adhesion to plastic, confluent monolayer formation during cultivation, and the fact that osteogenic differentiation in vitro resulted in osteoblast maturation and calcium deposit formation, which indicated their multipotent nature. Irradiation of laboratory rodents was conducted using theX-ray therapy unit “RUM-17”. Stromal cells were obtained from subcutaneous adipose tissue of a mouse and grown in a culture of 3–4 passages and used as a cell product. Cell transplantation was performed 24 h after uniformX-ray irradiation of mice at a dose of 7.8 Gy. This is the first study to compare the therapeutic efficacy of allogeneic transplantation of multipotent mesenchymal stem cells with the different routes (intravenous and intraperitoneal) of cell suspension administration. A significant increase was found in the survival rate of mice during the 30-day follow-up period after lethal dose irradiation, which depended on the number of injected cells and delivery method of the biomedical cell product. Thus, with intravenous administration of 30 and 60 × 103multipotent mesenchymal stem cells, the 30-day survival rate of mice after irradiation at a dose of 7.8 Gy increased by 54.5% and 40%, respectively, compared with that of untreated animals (p= 0.03). An increase in the number of cells in the cell product to 120 × 103/mouse led to a decrease in therapy effectiveness. In intraperitoneal administration, the protection of animals from death was 57% after transplantation of 30 and 60 × 103cells (p= 0.039) and 50% after application of 120 × 103cells. On day 30 after irradiation, in the introduction of a cellular product in different schemes, 70%–80% of animals showed restoration of the values of the main indicators of the hematopoiesis system to initial levels. Thus, cell therapy using multipotent mesenchymal stem cells isolated from adipose tissue with intravenous and intraperitoneal delivery routes of the cellular product to the irradiated body protects mice from death after exposure toX-ray radiation in lethal doses, decreasing the severity of radiation damage to the hematopoietic system in mice, and provides prospects for further research as an effective and safe treatment for acute radiation sickness.

Pathology of acute sub-lethal or near-lethal irradiation of nonhuman primates prophylaxed with the nutraceutical, gamma tocotrienol

Exposure to high, marginally lethal doses or higher of ionizing radiation, either intentional or accidental, results in injury to various organs. Currently, there is only a limited number of safe and effective radiation countermeasures approved by US Food and Drug Administration for such injuries. These approved agents are effective for only the hematopoietic component of the acute radiation syndrome and must be administered only after the exposure event: currently, there is no FDA-approved agent that can be used prophylactically. The nutraceutical, gamma-tocotrienol (GT3) has been found to be a promising radioprotector of such exposure-related injuries, especially those of a hematopoietic nature, when tested in either rodents or nonhuman primates. We investigated the nature of injuries and the possible protective effects of GT3 within select organ systems/tissues caused by both non-lethal level (4.0 Gy), as well as potentially lethal level (5.8 Gy) of ionizing radiation, delivered as total-body or partial-body exposure. Results indicated that the most severe, dose-dependent injuries occurred within those organ systems with strong self-renewing capacities (e.g., the lymphohematopoietic and gastrointestinal systems), while in other tissues (e.g., liver, kidney, lung) endowed with less self-renewal, the pathologies noted tended to be less pronounced and less dependent on the level of exposure dose or on the applied exposure regimen. The prophylactic use of the test nutraceutical, GT3, appeared to limit the extent of irradiation-associated pathology within blood forming tissues and, to some extent, within the small intestine of the gastrointestinal tract. No distinct, global pattern of bodily protection was noted with the agent’s use, although a hint of a possible radioprotective benefit was suggested not only by a lessening of apparent injury within select organ systems, but also by way of noting the lack of early onset of moribundity within select GT3-treated animals.

An Overview of Appropriate Medical Practice and Preparedness in Radiation Emergency Response.

Radiation emergencies involving high doses of nuclear radiation pose significant risks from exposure to ionizing radiation in various scenarios. These situations include transportation accidents involving radioactive materials, occupational exposure, nuclear detonations, dirty bombs, and nuclear power plant accidents. In addition to the immediate risks of acute radiation syndrome (ARS) and related diseases, long-term exposure can increase the risk of other health issues such as cardiovascular disease and cancer. Vulnerable populations, including pregnant women and children, face particular concern due to potential impacts on their health and the health of unborn babies. The severity of ARS depends on several factors such as radiation dose, quality, dose rate, exposure uniformity, and individual biological responses. Bioindicators are biological responses or markers that help assess the severity and effects of radiation exposure on an individual. Bioindicators can include physical symptoms such as nausea, vomiting, and diarrhea, or laboratory tests such as changes in blood cell counts and gene expression that can help in assessing and treating exposed individuals. Additionally, early prodromal symptoms such as vomiting, diarrhea, and erythema can provide important clues for diagnosis and treatment. Developing a comprehensive plan for radiation emergencies is vital for safeguarding public health, infrastructure, and the environment. First responders play a critical role in establishing safety perimeters, triage, and coordination with various stakeholders. Education and training are essential for medical personnel and the public. This article provides general recommendations and identifies challenges to effective radiation emergency preparedness and response.

Effects of radiation mitigating amino acid mixture on mice of different sexes.

To date, few FDA-approved medical countermeasures are available for addressing hematopoietic acute radiation syndrome (H-ARS). In this study, we present our latest research findings focusing on the evaluation of a novel radiation mitigator known as the mitigating amino acid mixture (MAAM). MAAM is composed of five amino acids as the recently reported amino acid-based oral rehydration solution for mitigating gastrointestinal (GI)-ARS. CD2F1 male and female mice were exposed to 60Co-γ total body irradiation (TBI) at 9.0 or 9.5 Gy. Following irradiation, mice were orally administered with MAAM or a saline vehicle control once daily for a duration of 14 days, commencing 24 h after TBI. Mouse survival and body weight change were monitored for 30 days after irradiation. Complete blood counts (CBCs), bone marrow (BM) stem and progenitor cell survival (clonogenicity), and a serum cytokine antibody array were analyzed using samples from day 30 surviving mice. Our data revealed that MAAM treatment significantly enhanced survival rates in irradiated male CD2F1 mice, and the survival rate increased from 25% in the vehicle control group to 60% in the MAAM-treated group (p < 0.05) after 9.0 Gy TBI. The number of BM colonies significantly increased from 41.8 ± 6.4 /104 cells (in the vehicle group) to 78.5 ± 17.0 /104 cells (in the MAAM group) following 9.0 Gy TBI. Furthermore, MAAM treatment led to a decrease in the levels of six cytokines/proteins [cluster of differentiation 40 (CD40), interleukin (IL)-17A, C-X-C motif chemokine 10 (CXCL10/CRG-2), cutaneous T cell-attracting chemokine (CTACK), macrophage inflammatory protein (MIP)-3β, and IL-1β] and an increase in the levels of five other cytokines/proteins [IL-3Rβ, IL-5, leptin, IL-6, and stem cell factor (SCF)] in mouse serum compared to the vehicle group after 9.0 Gy TBI. However, similar alleviating effects of MAAM were not observed in the irradiated CD2F1 female mice. The serum cytokine profile in the irradiated female mice was different compared to the irradiated male mice. In summary, our data suggest that the beneficial effects of the mitigative amino acid combination treatment after radiation exposure may depend on sex.

ИЗУЧЕНИЕ КЛИНИКО-ГЕМАТОЛОГИЧЕСКИХ И ИММУНОЛОГИЧЕСКИХ ПОКАЗАТЕЛЕЙ ПРИ ОЦЕНКЕ ПРОТИВОРАДИАЦИОННОЙ ЭФФЕКТИВНОСТИ ТЕРАПЕВТИЧЕСКОГО СРЕДСТВА НА ОСНОВЕ МИКРООРГАНИЗМА FUSOBACTERIUM NECROPHORUM

Purpose: To study clinical, hematologic and immunologic parameters in assessing the anti-radiation efficacy of the therapeutic agent based on the microorganism Fusobacterium necrophorum. Material and methods: The studies on determination of the anti-radiation efficacy of the strains of microorganisms killed by gamma-irradiation were carried out on sexually mature sexless white mice and white rats with live weight of 18–20 and 180–200 g, respectively, divided into experimental and control groups according to the principle of analogs. Modeling of acute radiation sickness was carried out on a Puma gamma unit with a radioactive source of cesium-137 at a dose of LD100/30. As potential anti-radiation drugs we used inactivated by irradiation on the gamma unit Explorer preparations of microbial origin F. necrophorum strain 8. necrophorum strain 8TS630501 at doses of 15, 20, 25 and 30 kGy. The tested preparations were injected subcutaneously in the volume of 0.2 cm3 to white mice and 2.0 cm3 to white rats 3 days after radiation exposure. Results: It was experimentally established that complete sterilization of the microbe occurs at doses of 25 and 30 kGy. The culture of F. necrophorum, irradiated at doses of 25 and 30 kGy and administered to animals 3 days after external radiation exposure, promoted survival, preservation of 60 to 80 % of lethally irradiated white mice and rats. At the same time the recovery of leukocytes and hemoglobin number was slow and continued until the end of the study. In animals treated with the developed therapeutic agents, there was also a decrease in the number of T-cells, but it was less pronounced than in the irradiation control group. The number of B-lymphocytes was affected similarly to T-lymphocytes. The minimum of the number of B-lymphocytes in the experimental groups was noted at 14 days. Studies on the intensity of the process of lipid peroxidation (LPO) in the content of malonic dialdehyde in peripheral blood of gamma-irradiated, treated and intact rats, it was found that in the irradiated control group there is a significant increase in the LPO index in blood in relation to biological control and treatment groups. Conclusion: It has been established that the highest anti-radiation efficacy is possessed by a therapeutic agent of microbial origin (RNF-30), which was obtained by gamma-irradiation at a dose of 30 kGy of the culture of F. necrophorum.

Long-term prognosis in patients with pulmonary embolism

Venous thromboembolism (VTE), clinically expressed as deep vein thrombosis (DVT) or pulmonary embolism (PE), is, globally, the third most common acute cardiovascular syndrome after myocardial infarction and stroke. Pulmonary embolism is associated with high morbidity and mortality. The long-term prognosis of these patients is insufficiently studied.Aim: To analyze mortality and clinical events at long-term follow-up in patients with confirmed PE. Material and methods: The study included 168 patients with PE, 53% men and 47% women, mean age 61.2±12.8 years, consecutively hospitalized in the Institute of Cardiology. Patients were classified into four risk groups according to the 2019 European Society of Cardiology Guidelines. Patients were followed-up for a mean period of 11.4±0.9 months. Results. During the study period died 23 people (13.7%), 8 of them during hospitalization and another 15 - after discharge from the hospital; in the latter, death occurred suddenly - in 4 cases (26.6%), it was due to cardiovascular causes- in 4 cases (26.6%), through cancer - in 5 (30%) people and from other causes - in 2 (13.3%) patients. Recurrent VTE was observed in 4 (2.5%) subjects, including PE - in 3 and DVT in 1 patient. During the surveillance period 4 (2.5%) patients developed stroke, 5 (3.1%) - acute myocardial infarction, 1 (0.2%) patient - another arterial event. Hemorrhagic complications suffered 20 patients. Chronic thromboembolic pulmonary hypertension was detected in 12.4% of people over 5.4±2.8 months after primary PE. Newly diagnosed cancer was observed in 2 (1.25%) people.Conclusions. The mortality rate in PE patients over an average period of 11.4±0.9 months was 13.7%, including 4.7% - in hospital and 8.9% - at long-term follow-up; in-hospital death was significantly higher in patients in the high and intermediate high risk category compared to those with intermediate-low and low risk and no statistically significant differences were established between these groups in the long-term mortality rate; the main cause of death in the hospital was PE, and during the surveillance period death from cardiovascular causes predominated, followed by death from cancer.

Oral administration of probiotic spore ghosts for efficient attenuation of radiation-induced intestinal injury

Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients’ quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.

Combination of arrythmogenic right ventricular cardiomyopathy with Loeys-Dietz syndrome: case report

Arrhythmogenic right ventricular dysplasia is a hereditary cardiomyopathy - a common cause of sudden cardiac death in children and young adults. Loeys-Dietz syndrome is an ultra-rare connective tissue disorder characterized by aneurysms of the aorta and other large arteries, arterial tortuosity, and joint hypermobility and is associated with pathogenic variants in genes encoding protein components TGF-β pathway. We present a rare case of a two-abovementioned genetic disorders combination in a proband with a complex and rapidly progressive cardiovascular syndrome.

Chronic spindle assembly checkpoint activation causes myelosuppression and gastrointestinal atrophy

Interference with microtubule dynamics in mitosis activates the spindle assembly checkpoint (SAC) to prevent chromosome segregation errors. The SAC induces mitotic arrest by inhibiting the anaphase-promoting complex (APC) via the mitotic checkpoint complex (MCC). The MCC component MAD2 neutralizes the critical APC cofactor, CDC20, preventing exit from mitosis. Extended mitotic arrest can promote mitochondrial apoptosis and caspase activation. However, the impact of mitotic cell death on tissue homeostasis in vivo is ill-defined. By conditional MAD2 overexpression, we observe that chronic SAC activation triggers bone marrow aplasia and intestinal atrophy in mice. While myelosuppression can be compensated for, gastrointestinal atrophy is detrimental. Remarkably, deletion of pro-apoptotic Bim/Bcl2l11 prevents gastrointestinal syndrome, while neither loss of Noxa/Pmaip or co-deletion of Bid and Puma/Bbc3 has such a protective effect, identifying BIM as rate-limiting apoptosis effector in mitotic cell death of the gastrointestinal epithelium. In contrast, only overexpression of anti-apoptotic BCL2, but none of the BH3-only protein deficiencies mentioned above, can mitigate myelosuppression. Our findings highlight tissue and cell-type-specific survival dependencies in response to SAC perturbation in vivo.