Radiation Syndrome Research Articles

Preliminary Promising Findings for Manganese Chloride as a Novel Radiation Countermeasure Against Acute Radiation Syndrome.

Military members and first responders may, at moment's notice, be asked to assist in incidents that may result in radiation exposure such as Operation Tomadachi in which the U.S. Navy provided significant relief for the Fukushima Daiichi Nuclear Reactor accident in Japan after an earthquake and tsunami in 2011. We are also currently facing potential threats from nuclear power plants in the Ukraine should a power disruption to a nuclear plant interfere with cooling or other safety measures. Exposure to high doses of radiation results in acute radiation syndrome (ARS) characterized by symptoms arising from hematopoietic, gastrointestinal, and neurovascular injuries. Although there are mitigators FDA approved to treat ARS, there are currently no FDA-approved prophylactic medical interventions to help protect persons who may need to respond to radiation emergencies. There is strong evidence that manganese (Mn) has radiation protective efficacy as a promising prophylactic countermeasure. All animal procedures were approved by the Institutional Animal Care and Use Committee. Male and female B6D2F1J mice, 10 to 11 weeks old, were used for neurotoxicity studies and temporal effects of Mn. Four groups were evaluated: (1) vehicle injection, (2) dose of 4.5 mg/kg for 3 days, (3) dose of 13.5 mg/kg, and (4) sham. Irradiated mice were exposed to 9.5 Gy whole body Co60 γ-radiation. MRI was performed with a high dose of manganese chloride (MnCl2) (150 mg/kg) to assess the distribution of the MnCl2. The mice have promising survival curves (highest survival-13.5 mg/kg dose over 3 days of MnCl2 at 80% [87% female, 73% male] P = 0.0004). The complete blood count (CBC) results demonstrated a typical hematopoietic response in all of the irradiated groups, followed by mildly accelerated recovery by day 28 in the treated groups. No difference between groups was measured by Rota Rod, DigiGait, and Y-maze. Histologic evaluation of the bone marrow sections in the group given 13.5 mg/kg dose over 3 days had the best return to cellularity at 80%. MRI showed a systemic distribution of MnCl2. The preliminary data suggest that a dose of 13.5 mg/kg of MnCl2 given over 3 days prior to exposure of radiation may have a protective benefit while not exhibiting the neurobehavioral problems. A countermeasure that can prophylactically protect emergency personnel entering an area contaminated with high levels of radiation is needed, especially in light that nuclear accidents are a continued global threat. There is a need for a protective agent with easy long-term storage, easy to transport, easy to administer, and low cost. Histologic evaluation supports the promising effect of MnCl2 in protecting tissue, especially the bone marrow using the dose given over 3 days (4.5 mg/kg per day) of MnCl2. Initial experiments show that MnCl2 is a promising safe and effective prophylactic countermeasure against ARS. MRI data support the systemic distribution of MnCl2 which is needed in order to protect multiple tissues in the body. The pathology data in bone marrow and the brain support faster recovery from radiation exposure in the treated animals and decreased organ damage.

BIO 300: A Prophylactic Radiation Countermeasure for Acute Radiation Syndrome.

Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome. Currently, there is no radiation medical countermeasure approved by the U.S. FDA which can be used before radiation exposure to protect exposed individuals. Here we aimed to evaluate the therapeutic potential of an aqueous suspension of synthetic genistein nanoparticles (BIO 300) as a radioprotectant in a pilot efficacy study using a nonhuman primate model of total body irradiation. Eight rhesus macaques were divided into two groups; four received vehicle and four received BIO 300 Injectable Suspension 24 h before 5.8 Gy total-body irradiation. Survival, blood cell counts, blood chemistry, and clinical parameters were monitored over the 60 days of the study. Tissues were collected at necropsy 60 days post-irradiation or from animals that met unscheduled euthanasia criteria and subjected to histopathological analysis. Tissues analyzed included the duodenum, jejunum, ileum, sternum, lung, heart, liver, kidney, spleen, gut-associated lymphoid tissue, and urinary bladder. In this pilot study, all BIO 300 Injectable Suspension treated animals survived to day 60, while only 50% of the vehicle-treated animals survived. We found that BIO 300 Injectable Suspension did not mediate an improvement in blood cell counts (e.g., neutrophils, platelets, white blood cells). However, BIO 300 Injectable Suspension treated animals had a lower incidence of fever and febrile neutropenia, were able to better maintain their body weight post radiation exposure, and exhibited less anemia and faster recovery from anemia. Histopathological analysis revealed that BIO 300-treated animals had less irradiation-induced damage to the sternum and other tissues compared to vehicle controls. BIO 300's mechanism of action is complex and protection against irradiation is attainable without much improvement in the complete blood count (CBC) profile. BIO 300's mechanism for radioprotection involves multiple biological pathways and systems.

Long-term exposure to air pollution and the risks of venous thromboembolism: a nationwide population-based retrospective cohort study.

To delineate the effects of exposure to air pollution on the risk of venous thromboembolism (VTE). The association between air pollution and arterial occlusive diseases has been well reported in the literature. VTE is the third most common acute cardiovascular syndrome; however, its relationship with exposure to air pollution has been controversial. This study linked data from the Taiwan National Health Insurance Research Database with that from the Taiwan Environmental Protection Administration. Patients who were first admitted for VTE between January 1, 2001, and December 31, 2013, were analyzed. A time-stratified, case-crossover design was employed. Three different exposure periods were defined: exposure for 1month, one quarter, and 1year. Four control periods were designated for each exposure period. The association between exposure to air pollutants and the risk of VTE was tested using logistic regression analysis. Subgroup analyses were also performed, stratified by age, sex, type of VTE, the use of hormone therapy, and level of urbanization at the site of residence. Exposures to particulate matter (PM) smaller than 2.5µm (PM2.5) and those smaller than 10µm (PM10) were associated with higher risks of VTE, with longer exposures associated with higher risk. The concentration of PM2.5 exposure for 1month was linearly associated with a greater risk of VTE up to 28.0µg/m3, beyond which there was no association. PM2.5 exposure for one quarter or 1year remained significantly associated with higher risks of VTE at higher concentrations. The increased risk in VTE associated with exposure to PM2.5 was more prominent in older patients and in patients not under hormone therapy. Similar results were observed for PM10 exposures. Exposure to PM, particularly PM2.5, leads to an increased risk of VTE, with possible accumulative effects. With increased PM production in industrializing countries, the effects of PM on VTE occurrence warrant further attention.

Significant Reduction of Radiation-Induced Death in Mice Treated with PrC-210 and G-CSF after Irradiation.

The search for single or combined radiation countermeasures that mitigate the development of Acute Radiation Syndrome (ARS) after radiation exposure remains a prominent goal of the U.S. government. This study was undertaken to determine whether PrC-210 and G-CSF, when administered 24-48 h postirradiation, would confer an additive or synergistic survival benefit and mitigate ARS in mice that had received an otherwise 96% lethal radiation dose. Our results show that optimum systemic doses of PrC-210 and G-CSF, when administered 24 h or later after a 96% lethal dose of whole-body irradiation, conferred: 1. strong individual survival benefits (PrC-210 44%, P = 0.003), (G-CSF 48%, P = 0.0002), 2. a profound combined 85% survival benefit (P < 0.0001) when administered together, and on day 14 postirradiation, 3. peripheral white blood cell/lymphocyte counts equal to unirradiated controls, 4. dense bone marrow cell density (>65% of unirradiated controls), 5. jejunal villi density that equaled 90% of unirradiated controls, and 6. spleen weights that equaled 93% of unirradiated controls. Our results show that PrC-210 and G-CSF given together 24 h after irradiation confer strong additive efficacy by protecting the immune system, and enabling recovery of the bone marrow, and they work synergistically to enable recovery of peripheral white blood cells in circulating blood.

Biomarker dosimetry of acute low level of thermal neutrons and radiation adaptive response effect on rats

In this paper, we demonstrated the biological effects of acute low-dose neutrons on the whole body of rats and investigated the impact of that level of neutron dose to induce an in vivo radio-adaptive response. To understand the radio-adaptive response, the examined animals were exposed to acute neutron radiation doses of 5 and 10 mSv, followed by a 50 mSv challenge dose after 14 days. After irradiation, all groups receiving single and double doses were kept in cages for one day before sampling. The electron paramagnetic resonance (EPR) method was used to estimate the radiation-induced radicals in the blood, and some hematological parameters and lipid peroxidation (MDA) were determined. A comet assay was performed beside some of the antioxidant enzymes [catalase enzyme (CAT), superoxide dismutase (SOD), and glutathione (GSH)]. Seven groups of adult male rats were classified according to their dose of neutron exposure. Measurements of all studied markers are taken one week after harvesting, except for hematological markers, within 2 h. The results indicated lower production of antioxidant enzymes (CAT by 1.18–5.83%, SOD by 1.47–17.8%, and GSH by 11.3–82.1%). Additionally, there was an increase in red cell distribution width (RDW) (from 4.61 to 25.19%) and in comet assay parameters such as Tail Length, (from 6.16 to 10.81 µm), Tail Moment, (from 1.17 to 2.46 µm), and percentage of DNA in tail length (DNA%) (from 9.58 to 17.32%) in all groups exposed to acute doses of radiation ranging from 5 to 50 mSv, respectively. This emphasizes the ascending harmful effect with the increased acute thermal neutron doses. The values of the introduced factor of radio adaptive response for all markers under study reveal that the lower priming dose promotes a higher adaptation response and vice versa. Ultimately, the results indicate significant variations in DNA%, SOD enzyme levels, EPR intensity, total Hb concentration, and RDWs, suggesting their potential use as biomarkers for acute thermal neutron dosimetry. Further research is necessary to validate these measurements as biodosimetry for radiation exposure, including investigations involving the response impact of RAR with varied challenge doses and post-irradiation behavior.

Molecular prevalence and subtype characteristics of Blastocystis among school children in Hainan, the tropical island province of China

Blastocystis is one of the most common zoonotic intestinal protozoa with global distribution and can cause gastrointestinal syndrome mainly characterized by diarrhea. School children are the main susceptible population. No epidemiological data on Blastocystis among school children in Hainan, the only tropical island province in China. Between March 2021 and June 2023, 1973 fecal samples were collected from school children across three regions in Hainan province. Blastocystis was examined by amplifying the small subunit ribosomal RNA (SSU rRNA) gene via polymerase chain reaction (PCR), and subtypes were identified through DNA sequencing and phylogenetic analysis. The overall prevalence of Blastocystis was 7.3 % (144/1973). The differences in infection rates across different regions, nationalities, and educational stages are statistically significant (P < 0.001). Five subtypes were identified, of which ST3 was the dominant subtype (60.4 %; 87/144), followed by ST1 (27.8 %; 40/144), ST7 (10.4 %; 15/144), ST6 (0.7 %; 1/144), and ST2 (0.7 %; 1/144). 42 known sequences and 15 novel sequences were identified including eight new variations of the ST1 (ST1–16∼ST1–23) with similarities ranging from 98.3 % to 99.78 % and seven new variations of the ST7 (ST7–7∼ST7–13) with similarities ranging from 97.7 % to 99.79 % by intra-subtype genetic polymorphisms analysis. The results evaluate the public health risks of Blastocystis among school children in Hainan and the sources of infection were discussed, providing important basic data for the effective prevention and control of intestinal parasitic diseases in Hainan.

Clinicopathologic findings and causes of mortality in 100 pet rabbits from the Canary Islands, Spain, 2011-2022.

The European domestic rabbit (Oryctolagus cuniculus domesticus) is commonly kept as a pet, with increasing popularity among pet owners. Despite the increasing body of information on lagomorph medicine and pathology, comprehensive published compilations of causes of mortality in pet rabbits are limited. We analyzed health disorders, pathology findings, and most probable causes of death in 100 pet rabbits submitted to the Anatomopathological Diagnostic Service of the Veterinary School of the University of Las Palmas de Gran Canaria, Canary Islands, Spain, from 2011 to 2022. We reviewed clinical data and gross and histopathologic findings to classify the various disorders into infectious (n = 39), noninfectious (n = 45), and idiopathic conditions (n = 16). Within infectious disease processes, Encephalitozoon cuniculi infection (n = 14) and rabbit hemorrhagic viral disease (n = 14) had the highest prevalence. Regarding the noninfectious conditions, perioperative mortality (n = 10), gastrointestinal syndrome (n = 7), and trauma (n = 6) were the most common clinicopathologic entities observed.

Effect of Age at Time of Irradiation, Sex, Genetic Diversity, and Granulopoietic Cytokine Radiomitigation on Lifespan and Lymphoma Development in Murine H-ARS Survivors.

Acute, high-dose radiation exposure results in life-threatening acute radiation syndrome (ARS) and debilitating delayed effects of acute radiation exposure (DEARE). The DEARE are a set of chronic multi-organ illnesses that can result in early death due to malignancy and other diseases. Animal models have proven essential in understanding the natural history of ARS and DEARE and licensure of medical countermeasures (MCM) according to the FDA Animal Rule. Our lab has developed models of hematopoietic (H)-ARS and DEARE in inbred C57BL/6J and Jackson Diversity Outbred (JDO) mice of both sexes and various ages and have used these models to identify mechanisms of radiation damage and effective MCMs. Herein, aggregate data from studies conducted over decades in our lab, consisting of 3,250 total-body lethally irradiated C57BL/6J young adult mice and 1,188 H-ARS survivors from these studies, along with smaller datasets in C57BL/6J pediatric and geriatric mice and JDO mice, were examined for lifespan and development of thymic lymphoma in survivors up to 3 years of age. Lifespan was found to be significantly shortened in H-ARS survivors compared to age-matched nonirradiated controls in all four models. Males and females exhibited similar lifespans except in the young adult C57BL/6J model where males survived longer than females after 16 months of age. The incidence of thymic lymphoma was increased in H-ARS survivors from the young adult and pediatric C57BL/6J models. Consistent with our findings in H-ARS, geriatric mice appeared more radioresistant than other models, with a lifespan and thymic lymphoma incidence more similar to nonirradiated controls than other models. Increased levels of multiple pro-inflammatory cytokines in DEARE bone marrow and serum correlated with shortened lifespan and malignancy, consistent with other animal models and human data. Of interest, G-CSF levels in bone marrow and serum 8-11 months after irradiation were significantly increased in females. Importantly, treatment with granulopoietic cytokine MCM for radiomitigation of H-ARS did not influence the long-term survival rate or incidence of thymic lymphoma in any model. Taken together, these findings indicate that the lifespan of H-ARS survivors was significantly decreased regardless of age at time of exposure or genetic diversity, and was unaffected by earlier treatment with granulopoietic cytokines for radiomitigation of H-ARS.

Comparison of early characteristics of multisystemic inflammatory syndrome and Kawasaki disease in children and the course of Kawasaki disease in the pandemic

IntroductionMultisystemic inflammatory syndrome (MIS-C) is a newly described disease manifestation in children associated with the novel coronavirus SARS-CoV-2 infection and can be easily confused with Kawasaki disease with its clinical and laboratory findings. In this study, the clinical findings, organ involvements, similarities, and differences in laboratory and imaging of the children with MIS-C and KD at the time of admission will be revealed in detail, and the treatment methods and follow-up results will be revealed.Material and methodOur study was a single-center study and included pediatric patients who were treated with a diagnosis of MIS-C between March 2020 and July 2023 in the pediatric cardiology, pediatric emergency, pediatric infection, and pediatric intensive care clinics at Celal Bayar University and who were treated with a diagnosis of KD (complete/incomplete) between January 2015 and July 2023. MIS-C diagnosis was made according to the Turkish Ministry of Health COVID-19 guidelines. Sociodemographic characteristics, clinical, laboratory, and echocardiography findings, treatments given, and clinical course of all patients included in the study were evaluated.ResultsThe median age was 30 months (7–84) in KD and 96 months (6-204) in MIS-C, and it was significantly higher in the MIS-C group (p = 0.000). Symptom duration was significantly longer in the MIS-C group (p = 0.000). In terms of clinical features, gastrointestinal syndrome findings (nausea, vomiting, abdominal pain) and respiratory findings (dyspnea) were significantly higher in the MIS-C group (p = 0.007, p = 0.000, p = 0.002, respectively). Regarding cardiovascular system involvement, coronary involvement was significantly higher in the KD group. However, valvular involvement, left ventricular systolic dysfunction, and pericardial effusion were significantly higher in the MIS-C group (p = 0.000, p = 0.001, p = 0.003, p = 0.023, respectively). In terms of laboratory findings, white blood cell count was higher in KD (p = 0.000), absolute lymphocyte count, platelet level, blood sodium, and albumin levels were lower in MIS-C group (p = 0.000, p = 0.000, p = 0.000, p = 0.000, p = 0.003, respectively), ferritin and troponin levels were significantly higher in MIS-C group. These results were statistically significant (p = 0.000, p = 0.000, respectively). D-dimer and fibrinogen levels were high in both groups, and no significant statistical difference was detected between the two groups. There was no significant difference between the two groups regarding the length of hospitalization and mortality, but steroid use was significantly higher in the MIS-C group (p = 0.000).ConclusionIn conclusion, this study has demonstrated the similarities and differences between MIS-C and KD regarding clinical findings, organ involvement, and laboratory and imaging results. The results of our study have important implications in terms of contributing to the data in the existing literature on these two diseases and for the correct diagnosis and better management of pediatric patients presenting with these disorders.What is knownMultisystemic inflammatory syndrome (MIS-C) is a newly described disease manifestation in children associated with the novel coronavirus SARS-CoV-2 infection and can be easily confused with Kawasaki disease with its clinical and laboratory findings.What is newAlthough MIS-C and KD have many similarities, their symptoms, disease processes, possible complications, and treatment regimens may differ.

Assessing the Mental Model State of Emergency Responders in the Context of Radiological Dispersal Device (RDD) Incidents: A Multi-state Study.

Hazardous Materials (HAZMAT) Technicians' notions of mental model, or cognitive representations of their understanding and beliefs regarding Radiological Dispersal Devices (RDDs) incidents, have not been previously explored. A prior study developed an Expected Mental Model State (EMMS) framework specific to RDD incident response for HAZMAT technicians. The work herein presents the development of a derivative of this framework, the EMMS Diagnostic Matrix, to evaluate the actual Mental Model State (MMS) of HAZMAT technicians in the context of RDD incidents. The EMMS Diagnostic Matrix was administered via a survey and simulation activity in four U.S. states representing the Northeast, West, South, and Midwest regions. Data were collected and coded using grounded theory methodology. Reflexive thematic analysis was employed to identify themes across related areas where the notions of mental model for the HAZMAT technician responders' actual MMS differed from the EMMS. The analysis of the collected data revealed four significant themes representing incomplete notions of the mental model spanning various EMMS conceptual domains: Overestimation of Radiation Dose and Health Effects, indicating misunderstandings about the health impacts of radiation exposure, Acute Radiation Syndrome (ARS), particularly in the lower range of radiation doses; Overreliance on Responder Protection [personal protective equipment (PPE)/self-contained breathing apparatus (SCBA)], highlighting gaps in understanding radiation principles and radioactive material dispersal properties from a radiological dispersal device; Misunderstanding Radiation Detection and Units, signifying confusion about radiation units and differentiation between dose rate and accumulated dose; and Incomplete Understanding of Radiation Characteristics and Dispersal Properties, outlining a limited grasp of inhalation risks from radiation and the dispersal traits of a radiological dispersal device. The interconnectedness of these technical misunderstandings can guide the development of a strategic plan to evaluate and modify existing training, aiming at these specific themes to improve the efficiency of HAZMAT technicians in emergency situations and to identify areas for further research.

Biomarkers for Radiation Biodosimetry and Correlation with Hematopoietic Injury in a Humanized Mouse Model.

After a large-scale radiological or nuclear event, hundreds of thousands of people may be exposed to ionizing radiation and require subsequent medical management. Acute exposure to moderate doses (2-6 Gy) of radiation can lead to the hematopoietic acute radiation syndrome, in which the bone marrow (BM) is severely compromised, and severe hemorrhage and infection are common. Previously, we have developed a panel of intracellular protein markers (FDXR, ACTN1, DDB2, BAX, p53 and TSPYL2), designed to reconstruct absorbed radiation dose from human peripheral blood (PB) leukocyte samples in humanized mice up to 3 days after exposure. The objective of this work was to continue to use the humanized mouse model to evaluate biomarker dose-/time- kinetics in human PB leukocytes invivo, at an earlier (day 2) and later (day 7) time point, after exposure to total-body irradiation (TBI) doses of 0 to 2 Gy of X rays. In addition, to assess hematological sensitivity and radiation-induced injury, PB leukocyte cell counts, human BM hematopoietic stem cell (HSC) and progenitor cell [multipotent progenitor (MPP), common myeloid progenitor (CMP), granulocyte myeloid progenitor (GMP), megakaryocyte/erythrocyte progenitor (MEP) and multi-lymphoid progenitor (MLP)] levels were measured, and their correlation was also examined as the BM damages are difficult to assess by routine tests. Peripheral blood B-cells were significantly lower after TBI doses of 0.5 Gy on day 2 and 2 Gy on days 2 and 7; T-cells were significantly reduced only on day 2 after 2 Gy TBI. Bone marrow HSCs and MPP cells showed a dose-dependent depletion after irradiation with 0.5 Gy and 2 Gy on day 2, and after 1 Gy and 2 Gy on day 7. Circulating B cells correlated with HSCs, MPP and MLP cells on day 2, whereas T cells correlated with MPP, and myeloid cells correlated with MLP cells. On day 7, B cells correlated with MPP, CMP, GMP and MEP, while myeloid cells correlated with CMP, GMP and MEP. The intracellular leukocyte biomarkers were able to discriminate unirradiated and irradiated samples at different time points calculated by receiver operating characteristic (ROC) curve. Using machine learning algorithm methods, combining ACTN1, p53, TSPYL2 and PB-T cell and PB-B cell counts served as a strong predictor (area under the ROC >0.8) to distinguish unirradiated and irradiated samples independent of the days after TBI. The results further validated our biomarker-based triage assay and additionally evaluated the radiation sensitivity of the hematopoietic system after TBI exposures.

A clinical case of acute polyneuropathy, with the onset of bilateral facial nerve palsy in an early childhood

BACKGROUND: The differential diagnosis of peripheral nervous system damage depends on a thorough collection of history, comprehensive assessment of clinical manifestations, and dynamic examination of the patient. This article describes a clinical case of acute polyneuropathy in a young child, which began with gastrointestinal symptoms and bilateral facial neuropathy. CLINICAL CASE DESCRIPTION: The article presents a case of a child with an atypical course of acute polyneuropathy, which began with bilateral facial neuropathy combined with gastrointestinal complaints and pain syndrome. Features of the clinical presentation of the disease required extended laboratory and instrumental testing. Protocols for instrumental verification of diagnosis included nerve conduction studies examining neural conduction and axonal excitability of the affected facial nerve and the healthy side. Additionally, the functional status of the peripheral nerves in the upper and lower limbs was assessed. Polyneuropathic alterations revealed through nerve conduction studies confirmed diagnostic lumbar puncture to determine the presence of neuroinfectious processes. Magnetic resonance imaging of the brain, brachial, and lumbosacral plexuses using intravenous contrast showed the nature and prevalence of a lesion. Based on the overall clinical, laboratory, and instrumental examination data of the patient, “acute inflammatory demyelinating polyneuropathy” was diagnosed; timely etiopathogenetic treatment was initiated. CONCLUSION: In children, the course of a neuroinfection may be atypical. Sometimes, when dissociating the clinical manifestations of the disease from the results of a standard laboratory and instrumental test, expert diagnostic techniques should be used for differential diagnosis purposes.

Santalum album L. alleviates cardiac function injury in heart failure by synergistically inhibiting inflammation, oxidative stress and apoptosis through multiple components

BackgroundHeart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. MethodsThe active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model.ResultsWe initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated.ConclusionsMechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF.Graphical

Clinical Presentation and Risk Factors of Acalculous Cholecystitis in Outpatients: Retrospective Study

Aim: Acalculous cholecystitis (AAC) accounts for only 5-10% of cholecystitis cases, primarily studied in intensive care units (ICU) patients. The aim of this study to identify risk factors and clinical presentation of AAC in non-ICU patients. Material and methods: We conducted a literature review using PubMed MeshTerms “acalculous cholecystitis” and searched our institution’s database (2018-2022) for “cholecystitis” and “acalculous cholecystitis,” including patients with histopathological findings. Results: 23 patients met the inclusion criteria. based on histopathology report and diagnosis. The most common co-morbidities were cardiovascular and metabolic syndrome. Abdominal pain was the predominant complaint. Ten patients (50%) presented with elevated CRP, bilirubin, and leukocytosis. No mortality was reported at 30 days. Conclusion: AAC in outpatients is not associated with high mortality, unlike in ICU settings. However, it is more frequent in polymorbid patients with cardiovascular risk factors.

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.