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Introduction 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. Materials and Methods 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

Aim: The success of vital pulp treatment (VPT) procedures is dependent on an accurate diagnosis of the pulpal inflammatory condition. Compared with current subjective pulpal diagnostic tests, inflammatory molecular biomarkers involved in the pathogenesis of pulpitis represent potential objective indicators of the degree of pulpal inflammation. Therefore, the aim of this study was to quantify level of inflammatory biomarkers – Interleukin 8 (IL‐8) and TNF‐α in patients diagnosed with reversible pulpitis (RP), irreversible pulpitis (IR) and normal pulp (NP) and investigate their diagnostic accuracy in differentiating between healthy and inflamed conditions. Methodology: This prospective, cross‐sectional study enrolled 72 patients aged 14–53 years with extremely deep carious lesions after establishing a clinical diagnosis of RP (n = 42), symptomatic IR (n = 22) and NP (n = 8). 50 μL of pulpal blood sample was collected from all the patients using a micropipette after pulpal exposure. The level of IL‐8 and TNF‐α was assessed in pg/mL using enzyme‐linked immunosorbent assays. Mann–Whitney U test was applied to establish the association between IL‐8/TNF‐α level and degree of pulp inflammation. Receiver operating curve (ROC) analysis was carried out to calculate area under the curve (AUC) for RP versus IR. Cut‐off values were established using Youden's index. Results: IL‐8 and TNF‐α levels differed significantly between RP and IR groups (p ≤.001). The median value of IL‐8 in RP and IP groups was 259.8 pg/mL [187.5–310.0] and 1357.8 pg/mL [1036.7–2177.6] respectively. The AUC‐ROC curve for RP versus IR was 0.997 with 95.5% sensitivity and 99.76% specificity. The median value of TNF‐α in RP and IR groups was 75.4 pg/mL [62.7–95.8] and 157.6 pg/mL [94.1–347.3]. The AUC‐ROC curve for TNF‐α was 0.812 with a sensitivity and specificity of 59.1% and 92.1%, respectively. IL‐8 and TNF‐α levels were below detection levels for all NP samples. Conclusion: This study showed that pulpal blood could provide an excellent medium for establishing pulpal diagnosis under extremely deep carious lesions. The selected cytokines, IL‐8 and TNF‐α, demonstrated excellent discriminatory performance for reversible and irreversible pulpitis. Future studies should correlate the IL‐8/TNF‐α levels with VPT treatment outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A complex cascade of systemic and tissue-specific responses induced by exposure to ionizing radiation can lead to functional impairment over time in the surviving population. Current methods for management of survivors of unintentional radiation exposure episodes rely on monitoring individuals over time for the development of adverse clinical symptoms due to the lack of predictive biomarkers for tissue injury. In this study, we report on changes in metabolomic and lipidomic profiles in multiple tissues of nonhuman primates (NHPs) that received either 4.0 Gy or 5.8 Gy total-body irradiation (TBI) of 60Co gamma rays, and 4.0 or 5.8 Gy partial-body irradiation (PBI) from LINAC-derived photons and were treated with a promising radiation countermeasure, gamma-tocotrienol (GT3). These include small molecule alterations that correlate with radiation effects in the jejunum, lung, kidney, and spleen of animals that either survived or succumbed to radiation toxicities over a 30-day period. Radiation-induced metabolic changes in tissues were observed in animals exposed to both doses and types of radiation, but were partially alleviated in GT3-treated and irradiated animals, with lung and spleen being most responsive. The majority of the pathways protected by GT3 treatment in these tissues were related to glucose metabolism, inflammation, and aldarate metabolism, suggesting GT3 may exert radioprotective effects in part by sparing these pathways from radiation-induced dysregulation. Taken together, the results of our study demonstrate that the prophylactic administration of GT3 results in metabolic and lipidomic shifts that likely provide an overall advantage against radiation injury. This investigation is among the first to highlight the use of a molecular phenotyping approach in a highly translatable NHP model of partial- and total-body irradiation to determine the underlying physiological mechanisms involved in the radioprotective efficacy of GT3. [ABSTRACT FROM AUTHOR]