Metabolomics identifies plasma biomarkers of localized radiation injury.

A radiological accident may result in the development of a local skin radiation injury (LRI) which may evolve, depending on the dose, from dry desquamation to deep ulceration and necrosis through unpredictable inflammatory waves. Therefore, early diagnosis of victims of LRI is crucial for improving medical care efficiency. This preclinical study aims to identify circulating metabolites as biomarkers associated with LRI using a C57BL/6J mouse model of hind limb irradiation.

Radiation-induced gastrointestinal and cutaneous injuries: understanding models, pathologies, assessments, and clinically accepted practices.

Purpose: A U. S. and European joint effort fostering the development of medical countermeasures (MCMs) operable in case of radiological or nuclear emergencies.

microRNA blood signature for localized radiation injury.

A radiological accident, whether from industrial, medical, or malicious origin, may result in localized exposure to high doses of ionizing radiations, leading to the development of local radiation injury (LRI), that may evolve toward deep ulceration and necrosis of the skin and underlying tissues. Early diagnosis is therefore crucial to facilitate identification and management of LRI victims. Circulating microRNAs (miRNA) have been studied as potential diagnostic biomarkers of several diseases including hematological defects following whole-body irradiation (WBI).

Review of the PRIODAC project on thyroid protection from radioactive iodine by repeated iodine intake in individuals aged 12.

Background: Intake of potassium iodide (KI) reduces the accumulation of radioactive iodine in the thyroid gland in the event of possible contamination by radioactive iodine released from a nuclear facility. The WHO has stated the need for research for optimal timing, appropriate dosing regimen and safety for repetitive iodine thyroid blocking (ITB). The French PRIODAC project, addressed all these issues, involving prolonged or repeated releases of radioactive iodine.

Generation of transgene-free hematopoietic stem cells from human induced pluripotent stem cells.

Hematopoietic stem cells (HSCs) are the rare cells responsible for the lifelong curative effects of hematopoietic cell (HC) transplantation. The demand for clinical-grade HSCs has increased significantly in recent decades, leading to major difficulties in treating patients. A promising but not yet achieved goal is the generation of HSCs from pluripotent stem cells.

Circulating microvesicles correlate with radiation proctitis complication after radiotherapy.

In a large retrospective study, we assessed the putative use of circulating microvesicles (MVs), as innovative biomarkers of radiation toxicity in a cohort of 208 patients with prostate adenocarcinoma overexposed to radiation. The level of platelet (P)-, monocyte (M)- and endothelial (E)-derived MVs were assessed by flow cytometry. Rectal bleeding toxicity scores were collected at the time of blood sampling and during the routine follow-up and were tested for association with MVs using a multivariate logistic regression.

HuMSC-EV induce monocyte/macrophage mobilization to orchestrate neovascularization in wound healing process following radiation injury.

This study aims to investigate the mechanisms of human mesenchymal stem cell-derived extracellular vesicles (HuMSC-EV)-induced proangiogenic paracrine effects after radiation injury. HuMSC-EV were locally administered in mice hindlimb following 80-Gy X-ray irradiation and animals were monitored at different time points. HuMSC-EV improved neovascularization of the irradiated tissue, by stimulating angiogenesis, normalizing cutaneous blood perfusion, and increasing capillary density and production of proangiogenic factors.

Mesenchymal stem cells limit vascular and epithelial damage and restore the impermeability of the urothelium in chronic radiation cystitis.

Background: Cellular therapy seems to be an innovative therapeutic alternative for which mesenchymal stem cells (MSCs) have been shown to be effective for interstitial and hemorrhagic cystitis. However, the action of MSCs on chronic radiation cystitis (CRC) remains to be demonstrated. The aim of this study was to set up a rat model of CRC and to evaluate the efficacy of MSCs and their mode of action.

Differential Recruitment of DNA Repair Proteins KU70/80 and RAD51 upon Microbeam Irradiation with α-Particles.

In addition to representing a significant part of the natural background radiation exposure, α-particles are thought to be a powerful tool for targeted radiotherapy treatments. Understanding the molecular mechanisms of recognition, signaling, and repair of α-particle-induced DNA damage is not only important in assessing the risk associated with human exposure, but can also potentially help in identifying ways of improving the efficacy of radiation treatment. α-particles (He ions), as well as other types of ionizing radiation, and can cause a wide variety of DNA lesions, including DNA double-strand breaks (DSBs).

Molecular Mechanisms and Key Processes in Interstitial, Hemorrhagic and Radiation Cystitis.

Cystitis is a bladder disease with a high rate of prevalence in the world population. This report focuses on Interstitial Cystitis (IC), Hemorrhagic Cystitis (HC) and Chronic Radiation Cystitis. These pathologies have different etiologies, but they share common symptoms, for instance, pain, bleeding, and a contracted bladder.

Mesenchymal stromal cells in the regeneration of radiation-induced organ sequelae: will they make the difference?

Mesenchymal stromal cells (MSCs) are a stem cell product with good safety that demonstrate significant clinical efficacy in the treatment of different pathologies, including radiation diseases (e.g. radiological burns, pelvic radiation disease).

Understanding Molecular Mechanisms and Identifying Key Processes in Chronic Radiation Cystitis.

Chronic radiation cystitis (CRC) is a consequence of pelvic radiotherapy and affects 5-10% of patients. The pathology of CRC is without curative treatment and is characterized by incontinence, pelvic pain and hematuria, which severely degrades patients' quality of life. Current management strategies rely primarily on symptomatic measures and have certain limitations.

Protection and safety of a repeated dosage of KI for iodine thyroid blocking during pregnancy.

In case of nuclear power plant accidents resulting in the release of radioactive iodine (I) in large amounts, a single intake of stable iodine is recommended in order to preventI fixation to the thyroid gland. However, in situations of prolonged exposure toI (e.g.

Hematopoietic Recovery using Multi-Cytokine Therapy in 8 Patients Presenting Radiation-Induced Myelosuppression after Radiological Accidents.

Treatment of accidental radiation-induced myelosuppression is primarily based on supportive care and requires specific treatment based on hematopoietic growth factors injection or hematopoietic cell transplantation for the most severe cases. The cytokines used consisted of pegylated erythropoietin (darbepoetin alfa) 500 IU once per week, pegylated G-CSF (pegfilgrastim) 6 mg × 2 once, stem cell factor 20 µg.kg-1 for five days, and romiplostim (TPO analog) 10 µg.

The stromal vascular fraction mitigates radiation-induced gastrointestinal syndrome in mice.

Background: The intestine is particularly sensitive to moderate-high radiation dose and the development of gastrointestinal syndrome (GIS) leads to the rapid loss of intestinal mucosal integrity, resulting in bacterial infiltration, sepsis that comprise patient survival. There is an urgent need for effective and rapid therapeutic countermeasures. The stromal vascular fraction (SVF) derived from adipose tissue is an easily accessible source of cells with angiogenic, anti-inflammatory and regenerative properties.

HGF and TSG-6 Released by Mesenchymal Stem Cells Attenuate Colon Radiation-Induced Fibrosis.

Fibrosis is a leading cause of death in occidental states. The increasing number of patients with fibrosis requires innovative approaches. Despite the proven beneficial effects of mesenchymal stem cell (MSC) therapy on fibrosis, there is little evidence of their anti-fibrotic effects in colorectal fibrosis.

Evaluation of the Effectiveness of Mesenchymal Stem Cells of the Placenta and Their Conditioned Medium in Local Radiation Injuries.

Background: The search for an effective therapy for local radiation injuries (LRI) is urgent; one option is mesenchymal stem cells (MSC) derived from the placenta and their conditioned medium for the regenerative processes of the skin.

Methods: We used 80 animals, randomly assigned to four groups: control (C) animals that did not receive therapy; control with the introduction of culture medium concentrate (CM); introduction of MSCs (PL); introduction of CMPL. LRI modeling was performed on an X-ray machine at a dose of 110 Gy.

Effect of repetitive potassium iodide on thyroid and cardiovascular functions in elderly rats.

Background: To date, paediatric thyroid cancer has been the most severe health consequence of the Chernobyl accident, caused by radioactive iodine (I) aerosol's dispersion. WHO recommends a single dose of potassium iodide (KI) to reduce this risk. Following the Fukushima accident, it became obvious that repetitive doses of KI may be necessary due to multiple exposures to I.

Prophylactic treatment prevents the acute breakdown of colonic epithelial barrier in a preclinical model of pelvic radiation disease.

Every year, millions of people around the world benefit from radiation therapy to treat cancers localized in the pelvic area. Damage to healthy tissue in the radiation field can cause undesirable toxic effects leading to gastrointestinal complications called pelvic radiation disease. A change in the composition and/or function of the microbiota could contribute to radiation-induced gastrointestinal toxicity.

Effects of repetitive Iodine thyroid blocking on the foetal brain and thyroid in rats: a systems biology approach.

A single administration of an iodine thyroid blocking agent is usually sufficient to protect thyroid from radioactive iodine and prevent thyroid cancer. Repeated administration of stable iodine (rKI) may be necessary during prolonged or repeated exposure to radioactive iodine. We previously showed that rKI for eight days offers protection without toxic effects in adult rats.

Metabolomics evaluation of repeated administration of potassium iodide on adult male rats.

The long-lasting consequence of a new iodine thyroid blocking strategy (ITB) to be used in case of nuclear accident is evaluated in male Wistar rats using a metabolomics approach applied 30 days after ITB completion. The design used 1 mg/kg/day of KI over 8 days. Thyroid hormones remained unchanged, but there was a metabolic shift measured mainly in thyroid then in plasma and urine.

[RadioTransNet, the French network for preclinical research in oncological radiotherapy].

The ambition of the RADIOTRANSNET network, launched by the INCa at the end of 2018, is to create a French research consortium dedicated to preclinical radiotherapy to foster scientific and clinical interactions at the interface of radiotherapy and radiobiology, and to identify research priorities dedicated to innovation in radiotherapy. The activities of the network are organized around four major axes that are target definition, normal tissue, combined treatments and dose modelling. Under the supervision of the Scientific Council, headed by a coordinator designated by the SFRO and a co-coordinator designated by the SFPM, three leaders coordinate each axis: a radiation-oncologist, a medical physicist and a biologist, who are responsible for organizing a scientific meeting based on the consensus conference methodology to identify priority issues.

Assessment of the effects of repeated doses of potassium iodide intake during pregnancy on male and female rat offspring using metabolomics and lipidomics.

Preparedness for nuclear accident responsiveness includes interventions to protect pregnancies against prolonged exposure to radioactive iodine. The aim of this study was to investigate a new design consisting of repeated administration of potassium iodide (KI, 1 mg/kg) for 8 days in late pregnancy gestational day 9-16 (GD9-GD16) in rats. The later-life effects of this early-life iodine thyroid blocking (ITB) strategy were assessed in offspring two months afterbirth.