Search Results (279)

Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved. Full article

Backgrounds and aim: Protective effects of natural compounds have been suggested in the prevention and treatment of radiation-induced mucositis or bacterial infections. In this study, the protective effects of proanthocyanidin-rich grape seed extract (GSE) on bacterial Lipopolysaccharide (LPS) and radiation-induced epithelial barrier damage and Reactive Oxygen Species (ROS) production were investigated in an in vitro model. Methods: Human intestinal epithelial cells Caco-2, previously treated with LPS, GSE, or LPS + GSE, were irradiated with 10 Gy divided into five daily treatments. Epithelial barrier integrity and ROS production were measured before and after each treatment. Results: Irradiation, at different doses, significantly increased intestinal permeability and ROS production; pretreatment with GSE was able to significantly prevent the increased intestinal permeability (4.63 ± 0.76 vs. 15.04 ± 1.5; p < 0.05) and ROS production (12.9 ± 1.08 vs. 1048 ± 0.5; p < 0.0001) induced by irradiation treatment. When the cells were pretreated with LPS, the same results were observed: GSE cotreatment was responsible for preventing permeability alterations (5.36 ± 0.16 vs. 49.26 ± 0.82; p < 0.05) and ROS production (349 ± 1 vs. 7897.67 ± 1.53; p < 0.0001) induced by LPS exposure when added to the irradiation treatment. Conclusions: The results of the present investigation demonstrated, in an in vitro model, that GSE prevents the damage to intestinal permeability and the production of ROS that are induced by LPS and ionizing radiation, suggesting a potential protective effect of this extract on the intestinal mucosa during irradiation treatment. Full article

This study systematically reviews the non-traditional pharmacological effects of diclofenac, a well-known nonsteroidal anti-inflammatory drug, to explore its potential for drug repositioning beyond its established analgesic and anti-inflammatory applications. A comprehensive literature search was conducted using the PubMed, Scopus and Web of Science databases, covering studies from 1981 to 2025. It was revealed that over 94% of records in Scopus and Web of Science are duplicated in PubMed, so the latter was used for the search in our study. After duplicate removal and independent screening, 89 from 1123 retrieved studies were selected for the search. The analysis revealed a broad spectrum of diclofenac’s non-traditional pharmacological activities, including neuroprotective, antiamyloid, anticancer, antiviral, immunomodulatory, antibacterial, antifungal, anticonvulsant, radioprotective, and antioxidant properties, primarily identified through preclinical In vitro and In vivo studies. These effects are mediated through diverse molecular pathways beyond cyclooxygenase inhibition, such as modulation of neurotransmitter release, apoptosis, and cellular proliferation. Diclofenac showed potential for repositioning in oncology, neurodegenerative disorders, infectious diseases, and immune-mediated conditions. Its hepatotoxicity and cardiovascular risks necessitate strategies like advanced drug formulations, dose optimization, and personalized medicine to enhance safety. Large-scale randomized clinical trials are essential to validate these findings and ensure safe therapeutic expansion. Full article

Ionizing radiation (IR) poses a dual challenge in medicine; while essential for cancer therapy, it inflicts collateral damage to normal tissues, particularly the gastrointestinal (GI) tract. High-dose IR triggers acute radiation syndrome (ARS), characterized by crypt stem cell depletion, mucosal barrier disruption, inflammation, and potential progression to fibrosis and secondary malignancy. Emerging evidence identifies the epithelial kinase doublecortin-like kinase 1 (DCLK1)—highly expressed in GI tuft cells and cancer stem-like cells—as a master regulator of post-IR responses. DCLK1 integrates DNA repair (via p53/ATM), and survival signaling (via NF-κB, TGF-β, and MAPK) to promote epithelial regeneration, yet these same mechanisms contribute to therapy resistance and oncogenesis. DCLK1 further modulates the immune microenvironment by skewing macrophages toward an immunosuppressive M2 phenotype, enhancing tissue remodeling, angiogenesis, and immune evasion. Preclinical studies demonstrate that DCLK1 inhibition sensitizes tumors to radiotherapy while preserving mucosal repair. Therapeutic strategies targeting DCLK1, alongside radioprotective agents, immunomodulators, and senolytics, may enhance regeneration, limit fibrosis, and eradicate therapy-resistant cancer stem cells. This review highlights DCLK1’s dual role in regeneration and tumorigenesis and evaluates its potential as a therapeutic target and biomarker in IR-induced GI damage. Full article

With growing public concern about the health effects of low-dose radiation, numerous studies have demonstrated that low-dose radiation can cause damage to the immune system, making intervention measures essential. This study investigated the protective effects of silybin against low-dose radiation-induced immune system damage and its underlying mechanisms at both the cellular and animal levels. At the cellular level, CCK-8 assays, ROS measurements, and RT-qPCR analysis revealed that silybin alleviated the reduction in RAW264.7 cell proliferation, intracellular ROS levels, and inflammatory cytokine expression following low-dose radiation exposure. At the animal level, comparative analyses of post-irradiation body weight, peripheral blood cell counts, immune organ coefficients, spleen HE/IHC staining, and spleen immune cell numbers demonstrated that silybin mitigated the radiation-induced decrease in body weight, reduction in peripheral blood leukocyte counts, inflammatory cell infiltration in the spleen, decline in spleen immune cell numbers, and increase in cGAS protein-positive cells. These findings indicate that silybin exerts protective effects against low-dose radiation-induced immune system damage, potentially by regulating the cGAS signaling pathway to reduce radiation-induced cellular injury, thereby enhancing its radioprotective properties. Full article

Substantial progress has been made in the development of radiation countermeasures, resulting in the recent approval of several mitigators; however, there has yet to be an approved prophylactic radioprotectant. Research on countermeasure performance in mixed neutron and gamma radiation fields has also been scarce. Fibroblast-stimulating lipopeptide (FSL-1) is a novel synthetic agonist for toll-like receptor 2/6. In previous studies, the administration of FSL-1 before and after gamma radiation significantly improved survival outcomes for mice through the activation of the NF-κB pathway. In the current study, we tested FSL-1’s radioprotective abilities in a mixed radiation field that models one produced by a nuclear detonation in 11–14-week-old C57BL/6 male and female mice. We demonstrate that a single dose of 1.5 mg/kg of FSL-1 administered 12 h prior to 65% neutron 35% gamma mixed-field (MF) irradiation enhances survival, accelerates recovery of hematopoietic cell and stem cell populations, reduces inflammation, and protects innate immune function in mice. FSL-1’s ability to recover blood and protect immune functions is important in countering the high rate of incidence of sepsis caused by MF radiation’s damaging effects. These results demonstrate that FSL-1 is a promising prophylactic countermeasure where exposure to MF radiation is anticipated. Full article

Ionizing radiation at early stages leads to radiation-induced death of Langerhans islet cells and acinar cells, resulting in the development of acute/subacute pancreatitis. Conducting studies on radiation-induced changes in the pancreas following electron beam irradiation appears to be of great interest, and the evaluation of radioprotective agents for safeguarding normal tissues from radiation is equally important. The aim of this study was to preclinically investigate the antioxidant properties of N-Acetylcysteine in an animal model of radiation-induced pancreatitis over a three-month period. In this study, it was proven for the first time that even electrons can lead to characteristic signs of radiation-induced pancreatitis, the degree of which was assessed based on the levels of insulin, glucose, and amylase. Thus, conducting electron therapy also increases the risks of insulin resistance, as well as X-ray and gamma radiation. For the first time, a comprehensive analysis of biochemical, morphological, and immunohistochemical markers in the pancreas of a large cohort of electron-irradiated animals was conducted, including both acute and delayed effects of electron exposure. The crucial role of interleukins in shaping both the cellular and vascular components of the inflammatory response was identified. Additionally, the radioprotective properties of N-Acetylcysteine during electron irradiation of the pancreas were evaluated for the first time, and its effectiveness in reducing both acute and late complications of electron therapy was demonstrated. Thus, it can be concluded that N-Acetylcysteine is capable of effectively suppressing the inflammatory response in the pancreas. Full article

This study investigated the spatial distribution and radiological risks of naturally occurring radionuclides (²²⁶Ra, ²³²Th, ⁴⁰K) in 37 soil samples from Zacatecas, located in north-central Mexico, using high-resolution gamma spectrometry. Results revealed ⁴⁰K concentrations (mean: 736.81 Bq kg⁻¹), nearly double the global average, while ²²⁶Ra (29.96 Bq kg⁻¹) and ²³²Th (29.72 Bq kg⁻¹) aligned with worldwide norms. Geoaccumulation indices identified moderate ⁴⁰K accumulation at 22 sites, with El Capulín classified as moderately contaminated (I_geo = 1.07). Radiological risk indices showed absorbed dose rates (62.52 nGy h⁻¹) and excess lifetime cancer risk (0.330 × 10⁻³) exceeding global thresholds by 4% and 14%, respectively. Multivariate analyses demonstrated strong Spearman correlations (ρ = 0.75–1.00) among risk indices, while spatial interpolation identified southern/western regions as high-risk zones. These findings emphasize the necessity of integrating spatial analysis with multivariate statistical techniques in environmental radioprotection frameworks. While most of the study area complies with international safety standards, the identified zones exceeding dose thresholds warrant prioritized management to mitigate potential cumulative health risks. Full article

Background: The aim of this study was to investigate the radioprotective efficacy of polymer complexes constructed from amifostine (WR-2721) and poly(hydroxyoxyethylene phosphate)s with different molecular weights. The use of suitable polymers for the immobilization of radioprotective drugs is aimed at improving or obtaining important new properties. Methods: The radioprotective efficacy of the compounds was investigated by cytotoxicity and the survival of mouse embryonic fibroblasts MEF LIG4^+/+ and MEF LIG4^−/− cells irradiated with 2, 6 and 12 Gy in the presence of amifostine (WR-2721) and its polymer complexes. Results: The radioprotective efficacy of the polymer complexes constructed of amifostine (WR-2721) and poly(hydroxyoxyethylene phosphate)s with different molecular weights showed promising activity and dose regimens. Conclusions: Cytotoxicity studies for tested cell lines MEF LIG4^+/+ and MEF LIG4^−/− cells showed that the polymer complexes were not toxic when equivalent doses of the drug amifostine (WR-2721) were applied to the cells. Irradiated MEF LIG4^+/+ cells demonstrated an increase in the surviving fraction when pre-treated with 0.5–5 mM polymer complexes when equivalent doses of amifostine (WR-2721) were applied to the cells and irradiated. The radioprotective efficacy had increased when the cells MEF LIG4^+/+ were irradiated with 12 Gy. These findings demonstrate that poly(hydroxyoxyethylene phosphate)s are suitable carriers of the radioprotective drug amifostine (WR-2721). They further suggest that they may be interesting for researchers seeking new challenges in discovering advanced radioprotective active substances. Full article

Acute radiation syndrome (ARS) occurs when hematopoietic or gastrointestinal cells are damaged by radiation exposure causing DNA damage to the bone marrow and gastrointestinal epithelial stem cell populations. In these highly proliferative cell types, DNA damage inhibits stem cell repopulation. In humans and animals, this inability to regenerate stem cells is lethal. Within this manuscript, several compounds, Amifostine, Captopril, Ciprofloxacin, PrC-210, 5-AED (5-androstene-3β,17β-diol), and 5-AET (5-androstene-3β,7β,17B-triol), are assessed for their ability to protect against ARS in an in vitro and/or in vivo setting. ARS was accomplished by irradiating mouse bone marrow cells or rat intestinal epithelial (IEC-6) cells in vitro with 4–8 Gy and in vivo by exposing Mus musculus to 7.3 Gy of whole-body irradiation. The primary endpoints of this study include cellular viability, DNA damage via γ-H2AX, colony formation, and overall survival at 30-days post-irradiation. In addition to evaluating the radioprotective performance of each compound, this study establishes a distinct set of in vitro assays to predict the overall efficacy of potential radioprotectors in an in vivo model of ARS. Furthermore, these results highlight the need for FDA-approved medical intervention to protect against ARS. Full article

The impact of the microbiota on radiation (RT)-induced toxicity and cancer response to radiotherapy is an emerging area of interest. In this review, we summarize the available preclinical and clinical evidence concerning microbiota modulation of RT toxicity and efficacy in the main gastrointestinal (GI) districts. A huge amount of data supports the clinical application of microbiota modulation, particularly through prebiotics and probiotics, to prevent or mitigate radiotherapy-induced toxicity in rectal cancer. Preclinical and clinical studies also support the observation of microbiota modulation to impact the toxicity and efficacy of treatment in esophageal cancer, hepatocellular carcinoma (HCC), and anal squamous cell carcinoma (ASCC). However, insufficient evidence remains to endorse microbiota modulation as a strategy to enhance tumor radiosensitivity in clinical practice. Well-designed studies focusing on prebiotics, probiotics, and fecal microbiota transplantation are needed across all GI sites to evaluate their potential to improve treatment efficacy, as suggested by promising preclinical findings. The impact of pre-treatment microbiota analyses should be addressed in prospective studies to verify the efficacy of patient-level tailored strategies. Additionally, the repurposing of radioprotective agents with innovative delivery systems, such as encapsulated amifostine, holds significant promise for mitigating small bowel toxicity, thereby enabling more effective RT treatment. Full article

FLASH radiotherapy is a novel irradiation modality that employs ultra-high mean dose rates exceeding 40–150 Gy/s, far surpassing the typical ~0.03 Gy/s used in conventional radiotherapy. This advanced technology delivers high doses of radiation within milliseconds, effectively targeting tumors while minimizing damage to the surrounding healthy tissues. However, the precise mechanism that differentiates responses between tumor and normal tissues is not yet understood. This study primarily examines the ROD hypothesis, which posits that oxygen undergoes transient radiolytic depletion following a radiation pulse. We developed a computational model to investigate the effects of dose rate on radiolysis in an aqueous environment that mimics a confined cellular space subjected to instantaneous pulses of energetic protons. This study employed the multi-track chemistry Monte Carlo simulation code, IONLYS-IRT, which has been optimized to model this radiolysis in a homogeneous and aerated medium. This medium is composed primarily of water, alongside carbon-based biological molecules (RH), radiation-induced bio-radicals (R^●), glutathione (GSH), ascorbate (AH⁻), nitric oxide (^●NO), and α-tocopherol (TOH). Our model closely monitors the temporal variations in these components, specifically focusing on oxygen consumption, from the initial picoseconds to one second after exposure. Simulations reveal that cellular oxygen is transiently depleted primarily through its reaction with R^● radicals, consistent with prior research, but also with glutathione disulfide radical anions (GSSG^●−) in roughly equal proportions. Notably, we show that, contrary to some reports, the peroxyl radicals (ROO^●) formed are not neutralized by recombination reactions. Instead, these radicals are rapidly neutralized by antioxidants present in irradiated cells, with AH⁻ and ^●NO proving to be the most effective in preventing the propagation of harmful peroxidation chain reactions. Moreover, our model identifies a critical dose rate threshold below which the FLASH effect, as predicted by the ROD hypothesis, cannot fully manifest. By comparing our findings with existing experimental data, we determine that the ROD hypothesis alone cannot entirely explain the observed FLASH effect. Our findings indicate that antioxidants might significantly contribute to the FLASH effect by mitigating radiation-induced cellular damage and, in turn, enhancing cellular radioprotection. Additionally, our model lends support to the hypothesis that transient oxygen depletion may partially contribute to the FLASH effect observed in radiotherapy. However, our findings indicate that this mechanism alone is insufficient to fully explain the phenomenon, suggesting the involvement of additional mechanisms or factors and warranting further investigation. Full article

Ionizing radiation (IR) is widely present in the environment, with ¹³⁷Cesium (Cs) radiation having particularly severe impacts during nuclear accidents. The objective of our study was to assess the radiation protection or repair effect of one year (WT-1Y) or seven years (WT-7Y) of storage on white teas, as well as to investigate the mechanism of radioprotection. HGC-27 cells exposed to ¹³⁷Cs γ-rays (30 Gy) exhibited significant changes in cell structure, apoptosis, ROS, LDH, and their expression of p53 and Caspase-3. The results showed that WT-1Y and WT-7Y acted as antioxidants, showed reduced ROS and LDH levels, and had increased CAT and SOD activities as well as cell survival rate. The WT treatments significantly inhibited apoptosis in both the pre- and post-radiation groups, with WT-1 showing stronger effects in pretreatment by reducing LDH, p53, and Caspase-3 levels and enhancing ROS scavenging and enzyme activities. Post-treatment analysis revealed WT-7 had greater effects on cell viability and SOD activity. Overall, both WT-1 and WT-7 mitigated radiation damage, likely by inhibiting the p53/Caspase-3 apoptosis pathway. A Spearman analysis of the differential metabolites in WT-1Y and WT-7Y with cellular radioprotective indicators revealed that metabolites, such as EGC, procyanidin B4, and phenolic acids (abundant in WT-1Y), quercetin-3-glucosylrutinoside, and caffeine (enriched in WT-7Y) contributed to their distinct effects in the pre- and post-treatment of ¹³⁷Cs γ-rays. Full article

Purpose: This study aimed to clarify the protective effect of astilbin (AST) on radiation-induced pulmonary fibrosis (RIPF) and explore its underlying molecular mechanism, focusing on non-coding RNAs. Methods: Mouse lung epithelial cells (MLE-12 and TC-1) and C57BL/6J mice were used to establish in vitro radiation injury models and in vivo RIPF models, respectively. Cell viability, apoptosis, the epithelial-to-mesenchymal transition (EMT), and fibrosis-related markers were assessed using cell-counting kit-8 assays, Western blotting, immunohistochemistry, and histological staining. High-throughput sequencing identified differentially expressed circRNAs. The mechanistic studies included RNA-FISH, a dual-luciferase reporter assay, an RNA immunoprecipitation (RIP) assay, and loss-of-function experiments. Results: AST significantly alleviated radiation-induced apoptosis and EMT in vitro, as well as RIPF in vivo. AST treatment reduced collagen deposition, fibrosis-related protein expression, and EMT marker changes. High-throughput sequencing revealed that AST upregulated circPRKCE, a non-coding RNA that functions through a ceRNA mechanism by binding to miR-15b-5p, thereby promoting Smad7 expression and suppressing the TGF-β/Smad7 pathway. Knockdown of circPRKCE abolished AST’s protective effects, confirming its pivotal role in mediating AST’s anti-fibrotic activity. Conclusions: This study demonstrates that Astilbin alleviates radiation-induced pulmonary fibrosis via circPRKCE targeting the TGF-β/Smad7 pathway to inhibit EMT, suggesting AST as a potential therapeutic agent for managing this severe complication of radiotherapy. Full article

Radioresistance remains a major obstacle in cervical cancer treatment, frequently engendering tumor relapse and metastasis. However, the details of its mechanism of action remain largely enigmatic. This study delineates the prospective impacts of short-form human T-cell lymphoma invasion and metastasis 2 (TIAM2S) involving the radiation resistance of cervical cancer. In this study, we established three pairs of radioresistant (RR) cervical cancer cells (HeLa, C33A and CaSki) and their parental wild-type (WT) cells. We revealed a consistent augmentation of TIAM2S, but not long-form human T-cell lymphoma invasion and metastasis 2 (TIAM2L) were displayed in RR cells that underwent a 6 Gy radiation administration. Remarkably, RR cells exhibited decreased radiosensitivity and abridged apoptosis, as estimated through a clonogenic survival curve assay and Annexin V/Propidium Iodide apoptosis assay, respectively. TIAM2S suppression increased radiosensitivity and enhanced cell apoptosis in RR cells, whereas its forced introduction modestly abolished radiosensitivity and diminished WT cell apoptosis. Furthermore, TIAM2S overexpression notably aggravated RR cell migration, whereas its blockage reduced WT cell mobilities, as confirmed by an in vitro time-lapse recording assay. Notably, augmented lung localization was revealed after a tail-vein injection of CaSki-RR cells using the in vivo short-term lung locomotion BALB/c nude mouse model. TIAM2S impediment notably reduced radioresistance-increased lung locomotion. This study provides evidence that TIAM2S may operate as an innovative signature in cervical cancer that is resistant to radiotherapy. It displays multi-faceted roles including radioprotection, restricting apoptosis, promoting cell proliferation, and escalating cell migration/metastasis. Targeting TIAM2S, together with conventional radiotherapy, may be an innovative strategy for intensifying radiosensitivity and protecting against subsequent uncontrolled tumor growth and metastasis in cervical cancer treatment. Full article