Ionizing radiation-induced oxidative stress is attributed to generation of reactive oxygen species (ROS) due radiolysis water molecules and short lived. Persistent has also been observed after radiation exposure implicated in the late effects radiation. The goal this study was determine if long-term freshly isolated mouse intestinal epithelial cells (IEC) dependent on quality at a dose relevant fractionated radiotherapy. Mice (C57BL/6J; 6 8 weeks; female) were irradiated with 2 Gy γ-rays,...

Despite recent epidemiological evidences linking radiation exposure and a number of human ailments including cancer, mechanistic understanding how inflicts long-term changes in cerebral cortex, which regulates important neuronal functions, remains obscure. The current study dissects molecular events relevant to pathology cortex 6 8 weeks old female C57BL/6J mice two twelve months after γ dose (2 Gy) commonly employed fractionated radiotherapy. For comparative study, effects 1.6 Gy heavy...

Risk of colorectal cancer (CRC) after exposure to low linear energy transfer (low-LET) radiation such as γ-ray is highlighted by the studies in atom bomb survivors. On contrary, CRC risk prediction high-LET cosmic heavy ion hindered due scarcity vivo data. Therefore, intestinal tumor frequency, size, cluster, and grade were studied APCMin/+ mice (n = 20 per group; 6 8 wks old; female) 100 110 days 1.6 or 4 Gy 56Fe (energy: 1000 MeV/nucleon) results compared γ doses 2 5 Gy, which are...

Significance Coordinated epithelial cell migration is key to maintaining functional integrity and preventing pathological processes in gastrointestinal tissue, essential for astronauts’ health space mission success. Here we show that energetic heavy ions, which are more prevalent deep relative low-Earth orbit, could persistently decrease intestinal migration, alter cytoskeletal remodeling, increase proliferation with ongoing DNA damage senescence, even a year after irradiation. Our study has...

Tissue consequences of radiation exposure are dependent on quality and high linear energy transfer (high-LET) radiation, such as heavy ions in space is known to deposit higher tissues cause greater damage than low-LET γ radiation. While has been linked intestinal pathologies, there very few studies long-term effects fewer involved a therapeutically relevant dose, none explored persistent tissue metabolomic alterations after ion exposure. Using metabolomics approach, we report markers injury...

Exposure to ionizing radiation (IR), both low-LET (e.g., X-rays, γ rays) and high-LET heavy ions), increases the risk of gastrointestinal (GI) cancer. Previous studies have linked IR-induced GI cancer cellular senescence associated secretory phenotype (SASP) signaling. This study explores potential senolytic therapy mitigate carcinogenesis. Male <i>Apc</i>^1638N/+ mice were exposed ²⁸Si-ions (69 keV/μm) IR. Two months later, they treated with agent ABT-263 orally for 5...

Background: Ionizing radiation (IR) is a well-known inducer of cellular senescence and the senescence-associated secretory phenotype (SASP). SASP factors play dual roles in cancer, either promoting or inhibiting its development. This study investigates IR-induced specifically secreted by renal cortical epithelial (RCE) cells their role cell carcinoma (RCC) progression. Methods: Proteomic data from Atlas were analyzed to identify unique RCE cells, with subsequent evaluations performed at both...

Ionizing radiation is a known risk factor for gastrointestinal (GI) pathologies including cancer.Hormones and related signaling crosstalk, which could contribute to radiation-induced persistent pathophysiologic changes in the small intestine colon, remain be explored.The current study assessed perturbation of GI homeostasis-related hormones pathways at systemic as well tissue level colon.Mice (6-8 week old C57BL/6J) were exposed 2 Gy γ radiation, serum samples collected, insulin like growth...

Health risks from space radiations, particularly densely ionizing represent an important challenge for long-ranged manned missions. Reliable methods are needed scaling low-LET to high-LET radiation humans, based on animal or in vitro studies comparing these radiations. The current standard metric, relative biological effectiveness (RBE) compares iso-effect doses of two By contrast, a proposed new effects ratio (RER), radiations at the same dose. This definition RER allows direct humans dose...

Heavy ion radiation, prevalent in outer space and relevant for radiotherapy, is densely ionizing poses risk to stem cells that are key intestinal homeostasis.Currently, the molecular spectrum of heavy radiationinduced perturbations (ISCs), could trigger pathologies, remains largely unexplored.The Lgr5-EGFP-IRES-creERT mice were exposed 50 cGy iron radiation.Mice euthanized 60 d after exposure ISCs sorted using fluorescence activated cell sorting.Reactive oxygen species (ROS) mitochondrial...

The enteric nervous system (ENS), consisting of neurons and glial cells, is situated along the gastrointestinal (GI) tract’s wall plays a crucial role in coordinating digestive processes. Recent research suggests that optimal functioning GI relies on intricate connections between ENS, intestinal epithelium, immune system, microbiome, central (CNS). Inflammatory bowel disease (IBD) encompasses group chronic inflammatory disorders, such as Crohn’s (CD) ulcerative colitis (UC), characterized by...

Alzheimer's disease (AD) is a common neurodegenerative characterized by both extra-as well as intracellular deposition of amyloid beta peptides (Aβ).The accumulation Aβ in mitochondria associated with mitochondrial dysfunction and oxidative stress AD.Recent evidences suggest the involvement interaction proteins such cyclophilin-D (CypD) stress, permeability transition (MPT) neurodegeneration.The present study an effort to elucidate molecular other involved MPT like adenine nucleotide...

Ionizing radiation-induced hematopoietic injury could occur either due to accidental exposure or diagnostic and therapeutic interventions. Currently there is no approved drug mitigate radiation toxicity in cells. This study investigates the potential of ON 01210.Na, a chlorobenzylsulfone derivative, ameliorating when administered after radiation. We also investigate molecular mechanisms underlying this activity.Male C3H/HeN mice (n = 5 per group; 6-8 weeks old) were exposed sub-lethal dose...

The availability of robust classification algorithms for the identification high risk individuals with resectable disease is critical to improving early detection strategies and ultimately increasing survival rates in PC. We leveraged quality biospecimens extensive clinical annotations from patients that received treatment at Medstar-Georgetown University hospital. used a resolution mass spectrometry based global tissue profiling approach conjunction multivariate analysis developing...

Oxidative stress-mediated biomolecular damage is a characteristic feature of ionizing radiation (IR) injury, leading to genomic instability and chronic health implications. Specifically, dose- linear energy transfer (LET)-dependent persistent increase in oxidative DNA has been reported many tissues biofluids months after IR exposure. Contrary low-LET photon radiation, high-LET exposure known cause significantly higher accumulations damage, even at sublethal doses, compared IR. High-LET...

There is little information on the relative toxicity of highly charged (Z) high-energy (HZE) radiation in animal models compared to γ or X-rays, and general assumption based vitro studies has been that acute substantially greater.C57BL/6J mice were irradiated with (56)Fe ions (1 GeV/nucleon), (within 30 d) rays protons GeV). To assess hematopoietic gastrointestinal toxicity, effects using complete blood count (CBC), bone marrow granulocyte-macrophage colony forming unit (GM-CFU), terminal...

ON 01210.Na (Ex-RAD), a chlorobenzylsulfone derivative was investigated for its pharmacologic and radioprotective properties when administered via oral subcutaneous (SC) routes. The goals of the study were to assess comparative bioavailability by versus SC routes demonstrate that drug delivery afforded survival advantage similar dosing. Pharmacokinetics studied after two doses, 24 h apart, (500 mg/kg) male C3H/Hen mice (7–9 weeks) injection or route. dose response (100 750 at 15 min prior...

Breast tissue is among the most sensitive tissues to carcinogenic actions of ionizing radiation and epidemiological studies have linked exposure breast cancer. Currently, molecular understanding carcinogenesis in mammary gland hindered due scarcity vivo long-term follow up data. We undertook this study delineate radiation-induced persistent alterations gene expression mouse glands 2-month after exposure. Six eight week old female C57BL/6J mice were exposed 2 Gy whole body γ surgically...