Abrogation of radiation injury to human hematopoietic stem cells with tumor necrosis factor-α

Karkanitsa, Leonid V.; Komarovskaya, Marina; Krivenko, Svetlana

doi:10.1002/stem.5530150714

Cited by 7 publications

(5 citation statements)

References 14 publications

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“…Furthermore, TNF was found to regulate a high number of molecules in the datasets (S5 Table, S6 Fig). This cytokine was previously shown to be strongly protective at lower ionizing radiation doses for the hematopoietic stem cell system [68] and via selective destruction of blood vessels in T-cell tumors [69]. Interestingly, the activity of tumor necrosis factor-alpha ( TNF-α ) in cell lines was found to be antagonistic to the activity of TGFb [70].…”

Section: Discussionmentioning

confidence: 99%

Dose-dependent effects of gamma radiation on the early zebrafish development and gene expression

et al. 2017

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Ionizing radiation from natural sources or anthropogenic activity has the potential to cause oxidative stress or genetic damage in living organisms, through the ionization and excitation of molecules and the subsequent production of free radicals and reactive oxygen species (ROS). The present work focuses on radiation-induced biological effects using the zebrafish (Danio rerio) vertebrate model. Changes in developmental traits and gene expression in zebrafish were assessed after continuous external gamma irradiation (0.4, 3.9, 15 and 38 mGy/h) with corresponding controls, starting at 2.5 hours post fertilization (hpf) and lasting through embryogenesis and the early larval stage. The lowest dose rate corresponded to recommended benchmarks at which adverse effects are not expected to occur in aquatic ecosystems (2–10 mGy/day). The survival observed at 96 hours post fertilization (hpf) in the 38 mGy/h group was significantly lower, while other groups showed no significant difference compared to controls. The total hatching was significantly lower from controls in the 15 mGy/h group and a delay in hatching onset in the 0.4 mGy/h group was observed. The deformity frequency was significantly increased by prolonged exposure duration at dose rates ≥ 0.4 mGy/h. Molecular responses analyzed by RNA-seq at gastrulation (5.5 hpf transcriptome) indicate that the radiation induced adverse effects occurred during the earliest stages of development. A dose-response relationship was found in the numbers of differentially regulated genes in exposure groups compared to controls at a total dose as low as 1.62 mGy. Ingenuity Pathway Analysis identified retinoic acid receptor activation, apoptosis, and glutathione mediated detoxification signaling as the most affected pathways in the lower dose rate (0.54 mGy/h), while eif2 and mTOR, i.e., involved in the modulation of angiogenesis, were most affected in higher dose rates (5.4 and 10.9 mGy/h). By comparing gene expression data, myc was found to be the most significant upstream regulator, followed by tp53, TNF, hnf4a, TGFb1 and cebpa, while crabp2b and vegfab were identified as most frequent downstream target genes. These genes are associated with various developmental processes. The present findings show that continuous gamma irradiation (≥ 0.54 mGy/h) during early gastrula causes gene expression changes that are linked to developmental defects in zebrafish embryos.

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Section: Discussionmentioning

confidence: 99%

Dose-dependent effects of gamma radiation on the early zebrafish development and gene expression

et al. 2017

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“…However, CBLB502 injection (in the absence of irradiation) led to induction of multiple cytokines in mouse plasma (Fig. 2F), including radioprotective cytokines such as granulocyte colony-stimulating factor (G-CSF) (26), interleukin 6 (IL-6) (27) and tumor necrosis factor-α (TNFα) (28). Consistent with its low toxicity, CBLB502 activated only sub-inflammatory levels of TNFα.…”

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confidence: 88%

An Agonist of Toll-Like Receptor 5 Has Radioprotective Activity in Mouse and Primate Models

Burdelya

Krivokrysenko

Tallant

et al. 2008

Science

621

651

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The toxicity of ionizing radiation is associated with massive apoptosis in radiosensitive organs. Here, we investigate whether a drug that activates a signaling mechanism used by tumor cells to suppress apoptosis can protect healthy cells from the harmful effects of radiation. We studied CBLB502, a polypeptide drug derived from Salmonella flagellin that binds to Toll-like receptor 5 (TLR5) and activates nuclear factor-kappaB signaling. A single injection of CBLB502 before lethal total-body irradiation protected mice from both gastrointestinal and hematopoietic acute radiation syndromes and resulted in improved survival. CBLB502 injected after irradiation also enhanced survival, but at lower radiation doses. It is noteworthy that the drug did not decrease tumor radiosensitivity in mouse models. CBLB502 also showed radioprotective activity in lethally irradiated rhesus monkeys. Thus, TLR5 agonists could potentially improve the therapeutic index of cancer radiotherapy and serve as biological protectants in radiation emergencies.

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“…Fig. 1 The nucleus of chemical structure of flavonoids, and the basic mechanisms of molecule in the protection against the radiation by eight key types of flavonoids [58], [32], [49], [65], [34], [52], [9], [7], [14]. IV.…”

Section: Flavonoidsmentioning

confidence: 99%

“…Inflammatory cytokines can cause damage or necrosis in the tissues and organs of any part of the body. Such injuries are more common in lungs and kidneys [34].…”

Section: Xmentioning

confidence: 99%

Flavonoids and Effective Factors for Protection against Radiations

Aliyar,

Neda,

Darwish

2023

CJMS

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As the title indicated, this paper studies flavonoids which is a plant composition having the antioxidant characteristics which plays a key role in strengthening the health, decreasing the risk of the diabetes, cancer, and heart diseases. It also focuses on the effective factors for protecting the human beings against the radiations. The data for this study are extracted from different scientific papers published in international journals such as Google Scholar, Scopus, Web of Science, and PubMed. This paper first discusses the damages caused by the ionizing radiations, next, I have talked about the classification of flavonoids. A table containing the data such as the affected animals or cells, the prescribed dosage of the flavonoids, the timing of dosage, the type of radiation, and the result seen on the animals. The result of the study shows that flavonoids truly reduce the adverse effects of the radiations on healthy cells during radio-therapy, accidental radiations, or radiations caused by terrorist attacks on nuclear power plants.

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Abrogation of radiation injury to human hematopoietic stem cells with tumor necrosis factor-α

Cited by 7 publications

References 14 publications

Dose-dependent effects of gamma radiation on the early zebrafish development and gene expression

Dose-dependent effects of gamma radiation on the early zebrafish development and gene expression

An Agonist of Toll-Like Receptor 5 Has Radioprotective Activity in Mouse and Primate Models

Flavonoids and Effective Factors for Protection against Radiations

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