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The modulation of macrophage polarization is a promising strategy for maintaining homeostasis and improving innate and adaptive immunity. Low-dose ionizing radiation has been implicated in macrophage immunomodulatory responses. However, studies on the relationship between exosomes and regulation of macrophage polarization induced by ionizing radiation are limited. Therefore, this study investigated the alterations in macrophages and exosomes induced by gamma irradiation and elucidated the underlying mechanisms. We used the mouse macrophage cell line RAW 264.7 to generate macrophages and performed western blot, quantitative reverse transcription-PCR, and gene ontology analyses to elucidate the molecular profiles of macrophage-derived exosomes under varying treatment conditions, including 10 Gy gamma irradiation. Exosomes isolated from gamma-irradiated M1 macrophages exhibited an enhanced M1 phenotype. Irradiation induced the activation of NF-κB and NLRP3 signaling in M1 macrophages, thereby promoting the expression of pro-inflammatory cytokines. Cytokine expression was also upregulated in gamma-irradiated M1 macrophage-released exosomes. Therefore, gamma irradiation has a remarkable effect on the immunomodulatory mechanisms and cytokine profiles of gamma-irradiated M1 macrophage-derived exosomes, and represents a potential immunotherapeutic modality. [ABSTRACT FROM AUTHOR]

Radiation molecularly transforms naturally occurring products by inducing the methoxylation, hydroxylation, and alkylation of parent compounds, thereby affecting the anti-inflammatory capacities of those compounds. Minaprine (1) modified by ionizing radiation generated the novel hydroxymethylation hydropyridazine (2), and its chemical structure was determined based on NMR and HRESIMS spectra. Compared to the original minaprine, the novel generated product showed a highly enhanced anti-inflammatory capacity inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 and DH82 macrophage cells. In addition, minaprinol (2) effectively inhibited cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) at the protein level and pro-inflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10) production in macrophages. [ABSTRACT FROM AUTHOR]

Nialamide is a non-selective monoamine oxidase inhibitor that was widely used as an antidepressant. However, it has been prohibited for decades in the depressive medicine market due to the adverse hepatotoxic side effects. The re-use of drugs that have been withdrawn from the market represents a promising approach for the development of novel incrementally modified drugs and, in this context, ionizing radiation can serve as a powerful tool for producing new drug candidates. The present study exposed nialamide to γ radiation at 50 kGy to obtain the novel cyclized benzylamide, nialaminosin (compound 2), along with five known compounds, 3-amino-N-benzylpropanamide (compound 3), 3-methoxy-N-benzylpropanamide (compound 4), 3-hydroxy-N-benzylpropanamide (HBPA; compound 5), N-benzylpropanamide (compound 6) and isonicotinamide (compound 7). Among the isolated compounds, HBPA was established to inhibit the lipopolysaccharide-induced overproduction of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E2 and cytokines including TNF-α, IL-6 and IL-10, without causing cytotoxicity to both RAW 264.7 and DH82 cells. Furthermore, HBPA was found to reduce the protein expression of inducible NO synthase and cyclooxygenase-2 in macrophages and compared with nialamide, it was established to have more potent radical scavenging activity. The present study therefore suggested the application of HBPA for the improvement of anti-inflammatory properties using ionizing radiation technology on the withdrawn drug nialamide. [ABSTRACT FROM AUTHOR]

This study examined differential regulation of volatile terpenoids produced by rosemary (Rosmarinus officinalis L.) leaves in response to ionizing irradiation. Headspace volatile collection from rosemary leaves by solid-phase microextraction-gas chromatography-mass spectrometry analyses revealed that rosemary leaves biologically synthesized 26 species of volatile terpenoids and their relative ratio were changed after the exposure to γ-irradiation. Relative ratio of oxygenated monoterpenes such as borneol, (-)-verbenone, lemonol, and bornyl acetate (except for 1,8-cineol, linalool, chrysanthenone, camphor, and (+)-verbenone) and sesquiterpene hydrocarbons (i.e., caryophyllene-type) increased when the rosemary leaves were exposed to γ-ray in a dose-dependent manner. On the contrary, the change of the ratio of oxygenated sesquiterpenes such as caryophyllene oxide was negligible, and that of monoterpene hydrocarbons like α-pinene, camphene, myrcene, and limonene was down-regulated. These results indicate that γ-irradiation can modify chemical structures of volatile terpenes, and can, thus, be applied to reconstitute chemical constituents in aromatic plants. [ABSTRACT FROM AUTHOR]

Dexamethasone (Dex) is widely used in the management of leukemia and lymphoma. While Dex is commonly used for hematological malignancies, the effects of Dex in solid cancer cells remain controversial. To develop a more effective anticancer drug for solid cancers, Dex was modified by ionizing radiation and the anticancer activity of ionizing-radiation-irradiated Dex (Dex-IR) was investigated in human lung cancer cells. Using the MTT assay, the proliferation of non-small cell lung cancer cells was significantly inhibited after treatment with Dex-IR compared with Dex. Furthermore, Dex-IR induced apoptotic cell death and cell cycle arrest of H1650 human lung cancer cells. The invasiveness of H1650 cells was significantly reduced and the matrix metalloproteinase activity was strongly suppressed. These results indicate that Dex-IR acts as a tumor suppressor by both inducing apoptosis and arresting the cell cycle. Although the structure of Dex-IR remains to be determined, our results suggest it may be useful as a novel anticancer agent for the treatment of solid cancers. [ABSTRACT FROM AUTHOR]

Prednisolone is an anti-inflammatory drug used to treat a number of conditions, including liver disease and cancer. Numerous studies have demonstrated that glucocorticoids such as prednisolone modified by ionizing radiation can promote anticancer activity in cancer cells. To the best of our knowledge, however, the effect of ionizing radiation on prednisolone structure and cancer cells has not yet been identified. The present study created a novel prednisolone derivative using γ-irradiation, and its anticancer properties were investigated in liver cancer cells. The present study confirmed the structure of the new prednisolone derivative using liquid chromatogram-mass spectrometry. MTT assays determined the cytotoxic effects of γ-irradiated (IR)-prednisolone in liver cancer cells. Flow cytometry analysis evaluated apoptosis, mitochondrial membrane potential and cell cycle distribution. Western blotting was used to analyze the proteins associated with apoptosis. The chromatogram profile revealed that IR-prednisolone produced a number of peaks compared with the single peak of the original prednisolone. In contrast to prednisolone, the MTT results showed that IR-prednisolone significantly prevented the growth of liver cancer cells. IR-prednisolone promoted apoptosis and arrested the cell cycle at the G0/G1 stage in Huh7 cells. IR-prednisolone also altered the mitochondrial membrane potential and activated caspase-associated proteins, which activated the intrinsic apoptotic signaling pathway. In conclusion, IR-prednisolone promoted anticancer effects in liver cancer cells via apoptosis activation. The present study demonstrated that IR-prednisolone may be a potential anticancer agent against liver cancer, although specific molecules have yet to be identified. [ABSTRACT FROM AUTHOR]

Abstract: This study was carried out to evaluate the efficiency of degradation of antibiotic ampicillin in pig manure slurry and an aqueous ampicillin solution with the use of electron beam irradiation as a function of the absorbed dose. The degradation efficiency of ampicillin was close to 95% at an absorbed dose of 10kGy. The degradation of ampicillin followed a “first-order” reaction rate with respect to absorbed dose. The results demonstrate that the electron beam irradiation technology is an effective means to remove antibiotics in manure and bodies of water. [Copyright &y& Elsevier]

Highlights • Update on DNA damage response (DDR) signaling pathways in plants. • Recent advances in cellular and phenotypic DDRs, especially induced by IR. • Epigenetic regulation of DDRs associated with genome instability in plants. • Genotoxic agents and their DDRs in plants. Abstract Plants orchestrate various DNA damage responses (DDRs) to overcome the deleterious impacts of genotoxic agents on genetic materials. Ionizing radiation (IR) is widely used as a potent genotoxic agent in plant DDR research as well as plant breeding and quarantine services for commercial uses. This review aimed to highlight the recent advances in cellular and phenotypic DDRs, especially those induced by IR. Various physicochemical genotoxic agents damage DNA directly or indirectly by inhibiting DNA replication. Among them, IR-induced DDRs are considerably more complicated. Many aspects of such DDRs and their initial transcriptomes are closely related to oxidative stress response. Although many key components of DDR signaling have been characterized in plants, DDRs in plant cells are not understood in detail to allow comparison with those in yeast and mammalian cells. Recent studies have revealed plant DDR signaling pathways including the key regulator SOG1. The SOG1 and its upstream key components ATM and ATR could be functionally characterized by analyzing their knockout DDR phenotypes after exposure to IR. Considering the potent genotoxicity of IR and its various DDR phenotypes, IR-induced DDR studies should help to establish an integrated model for plant DDR signaling pathways by revealing the unknown key components of various DDRs in plants. [ABSTRACT FROM AUTHOR]

Abstract: Studies focused on the responses of plants to ionizing radiation are becoming more important due to the increased need for radiation-induced mutations, post-harvest or phytosanitary irradiation treatment of plants, and environmental monitoring of radioactive sites. To elucidate the influence of ionizing radiation on genome-wide transcription in plants, we performed integrated analysis of diverse transcriptomic data from different Arabidopsis samples and at various time points after γ irradiation or H2O2 treatment. The expression levels of most of the differentially expressed genes (DEGs) that were induced or repressed after γ irradiation returned to baseline levels of transcription within 12h, while some of these genes showed prolonged transcriptional changes. Expression of the DEGs did not correlate with genomic DNA methylation; however, there were substantial differences in DEG levels between the wild type and the cmt3-11 mutant, which has a defect in non-CG DNA methylation. Moreover, the proportion of the DEGs in common between 2 independent experiments using different batches of samples was only 12–18%. These results suggest that there is a diversity or randomness in radiation-induced physiological or phenotypic alterations. However, the results also indicated that 47 DEGs maintained a transcriptional change until 48h, and 7 of them, until 16d. Forty-five additional DEGs were found to be sustainably induced or repressed until 24h after γ irradiation regardless of sample-to-sample variation or genotype, and 4 or 2 of them, until 5d or 16d, respectively. Therefore, we suggest that the 4 γ-ray-responsive genes that showed sustainable transcriptional changes until day 5 would be reliable and reproducible genetic markers when evaluating the responsiveness of plants to γ-rays. [Copyright &y& Elsevier]