A series of physiological and pathological changes occur after radiotherapy and accidental exposure to ionizing radiation (IR). These changes cause serious damage to human tissues and can lead to death. Radioprotective countermeasures are radioprotective agents that prevent and reduce IR injury or have therapeutic effects. Based on a good understanding of radiobiology, a number of protective agents have achieved positive results in early clinical trials. The present review grouped known radioprotective agents according to biochemical categories and potential clinical use, and reviewed radiation countermeasures, i.e., radioprotectors, radiation mitigators and radiotherapeutic agents, with an emphasis on their current status and research progress. The aim of the present review is to facilitate the selection and application of suitable radioprotectors for clinicians and researchers, to prevent or reduce IR injury.

Radiotherapy has been used for decades in the treatment of liver cancer. We previously found that adiponectin receptor (AdipoR1) is a prognostic biomarker for hepatoma carcinoma (HCC) after stereotactic body radiation therapy (SBRT) and blocking AdipoR1 enhances radiation sensitivity in hepatoma carcinoma cells. In the current study, we aimed to elucidate the roles of AdipoR1 in ionizing radiation‐ (IR‐) induced radiosensitivity by activating ferroptosis pathway in HCC cells. We found that IR upregulated the expression of AdipoR1 and furthermore promoted the protein stability of transcription factor Nrf2, Nrf2 binded to the xCT promoter and increased xCT transcription and expression, and this directly contributed to the protective function in the early stage of radiation in HCC cells. AdipoR1 knockdown significantly inhibited expression of Nrf2 and xCT and, furthermore, increased both IR‐ and erastin‐induced ferroptosis, which could be abolished by the rescue of Nrf2 and xCT. For the first time, we found that radiation‐induced ferroptosis was mediated by AdipoR1‐Nrf2‐xCT pathway in HCC cells. These results provide new insights to the development and application of novel therapeutic strategies for hepatoma carcinoma.

Protein arginine methyltransferase 5 (PRMT5) is an epigenetic regulator which has been proven to be a potential target for cancer therapy. We observed that PRMT5 underwent alternative splicing (AS) and generated a spliced isoform PRMT5-ISO5 in hepatocellular carcinoma (HCC) patients after radiotherapy. However, the regulatory mechanism and the clinical implications of IR-induced PRMT5 AS are unclear. This work revealed that serine and arginine rich splicing factor 3 (SRSF3) silencing increased PRMT5-ISO5 level, whereas heterogeneous nuclear ribonucleoprotein H 1 (HNRNPH1) silencing reduced it. Then, we found that SRSF3 and HNRNPH1 competitively combined with PRMT5 pre-mRNA located at the region around the 3′- splicing site on intron 2 and the alternative 3′- splicing site on exon 4. IR-induced SRSF3 downregulation led to an elevated level of PRMT5-ISO5, and exogenous expression of PRMT5-ISO5 enhanced cell radiosensitivity. Finally, we confirmed in vivo that IR induced the increased level of PRMT5-ISO5 which in turn enhanced tumor killing and regression, and liver-specific Prmt5 depletion reduced hepatic steatosis and delayed tumor progression of spontaneous HCC. In conclusion, our data uncover the competitive antagonistic interaction of SRSF3 and HNRNPH1 in regulating PRMT5 splicing induced by IR, providing potentially effective radiotherapy by modulating PRMT5 splicing against HCC.

Kim YJ, et al. J Korean Med Sci. 2023 Apr;38(17):e164. https://doi.org/10.3346/jkms.2023.38.e164

Purpose: Saeu-jeot, or shrimp paste, is a traditional Korean high-salt fermented seafood. This study elucidated the effects of saeu-jeot extract (SJE) on NLRP3 inflammasome activation and radiation-induced micronucleus formation. Method: We treated lipopolysaccharide-primed mouse bone marrow-derived macrophages with the NLRP3 inflammasome activators ATP and nigericin. We also analyzed the acute effects of ionizing radiation on micronucleated polychromatic erythrocytes (MnPCEs) in whole-body gamma-irradiated male BALB/c and C57BL/6 mice after oral administration of SJE. Results: SJE significantly inhibited NLRP3 inflammasome activation, reducing IL-1 beta secretion in vitro. In addition, the frequency of MnPCEs was significantly lower in SJE-treated mice. Conclusions: SJE has anti-inflammatory effects and reduces radiation-induced chromosome damage. Advance in knowledge: There are no reports concerning the effects of SJE on NLRP3 inflammasome activation or radioprotection. This experiment showed the radioprotective effects of saeu-jeot.

Background: Pancreatic adenocarcinoma (PAAD) is a highly aggressive form of cancer characterized by a low survival rate. Adhesion molecule with Ig like domain family 2 (AMIGO2), a cell adhesion molecule, has been found to be expressed abnormally in various solid tumors, but its specific role in PAAD has not yet been investigated. This study aimed to investigate the potential prognostic value of AMIGO2 in pan-cancer, especially in PAAD. Methods: RNA profiles and corresponding clinical data of PAAD patients in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were obtained. Kaplan-Meier survival analysis was conducted to assess the relationship between AMIGO2 expression and overall survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to evaluate the functional enrichment of AMIGO2 in PAAD. Subsequently, immune infiltration and single-cell RNA (scRNA) sequencing analyses were employed to investigate the composition of immune cells. The half maximal inhibitory concentration (IC50) value was utilized to estimate the drug sensitivity associated with AMIGO2. Finally, in vitro experiments were conducted to assess the biological function of AMIGO2 in PAAD. Results: AMIGO2 exhibited abnormal expression patterns and demonstrated prognostic significance in various types of cancer. AMIGO2 was observed to be up-regulated in PAAD tissues. Its high expression was indicative of a poor prognosis. Additionally, elevated level of AMIGO2 was found to be associated with mutations in KRAS and TP53, as well as with dysregulation of key cellular processes such as “MAPK signaling” and “p53 signaling pathway”. Furthermore, AMIGO2 expression exhibited correlations with the infiltration of macrophages and cancer-associated fibroblasts. PAAD patients with high AMIGO2 expression were more sensitive to BRD4 inhibitor BI-2536. The growth of PAAD cells was found to be inhibited upon knockdown of AMIGO2. Conclusions: AMIGO2 was identified as prognostic factor in PAAD, suggesting its potential as a biomarker and therapeutic target for PAAD patients.