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Identifying new targets for overcoming radioresistance is crucial for improving the efficacy of lung cancer radiotherapy, given that tumor cell resistance is a leading cause of treatment failure. Recent research has spotlighted the significance of Musashi2 (MSI2) in cancer biology. In this study, we first demonstrated that MSI2 plays a key function in regulating the radiosensitivity of lung cancer. The expression of MSI2 is negatively correlated with overall survival in cancer patients, and the knockdown of MSI2 inhibits tumorigenesis and increases radiosensitivity of lung cancer cells. Cellular radiosensitivity, which is closely linked to DNA damage, is influenced by MSI2 interaction with ataxia telangiectasia mutated and Rad3‐related kinase (ATR) and checkpoint kinase 1 (CHK1) post‐irradiation; moreover, knockdown of MSI2 inhibits the ATR‐mediated DNA damage response pathway. RNA‐binding motif protein 17 (RBM17), which is implicated in DNA damage repair, exhibits increased interaction with MSI2 post‐irradiation. We found that knockdown of RBM17 disrupted the interaction between MSI2 and ATR post‐irradiation and increased the radiosensitivity of lung cancer cells. Furthermore, we revealed the potential mechanism of MSI2 recruitment into the nucleus with the assistance of RBM17 to activate ATR to promote radioresistance. This study provides novel insights into the potential application of MSI2 as a new target in lung cancer radiotherapy. [ABSTRACT FROM AUTHOR]

Radiation‐induced lung injury (RILI), divided into early radiation pneumonia (RP) and late radiation‐induced pulmonary fibrosis (RIPF), is a common serious disease after clinical chest radiotherapy or nuclear accident, which seriously threatens the life safety of patients. There has been no effective prevention or treatment strategy till now. Epithelial‐mesenchymal transition (EMT) is a key step in the occurrence and development of RILI. In this study, we demonstrated that emetine dihydrochloride (EDD) alleviated RILI through inhibiting EMT. We found that EDD significantly attenuated EMT‐related markers, reduced Smad3 phosphorylation expression after radiation. Then, for the first time, we observed EDD alleviated lung hyperaemia and reduced collagen deposit induced by irradiation, providing protection against RILI. Finally, it was found that EDD inhibited radiation‐induced EMT in lung tissues. Our study suggested that EDD alleviated RILI through inhibiting EMT by blocking Smad3 signalling pathways. In summary, our results indicated that EDD is a novel potential radioprotector for RILI. [ABSTRACT FROM AUTHOR]

DNA double‐strand breaks can seriously damage the genetic information that organisms depend on for survival and reproduction. Therefore, cells require a robust DNA damage response mechanism to repair the damaged DNA. Homologous recombination (HR) allows error‐free repair, which is key to maintaining genomic integrity. Long non‐coding RNAs (lncRNAs) are RNA molecules that are longer than 200 nucleotides. In recent years, a number of studies have found that lncRNAs can act as regulators of gene expression and DNA damage response mechanisms, including HR repair. Moreover, they have significant effects on the occurrence, development, invasion and metastasis of tumor cells, as well as the sensitivity of tumors to radiotherapy and chemotherapy. These studies have therefore begun to expose the great potential of lncRNAs for clinical applications. In this review, we focus on the regulatory roles of lncRNAs in HR repair. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) toxicity caused by ionizing radiation (IR) is a dose limiting factor in radiotherapy and a great threat for individual nuclear-related military missions. However, there are currently no available strategies to effectively prevent the damage on the intestine induced by IR. In the present study, the protective activity of Heat Killed Salmonella typhimurium (HKST) on intestine against IR was investigated. Through mouse intestinal organoids and whole body irradiation of mice, we found that the pretreatment with HKST significantly preserved the structure of small intestine upon IR exposure and promoted the proliferation of intestinal cells post-IR. Further study revealed that the radioprotective effects of HKST were involved in DNA damage response (DDR) signaling. Moreover, the stimulation of DDR signaling by HKST upon radiation damage was mediated by Wnt signaling, in which the inhibition of Wnt signaling diminished the radioprotective effects of HKST. To sum up, our study suggested HKST as a potential radioprotectant used for prevention of IR-induced GI toxicity. [ABSTRACT FROM AUTHOR]

Injury‐induced by ionizing radiation (IR) severely reduces the quality of life of victims. The development of radiation protectors is regarded as one of the most resultful strategies to alleviate damages caused by IR exposure. In the present study, we investigated the radioprotective effects of the agonist of nucleotide‐binding‐oligomerization‐domain‐containing proteins 2 called murabutide (MBD) and clarified the potential mechanisms. Our results showed that the pretreatment with MBD effectively protected cultured cells and mice against IR‐induced toxicity and the pretreatment with MBD in vitro and in vitro also inhibited apoptosis caused by IR exposure. The downregulation of γ‐H2AX and the upregulation of ATR signaling pathways by MBD treatment indicated that the radioprotective effects of MBD were due to the stimulation of DNA damage response (DDR) pathway to repair DNA double‐strand breaks caused by IR exposure. As the radioprotective effects of MBD were diminished by the ATR selective inhibitor rather than the ATM inhibitor, ATR pathway was confirmed to be a more crucial checkpoint pathway in mediating the stimulation of DDR pathway by MBD. Taken together, our data provide a novel and effective protector to relieve the injury induced by IR exposure. [ABSTRACT FROM AUTHOR]

The small intestine is one of the most sensitive organs to irradiation injury, and the development of high effective radioprotectants especially with low toxicity for intestinal radiation sickness is urgently needed. Monophosphoryl lipid A (MPLA) was found to be radioprotective in our previous study, while its effect against the intestinal radiation injury remained unknown. In the present study, we firstly determined the intestinal apoptosis after irradiation injury according to the TUNEL assay. Subsequently, we adopted the immunofluorescence technique to assess the expression levels of different biomarkers including Ki67, γ-H2AX, and defensin 1 in vivo. Additionally, the inflammatory cytokines were detected by RT-PCR. Our data indicated that MPLA could protect the intestine from ionizing radiation (IR) damage through activating TLR4 signal pathway and regulating the inflammatory cytokines. This research shed new light on the protective effect of the novel TLR4 agonist MPLA against intestine detriment induced by IR. [ABSTRACT FROM AUTHOR]

As natural nanoparticles, exosomes regulate a wide range of biological processes via modulation of its components, including circular RNAs (circRNAs). CircRNAs are a novel class of closed-loop single-stranded RNAs with a wide distribution, and play diverse biological roles. Due to its stability in exosomes, exosomal circRNAs serve as biomarkers, pathogenic regulators and exert therapeutic potentials in some cardiovascular diseases, including atherosclerosis, acute coronary syndrome, ischemia/reperfusion injury, heart failure, and peripheral artery disease. In this review, we detailed the current knowledge on the biogenesis and functions of exosomes, circRNAs, and exosomal circRNAs, as well as their involvement in these cardiovascular diseases, providing novel insights into the diagnosis and treatment of these diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Qin, Yan, Wu, Gong, Wang, Jiang, Zhao, Sun, Wang, Wang, Zhao, Liu and Yuan.)