Objective: To investigate the role of integrin beta-1 (Itgb1) in radiation-induced tissue injury and elucidate its underlying molecular mechanisms. Methods: Differentially expressed genes associated with radiation injury were identified from the Gene Expression Omnibus (GEO) microarray database through bioinformatics analysis, followed by enrichment analysis to determine core hub genes. In vitro, Itgb1 was silenced using siRNA transfection in human chronic myeloid leukemia K562 and mouse alveolar epithelial MLE-12 cells. Protein expression was assessed by Western blot, while cell proliferation, apoptosis, and reactive oxygen species (ROS) levels were quantified by flow cytometry following Itgb1 inhibition. In vivo, C57BL/6 mice were divided into 4 experimental groups (n = 5 per group): Control (intraperitoneal injection of PBS without irradiation), RGD (intraperitoneal injection of RGD 10 mg/kg without irradiation), IR + PBS (8 Gy 60Co γ-ray total body irradiation with PBS), and IR + RGD (intraperitoneal injection of RGD 10 mg/kg, 2 h prior to 8 Gy 60Co γ-ray total body irradiation). Bronchoalveolar lavage fluid (BALF) was collected for macrophage analysis. Lung and intestine tissues were subjected to hematoxylin-eosin (H&E) staining and immunofluorescence (IF) examination. Peripheral blood samples were analyzed to evaluate hematopoietic function. Results: Bioinformatics analysis identified Itgb1 as a hub gene in radiation-induced injury. Western blot analysis demonstrated significant upregulation of Itgb1 protein following irradiation. In K562 cells, Itgb1 expression peaked at 12 h post-irradiation (t = 3.07, P < 0.01) and declined by 24 h, whereas MLE-12 cells exhibited sustained elevation at both time points (t = 10.44, P < 0.0001). Itgb1 silencing significantly exacerbated radiation-induced cellular damage. In K562 cells, knockdown reduced S-phase proliferation from 52.49% to 36.41% (t = 9.64, P < 0.01), increased apoptosis (t = 11.36, P < 0.001), and elevated ROS levels (t = 3.62, P < 0.05). Comparable effects were observed in MLE-12 cells: reduced proliferation (46.82% to 37.98%, t = 12.78, P < 0.0001), enhanced apoptosis (t = 10.16, P < 0.0001), and increased ROS (t = 5.58, P < 0.0001). In vivo, Itgb1 inhibition aggravated radiation-induced pulmonary, intestinal and hematopoietic injuries, characterized by increased inflammatory infiltration, alveolar septal thickening, and decreased peripheral blood cell counts (t = 2.34, P < 0.01). These findings indicate that Itgb1 functions as a protective factor against radiation injury. Conclusions: This study elucidates Itgb1 critical radioprotective role, where compensatory upregulation constitutes an endogenous defense mechanism, while its deficiency exacerbates injury through amplified apoptosis and inflammation, highlighting its clinical utility as a therapeutic target.

Objective To investigate the role of integrin beta-1 (Itgb1) in radiation-induced tissue injury and elucidate its underlying molecular mechanisms. Methods Differentially expressed genes associated with radiation injury were identified from the Gene Expression Omnibus (GEO) microarray database through bioinformatics analysis, followed by enrichment analysis to determine core hub genes. In vitro, Itgb1 was silenced using siRNA transfection in human chronic myeloid leukemia (K562) and mouse alveolar epithelial (MLE-12) cells. Protein expression was assessed by Western blot, while cell proliferation, apoptosis, and reactive oxygen species (ROS) levels were quantified by flow cytometry following Itgb1 inhibition. In vivo, C57BL/6 mice (n=5 per group) were divided into 4 experimental groups: Control (intraperitoneal injection of PBS without irradiation), RGD (intraperitoneal injection of RGD 10 mg/kg without irradiation), IR+PBS (8 Gy 60Co γ-ray total body irradiation with PBS), and IR+RGD (intraperitoneal injection of RGD 10 mg/kg, 2 h prior to 8 Gy 60Co γ-ray total body irradiation). Bronchoalveolar lavage fluid (BALF) was collected for macrophage analysis. Lung and intestine tissues were subjected to hematoxylin-eosin (H&E) staining and immunofluorescence (IF) examination. Peripheral blood samples were analyzed to evaluate hematopoietic function. Results Bioinformatics analysis identified Itgb1 as a hub gene in radiation-induced injury. Western blot analysis demonstrated significant upregulation of Itgb1 protein following irradiation. In K562 cells, Itgb1 expression peaked at 12 h post-irradiation (t= 3.07, P < 0.01) and declined by 24 h, whereas MLE-12 cells exhibited sustained elevation at both time points (t = 10.44, P < 0.0001). Itgb1 silencing significantly exacerbated radiation-induced cellular damage. In K562 cells, knockdown reduced S-phase proliferation from 52.49% to 36.41% (t = 9.64, P < 0.01), increased apoptosis (t = 11.36, P < 0.001), and elevated ROS levels (t =3.62, P < 0.05). Comparable effects were observed in MLE-12 cells: reduced proliferation (46.82% to 37.98%, t = 12.78, P < 0.0001), enhanced apoptosis (t = 10.16, P < 0.0001), and increased ROS (t = 5.58, P < 0.0001). In vivo, Itgb1 inhibition aggravated radiation-induced pulmonary, intestinal and hematopoietic injuries, characterized by increased inflammatory infiltration, alveolar septal thickening, and decreased peripheral blood cell counts (t = 2.34, P < 0.01). These findings indicate that Itgb1 functions as a protective factor against radiation injury. Conclusions This study elucidates Itgb1 critical radioprotective role, where compensatory upregulation constitutes an endogenous defense mechanism, while its deficiency exacerbates injury through amplified apoptosis and inflammation, highlighting its clinical utility as a therapeutic target.

The evolving geopolitical landscape has heightened the probability of nuclear incidents, including accidental release or deliberate detonation, which can cause acute, life-threatening radiation injury to large populations. High-dose ionizing radiation (IR) is highly likely to cause radiation injury to the intestines and lead to intestinal radiation sickness. This study systematically explored the protective effect of cobalt chloride (CoCl2) on intestinal radiation injury and its preliminary mechanism from multiple levels, including cells, intestinal tissues, intestinal organoids, and live mice. The results showed that CoCl2 pretreatment could significantly enhance the radiation tolerance of mice, not only greatly improving the survival rate and multiple indicators such as intestinal injury score, but also maintaining the integrity of the small intestinal epithelial villi structure. At the same time, it promotes the proliferation and differentiation of intestinal organoids, inhibits the apoptosis of intestinal epithelial cells, and enhances the expression of barrier protection genes, thereby enhancing the intestinal resistance to radiation injury. Mechanism studies have shown that CoCl2 can up-regulate the expression of hypoxia-inducible factor-2 α (HIF-2α) via hypoxia-mimetic action and activate downstream signaling pathways related to cell proliferation, anti-apoptosis, and angiogenesis. This study initially clarified the mechanism by which CoCl2 protects the intestinal tract from radiation injury, providing a scientific basis and strategic support for the development of new radiation protection targets. Its in-depth research and application transformation are expected to play an important role in the future field of nuclear radiation protection.

PURPOSE:Ionizing radiation (IR) has been shown to induce epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AECs), which is a critical cause of radiation-induced pulmonary fibrosis (RIPF). In this study, we investigated the role and molecular mechanisms of musashi2 (MSI2), an RNA-binding protein, in IR-induced EMT of AECs for aiming at potential therapeutic strategies to prevent RIPF. MATERIALS AND METHODS:Changes in the expression levels of MSI2 and EMT markers (E-cadherin, N-cadherin, and Vimentin) induced by IR in AECs were detected by western blot (WB). Then, the effect of MSI2 on IR-induced EMT of AECs was investigated by observing morphological changes and detecting expression of MSI2 and EMT markers by WB and immunofluorescence (IF). RNA-Seq analysis, WB and RT-qPCR were used to identify the targets of MSI2. RESULTS:We observed that IR could cause a significant increase of MSI2 protein expression, a down-regulation of E-cadherin and an up-regulation of Vimentin and N-cadherin in AECs (MLE-12 and RLE-6TN cells). We also revealed that MSI2 was involved in regulating the alteration of morphology and EMT-related markers in AECs after irradiation, suggesting the occurrence of EMT regulated by MSI2. Moreover, we found the mechanism of MSI2 participating in EMT by regulating the expression of transcription factor ZEB1, acting as a downstream target of MSI2 in IR-induced EMT of AECs. CONCLUSIONS:Our study unveils the critical role of MSI2 in IR-induced EMT of AECs and preliminarily elucidates its molecular mechanisms, providing new insights into the process of IR-induced pulmonary fibrosis.

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.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with no cure. Bufotalin (BT), an active component extracted from Venenum Bufonis, has been prescribed as a treatment for chronic inflammatory diseases. However, whether BT has antifibrotic properties has never been investigated. In this study, we report on the potential therapeutic effect and mechanism of BT on IPF. BT was shown to attenuate lung injury, inflammation, and fibrosis as well as preserve pulmonary function in bleomycin (BLM)-induced pulmonary fibrosis model. We next confirmed BT's ability to inhibit TGF-β1-induced epithelial-mesenchymal transition (EMT) and myofibroblast activation (including differentiation, proliferation, migration, and extracellular matrix production) in vitro. Furthermore, transcriptional profile analysis indicated the Wnt signaling pathway as a potential target of BT. Mechanistically, BT effectively prevented β-catenin from translocating into the nucleus to activate transcription of profibrotic genes. This was achieved by blunting TGF-β1-induced increases in phosphorylated Akt Ser437 (p-Akt S437) and phosphorylated glycogen synthase kinase (GSK)-3β Ser9 (p-GSK-3β S9), thereby reactivating GSK-3β. Additionally, the antifibrotic effects of BT were further validated in another in vivo model of radiation-induced pulmonary fibrosis. Collectively, these data demonstrated the potent antifibrotic actions of BT through inhibition of Akt/GSK-3β/β-catenin axis downstream of TGF-β1. Thus, BT could be a potential option to be further explored in IPF treatment.

本教研室创新性地建立了现场技能训练-虚拟仿真实践教学-部队防护训练基地"三位一体"的混合式综合能力培养模式,发现新的培训模式虽然提高了学员核应急医学救援的综合实践能力,但由于将学员实践能力的教学划分为三个部分,使得原来单一的教学评价模式已经不能够适用现有教学模式.基于此,本教研室构建了以教学评价指标化为核心的核应急医学救援任职教育实践教学评价体系.本教研室将评价维度分为三个:教学支持、教学效果、学员满意度,同时结合评价维度最终确定了九个核心教学评价指标,并将所构建的教学评价体系运用于教学评价实践,对所存在的问题给出相应的建议.本教研室通过该体系的构建与实施,对现有的教学进一步评价与优化,以更好地加强教学效果,提升教学质量.

Migrasome is a novel cellular organelle produced during cell migration, and its biogenesis depends on the migration process. It is generated in a variety of cells such as immune cells, metastatic tumor cells, other special functional cells like podocytes and cells in developing organisms. It plays important roles in various fields especially in the information exchange between cells. The discovery of migrasome, as an important supplement to the extracellular vesicle system, provides new mechanisms and targets for comprehending various biological or pathological processes. In this article, we will review the discovery, structure, distribution, detection, biogenesis, and removal of migrasomes and mainly focus on summarizing its biological functions in cell-to-cell communication, homeostatic maintenance, embryonic development and multiple diseases. This review also creates prospects for the possible research directions and clinical applications of migrasomes in the future.

Radiation injury is a common side effect of nuclear and radiation accidents as well as clinical oncologic radiotherapy. The organism undergoes a series of pathological responses after irradiation, especially in the short term, accompanied by an intense inflammatory storm [1], and effective targets for intervention have not been identified [2]. In this study, we screened differential genes in gene microarray data from the GEO database and then identified the core gene Itgb1 by enrichment analysis. Subsequently, the expression of Itgb1 was knocked down by siRNA interference and was functionally blocked by RGD, a Itgb1 inhibitor. Next, the proliferation and apoptosis of irradiated cells was detected, and injury of lung tissues and hemopoietic system were also investigated. As a result, knockdown of Itgb1 protected pulmonary epithelial cells and blood cell from irradiation, and RGD remitted the irradiation-induced lung injury and hematopoietic injury. This study suggests that Itgb1 plays a key role in radiation injury and provides new ideas for the prevention and treatment of radiation therapy.

Radiation-induced lung injury (RILI) is one of the common complications of radiotherapy for chest tumors and nuclear radiation accidents. The excessive reactive oxygen species induced by radiation is the main mediator. So far, the effective prevention and treatment for RILI are still lacking. Astaxanthin is a carotenoid that belongs to red natural lutein family and is commonly found in Marine organisms such as shrimp, oysters and salmon. It has been confirmed that astaxanthin has strong antioxidant and anti-inflammatory properties, therefore we speculated that astaxanthin may be a potential treatment for RILI. First, with a mice model of RILI, the protected effects of astaxanthin were observed. Furthermore, the experiments in vitro were performed by detecting apoptosis. As a result, astaxanthin protects the RILI, inhibits the process of pulmonary fibrosis, and reduces the elevation of inflammatory factors. The experiments in vitro demonstrated that astaxanthin could reduce radiation-induced apoptosis and especially inhibit activation of apoptosis pathway. In conclusion, astaxanthin could protect RILI of mice, which is mediated by inhibiting activation of apoptosis pathway.

BackgroundAcquired radio-resistance and the undesired normal tissue radiation injuries seriously discount the therapeutic effect of lung cancer radiotherapy. In this study, we aimed to explore the role and potential mechanism of polydatin in simultaneously decreasing radioresistance and radiation injuries.MethodsThe tumor-bearing model of nude mice was used to investigate the tumor inhibition of polydatin on lung cancer and its effect on radiosensitivity, and the effect of polydatin on B cell infiltration in cancerous tissue was investigated. In addition, we performed systemic radiotherapy on BABL/C mice and evaluated the protective effect of polydatin on radiation injury by the Kaplan-Meier survival curve. Moreover, the regulation of polydatin on proliferation and apoptosis of A549 cells was also investigated in vitro.ResultsIn this study, it is first found that polydatin inhibits the growth and promotes the radiosensitivity of lung cancer while reducing the radiation damage of the healthy tissue. Further, it is evidenced that the major mechanism relies on its regulation on body's immune function, and in particular, the inhibition of radiation-induced B cell infiltration in tumor tissue.ConclusionThese findings show that in addition to tumor inhibition, polydatin also promotes the sensitivity and reduces the adverse reactions of radiotherapy, making itself a promising candidate for boosting lung cancer radiotherapy efficacy.

There are differences and inconsistencies to some degree in the radioactive contamination control level of personnel′s body surface availiable in many national standards, thus puzzling the users. Therefore, it is proposed to compare the applicable scope, conditions and differences between relevant national standards, and combine with similar clinical nuclear medicine standards of radiological protection content to presevent recommendations on the contamination control level that should be correctly applied in an event of nuclear and radiological emergency. Based on the discussion of similar standards, the contaminated personnel with α of 0.04-10 Bq/cm 2 and β of 0.4-100 Bq/cm 2 are advised to be treated in the institutions with higher than secondary medical insititution. Both α econtamination control levels less than 0.04 Bq/cm 2 and β levels less than 0.4 Bq/cm 2 could be achivable, if fully decontaminated.

The lung is one of the most sensitive tissues to ionizing radiation, thus, radiation-induced lung injury (RILI) stays a key dose-limiting factor of thoracic radiotherapy. However, there is still little progress in the effective treatment of RILI. Ras-related C3 botulinum toxin substrate1, Rac1, is a small guanosine triphosphatases involved in oxidative stress and apoptosis. Thus, Rac1 may be an important molecule that mediates radiation damage, inhibition of which may produce a protective effect on RILI. By establishing a mouse model of radiation-induced lung injury and orthotopic lung tumor-bearing mouse model, we detected the role of Rac1 inhibition in the protection of RILI and suppression of lung tumor. The results showed that ionizing radiation induces the nuclear translocation of Rac1, the latter then promotes nuclear translocation of P53 and prolongs the residence time of p53 in the nucleus, thereby promoting the transcription of Trp53inp1 which mediates p53-dependent apoptosis. Inhibition of Rac1 significantly reduce the apoptosis of normal lung epithelial cells, thereby effectively alleviating RILI. On the other hand, inhibition of Rac1 could also significantly inhibit the growth of lung tumor, increase the radiation sensitivity of tumor cells. These differential effects of Rac1 inhibition were related to the mutation and overexpression of Rac1 in tumor cells.

Intestinal stem cells (ISCs) are responsible for intestinal tissue homeostasis and are important for the regeneration of the damaged intestinal epithelia. Through the establishment of ionizing radiation (IR) induced intestinal injury model, we found that a TLR2 agonist, Zymosan-A, promoted the regeneration of ISCs in vivo and in vitro. Zymosan-A improved the survival of abdominal irradiated mice (81.82% of mice in the treated group vs. 30% of mice in the PBS group), inhibited the radiation damage of intestinal tissue, increased the survival rate of intestinal crypts and the number of ISCs after lethal IR in vivo. Through organoid experiments, we found that Zymosan-A promoted the proliferation and differentiation of ISCs after IR. Remarkably, the results of RNA sequencing and Western Blot (WB) showed that Zymosan-A reduced IR-induced intestinal injury via TLR2 signaling pathway and Wnt signaling pathway and Zymosan-A had no radioprotection on TLR2 KO mice, suggesting that Zymosan-A may play a radioprotective role by targeting TLR2. Moreover, our results revealed that Zymosan-A increased ASCL2, a transcription factor of ISCs, playing a core role in the process of Zymosan-A against IR-induced intestinal injury and likely contributing to the survival of intestinal organoids post-radiation. In conclusion, we demonstrated that Zymosan-A promotes the regeneration of ISCs by upregulating ASCL2.

伤口局部洗消是防原医学实践教学的重要内容,对学员核应急医学救援处置能力的提高发挥了重要作用.构建手部精细动作虚拟仿真训练系统并应用于伤口局部洗消的实践教学,有效克服了传统虚拟仿真技术动作单一、缺乏协同、考核困难等不足,提高了授课质量,促进了新型军事医学人才的培养.

Abstract As a potent target for cancer therapy, ATR mainly regulates homologous recombination (HR)-mediated DNA damage repair. Our previous study first identified that ATR binding long noncoding RNA (lncRNA) is necessary for ATR function and promotes cancer resistance. However, most important lncRNAs, as critical factors for ATR activation, are largely unknown. In the present study, scaRNA2, the most enriched ATR-binding lncRNA, was identified and well characterized. ScaRNA2 was found to be essential for HR-mediated DNA damage repair. Furthermore, scaRNA2 knockdown abrogated the mobilization of ATR and its substrates in response to DNA damage. Mechanistically, scaRNA2 was observed to be necessary for Exo1-mediated DNA end resection and bridged the MRN complex to ATR activation. Using cancer cells and a cell-derived xenograft model, we demonstrated that lentivirus-based knockdown of scaRNA2 effectively increases sensitivity to multiple kinds of chemoradiotherapy. Preclinically, knockdown of scaRNA2 improved the therapeutic effects of radiotherapy on patient-derived organoids and xenograft models. Finally, upregulation of scaRNA2 colocalized with ATR was also found in clinical patients who are resistant to radiotherapy based on tumor regression grades. In conclusion, we identified scaRNA2 as the most abundant lncRNA bound to ATR and uncovered its mechanism in bridging DNA end resection to ATR activation, which could be applied as a potent target for combined cancer treatments with chemoradiotherapy.

为了保证防原医学实践课教学授课的顺利进行,海军军医大学舰船辐射医学防护教研室借助核应急医学救援虚拟仿真实践教学平台,开展了基于虚拟仿真的防原医学线上小班实践教学活动,针对教学设计、教学过程、教学效果等进行了一系列有益的探索,并与以往线下授课的实践教学效果进行对比,发现基于虚拟仿真的防原医学线上实践教学能够克服现场实践教学无法开展的不足,有效满足实践教学需求.课程结束后通过与学员和主讲教员进行交流发现,基于虚拟仿真的线上实践教学比现场实践教学更能调动学员积极性,在切实提高了学员操作能力与协作能力的同时,取得了非常好的实践教学效果.

核安全是国家安全体系的重要组成部分,核伤员应急医学救援是核安全体系的最后一道防线.为了适应核能快速发展新形势带来的核防护新需求,提高核辐射损伤防治教学效果,提升受训学员实战能力,文章围绕核辐射损伤防治教学理论体系、特种技能平台、专用教学装备、训练方法手段四个方面进行改革创新,形成核辐射损伤理论教学新体系,自主研发特种教学训练器材,新建多个核辐射防治技能训练平台,创建"三位一体"综合训练模式,显著提高了人才培养水平.

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.