Glycyrrhizin mitigates radiation-induced acute lung injury by inhibiting the HMGB1/TLR4 signalling pathway.

Radiation-induced lung injury (RILI) is the major complication of thoracic radiation therapy, and no effective treatment is available. This study explored the role of high-mobility group box 1 (HMGB1) in acute RILI and the therapeutic effect of glycyrrhizin, an inhibitor of HMGB1, on RILI. C57BL/6 mice received a 20 Gy dose of X-ray radiation to the whole thorax with or without administration of glycyrrhizin. Severe lung inflammation was present 12 weeks after irradiation, although only a mild change was noted at 2 weeks and could be alleviated by administration of glycyrrhizin. Glycyrrhizin decreased the plasma concentrations of HMGB1 and sRAGE as well as TNF-α, IL-1ß and IL-6 levels in the bronchoalveolar lavage fluid (BALF). The expression of RAGE was decreased while that of TLR4 was significantly increased at 12 weeks, but not 2 weeks, after irradiation in mouse lung tissue. In vitro, the expression of TLR4 increased in RAW 264.7 cells after conditioning with the supernatant from the irradiated MLE-12 cells containing HMGB1 but showed no change when conditioned medium without HMGB1 was used. However, conditioned culture had no effect on RAGE expression in RAW 264.7 cells. Glycyrrhizin also inhibited the related downstream transcription factors of HMGB/TLR4, such as NF-κB, JNK and ERK1/2, in lung tissue and RAW 264.7 cells when TLR4 was activated. In conclusion, the HMGB1/TLR4 pathway mediates RILI and can be mitigated by glycyrrhizin.

Pituitary adenylate cyclase-activating polypeptide ameliorates radiation-induced cardiac injury.

Radiation-induced heart disease (RIHD) is a common sequelae of thoracic irradiation. Currently, there is no effective prevention and treatment strategy. Oxidative stress is associated with the development of RIHD. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) has been defined as the multipotent properties of cytoprotective effect on its anti-apoptotic and antioxidant activities. Here, we set to investigate whether PACAP38 plays a role in attenuating RIHD. We established radiation-related cardiac injury models using 6MV X-ray based on H9C2 cardiomyocytes and male C57/BL6 mice which were pre-treated with PACAP38 prior to radiation exposure. PACAP38 protected mice from radiation-induced histological damage including myocardial apoptosis and fibrosis. Also, cell viability and colony-forming efficiency were enhanced and intracellular ROS generation was reduced in PACAP38 treated H9C2 cardiomyocytes exposed to radiation. Moreover, PACAP38 suppressed myocardial apoptosis and G2/M arrest through blunting the radiation-induced down-regulation of Bcl-2, CyclinB1 and CDC2, and inhibiting the up-regulation of Bax. Furthermore, irradiation resulted in activating of NRF2 and HO-1 expressions were further enhanced by PACAP38 in H9C2 cells and the protective effect of PACAP38 was partially blocked by NRF2 siRNA silencing. In summary, PACAP38 has the potential to effectively protect against acute radiation-induced cardiac injury and its cardioprotective effect involves upregulation of NRF2/HO-1-dependent signaling activation.

Intraoperative radiotherapy for the treatment of thyroid cancer: a pilot study.

We preliminarily evaluated the clinical feasibility and efficacy of intraoperative radiotherapy in patients with thyroid carcinoma. Nine thyroid cancer patients received intraoperative radiotherapy using an Intrabeam system. The dose was 3-4 Gy and the irradiation time ranged from 1 min 32 s to 7 min 33s. One case was a primary thyroid carcinoma, while the other cases were recurrent disease. Adverse effects, recurrence and survival were analyzed. In one patient, poorly differentiated thyroid carcinoma recurred 5 months after treatment, one patient developed a postoperative tracheal skin fistula, and one patient developed a wound infection. Because the affected areas were treated with both surgical resection and then radiotherapy, it is difficult to know which of those led to the adverse effects. Nonetheless, our results indicate that intraoperative radiotherapy can relieve the symptoms associated with thyroid cancer and improve the quality of life for these patients. It thus appears feasible to treat thyroid cancer patients with intraoperative radiotherapy.