Heat-killed Salmonella typhimurium mitigated radiation-induced lung injury.

Radiation-induced lung injury (RILI) is a serious complication in thoracic tumour radiotherapy. It often occurs in clinical chest radiotherapy and acute whole-body irradiation (WBI) caused by nuclear accidents or nuclear weapon attack. Some radioprotective agents have been reported to exert protective effects when given prior to radiation exposure, however, there is no treatment strategy available for preventing RILI. In this study, we demonstrated that heat-killed Salmonella typhimurium (HKST), a co-agonist of Toll-like receptors 2 (TLR2), Toll-like receptors 4 (TLR4) and Toll-like receptors 5 (TLR5), mitigated radiation-induced lung injury through the transforming growth factor-ß (TGF-ß) signalling pathway. We found that HKST alleviated lung hyperaemia and pathological damage after irradiation, indicated that HKST inhibits the early inflammatory reaction of radiation-induced lung injury. Then, for the first time, we observed HKST reduced collagen deposit induced by irradiation in the later phase (7-14 week) of RILI, and we found that HKST inhibited radiation-induced cell apoptosis in lung tissues. We found that HKST reduced the level of TGF-ß and regulated its downstream signalling pathway. Finally, it was found that HKST inhibited radiation-induced epithelial-mesenchymal transition (EMT) in lung tissues. In conclusion, our data showed that HKST effectively mitigated RILI through regulating TGF-ß, provide novel treatment strategy for RILI in whole-body irradiation and radiotherapy.

Predictors of Progression in Intraplaque Hemorrhage Volume in Patients With Carotid Atherosclerosis: A Serial Magnetic Resonance Imaging Study.

Background and Purpose: This study aimed to investigate the arterial disease risk factors for the progression of intraplaque hemorrhage (IPH) in patients with carotid atherosclerosis using serial high-resolution magnetic resonance (MR) imaging. Methods: Consecutive symptomatic patients who had MRI evidence of intraplaque hemorrhage present in the ipsilateral carotid artery with respect to the side of the brain affected by stroke or TIA were recruited in the study. All the patients underwent follow-up MR imaging at least 6 months after baseline. The annual change in IPH and other carotid plaque morphology was calculated, and a tertile method was used to classify the plaques as progressed or not with respect to IPH volume using the software CASCADE. Logistic regression and receiver operating characteristic (ROC) curve were conducted to evaluate the risk factors for the progression of IPH. Results: A total of thirty-four symptomatic patients (mean age: 67.1 years, standard deviation [SD]: 9.8 years, 27 men) were eligible for the final analysis, and contralateral plaques containing IPH were seen in 11 of these patients (making 45 plaques with IPH in total). During mean 16.6-month (SD: 11.0 months) follow-up, the overall annual change in IPH volume in 45 plaques with IPH was mean -10.9 mm3 (SD: 49.1 mm3). Carotid plaques were significantly more likely to be classified in progressed IPH group if the patient was taking antiplatelet agent at baseline (OR: 9.76; 95%CI: 1.05 to 90.56; p = 0.045), had a baseline history of current or past smoking (OR: 9.28; 95%CI: 1.26 to 68.31; p = 0.029), or had a larger baseline carotid plaque-containing vessel wall volume (OR: 1.36 per 10 mm3; 95%CI: 1.02 to 1.81; p = 0.032) after adjustments for confounding factors. ROC analysis indicated that the combination of these three risk factors in the final model produced good discriminatory value for the progressed IPH group (area under the curve: 0.887). Conclusions: Taking an antiplatelet agent at baseline, a baseline history of current or past smoking and larger baseline carotid plaque-containing vessel wall volume were independently predictive of plaques being in the progressed IPH group. Our findings indicate that awareness and management of such risk factors may reduce the risk of intraplaque hemorrhage progression.