Radioprotective Effects of Heat-Killed Mycobacterium Tuberculosis in Cultured Cells and Radiosensitive Tissues.

BACKGROUND: Exposure to ionizing radiation (IR) often causes severe damage to radiosensitive tissues, which limits the use of radiotherapy in cancer patients. Novel safe and effective radioprotectant is urgently required. It has been reported toll like receptor 2 (TLR2) plays a critical role in radioresistance. In this study, we demonstrated the protective effects of Heat-Killed Mycobacterium tuberculosis (HKMT), a potent TLR2 agonist, against IR. METHODS: Cell survival and apoptosis were determined by CCK-8 assay and Annexin V assay, respectively. An immunofluorescence staining assay was used to detect the translocation of nuclear faktor-kappa beta (NF-kB) p65. Tissue damage was evaluated by Haematoxilin-Eosin (HE) staining assay. We also used a flow cytometry assay to measure the number of nucleated cells and CD34+ hemopoietic stem cells in bone marrow. A western blot assay was used to detect the changes of proteins involving TLR signaling pathway. RESULTS: We found that HKMT increased cell viability and inhibited cell apoptosis after irradiation. HKMT induced NF-kB translocation and activated Erk1/2, p38 signaling pathway. HKMT also protected bone marrow and testis from destruction. Radiation-induced decreases of nucleated cells and CD34+ hemopoietic stem cells in bone marrow were also inhibited by HKMT treatment. We found that radiation caused increase of inflammatory cytokines was also suppressed by HKMT. CONCLUSION: Our data showed that HKMT exhibited radioprotective effects in vivo and in vitro through activating NF-kB and MAPK signaling pathway, suggesting a potential of HKMT as novel radioprotector.

Military Trauma and Surgical Procedures in Conflict Area: A Review for the Utilization of Forward Surgical Team.

Introduction: Forward surgical teams (FSTs) have been used as highly mobile surgical facilities that provide "damage control" medical support in modern wars. FST regiments differ greatly in different armed services and nations. We systemically reviewed the utilization of FSTs around the world with an emphasis on the medical conditions and workloads encountered by FSTs in modern wars. Materials and Methods: We searched for terms related to FSTs, such as "Forward Surgical Team" and "Field Surgical Team," in the PubMed, EMBASE, Web of Science, and MEDLINE databases and collected any articles that provided numerical data on the organization of medical personnel combat casualty characteristics, including the casualty composition, injury types and locations, and mechanisms of injury, and surgical procedures performed. Technical articles, case reports of specific types of injury or disease, and literature reviews of previous experiences and logistical theories were discarded. Results: We identified 24 articles involving 29 FSTs that were included in the analysis. The FSTs were typically composed of 8-20 medical personnel and had limited medical capacity. Battle-related injuries constituted approximately two-thirds of all injury types treated by the FSTs. The extremities, torso, and head and neck were the three most frequently injured sites and accounted for approximately 51.1%, 16.6%, and 13.2% of all wounds, respectively. The three most frequent injury mechanisms were fragments or explosive injuries (44.8%), gunshot wounds (28.1%), and motor vehicle accidents/road traffic accidents (9.1%). Soft tissue surgeries (41.0%) and orthopedic operations (31.6%) were the two procedures that were most frequently performed by the FSTs. The average numbers of surgical procedures performed by small FSTs (1.27/unit·day) and full FSTs (1.28/unit·day) seemed to be comparable. Conclusion: Modern conflict may require more flexible small FSTs, especially during the initial phases of war. More orthopedic surgeons should be included in FSTs, and orthopedic skill training should be intensified before deployment. The utilization of FSTs and level III facilities must be evaluated within the context of the battlefield conditions, medical care requirements, and evacuation efficiency.

Heat-killed salmonella typhimurium (HKST) protects mice against radiation in TLR4-dependent manner.

It is urgently required to develop novel safe and effective radioprotectors to alleviate radiation damages. Recently, several toll like receptors (TLRs), including TLR2, TLR4, TLR5, TLR9, have been proved to exert protective effects against ionizing radiation. Due to different tissue-distribution and distinct functions of TLRs, we hypothesized that co-activation of multiple TLRs simultaneously may produce extensive and stronger radioprotective effects. In this study, we found the co-agonist of TLR2, TLR4 and TLR5, heat-killed salmonella typhimurium (HKST) significantly inhibited radiation-induced cell apoptosis, increased cell survival and alleviated DNA damage. HKST also prolonged animal survival and protected radiosensitive tissues against radiation damages, such as bone marrow, spleen and testis. Decrease of CD4+ and CD8+ cells were also reversed by HKST treatment. By using TLR2 and TLR4 knockout mice, we found that most of radioprotective effects of HKST were abrogated in TLR4 knock out mice. And HKST failed to inhibited cell apoptosis in TLR5 knock down cells. In conclusion, we demonstrated that HKST effectively protected cells and radiosensitive tissues against radiation injury in a TLR4 biased mechanism, suggesting HKST as a potential radioprotector with low toxicity.