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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]

This study investigates the elastoplastic stable bearing capacity of prestressed columns. The end restraint of the novel dual-steering plate brace prestressed column is enhanced, augmenting the efficiency of utilizing steel material. The elastoplastic stable bearing capacity of this new prestressed column is 5.41 times greater than that of a standard non-prestressed column. In contrast, the traditional prestressed columns with identical parameters show only a 2.49 to 3.55 times increase. In addition, this study conducts parameter optimization on the prestressed value, the position of the transverse brace, and the size of the transverse brace in the prestressed column. The buckling load escalates rapidly with an increase in the prestress value within a specific range and then diminishes gradually. The bearing capacity peaks when the transverse brace is positioned at the midpoint. As the size of the transverse brace expands, the load-bearing capacity initially rises linearly and subsequently stabilizes. The findings on the elastoplastic stable bearing capacity and parameter optimization are significantly relevant for practical engineering applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A new type of dual-steering prestressed plate column is introduced. Compared to the previous prestressed strut column, this proposed column considers both bending and constraints at ends. The calculation results indicated that the support plate significantly improves the stable bearing capacity and buckling performance of the core steel column. When compared to the proposed column, the bearing capacity of the three-transverse prestressed beam column is 1.51 times smaller, the single-transverse prestressed beam column is 2.43 times lower, and the non-prestressed column is 4.51 times smaller. Moreover, this study examines the influences of effective length, buckling mode, stress nephogram detail, and prestress value. It explores the possibility of implementing this new type of dual-steering prestressed plate column in practical engineering. In addition, the variety and mechanical models of prestressed columns are expanded and refined. [ABSTRACT FROM AUTHOR]

Hydroxyl radicals play an important role in ionizing radiation-induced cellular damage, while hydrogen can selectively reduce hydroxyl radicals in vitro. This study was designed to test the hypothesis that hydrogen-rich PBS may be an effective radioprotective agent in vitro. Compared to cells pretreated without hydrogen, we demonstrated that treating cells with hydrogen-rich PBS before irradiation could significantly inhibit IR-induced apoptosis, increase viability of human intestinal crypt cells, significantly increase endogenous antioxidant, and decrease malondialdehyde and 8-hydroxydeoxyguanosine concentrations of human lymphocyte AHH-1 cells. It is concluded that hydrogen has a potential as an effective and safe radioprotective agent.

Flexible retaining structure is demonstrated to be an effective measure for debris flow prevention in mountainous areas, which can effectively separate water and stone, reduce particle mass, and dissipate kinetic energy. In order to explore the impulsive force and dynamic response of flexible retaining structure impacted by solid-liquid two-phase debris flow, a complex dynamic interaction model of particle-fluid-structure has been established by employing the SPH-DEM-FEM coupling numerical analysis method. In the present study, the process, impulse force, and dynamic response of a flexible retaining structure subjected to debris flow under different slopes were investigated, respectively. The numerical results are compared with those of the calculation formula of the peak impulsive force of the semiempirical debris flow. Meanwhile, the effectiveness of the coupling numerical simulation is verified. The simulation results show that the coupled SPH-DEM-FEM numerical analysis method can visualise the impact of the solid-liquid two-phase debris flow on the flexible retaining structure, reproducing the impact, retaining, water-stone separation, climbing, silting, and deposition process of debris flow. The dynamic time-history curve of the coupling numerical analysis method for the flexible retaining structure is consistent with the results of the existing literature. The debris flow evaluation results of flexible retaining structure impacted by solid-liquid two-phase debris flow are in an order of magnitude with the empirical formula results. Moreover, the results are reliable. The obtained results have a certain reference value for the study on the impulsive force and dynamic response of the flexible retaining structure impacted by solid-liquid two-phase debris flow and the engineering design of the flexible retaining structure. [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]

Reasonable depth of pile embedment is one of the key factors for the success of deep foundation pit projects. This paper has taken a deep foundation pit project in a granite residual soil area in Shenzhen as an example and used physical model tests to study the deformation law of the piles and the surrounding soil during the excavation of the deep foundation pit, revealing the variation law of earth pressure in time and space in the pit and then verified it by numerical simulation. The influence of the embedded depth of the pile on the deformation and earth pressure of the deep foundation pit is then explicitly discussed. The study shows that the embedded depth has a significant effect on the deformation and earth pressure distribution of the foundation pit. The earth pressure in front of the pile tends to approach the passive earth pressure as the embedment depth decreases, while the earth pressure behind the pile is in between the Rankine active earth pressure and the static soil pressure; the settlement value and settlement range of the surrounding soil are doubled. The pile displacement increases as the maximum displacement point rises. The maximum displacement of the pile body was used as the basis for determining the instability of the foundation pit. The optimum embedded depth is obtained when the depth of embedment of the pile is 0.22 H (H is the excavation depth of the foundation pit). [ABSTRACT FROM AUTHOR]

Based on the coupled SPH-DEM-FEM numerical method, this paper analyzes the dynamic interaction of solid debris flow particle-liquid debris flow slurry-retaining dam in order to explore the dynamic response of retaining dam under the impact of the solid-liquid two-phase debris flow and delves into the process of the debris flow impact on the dam, the impact force of debris flow, and the elastic-plastic time-history characteristics of the dam under different slopes of trapezoidal grooves. The calculation results show that the coupled SPH-DEM-FEM method can vividly simulate the impact behavior of the solid-liquid two-phase debris flow on the dam, reproduce the impact, climbing, and siltation in the process of the debris flow impact; the dynamic time-history curve of the retaining dam is consistent with the law of the literature, and the result of the debris flow impact force obtained is close to that of the empirical formula. Moreover, this paper studies the impact force distribution of the debris flow impact process. The results have a certain reference value for the study of the dynamic response of the retaining dam under the impact of the solid-liquid two-phase debris flow and the engineering design of the debris flow-retaining dam. [ABSTRACT FROM AUTHOR]

Thermophilic membrane biofilm reactor (TMBR) for elemental mercury (Hg0) and NO removal in simulated flue gas was investigated at oxygen content of 6% and 60 °C. The performance, the microbial community structures, gene function and the mechanism for Hg0 and NO removal in the TMBR were evaluated. TMBR achieved effective simultaneous Hg0 and NO removal in 210 days of operation, Hg0 and NO removal efficiency were up to 88.9% and 85.3%, respectively. Mercury induced thermophilic community had been formed significantly. Comamonas , Pseudomonas , Desulfomicrobium, Burkholderia and Halomonas were thermophilic mercury resistant bacteria. Brucella , Paracoccus , Tepidiphilus , Proteobacteria, Pseudomonas and Symbiobacterium were nitrifying/denitrifying genera, and had functional genes of mercury and nitrogen metabolism, as shown by16S rDNA and metagenomic sequencing. The biofilm in TMBR was characterized by XPS, HPLC. XPS and HPLC spectra indicate the formation of a mercuric species (Hg2+) from mercury oxidation. TMBR used oxygen as electron acceptor, NO and Hg0 as electron donor in nitrification; O 2 , NO and NO 3 − could be used as electron acceptor and Hg0 as electron donor in denitrification. • Thermophilic membrane bioreactor achieved Hg0 and NO removal simultaneously. • Mercury induced community had been formed significantly. • XPS and HPLC spectra indicate the formation of a mercuric species from mercury oxidation. • The mechanism for Hg0 and NO removal was proposed. [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]

Background: Ionizing radiation often causes severe injuries to radiosensitive tissues, especially haematopoietic system. Novel radioprotective drugs with low toxicity and high effectiveness are required. Prolyl hydroxylases domain (PHD) inhibitors have been reported to protect against radiation‐induced gastrointestinal toxicity. In this study, we demonstrated the protective effects of a PHD inhibitor, roxadustat (FG‐4592), against radiation‐induced haematopoietic injuries in vitro and in vivo. Methods: Tissue injuries were evaluated by Haematoxilin‐Eosin (HE) staining assay. HSCs were determined by flow cytometry with the Lin−Sca‐1+c‐Kit+ (LSK) phenotype. Cell apoptosis was determined by Annexin V/PI staining assay. Immunofluorescence was performed to measure radiation‐induced DNA damage. A western blot assay was used to detect the changes of proteins related to apoptosis. Results: We found that FG‐4592 pretreatment increased survival rate of irradiated mice and protected bone marrow and spleen from damages. Number of bone marrow cells (BMCs) and LSK cells were also increased both in irradiated mice and recipients after bone marrow transplantation (BMT). FG‐4592 also protected cells against radiation‐induced apoptosis and double strand break of DNA. Conclusions: Our data showed that FG‐4592 exhibited radioprotective properties in haematopoietic system both in vivo and in vitro through up‐regulating HIF‐1α, indicating a potential role of FG‐4592 as a novel radioprotector. [ABSTRACT FROM AUTHOR]

Background/Aims: This study investigated the radioprotective properties of three classes of CpG-oligodeoxynucleotides (CpG-ODNs) and the underlying mechanisms. Methods: Mice irradiated at different doses(7Gy or 9Gy) were treated with or without ODNs(50μg via intraperitoneal injection). Assays were performed to determine survival rate and the number of white blood cell in peripheral blood. The levels of granulocyte-colony stimulating factor(G-CSF), interleukin 6(IL-6) and interferon-α(IFN-α) were measured using enzyme-linked immunosorbent assay (ELISA). Results: Survival rate of mice irradiated in 7Gy was increased from 50% to about 100% with ODNs pretreatment. ODNs administration increased the number of WBCs of irradiated mice. G-CSF, IL-6 and IFN-α levels were up-regulated with ODNs treatment. Conclusion: All three classes of ODNs protected mice from irradiationinduced injuries. B-class ODNs exhibited the most potent radioprotective property via the up-regulation of G-CSF and IL-6. [ABSTRACT FROM AUTHOR]

Background/Aims: Radiation therapy is an important treatment for thoracic cancer; however, side effects accompanied with radiotherapy lead to limited tumor control and a decline in patient quality of life. Among these side effects, radiation-induced lung injury (RILI) is the most serious and common. Hence, an effective remedy for RILI is needed. Mesenchymal stromal cells (MSCs) are multipotent adult stem cells that have been demonstrated to be an effective treatment in some disease caused by tissue damage. However, unlike other injuries, RILI received limited therapeutic effects from implanted MSCs due to local hypoxia and extensive reactive oxygen species (ROS) in irradiated lungs. Since the poor survival of MSCs is primarily due to hypoxia and ROS generation, we hypothesize that persistent and adaptive hypoxia treatment induces enhanced resistance to hypoxic stress in implanted MSC. The aim of this study is to investigate whether persistent and adaptive hypoxia treatment of bmMSCs prior to their transplantation in injured mice enhanced survival and improved curative effects in RILI. Methods: Primary bmMSCs were obtained from the marrow of six week-old male C57BL6/J mice and were cultured either under normoxic conditions (21% O2) or hypoxic conditions (2.5% O2). Mice were injected with normoxia/hypoxia MSCs after thoracic irradiation (20 Gy). The therapeutic effects of MSCs on RILI were assessed by pathological examinations that included H&E staining, Masson staining and α-SMA staining; meanwhile, inflammatory factors were measured using an ELISA. The morphology of MSCs in vitro was recorded using a microscope and identified by flow cytometry, cell viability was measured using the CCK-8 assay, the potential for proliferation was detected by the EdU assay, and ROS levels were measured using a ROS fluorogenic probe. In addition, HIF-1α and several survival pathway proteins (Akt, p-Akt, Caspase-3) were also detected by western blotting. Results: Implanted MSCs alleviated both early radiation-induced pneumonia and late pulmonary fibrosis. However, hypoxia MSCs displayed a more pronounced therapeutic effect compared to normoxia MSCs. Compared to normoxia MSCs, the hypoxia MSCs demonstrated greater cell viability, an enhanced proliferation potential, decreased ROS levels and increased resistance to hypoxia and ROS stress. In addition, hypoxia MSCs achieved higher activation levels of HIF-1α and Akt, and HIF-1α played a critical role in the development of resistance. Conclusion: Hypoxia enhances the therapeutic effect of mesenchymal stromal cells on radiation-induced lung injury by promoting MSC proliferation and improving their antioxidant ability, mediated by HIF-1α. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play an important role in regulating cancer stem cell (CSC). Previous studies have shown that microRNA-221/222 (miR-221/222) cluster are involved in the propagation of breast cancer stem cell (BCSC), however, the underlying molecular mechanisms are still not fully understood. In this study, we found that miR-221/222 were overexpressed in highly aggressive breast cancer MDA-MB-231 cells, that are enriched in markers for epithelial-mesenchymal transition (EMT) and BCSCs, than in MCF-7 cells. Phosphatase and tensin homolog (PTEN) was confirmed to be the target of miR-221/222 in breast cancer cells. MiR-221/222 enhanced breast cancer cell growth, migration and invasion by downregulating PTEN. Importantly, both ectopic expression of miR-221/222 and PTEN knockdown increased the mammosphere formation capacity and the expression of the stemness marker ALDH1. MiR-221/222 lentivirus vector infected MCF-7 cells produced larger subcutaneous tumors, while shRNA vector of PTEN showed similar trend. Along with the downregulation of PTEN caused by miR-221/222 in the breast cancer cells and the xenograft tumor tissues, Akt phosphorylation (p-Akt), NF-κB p65 and phosphorylated p65 (p-p65), and cyclooxygenase-2 (COX-2) were all overexpressed compared to the negative control. Taken together, our findings indicate that miR-221/222 play a critical role in the propagation of BCSCs and tumor growth possibly through targeting PTEN, which in turn activating the Akt/NF-κB/COX-2 pathway. MiR-221/222 might represent the potential target of breast cancer therapy. [ABSTRACT FROM AUTHOR]

Exposure to ionizing radiation (IR) often reduce the helper T (Th) 1 like function, resulting in a Th1/Th2 imbalance, which could affect the efficacy of cancer radiotherapy. As the most potent antigen presenting cells, dendritic cells (DC) can be divided into several subsets with specialized function. However, there is no literature covering the changes of DC subsets and their roles in immune regulation in response to IR. In the present study, we were aimed to investigate the changes of DC subsets after IR and its relationship with Th1/Th2 immunity. We found a significant decrease of BDCA3 + DC in the blood of patients treated with radiotherapy. CD8 + DC, a mouse equivalent of human BDCA3 + DC, was also found decreased in mice spleen, peripheral blood and lymph node tissues after irradiation. As CD8 + DC mainly induce Th1 immunity, we tested the changes of Th1/Th2 response and found that IR caused a repression of Th1 immunity, indicating a possible role of CD8 + DC in radiation-induced Th1/Th2 imbalance. We also found that a CD8 + DC-inducing cytokine, Fms-like tyrosine kinase 3 ligand (FLT3 ligand), restored CD8 + DC and reversed Th1/Th2 shift. And then we found that bone marrow cells from irradiated mice differentiated into less CD8 + DC, which was also protected by FLT3 ligand. In conclusion, our data showed that IR induced a decrease of CD8 + DC and Th1/Th2 shift, which was reversed by Flt3 ligand treatment, suggesting a novel mechanism for radiation-induced immunosuppression. [ABSTRACT FROM AUTHOR]

Background The miR-221/222 cluster has been discovered to function as oncogene in human malignancies including breast cancer. However, the role of miR-221/222 in the self-renewal of breast cancer stem cells (BCSCs) is not fully understood. In this study, we examined the impact and mechanism of miR-221/222 on the breast cancer cell viability, migration and invasion, and propagation of BCSCs. Methods Human breast cancer cell line MCF-7 was transfected with miR-221/222 mimics or inhibitors to overexpress or knock down miR-221/222 respectively using Lipofactamine 2000. The biological effects of miR-221 and miR-222 were then assessed by cell proliferation assay, colony formation assay and transwell chamber assays. CD44/CD24 staining and mammosphere formation assay were performed to evaluate the ability of BCSCs self-renewal. Potential target gene phosphatase and tensin homolog (PTEN) and its downstream effector, phosphorylated Akt (p-Akt) were identified by Western blot and qRT-PCR methods. Results PTEN, a tumor suppressor gene, was confirmed as a target of miR-221/222 in breast cancer cell line MCF-7. Downregulation of PTEN by miR-221/222 increased the phosphorylation of Akt. Enforced expression of miR-221/222 promoted breast cancer cell proliferation, migration and invasion via targeting PTEN/Akt pathway. Importantly, ectopic expression of miR-221/222 enriched the proportion of CD44 + /CD24 − BCSCs and improved the mammosphere formation capacity through targeting PTEN/Akt pathway. Blocking the endogenous miR-221/222 restored PTEN expression and subsequently decreased Akt phosphorylation, and thereby reversed this phenotype. Conclusions Our results suggested that miR-221/222 enhance breast cancer growth, migration and invasion, meanwhile propagate the self-renewal of BCSCs. This is achieved possibly through targeting PTEN/Akt pathway. miR-221/222 might be a novel therapeutic candidate for human breast cancer. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy produced unwanted side effect on normal tissues, such as radiodermatitis. Hydrogen was previously shown capable of radiation protective in both animals and cell cultures. The effect of hydrogen was now to be investigated on radiation-induced cutaneous. Objective: Development of dermatitis is a frequent side effect of radiotherapy of patients with head-and-neck cancer. Here we analyzed the radioprotective efficacy of hydrogen under conditions of local, single-dose or fractionated radiation treatment, and its possible molecular mechanisms. Methods: Rats received either single-dose or fractioned irradiation of the head-and-neck area with or without subcutaneous injection of hydrogen solution before irradiation. In vitro, the effect of hydrogen medium on radiation-induced cell viability, apoptosis, and biochemical assays was measured. Result: Hydrogen significantly reduced the severity of dermatitis, accelerated tissue recovery, and reduced the extent of radiation-induced weight loss in rats after a single dose of 15 or 20 Gy but not 25 Gy of radiation. Hydrogen was also protective from cumulative doses of 30 Gy delivered in three fractions, respectively. Hydrogen also protect HaCaT cells from radiation-induced injury, it could significantly inhibit ionizing injury. Conclusion: These results suggest that hydrogen has a positive effect on acute radiodermatitis. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs, which usually bind to the 3'-untranslated region of target mRNAs and are capable of inducing posttranscriptional gene regulation by blocking translation or by degrading the target mRNA. However, the expression level of miR-23 in radiation induced carcinogenesis is largely unknown. Methods: Radiation induced thymic lymphoma model in BALB/c mice was set up. miR-23a & miR-23b miRNA levels in different tissues and cells were detected by real-time qPCR. miR-23a/b inhibitor and miR-23a/b mimics were transfected to lymphoma cells and the target of miR-23a/b was identified by microRNA target prediction and Luciferase assays. Results: We found that miR-23a & miR-23b were up-regulated in radiation induced thymic lymphoma tissue samples. Cell death and apoptosis were increased by miR-23a/b inhibitor and decreased by miR-23a/b mimics in lymphoma cells. Computational analysis found a putative target site of miR-23a/b in the 3′UTR of Fas mRNA, which was verified by luciferase reporter assay. Forced over-expression of miR-23a/b decreased the level of Fas protein. Moreover, over-expression of Fas rescued the pro-proliferation effect of miR-23, indicating Fas is a direct mediator of miR-23 functions. Furthermore, contrast to miR-23a/b which was up regulated, the Fas expression level was down-regulated and inversely correlated with miR-23 in split radiation induced lymphoma tissue samples. Finally, our data also indicates that miR-23a could repress Fas much more potent than miR-23b and the additional region besides conserved seed pairing enables miR-23a's higher regulation. Conclusions: In this study, using a radiation induced thymic lymphoma model in BALB/c mice, We conclude that the expression of miR-23a/b is up-regulated in radiation-induced thymic lymphoma and it maybe a novel therapeutic target of that cancer. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Exposure of high dose ionizing radiation is lethal. Signal pathways involved in radiation biology reaction still remain illdefined. Lipopolysaccharides (LPS), the ligands of Toll-like receptor 4(TLR4), could elicit strong immune responses. Glycogen synthase kinase-3β(GSK-3β) promotes the production of inflammatory molecules and cell migration. Inhibition of GSK-3β provides protection against inflammation in animal models. The aim of the study was to investigate role of GSK-3β in LPS shock and ionizing radiation. Methods: WT or IL-6-/-mice or cells were pretreated with SB216763, a GSK-3β inhibitor, and survival of the mice was determined. Cell viability was assayed by Cell Counting Kit. Apoptosis was assayed by Annexin V-PI double staining. Serum concentrations of IL-6 and TNF-α were determined by ELISA. Results: SB216763 attenuated LPS induced mice or cell death but aggravated radiation induced mice or cell death. SB216763 reduced IL-6, but not TNF-α levels in vivo. IL-6-/- mice were more resistant to LPS-induced death but less resistant to radiation-induced death than wild type mice. Conclusions: Inhibition of GSK-3β conferred resistance to LPS shock but fostered death induced by ionizing radiation. Inhibition of GSK-3β was effective by reducing IL-6. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To investigate the potential protective role of molecular hydrogen (H2) against 12C6+ heavy ion radiation, which is a major hazard for space travel and has been also widely used in heavy ion radiotherapy. Materials and methods: H2 was dissolved in Roswell Park Memorial Institute (RPMI) 1640 medium under high pressure (0.4 Mpa) to a saturated level by using an apparatus produced by our department. A 2-[6-(4′-hydroxy) phenoxy-3H-xanthen-3-on-9-yl] benzoate (HPF) probe and a 2′,7′-Dichlorodihydrofluorescein diacetate (H2DCFH-DA) fluorescent dye were used to measure the intracellular reactive oxygen species (ROS) level. Cell apoptosis were determined by double-staining with Annexin V-fluorescein isothiocyanate (Annexin V-FITC) and propidium iodide (PI) as well as a Hoechst 33342 staining method alternatively. Subsequently, cell cycle analysis was performed using a PI staining method and the expression of apoptotic protein was examined by Western blot. Results: In this study, we demonstrated H2 reduced ROS level in Human lymphocyte AHH-1 cells as well as in the radiolysis of water. Our data also showed H2 attenuated 12C6+ radiation- induced cell apoptosis and also alleviated radiation-induced G2/M cell cycle arrest. Heavy ion radiation-induced Caspase 3 activation was also inhibited by H2 treatment. Conclusion: In conclusion, these data showed that H2 attenuated 12C6+ radiation-induced cell apoptosis through reducing the ROS level and modulating apoptotic molecules, thus indicating the potential of H2 as a safe and effective radioprotectant. [ABSTRACT FROM AUTHOR]

Background/Aims: The ionizing radiation (IR) has been applied in clinical treatment for many years and the radiosensitivity is crucial to the treatment. Radiosensitivity of cells is subjected to many environmental factors, such as hypoxia and temperature. Hyperosmolality as a common environmental factor has been demonstrated to be associated with survival and apoptosis of cells in many studies. Thus we investigated the influence of hyperosmolality on cells radiosensitivity. Methods: We examined the viability and surviving fraction of L-O2 cells of irradiated L-O2 cells, and detected the effect on AHH-1 cells by flow cytometry, in order to investigate the effect of short-term hyperosmolality pretreatment on cells radiosensitivity. Comet assay was used to assess the DNA strand breaks. Then the detection of Akt1 by western blot and the process of regulatory volume increase by CYSY-TT were involved in the mechanism. Result: We demonstrated that a short-term hyperosmolality pretreatment on cells could reduce their radiosensitivity. Further research indicated that the short-term hypertonic condition could induce regulatory volume increase (RVI), which activated Akt1 and degenerated the IκB-α. This process was associated with reduced cells radiosensitivity. Finally, we used the flufenamic acid (FFA), a blocker to cation channels (HICCs) to inhabit RVI and consequently inhabit the protective effect of hyperosmolality on irradiated cells. Conclusion: a short-term hyperosmolality pretreatment could reduce the cells radiosensitivity by RVI and following activation of Akt1. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Aplasitc anemia (AA) is a bone marrow failure syndrome characterized by an immune-mediated destruction of hematopoietic stem cells. Though clinical symptoms could be ameliorated by bone marrow transplantation and/or immunosuppressive therapy, frequent recurrence and especially evolution of clonal hematologic diseases remains problematic clinically. Cytokines such as interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secreted by autologous T cells are closely related with the development of AA. Hydrogen-rich solution was reported to inhibit the levels of cytokines including INF-γ, TNF-α and IL-6 in vivo in recent studies. This study was to investigate the potential therapeutic effects of hydrogen-rich solution on AA in vivo. Methods: AA model was determined in vivo by mice and body weights of the mice were used as the basic physiological index. Peripheral blood cells were calculated to evaluate the hematologic recovery degree. Bone marrow nucleated cells (BMNCs), tissue histology, as well as CFU-S and CFU-GM forming units were used to evaluate the recovery of bone marrow microenvironment. The ratio of CD4+ and CD8+ cells were examined along with cytokine levels in serum to determine the efficacy of H2-rich solution on the affected immunological functions. Results: Body weight and number of peripheral blood cells were significantly improved for mice in the H2-rich solution treated groups as compared with those with AA. The number of BMNCs and CFUs increased markedly and the bone marrow microenvironment was also improved significantly. The experimental group restrained the cell apoptosis, relieved hyperemia and accelerated tissue repair. The number of CD4+ and CD8+ cells as well as the ratio of CD4/CD8 increased to normal gradually, while the levels of TNF-α, IFN-γ, and IL-6 in serum decreased after H2-rich solution treatment. Conclusion: Our study firstly showed that hydrogen-rich solution accelerated the recovery of either hematological or immunological recovery on aplastic anemia mice. This finding suggests hydrogen-rich solution as a potential clinical therapeutic agent for AA. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Effect of ionizing radiation on cutaneous dendritic cells (cDC) is critical to its influence on immune status of the skin, which plays an important role in the progression and recovery of radiation skin sickness. This study was to study the influence of whole body irradiation (WBI) on the cDC. Methods: Density of epidermal and dermal DC was determined with a fluorescent microscopy and the DC numbers in lymph node were measured by flow cytometry. A FITC induced migration assay was also used to study the migration of DC. The expressions of cytokines and chemokines were evaluated by Realtime PCR, and the protein level of was measured by Western blot. Results: WBI caused depletion of cDC in epidermal as well as dermal and augmented FITC-induced migration of DC to the draining lymph node (LN). The number of DC migrated from ear explants to the CCL19-containing medium also increased after exposure to WBI. It was also found that WBI increased mRNA level of CCL19/CCL21 as well as CCR7 in LN and skin tissue. The expressions of TNFα, IL-1α, IL-1β, and IL-6 in skin tissues were also greatly induced by WBI in a dose dependent manner. Finally, we found that WBI induced translocation of nuclear factor κB (NF-κB) and that the radiation-induced migration of DC was blocked by NF-κB inhibitor or TLR4 knockout. Conclusion: WBI caused cDC depletion through induction of DC migration to the draining LN, which might result from the activation of NF-κB and the induction of inflammatory microenvironment within the skin. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Our recent studies suggest that H2 (hydrogen) has a potential as a novel radioprotector without known toxic side effects. The present study was designed to examine the underlying radioprotective mechanism of H2 and its protective role on irradiated germ cells. Produced by the Fenton reaction and radiolysis of H2O, hydroxyl radicals (•OH) were identified as the free radical species that were reduced by H2. We used a H2 microelectrode to dynamically detect H2 concentration in vivo, and found H2 significantly reduced in situ fluorescence intensity of hydroxyphenyl fluorescein; however, as we treated the mice with H2 after irradiation, the decrease is not significant. We found that pre-treatment of H2 to IR (ionizing radiation) significantly suppressed the reaction of •OH and the cellular macromolecules which caused lipid peroxidation, protein carbonyl and oxidatively damaged DNA. The radioprotective effect of H2 on male germ cells was supported by ameliorated apoptotic findings examined by morphological changes and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) in testicular tissue, and by preserved viability of stem spermatogonia examined for testicular histological parameters, daily sperm production and sperm quality; we used WR-2721 [S-2-(3-aminopropylamino)ethyl phosphorothioic acid] as a reference compound. Our results represent the first in vivo evidence in support of a radioprotective role of H2 by neutralizing •OH in irradiated tissue with no side effects. [ABSTRACT FROM AUTHOR]

Landslides frequently occur because of natural or human factors. Landslides cause huge losses to the economy as well as human beings every year around the globe. Landslide susceptibility prediction (LSP) plays a key role in the prevention of landslides and has been under investigation for years. Although new machine learning algorithms have achieved excellent performance in terms of prediction accuracy, a sufficient quantity of training samples is essential. In contrast, it is hard to obtain enough landslide samples in most the areas, especially for the county-level area. The present study aims to explore an optimization model in conjunction with conventional unsupervised and supervised learning methods, which performs well with respect to prediction accuracy and comprehensibility. Logistic regression (LR), fuzzy c-means clustering (FCM) and factor analysis (FA) were combined to establish four models: LR model, FCM coupled with LR model, FA coupled with LR model, and FCM, FA coupled with LR model and applied in a specific area. Firstly, an inventory with 114 landslides and 10 conditioning factors was prepared for modeling. Subsequently, four models were applied to LSP. Finally, the performance was evaluated and compared by k-fold cross-validation based on statistical measures. The results showed that the coupled model by FCM, FA and LR achieved the greatest performance among these models with the AUC (Area under the curve) value of 0.827, accuracy of 85.25%, sensitivity of 74.96% and specificity of 86.21%. While the LR model performed the worst with an AUC value of 0.736, accuracy of 77%, sensitivity of 62.52% and specificity of 72.55%. It was concluded that both the dimension reduction and sample size should be considered in modeling, and the performance can be enhanced by combining complementary methods. The combination of models should be more flexible and purposeful. This work provides reference for related research and better guidance to engineering activities, decision-making by local administrations and land use planning. [ABSTRACT FROM AUTHOR]