Space Radiation-Induced Hematopoietic Stem Cell Injury

Space radiation is an unavoidable health risk during space activities. Hematopoietic cells are sensitive to radiation including proton and oxygen radiation and so on. Understanding the mechanisms responsible for detrimental effects of space radiation is important to achieve countermeasures protecting hematopoietic stem cells (HSCs), which generates different hematopoietic populations. However, the biological effects of various sources of space radiation on HSCs are not understood well. Induction of cellular apoptosis, reactive oxygen species (ROS), and DNA damage upon space radiation is believed to be critical mediators for HSC damage. In this chapter, we will mainly discuss the biological effectiveness of proton and oxygen radiation on the numbers and function of HSCs. Space radiation-induced apoptosis, ROS, and DNA damage were examined as well, which will provide foundation to develop novel strategies protecting HSCs from space radiation

DNA Checkpoint and Repair Factors Are Nuclear Sensors for Intracellular Organelle Stresses-Inflammations and Cancers Can Have High Genomic Risks.

Under inflammatory conditions, inflammatory cells release reactive oxygen species (ROS) and reactive nitrogen species (RNS) which cause DNA damage. If not appropriately repaired, DNA damage leads to gene mutations and genomic instability. DNA damage checkpoint factors (DDCF) and DNA damage repair factors (DDRF) play a vital role in maintaining genomic integrity. However, how DDCFs and DDRFs are modulated under physiological and pathological conditions are not fully known. We took an experimental database analysis to determine the expression of 26 DNA D

Transient Inhibition of mTORC1 Signaling Ameliorates Irradiation-Induced Liver Damage

Recurrent liver cancer after surgery is often treated with radiotherapy, which induces liver damage. It has been documented that activation of the TGF-β and NF-κB signaling pathways plays important roles in irradiation-induced liver pathologies. However, the significance of mTOR signaling remains undefined after irradiation exposure. In the present study, we investigated the effects of inhibiting mTORC1 signaling on irradiated livers. Male C57BL/6J mice were acutely exposed to 8.0 Gy of X-ray total body irradiation and subsequently treated with rapamycin. The effects of rapamycin treatment on irradiated livers were examined at days 1, 3, and 7 after exposure. The results showed that 8.0 Gy of irradiation resulted in hepatocyte edema, hemorrhage, and sinusoidal congestion along with a decrease of ALB expression. Exposure of mice to irradiation significantly activated the mTORC1 signaling pathway determined by pS6 and p-mTOR expression via western blot and immunostaining. Transient inhibition of mTORC1 signaling by rapamycin treatment consistently accelerated liver recovery from irradiation, which was evidenced by decreasing sinusoidal congestion and increasing ALB expression after irradiation. The protective role of rapamycin on irradiated livers might be mediated by decreasing cellular apoptosis and increasing autophagy. These data suggest that transient inhibition of mTORC1 signaling by rapamycin protects livers against irradiation-induced damage

Transfer pricing of innovation considering matches between innovation and technology in firms

Firms can purchase innovation results to improve their technology. In this context, the key to transfer success is reasonably priced innovation results. Considering the match between innovation results and firm technology, this study analyzes the nonlinear improvement effect of innovation results on technology. The pricing decision is then assessed by a game model of the innovation results transfer and pricing that is based on the entire innovation process, including research and development (R&D) and transfer. Then the method for transfer pricing of innovation results is obtained from the equilibrium of game. The results show that firms tend to evaluate innovation results by matching them with their own technologies, and then make bids based on the R&D costs. Here, innovation results are obtained by firms with high-level matching. After considering the matching, the transfer pricing of innovative results will prosper the transfer market and improve the success rate of transfer. Several factors affect the possibility of transfer of innovation results and their price, including the R&D ability of the institution, the technology levels of firms, and the technological competition between firms. These conclusions were validated using a numerical example

Comprehensive Evaluation of Low-Carbon City Competitiveness under the “Dual-Carbon” Target: A Cross-Sectional Comparison between Huzhou City and Neighboring Cities in China

Under the background of “dual-carbon” target construction, the low-carbon environmental protection and ecological construction of Huzhou city in China have received high attention. To scientifically measure the low-carbon construction effect of the city, this study constructs a reasonable comprehensive evaluation system of low-carbon city competitiveness from four aspects, including low-carbon economic foundation, low-carbon lifestyle, low-carbon environmental construction, and low-carbon technology development. An integrated weight model of attributes consisting of the analytic hierarchy process (AHP) and entropy weight method is then established, and on this basis, an integrated TOPSIS model is constructed to assess the development of low-carbon competitiveness in Huzhou City. A horizontal comparative analysis of five cities around Huzhou is also conducted, and the current level of low-carbon competitiveness of cities in the central region of the Yangtze River Delta is further explored. Finally, several relevant reference suggestions for Huzhou city are provided to build an ecological model city and a green low-carbon national model and help the government to accelerate the pace of building a low-carbon city in the whole region

Molecular Modulation of Fetal Liver Hematopoietic Stem Cell Mobilization into Fetal Bone Marrow in Mice

Development of hematopoietic stem cells is a complex process, which has been extensively investigated. Hematopoietic stem cells (HSCs) in mouse fetal liver are highly expanded to prepare for mobilization of HSCs into the fetal bone marrow. It is not completely known how the fetal liver niche regulates HSC expansion without loss of self-renewal ability. We reviewed current progress about the effects of fetal liver niche, chemokine, cytokine, and signaling pathways on HSC self-renewal, proliferation, and expansion. We discussed the molecular regulations of fetal HSC expansion in mouse and zebrafish. It is also unknown how HSCs from the fetal liver mobilize, circulate, and reside into the fetal bone marrow niche. We reviewed how extrinsic and intrinsic factors regulate mobilization of fetal liver HSCs into the fetal bone marrow, which provides tools to improve HSC engraftment efficiency during HSC transplantation. Understanding the regulation of fetal liver HSC mobilization into the fetal bone marrow will help us to design proper clinical therapeutic protocol for disease treatment like leukemia during pregnancy. We prospect that fetal cells, including hepatocytes and endothelial and hematopoietic cells, might regulate fetal liver HSC expansion. Components from vascular endothelial cells and bones might also modulate the lodging of fetal liver HSCs into the bone marrow. The current review holds great potential to deeply understand the molecular regulations of HSCs in the fetal liver and bone marrow in mammals, which will be helpful to efficiently expand HSCs in vitro

Inhibition of mTORC1 signaling protects kidney from irradiation-induced toxicity via accelerating recovery of renal stem-like cells

Abstract Background Irradiation-induced kidney damage is inevitable during radiotherapeutic practice, which limits effective radiotherapy doses on tumor treatment. In the present study, the role of mTOR complex 1 (mTORC1) signaling was investigated in irradiation-induced renal injuries. Methods Mice were exposed to 8.0-Gy X-ray of total body irradiation and subsequently treated with rapamycin. Changes of renal morphology were assessed by hematoxylin and eosin staining. Expression of pS6 and CD133 was detected via immunostaining. Cellular apoptosis and proliferation were measured by TUNEL, caspase-3 and BrdU staining. Activation of mTORC1, TGF-β and NF-κB signaling pathways was determined through western blot analysis. Results Our data displayed that irradiation disrupted the structures of renal corpuscles and tubules and decreased the density of CD133+ renal stem-like cells, which were related with increasing cellular apoptosis and decreasing cell proliferation post exposure. Activation of mTORC1, TGF-β and NF-κB signaling pathways was determined in irradiated renal tissues, which were inhibited by rapamycin treatment. Application of rapamycin after irradiation decreased cellular apoptosis and increased autophagy and cell proliferation in renal tissues. The density of CD133+ renal stem-like cells was significantly increased in irradiated kidneys after rapamycin treatment. The morphology of irradiated renal corpuscles and tubules was gradually recovered upon rapamycin treatment. Conclusions These findings indicate that inhibition of mTORC1 signaling by rapamycin ameliorates irradiation-induced renal toxicity mediated by decreasing cellular apoptosis and increasing CD133+ renal stem-like cells

Additional file 1: of Droxinostat sensitizes human colon cancer cells to apoptotic cell death via induction of oxidative stress

Figure S1 Colony-forming assay. 100–4000 HT-29 cells were seeded in 6-well plates. The cell culture medium was changed every two days. The colonies were counted ten days after plating (A). Plating efficiency (%) was calculated as the number of colonies observed/the number of cells plated (B). (PPTX 179 kb