CTC1 is a component of the mammalian CST (CTC1–STN1–TEN1) complex which plays essential roles in resolving replication problems to facilitate telomeric DNA and genomic DNA replication. We previously reported that the depletion of CTC1 leads to stalled replication fork restart defects. Moreover, the mutation in CTC1 caused cancer-prone diseases including Coats plus (CP) or dyskeratosis congenita (DC). To better understand the CTC1 regulatory axis, the microRNAs (miRNAs) targeting to CTC1 were predicted by a bioinformatics tool, and the selected candidates were further confirmed by a dual-luciferase reporter assay. Here, our current results revealed that miR-376a significantly reduced CTC1 expression at the transcription level by recognizing CTC1 3′-UTR. In addition, the overexpression of miR-376a induced telomere replication defection and resulted in direct replicative telomere damage, which could be rescued by adding back CTC1. Telomere shortening was also observed upon miR-376a treatment. Furthermore, for the clinical patient samples, the high expression of miR-376a was associated with the deregulation of CTC1 and a poor outcome for the rectum adenocarcinoma patients. Together, our results uncovered a novel role of miR-376a in stimulating rectum adenocarcinoma progression via CTC1 downregulating induced telomere dysfunction.

To investigate the protective function of low-level laser irradiation (LLLI) against ionizing irradiation and explore the molecular mechanism of photomodulation of Nrf2 protein, the impact of LLLI (635 nm, 5.7 J/cm(2)) before 2 Gy gamma ray radiation of radio-sensitive tissue hematopoietic stem cells was evaluated. As a result, reduced levels of reactive oxygen species and increased expression of antioxidant enzymes were detected. Moreover, increased expression of Nrf2 was observed after LLLI, whereas brusatol pretreatment before LLLI abolished this effect. In vivo, transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) was employed for therapy of hematopoietic function in an acute radiation sickness (H-ARS) mouse model, which was induced by 6-Gy ionizing irradiation; different hUC-MSC pretreatments including LLLI and Nrf2 RNAi were accounted for during experimental grouping. LLLI treatment of cells significantly increased the erythrocyte count and number of myelopoiesis clones (P < 0.05), but such improvements were reduced by Nrf2 RNAi pretreatment compared with cells transplanted without intervention. Therefore, LLLI may improve the radiation protection effect through molecular mechanisms related to the Nrf2 antioxidant pathway.

For electrical impedance tomography (EIT) lung imaging, chest expansion and contraction could change the electrode placement and deform the boundary of the image area, which changes the electric field distribution and distorts the reconstructed images. EIT images of lung function often produce severe artifacts due to the expansion of the thoracic cage, so it is necessary to study the effect of thoracic boundary deformation on EIT images. In this paper, we established several elliptical image reconstruction models, which deform from 1% to 15% in the anterior–posterior (AP) dimension from the circle field domain, to emulate chest expansion. The Quantitative evaluation of the influence of the deformation on the reconstruction images has been made. Images are estimated by parameter DORI and SSIM. The results show that these two parameters can evaluate image quality effectively, and image error increases with the increasing of boundary deformation. Although the error is small when the deformation extent of the boundary shape is small, images are seriously distorted when the deformation increases. Image error increases significantly when the boundary deformation increases, which may lead to image artifacts and maybe result in misdiagnosis.

Maintenance of genome integrity is critical for faithful propagation of genetic information and the prevention of the mutagenesis induced by various DNA damage events. RecQ-mediated genome instability protein 1 (RMI1), together with Bloom syndrome protein and topoisomerase III alpha, form an evolutionarily conserved complex that is critical for the maintenance of genomic stability. Herein, we report that RMI1 depletion increases cell sensitivity to camptothecin treatment, as shown by an elevation of genotoxic stress-induced DNA double-strand breaks, a stronger activation of the DNA damage response, and a greater G2/M cell cycle delay. Our findings support that, upon DNA damage, RMI1 forms nuclear foci at the damaged regions, interacts with RAD51, and facilitates the recruitment of RAD51 to initiate homologous recombination. Our data reveal the importance of RMI1 in response to DNA double-strand breaks and shed light on the molecular mechanisms by which RMI1 contributes to maintain genome stability.

Resveratrol (RSV) has broad prospective applications as a radiation protection drug, but its mechanism of action is not yet clear. Here, we found that 5 μM RSV can effectively reduce the cell death caused by irradiation. Irradiation leads to G2/M phase arrest in the cell cycle, whereas RSV treatment increases S-phase cell cycle arrest, which is associated with sirtuin 1 (SIRT1) regulation. Meanwhile, RSV promotes DNA damage repair, mainly by accelerating the efficiency of homologous recombination repair. Under oxidative stress, tyrosyl-tRNA synthetase (TyrRS) is transported to the nucleus to protect against DNA damage. RSV can promote TyrRS acetylation, thus promoting TyrRS to enter the nucleus, where it regulates the relevant signaling proteins and reduces apoptosis and DNA damage. SIRT1 is a deacetylase, and SIRT1 knockdown or inhibition can increase TyrRS acetylation levels, further reducing radiation-induced apoptosis after RSV treatment. Our study revealed a new radiation protection mechanism for RSV, in which the acetylation of TyrRS and its translocation into the nucleus is promoted, and this mechanism may also represent a novel protective target against irradiation.-Gao, P., Li, N., Ji, K., Wang, Y., Xu, C., Liu, Y., Wang, Q., Wang, J., He, N., Sun, Z., Du, L., Liu, Q. Resveratrol targets TyrRS acetylation to protect against radiation-induced damage.

The aim of this study was to find a non-invasive pulse wave waveform index that was highly correlated with cardiovascular disease and to establish an effective model for cardiovascular health assessment in middle-aged men to provide early warning of possible cardiovascular and cerebrovascular diseases. Considering the characteristics of pulse wave easy to detect and rich physiological information, the paper collected pulse waves of healthy males at six age groups, and collected 50 samples per age group. The pulse wave waveform parameters of each sample were extracted, including inflow time, outflow time, total beat time, fast inflow time, inflow time ratio and waveform coefficient [Formula: see text] value, the differences of which in different age groups were analyzed. Stepwise regression analysis was used to establish the relationship between age and pulse waveform parameters. The results show that the indicators of inflow time, inflow time ratio and fast inflow time have obvious differences with age, and with the increase of age, these three indicators show a steady upward trend. The indicators of outflow time, total beat time, and waveform coefficient are not sensitive to age changes. A predictive model of vessel age was established: [Formula: see text] time ([Formula: see text]). The pulse wave inflow time of hypertensive patients was substituted into the above-mentioned model, and the calculated blood vessel age was greater than the actual age. The age difference is greater than 5 years old. This study suggests that the pulse wave parameters of inflow time, fast inflow time and inflow time ratio has a significant and stable trend with age, indicating that they are closely related to vascular elasticity, compliance and stiffness, and can be used as predictors of cardiovascular disease.

Gastrointestinal mucosal damage is a catastrophic effect of abdominal or pelvic radiation used in cancer therapy or pretreatment for hematopoietic stem cell transplantation. 6-Shogaol is the constituent of ginger biophenolic, possesses both anti-inflammatory and antioxidant effects. We therefore investigated 6-shogaol’s candidacy as a protector against radiation-induced intestinal injury. Herein, we found that pretreatment with 6-shogaol improved animal survival and intestinal function following irradiation injury. Furthermore, the potential radioprotective role of 6-shogaol may be partially attributed to its antioxidant and anti-inflammatory properties, which alleviated radiation toxicity to the gastrointestinal tract. Additionally, we observed that 6-shogaol might reduce bacterial translocation and endotoxin levels following abdominal irradiation, and thereby protect against radiation-induced intestinal injury. Our results show a potential role for 6-shogaol as a protective agent to obviate the treatment-limiting intestinal side-effects and thereby may be useful in radiotherapy of patients.

NF-E2-related factor 2 (Nrf2) has been identified as a master regulatory factor in the protection of cells from oxidative and electrophilic stress. However, overexpression of Nrf2 in lung cancer may cause chemoresistance, as well as radioresistance. In this study, we examined the relationship between radioresistance and Nrf2 protein levels in H1299, A549, and H460 cells, and finally chose the A549 cell line to continue with due to its strong radioresistance and high Nrf2 protein levels. We found that the Nrf2 inhibitor, brusatol, could prevent the increase and accumulation of Nrf2 after exposure to irradiation. Additionally, following treatment with 80 nM brusatol, A549 cells became sensitive to irradiation, suffering severe DNA damage. Combination treatment with brusatol and ionizing radiation (IR) can distinctly increase the level of reactive oxygen species in A549 cells, causing a 1.8-fold increase compared with the control, and a 1.4-fold increase compared with IR alone. In fact, in the treatment with both brusatol and IR, lung cancer cell proliferation is halted, gradually leading to cell death. Because Nrf2 is closely linked to DNA damage repair, inhibiting the function of Nrf2, as in brusatol treatment, may increase the DNA damage caused by radiotherapy or chemotherapy, possibly enhancing the efficacy of chemotherapeutic drugs. Our study is the first to demonstrate brusatol's ability to enhance the responsiveness of lung cancer cells to irradiation, and its potential application as a natural sensitizer in radiotherapy.

In the present study, we examined the protective effects of human umbilical cord mesenchymal stem cells (hMSCs) against intestinal stem cell (ISC) death and intestinal damage in a mouse model of radiation injury.

Reactive oxygen species can lead to functional alterations in lipids, proteins, and nucleic acids, and an accumulation of ROS (Reactive oxygen species) is considered to be one factor that contributes to neurodegenerative changes. An increase in ROS production occurs following irradiation. Neuronal tissue is susceptible to oxidative stress because of its high oxygen consumption and modest antioxidant defenses. As a polyphenolic compound, resveratrol is frequently used as an activator of Sirt1 (Sirtuin 1). The present study was designed to explore the radioprotective and antioxidant effect of resveratrol on Sirt1 expression and activity induced by radiation and to provide a new target for the development of radiation protection drugs. Our results demonstrate that resveratrol inhibits apoptosis induced by radiation via the activation of Sirt1. We demonstrated an increase in Sirt1 mRNA that was present on 21 days of resveratrol treatment following irradiation in a concentration-dependent manner. Such mRNA increase was accompanied by an increase of Sirt1 protein and activity. Resveratrol effectively antagonized oxidation induced by irradiation, supporting its cellular ROS-scavenging effect. These results provide evidence that the mitochondrial protection and the antioxidant effect of resveratrol contribute to metabolic activity. These data suggest that Sirt1 may play an important role to protect neurons from oxidative stress.

In this study, a novel non-enzymatic hydrogen peroxide (H2O2) sensor was fabricated based on gold nanoparticles/carbon nanotube/self-doped polyaniline (AuNPs/CNTs/SPAN) hollow spheres modified glassy carbon electrode (GCE). SPAN was in-site polymerized on the surface of SiO2 template, then AuNPs and CNTs were decorated by electrostatic absorption via poly(diallyldimethylammonium chloride). After the SiO2 cores were removed, hollow AuNPs/CNTs/SPAN spheres were obtained and characterized by transmission electron microscopy (TEM), field-emission scanning electron microscopy (FESEM) and Fourier transform infrared spectroscopy (FTIR). The electrochemical catalytic performance of the hollow AuNPs/CNTs/SPAN/GCE for H2O2 detection was evaluated by cyclic voltammetry (CV) and chronoamperometry. Using chronoamperometric method at a constant potential of -0.1 V (vs. SCE), the H2O2 sensor displays two linear ranges: one from 5 mu M to 0.225 mM with a sensitivity of 499.82 mu A mM(-1)cm(-2); another from 0.225 mM to 8.825 mM with a sensitivity of 152.29 mu A mM(-1)cm(-2). The detection limit was estimated as 0.4 mM (signal-to-noise ratio of 3). The hollow AuNPs/CNTs/SPAN/GCE also demonstrated excellent stability and selectivity against interferences from other electroactive species. The sensor was further applied to determine H2O2 in disinfectant real samples.

There is increasing evidence that neuronal cell death occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. Radiation induces caspase activation fundamentally via the mitochondrial pathway. Caspases are the key regulators of apoptosis. Healthy male Sprague-Dawley rats were used in the present study to examine the radioprotective effect of a type of pan-caspase inhibitor, z-VAD-fmk, following radiation, to investigate the effects of caspase blockade in a model of the nucleus of the abducens nerve. z-VAD-fmk was injected intracerebroventricularly as a bolus injection (0.2 mu g/h for 1 h) into rats prior to exposure to radiation. Irradiation was conducted at room temperature at a dose of radiation of 4 Gy. The present study performed immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and western blot analysis and identified no significant changes in the expression of the X-linked inhibitor of apoptosis protein (XIAP) following radiation (P>0.05). As compared with the radiation alone group, the quantification of TUNEL-positive neurons was reduced in z-VAD-fmk-treated animals following radiation (P<0.01). Inhibition of caspase induced by z-VAD-fmk reduced the expression and activation of caspase-3, -8 and -9 (P<0.01). z-VAD-fmk effectively prevented radiation-induced apoptosis and this caspase inhibitor may be a potential therapeutic target in the treatment of brain radiation injury. The nucleus of the abducens nerve may be used as a radiation injury model, providing visual information and data on the apoptotic morphology of the abducens nucleus.

Three dimensional electrical impedance tomography (3D-EIT) became an important branch of EIT recently. It is important to research imaging and image quality evaluation methods for single targets of different positions and multi-targets in 3D field. Using finite element subdivision method, 3D-EIT field was dispersed into cube unit in the present study for models with single target located in the center of field, middle of field, and near to the edge, respectively. For models with two targets and four targets near to the field edge, Tikhonov-Noser algorithm was adopted in image reconstruction. Imaging error function ER and structure similarity degree function SSIM were introduced to evaluate the reconstructed images. For the models with signal target, with the movement of the target from the center to the edge of the field, the value of ER increased and SSIM decreased, and reconstruction quality decreased. For the models with multi-targets near to the field edge, ER and SSIM increased and decreased respectively with the increase of target number, mage quality also decreased. Tikhonov-Noser algorithm is an effective 3D-EIT algorithm. ER and SSIM are adaptive for the characteristic of 3D-EIT images, and it can quantitatively evaluate the 3D-EIT imaging effect from the two perspective of imaging error and structure quality.

The prediction of the image quality of a practical electrical impedance tomography (EIT) system is challenging. The reconstructed image quality of a practical EIT system with different measurement accuracy and under different excitation patterns for the object at different positions have been studied. The results show that a practical EIT system with limited accuracy is often deficient in the data distinction and the tiny difference of boundary voltages cannot be detected. Sequentially different system accuracy and excitation patterns make different impacts on the image reconstruction. The method in this study will be useful in the image quality prediction of a practical EIT system.

Telocyte (TC) as a special stromal cell exists in mammary gland and might play an important role in the balance of epithelium-stroma of mammary gland. Considering that different types of breast interstitial cells influence the development and progression of breast cancer, TCs may have its distinct role in this process. We here studied the roles of TCs in the self-assembly of reconstituted breast cancer tissue. We co-cultured primary isolated TCs and other breast stromal cells with breast cancer EMT-6 cells in collagen/Matrigel scaffolds to reconstitute breast cancer tissue in vitro. Using histology methods, we investigated the immunohistochemical characteristics and potential functions of TCs in reconstituted breast cancer tissue. TCs in primary mammary gland stromal cells with long and thin overlapping cytoplasmic processes, expressed c-kit/CD117, CD34 and vimentin in reconstitute breast cancer tissue. The transmission electron microscopy showed that the telocyte-like cells closely communicated with breast cancer cells as well as other stromal cells, and might serve as a bridge that directly linked the adjacent cells through membrane-to-membrane contact. Compared with cancer tissue sheets of EMT-6 alone, PCNA proliferation index analysis and TUNEL assay showed that TCs and other breast stromal cells facilitated the formation of typical nest structure, promoted the proliferation of breast cancer cells, and inhibited their apoptosis. In conclusion, we successfully reconstituted breast cancer tissue in vitro, and it seems to be attractive that TCs had potential functions in self-assembly of EMT-6/stromal cells reconstituted breast cancer tissue.

Cell migration is an early‐stage and critical step for cancer metastasis. The most common approach to monitor this process is wound‐healing assay. However, this traditional method has some unavoidable limitations. We observed that simply scratching the monolayer of cultured cells might cause local cell damage around the injury line. The cells along the scratched border seemed to be irritated and exhibited abnormal distribution of cytoskeleton reassembly with protruding “cell islands” and “pseudopodia” during wound healing, which might potentially affect the assessment of cell migration behavior. Herein, we applied a microfluidic device that mechanically constrained cells seeded in a designed pattern inside microchannels, and monitored cell movement in a way of mimicking the natural microenvironment of cancerous tissues. We illustrated the capacity of this simple method to probe cellular migration behaviors and to screen some biological active agents that reflected in their influence on cellular motility.

An EIT method with planar electrode array has been proposed and a hand-held planar electrode system has developed. Based on a 3-dimentional finite element model, a modified weighted backprojection algorithm, which is back-projected along equipotential surfaces of the 3D electric filed, is used to reconstruct slice images of 3D conductivity distribution under electrode array. The electrical field distribution has been calculated and several slice images beneath the electrode plane have been reconstructed. The result showed that superficial object can be distinguished well, but image of deeper object needs to be improved sequentially in the future.

Metastasis is a major cause of death from malignant diseases, and the underlying mechanisms are still largely not known. A detailed probe into the factors which may regulate tumour invasion and metastasis contributes to novel anti‐metastatic therapies. We previously identified a novel metastasis‐associated gene 1 ( mag‐1 ) by means of metastatic phenotype cloning. Then we characterized the gene expression profile of mag‐1 and showed that it promoted cell migration, adhesion and invasion in vitro . Importantly, the disruption of mag‐1 via RNA interference not only inhibited cellular metastatic behaviours but also significantly reduced tumour weight and restrained mouse breast cancer cells to metastasize to lungs in spontaneous metastatic assay in vivo . Furthermore, we proved that mag‐1 integrates dual regulating mechanisms through the stabilization of HIF ‐1α and the activation of m TOR signalling pathway. We also found that mag‐1 ‐induced metastatic promotion could be abrogated by m TOR specific inhibitor, rapamycin. Taken together, the findings identified a direct role that mag‐1 played in metastasis and implicated its function in cellular adaptation to tumour microenvironment.

Objective To evaluate the expression of lysophosphatidic acid acyltransferase(LPAAT) β in different cancer cell lines and to investigate the effect of LPAAT β overexpression on cell proliferation,migration and adhesion in vitro.Methods Western blotting assay was used to detect the expression of LPAAT β.The cDNA of LPAAT β was cloned into pcDNA3.1A(+) and transfected into human lung fibroblast cells(HLF).The proliferation of LPAAT β stably-expressing HLF cells was analyzed by MTT assay.Wound healing assay was applied to evaluate the cell migration ability and adhesion assay was employed to examine the adhesion of LPAAT β stably-expressing HLF cells to an extracellular matrix,Matrigel.Results LPAAT β protein expression levels were different in tumor cells.LPAAT β stably-expressing HLF cells displayed elevated cell proliferation and migration ability.Moreover,the transfected cells adhered to Matrigel were also increased.Conclusion LPAAT β is universally expressed in eukaryotic and tumor cells,and its overexpression in HLF cells promotes proliferation,migration and adhesion ability of cells,indicating the important role of LPAAT β in cell growth in vitro.