Increased Global and Local Efficiency of Human Brain Anatomical Networks Detected with FLAIR-DTI Compared to Non-FLAIR-DTI

Diffusion-weighted MRI (DW-MRI), the only non-invasive technique for probing human brain white matter structures in vivo, has been widely used in both fundamental studies and clinical applications. Many studies have utilized diffusion tensor imaging (DTI) and tractography approaches to explore the topological properties of human brain anatomical networks by using the single tensor model, the basic model to quantify DTI indices and tractography. However, the conventional DTI technique does not take into account contamination by the cerebrospinal fluid (CSF), which has been known to affect the estimated DTI measures and tractography in the single tensor model. Previous studies have shown that the Fluid-Attenuated Inversion Recovery (FLAIR) technique can suppress the contribution of the CSF to the DW-MRI signal. We acquired DTI datasets from twenty-two subjects using both FLAIR-DTI and conventional DTI (non-FLAIR-DTI) techniques, constructed brain anatomical networks using deterministic tractography, and compared the topological properties of the anatomical networks derived from the two types of DTI techniques. Although the brain anatomical networks derived from both types of DTI datasets showed small-world properties, we found that the brain anatomical networks derived from the FLAIR-DTI showed significantly increased global and local network efficiency compared with those derived from the conventional DTI. The increases in the network regional topological properties derived from the FLAIR-DTI technique were observed in CSF-filled regions, including the postcentral gyrus, periventricular regions, inferior frontal and temporal gyri, and regions in the visual cortex. Because brain anatomical networks derived from conventional DTI datasets with tractography have been widely used in many studies, our findings may have important implications for studying human brain anatomical networks derived from DW-MRI data and tractography.     

MRI Findings of Otic and Sinus Barotrauma in Patients with Carbon Monoxide Poisoning during Hyperbaric Oxygen Therapy

Background and Purpose

To study the MRI findings of otic and sinus barotrauma in patients with carbon monoxide(CO) poisoning during hyperbaric oxygen (HBO) therapy and examine the discrepancies of otic and sinus abnormalities on MRI between barotrauma and acute otitis media with effusion.

Materials and Methods

Eighty patients with CO-poisoning diagnosed with otic and sinus barotrauma after HBO therapy were recruited. Brain MRI was performed to predict delayed encephalopathy. Over the same period, 88 patients with acute otitis media with effusion on MRI served as control. The abnormalities of the middle ear and paranasal sinuses on MRI were noted and were compared between groups. Nine patients with barotrauma were followed up by MRI.

Results

In the barotrauma group, 92.5% of patients had bilateral middle ear abnormalities on MRI, and 60% of patients had both middle ear cavity and mastoid cavity abnormalities on MRI in both ears. Both rates were higher than those in the control group (p = 0.000). In the two groups, most abnormalities on MRI were observed in the mastoid cavity. The rate of sinus abnormalities of barotrauma was 66.3%, which was higher than the 50% in the control group (p = 0.033). In the nine patients with barotrauma followed up by MRI, the otic barotrauma and sinus abnormalities had worsened in 2 patients and 5 patients, respectively.

Conclusion

MRI is able to depict the abnormalities of otic and sinus barotrauma in patients with CO-poisoning during HBO therapy and to differentiate these from acute otitis media with effusion.     

Deregulation of UCA1 expression may be involved in the development of chemoresistance to cisplatin in the treatment of non-small-cell lung cancer via regulating the signaling pathway of microRNA-495/NRF2

Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. As a platinum-based chemotherapeutic drug, cisplatin has been used for over 30 years in NSCLC treatment while its effects are diminished by drug resistance. Therefore, we aimed to study the potential role of UCA1 in the development of chemoresistance against cisplatin. Real-time polymerase chain reaction, western-blot analysis, and immunofluorescence were used to study the involvement of UCA1, miR-495, and NRF2 in chemoresistance against cisplatin. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the effect of cisplatin on cell proliferation. Computational analysis and luciferase assay were carried out to explore the interaction among UCA1, miR-495, and NRF2. The cisplatin-R group exhibited lower levels of UCA1 and NRF2 expression but a higher level of miR-495 expression than the cisplatin-S group. The growth rate and half-maximal inhibitory concentration of cellular dipeptidyl peptidase (cisplatinum) of the cisplatin-R group were much higher than those in the cisplatin-S group. MiR-495 contained a complementary binding site of UCA1, and the luciferase activity of wild-type UCA1 was significantly reduced after the transfection of miR-495 mimics. MiR-495 directly targeted the 3′-untranslated region (3′-UTR) of NRF2, and the luciferase activity of wild-type NRF2 3′-UTR was evidently inhibited by miR-495 mimics. Finally, UCA1 and NRF2 expressions in the effective group were much lower than that in the ineffective group, along with a much higher level of miR-495 expression. We suggested for the first time that high expression of UCA1 contributed to the development of chemoresistance to cisplatin through the UCA1/miR-495/NRF2 signaling pathway.     

三株芽胞杆菌菌株对松材线虫低温存活与繁殖的影响

为明确细菌在松材线虫生态适应性中的作用,本研究选择与致病相关的松材线虫伴生细菌GD1、马尾松内生细菌GD2以及具有杀松材线虫活性的湿地松内生细菌NJSZ-13为试验对象,测定经这3株芽胞杆菌菌株3个浓度低温驯化10、15和20 d后,在冷冻条件下松材线虫强毒虫株AMA3、中毒虫株AA3和弱毒虫株YW4的存活率和繁殖量。结果表明：低温驯化15 d和20 d后3株菌株对不同毒力线虫的活力影响较驯化10 d后的更显著。在低温驯化15 d、-20℃冷冻处理1 h后,5×10⁶ CFU/mL浓度菌株GD1处理下,虫株AMA3、AA3和YW4的存活率分别为77.22%、83.68%和84.26%,与对照差异显著;5×10⁵ CFU/mL浓度菌株GD1处理下,虫株AMA3、AA3和YW4的存活率分别为75.76%、80.67%和81.50%,与对照差异显著。5×10⁶ CFU/mL和5×10⁵ CFU/mL浓度菌株GD2处理下,与GD1处理组结果相似,菌株NJSZ-13处理组则与菌株GD1和GD2的结果相反。低温驯化15 d、-20℃冷冻处理1 h后,5×10⁶ CFU/mL浓度菌株GD1处理下,虫株AMA3、AA3和YW4的繁殖量分别为7 530、9 317和12 793条/皿,与对照（3 192、3 840和5 823条/皿）差异显著;5×10⁵ CFU/mL浓度菌株GD1处理时,3个虫株的繁殖量均与对照差异显著。而菌株GD2和NJSZ-13处理后,3个虫株的繁殖量均无显著变化。表明不同芽胞杆菌对松材线虫的低温适应性影响存在差异,松材线虫伴生细菌GD1和马尾松内生细菌GD2能增强其低温适应性,而湿地松内生细菌NJSZ-13菌株则相反。     

Investigation on bioactive protection of the amino acids derived from LEA protein on insulin by molecular simulation

Nowadays heat-sensitive protein medicines are increasingly showing their importance in the treatment of various diseases. Their popularisation and application are meeting a great challenge because of their heat lability. In this study, human insulin as a heat-sensitive protein medicine and 66 amino acids derived from a Group 3 late embryogenesis abundant protein fragment as a complex bioactive protectant, were chosen to be investigated to determine whether these amino acids can be used to protect the insulin from denaturation due to drying. The experiments were carried out by using a replica exchange molecular dynamics (REMD) simulation and GROMACS software with Gromos96 (53a6) force field. The REMD results indicate that those amino acids can effectively prevent the reversal between hydrophilic and hydrophobic surface. Both the configurations and secondary structures of the protected insulin were preserved very well. The H-bonding and electrostatic interactions between the insulin and the protectant play key roles in the bioactive protection of insulin. These results agree well with the water replacement hypothesis. All the results prove that these amino acids are a perfect bioactive protectant for heat-sensitive protein medicines.     

ATM pathway is essential for ionizing radiation-induced autophagy

BackgroundATM plays an important role in response to DNA damage, while the roles of ATM in radiation-induced autophagy are still unclear in cervical cancer cells.MethodsHuman cervical cancer cells, Hela, were used, and cell models with ATM^?/? and MAPK14^?/? were established by gene engineering. Western blot was implemented to detect protein expression. MDC staining and GFP-LC3 relocalization were used to detect autophagy. CCK-8 was used to detect cell viability. Radiosensitivity was analyzed by colony formation assays. Co-immunoprecipitation was used to detect the interaction between different proteins, and apoptosis was detected by flow cytometry.ResultsAfter radiation autophagy was induced, illustrated by the increase of MAPLC3-II/MAPLC3-I ratio and decrease of p62, and phosphorylation of ATM simultaneously increased. ATM^?/? cells displayed hypersensitivity but had no influence on IR-induced apoptosis. Then inhibitor of ATM, KU55933, ATM and MAPK14 silencing were used, and autophagy was induced by IR more than 200% in control, and only by 35.72%, 53.18% and 24.76% in KU55933-treated cells, ATM^?/? and MAPK14^?/? cells, respectively. KU55933 inhibited IR-induced autophagy by activating mTOR pathways. ATM silencing decreased the expression of MAPK14 and mTOR signals significantly. Beclin's bond to PI3KIII and their interaction increased after IR, while in ATM^?/? and MAPK14^?/? cells this interaction decreased after IR. Both ATM and MAPK14 interacted with Beclin, while ATM^?/? and MAPK14^?/? cells showed no interaction.ConclusionsATM could promote IR-induced autophagy via the MAPK14 pathway, the mTOR pathway, and Beclin/PI3KIII complexes, which contributed to the effect of ATM on radiosensitivity.     

Serum proteomic profiling for the early diagnosis of colorectal cancer

No ideal serum biomarker currently exists for the early diagnosis of colorectal cancer (CRC). Magnetic bead‐based fractionation coupled with MALDI‐TOF MS was used to screen serum samples from CRC patients, healthy controls, and other cancer patients. A diagnostic model with five proteomic features (m/z 1778.97, 1866.16, 1934.65, 2022.46, and 4588.53) was generated using Fisher algorithm with best performance. The Fisher‐based model could discriminate CRC patients from the controls with 100% (46/46) sensitivity and 100% (35/35) specificity in the training set, 95.6% (43/45) sensitivity and 83.3% (35/42) specificity in the test set. We further validated the model with 94.4% (254/269) sensitivity and 75.5% (83/110) specificity in the external independent group. In other cancers group, the Fisher‐based model classified 25 of 46 samples (54.3%) as positive and the other 21 as negative. With FT‐ICR‐MS, the proteomic features of m/z 1778.97, 1866.16, 1934.65, and 2022.46, of which intensities decreased significantly in CRC, were identified as fragments of complement C3f. Therefore, the Fisher‐based model containing five proteomic features was able to effectively differentiate CRC patients from healthy controls and other cancers with a high sensitivity and specificity, and may be CRC‐specific. Serum complement C3f, which was significantly decreased in CRC group, may be relevant to the incidence of CRC. J. Cell. Biochem. 114: 448–455, 2013. © 2012 Wiley Periodicals, Inc.