Efficiency of Ferritin as an MRI Reporter Gene in NPC Cells Is Enhanced by Iron Supplementation

Background. An emerging MRI reporter, ferritin heavy chain (FTH1), is recently applied to enhance the contrast and increase the sensitivity of MRI in the monitoring of solid tumors. However, FTH1-overexpression-related cytotoxicity is required to be explored. Methods. By using the Tet-Off system, FTH1 overexpression was semi-quantitativiely and dynamicly regulated by doxycycline in a NPC cell line. Effects of FTH1 overexpression on the proliferation, cytotoxicity, apoptosis and migration of NPC cells were investigated in vitro, and MR relaxation rate was measured in vitro and in vivo. Results. In vitro and in vivo overexpression of FTH1 significantly increased the transverse relaxivity (R2), which could be enhanced by iron supplementation. In vitro, overexpression of FTH1 reduced cell growth and migration, which were not reduced by iron supplementation. Furthermore, cells were subcutaneously inoculated into the nude mice. Results showed FTH1 overexpression decreased tumor growth in the absence of iron supplementation but not in the presence of iron supplementation. Conclusion. To maximize R2 and minimize the potential adverse effects, supplementation of iron at appropriate dose is recommended during the application of FTH1 as a reporter gene in the monitoring of NPC by MRI

Detection of femtomolar level osteosarcoma-related gene via a chronocoulometric DNA biosensor based on nanostructure gold electrode

In this paper, a sensitive chronocoulometric deoxyribonucleic acid (DNA) biosensor based on a nanostructure gold electrode was fabricated for detection of the femtomolar level survivin gene which was correlated with osteosarcoma by using hexaamine-ruthenium III complexes, [Ru(NH3)6]3+, as the electrochemical indicator. The effect of different frequencies on the real surface area of the nanostructure gold electrode obtained by repetitive square-wave oxidation reduction cycle was investigated. At the optimal frequency of 8000 Hz, the real surface of the developed nanostructure gold electrode was about 42.5 times compared with that of the bare planar gold electrode. The capture probe DNA was immobilized on the nanostructure gold electrode and hybridized with target DNA. Electrochemical signals of hexaamine-ruthenium III bound to the anionic phosphate of DNA strands via electrostatic interactions were measured by chronocoulometry before and after hybridization. The increase of the charges of hexaamine-ruthenium III was observed upon hybridization of the probe with target DNA. Results indicate that this DNA biosensor could detect the femtomole (fM) concentration of the DNA target quantitatively in the range of 50 fM to 250 fM; the detection limit of this DNA biosensor was 5.6 fM (signal to noise = 3). This new biosensor exhibits excellent sensitivity and selectivity and has been used for an assay of polymerase chain reaction (PCR) with a satisfactory result

Calcitonin gene-related peptide: a potential protective agent in cerebral ischemia–reperfusion injury

Ischemic stroke is the most common type of cerebrovascular disease with high disability and mortality rates, which severely burdens patients, their families, and society. At present, thrombolytic therapy is mainly used for the treatment of ischemic strokes. Even though it can achieve a good effect, thrombolytic recanalization can cause reperfusion injury. Calcitonin gene-related peptide (CGRP) is a neuropeptide that plays a neuroprotective role in the process of ischemia–reperfusion injury. By combining with its specific receptors, CGRP can induce vasodilation of local cerebral ischemia by directly activating the cAMP–PKA pathway in vascular smooth muscle cells and by indirectly activating the NO–cGMP pathway in an endothelial cell-dependent manner,thus rapidly increasing ischemic local blood flow together with reperfusion. CGRP, as a key effector molecule of neurogenic inflammation, can reduce the activation of microglia, downregulates Th1 classical inflammation, and reduce the production of TNF-α, IL-2, and IFN-γ and the innate immune response of macrophages, leading to the reduction of inflammatory factors. CGRP can reduce the overexpression of the aquaporin-4 (AQP-4) protein and its mRNA in the cerebral ischemic junction, and play a role in reducing cerebral edema. CGRP can protect endothelial cells from angiotensin II by reducing the production of oxidants and protecting antioxidant defense. Furthermore, CGRP-upregulated eNOS can further induce VEGF expression, which then promotes the survival and angiogenesis of vascular endothelial cells. CGRP can also reduce apoptosis by promoting the expression of Bcl-2 and inhibiting the expression of caspase-3. These effects suggest that CGRP can reduce brain injury and repair damaged nerve function. In this review, we focused on the role of CGRP in cerebral ischemia–reperfusion injury

Fault Diagnosis of Rotating Machinery under Noisy Environment Conditions Based on a 1-D Convolutional Autoencoder and 1-D Convolutional Neural Network

Deep learning methods have been widely used in the field of intelligent fault diagnosis due to their powerful feature learning and classification capabilities. However, it is easy to overfit depth models because of the large number of parameters brought by the multilayer-structure. As a result, the methods with excellent performance under experimental conditions may severely degrade under noisy environment conditions, which are ubiquitous in practical industrial applications. In this paper, a novel method combining a one-dimensional (1-D) denoising convolutional autoencoder (DCAE) and a 1-D convolutional neural network (CNN) is proposed to address this problem, whereby the former is used for noise reduction of raw vibration signals and the latter for fault diagnosis using the de-noised signals. The DCAE model is trained with noisy input for denoising learning. In the CNN model, a global average pooling layer, instead of fully-connected layers, is applied as a classifier to reduce the number of parameters and the risk of overfitting. In addition, randomly corrupted signals are adopted as training samples to improve the anti-noise diagnosis ability. The proposed method is validated by bearing and gearbox datasets mixed with Gaussian noise. The experimental result shows that the proposed DCAE model is effective in denoising and almost causes no loss of input information, while the using of global average pooling and input-corrupt training improves the anti-noise ability of the CNN model. As a result, the method combined the DCAE model and the CNN model can realize high-accuracy diagnosis even under noisy environment

Integrated analysis reveals potential long non-coding RNA biomarkers and their potential biological functions for disease free survival in gastric cancer patients

Abstract Background Increasing evidences supported the association between long non-coding RNA (lncRNA) and disease free survival in gastric cancer (GC) patients. The purpose of the current study was to construct and verify a noninvasive preoperative predictive tool for disease free survival in GC patients. Methods There were 265 and 300 GC patients in model dataset and validation dataset respectively. The associations between the lncRNA biomarkers and disease free survival were evaluated by univariate and multivariate Cox regression. Results Thirteen lncRNA biomarkers (GAS5-AS1, AL109615.3, KDM7A-DT, AP000866.2, KCNJ2-AS1, LINC00656, LINC01777, AC046185.3, TTTY14, LINC01526, LINC02523, LINC00592, and C5orf66) were identified as prognostic biomarkers with disease free survival. These thirteen lncRNA biomarkers were combined to construct a prognostic signature for disease free survival. The C-indexes of the current predictive signature in model cohort were 0.849 (95% CI 0.803–0.895), 0.859 (95% CI 0.813–0.905) and 0.888 (95% CI 0.842–0.934) for 1-year, 3-year and 5-year disease free survival respectively. Based on thirteen-lncRNA prognostic signature, patients in model cohort could be stratified into high risk group and low risk group with significant different disease free survival rate (hazard ratio [HR] = 7.355, 95% confidence interval [CI] 4.378–12.356). Good reproducibility of thirteen-lncRNA prognostic signature was confirmed in an external validation cohort (GSE62254) with HR 3.919 and 95% CI 2.817–5.453. Further analysis demonstrated that the prognostic significance of thirteen-lncRNA prognostic signature was independent of other clinical characteristics. Conclusions In conclusion, a simple noninvasive prognostic signature was established for preoperative prediction of disease free survival in GC patients. This prognostic signature might predict the individual mortality risk of disease free survival without pathological information and facilitate individual treatment decision-making

A Review of Adropin as the Medium of Dialogue between Energy Regulation and Immune Regulation

Adropin is a secretory protein encoded by the energy balance gene and is closely associated with regulation of energy metabolism and insulin resistance. The clinical findings demonstrated its decreased expression in various inflammatory diseases, its negative correlation with the expression levels of inflammatory cytokines, and its potential anti-inflammatory effects. We speculate that adropin plays a pivotal regulatory role in immune cells and inflammatory factors. In this study, we reviewed the advances in researches concentrated on immunological effects of adropin

Framework for interpretation of trypsin-antitrypsin imbalance and genetic heterogeneity in pancreatitis

Early intracellular premature trypsinogen activation was interpreted as the key initiator of pancreatitis. When the balance in the homeostasis of trypsin and antitrypsin system is disequilibrated, elevated aggressive enzymes directly attack the pancreatic tissue, which leads to pancreatic destruction and inflammation. However, trypsin alone is not enough to cause complications in pancreatitis, which may play a crucial role in modulating signaling events in the initial phase of the disease. NFκB activation is the major inflammatory pathway involved in the occurrence and development of pancreatitis and it can be induced by intrapancreatic activation of trypsinogen. Synthesis of trypsinogen occurs in endoplasmic reticulum (ER), and ER stress is an important early acinar cell event. Components of ER stress response are known to be able to trigger cell death as well as NFκB signaling cascade. The strongest evidence supporting the trypsin-centered theory is that gene mutations, which lead to the generation of more trypsin, or reduce the activity of trypsin inhibitors or trypsin degradation, are associated with pancreatitis. Thus, trypsin–antitrypsin imbalance may be the first step leading to pancreatic autodigestion and inducing other pathways. Continued experimental studies are necessary to determine the specific relationships between trypsin–antitrypsin imbalance and genetic heterogeneity in pancreatitis. In this article, we review the latest advances that contributed to the understanding of the basic mechanisms behind the occurrence and development of pancreatitis with a focus on the interpretation of trypsin–antitrypsin imbalance and their relationships with other inflammation pathways. We additionally highlight genetic predispositions to pancreatitis and possible mechanisms associated with them

EZH2 G553C significantly increases the risk of brain metastasis from lung cancer due to salt bridge instability

Abstract Background The incidence and mortality of lung cancer is the highest in China and the world. Brain is the most common distant metastasis site of lung cancer. Its transfer mechanism and predictive biomarkers are still unclear. EZH2 participates in the catalysis of transcriptional inhibition complex, mediates chromatin compactness, leads to the silencing of its downstream target genes, participates in the silencing of multiple tumor suppressor genes, and is related to cell proliferation, apoptosis and cycle regulation. In physiology, EZH2 has high activity in stem cells or progenitor cells, inhibits genes related to cell cycle arrest and promotes self-renewal. To detect the expression and mutation of EZH2 gene in patients with brain metastasis of lung cancer, and provide further theoretical basis for exploring the pathogenesis of brain metastasis of lung cancer and finding reliable biomarkers to predict brain metastasis of lung cancer. Methods This study investigated susceptible genes for brain metastasis of lung cancer. The second-generation sequencing technology was applied to screen the differential genes of paired samples (brain metastasis tissues, lung cancer tissues and adjacent tissues) of lung cancer patients with brain metastasi. Results It revealed that there was a significant difference in the G553C genotype of EZH2 between lung cancer brain metastasis tissues and lung cancer tissues (p = 0.045). The risk of lung cancer brain metastasis in G allele carriers was 2.124 times higher than that in C allele carriers. Immunohistochemistry showed that compared with lung cancer patients and lung cancer patients with brain metastasis, the expression level of EZH2 in lung cancer tissues of lung cancer patients was significantly higher than that in adjacent lung tissues (p < 0.0001), and higher than that in brain metastasis tissues (p = 0.0309). RNA in situ immunohybridization showed that EZH2 mRNA expression was gradually high in lung cancer adjacent tissues, lung cancer tissues and lung cancer brain metastasis tissues. Conclusions EZH2 G553C polymorphism contributes to the prediction of brain metastasis of lung cancer, in which G allele carriers are more prone to brain metastasis

Application of an Electrochemical Immunosensor with a MWCNT/PDAA Modified Electrode for Detection of Serum Trypsin

Objective: To establish an electrochemical immunosensor for the determination of serum trypsin levels using a multiwall carbon nanotubes (MWCNTs)-composite-modified electrode. Method: A MWCNT composite coated on the surface of bare gold electrodes was used for fixation of an anti-trypsin antibody. The assembly process and the performance indicators, including sensitivity, linear range of detection, anti-jamming performance, and stability, of the electrochemical immunosensor were examined by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Results: With optimized experimental conditions, the difference of the current value measured by differential pulse voltammetry (DPV) showed a linear relationship with the concentration of serum trypsin within 0.10–100 ng/mL. The detection limit for trypsin using this sensor was 0.002 ng/mL. Conclusions: The electrochemical immunosensor built using the MWCNT-composite-modified electrode is simple to operate and has a fast response time, along with a wide linear range, high sensitivity, and accuracy, making it suitable for serum trypsin detection