Purpose
To investigate the potential candidate microRNA (miRNA) biomarkers for the clinical diagnosis, classification, and prognosis of gastric cancer (GC).
Methods
We use bioinformatics overlapping ...subclasses analysis to find the tumor grade and lymphatic metastasis-related GC specific miRNAs from the Cancer Genome Atlas (TCGA) database. Then, we further investigated these GC specific miRNAs distributions in different GC clinical features and their correlations overall survival on the basis of GC patients’ information and their related RNA sequencing profile from TCGA. Finally, we randomly selected some of key miRNAs use qRT-PCR to confirm the reliability and validity.
Results
22 GC specific key miRNAs were identified (Fold-change >2,
P
< 0.05), 11 of them were discriminatively expressed with tumor size, grade, TNM stage and lymphatic metastasis (
P
< 0.05). In addition, nine miRNAs (miR-196b-5p, miR-135b-5p, miR-183-5p, miR-182-5p, miR-133a-3p, miR-486-5p, miR-144-5p, miR-129-5p and miR-145-5p) were found to be significantly associated with overall survival (log-rank
P
< 0.05). Finally, four key miRNAs (miR-183-5p, miR-486-5p, miR-30c-2-3p and miR-133a-3p) were randomly selected to validation and their expression levels in 53 newly diagnosed GC patients by qRT-PCR. Results showed that the fold-changes between TCGA and qRT-PCR were 100 % in agreement. We also found miR-183-5p and miR-486-5p were significantly correlated with tumor TNM stage (
P
< 0.05), and miR-30c-2-3p and miR-133a-3p were associated with tumor differentiation degree and lymph-node metastasis (
P
< 0.05). These verified miRNAs clinically relevant, and the bioinformatics analysis results were almost the same.
Conclusion
These key miRNAs may functions as potential candidate biomarkers for the clinical diagnosis, classification and prognosis for GC.
In this brief, the high-quality carbon nanotubes (CNTs) is grown by a chemical vapor deposition (CVD) method, and it is used as an ultrafine flip-chip interconnection material in the proposed 3-D ...integrated circuit (3DIC) system. We show a patterned growth of multiwalled CNTs on the substrate with prestructured bond pads including a complete metallization system for an electrical characterization. We succeeded in achieving reliable flip-chip connections between CNT-covered contact pads and metal pads during the room temperature bonding process. The goal is a reversible electrical and mechanical chip assembly with CNT bumps. Based on the current-voltage (<inline-formula> <tex-math notation="LaTeX">{I} </tex-math></inline-formula>-<inline-formula> <tex-math notation="LaTeX">{V} </tex-math></inline-formula>) measurements, the resistivity (<inline-formula> <tex-math notation="LaTeX">\rho </tex-math></inline-formula>) of the grown CNTs is found to be close to <inline-formula> <tex-math notation="LaTeX">\sim 10^{-{6}}\,\,{\sf \Omega }\text{m} </tex-math></inline-formula>. With the proposed 3DIC process flow, the vertically electrical connection between two different Si substrates is demonstrated successfully. The connection resistance in the full 3-D system is very promising (<inline-formula> <tex-math notation="LaTeX">\sim 2.43~{\sf \Omega } </tex-math></inline-formula>), compared with other's work (<inline-formula> <tex-math notation="LaTeX">\sim 12~{\sf \Omega } </tex-math></inline-formula>). The different bonding materials (In versus Sn) and bonding times are also investigated systemically and further optimized. This brief provides a useful solution for the future electrical connection in the high-performance and high-dense 3-D integrated devices.
Oesophageal carcinoma is the sixth most lethal cancer in the world. At present, the choice of specific surgical methods is controversial. This study compares the safety and efficacy of endoscopic ...submucosal dissection and endoscopic mucosal resection in treating early oesophageal carcinoma.
We carried out a search of online databases including the Web of Science, PubMed, Embase and the Cochrane Library with no language restrictions. The inclusion criteria were patients with early oesophageal carcinoma who accepted the treatment of endoscopic submucosal dissection compared with endoscopic mucosal resection.
A total of 1,462 patients with 1,650 lesions from nine studies were included in the meta-analysis. When compared with the endoscopic mucosal resection group, the en bloc resection (endoscopic submucosal dissection 67.94% vs endoscopic mucosal resection 52.78%; odds ratio 19.79,
= 0.000) and complete resection (endoscopic submucosal dissection 75.57% vs endoscopic mucosal resection 59.47%; odds ratio 16.10,
= 0.000) rates were significantly higher in the endoscopic submucosal dissection group, while the local recurrence rate was significantly lower in the endoscopic submucosal dissection group (endoscopic submucosal dissection 0.08% vs endoscopic mucosal resection 2.66%; odds ratio 0.08,
= 0.000). The incidence of complications and procedural time were also tested.
Accumulating studies have reported that circular RNAs (circRNAs) can act as novel prognostic biomarkers in multiple malignant tumors. Here, we conducted a study to investigate the potential function ...and molecular mechanism of action of hsa_circ_0010882 in gastric cancer (GC).
The expression of hsa_circ_0010882 in the plasma of GC patients and in GC cell lines was verified by qRT-PCR. Its association with overall survival of GC patients was then analyzed by statistical analysis. Gain-of-function and loss-of-function assays were used to investigate the physiological function of hsa_circ_0010882 in GC cells in vitro in the context of proliferation, apoptosis, migration, and invasion. Moreover, the molecular mechanism of action of hsa_circ_0010882 was predicted using online databases and a literature review. A Western blot assay was used to detect the levels of proteins in the PI3K/Akt/mTOR signaling pathway.
We found that hsa_circ_0010882 expression was significantly upregulated in the plasma of GC patients and GC cell lines. Increased expression of hsa_circ_0010882 was significantly correlated with tumor size and histological grade. In addition, GC patients with higher expression of hsa_circ_0010882 had significantly lower overall survival than patients with lower expression of hsa_circ_0010882. Multivariate analysis showed that hsa_circ_0010882 expression could be an independent prognostic factor for overall survival. The proliferation, migration, and invasiveness of GC cell lines were inhibited following hsa_circ_0010882 knock-down, while GC cellular apoptosis increased. Further, overexpression of hsa_circ_0010882 leads to increased proliferation, migration, and invasiveness of GC cell lines. While apoptosis was higher in the GC cell line group with low expressing hsa_circ_0010882 than the control group, no significant difference in apoptosis was detected between the hsa_circ_0010882 overexpressing and the control group. Finally, a mechanistic analysis demonstrated that the hsa_circ_0010882 was positively associated with PI3K/Akt/mTOR signaling pathway.
Hsa_circ_0010882, as an oncogenic molecule, is highly expressed in the plasma of patients with GC and is associated with poor prognosis. It plays an important role in proliferation, migration, and invasive genotypes of GC cell lines via regulation of the PI3K/Akt/mTOR signaling pathway. Additionally, it might be a potential prognostic biomarker for GC patients.
The disseminated neoplastic foci of malignant gliomas are essentially responsible for the limited efficacy of current available therapeutic modalities. Bone marrow-derived stem cells (BMSCs) have the ...ability to migrate into these tumors and even track infiltrating tumor cells, making them to be promising cellular vehicles for delivering therapeutic agents to glioma cells. The herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) suicide gene therapy with a potent bystander effect has been considered as one of the most promising therapeutic strategies for malignant gliomas. In this study, we evaluate the anti-glioma effect of suicide gene therapy using BMSCs expressing HSV-TK combined with overexpression of connexin 43 (Cx43), which can restore the gap junction of intercellular communication and may enhance the bystander effect of suicide gene therapy. To assess the potential of BMSCs to track glioma cells, a spheroid co-culture system in matrigel was used to show that some BMSCs migrated to C6 glioma cell microspheres. Transwell assay showed the tumor tropic property of BMSCs. In addition, BrdU-labeled BMSCs injected directly into the cerebral hemisphere opposite to the established C6 rat gliomas were capable of migrating into the xenograft gliomas. C6 cell growth was more intensively inhibited by HSV-TK/GCV treatment mediated by BMSCs, and could be further enhanced by combination with Cx43 transfection into glioma cells. The same result was observed in vivo by the growth of C6 gliomas and the survival analysis of rats bearing C6 glioma. In conclusion, Cx43 combined with HSV-TK/GCV gene therapy using BMSCs as vehicles was highly effective in a rat glioma model and therefore hold great potential as a novel approach for the gene therapy of human malignant gliomas.
Tau plays important roles in the assembly and stabilization of the microtubule structure to facilitate axonal transport in mammalian brain. The intracellular tau aggregates to form paired helical ...filaments leading to neurodegenerative disorders, collectively called tauopathies. In our previous report, we established a zebrafish model to express tau-GFP to induce neuronal death, which could be directly traced in vivo. Recently, we used this model to screen 400 herbal extracts and found 45 of them to be effective on reducing tau-GFP-induced neuronal death. One of the effective herbal extracts is the Tripterygium wilfordii stem extract. HPLC analysis and functional assay demonstrated that epicatechin (EC) is the major compound of Tripterygium wilfordii stem extract to decrease the neurotoxicity induced by tau-GFP. Using a luciferase reporter assay in the zebrafish, we confirmed that EC could activate Nrf2-dependent antioxidant responses to significantly increase the ARE-controlled expression of luciferase reporter gene. These data suggest that EC from the Tripterygium wilfordii stem extract could diminish tau-GFP-induced neuronal death through the activation of Nrf2.
•Tripterygium wilfordii stem extract decreases the neurotoxicity induced by tau-GFP.•Epicatechin (EC) is the major compound of the extract for the activity.•EC could diminish tau-GFP-induced neuronal death through the activation of Nrf2.
Epidermal growth factor receptor (EGFR) had been reported as one of the major responsible genes for malignant progression and phenotype reversion of gliomas, and has been used as one of the most ...important therapeutic targets. In the present study, small interference RNA (siRNA) and antisense EGFR expression constructs, which target sequences of human EGFR catalytic domain (2400-2420) and the 3'-coding region, respectively, were used to examine the growth inhibition effects on U251 glioma cells. Cell growth was significantly inhibited and G2/M arrest was observed in antisense- and siRNA-treated groups. Matrigel matrix demonstrated spotted cell clustering pattern in antisense- and siRNA-transfected U251 cells, indicating poor cell growth activities. In addition, the tumor volumes in U251 subcutaneous mice model treated with antisense and siRNA were significantly smaller than those treated with control siRNA and phosphate-buffered saline. Also, glial fibrillary acidic protein expression was upregulated in antisense- and siRNA-treated groups than the control groups. Our results demonstrated that antisense- or siRNA-targeting intracellular region of EGFR can inhibit EGFR expression, exerted growth inhibition effect on U251 glioma cells in vitro and in vivo. Consequently, siRNA expression plasmid-mediated gene therapy would be a new strategy in treatment of gliomas.
The influence of van der Waals (vdW) and Casimir forces on the stability of the electrostatic torsional nanoelectromechanical systems (NEMS) actuators is analyzed in the paper. With the consideration ...of vdW and Casimir effects, the dependence of the critical tilting angle and pull-in voltage on the sizes of structure is investigated. The influence of vdW torque is compared with that of Casimir torque. The modified coefficients of vdW and Casimir torques on the pull-in voltage are, respectively, calculated. When the gap is sufficiently small, pull-in can still take place with arbitrary small angle perturbation because of the action of vdW and Casimir torques even if there is not electrostatic torque. And the critical pull-in gaps for two cases are, respectively, derived.
Fenton's oxidation is traditionally used to remove inorganic and organic pollutants from water in waster water treatment. It is an advanced oxidation process in which H2O2 is catalytically decomposed ...by ferrous irons into hydroxyl radicals (*OH) which have a higher oxidation potential (2.8V) than H2O2. In the work reported here, we for the first time use Fenton's oxidation to modify the surface of biomedical NiTi shape memory alloy (SMA). The influences of Fenton's oxidation on the surface microstructure, blood compatibility, leaching of harmful Ni ions and corrosion resistance in simulated body fluids is assessed using scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, inductively coupled plasma mass spectrometry, electrochemical tests, hemolysis analysis and the blood platelet adhesion test. The mechanical stability of the surface titania film produced by Fenton's oxidation as well as their effects on the shape memory behavior of the SMA are studied by bending tests. Our results show that Fenton's oxidation produces a novel nanostructured titania gel film with a graded structure on the NiTi substrate without an intermediate Ni-rich layer that is typical of high-temperature oxidation. Moreover, there is a clear Ni-free zone near the top surface of the titania film. The surface structural changes introduced by Fenton's oxidation improve the electrochemical corrosion resistance and mitigate Ni release. The latter effects are comparable to those observed after oxygen plasma immersion ion implantation reported previously and better than those of high-temperature oxidation. Aging in boiling water improves the crystallinity of the titania film and further reduces Ni leaching. Blood platelet adhesion is remarkably reduced after Fenton's oxidation, suggesting that the treated SMA has improved thrombo resistance. Enhancement of blood compatibility is believed to stem from the improved hemolysis resistance, the surface wettability and the intrinsic electrical characteristics of the titania film. The titania film produced by Fenton's oxidation has good mechanical stability and does not adversely impact the shape memory behavior of NiTi. Our work suggests that Fenton's oxidation is a promising low-temperature, low-cost surface modification method for improving the surface properties of biomedical NiTi SMA.
Endoplasmic reticulum (ER) chaperone Prolyl 4-hydroxylase, beta polypeptide (P4HB) has previously been identified as a novel target for chemoresistance in glioblastoma multiforme (GBM). Yet its ...functional roles in glioma carcinogenesis remain elusive. In clinical analysis using human glioma specimens and Gene Expression Omnibus (GEO) profiles, we found that aberrant expression of P4HB was correlated with high-grade malignancy and an angiogenic phenotype in glioma. Furthermore, P4HB upregulation conferred malignant characteristics including proliferation, invasion, migration and angiogenesis
, and increased tumor growth
via the mitogen-activated protein kinase (MAPK) signaling pathway. Pathway analysis suggested genetic and pharmacologic inhibition of P4HB suppressed MAPK expression and its downstream targets were involved in angiogenesis and invasion. This is the first study that demonstrates the oncogenic roles of P4HB and its underlying mechanism in glioma. Since tumor invasion and Vascularisation are typical hallmarks in malignant glioma, our findings uncover a promising anti-glioma mechanism through P4HB-mediated retardation of MAPK signal transduction.
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