Diagnostic value of circulating microRNAs in thyroid carcinoma: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Thyroid cancer (TC) is the most common endocrine system tumour. Several studies had revealed the potential of circulating microRNAs (miRNAs) as novel biomarkers for the diagnosis of TC. The purpose of this meta-analysis is to summarize published studies and evaluate the diagnostic accuracy of circulating miRNAs in TC detection. METHODS: In this meta-analysis, we systematically searched three databases: PubMed, EMBASE and Cochrane Library. We used the bivariate mixed-effects regression model to calculate the pooled diagnostic parameters and conduct the summary receiver operator characteristic curve (SROC). All calculations were performed using stata software. RESULTS: Thirty-five studies from 9 articles, including 663 TC patients, 519 patients with benign thyroid nodules (BTNs), and 84 healthy controls were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the SROC curve (AUC) were 0.81 (95% CI 0.75-0.86), 0.81 (95% CI 0.75-0.86), 4.3 (95% CI 3.2-5.6), 0.24 (95% CI 0.18-0.31), 18 (95% CI 12-28) and 0.88 (95% CI 0.85-0.90), respectively in BTN controls, and 0.81 (95% CI 0.75-0.86), 0.85 (95% CI 0.75-0.91), 5.3 (95% CI 3.3-8.7), 0.23 (95% CI 0.18-0.29), 24 (95% CI 14-39), 0.89 (95% CI 0.86-0.91) in healthy controls. The subgroup analysis found that multiple miRNA assays had higher diagnostic accuracy than single miRNA assays with sensitivity of 0.88, specificity of 0.89 and AUC of 0.94. CONCLUSION: Circulating miRNAs have good values to diagnose TC and distinguish TC patients from BTN patients. MiRNAs can assist in the diagnosis of malignancy and avoid unnecessary surgery. In summary, circulating miRNAs should be added to our current clinical tools.

Tea Polysaccharide Prevents Colitis-Associated Carcinogenesis in Mice by Inhibiting the Proliferation and Invasion of Tumor Cells.

The imbalance between cell proliferation and apoptosis can lead to tumor progression, causing oncogenic transformation, abnormal cell proliferation and cell apoptosis suppression. Tea polysaccharide (TPS) is the major bioactive component in green tea, it has showed antioxidant, antitumor and anti-inflammatory bioactivities. In this study, the chemoprophylaxis effects of TPS on colitis-associated colon carcinogenesis, especially the cell apoptosis activation and inhibition effects on cell proliferation and invasion were analyzed. The azoxymethane/dextran sulfate sodium (AOM/DSS) was used to induce the colorectal carcinogenesis in mice. Results showed that the tumor incidence was reduced in TPS-treated AOM/DSS mice compared to AOM/DSS mice. TUNEL staining and Ki-67 immunohistochemistry staining showed that the TPS treatment increased significantly the cell apoptosis and decreased cell proliferation among AOM/DSS mice. Furthermore, TPS reduced the expression levels of the cell cycle protein cyclin D1, matrix metalloproteinase (MMP)-2, and MMP-9. In addition, in vitro studies showed that TPS, suppressed the proliferation and invasion of the mouse colon cancer cells. Overall, our findings demonstrated that TPS could be a potential agent in the treatment and/or prevention of colon tumor, which promoted the apoptosis and suppressed the proliferation and invasion of the mouse colon cancer cells via arresting cell cycle progression.

Tumor Microenvironment as a New Target for Tumor Immunotherapy of Polysaccharides.

Many researches show that polysaccharides derived from fungi and plants have strong pharmacological activities such as enhancing the organism immune and anti-tumor function, and have few toxic and side effects. So the polysaccharides show a wide application prospect in the prevention and therapy of tumor. The tumor microenvironment consists of tumor cells and tumor cells' surrounding environment. The tumor microenvironment not only plays a key role in the development of tumor, but also is a potential treasure for searching new ways to treat tumor. In this review, we summarized polysaccharides' regulation effects on tumor microenvironment progression and tried to give a new theoretical basis for the exploitation of polysaccharides with anti-tumor activity.

Role of the mTOR Signalling Pathway in Experimental Rabbit Vein Grafts.

BACKGROUND: Coronary artery bypass grafting is employed for the treatment of multiple-vessel lesions. Studies have shown that continued maladaptive remodelling expedites atherosclerosis and that excessive remodelling leads to graft restenosis. However, few studies have focussed on mechanistic target of rapamycin (mTOR) signalling involved during remodelling of transplanted veins. METHODS: Rabbits were randomly allocated to groups undergoing vein-graft restenosis or sham surgery. At 1, 3, 7, 14, 28 and 90 days after surgery, we removed bypassed grafts and placed them in groups named T1, T2, T3, T4, T5 and T6, respectively. Group T0 denoted the control group. Analysis included vessel thickness, electron microscope data, TUNEL staining, and expression of the proliferation-associated gene proliferating cell nuclear antigen (PCNA). We chose specific time-points of gene expression, and then observed changes in the mTOR signalling. RESULTS: The early stage of vein grafting (one to three days after surgery) led to apoptosis and degradation of the extracellular matrix. Seven days after surgery, cells began to proliferate. RICTOR expression in mTOR complex 2 (mTORC2) and that of its downstream substrate protein kinase C was enhanced in the early stage (T1 and T3), and was higher in T1. mTORC1's upstream gene regulation decreased in T1 and increased in T3. Its downstream genes eIF4b and 4E-BP showed similar changes. Expression of eIF4e and eIF4b increased, and led to an increase in protein composition. CONCLUSIONS: After transplantation, mTORC1 function and its upstream and downstream genes were inhibited on the first day after grafting, but mTORC2 function was enhanced. One week after surgery, mTORC2 was still overexpressed when mTORC1 function had recovered and became enhanced. Hence, mTORC2 plays a major role in arterialisation of veins.

Natural polysaccharides exhibit anti-tumor activity by targeting gut microbiota.

Natural polysaccharides, the abundant dietary components, show potent antitumor bioactivity in treatment and chemoprevention. Compared with traditional tumor therapy, natural polysaccharides are characterized by the low toxicity and immuno-regulation function. Recent researches have indicated that the anti-tumor of polysaccharides was partly attributable to modification in the composition of gut microbiota when polysaccharides were digested. Indeed, microbial dysbiosis or alteration of certain bacterial species has been reported in tumorigenesis. Natural polysaccharides intake can reverse such changes by enriching health-promoting bacteria and metabolite the intestine. In this review, we first summarize current knowledge on the anti-tumor activity of polysaccharides, and demonstrate the relationship between bacteria and metabolite in the intestine tumorigenesis and microbial dysbiosis. Thereafter, and the "polysaccharides-gut microbiota" is put forward for polysaccharides to exhibit their antitumor activity, which may attribute to the improved leaky gut, avoided hypernutrition, and reinforced immune homeostasis, finally creating a systemic environment to lower the risks of tumor.

Impact of Taurine on the proliferation and apoptosis of human cervical carcinoma cells and its mechanism.

BACKGROUND: Cervical cancer has the fourth highest incidence and mortality rate of all cancers in women worldwide; it seriously harms their physical and mental health. The aim of this study was to observe the roles and preliminary mechanism of Taurine (Tau)-induced apoptosis in cervical cancer cells. METHODS: Cells from the human cervical cancer cell line SiHa were transfected with the recombinant plasmid pEGFP-N1-MST1 (mammalian sterile 20-like kinase 1); then, the cell proliferation activity was analyzed by the MTT assay, cell apoptosis by flow cytometry, and the related protein levels by Western blotting. RESULTS: Tau inhibited the proliferation of SiHa cells and induced apoptosis in these cells (the apoptotic rate was 21.95% in the Tau 160 mmol/L group and 30% in the Tau 320 mmol/L group), upregulated the expression of the MST1 (control, 0.53; Tau 40-320 mmol/L groups, 0.84-1.45) and Bax (control, 0.45; Tau 40-320 mmol/L groups, 0.64-1.51) proteins (P < 0.01), and downregulated the expression of Bcl-2 (control, 1.28, Tau 40-320 mmol/L groups, 0.93-0.47) (P < 0.01). The overexpression of MST1 promoted the apoptosis of SiHa cells, enhanced the apoptosis-inductive effects of Tau (P < 0.01), upregulated the expression of the proapoptotic proteins p73, p53, PUMA (p53 upregulated modulator of apoptosis), and caspase-3, and promoted the phosphorylation of YAP (Yes-associated protein). CONCLUSIONS: Tau inhibited the proliferation and induced the apoptosis of cervical cancer SiHa cells. The MST1 protein plays an important role in the Tau-induced apoptosis of cervical cancer cells.

Identification of potential crucial genes and pathways associated with vein graft restenosis based on gene expression analysis in experimental rabbits.

Occlusive artery disease (CAD) is the leading cause of death worldwide. Bypass graft surgery remains the most prevalently performed treatment for occlusive arterial disease, and veins are the most frequently used conduits for surgical revascularization. However, the clinical efficacy of bypass graft surgery is highly affected by the long-term potency rates of vein grafts, and no optimal treatments are available for the prevention of vein graft restenosis (VGR) at present. Hence, there is an urgent need to improve our understanding of the molecular mechanisms involved in mediating VGR. The past decade has seen the rapid development of genomic technologies, such as genome sequencing and microarray technologies, which will provide novel insights into potential molecular mechanisms involved in the VGR program. Ironically, high throughput data associated with VGR are extremely scarce. The main goal of the current study was to explore potential crucial genes and pathways associated with VGR and to provide valid biological information for further investigation of VGR. A comprehensive bioinformatics analysis was performed using high throughput gene expression data. Differentially expressed genes (DEGs) were identified using the R and Bioconductor packages. After functional enrichment analysis of the DEGs, protein-protein interaction (PPI) network and sub-PPI network analyses were performed. Finally, nine potential hub genes and fourteen pathways were identified. These hub genes may interact with each other and regulate the VGR program by modulating the cell cycle pathway. Future studies focusing on revealing the specific cellular and molecular mechanisms of these key genes and pathways involved in regulating the VGR program may provide novel therapeutic targets for VGR inhibition.

Roles of the MST1-JNK signaling pathway in apoptosis of colorectal cancer cells induced by Taurine.

The aim of this study was to observe the impact of the mammalian sterile 20-like kinase 1-c-Jun N-terminal kinase (MST1-JNK) signaling pathway on apoptosis in colorectal cancer (CRC) cells induced by Taurine (Tau). Caco-2 and SW620 cells transfected with p-enhanced green fluorescent protein (EGFP)-MST1 or short interfering RNA (siRNA)-MST1 were treated with Tau for 48 h. Apoptosis was detected by flow cytometry, and the levels of MST1 and JNK were detected by western blotting. Compared with the control group, 80 mM Tau could significantly induce apoptosis of CRC cells, and the apoptotic rate increased with increasing Tau concentration (P < 0.01). Meanwhile, the protein levels of MST1 and phosphorylated (p)-JNK in Caco-2 cells increased significantly (P < 0.01). The apoptotic rate of the p-EGFP-MST1 plasmid-transfected cancer cells was significantly higher than that of the control group (P < 0.05); however, the apoptotic rate of the p-EGFP-MST1+Tau group was increased further (P < 0.01). Silencing the MST1 gene could decrease the apoptotic rate of cancer cells, and Tau treatment could reverse this decrease. Blocking the JNK signaling pathway significantly reduced the Tau-induced apoptotic rate of CRC cells. Thus, the MST1-JNK pathway plays an important role in Tau-induced apoptosis of CRC cells.

Inhibitory effect and mechanism of exogenous mammalian sterile 20-like kinase 1 on the growth of human colorectal cancer.

The present study aimed to observe the inhibitory effect and preliminary mechanism of exogenous mammalian sterile 20-like kinase 1 (MST1) on the growth of colorectal cancer SW480 cells. The SW480 cells were randomly divided into the following groups: Control, empty enhanced green fluorescent protein (EGFP) plasmid (pEGFP-N1), MST1 EGFP plasmid (pEGFP-MST1), 20 µmol/l fluorouracil (5-FU) and pEGFP-MST1 + 5-FU. An MTS colorimetric assay was used to detect cell viability, Hoechst 33342 staining was used to observe cell apoptosis, and western blotting and immunohistochemistry were used to detect the levels of the proteins MST1, yes-associated protein (YAP), phospho-YAP1 (Ser127), p53 and p53 upregulated modulator of apoptosis (PUMA). In addition, nude mice were injected with SW480 cells to assess the tumor inhibition rates. Compared with the control group, the growth inhibition and apoptosis rates, the levels of MST1, p53 and PUMA, and the ratios of phospho-YAP1/YAP in the pEGFP-MST1 and pEGFP-MST1 + 5-FU groups were increased significantly (P<0.01). Additionally, relative to the control group, the tumor inhibition rates in the nude mice transplanted with SW480 cells of the pEGFP-MST1 and pEGFP-MST1 + 5-FU groups were 48.52±1.63 and 87.28±2.58%, respectively, and the positive rates of phospho-YAP1 (Ser127) protein in nuclei increased significantly (P<0.01). Overall, exogenous MST1 effectively inhibited the proliferation and growth of transplanted human colorectal cancer cells and promoted cancer cell apoptosis. The mechanism involved may be associated with the increase of intracellular phospho-YAP1 (Ser127) protein.

Bi-layer Channel AZO/ZnO Thin Film Transistors Fabricated by Atomic Layer Deposition Technique.

This letter demonstrates bi-layer channel Al-doped ZnO/ZnO thin film transistors (AZO/ZnO TFTs) via atomic layer deposition process at a relatively low temperature. The effects of annealing in oxygen atmosphere at different temperatures have also been investigated. The ALD bi-layer channel AZO/ZnO TFTs annealed in dry O2 at 300 °C exhibit a low leakage current of 2.5 × 10-13A, I on/I off ratio of 1.4 × 107, subthreshold swing (SS) of 0.23 V/decade, and high transmittance. The enhanced performance obtained from the bi-layer channel AZO/ZnO TFT devices is explained by the inserted AZO front channel layer playing the role of the mobility booster.