Search

Thyroid-carcinoma (THCA) is the most common malignancy with an increasing incidence. Recent evidence has emphasized the role of microRNA (miRNA) in THCA. However, knowledge concerning the roles of miRNAs in THCA is still limited. We therefore use a miRNA-target gene differential regulatory network (MGDRN) to identify key miRNAs and characterize their synergistic regulation in THCA. Both miRNA-target gene interactions from multiple databases and negative expression correlations between miRNA-target genes were used to characterize the interactions. Then, two regulatory networks involving normal and tumor conditions were constructed, respectively. The MGDRN was finally constructed using different interactions between the above two regulatory networks. By analyzing topological features of the MGDRN, four miRNAs (hsa-mir-152-3p, hsa-mir-148a, hsa-mir-130b and hsa-mir-15b) are identified as key miRNAs in THCA. Over-expression of mir-152-3p inhibited proliferation and colony formation of TPC-1 cells. Furthermore, mir-152-3p negatively regulated ERBB3 by binding to the 3'-UTR of ERBB3, and down-regulation of ERBB3 by small interfering (si)RNAs inhibited proliferation and colony formation of TPC-1 cells, indicating that mir-152-3p acted as an anti-tumor miRNA by negatively regulating ERBB3. Finally, two synergistically dysregulated modules were identified which may contribute to the initiation and progression of THCA. Overall, the results provided a better understanding of the molecular basis of THCA, and suggested novel treatment strategies for this cancer. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is associated with systemic inflammatory conditions, such as diabetes. The aim of this study was to assess the serum BDNF levels in Chinese patients with type 2 diabetes (T2DM). From the outpatient clinic at the endocrinology department of our hospital, all patients with long-standing T2DM were recruited for this study between August 2014 and December 2014. Serum levels of BDNF were assayed with solid-phase sandwich ELISA, and the demographical and clinical data were evaluated on admission. Median serum BDNF levels were significantly lower in patients with T2DM compared to control subjects (15.9 ng/mL (interquartile range (IQR), 12.6-19.8) VS. 24.6 ng/mL (IQR, 17.2-27.8); P < 0.0001). Serum BDNF levels were inversely correlated with fasting glucose ( r = −0.394, P < 0.0001) and duration of illness ( r = −0.272, P < 0.0001) in T2DM patients. Based on the receiver operating characteristic (ROC) curve, the optimal cutoff value of serum BDNF levels as an indicator for diagnosis of T2DM was projected to be 23.0 ng/mL, which yielded a sensitivity of 89.0 % and a specificity of 60.9 %, with the area under the curve at 0.794 (95 % confidence interval (CI), 0.747-0.841; P < 0.001). In multivariate logistic regression analysis, after adjusting for other significant factors, BDNF can be seen as an indicator of independent diabetes complications with an odds ratio (OR) of 0.84 (95 % CI, 0.75-0.89; P < 0.001) and obesity with an OR of 0.88 (95 % CI, 0.80-0.92; P < 0.001). Our study suggested that low levels of BDNF accompany impaired glucose metabolism. Importantly, we found that decreased BDNF were correlated with obesity and diabetes complications. [ABSTRACT FROM AUTHOR]

GM1 ganglioside has a great impact on the function of nodes of Ranvier on myelinated fiber, suggesting its potential role to maintain the electrical and neuronal excitability of neurons. Here we first demonstrate that visceral afferent conduction velocity of myelinated and unmyelinated fibers are reduced significantly by tetrodotoxin (TTX) or cholera toxin-B subunits (CTX-B), and only the effects mediated by CTX-B are prevented by GM1 pre-treatment. At soma of myelinated A and unmyelinated C-type nodose ganglion neurons (NGNs), the action potential spike frequency reduced by CTX-B is also prevented by GM1. Additionally, the current density of both TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ channels were significantly decreased by CTX-B without changing the voltage-dependent property. These data confirm that endogenous GM1 may play a dominant role in maintaining the electrical and neuronal excitability via modulation of sodium (Na+) channel around nodes and soma as well, especially TTX-S Na+ channel, which is also confirmed by the reduction of spike amplitude and depolarization. Similar data are also extended to fluorescently identified and electrophysiologically characterized aortic baroreceptor neurons. These findings suggest that GM1 plays an important role in the neural modulation of electric and neuronal excitability in visceral afferent system. [ABSTRACT FROM AUTHOR]