Yanwen Yao

Long non-coding RNAs: a new frontier in the study of human diseases.

With the development of whole genome and transcriptome sequencing technologies, long noncoding RNAs (lncRNAs) have received increased attention. Multiple studies indicate that lncRNAs act not only as the intermediary between DNA and protein but also as important protagonists of cellular functions. LncRNAs can regulate gene expression in many ways, including chromosome remodeling, transcription and post-transcriptional processing. Moreover, the dysregulation of lncRNAs has increasingly been linked to many human diseases, especially in cancers. Here, we reviewed the rapidly advancing field of lncRNAs and described the relationship between the dysregulation of lncRNAs and human diseases, highlighting the specific roles of lncRNAs in human diseases.

Doping effect on the dielectric property in bismuth titanate

The dielectric property complemented by the mechanical measurement (internal friction) in the doped Bi4Ti3O12 [Bi4−xLaxTi3O12 (x=0.5,0.75,1) and Bi4−y/3Ti3−yNbyO12 (y=0.015,0.03,0.06)] was systematically investigated from room temperature to 350 °C. In the plot of dielectric loss versus temperature for Bi4Ti3O12 (BiT), a relaxation peak was confirmed to be associated with the motion of the oxygen vacancy. It is found that the La doping at site A is in favor of improvement of the fatigue property, in contrast, the Nb doping at site B can mainly enhance the remanent polarization. Appropriate La doping at site A of perovskite-type unit in BiT enhances the chemical stability of oxygen vacancy by improving the height of the potential barrier for hopping and enhances the mobility of domain by the changing of domain structures. While the Nb doping at site B could induce the distortion of oxygen octahedral and reduce the oxygen vacancy concentration by a compensating effect so that it results in an enhancement of...

A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer.

In more recent years, long non‐coding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. Although lncRNAs are dysregulated in numerous cancer types, limited data are available on the expression profile and functional role of lncRNAs in non‐small cell lung cancer (NSCLC). In the present study, we determined the expression pattern of the growth arrest‐specific transcript 5 (GAS5) in 72 NSCLC specimens by qRT‐PCR and assess its biological functions in the development and progression of NSCLC. The results revealed that GAS5 expression was down‐regulated in cancerous tissues compared to adjacent noncancerous tissues (P < 0.05) and was highly related to tumor size and TNM stage (P < 0.05). This correlation between GAS5 and clinicopathological parameters indicates that GAS5 might function as a tumor suppressor. Furthermore, GAS5 overexpression increased tumor cell growth arrest and induced apoptosis in vitro and in vivo. Meanwhile, siRNA‐mediated knockdown of GAS5 promoted tumor cell growth. Importantly, through western blot analysis, we found that ectopic expression of GAS5 significantly up‐regulated p53 expression and down‐regulated transcription factor E2F1 expression. Taken together, these findings suggest that GAS5 is a tumor suppressor in NSCLC, and the action of GAS5 is mediated by p53‐dependent and p53‐independent pathways. GAS5 could serve as a potential diagnostic marker for NSCLC and may be a novel therapeutic target in patients with NSCLC.

The growth arrest-specific transcript 5 (GAS5): a pivotal tumor suppressor long noncoding RNA in human cancers

Long noncoding RNAs (lncRNAs), which refer to a group of RNAs with length more than 200 nucleotides and limited protein-coding potential, play a widespread role in regulating biological processes, such as cell differentiation, proliferation, apoptosis, and migration. LncRNAs are dysregulated in multiple cancers, playing an either oncogenic or tumor-suppressive role. LncRNA GAS5 is a recently identified tumor suppressor involved in several cancers, like breast cancer, prostate cancer, lung cancer, and colorectal cancer. The low-expression pattern confers tumor cells elevated capacity of proliferation and predicts poorer prognosis. Existing studies mirror that lncRNA GAS5 promises to be a novel diagnostic biomarker, therapy target, as well as prognostic biomarker. In this review, we will summarize the current knowledge about this vital lncRNA, from its discovery, characteristics, and biological function to molecular mechanism in various neoplasms.

The plasma mitochondrial DNA is an independent predictor for post-traumatic systemic inflammatory response syndrome.

Background and Purpose Mitochondrial DNA (mtDNA), a newly identified damage-associated molecular pattern, has been observed in trauma patients, however, little is known concerning the relationship between plasma mtDNA levels and concrete post-traumatic complications, particularly systemic inflammatory response syndrome (SIRS). The aim of this study is to determine whether plasma mtDNA levels are associated with injury severity and cloud predict post-traumatic SIRS in patients with acute traumatic injury. Patients and Methods Eighty-six consecutive patients with acute traumatic injury were prospectively enrolled in this study. The plasma mtDNA concentration was measured by a real-time, quantitative PCR assay for the human ND2 gene. The study population’s clinical and laboratory data were analyzed. Results The median plasma mtDNA was higher in trauma patients than in healthy controls (865.196 (251.042-2565.40)pg/ml vs 64.2147 (43.9049-80.6371)pg/ml, P<0.001) and was independently correlated with the ISS score (r=0.287, P<0.001). The plasma mtDNA concentration was also significantly higher in patients who developed post-traumatic SIRS than in patients who did not (1774.03 (564.870-10901.3)pg/ml vs 500.496 (145.415-1285.60)pg/ml, P<0.001). Multiple logistic regression analysis revealed that the plasma mtDNA was an independent predictors for post-traumatic SIRS (OR, 1.183 (95%CI, 1.015-1.379), P=0.032). Further ROC analysis demonstrated that a high plasma mtDNA level predicted post-traumatic SIRS with a sensitivity of 67% and a specificity of 76%, with a cut-off value of 1.3185 µg/ml being established, and the area under the ROC curves (AUC) was 0.725 (95% CI 0.613-0.837). Conclusions Plasma mtDNA was an independent indictor with moderate discriminative power to predict the risk of post-traumatic SIRS.

Study on ferroelectric and dielectric properties of niobium doped Bi4Ti3O12 ceramics and thin films prepared by PLD method

Abstract Nb doped bismuth titanate Bi 4− x (Ti 1− x Nb x ) 3 O 12 ( x =0%, 0.2%, 0.4%, 1%, 1.5%) ceramic samples were sintered and random oriented Bi 4− x (Ti 1− x Nb x ) 3 O 12 ( x =1%) thin films were fabricated on (111)Pt/TiO 2 /SiO 2 /Si with Pulsed Laser Deposition (PLD) method. The dielectric and ferroelectric properties of Nb doped Bi 4 Ti 3 O 12 (BTO) were investigated. A small amount of niobium doping results in a marked improvement in 2 P r . The 2 P r , 2 E c , dielectric constant and loss factor of Bi 4− x (Ti 1− x Nb x ) 3 O 12 ( x =1%) thin film are about 30 μC/cm 2 , 130 kV/cm, 175 and 0.02, respectively. However, after 3×10 9 switching cycles, 45% degradation of 2 P r was observed in the film.

Pretreatment platelet-to-lymphocyte ratio (PLR) as a predictor of response to first-line platinum-based chemotherapy and prognosis for patients with non-small cell lung cancer.

BACKGROUND Previous studies showed the platelet-to-lymphocyte ratio (PLR) was associated with the prognosis of many tumors. However, to our knowledge, no study has explained the role of PLR in predicting response to first-line chemotherapy and prognosis for patients with non-small cell lung cancer (NSCLC). The aim of this study was to characterize the role of pretreatment PLR in NSCLC. METHODS We consecutively enrolled 210 patients who were diagnosed with NSCLC in Jinling hospital (Nanjing, China) between January 2001 and August 2012. The platelet and lymphocyte counts of peripheral blood were measured before treatment was initiated. Each patient received at least two cycles of standardized combination chemotherapy. The response to chemotherapy was assessed after two cycles. RESULTS Based on a receiver operator characteristic (ROC) curve, 152.6 was defined as the cut-off value of PLR for predicting response. An evaluated PLR (≥152.6) was an independent risk factor for response to first-line chemotherapy [odds ratio (OR), 4.503; 95% confidence interval (CI): 2.213-9.166, P=0.000]. Univariate and multivariate survival analyses showed that an elevated PLR was associated with a poor prognosis for patients with NSCLC [hazard ratio (HR), 1.867; 95% CI: 1.328-2.625; HR, 2.025; 95% CI: 1.405-2.919, respectively]. CONCLUSIONS Our study shows that PLR maybe a potentially useful biomarker for predicting response to first-line chemotherapy and prognosis in NSCLC.

Intratracheal administration of mitochondrial DNA directly provokes lung inflammation through the TLR9-p38 MAPK pathway

An increasing number of studies have focused on the phenomenon that mitochondrial DNA (mtDNA) activates innate immunity responses. However, the specific role of mtDNA in inflammatory lung disease remains elusive. This study was designed to examine the proinflammatory effects of mtDNA in lungs and to investigate the putative mechanisms. C57BL/6 mice were challenged intratracheally with mtDNA with or without pretreatment with chloroquine. Changes in pulmonary histopathology, cytokine concentrations, and phosphorylation levels of p38 MAPK were assayed at four time points. In in vitro experiments, THP-1 macrophages were pretreated or not pretreated with chloroquine, TLR9 siRNA, p38 MAPK siRNA, or SB203580 and then incubated with mtDNA. The levels of cytokines and p-p38 MAPK were detected by ELISA and Western blot, respectively. The intratracheal administration of mtDNA induced infiltration of inflammatory cells, production of proinflammatory cytokines (including IL-1β, IL-6, and TNF-α), and activation of p38 MAPK. The chloroquine pretreatment resulted in an abatement of mtDNA-induced local lung inflammation. In vitro experiments showed that the exposure of THP-1 macrophages to mtDNA also led to a significant upregulation of IL-1β, IL-6, and TNF-α and the activation of p38 MAPK. And these responses were inhibited either by chloroquine and TLR9 siRNA or by SB203580 and p38 MAPK siRNA pretreatment. The intratracheal administration of mtDNA induced a local inflammatory response in the mouse lung that depended on the interactions of mtDNA with TLR9 and may be correlated with infiltrating macrophages that could be activated by mtDNA exposure via the TLR9-p38 MAPK signal transduction pathway.

Post-transcriptional regulation of long noncoding RNAs in cancer.

It is a great surprise that the genomes of mammals and other eukaryotes harbor many thousands of long noncoding RNAs (lncRNAs). Although these long noncoding transcripts were once considered to be simply transcriptional noise or cloning artifacts, multiple studies have suggested that lncRNAs are emerging as new players in diverse human diseases, especially in cancer, and that the molecular mechanisms of lncRNAs need to be elucidated. More recently, evidence has begun to accumulate describing the complex post-transcriptional regulation in which lncRNAs are involved. It was reported that lncRNAs can be implicated in degradation, translation, pre-messenger RNA (mRNA) splicing, and protein activities and even as microRNAs (miRNAs) sponges in both a sequence-dependent and sequence-independent manner. In this review, we present an updated vision of lncRNAs and summarize the mechanism of post-transcriptional regulation by lncRNAs, providing new insight into the functional cellular roles that they may play in human diseases, with a particular focus on cancers.

A Serum Vitamin D Level <25nmol/L Pose High Tuberculosis Risk: A Meta-Analysis

Background Low serum Vitamin D is considered to be associated with tuberculosis while the “dangerous” level was not clear. The aim of this study was to identify the association between tuberculosis and serum Vitamin D levels via synthesis of available evidence. Methods A search of EMBASE, Medline, ISI Web of knowledge, and Pubmed was conducted. The number of subjects of tuberculosis and no-tuberculosis groups in four Vitamin D range. Meta-analyses were performed and presented by odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results A total of 15 studies involving 1440 cases and 2558 controls were included. A significantly increased risk of tuberculosis was found in two ranges: ≤ 12.5 nmol/L: pooled OR = 4.556, 95% CI = 2.200-9.435; 13-25 nmol/L: pooled OR = 3.797, 95% CI = 1.935-7.405. No statistically significant risk of tuberculosis was found in the range of 26–50 nmol/L (pooled OR = 1.561, 95% CI =0.997-2.442). In range 51–75 nmol/L, no positive association was found (pooled OR =1.160, 95% CI = 0.708-1.900). Conclusions This study found that a serum Vitamin D level ≤ 25 nmol/L was significantly associated with an increased risk of tuberculosis while the range of 51–75 nmol/L was not. The range 26-50nmol/L posed potential high tuberculosis risk. Future large-scale, well-designed studies are needed to verify these results.