Our data suggest that lncRNAs in exosomes isolated from cervicovaginal lavage are differentially expressed in cervical cancer patients and cancer-free volunteers. Exosomal lncRNAs may have great potential to be used for the early detection and diagnosis of cervical cancer, and serve as convenient and noninvasive biomarkers.

Malignant gliomas are a heterogeneous group of brain tumors with a poor prognosis, which is largely due to its aggressive invasiveness and angiogenesis. In recent years, it has been found that multiple long noncoding RNAs (lncRNAs) participate in a wide range of biological functions including angiogenesis through the regulation of gene expression in cancers. In this study, we investigate and report the novel role of lncRNA SLC26A4‐AS1 in gliomas, with a novel mechanism involving transcription factors NFKB1 and NPTX1. We determined that SLC26A4‐AS1 was downregulated in human glioma tissues and cells. Furthermore, overexpression of SLC26A4‐AS1 or NPTX1 restrained the aggressiveness of glioma cells and their pro‐angiogenic ability. SLC26A4‐AS1 was also found to upregulate NPTX1 by recruiting NFKB1 into the NPTX1 promoter. Moreover, silencing of either NPTX1 or NFKB1 restored the aggressive and pro‐angiogenic properties of glioma cells in the presence of SLC26A4‐AS1. Taken together, we demonstrate that SLC26A4‐AS1 promotes NPTX1 transcriptional activity by recruiting NFKB1 and thus exerting antiangiogenic effects on glioma cells. This study provides an experimental basis for the intervention of SLC26A4‐AS1 in the treatment of gliomas.

IntroductionA high incidence of myocardial infarction among patients with gout has been suggested by several observational studies. We performed a meta-analysis to evaluate the association between gout and the risk of myocardial infarction.Materials and MethodsThe PubMed and Embase databases were searched from inception to October 2014 for cohort studies that evaluating the association between gout and the risk of myocardial infarction. Summary estimates were derived using a random-effects model and reported as relative risks (RRs) with 95% confidence intervals (CIs).ResultsFive studies involving 8,656,413 participants with a total of 1000 MI events were included. Overall, gout was associated with an increased risk of myocardial infarction (RR 1.45; 95% CI, 1.19–1.75; p<0.001), and the association referred to non-fatal myocardial infarction (RR 1.29; 95% CI, 1.19–1.39; p <0.001) but not fatal myocardial infarction (RR 1.11; 95% CI, 0.96–1.28; p = 0.174). The increased risk was observed in both women (RR 1.62; 95% CI, 1.18–2.21; p = 0.003) and men (RR 1.45; 95% CI, 1.21–1.74; p <0.001). Stratified analysis revealed a gradual increase in myocardial infarction risk with a younger age of gout onset (age 20–44 years old (RR 2.82; 95% CI, 1.38–5.79; p = 0.05); 45–69 years old (RR 1.85; 95% CI, 1.22–2.82; p = 0.04); ≥70 years old (RR 1.52; 95% CI, 1.22–1.88; p <0.001)).ConclusionThis meta-analysis suggests that patients with gout have an increased risk of myocardial infarction.

Background: Never in mitosis gene A (NIMA)-related kinase 8 (NEK8) regulation is poorly understood. Results: Hypoxia induced NEK8 expression in vitro and in vivo. NEK8-siRNA transfection blocked pVHL-knockdown-induced cilia disassemble. Conclusion: pVHL down-regulates NEK8 via HIFs to maintain the primary cilia. Significance: Identification of a new target for HIF. NEK8 was involved in pVHL modulating cilia.

Skin injury can trigger formation of new lesions in psoriasis (Koebner phenomenon). The mechanisms through which injury exacerbates psoriasis are unclear. During wound repair, epidermal keratinocytes are activated and produce abundant IL‐36γ, further promoting the skin inflammation. IL‐17A is the cornerstone cytokine in the pathogenesis of psoriasis. We sought to investigate the effects of IL‐17A on injury‐induced keratinocyte activation and IL‐36γ production. Here, we demonstrated that dsRNA released from necrotic keratinocytes induced the expression of IL‐36γ. Silencing of TLR3 by siRNA decreased the IL‐36γ induction by necrotic keratinocyte supernatant. Co‐stimulation with dsRNA and IL‐17A synergistically increased the expression of IL‐36γ and other proinflammatory mediators (CCL20, CXCL8, DEFB4 and LCN2) in keratinocytes. The synergistic effects were not dependent on TLR3 upregulation, TNF receptor signalling and mRNA stabilization. Co‐stimulation with dsRNA and IL‐17A resulted in an accumulation of IκBζ. The synergistic upregulation of IL‐36γ and proinflammatory mediators were inhibited by IκBζ siRNA. Co‐stimulation with IL‐17A and poly(I:C) markedly activated the p38 MAPK and NF‐κB pathway, compared with poly(I:C). Blockade of p38 MAPK and NF‐κB suppressed dsRNA/IL‐17A–mediated IκBζ and IL‐36γ induction. These findings demonstrated that IL‐17A synergistically enhanced the dsRNA‐mediated IL‐36γ production through a p38 MAPK‐, NF‐κB–, and IκBζ‐dependent mechanism.

Twenty‑three clinical Streptococcus pneumoniae (SP) strains were isolated from blood and sputum specimens from the Second Affiliated Hospital of Wenzhou Medical College in 2009. These strains and the ATCC 49619 standard strain were cultured and suspended in normal saline (at a turbidity of 1.0 McFarland). The production of interleukin (IL)‑8, intracellular adhesion molecule‑1 (ICAM‑1) and IL‑10 in THP‑1 cells following stimulation with the SP suspension was analyzed by an enzyme-linked immunosorbent assay. The concentrations of IL‑8, ICAM‑1 and IL‑10 from the THP‑1 monocytes were greater than those of the blank control following stimulation with the SP suspension. No significant difference was identified in the levels of IL‑8, ICAM‑1 and IL‑10 secretion between THP‑1 monocytes stimulated by blood‑borne SP (bb‑SP) and sputum‑borne SP (sb‑SP).

Background. mTOR signaling would be a promising target for thyroid cancer therapy. However, in clinical trials, objective response rate with mTOR inhibitor monotherapy in most cancer types was modest. A new focus on development of combinatorial strategies with rapalogs is increasing. Objective. Investigating the combinatorial antitumor effect of rapamycin and β-elemene in follicular thyroid cancer cells. Methods. MTT assay was used to determine the FTC-133 cell proliferation after culturing with rapamycin and/or β-elemene. To analyze their combinatorial effect, immunoblotting was performed to analyze the activation status of AKT. Moreover, β-elemene attenuated rapamycin-induced immunosuppression was tested in mice. Results. Combination of rapamycin and β-elemene exerted significant synergistic antiproliferative effects in FTC-133 cell lines in vitro, based on inhibiting the AKT feedback activation induced by rapamycin. In vivo, the β-elemene could attenuate rapamycin-induced immunosuppression via reversing imbalance of Treg/Th17, with the underlying mechanism needed to be declared. Conclusions. We demonstrate that the novel combination of mTOR inhibitor with β-elemene synergistically attenuates tumor cell growth in follicular thyroid cancer, which requires additional preclinical validation.

Intercellular adhesion molecule-1 (ICAM-1) expression has been detected in melanocytes around active vitiligo patches as well as in surgically transplanted melanocytes. However, it is unclear whether and how skin injury induces the inappropriate expression of ICAM-1 and other proinflammatory genes in melanocytes. We previously reported that human melanocytes expressed TLR3. We hypothesized that the TLR3 expressed in melanocytes may recognize skin injury by binding to the endogenous ligands secreted by the damaged keratinocytes. Here we showed that RNA released from necrotic keratinocytes induced the upregulation of ICAM-1 protein and mRNA, as shown by FACS and real-time RT-PCR. Use of NF-κB inhibitor prevents upregulation of ICAM-1 in melanocytes indicating a direct role of NF-κB in necrotic keratinocyte-mediated upregulation of ICAM-1. Using a shRNA-expressing lentivirus, we demonstrated that in human melanocytes, TLR3 seems to be necessary for the upregulation of ICAM-1. Using oligonucleotide microarray, we demonstrated a dramatic increase in proinflammatory cytokine and chemokine transcripts (CXCL10, CXCL11, TNFSF10, CCL5, CCL4, CCL2, IFNB1, CCL20, IL-8, and CCL11). These observations suggested that RNA released from necrotic keratinocytes might act as an endogenous TLR3 ligand for the stimulation of ICAM-1 and other proinflammatory gene expression in human melanocytes, which might be involved in the pathogenesis of vitiligo following skin physical trauma.