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Registration between the baseline and follow-up lung computed tomography (CT) volumes plays an important role in computer-aided diagnosis and following-up care during adaptive radiotherapy. Diffeom...

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.

Additional file 1. A summarizing statement in the methodology.

Background: Streptococcus pneumoniae is a leading pathogen worldwide and its pathogenesis remains unclear. Objectives: The study aimed to investigate the secretion of interleukin-8 (IL-8) and soluble intercellular adhesion molecule-1 (ICAM-1) from A549 pneumocytes stimulated by different S. pneumoniae strains and the mechanism of blood-derived S. pneumoniae (bd-SP) in invading the blood system. Methods: Twenty-three clinical strains of S. pneumoniae isolated in 2009 along with ATCC49619 were cultured and suspended in 2018. Then, A549 pneumocytes were resuspended after culture and collection, and inoculated into culture plates. Streptococcus pneumoniae suspensions were then inoculated. Normal saline was blank control. The plates were incubated for four and eight hours. Then, the suspensions were collected and centrifuged. The supernatant was analyzed for IL-8 and ICAM-1 by ELISA. Results: The concentrations of IL-8 were 180.6, 188.5, 223.4 ± 19.9, and 230.3 ± 38.6 pg/mL for blank control, ATCC49619, blood-derived S. pneumoniae (bd-SP) and sputum-derived S. pneumoniae (sd-SP) at four-hour stimulation, respectively, and 249.2, 275.7, 224.0 ± 27.8, and 242.3 ± 33.1 pg/mL at eight-hour stimulation. The concentrations of ICAM-1 were 14.8, 12.1, 19.9 ± 17.2, and 26.1 ± 28.6 ng/mL for blank control, ATCC49619, bd-SP, and sd-SP at 4 hours, respectively, and 32.6, 150.8, 69.4 ± 45.1, and 58.7 ± 30.1 ng/mL at 8 hours. Conclusions: Streptococcus pneumoniae could upregulate the secretion of IL-8 and ICAM-1 from A549 pneumocytes. No significant difference was found between bd-SP and sd-SP which was in contrast to what was found between clinical S. pneumoniae and ATCC49619. Host response may not be a vital factor for different S. pneumoniae infections.

BACKGROUND Streptococcus pneumoniae (SP) is a Gram-positive, alpha-hemolytic, facultative anaerobic member of the genus Streptococcus. The erythromycin-resistant methylase (erm) gene and macrolide efflux (mef) gene are the 2 main genes that can mediate SP. Transposon (Tn) also plays an important role in the collection and metastasis of the gene. In the present study we investigated the drug resistance characteristics and the macrolide-resistant mechanisms of SP in Wenzhou City, China. MATERIAL AND METHODS Sixty-eight strains of SP were isolated from sputum samples of hospitalized children in the Second Affiliated Hospital of Wenzhou Medical University. These strains were analyzed using antimicrobial susceptibility tests to determine their drug resistance to 10 kinds of antibacterials. Macrolide-resistant phenotypes were identified using K-B method. PCR method was used to analyze the erm B gene, mef A gene, and int Tn gene. RESULTS Drug resistance rates of 68 strains of SP were 98.5%, 100.0%, 63.2%, 52.9%, 94.1%, 89.7%, 0.0%, 0.0%, 16.2%, and 14.7% for clindamycin, erythromycin, penicillin G, cefotaxime, tetracycline, sulfamethoxazole/trimethoprim, levofloxacin, vancomycin, chloramphenicol, and amoxicillin, respectively. Total detection rates of the erm B gene, mef A gene, and int Tn gene were 98.5%, 91.2%, and 100.0%, respectively. CONCLUSIONS SP shows significant multi-drug resistance in Wenzhou City, whereas there is no clinical value of macrolides antibiotics for SP. cMLSB mediated by erm B gene is the most predominant phenotype among macrolide-resistant SP. The int Tn gene may play an important role in horizontal transfer and clonal dissemination of SP drug resistance genes in Wenzhou City.

Both Von Hippel-Lindau tumor suppressor (VHL) and Never-in-mitosis A (NIMA)-related kinase 1 (NEK1) are involved in primary cilium formation, but whether VHL could regulate NEK1 is unknown. Here, we demonstrated that renal cancer cells Caki-1 and ACHN with wild-type VHL expressed lower level of NEK1 than that of VHL-defective cells including 786-O, 769-P and A498 cells. VHL-overexpression down-regulated NEK1 in 769-P cells, while VHL-knockdown up-regulated NEK1 in Caki-1 cells. In addition, we found the hypoxia response element (HRE) in the promoter sequence of NEK1 and hypoxia induced NEK1 expression both in vitro and in vivo. HIF-2α knockdown blocked hypoxia induced NEK1 upregulation instead of HIF-1α, which indicates that NEK1 may be a new target of HIF-2α. Moreover, we confirmed the association between VHL and NEK1 in Caki-1 cell, then showed VHL promoted NEK1 protein degradation and ubiquitination. In conclusion, our findings showed VHL regulates NEK1 via both HIF-2α pathway and ubiquitin-proteasome pathway in renal cancer cells.

Background As the second leading cause of cancer morbidity and death in women, cervical cancer remains an important public health problem worldwide. Novel biomarkers with high sensitivity and specificity for the early detection and diagnosis of cervical cancer are urgently needed. Increasing evidence shows that long noncoding RNAs (lncRNAs) are differentially expressed in cancer tissues and may serve as diagnostic markers. In multiple tumor types, exosomes harboring lncRNAs are actively released from tumor cells. In this study, we investigate the potential association of exosomal lncRNA expression with cervical cancer. Methods Cervicovaginal lavage specimens were collected from patients with cervical cancer and cancer-free volunteers who are HPV-positive or HPV-negative. Exosomes in these specimens were isolated by ultracentrifugation and confirmed by transmission electron microscopy. The exosomal lncRNAs HOTAIR, MALAT1, and MEG3 were quantified by qRT-PCR. Results Expression of HOTAIR, MALAT1 and MEG3 was predominantly observed in cervical cancer-derived exosomes in cervicovaginal lavage samples. The expression levels of lncRNAs were significantly different in exosomes isolated from cervical cancer patients compared to normal controls. Conclusions 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.

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 andβ-elemene in follicular thyroid cancer cells.Methods.MTT assay was used to determine the FTC-133 cell proliferation after culturing with rapamycin and/orβ-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 andβ-elemene exerted significant synergistic antiproliferative effects in FTC-133 cell linesin vitro, based on inhibiting the AKT feedback activation induced by rapamycin.In vivo, theβ-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 withβ-elemene synergistically attenuates tumor cell growth in follicular thyroid cancer, which requires additional preclinical validation.

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; pConclusionThis meta-analysis suggests that patients with gout have an increased risk of myocardial infarction.

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).