BackgroundBladder cancer (BCa) is the ninth most common form of cancer in the world. There is a continuing need not only for improving the accuracy of diagnostic markers but also for the development of new treatment strategies. Recent studies have shown that the renin-angiotensin system (RAS), which include the angiotensin type 1 (AT1R), type 2(AT2R), and Mas receptors, play an important role in tumorigenesis and may guide us in meeting those needs.ResultsIn this study, we first observed that AT1R and Mas expression levels were significantly upregulated in BCa specimens while AT2R was significantly downregulated. Viral vector mediated overexpression of AT2R induced apoptosis and dramatically suppressed BCa cell proliferation in vitro, suggesting a therapeutic effect. Investigation into the mechanism revealed that the overexpression of AT2R increases the expression levels of caspase-3, caspase-8, and p38 and decreases the expression level of pErk. AT2R overexpression also leads to upregulation of 2 apoptosis-related genes (BCL2A1, TNFSF25) and downregulation of 8 apoptosis-related genes (CASP 6, CASP 9, DFFA, IGF1R, PYCARD, TNF, TNFRSF21, TNFSF10, NAIP) in transduced EJ cells as determined by PCR Array analysis. In vivo, we observed that AT2R overexpression caused significant reduction in xenograft tumors sizes by downregulation VEGF and induction of apoptosis.ConclusionsTaken together, the data suggest that AT1R, AT2R or Mas could be used as a diagnostic marker of BCa and AT2R is a promising novel target gene for BCa gene therapy.

Angiotensin-(1-7) [Ang-(1-7)] is an endogenous, heptapeptide hormone acting through the Mas receptor (MasR), with antiproliferative and antiangiogenic properties. Recent studies have shown that Ang-(1-7) has an antiproliferative action on lung adenocarcinoma cells and prostate cancer cells. In this study, we report that MasR levels were significantly upregulated in nasopharyngeal carcinoma (NPC) specimens and NPC cell lines. Viral vector–mediated expression of Ang-(1-7) dramatically suppressed NPC cell proliferation and migration in vitro. These effects were completely blocked by the specific Ang-(1-7) receptor antagonist A-779, suggesting that they are mediated by the Ang-(1-7) receptor Mas. In this study, Ang-(1-7) not only caused a significant reduction in the growth of human nasopharyngeal xenografts, but also markedly decreased vessel density, suggesting that the heptapeptide inhibits angiogenesis to reduce tumor size. Mechanistic investigations revealed that Ang-(1-7) inhibited the expression of the proangiogenic factors VEGF and PlGF. Taken together, the data suggest that upregulation of MasR could be used as a diagnostic marker of NPC and Ang-(1-7) may be a novel therapeutic agent for nasopharyngeal cancer therapy because it exerts significant antiangiogenic activity. Mol Cancer Ther; 15(1); 37–47. ©2015 AACR.

Circular RNAs (circRNAs) are covalently closed circular structures without 5′ caps and 3′ tails, which are mainly formed from precursor mRNAs (pre-mRNAs) via back-splicing of exons. With the development of RNA sequencing and bioinformatic analysis, circRNAs were recently rediscovered and found to be widely expressed in the tree of life. Cerebellar degeneration-related protein 1 antisense RNA (CDR1as) is recognized as one of the most well-identified circRNAs. It contains over 70 miR-7 binding sites and can regulate gene activity by sponging miR-7. Increasing numbers of studies have recently demonstrated that CDR1as is abnormally expressed in many types of tumors, such as colorectal cancer, cholangiocarcinoma and osteosarcoma, and plays a vital role in the development of cancer. However, there are few reviews focusing on CDR1as and cancer. Hence, it is important to review and discuss the role of CDR1as in cancer. Here, we first review the main biological features of CDR1as. We then focus on the expression and roles of CDR1as in cancer. Finally, we summarize what is known on the role of CDR1as in cancer and discuss future prospects in this area of research.

LLH is a safe and effective treatment for selected patients with hepatolithiasis, with an advantage over OLH in the field of intraoperative blood loss, intraoperative transfusion, overall complication and postoperative recovery.

Accumulating studies have suggested that microRNAs (miRs) play a significant role in lung cancer development and progression, especially in non-small cell lung cancer (NSCLC). The present study aimed to investigate the associations between miR-454-3p and NSCLC progression. qPCR assay was applied to examine the expression of miR-454-3p and transforming growth factor-β2 (TGFB2) in tissues and cell lines. CCK-8 and EdU assays were used to detect cell proliferation. Wound-healing and Transwell assays were conducted to assess cell migration and invasion. Western blotting assay was performed to explore the protein levels of epithelial-mesenchymal transition (EMT) markers. The interaction between miR-454-3p and TGFB2 was investigated with a luciferase reporter assay. miR-454-3p was downregulated in NSCLC tissues and NSCLC cell lines. miR-454-3p overexpression led to the suppression of proliferation, migration, and invasion in A549 and NCI-H1650 cells. In addition, the overexpression of miR-454-3p in A549 and NCI-H1650 cells significantly inhibited EMT. TGFB2 was revealed to be a direct target of miR-454-3p by using TargetScan database and luciferase reporter assay. TGFB2 was observed to be upregulated in NSCLC tissues and cell lines. Further mechanistic studies revealed that the inhibitory effects of miR-454-3p on NSCLC were reversed upon overexpression of TGFB2. These findings provided strong evidence that miR-454-3p suppressed NSCLC cell proliferation and metastasis by targeting TGFB2. The study suggests that targeting miR-454-3p could be a promising strategy for treating NSCLC.

Red cell distribution width (RDW) has been found to be a novel prognostic biomarker in patients with coronary artery disease (CAD); however, the association between RDW and the risk of heart events in patients with CAD is yet to be fully elucidated. Thus, the aim of the present study was to determine whether an elevated RDW was associated with the Framingham risk score (FRS) in patients with CAD. Data were retrospectively collected from Affiliated Dongyang Hospital of Wenzhou Medical University (Dongyang, China). The patients had undergone a coronary angiography and their clinical data were integrated. The patients (male, 260; female, 132) were divided into two groups based on the results of the coronary angiography, namely the CAD (n=283) and control groups (n=109). The FRS was calculated for all the subjects, and complete blood count testing with biochemical measurements was performed. The mean RDW level was 13.7±1.8% in the CAD group and 13.1±1.0% in the control group, while the mean FRS was 9.0±4.9 in the CAD group and 6.4±3.9 in the control group. The RDW and FRS were significantly higher in the CAD group compared with the control group (P<0.001). No statistically significant differences were observed between the groups with regard to the hematocrit, mean corpuscular volume, platelets, glucose, urea, albumin, aspartate aminotransferase, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and N-terminal pro-brain natriuretic peptide (P>0.05). The RDW was shown to significantly correlate with the red blood cell (RBC) count (r=−0.133, P=0.029), hemoglobin level (r=−0.207, P=0.001) and TG level (r=0.226, P<0.001) within the laboratory parameters, as well as the FRS (r=0.206, P<0.001). In the stepwise multivariate linear regression, which included the RBC count, hemoglobin level, TG level and RDW, the FRS was predicted by hemoglobin (r2=0.034, P=0.001), TG (r2=0.059, P<0.001) and RDW (r2=0.030, P=0.003) parameters. Therefore, a novel association was revealed between higher levels of RDW and an elevated FRS in patients with CAD, which raises the possibility that a simple marker, RDW, may be associated with an increased risk of heart events in CAD patients.

Ammonia-oxidizing archaea (AOA) are ubiquitous in diverse ecosystems, and play a pivotal role in global nitrogen and carbon cycling. Although AOA diversity and distribution are widely studied mainly based on the amoA (alpha subunit of ammonia monooxygenase) genotypes, only limited investigations addressed the relationship between AOA genetic adaptation, metabolic features, and ecological niches, especially in estuaries. Here, we have described the AOA communities along the Jiulong River Estuary in Southern China. Nine high-quality AOA metagenome-assembled genomes (MAGs) were obtained by metagenomics. Five of the MAGs are proposed to constitute a new species, Ca. Nitrosopumilus aestuariumsis sp. nov., based on the phylogenies of the 16S–23S rRNA genes and concatenated ribosomal proteins, as well as the average amino acid identity. Comparative genomic analysis revealed unique features of the new species, including a high number of genes related to diverse carbohydrate-active enzymes, phosphatases, heavy metal transport systems, flagellation, and chemotaxis. These genes may be crucial for AOA adaptation to the eutrophic and heavy metal-contaminated Jiulong River Estuary. The uncovered detailed genomic characteristics of the new estuarine AOA species highlights AOA contribution to ammonia oxidation in the Jiulong River Estuary. IMPORTANCE In this study, AOA communities along a river of Southern China were characterized and metagenome-assembled genomes (MAGs) of a novel AOA clade were also obtained. Based on the characterization of AOA genomes, this study suggested adaptation of the novel AOAs to estuarine environments, providing new information for ecology of estuarine AOA and nitrogen cycle in contaminated estuarine environments.

Rationale:Situs inversus totalis (SIT) is a rare anatomical variation of the internal organs, and solid pseudopapillary tumor of the pancreas (SPTP) is a rare tissue type of pancreatic tumors, classified as benign or low-grade malignancy. However, to our knowledge, a patient with SIT and SPTP is extremely rare and has never been reported.Patient concerns:We retrospectively analyzed a case of SIT with SPTP in a 45-year-old woman. The main complaints were abdominal pain and sensation of heaviness for 2 weeks. There was tenderness and a mass that could be palpated in the right upper abdomen.Diagnoses:Heart ultrasonography (USG), chest x-ray, computed tomography (CT), and contrast-enhanced computerized tomography (CECT) revealed a mirror-image dextrocardia and inversion of all abdominal viscera and a space-occupying lesion in the pancreas tail. Abdominal computed tomography angiography (CTA) showed no obvious abnormality of artery. The diagnosis of SPTP was finally made by postoperative pathological examination.Interventions:The patient underwent resection of the pancreatic body and tail and splenectomy via laparotomy to completely remove the tumor.Outcomes:The patient was discharged with specific discomfort on postoperative day 7. At the 1.5-year follow-up, she recovered without issue.Lessons:Surgical resection remains the only effective treatment of SPTP. SIT with SPTP can be accurately diagnosed by heart USG, chest x-ray, CT, and CECT of the upper abdomen. Abdominal aorta CTA before surgery can decrease the injury risk of blood vessels.