Search

Background: Rectal adenocarcinoma (READ) is one of the deadliest malignancies, and the molecular mechanisms underlying the initiation and development of READ remain largely unknown. In this study, we aimed to find key long noncoding RNAs (lncRNAs) and mRNAs in READ by RNA sequencing. Methods: RNA sequencing was performed to identify differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between READ and normal tissue. READ‐specific protein‐protein interaction (PPI), DElncRNA‐DEmRNA coexpression, and DElncRNA‐nearby DEmRNA interaction networks were constructed. DEmRNAs and DEmRNAs coexpressed with DElncRNAs were functionally annotated. Results: A total of 2113 DEmRNAs and 150 DElncRNAs between READ and normal tissue were identified. The PPI network identified several hub proteins, including CDK1, AURKB, CDC6, FOXQ1, NUF2, and TOP2A. The DElncRNA‐DEmRNA coexpression and DElncRNA‐nearby DEmRNA interaction networks identified some hub lncRNAs, including CCAT1, LOC105374879, GAS5, and B3GALT5‐AS1. The colorectal cancer pathway, the intestinal immune network for IgA production and the p53 signaling pathway were three pathways significantly enriched in DEmRNAs and DEmRNAs coexpressed with DElncRNAs. MSH6 coexpressed with two DElncRNAs (LOC105374879 and CASC15) and BCL2 coexpressed with B3GALT5‐AS1 were significantly enriched in the colorectal cancer signaling pathway. TNFRSF17 coexpressed with B3GALT5‐AS1 was enriched in the intestinal immune network for IgA production. CCNB2 coexpressed with LOC105374879 was enriched in the p53 signaling pathway. Conclusion: A total of four DEmRNAs (MSH6, BCL2, TNFRSF17, and CCNB2) and three DElncRNAs (LOC105374879, CASC15, and B3GALT5‐AS1) may be involved in the pathogenesis of READ; this data may contribute to understanding the mechanisms of READ and the development of therapeutic strategies for READ. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancer worldwide and chronic infection of hepatitis B virus (HBV) serve as one of leading causes of HCC. OBJECTIVE: : This study aimed to identify the novel long noncoding RNAs (lncRNAs) biomarkers for HBV-associated HCC. METHODS: The lncRNA and mRNA expression profiles of HCC patients with HBV infection were downloaded from The Cancer Genome Atlas. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between HCC and adjacent tissues were identified. The optimal diagnostic and prognostic lncRNA biomarkers for HCC were identified by using feature selection procedure and classification model. Functional annotation of DEmRNAs co-expressed with these lncRNAs biomarkers were performed. Receiver operating characteristic (ROC) curve and survival analysis of these lncRNAs biomarkers were performed. qRT-PCR validation was performed. RESULTS: A total of 82 DElncRNAs and 805 DEmRNAs between HBV-associated HCC and normal tissues were identified. CAPN10-AS1, LINC01093, RP5-890E16.2, FENDRR and C17orf82 were selected as optimal diagnostic and prognostic lncRNA biomarkers for HBV-associated HCC that were co-expressed with 105, 86, 70, 30 and 1 DEmRNAs, respectively. Based on the DEmRNAs co-expressed with these five lncRNAs biomarkers, Jak-STAT signaling pathway and retinol metabolism were two significantly enriched pathways. The result in qRT-PCR validation were consistent with our analysis based on TCGA, generally. CONCLUSIONS: This study identified five potential lncRNAs biomarkers for HBV-associated HCC with great diagnostic and prognostic value and provided clues for their functions in HBV-associated HCC. [ABSTRACT FROM AUTHOR]

Genome-wide association studies have led to the discovery of several susceptibility genes related to autoimmune thyroid diseases (AITDs). However, controversial results have been reported regarding the role of single-nucleotide polymorphism (SNP) of CD40 in the disease susceptibility. The objective of this study was to identify the relationship of the polymorphisms of three sites of CD40 with the susceptibility to AITD in the Chinese population. We genotyped three polymorphisms of CD40: C/T −1 SNP, 58038T site of the third exon and C64610G site of the ninth exon in 196 GD cases, 121 HT cases and 122 control subjects. The three putative polymorphism sites were amplified by PCR for sequencing and analysis. The genotype frequencies of CD40 −1 C/C genotype and C allele were significantly higher in the GD group than those in normal control. For the C64610G polymorphism, the C/G genotype was significantly more frequent in HT group than in control group, and the G allele frequencies in the GD and HT group were both higher than those in control group. These results indicated that there exist different susceptibility loci for AITD within CD40, each contributing a different effect in the onset and development of AITDs. [ABSTRACT FROM AUTHOR]

Novel mdfA gene variants were identified simultaneously from 3 of 13 positive isolates of PCR amplification in Escherichia coli from patients. These 13 positive isolates showed resistance to chloramphenicol, tetracycline, and erythromycin. The 3 mdfA gene variants were of the same genotype and all the 13 positive isolates were investigated by conjugation experiment, EcoRI restriction, and gene mapping. Conjugation experiments demonstrated that the novel mdfA variant and mdfA genes were located on plasmids that were restricted by EcoRI for ∼8.2 kb-length, which was also validated by gene mapping. Further study indicated three types of genetic structures (A, B, and C) in the recombinant plasmids harboring mdfA and surrounding genes, and structure B was first reported in the article. Structure A comprises two partial-length and six full-length genes, including the mdfA gene variant in the recombinant plasmid; structure B comprises four full-length genes, the mdfA, ybjG, dacC, and ybjI; structure C comprises two full-length genes, the mdfA and dacC. These results suggested that the mdfA gene can function as transporter responsible for multidrug resistance and also mediated the synergistic function with its surrounding genes in conjugative plasmids. [ABSTRACT FROM AUTHOR]

Sixteen different variants (KPC-2 to KPC-17) in the KPC family have been reported, and most current studies are focusing on KPC-2 and KPC-3. The KPC-15 variant, which isolated from Klebsiella pneumoniae in a Chinese hospital, was a recently discovered KPC enzyme. To compare the characteristics of KPC-15 and KPC-2, the variants were determined by susceptibility testing, PCR amplification and sequencing, and study of kinetic parameters. The strain harboring the KPC-15 showed resistance to 18 conventional antimicrobial agents, especially to cabapenem antibiotics, and the strain involving the KPC-2 also indicated resistance to cabapenem antibiotics, but both strains were susceptible to polymyxin B and colistin. The conjugation experiments showed that the changes of MIC values to the antibiotics were due to the transferred plasmids. The differences of amino acids were characterised at sites of 119 leucine and 146 lysine with KPC-15 and KPC-2. The minimum evolution tree indicated the KPC alleles evolution, and showed that the KPC-15 appeared to be homogenous with KPC-4 closely. Steady-state kinetic parameters showed the catalytic efficiency of KPC-15 was higher than that of KPC-2 for all tested antibiotics in this study. The catalytic efficiency of KPC-15 caused resistance to β-lactam antibiotics was higher than that of KPC-2. Meanwhile, an evolutionary transformation changed KPC from an efficient carbapenemase to its variants (KPC-15) with better ceftazidimase catalytic efficiency, and the old antibiotics polymyxin B and colistin might play a role in the therapy for multi-resistant strains. [ABSTRACT FROM AUTHOR]

Background/Aims: The endothelial nitric oxide synthase (eNOS) gene has been enlisted by previous research as a candidate gene of preeclampsia predisposition. This study investigates the specific roles of 3 polymorphisms of the eNOS gene in a population of Chinese origin from mainland China. Methods: We studied the association of 3 commonly studied polymorphisms of the eNOS gene, namely 4b/a, T-786C and Glu298Asp, in a case-controlled sample of 220 patients diagnosed with preeclampsia and 200 healthy controls. The association between eNOS polymorphisms and preeclampsia was evaluated by performing genotyping for the eNOS variants and calculating odds ratios (OR) and 95% confidence intervals. The plasma nitrite concentration in participants was determined to examine how 3 eNOS polymorphisms affect plasma nitric oxide (NO) concentrations in pregnant women. Results: The frequencies of both the variant 298Asp allele and eNOS 4a allele were significantly lower in preeclamptic women than in the control group and had a significantly lower OR. The variant 298Asp allele and eNOS 4a are strongly associated with higher plasma NO concentrations in pregnant women. Conclusions: Polymorphisms in the eNOS gene may be protective against preeclampsia in a Chinese population, and this protective effect may be associated with NO formation in plasma in pregnant women. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Today, Klebsiella pneumoniae strains are sophisticatedly associated with the transmission of KPC, and ST11 clones carrying KPC-2 are an important target for anti-infective clinical therapy, posing a very high threat to patients. To present the detailed genetic features of two KPC-2 core structures of F94_plasmid pA, the whole genome of K. pneumoniae strain F94 was sequenced by nanopore and illumina platform, and mobile genetic elements associated with antibiotic-resistance genes were analyzed with a series of bioinformatics methods. K. pneumoniae strain F94, identified as a class A carbapenemase-resistant Enterobacteriaceae, was resistant to most tested antibiotics, especially to low-levels of ceftazidime/avibactam (avibactam ≤ 4 mg/L), owing to overexpression of the two KPC-2 in F94_plasmid pA. However, strain F94 was sensitive to high-levels of ceftazidime/avibactam (avibactam ≥ 8 mg/L), which correlated with further inhibition of ceftazidime hydrolysis by the KPC-2 enzyme due to the multiplication of avibactam. Collinearity analysis indicated that multi-drug resistance (MDR) regions of plasmids with the tandam repeats of two or more KPC-2 core structures share highly similar structures. This study characterized the MDR region of the F94_ plasmid pA as homologous to plasmids pKPC2_090050, pKPC2_090374, plasmid unnamed 2, pC2414-2-KPC, pKPC2-020037, pBS1014-KPC2, pKPC-J5501, and pKPC2-020002, which contained the tandem repeats of one, two, or more KPC-2 core structures, providing insight into the evolution of multidrug resistance in K. pneumoniae. An alternative theoretical basis for exploring the tandem repeats of two or more KPC-2 core structures was developed by analyzing and constructing the homologous sequence of F94_ plasmid pA. [ABSTRACT FROM AUTHOR]

The purpose of the present study is to investigate the prevalence of Th17 and regulatory T (Treg) cells in children with allergic rhinitis (AR) accompanying with bronchial asthma (BA). 24 children with AR, 22 children with BA, 18 children with AR accompanying with BA, and 20 healthy controls were recruited. The prevalence of peripheral blood Th17 and Treg cells were determined by flow cytometry. mRNA expression of retinoid-acid receptor-related orphan receptor (ROR)-γt and forkhead box P3 (Foxp3) were determined by realtime polymerase chain reaction. Cytokine expressions in plasma were determined by enzyme linked immunosorbent assay. The frequency of Th17 cells, ROR-γt mRNA expression, and the plasma levels of IL-17 were significantly higher, while Treg cells and Transforming growth factor (TGF)-β1 were significantly lower in children with AR accompanying with BA compared with those in children with AR or BA alone or control subjects. In children with allergic airway disease, total IgE levels were positively correlated to the frequency of Th17 cells (r=0.607, p<0.01), plasma IL-17 levels, and negatively correlated to the frequency of Treg cells (r=-0.429, p<0.01) and TGF-β1 levels (r=-0.224, p<0.01). While Forced expiratory volume in one second (FEV1) (% predicted) was negatively correlated to the frequency of Th17 cells (r=-0.602, p<0.01), plasma IL-17 levels (r=-0.577, p<0.01), and positively correlated to the frequency of Treg cells r=0.504, p<0.01) and TGF-β1 levels (r=0.231, p<0.05). Our results demonstrate that the imbalance of peripheral Th17/Treg cells plays an important role in the pathogenesis of AR accompanying with BA. [ABSTRACT FROM AUTHOR]

The rising incidence and complications of diabetes constitutes a major public health issue. The mortality rate of diabetes-induced myocardial ischemia/reperfusion (I/R) injury is significantly elevated. Resveratrol (RSV) is a naturally occurring polyphenol considered to be a potent cardioprotective compound. The aim of the present study was to explore the function and molecular mechanism of RSV on diabetes-induced myocardial I/R injury. Left anterior descending coronary artery ligation was performed to stimulate myocardial I/R injury in streptozotocin-induced diabetic rats. Heart electrical activity was monitored through an electrocardiogram to confirm successful models. The myocardial infarct volume was detected via 2,3,5-triphenyltetrazolium chloride staining. Western blotting was employed to examine the levels of autophagy markers. It was found that the injection of RSV mitigated the ischemia- or I/R injury-induced myocardial damage on hemodynamic function and infarct size, but the autophagy inhibitor 3-methyladenine significantly blocked the function of RSV. Furthermore, the application of RSV significantly enhanced the expression of Beclin-1 and LC-3II but inhibited the serum levels of tumor necrosis factor-α and interleukin-6. These findings revealed an alleviating effect of RSV on diabetes-induced myocardial I/R injury and provided new evidence for the successful application of RSV on the diabetic myocardium. [ABSTRACT FROM AUTHOR]

Abstract Lidocaine is a conventional local anesthetic which is shown antiproliferative of colorectal cancer (CRC) in patients. MicroRNAs (miRNAs) have been consistently demonstrated to be involved in CRC, and miR-520a-3p could suppress CRC migration, promote apoptosis by targeting epidermal growth factor receptor (EGFR). However, the mechanism by which lidocaine regulated CRC proliferation and apoptosis remains unknown. In this study, quantitative RT-PCR were used to measure miR-520a-3p and EGFR expression levels, and western blotting assays ware performed to measure EGFR expression in CRC cells. Luciferase reporter assay was employed to validate the direct targeting of EGFR by miR-520a-3p. Cell proliferation and apoptosis assays ware utilized to analyze the role of lidocaine in CRC cells. The results indicated that 500 and 1000 μM lidocaine over 24 h inhibited proliferation and induced apoptosis of CRC cells. Compared with the control group, the expression of EGFR was suppressed by lidocaine (500 μM) in CRC cells. Furthermore, miR-520a-3p could directly targets EGFR in CRC cells. Lidocaine (500 μM) increased the expression of miR-520a-3p and rescued the reduction of miR-520a-3p caused by miR-520a-3p inhibitor. The results suggested that lidocaine could suppress the expression of EGFR by upregulating miR-520a-3p, and it could induce apoptosis and inhibit proliferation in CRC cells. Lidocaine may serve as potential therapeutic regimen for colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: To determine the accuracy of biplane transrectal ultrasonography (TRUS) plus ultrasonic elastosonography (UE) and contrast-enhanced ultrasonography (CEUS) in preoperative T staging after neoadjuvant chemoradiotherapy for rectal cancer.Materials and Methods: Fifty-three patients with advanced lower rectal cancer were examined before and after neoadjuvant chemoradiotherapy with use of TRUS plus UE and CEUS and were diagnosed as having T stage disease. We compared ultrasonic T stages before and after neoadjuvant chemoradiotherapy and analyzed any changes. Also, with postoperative pathological stages as the gold standard, we compared ultrasonic and pathological T stages and determined their consistency by the kappa statistic.Results: For patients with rectal cancer, ultrasonic T stages were lower after neoadjuvant chemoradiotherapy than before, with a statistically significant difference (P < 0.05). The posttreatment downstaging rate was 39.6% (21/53). A total of 84.9% received correct staging with use of biplane TRUS plus UE and CEUS in the evaluation of preoperative T staging after neoadjuvant chemoradiotherapy for rectal cancer, which was highly consistent with that of pathological staging (κ = 0.768, P < 0.05). Its sensitivities were 80.0%, 50.0%, 75.0%, 96.3%, and 100% in the diagnoses of stages T0 to T4 rectal cancers, respectively; the specificities were 95.4%, 97.9%, 95.1%, 88.5%, and 100% at stages T0 to T4, respectively.Conclusion: Biplane TRUS plus UE and CEUS can be used to accurately perform preoperative T staging in rectal cancer after neoadjuvant chemoradiotherapy; in addition, this procedure well reflects changes in depth of rectal cancer invasion into the intestinal wall before and after neoadjuvant chemoradiotherapy. It is of great value in clinically evaluating the efficacy of neoadjuvant chemoradiotherapy, in selecting therapeutic regimens, and in avoiding overtreatment. [ABSTRACT FROM AUTHOR]

Background: Cardiopulmonary bypass (CPB) is usually associated with inflammatory response that leads to various degrees of organ dysfunction in multiple systems, including lung injury. Our previous study showed that transforming growth factor beta1 (TGFβ1) was involved in CPB-induced lung injury. N-acetylcysteine (NAC) is an antioxidant and is able to prevent CPB-induced pneumocyte apoptosis through scavenging radical. Therefore, we investigated whether NAC may attenuate CPB-induced lung injury by inhibiting TGFβ1 expression.Methods: Fifty-four 18 to 24-month-old mongrel dogs (15-16 kg) were randomly divided into control group, CPB group and NAC group (n = 18). Six dogs in each group were killed prior to, as well as 30 and 60 minutes after the operation (T0, T1 and T2). Lung injury was evaluated by hematoxylin and eosin (H&E) staining. Respiratory index (RI), oxygenation index (OI), malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the lung were determined at each time point. TGFβ1 expression was determined using real time RT-PCR and immunohistochemistry.Results: A serious lung injury was observed after CPB in dogs. RI and MDA content were increased significantly after CPB, whereas OI and SOD activity were decreased. H&E staining showed that NAC treatment obviously attenuated CPB-induced lung injury. NAC treatment upregulated OI and SOD activity and downregulated RI and MDA content in the lung tissues of dogs after CPB. Treatment with NAC significantly suppressed the TGFβ1 expression in the lung tissues at both mRNA and protein levels.Conclusion: Our results suggest that NAC is a potent agent against CPB-induced acute lung injury through inhibiting TGFβ1 expression. [ABSTRACT FROM AUTHOR]