Identification of core genes in ovarian cancer by an integrative meta-analysis

Background

Epithelial ovarian cancer is one of the most ?severe public health threats in women. Since it is still challenging to screen in early stages, identification of core genes that play an essential role in epithelial ovarian cancer initiation and progression is of vital importance.

Results

Seven gene expression datasets (GSE6008, GSE18520, GSE26712, GSE27651, GSE29450, GSE36668, and GSE52037) containing 396 ovarian cancer samples and 54 healthy control samples were analyzed to identify the significant differentially expressed genes (DEGs). We identified 563 DEGs, including 245 upregulated and 318 downregulated genes. Enrichment analysis based on the gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the upregulated genes were significantly enriched in cell division, cell cycle, tight junction, and oocyte meiosis, while the downregulated genes were associated with response to endogenous stimuli, complement and coagulation cascades, the cGMP-PKG signaling pathway, and serotonergic synapse. Two significant modules were identified from a protein-protein interaction network by using the Molecular Complex Detection (MCODE) software. Moreover, 12 hub genes with degree centrality more than 29 were selected from the protein-protein interaction network, and module analysis illustrated that these 12 hub genes belong to module 1. Furthermore, Kaplan-Meier analysis for overall survival indicated that 9 of these hub genes was correlated with poor prognosis of epithelial ovarian cancer patients.

Conclusion

The present study systematically validates the results of previous studies and fills the gap regarding a large-scale meta-analysis in the field of epithelial ovarian cancer. Furthermore, hub genes that could be used as a novel biomarkers to facilitate early diagnosis and therapeutic approaches are evaluated, providing compelling evidence for future genomic-based individualized treatment of epithelial ovarian cancer.

     

Nebivolol attenuates redox-sensitive glomerular and tubular mediated proteinuria in obese rats

Obesity and insulin resistance-related proteinuria is associated with oxidative stress and impaired tissue bioavailable nitric oxide. Recent data suggest that nicotinamide adenine dinucleotide phosphate oxidase-mediated oxidative injury to the proximal tubule, like that seen in the glomerulus, contributes to proteinuria in insulin-resistant states. The vasodilator β-blocker nebivolol reduces nicotinamide adenine dinucleotide phosphate oxidase activity, increases bioavailable nitric oxide, and improves insulin sensitivity. To test the hypothesis that a treatment strategy that reduces oxidative stress and attenuates obesity-associated increases in glomerular and proximal tubule derived protein, we treated young Zucker obese (ZO) and age-matched Zucker lean male rats with nebivolol (10 mg · kg(-1) · d(-1)) for 21 d. Compared with Zucker lean, ZO controls exhibited increased proteinuria and γ-glutamyl transpeptidase, reductions in systemic insulin sensitivity in association with increased renal renin, (pro)renin receptor, angiotensin II type 1 receptor, and mineralocorticoid receptor immunostaining, oxidative stress, and glomerular tubular structural abnormalities that were substantially improved with in vivo nebivolol treatment. Nebivolol treatment also led to improvements in glomerular podocyte foot-process effacement and improvement in podocyte-specific proteins (nephrin and synaptopodin) as well as proximal tubule-specific proteins (megalin and lysosomal-associated membrane protein-2) and proximal tubule ultrastructural remodeling in the ZO kidney. Our findings support the notion that obesity and insulin resistance lead to increased glomerulotubular oxidative stress and resultant glomerular and tubular sources of excess urine protein. Furthermore, the results of this study suggest the beneficial effect of nebivolol on proteinuria was derived from improvements in weight and insulin sensitivity and reductions in renal oxidative stress in a state of obesity and insulin resistance.     

Early sexual initiation: the role of peer norms

OBJECTIVE: To elucidate which components of peer norms influence the process of sexual initiation for young adolescents. Design. Prospective cohort study. Setting. Fourteen elementary and middle schools in an urban public school district. Participants. The 1389 sixth-grade students who completed the questionnaire at the beginning (time 1) and at the end (time 2) of the school year comprise the study sample. Mean age at time 1 was 11.7 years. RESULTS: Of students entering the sixth grade, 30% (n = 416) reported having already initiated sexual intercourse, 5% (n = 74) reported initiating sexual intercourse during the sixth-grade school year (initiated group), and 63% (n = 873) reported not having initiated sexual intercourse by the end of the sixth-grade school year (never group). Demographic comparisons revealed that students in the initiated group were significantly more likely than students in the never group to be older (11.9 years vs 11.6 years), male (58% vs 37%), African-American (70% vs 51%), attending a poorer school (87% vs 85%), and living in an area with a high proportion of single-parent families (45% vs 41%). Self-reports and reports of peers' participation in nonsexual risk behaviors were more common for students in the initiated group. Students in the initiated group were more likely than students in the never group to perceive: 1) a high prevalence of sexual initiation among peers; 2) social gains associated with early sexual intercourse; and 3) younger age of peers' sexual initiation. Students in the never group were more likely to believe that sexually-experienced 12-year-old boys would be negatively stigmatized compared with students in the initiated group. Three predictive models were developed to test the relationship between peer norms and the process of initiation. These models demonstrate that the strongest predictor of sexual initiation in sixth grade is having high intention to do so at the beginning of sixth grade. The strongest predictor of high intention is belief that most friends have already had sexual intercourse. Perceptions of social gain and stigma for sexually-experienced 12-year-old boys act independently of intention to decrease risk of early sexual initiation. CONCLUSION: Early sexual intercourse is not an unplanned experience for many teens. Decisions about initiation are strongly bound to social context with peers playing an important role in creating a sense of normative behavior. Specific components of peer norms impact the process of sexual initiation in both positive and negative ways. Interventions aimed at delaying the onset of sexual initiation need to focus on cohort norms as well as on an individual's perceptions and behaviors.     

Pulp responses to the application of a self-etching adhesive in human pulps after controlling bleeding with sodium hypochlorite.

OBJECTIVE: To evaluate the pulp response to direct capping with self-etching adhesive systems using sodium hypochlorite as a hemostatic agent. METHOD AND MATERIALS: Twenty-six human third molars scheduled for extraction were selected from undergraduate students of dentistry. Class I cavities with pulp exposures were performed. To control bleeding, 2.5% sodium hypochlorite was used for 20 seconds, followed by washing with saline solution. The pulp exposures were capped with calcium hydroxide (n = 10) or adhesive system (n = 16). All cavities were restored with adhesive system and composite resin. Half of the samples of each capping material were extracted after 30 days and the remaining after 90 days. The samples were prepared for histological analysis (hematoxylin-eosin) and bacterial detection (Brown & Hopps) and evaluated according to standard ranking. Data were submitted to statistical analysis (Mann-Whitney test). RESULTS: There was a significant difference (P <.05) only in relation to dentin barrier formation. Pulps dressed with calcium hydroxide showed dentin barrier formation in all specimens, obliterating the exposure site. No inflammatory response was associated with material. In the experimental group, after 30 days, there was an attempt for healing with reparative dentin deposition, presenting a mild to moderate inflammatory infiltrate. Similar findings were found after 90 days, decreasing the inflammatory response. Bacteria were not detected in any specimen evaluated. Sodium hypochlorite was effective for hemostatic control. CONCLUSION: Calcium hydroxide produced better biological performance than the self-etching adhesive, and sodium hypochlorite did not interfere with the pulp repair.     

Intrahepatic bile duct and portal vein anatomy revisited

Seventeen normal cadaver livers were studied to assess the anatomic relationship of bile ducts to portal veins. The common bile duct, main portal vein, and hepatic artery were cannulated and injected with air, dilute contrast medium, and mineral oil, respectively. The livers were placed in anatomic position and examined with computed tomography. In the lateral segment of the left hepatic lobe, the bile ducts were anterior to the portal vein in seven cases, posterior in seven, and tortuous (ie, both anterior and posterior) in three. In the medial segment of the left lobe, the bile ducts were anterior in four cases, posterior in four, tortuous in three, and not seen in six. In the right lobe, the bile ducts were anterior in nine cases, posterior in five, tortuous in one, and not seen in two. In the porta hepatis, the bile ducts were anterior in ten cases, posterior in one, tortuous in five, and not seen in one. Histologic findings confirmed the anterior and posterior location of the bile ducts relative to the portal veins. These findings contradict the commonly held view of intrahepatic bile ducts being anterior to the portal vein and are clinically significant for techniques such as bile duct drainage.     

Rapid and simultaneous typing of hemoglobin S, hemoglobin C, and seven Mediterranean beta-thalassemia mutations by covalent reverse dot-blot analysis: application to prenatal diagnosis in Sicily

The molecular lesions causing beta-thalassemia in Sicily can be subdivided into two groups. One that occurs at a 71% frequency and consists of the beta 39, IVS 1,110 and IVS 1,6 mutations and the other group at a 20% frequency comprising the -87, beta s, IVS 1,1 and IVS 2,745 mutations. The identification of all these mutations by polymerase chain reaction (PCR) and conventional dot-blot hybridization has been time consuming and expensive. In this article, we describe the implementation of the reverse dot-blot (RDB) hybridization as a rapid nonradioactive method for the identification of the nine most frequent molecular lesions in the beta-globin gene (-87, beta s, beta c, IVS 1,1, IVS 1,6, IVS 1,110, beta 39, IVS 2,1, IVS 2,745) in Sicily. Sixty prenatal diagnoses were performed by this RDB assay, each of which was confirmed by dot-blot/ASO hybridization; thus demonstrating the accuracy of the RDB. The main advantage of this assay is the rapid typing of an individual's DNA for many mutations in a single working day. Because the mutations in this assay are representative for the Mediterranean region, this mutational panel can also be extended to the screening of beta-thalassemia from other Mediterranean regions.     

Immunization of guinea pigs with epitope C-rich lipopolysaccharide from Neisseria gonorrhoea; in vivo selection of gonococcal variants

The immunogenic potential of lipopolysaccharide (LPS) of a variant of Neisseria gonorrhoeae strain Gc 40 selected by growth in vivo (vivo variant) was investigated in guinea pigs. LPS extracts obtained from the water (WLPS) and the phenol (PLPS) phases of a hot phenol-water extraction were compared for their antigenic capacity and protective effect against infection in subcutaneous chambers. Immunization with PLPS induced significant levels of anti-LPS and anti-epitope C antibodies but WLPS was not antigenic. Two days after challenge, all guinea pigs immunized with WLPS had infections similar to those seen in unimmunized control animals while most animals immunized with PLPS and challenged with either 10(3) or 10(5) gonococci per ml showed low numbers of or no viable gonococci in their chambers. Five days after challenge, however, the same animals had chamber infections with high viable counts similar to controls. Gonococci reisolated from three such animals had physically and antigenically altered lipopolysaccharide and showed patterns of serum sensitivity to pre-challenge chamber fluid from immunized animals which were different from those of the parent vivo variant used for immunization and challenge. The results demonstrate that selection of LPS variants occurs in vivo. This could constitute an immune evasion mechanism.     

Scintigraphic Visualization of Haemostatic and Thromboembolic Processes Using 111Indium-labelled Platelets

ABSTRACT Five cases of scintigraphic imaging of haemostatic and thromboembolic processes after injection of autologous ¹¹¹In-labelled platelets are presented. The site of a liver puncture, atherosclerotic plaques in the abdominal aorta, deep vein thrombi, pulmonary embolism and the tip of an indwelling venous catheter could be visualized. Activity measurements corresponding to atherosclerotic plaques suggest that an increased sensitivity of this method may be achieved by extending the investigation period to 4–5 days after injection of ¹¹¹In platelets.     

Complications of percutaneous nephrostolithotomy

In 224 patients, renal stones were removed from the urinary tract using either direct extraction with a basket or forceps (59 patients), ultrasonic lithotripsy (164 patients), or infusion chemotherapy (one patient). Residual stone fragments were present more frequently in patients treated with ultrasonic lithotripsy (27%) than with direct extraction (5%). Other complications included hemorrhage (eight patients), catheter dislodgement (four patients), large amounts of urine extravasation (three patients), glycine ascites (three patients), infection (two patients), pneumothorax (one patient), and a prolonged ileus (one patient). More complications occurred among the first 50 patients than the last 50 patients, even though more difficult cases, including patients with staghorn calculi, were accepted during the latter period. Although a learning curve exists, complications can be minimized by attempting to treat more favorable cases during the initial experience.