Identification of PGC-related ncRNAs and their relationship with the clinicopathological features of Gastric Cancer.

Pepsinogen C (PGC) is considered to be the final product of mature differentiated gastric mucosa. The expression level of PGC in gastric mucosa is clearly decreased upon the development of gastric cancer (GC). However, the mechanism behind PGC's down-regulation remains unclear and needs to be clarified. This study aimed to identify PGC-related ncRNAs with the potential to be PGC post-transcriptional regulators and to further explore the association between these ncRNAs and the clinicopathological parameters of GC. Bioinformatic software was used to predict miRNAs binding specifically to PGC and circRNAs binding specifically to these candidate miRNAs. Dual-luciferase reporter assay was performed to validate the completely complementary pairing of PGC and PGC-related ncRNAs. qRT-PCR was applied to determine the expression levels of PGC and PGC-related ncRNAs in GC tissue. hsa-let-7c was predicted to bind to the PGC gene, which was confirmed by dual-luciferase reporter assay. hsa_circ_0001483 and hsa_circ_0001324 were identified to bind to hsa-let-7c by bioinformatic analysis and dual-luciferase reporter assay. In addition, the hsa_circ_0001483/hsa_circ_0001324 -hsa-let-7c-PGC axis was confirmed in tissue by qRT-PCR. The expression level of hsa_circ_0001483 was correlated with peritumoral inflammatory cell infiltration and lymphatic metastasis. hsa_circ_0001483, hsa_circ_0001324, and let-7c were newly identified and validated as PGC-related ncRNAs and showed associations with the clinicopathological features of GC. The hsa_circ_0001483/hsa_circ_0001324-hsa-let-7c-PGC axis in GC may account for the down-regulation of PGC in GC tissue.

Biomechanical and Morphometric Evaluation of a Strontium-Incorporated Implant and Four Commercially Available Implants: A Study in Rabbits.

PURPOSE: Strontium has shown a positive effect on osseointegration in experiments. This study compared surface characterization and osseointegration of a strontium-incorporated implant with four commercial implants with different surface treatments. MATERIALS AND METHODS: A strontium-oxide layer was created by hydrothermal treatment on the surface of the implant (SLA-Sr). Surface characterizations were observed using a scanning electron microscope, three-dimensional (3D) optical microscope, and x-ray energy-dispersive spectrometry. Implants of different surface treatments including resorbable blasting media (RBM), sandblasting with large grit and acid etching (SLA-1, SLA-2), sandblasting and thermal acid etching (STA), and SLA-Sr were implanted into the proximal tibiae and femoral condyles of rabbits. Biologic effects were evaluated by removal torque testing and histomorphometric analysis after 3, 6, and 12 weeks of implantation. RESULTS: Nanostructures were observed on the surface of SLA-Sr and STA. Calcium (Ca) was detected on the surface of RBM. Sr was detected on the surface of SLA-Sr. SLA-1 and STA had greater surface roughness than SLA-2, SLA-Sr, and RBM (P < .05). In vivo, SLA-Sr achieved better removal torque value (RTV) than that of RBM and SLA-2 at 3 weeks (P < .05), as well as increased bone area ratio (BA%) in cortical bone compared with RBM at 3 weeks (P < .05). STA showed higher bone-to-implant contact ratio (BIC%) in cortical bone than RBM at 3 and 6 weeks (P < .05). Compared with RBM, SLA-1 had better RTV at 6 weeks and higher BIC% in cortical bone at 12 weeks (P < .05). CONCLUSION: In vivo, compared with SLA-2 and RBM, the implant with the strontium-oxide layer displayed slight advantages in new bone formation and osseointegration in the early healing stage. In the later osseointegration stage, the results of SLA-Sr were comparable with other implants.

Association of Polymorphisms in three pri-miRNAs that Target Pepsinogen C with the Risk and Prognosis of Gastric Cancer.

We aimed to explore the associations of polymorphisms in three microRNAs (miRNAs) (let-7e rs8111742, miR-365b rs121224 and miR-4795 rs1002765) that target PGC with the risk and prognosis of gastric cancer/atrophic gastritis. Sequenom's MassArray was used to genotype the miRNA polymorphisms in 724 gastric cancer cases, 862 atrophic gastritis cases and 862 controls in a Chinese population. We found that let-7e rs8111742 and miR-4795 rs1002765 were associated with the risk of gastric cancer in the H. pylori-positive subgroup. MiR-365b rs121224 was associated with the risk of intestinal-type gastric cancer in the alcohol consumption subgroup. Intestinal-type gastric cancer patients at Borrmann stages III-IV who carry the miR-365b rs121224 GG genotype had better prognosis compared with those who carry the CG or CC genotypes. MiR-365b rs121224 was associated with Lauren typing and TNM staging, in which the distribution of GG genotype carriers in intestinal-type gastric cancer and the TNM stage I-II subgroup was higher than that of CG or CC genotypes, which contrasted with the distribution in diffuse-type gastric cancer or TNM III-IV groups. These findings suggested that the polymorphisms in these miRNAs might be biomarkers for gastric cancer risk and prognosis, especially for populations infected with Helicobacter pylori or who consume alcohol.

SNP-SNP interactions of three new pri-miRNAs with the target gene PGC and multidimensional analysis of H. pylori in the gastric cancer/atrophic gastritis risk in a Chinese population.

Gastric cancer (GC) is a multistep complex disease involving multiple genes, and gene-gene interactions have a greater effect than a single gene in determining cancer susceptibility. This study aimed to explore the interaction of the let-7e rs8111742, miR-365b rs121224, and miR-4795 rs1002765 single nucleotide polymorphisms (SNPs) with SNPs of the predicted target gene PGC and Helicobacter pylori status in GC and atrophic gastritis (AG) risk. Three miRNA SNPs and seven PGC SNPs were detected in 2448 cases using the Sequenom MassArray platform. Two pairwise combinations of miRNA and PGC SNPs were associated with increased AG risk (let-7e rs8111742 - PGC rs6458238 and miR-4795 rs1002765 - PGC rs9471643). Singly, miR-365b rs121224 and PGC rs6912200 had no effect individually but in combination they demonstrated an epistatic interaction associated with AG risk. Similarly, let-7e rs8111742 and miR-4795 rs1002765 SNPs interacted with H. pylori infection to increase GC risk (rs8111742: Pinteraction = 0.024; rs1002765: Pinteraction = 0.031, respectively). A three-dimensional interaction analysis found miR-4795 rs1002765, PGC rs9471643, and H. pylori infection positively interacted to increase AG risk (Pinteraction = 0.027). Also, let-7e rs8111742, PGC rs6458238, and H. pylori infection positively interacted to increase GC risk (Pinteraction = 0.036). Furthermore, both of these three-dimensional interactions had a dosage-effect correspondence (Ptrend < 0.001) and were verified by MDR. In conclusion, the miRNAs SNPs (let-7e rs8111742 and miR-4795 rs1002765) might have more superior efficiency when combined with PGC SNPs and/or H. pylori for GC or AG risk than a single SNP on its own.

Correlation between Vascular Endothelial Growth Factor and Somatostatin Receptor with Progression and Prognosis in Gastric Cancer.

BACKGROUND/AIMS: To investigate the expression of vascular endothelial growth factor (VEGF) and somatostatin receptor (SSTR) and their clinicopathological and prognostic value in gastric cancer (GC). METHODOLOGY: The expression of VEGF and SSTR in 107 cases of GC tissue and 30 cases of gastric mucosa were detected by immunohistochemistry. Clinicopathological and prognostic association of VEGF and SSTR in GC was analyzed RESULTS: The expression of VEGF in GC (70.1%) was significantly higher than that in gastric mucosa (20.0%) The expression of SSTR in GC (62.6%) was significantly lower than that in normal tissues (93.3%). VEGF and SSTR expression were both associated with histological differentiation, depth of invasion, TNM stage, and lymph node metastasis (P < 0.05). The negative expression of VEGF or the positive expression of SSTR was correlated with better overall survival of GC patients. The Cox analysis demonstrated that the expression of VEGF and SSTR, pathological type, TNM stage, and lymph node metastasis were the independent predictors for overall survival in GC (P = 0.005, P = 0.006, P = 0.003, P = 0.002, and P = 0.001, respectively). CONCLUSIONS: The expression of VEGF and SSTR were associated with progression and prognosis of GC.

DNA purification on a lab-on-valve system incorporating a renewable microcolumn with in situ monitoring by laser-induced fluorescence.

Bead injection in a lab-on-valve (LOV) system was adopted for DNA purification via micro solid-phase extraction (SPE) with a renewable silica microcolumn packed in a channel of the LOV unit. The complex matrix components in human whole blood, including proteins, were well eliminated by choosing properly the sample loading and elution media. The DNA purification process was monitored on-line by using laser-induced fluorescence in a demountable side part of the LOV unit incorporating optical fibers. The practical applicability of the entire system was demonstrated by separation/purification of lambda-DNA in a simulated matrix and human blood genetic DNA by performing SPE, in situ monitoring of the purified products, and postcolumn PCR amplification. When DNAs in a simulated matrix (10.0 ng microl-1 lambda-DNA, 50 ng microl-1 bovine serum albumin, 1.0% Triton X-100) were processed in the present system and laser-induced fluorescence was monitored at 610 nm, an overall extraction/collection efficiency of 70% was achieved by employing identical sample loading and an elution flow rate of 0.5 microl s-1, along with a precision of 3.8% relative standard deviation. DNA separation and purification from human whole-blood samples were performed under similar conditions.