Association of dietary diversity with uterine fibroids among urban premenopausal women in Shijiazhuang, China: A cross-sectional study.

BACKGROUND AND OBJECTIVES: Uterine fibroids (UFs) are the most common neoplasm affecting reproductive-age women. The purpose of the present study is to explore the association between dietary diversity and risk of UFs in a cross-sectional study of urban premenopausal women. METHODS AND STUDY DESIGN: A total of 248 urban premenopausal women with age of 20-45 were recruited in 3 randomly chosen hospitals in Shijiazhuang, China. Dietary diversity was assessed from food frequency intake data using dietary diversity score (DDS), Prime Diet Quality Score (PDQS) and food variety score (FVS). UFs were diagnosed by the methods of ultrasound, pelvic exam, or surgery. Binary logistic regression was used to estimate the relationship between dietary diversity and risk of UFs. RESULTS: 37 of the study subjects (14.9%) had UFs. Participants with a low education level and single marital status participants had a lower DDS and PDQS, respectively. After adjustment for confounding factors, a higher DDS 24 was associated with decreased UF risk (OR=0.22, 95% CI=0.05-1.01). Similar trends were observed for the plantbased FVS (ptrend=0.025). Carrot (OR=0.04, 95% CI=0.00-0.48) and kiwi fruit (OR=0.03, 95% CI=0.00-0.47) were also inversely associated with risk of UFs after adjustment for confounding factors. CONCLUSIONS: Multifarious food groups and the increase of variety of plant-based food, especially carrot and kiwi fruit, may be associated with the lower risk of UFs; they may play an important role in inhibiting the formation of UFs.

Genetic polymorphisms of microRNA machinery genes predict overall survival of esophageal squamous carcinoma.

BACKGROUND: MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in miRNA processing machinery genes are implicated in carcinogenesis, as they change the expression profiles of miRNA. Six miR-SNPs in miRNA processing machinery genes, including Dicer (rs3742330), RAN (rs14035), XPO5 (rs11077), TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348), were evaluated for their association with esophageal squamous cell carcinoma (ESCC). METHODS: The miR-SNP of the miRNA processing genes were genotyped using the polymerase chain reaction-ligase detection reaction (PCR-LDR) assay, while the XPO5 expression levels in ESCC tissues were measured by immunochemistry methods. RESULTS: Patients carrying the rs11077 AA allele exhibited a significantly increased lifespan than AC+CC carriers, as determined by univariate and multivariate analyses (relative risk: 2.490; 95% confidence interval [CI]: 1.225-5.058; P=.012). Furthermore, the rs11077 AA genotype displayed a trend for high XPO5 expression in ESCC tissues by immunochemistry analysis, and these high XPO5 expression levels were also associated with high survival rates among ESCC patients. CONCLUSION: Our results suggested that the miRNA machinery gene expression-associated miR-SNPs would modify cancer outcomes; in this light, XPO5 may be an important new target for ESCC therapy.

Mitochondrial DNA haplogroup N is associated good outcome of gastric cancer.

Accumulation of mutations and single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been identified for their association with cancer risk and disease outcome in a variety of cancers. We have identified cancer risk-associated D-loop SNPs in gastric cancer patients. In this study, we evaluated the predictive value of these SNPs for cancer outcome. Two SNP sites of nucleotides 489C/T and 523-524AC/del were identified for statistically significant prediction of postoperative survival in gastric cancer by univariate analysis with log-rank test. In addition, the mitochondrial DNA haplogroup N (489T) contributed to the good survival of gastric cancer patients compared with the mitochondrial DNA haplogroup M (489C) genotype (relative risk, 1.753; 95 %CI, 1.005-3.060; p = 0.048) by multivariate analysis with COX hazards model. In conclusion, analysis of genetic polymorphisms in the mitochondrial D-loop can help identify subgroups of patients who are at a high risk of a poor disease outcome.

8-Hydroxy-2'-deoxyguanosine expression predicts outcome of esophageal cancer.

Esophageal cancer is characterized by increased oxidative stress and the production of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is one of the main mutagenic modifications of DNA. We analyzed the predictive value of 8-OHdG expression on postoperative survival of patients with esophageal cancer with univariate and multivariate analysis. The high levels of 8-OHdG are associated with significantly shorter survival time by log-rank test using Kaplan-Meier methods. Moreover, the level of 8-OHdG expression was identified as an independent predictor for esophageal cancer outcome using Cox proportional hazards model analysis (relative risk, 0.294; 95% confidence interval, 0.178-0.487; P = .000). These results suggest that oxidative damage marker of 8-OHdG is a useful prognostic marker in esophageal cancer. The analysis of 8-OHdG levels can help in the identification of patient subgroups that are at high risk for poor disease outcomes.

Sirtuin-3 (SIRT3) expression is associated with overall survival in esophageal cancer.

Sirtuin-3 (SIRT3) was immunostained in 94 samples of esophageal cancer tissues and semiquantified using the HSCORE method to evaluate the predictive value of SIRT3 expression levels on esophageal cancer outcome. The relationship between SIRT3 expression and the 5-year survival rate of postoperational esophageal cancer patients was assessed with the Kaplan-Meier method. High expression of SIRT3 is associated with a shorter survival time in esophageal cancer patients, as shown by the log-rank test (P = .007), and the level of SIRT3 expression was identified as an independent predictor for esophageal cancer outcome using Cox proportional hazards model analysis (relative risk, 2.061; 95% confidence interval, 1.050-4.046; P = .036). SIRT3 expression was associated with esophageal cancer outcome. The analysis of SIRT3 levels can help in the identification of patient subgroups that are at high risk for poor disease outcomes.

Risk-associated single nucleotide polymorphisms of mitochondrial D-loop mediate imbalance of cytokines and redox in rheumatoid arthritis.

BACKGROUND: We have identified rheumatoid arthritis (RA) risk-associated single nucleotide polymorphisms (SNPs) in the mitochondrial displacement loop (D-loop) including the major alleles of nucleotides 195T/C, 16260C/T, and 16519C/T as well as the minor alleles of nucleotides 146T/C and 150C/T previously. OBJECTIVE: We evaluated the potential relationships of these SNPs with status for oxidative stress and inflammation cytokines. METHODS: The DNA was extracted from blood samples of RA patients, and the SNPs of DNA D-loop were verified by polymerase chain reaction amplification and sequence analysis. Serum levels of inflammatory cytokines including interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-10, and tumor necrosis factor-α (TNF-α) were determined by cytometric bead array. Plasma reactive oxygen species (ROS) levels were measured by fluorescent probe technology. RESULTS: The RA risk-related allele 16519C was significantly associated with high IFN-γ levels (100.576 ± 11.769 vs 64.268 ± 8.199, 95% confidence interval [CI] -66.317 to -6.299, P = 0.018). This allele also associated with ROS at borderline statistics level (619.295 ± 36.687 vs 526.979 ± 25.896, 95% CI -186.145 to -1.513, P = 0.054). The subsequent analysis also showed that the ROS levels were positively correlated with IFN-γ levels (R = 0.291, P = 0.002). Further analysis showed that RA patients with high C-reactive protein levels displayed a higher ROS level (P = 0.001). CONCLUSION: Our results imply that the 16519C allele of the mtDNA D-loop might promote ROS and IFN-γ levels by altering the replication and transcription of mtDNA, thereby modifying RA development. REMARK: The potential relationships of RA-associated SNPs in the mitochondrial D-loop with status for oxidative stress and inflammation were evaluated. The 16519C allele of the mtDNA D-loop might promote ROS and IFN-γ levels by altering the replication and transcription of mtDNA to modify RA development.

High-Modulus Laminated SiC/AZ91 Material with Adjustable Microstructure and Mechanical Properties Based on the Adjustment of the Densities of the Ceramic Layers.

To address the issue of inadequate strength and plasticity in magnesium matrix composites, SiC preforms were prepared using the freeze-casting process. The effects of sintering temperature on the microstructure, mechanical properties, and fracture behavior of SiCp/AZ91 magnesium matrix composites were studied by controlling the density of SiC preforms through low-temperature sintering. The results indicate that as the sintering temperature decreases, the reaction products in the SiC layer decrease, resulting in lower SiC preform density and increased content of AZ91 alloy filling in the layer. The increased alloy content in the ceramic layer not only inhibits crack initiation but also hinders crack propagation, thereby endowing the SiCp/AZ91 laminated material with excellent compressive strength and compressive strain. At the sintering temperature of 900 °C, the SiCp/AZ91 laminated material exhibits impressive compressive strength and strain values of 623 MPa and 8.77%, respectively, which demonstrates an excellent combination of strength and toughness.

Hot Tensile Deformation Mechanism and Fracture Behavior of the ZW31/PMMC Laminate.

In this work, a Mg-Zn-Y (ZW31) alloy with good plasticity was introduced into 10 µm 10 vol% SiCp/AZ91 composite materials (PMMCs) via the extrusion compound method, and then the ZW31/PMMC laminate was prepared via multi-pass hot rolling. The hot deformation mechanism and elevated temperature tensile fracture mechanism of ZW31/PMMC laminates were studied using the elevated temperature tensile test. The elevated temperature deformation mechanism is influenced by the strain rate. At low strain rates, grain boundary slip is the primary elevated temperature deformation mechanism of the ZW31/PMMC laminate. However, at high strain rates, the activation of pipeline diffusion is facilitated by the particle deformation zone (PDZ) in the PMMC layer with a high dislocation density, leading to the dominance of dislocation climbing as the main mechanism for elevated temperature deformation of the laminate. Additionally, the implementation of a ZW31/PMMC laminate structure effectively inhibits the initiation and propagation of cavities and microcracks within the laminate layer along the normal direction (ND) while simultaneously blunting crack tips via lattice dislocation emission toward the ZW31 layer. Upon cracking of the PMMC layer, stress concentration occurs in the fracture area of the ZW31 layer, ultimately resulting in necking-induced detachment.

CD14, a novel surface marker of esophageal cancer stem cells.

Studies on targeting cancer stem cells (CSCs) have not yielded satisfactory results regarding solid tumor treatments; one of the reasons for this is the difficulty associated with the identification of a relatively specific antigen in solid tumors. CD14, which is mainly expressed in certain immune cells, is associated with tumor recurrence, growth, metastasis and resistance to treatment, which is in conformity with the characteristics of CSCs. It was thus hypothesized that esophageal CSCs (ECSCs) express CD14. In the present study, paraffin­embedded sections of human esophageal carcinoma were used to determine the co­expression of CD14 and the ECSC marker aldehyde dehydrogenase­1 (ALDH1) using immunofluorescence. CD14+ cells were then isolated using immunomagnetic separation for stemness detection, including proliferation, migration, invasion and tumorigenicity. Cell Counting Kit­8 (CCK­8), EdU and colony­formation assays were utilized to investigate the proliferative ability, the metastatic capacity was examined using Transwell and wound­healing assays and a xenograft assay was performed to investigate the tumorigenic ability. It was indicated that the ALDH1­labeled ECSCs expressed CD14 and primary CD14+ cells possessed the characteristics of CSCs. On the whole, the results of the present study suggest the potential utility of CD14 as a novel surface marker for ECSCs.

Thermal conductivity and mechanical properties of graphite/Mg composite with a super-nano CaCO3 interfacial layer.

Incorporating graphite/graphene into a Mg alloy matrix is a promising approach for developing lightweight heat dissipation materials. However, carbon material is inherently incompatible with Mg because of their distinctly different surface characteristics, resulting in the challenge of composite fabricating and interface controlling. Herein, a new strategy of in situ interfacial modification was proposed to achieve excellent thermal conductivity and mechanical properties in graphite/Mg composites. A super-nano CaCO3 interfacial layer was reported in this paper. The detailed interfacial structure, reaction thermodynamics and kinetics, and interface strengthening mechanisms were analyzed and discussed. Several preferential epitaxial relationships of the Mg/CaCO3 interface were revealed, which are conducive to minimize the interfacial energy, stabilize and strengthen the interface. Moreover, strong ionic bond of graphite/CaCO3 interface was demonstrated. The strong chemical interface bonding of graphite-Mg via in situ interface modification facilitates both the interfacial cohesion and interfacial thermal conduction, which endows the graphite/Mg composites with superior strength-thermal conductivity synergy.

A polymorphism at the miR-502 binding site in the 3'-untranslated region of the histone methyltransferase SET8 is associated with hepatocellular carcinoma outcome.

MicroRNAs (miRNAs) can bind to the 3'-untranslated regions (UTRs) of messenger RNAs, where they interfere with translation and thereby regulate cell differentiation, apoptosis and tumorigenesis. Genetic polymorphisms in the 3'-UTRs targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behavior of individual miRNAs. The histone methyltransferase SET8 has been reported to methylate TP53 and regulate genomic stability. We analyzed a single-nucleotide polymorphism (rs16917496) within the miR-502 miRNA seed region for the 3'-UTR of SET8 in Chinese patients with hepatocellular carcinoma (HCC). The SET8 CC genotype was independently associated with longer postoperative survival in patients with HCC by multivariate analysis (relative risk, 0.175; 95% CI = 0.053-0.577; p = 0.004). The SET8 CC genotype was associated with reduced SET8 protein levels based on the immunostaining of 51 HCC tissue samples. We also found that the low SET8 levels were associated with longer HCC survival. Our data suggest that SET8 modifies HCC outcome by altering its expression, which depends, at least in part, on its binding affinity with miR-502. The analysis of genetic polymorphisms in miRNA binding sites can help to identify patient subgroups that are at high risk for poor disease outcomes.

Recrystallization Behavior of a Mg-5Zn Alloy Influenced by Minor SiCp during Hot Compression.

The influence of minor SiCp on the dynamic recrystallization (DRX) and dynamic precipitation behaviors of the Mg-5Zn matrix were investigated through the hot compression test. The results showed that the addition of SiCp improved the DRXed ratio of Mg-5Zn matrix, but the recrystallized grains in 1 vol.% 5 µm SiCp/Mg-5Zn material were mainly formed by the "bulging" nucleation of the grain boundary at a low compressive strain (~0.05, ~0.1 and ~0.35), and PDZ (particle deformation zone) around SiCp had little effect on the recrystallization nucleation. However, the fine recrystallized grains appeared around the particles when the compressive strain reached ~0.7, which was attributed to the promotion effect of PDZ on recrystallization nucleation. This shows that PDZ around particles can promote DRX nucleation under large strain. Meanwhile, compared to the Mg-5Zn alloy, the volume fraction and size of the secondary phase in the SiCp/Mg-5Zn material increased due to the influence of SiCp on the recrystallization behavior of Mg-5Zn matrix.

Sequence polymorphisms of mitochondrial D-loop and hepatocellular carcinoma outcome.

Accumulation of mutations and single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) might be associated with cancer risk and disease outcome. We investigated the prediction power of D-loop SNPs in hepatocellular carcinoma (HCC) patients. No mutation in these HCC patients has prediction power for post-operational survival, whereas two SNP sites (nucleotides 146 T/C and 150 C/T) were identified by the log-rank test for statistically significant prediction of HCC survival. In an overall multivariate analysis, allele 146 was identified as an independent predictor of HCC outcome. The length of survival of patients with allele 146C was significantly shorter than that of patients with allele 146T (relative risk, 2.781; 95% CI, 1.127-6.859; p=0.026). The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify patient subgroups at high risk of a poor disease outcome.

Dicer Enhances Bevacizumab-Related Inhibition of Hepatocellular Carcinoma via Blocking the Vascular Endothelial Growth Factor Pathway.

PURPOSE: Vascular endothelial growth factor (VEGF) family members contribute greatly to the development and angiogenesis of hypervascular hepatocellular carcinoma (HCC). We have previously shown that Dicer inhibited HCC growth. In this study, we aimed to determine the relationship between Dicer and VEGF in HCC. METHODS: Gain-of-function studies were performed to determine the effect of different treatments on the proliferation, migration, and invasion of HCC cells. Expression of VEGF-A in xenograft tumor tissues was analysed using Western blotting, and that of CD31 using immunohistochemical analysis. RESULTS: We found that Dicer inhibited proliferation, migration and invasion of HCC cells by suppressing VEGF-A expression. Interestingly, VEGF-A165, which is the most prominent VEGF-A isoform, counteracted Dicer-induced inhibition of HCC cells. In addition, a monoclonal anti-VEGF antibody (bevacizumab) enhanced Dicer-induced inhibition of HCC in vitro and in vivo. Further, immunohistochemical analysis of CD31 indicated bevacizumab and Dicer synergized to reduce tumor microvessel density. CONCLUSION: Our data demonstrated that Dicer enhanced bevacizumab-related inhibition of HCC cell via the VEGF pathway; therefore, Dicer in coordination with bevacizumab may provide another potential approach for HCC therapy.

Association of an miR-502-binding site polymorphism in the 3'-untranslated region of SET8 with colorectal cancer.

The histone methyltransferase SET8 is regulated by microRNA-502 through the binding site in its 3'-untranslated region, and the rs16917496 polymorphism at the miR-502-binding site in the SET8 gene has been implicated in a number of cancer types. The rs16917496 polymorphism including CC, CT and TT genotypes was analyzed in patients with colorectal cancer; the CC genotype was identified to be independently associated with longer post-operative survival times using multivariate analysis (relative risk, 2.406; 95% confidence interval, 1.017-5.691; P=0.046). In addition, decreased SET8 expression was associated with the SET8 CC genotype and longer survival times for patients with colorectal cancer. The results of the present study indicated that miR-502 mediates SET8 expression at least partly by altering the binding affinity between miR-502 and SET8 so as to modify the colorectal cancer outcome. The results indicate that SET8 may be a novel target for colorectal cancer therapy.

Overexpression of RhoA enhances peritoneal dissemination: RhoA suppression with Lovastatin may be useful for ovarian cancer.

Small guanosine triphosphatase RhoA has been known to re-organize cytoskeletons and regulate cell migration. The present authors have previously reported that expression of RhoA is significantly increased in advanced ovarian carcinomas and also in the peritoneal disseminated lesions. The present study investigated whether overexpression of RhoA could alter the progressive behavior of ovarian cancer cells. The effect of various Rho inhibitors on the biological behavior of ovarian cancer cells in vitro and in vivo was also examined. A stable RhoA-transfectant of an ovarian cancer cell line SKOV3 was generated and examined in vitro for alterations of proliferative activity and invasiveness, and also in the nude mice model for peritoneal dissemination. In addition, the effect of a specific Rho inhibitor (C3 exoenzyme), Rho kinase inhibitor (Y27632) and hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (Lovastatin and Pravastatin) were studied in vitro and in vivo. Forced overexpression of RhoA did not alter proliferative activity but significantly increased the invasiveness in vitro, which was suppressed by addition of C3 exoenzyme, Y27834, Lovastatin and Pravastatin. In the nude mice model, the frequency of dissemination and the number of disseminated lesions were significantly increased in the RhoA transfectant than in the control. In addition, oral administration of Lovastatin significantly decreased the number of metastatic sites compared with the control. These findings suggest that upregulation and/or activation of RhoA play an important role in the peritoneal dissemination of ovarian carcinoma, and that Lovastatin might be a candidate for the possible, novel treatment for ovarian carcinoma patients with peritoneal dissemination.

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is associated with colorectal cancer outcome.

Single nucleotide polymorphisms (SNPs) in the displacement loop (D-Loop) of mitochondrial DNA (mtDNA) has been identified for their association with the risk and outcome in many cancers. We have identified risk associated D-loop SNPs for colorectal cancer previously, in the present study, we evaluate their prognostic value for postoperative survival of colorectal cancer (CRC). The minor haplotype of nucleotides 16290T and frequent haplotype of nucleotide 16298T in the hypervariable segment 1 (HV1) region of the D-loop were identified for their association with high survival rate of CRC. After adjusted with COX proportional hazard model, the nucleotide site of 16290 was identified as independent predictor for CRC (RR, 0.379; 95% CI, 0.171-0.839; p = 0.017). In conclusion, SNPs in the mtDNA D-Loop were found to be valuable markers for colorectal cancer outcome evaluation.

miR-502 medaited histone methyltransferase SET8 expression is associated with outcome of esophageal squamous cell carcinoma.

The histone methyltransferase SET8, whose expression is regulated by miR-502 though the binding site in the 3' UTR of SET8, implicated in cancer development. Single nucleotide polymorphism (SNP) of rs16917496 located in the miR-502 and SET8 binding site was analyzed in esophageal squamous cell carcinoma (ESCC) patients, the SET8 C/C genotype was independently associated with longer post-operative survival by multivariate analysis (relative risk, 2.250; 95% CI, 1.041-4.857; p = 0.039). Moreover, the reduced SET8 expression mediated by SET8 C/C genotype was associated with longer ESCC survival. Functional assay indicated that the SET8 knock down could inhibit proliferation and promote apoptosis of ESCC cells. The subsequent assay also showed the markedly inhibition of ESCC cell migration and invasion by SET8 knock down. Our data suggested that the altering SET8 expression, which is mediated at least partly by miR-502 through changing the binding affinity between miR-502 and SET8 3' UTR, could modify the ESCC outcome by inhibiting the proliferation and invasion as well as promoting the apoptosis of ECSS cell. Our data indicated that SET8 was a new target for ESCC therapy.

A polymorphism at the microRNA binding site in the 3'-untranslated region of C14orf101 is associated with the risk of gastric cancer development.

MicroRNAs (miRNAs) bind to the 3'-untranslated regions (3'-UTRs) of mRNAs, affecting translation and regulating cell differentiation, tumorigenesis and apoptosis. Genetic polymorphisms in these regions in target genes are able to affect the binding affinity between miRNA and target genes, ultimately affecting the expression of individual miRNAs. In the present case-control study, genotyping of 5 microRNA single nucleotide polymorphisms (SNPs) located at the binding site of the 3'-UTR of RYR3 (rs1044129), C14orf101 (rs4901706), KIAA0423 (rs1053667), GOLGA7 (rs11337) and KRT81 (rs3660) genes was assessed in order to investigate its role in gastric cancer (GC). The results indicated that the rs4901706 SNP, which is located in the 3'-UTR of C14orf101, was associated with GC development risk, as determined by χ2 analysis (relative risk, 1.630; 95% confidence interval, 1.070-2.483; P=0.022). A Renilla/luciferase reporter assay also indicated the different binding affinity between the SNP of rs4901706 and microRNA. In conclusion, rs4901706 SNP of C14orf101 gene in the microRNA binding site may be used as a valuable biomarker when predicting GC risk.

Prognostic significance of Dicer expression in hepatocellular carcinoma.

Dicer is a RNaseIII endonuclease of the microRNA processing pathway, which is implicated in carcinogenesis of various types of human cancer. The present study assessed the expression level of Dicer in hepatocellular carcinoma (HCC) tissue to evaluate its association with HCC tumorigenesis. A low expression of Dicer was significantly associated with a shorter postoperative survival time of patients with HCC, which was assessed using the log-rank test with Kaplan-Meier survival analysis. Multivariate analysis identified that Dicer expression was an independent predictor for HCC outcome (relative risk, 0.660; 95% confidence interval, 0.506-0.861; P=0.002). A functional assay demonstrated that Dicer overexpression inhibited the proliferation and promoted the apoptosis of HCC cells. In addition, a Transwell assay revealed that Dicer markedly inhibited the migration and invasion of HCC cells. The present findings indicate that Dicer expression modified the outcomes of HCC patients by inhibiting proliferation, promoting apoptosis and inhibiting metastasis of HCC cells.