TRPS1 knockdown inhibits angiogenic vascular mimicry in human triple negative breast cancer cells.

PURPOSE: Vascular mimicry (VM) tubules are lumen structures comprised of malignant tumor cells without the participation of endothelial cells. VM simulates blood vessel function in tumors to deliver a sufficient blood supply for proliferation, invasion, and metastasis of malignant tumors, thereby reducing the clinical effects of anti-angiogenic treatments. The elimination or prevention of malignant tumor VM development therefore represents an urgent research goal as a therapeutic strategy to and cut off nutrients required for tumor growth. The GATA transcription factor TRPS1 is abnormally up-regulated in breast cancer, osteosarcoma, prostate cancer, and other tumor tissues, and is instrumental in regulating cell proliferation, differentiation, and tissue growth and development. METHODS: Here, we explored the effects of TRPS1 knockdown on VM and the proteins underlying its development in triple-negative breast cancer cell line MDA-MB-231. RESULTS: We found that TRPS1 knockdown resulted in obvious inhibition of VM development. Fluorescence microscopy of F-actin and tubulin revealed that loss of TRPS1 function resulted in disruption of cytoskeleton and microtubule formation, respectively. In addition, TRPS1-suppressed cells exhibited reduced accumulation of VM-associated proteins EphA2, MMP-2, MMP-9, VEGF, and VE-cadherin. Moreover, it is interesting to know that the capacity for migration and invasion were limited in MDA-MB-231cells after TRPS1 knockdown and that the average number of VM tubules, their length, and number of intersections were also significantly decreased. CONCLUSIONS: Based on our results, and in light of previous studies, we thus proposed that TRPS1 suppression negatively affects vascular mimicry possibly through reduced TRPS1-mediated transcriptional regulation of VM-related protein VEGF-A.

Exosome-mediated delivery of SCD-1 siRNA promoted the death of anaplastic thyroid carcinoma cells via regulating ROS level.

PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers in the world. Stearoyl-CoA desaturase-1 (SCD-1) is one of major enzymes in the de novo synthesis of fatty acids and is related to cancer aggressiveness and poor patient prognosis. The study aimed to construct exosomes loaded SCD-1 interference, investigate its effects and mechanisms on the cell proliferation and apoptosis of ATC cells. METHODS: The expressions of SCD-1 in normal thyroid cell line and ATC cell lines were determined by qRT-PCR and western blotting, respectively. Exosomes were prepared and purification then loaded with SCD-1 siRNA by electroporation and observed by transmission electron microscopy. Higher SCD-1 mRNA and protein levels were found in ATC cell lines compared than normal thyroid cell line (P < 0.05), and both Hth-7 and FRO cells could uptake PKH67-labeled exosomes. The effects of exosomes loaded SCD-1 siRNA on ATC cells were measured by CCK8 assay and apoptosis detection kit. RESULTS: When compared with control group, the cell viability significantly decreased in both two ATC cell lines taken up exosomes loaded SCD-1 siRNA (P < 0.001), and apoptotic and necrotic cells obviously increased (P < 0.05). In order to explore the mechanism of exosomes loaded SCD-1 on ATC, the ROS level was detected by fluorescence reagent. It was found that exosomes loaded SCD-1 siRNA significantly increased intracellular ROS level of ATC cells (P < 0.05). CONCLUSIONS: Exosomes loaded SCD-1 siRNA inhibited ATC cellular proliferation and promoted cellular apoptosis, and the mechanisms involved maybe the regulation of fatty acids metabolism and ROS level. Our study provides a promising therapeutic strategy for ATC.

Candidate Interneurons Mediating the Resetting of the Locomotor Rhythm by Extensor Group I Afferents in the Cat.

Sensory information arising from limb movements controls the spinal locomotor circuitry to adapt the motor pattern to demands of the environment. Stimulation of extensor group (gr) I afferents during fictive locomotion in decerebrate cats prolongs the ongoing extension, and terminates ongoing flexion with an initiation of the subsequent extension, i. e. "resetting to extension". Moreover, instead of the classical Ib non-reciprocal inhibition, stimulation of extensor gr I afferents produces a polysynaptic excitation in extensor motoneurons with latencies (∼3.5-4.0 ms) compatible with 3 interposed interneurons. We assume that some interneurons in this pathway actually belong to the rhythm-generating layer of the locomotor Central Pattern Generator (CPG), since their activity was correlated to a resetting of the rhythm. In the present work fictive locomotion was (mostly) induced by i.v. injection of nialamide followed by l-DOPA in paralyzed cats following decerebration and spinalization at C1 level. In some experiments, we extended previous observations during fictive locomotion on the emergence and locomotor state-dependence of polysynaptic excitatory postsynaptic potentials from extensor gr I afferents to ankle extensor motoneurons. However, the main focus was to record location and properties of interneurons (n = 62) that (i) were active during the extensor phase of fictive locomotion and (ii) received short-latency excitation (mono-, di- or polysynaptic) from extensor gr I afferents. We conclude that the interneurons recorded fulfill the characteristics to belong to the neuronal pathway activated by extensor gr I afferents during locomotion, and may contribute to the 'resetting to extension' as part of the locomotor CPG.

Cost-effectiveness analysis of capecitabine plus bevacizumab versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer from Chinese societal perspective.

PURPOSE: The aim of the study was to evaluate the cost-effectiveness of capecitabine plus bevacizumab compared with capecitabine alone in elderly patients with metastatic colorectal cancer (CRC) from a Chinese societal perspective. METHODS: A decision-analytic Markov model was conducted to simulate the process of metastatic CRC. Three distinct health states: progression-free survival (PFS), progressive disease and death were included. Clinical data were derived from the AVEX trial. Health effectiveness was denoted in quality-adjusted life years (QALYs) and health utilities were derived from previously published studies. Incremental cost-effectiveness ratio (ICER) was regarded as the primary endpoint and willingness-to-pay (WTP) threshold was set at $26,753.37/QALY (3 × per capita GDP of China, 2017). One-way sensitivity analyses and probabilistic sensitivity analysis were also performed to explore the parameters uncertainty in the study. RESULTS: Over a 10-year life horizon, capecitabine plus bevacizumab gained 1.14 QALYs at an average cost of $21,609.48, while the effectiveness and cost of capecitabine group were 0.99 QALYs and $7274.83, respectively. The ICER between the two groups was $95,564.33/QALY. Parameters that mostly influenced the results of the model were utility of PFS state, duration of PFS state for capecitabine plus bevacizumab, total cost of PFS state for capecitabine plus bevacizumab and price of bevacizumab. The probabilities of capecitabine plus bevacizumab and capecitabine as the dominant option were 0% and 100% at the WTP threshold of $26,753.37/QALY. CONCLUSIONS: The results of the study showed that capecitabine plus bevacizumab is unlikely to be a cost-effective treatment option for elderly patients with metastatic CRC.

Cost-effectiveness of trifluridine/tipiracil (TAS102) for heavily pretreated metastatic gastric cancer.

BACKGROUND AND AIM: Trifluridine/tipiracil (TAS102), a novel oral cytotoxic chemotherapy, significantly improved overall survival compared with placebo in heavily pretreated advanced gastric cancer. This study aimed to evaluate the cost-effectiveness of TAS102 in the third-line or later treatment for this population from the US payer perspective. METHODS: A Markov model was developed to simulate advanced gastric cancer, including three health states: progression-free survival (PFS), progressive disease (PD) and death. Model inputs were derived from a randomised, double-blind, placebo-controlled, phase 3 trial (TAGS trial, NCT02500043). Utilities were extracted from public resources. Costs were calculated from an American payer perspective. Sensitivity analyses were conducted to explore the impact of uncertainty. RESULTS: From the US payer perspective, treatment with TAS102 for patients with heavily pretreated advanced gastric cancer was estimated to increase costs by $59,180 compared with the placebo, with a gain of 0.06 quality-adjusted life years (QALYs) for an incremental cost-effectiveness ratio (ICER) of $986,333 per QALY. The costs for progression-free survival of TAS102 group had the greatest impact on the ICERs, as well as the cost of TAS102. CONCLUSION: Trifluridine/tipiracil (TAS102) is not a cost-effective choice for patients with heavily pretreated metastatic gastric cancer from an American payer perspective.

Correlation analysis of serum obestatin expression with insulin resistance in childhood obesity.

Childhood obesity is a serious public health concern condition, as excess body fat can negatively affect a child's health. Obestatin is a hormone that regulates body weight by suppressing appetite and reducing food intake; fasting obestatin level is negatively correlated with basal insulin level. This study aims to investigate the role of obestatin in insulin resistance. A total of 54 children with simple obesity and 57 healthy controls were recruited. Levels of serum insulin, fasting blood glucose, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were measured. Serum obestatin level was determined using an enzyme-linked immunosorbent assay. We found that body mass index and waist-hip ratio of obese children were significantly higher, while obestatin level in the obese group was significantly lower (P < 0.001), as compared to those of controls. In addition, obese children exhibited higher levels of insulin, total cholesterol, triglyceride, and low-density lipoprotein (P < 0.05) as compared to the controls. Fasting blood glucose and high-density lipoprotein levels were similar between the two groups (P > 0.05). Leptin level in the obese group was also higher (P < 0.05) as compared to that of control group. Results showed that insulin resistance index was positively correlated with body mass index, waist-hip ratio (r = 0.41, P < 0.001; r = 0.245, P < 0.001), and triglyceride level (r = 0.25, P = 0.04). Our study demonstrated that obestatin is negatively correlated with fasting insulin and leptin levels, and positively correlated with insulin resistance in obese children.

Analysis of the 19 Y-STR and 16 X-STR loci system in the Han population of Shandong province, China.

The sex-linked short tandem repeats (STR), Y-STR and X-STR, are important for autosomal STRs in forensic paternity testing. We evaluated the forensic parameters of 19 Y-STRs and 16 X-STRs in the Han population of Shandong province, China. A Goldeneye 20Y kit (DYS391, DYS389I, DYS390, DYS389II, DYS348, DYS456, Y-GATA-H4, DYS447, DYS19, DYS392, DYS393, DYS388, DYS439, DYS635, DYS448, DYS460, DYS458, DYS437, DYS385 a/b) was used to analyze the forensic parameters of 534 unrelated males. A Goldeneye17X system (DXS6795, DXS9902, DXS8378, HPRTB, GATA165B12, DXS7132, DXS7424, DXS6807, DXS6803, GATA172D05, DXS6800, DXS10134, GATA31E08, DXS10159, DXS6789, DXS6810, amelogenin) was used to analyze 97 unrelated males and 214 females. In addition, we used the kits to examine 5 cases with abnormal amelogenin test results, as well as a male child with agenosomia typed by autosomal STR. We found 203 Y-STR haplotypes with allele frequencies ranging from 0.0019 to 0.7959, and GD ranging from 0.3429 to 0.9667. Expect in DXS6803, the allele frequencies of the other 15 X-STR loci showed no differences between females and males. PDF ranged from 0.5504 to 0.9638, while PDM ranged from 0.3176 to 0.8377. With the exception of DXS6803 and DXS6810, the allele frequencies of other X-STR loci were in accordance with Hardy-Weinberg equilibrium in females. One amelogenin negative case was characterized as a deletion of Y-DYS458. This paper provided data regarding the genetic polymorphism of Y-STRs and X-STRs in the Han population, and demonstrated the importance of Y-STR and X-STR in forensic autosomal STR analysis.

Lack of association between CARD10/CARMA3 tag SNPs and psoriasis vulgaris in the southern Chinese population.

Previously, we determined that the CARD11 rs4722404 single nucleotide polymorphism (SNP) increases risk of early-onset psoriasis vulgaris (PsV). Moreover, the CARD14 gene polymorphism c.C2458T (p.Arg820Trp) is associated with clinical features of this disease. CARMA1/CARD11, CARMA2/CARD14, and CARMA3/CARD10 are conserved across many species and constitute a family of proteins, all of the members of which contain various functional domains characteristic of this group. The NF-κB signaling pathway, regulated by the CARMA family of scaffold proteins and its eponymous component, is a crucial mediator in the pathogenesis of psoriasis. However, little is known about the association between CARMA3/CARD10 and PsV. The aim of this study was to evaluate the relationship between the gene encoding this protein and risk of PsV in the southern Han Chinese population. Genomic DNA from 568 individuals of southern Chinese origin, including 355 patients with PsV and 213 control subjects, was analyzed. We selected seven tag SNPs in the CARMA3/CARD10 gene and genotyped them by the SNaPshot assay. Our results identified no significant association between these SNPs and PsV in the Chinese population examined. Future studies should focus on the potential function of the CARMA3/CARD10 gene in the pathogenesis of PsV.

Migration and invasion enhancer 1 (MIEN1) is overexpressed in breast cancer and is a potential new therapeutic molecular target.

Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein that is highly expressed in various types of cancer, and is correlated with the PI3K/AKT pathway. The aim of this study was to investigate the expression of MIEN1 and its clinical pathological significance in breast cancer. We used immunohistochemical staining to examine the expression of MIEN1 in 40 samples of human breast cancer tissue and 10 samples taken from regions adjacent to normal breast tissue. The rate of detection of MIEN1 protein was 67.5%, which was significantly higher than that in adjacent non-cancerous breast tissue (0%, P < 0.05). The expression of MIEN1 correlated with age, World Health Organization grade, and lymph node metastasis, but not with tumor size or family history of cancer. Kaplan-Meier survival analysis showed that patients with positive MIEN1 protein expression had a lower overall survival rate than patients who did not express MIEN1. Downregulation of MIEN1 suppressed the expression of matrix metallopeptidase 9 by downregulating the expression of protein kinase B (also known as AKT) in breast cancer cells. Our results indicate that MIEN1 overexpression may facilitate migration and invasion in breast cancer, and MIEN1 is a potential molecular target for cancer chemotherapy.

Methylation-sensitive amplified polymorphism analysis of Verticillium wilt-stressed cotton (Gossypium).

In this study, a methylation-sensitive amplification polymorphism analysis system was used to analyze DNA methylation level in three cotton accessions. Two disease-sensitive near-isogenic lines, PD94042 and IL41, and one disease-resistant Gossypium mustelinum accession were exposed to Verticillium wilt, to investigate molecular disease resistance mechanisms in cotton. We observed multiple different DNA methylation types across the three accessions following Verticillium wilt exposure. These included hypomethylation, hypermethylation, and other patterns. In general, the global DNA methylation level was significantly increased in the disease-resistant accession G. mustelinum following disease exposure. In contrast, there was no significant difference in the disease-sensitive accession PD94042, and a significant decrease was observed in IL41. Our results suggest that disease-resistant cotton might employ a mechanism to increase methylation level in response to disease stress. The differing methylation patterns, together with the increase in global DNA methylation level, might play important roles in tolerance to Verticillium wilt in cotton. Through cloning and analysis of differently methylated DNA sequences, we were also able to identify several genes that may contribute to disease resistance in cotton. Our results revealed the effect of DNA methylation on cotton disease resistance, and also identified genes that played important roles, which may shed light on the future cotton disease-resistant molecular breeding.

Association between TXNRD1 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in a prospective study.

Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse reaction to anti-tuberculosis (TB) treatment. Thioredoxin reductase 1 (TXNRD1), encoded by the TXNRD1 gene, is an important enzyme involved in oxidant challenge. TXNRD1 plays a key role in regulating cell growth and transformation, and protects cells against oxidative damage. We investigated the association between TXNRD1 polymorphisms and ATDH susceptibility. In this prospective study, 280 newly diagnosed TB patients were followed-up for 3 months after beginning anti-TB therapy. Tag single-nucleotide polymorphisms (tag-SNPs) of TXNRD1 were selected using Haploview 4.2 based on the HapMap database of the Chinese Han in Beijing (CHB) panel. Genotyping was performed using the MassARRAY platform. Of the 280 patients enrolled in this study, 33 were lost to follow-up, 24 had ATDH, and 223 were free from ATDH. After adjusting for sex, age, smoking status, and body mass index, there were no significant differences in the allele and genotype frequency distributions of TXNRD1 SNPs between the ATDH and non-ATDH groups (all P > 0.05). The haplotype analysis showed that haplotype TCAGCC was associated with an increased risk of ATDH susceptibility [P = 0.024, OR (95%CI) = 6.273 (1.023-38.485)]. Further stratified analyses showed that the haplotype TCAGCC was associated with ATDH susceptibility in female subjects [P = 0.036, OR (95%CI) = 5.711 (0.917-35.560)] and non-smokers [P = 0.029, OR (95%CI) = 6.008 (0.971-37.158)]. Our results suggest that TXNRD1 variants may favor ATDH susceptibility in females and non-smokers. Further studies are required to verify this association.

Molecular cloning and expression vector construction of bovine TRIM28.

The bovine TRIM28 gene was amplified from ovary tissue by using RT-PCR. The TRIM28 gene was inserted into the eukaryotic expression vector pIRES2-EGFP and transfected into bovine fetal fibroblasts by using Lipofectamine 3000. TRIM28 mRNA and protein were detected by fluorescence microscope and western blotting. The results showed that the full length of TRIM28 was cloned and pIRES2-EGFP-TRIM28 was constructed successfully. EGFP expression was observed, and the pIRES2-EGFP-TRIM28 transfected group expressed more TRIM28 protein than that by the pIRES2-EGFP group. The TIMR28 gene has been successfully transferred into bovine fetal fibroblasts.

Quercetin ameliorates LPS-induced inflammation in human peripheral blood mononuclear cells by inhibition of the TLR2-NF-κB pathway.

Quercetin, a dietary flavonoid abundant in fruits, vegetables, and herbs, presents various pharmacological effects. This study aimed to investigate the anti-inflammatory effect and the underlying mechanism of quercetin in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs). Cell viability was measured by the Cell Counting Kit-8 assay. The mRNA expression of Toll-like receptor 2 (TLR2) was assessed by quantitative real-time polymerase chain reaction. Inflammatory cytokine secretions and nuclear factor (NF)-kB levels were analyzed by enzyme-linked immunosorbent assay. Our findings showed that quercetin significantly reduced LPS-induced cytotoxicity in human PBMCs. Quercetin suppressed the secretion of tumor necrosis factor-a, interleukin (IL)-1b, and IL-6 in LPS-stimulated human PBMCs. Moreover, quercetin reduced the LPS-induced increase in the expression of TLR2 mRNA and decreased the NF-kB concentration in LPS-stimulated human PBMCs. The data indicates that quercetin plays an important role in LPS-induced inflammation in human PBMCs via suppression of the TLR2-NF-kB pathway.

Association of APOA1 gene polymorphisms (rs670, rs5069, and rs2070665) with dyslipidemia in the Kazakhs of Xinjiang.

The aim of this study was to investigate the potential association between apolipoprotein A1 (APOA1) gene rs670, rs5069, and rs2070665 polymorphisms and dyslipidemia in the Kazakh population of Xinjiang, China. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to identify APOA1 (rs670, rs5069, and rs2070665) genotypes in 736 subjects (341 dyslipidemia patients and 395 control subjects). The frequencies of the CC genotype for rs1421085 were found to be 7.2% (obese group), 4.4% (overweight group), and 5.6% (control group). Polymorphisms of the three loci of the APOA1 gene in Kazakh subjects met Hardy-Weinberg equilibrium. The frequencies of the A allele for rs670 were found to be 14.3% (dyslipidemia group) and 12.7% (control group). The frequencies of the T allele for rs5069 and rs2070665 were: dyslipidmia group (7.2 and 30.1%, respectively) and control group (7.7 and 32.5%, respectively). Frequency distributions of the 3 types of genotypes and alleles of the three loci showed no statistically significant difference (P > 0.05). Significant differences were observed in lipoprotein (α) [Lp(α)] between patients with the rs2070665 CT + TT and CC genotypes (P < 0.05); however, none of the other relevant indicators differed significantly between the two genotypes. No significant association was identified between rs670 or rs5069 and the lipid-related metabolic indices assessed in the study. These findings indicate that the polymorphisms in the APOA1 gene (rs670, rs5069, and rs2070665) are not associated with dyslipidemia in the Kazakh population assessed in this study.

Reference gene selection for gene expression studies in lily using quantitative real-time PCR.

Quantitative real-time polymerase chain reaction (qRT-PCR) is an important technology used to analyze gene-expression levels. Reference genes, which are assumed to be expressed consistently across various developmental stages and in different tissues, were selected for expression level analysis. Using digital gene expression technology, we selected nine reference genes (18S, EF, CYCOL, SAND, GAPDH, ACTIN, BHLH, TIP, and Clathrin) as candidate reference genes for further study. Using three different analysis methods (GeNorm, NormFinder, and BestKeeper), a total of 144 lily (Lilium x formolongi "Raizan 3") samples were analyzed. The samples were collected from four different tissues under various developmental stages. In addition, leaves treated with different plant hormones were collected and analyzed. The data showed that the stability of the nine reference genes differed among samples, but TIP, EF, Clathrin, and BHLH could be identified as the most stable genes overall. In addition, the relative expression level of LfFT in different lily tissues with the competence to flower was also analyzed to verify the selected reference genes. This study constitutes an important source for selecting reference genes when analyzing the expression patterns of flowering time and floral development regulation genes in lily cultivars.

Comparison of the expression of human equilibrative nucleotide transporter 1 (hENT1) and ribonucleotide reductase subunit M1 (RRM1) genes in seven non-Hodgkin lymphoma cell lines.

We investigated the variability in the expression of human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit M1 (RRM1) in non-Hodgkin lymphoma cell lines. hENT1 and RRM1 mRNA expression levels in natural killer (NK) cells and seven non-Hodgkin lymphoma cell lines (YTS, SNK-6, Jeko-1, ly-1, Raji, Karpas, and Jurket) were studied using reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) and the results were compared using the Student t-test. mRNA expression of hENT1 was detectable in YTS, SNK-6, Jeko-1, ly-1, Raji, Karpas, Jurket, and NK cells, which revealed variability in gene expression. There were significant differences in the mRNA expression values of hENT1 (P = 0.021) and RRM1 (P = 0.002) compared to those in NK cells. mRNA expression of both hENT1 and RRM1 was closely associated with non-Hodgkin lymphoma cell proliferation. Differential expression analysis of hENT1 and RRM1 in non-Hodgkin lymphoma cell lines may provide novel drug leads for precision medicine.

Structural chromosomal abnormalities in couples in cases of recurrent spontaneous abortions in Jilin Province, China.

Recurrent spontaneous abortions (RSAs) occur in approximately 15 to 20% of all clinically recognizable pregnancies. Structural chromosome abnormalities result in increased risk of pregnancy loss. Parental chromosomal abnormalities are an important genetic cause of RSAs. Some cytogenetic investigations have been performed in various countries and regions to determine the pattern of chromosomal abnormalities in parents with RSAs. The aim of this study was to report the prevalence and type of structural chromosomal abnormalities in couples in cases of RSAs in Jilin Province, China. The prevalence of structural chromosomal abnormalities in these couples was 2.98%. The number of female carriers with balanced chromosomal aberrations significantly exceeded that of such male carriers, and the ratio of female/male carriers was approximately 2:1. The number of abortions in the case of female carriers was more than that for male carriers before the structural chromosome abnormality was diagnosed. This indicates that genetic counseling for couples with structural chromosomal abnormalities should consider the gender of the carriers.

Gene expression profiling of epithelial ovarian cancer reveals key genes and pathways associated with chemotherapy resistance.

The aim of this study is to analyze gene expression data to identify key genes and pathways associated with resistance to platinum-based chemotherapy in epithelial ovarian cancer (EOC) and to improve clinical treatment strategies. The gene expression data set was downloaded from Gene Expression Omnibus and included 12 chemotherapy-resistant EOC samples and 16 chemotherapy-sensitive EOC samples. A differential analysis was performed to screen out differentially expressed genes (DEGs). A functional enrichment analysis was conducted for the DEGs using the database for annotation, visualization, and integration discovery. A protein-protein interaction (PPI) network was constructed with information from the human protein reference database. Pathway-pathway interactions were determined with a test based on the hypergeometric distribution. A total of 1564 DEGs were identified in chemotherapy-sensitive EOC, including 654 upregulated genes and 910 downregulated genes. The top three upregulated genes were HIST1H3G, AKT3, and RTN3, while the top three downregulated genes were NBLA00301, TRIM62, and EPHA5. A Gene Ontology enrichment analysis showed that cell adhesion, biological adhesion, and intracellular signaling cascades were significantly enriched in the DEGs. A KEGG pathway enrichment analysis revealed that the calcium, mitogen-activated protein kinase, and B cell receptor signaling pathways were significantly over-represented in the DEGs. A PPI network containing 101 interactions was acquired. The top three hub genes were RAC1, CAV1, and BCL2. Five modules were identified from the PPI network. Taken together, these findings could advance the understanding of the molecular mechanisms underlying intrinsic chemotherapy resistance in EOC.

PDK2 and ABCG2 genes polymorphisms are correlated with blood glucose levels and uric acid in Tibetan gout patients.

Previous studies have shown that the PDK2 and ABCG2 genes play important roles in many aspects of gout development in European populations. However, a detailed genotype-phenotype analysis was not performed. The aim of the present study was to investigate the potential association between variants in these two genes and metabolism-related quantitative phenotypes relevant to gout in a Chinese Tibetan population. In total, 316 Chinese Tibetan gout patients were recruited from rheumatology outpatient clinics and 6 single nucleotide polymorphisms in PDK2 and ABCG2 were genotyped, which were possible etiologic variants as identified in the HapMap Chinese Han Beijing population. A significant difference in blood glucose levels was detected between different genotypes of rs2728109 (P = 0.005) in the PDK2 gene. We also detected a significant difference in the mean serum uric levels between different genotypes of rs3114018 (P = 0.004) in the ABCG2 gene. All P values remained significant after Bonferroni's correction for multiple testing. Our data demonstrate potential roles for PDK2 and ABCG2 polymorphisms in the metabolic phenotypes of Tibetan gout patients, which may provide new insights into the etiology of gout. Further studies are required to confirm these findings.

ATAD2 is overexpressed in gastric cancer and serves as an independent poor prognostic biomarker.

OBJECTIVE: ATPase family, AAA domain containing 2 (ATAD2) has been found overexpressed in various cancer types and correlated with malignant status and poor prognosis. However, little is known about the clinical significance of ATAD2 in gastric cancer patients. The aim of this study was to explore the clinical and prognostic significance of ATAD2 in gastric cancer. METHODS: The mRNA and protein levels expression of ATAD2 were detected in clinical tissue samples by qRT-PCR and immunohistochemistry, respectively. We examined the ATAD2 protein expression by immunohistochemistry. Furthermore, we analyzed the association between ATAD2 expression and clinicopathological features including prognosis in 166 gastric cancer samples. RESULTS: In our results, ATAD2 mRNA and protein were highly expressed in gastric cancer samples. ATAD2 overexpression was correlated with advanced clinical stage, tumor depth, lymph node metastasis, and distant metastasis. According to the survival analysis, ATAD2 protein overexpression was a poor independent prognostic factor for gastric cancer patients. CONCLUSIONS: In summary, ATAD2 could serve as a prognostic biomarker for gastric cancer patients.