LncRNAs as potential diagnostic and prognostic biomarkers in gastric cancer: A novel approach to personalized medicine

Gastric cancer is the third leading cause of cancer death with 5-year survival rate of about 30–35%. Since early detection is associated with decreased mortality, identification of novel biomarkers for early diagnosis and proper management of patients with the best response to therapy is urgently needed. Long noncoding RNAs (lncRNAs) due to their high specificity, easy accessibility in a noninvasive manner, as well as their aberrant expression under different pathological and physiological conditions, have received a great attention as potential diagnostic, prognostic, or predictive biomarkers. They may also serve as targets for treating gastric cancer. In this review, we highlighted the role of lncRNAs as tumor suppressors or oncogenes that make them potential biomarkers for the diagnosis and prognosis of gastric cancer. Relatively, lncRNAs such as H19, HOTAIR, UCA1, PVT1, tissue differentiation-inducing nonprotein coding, and LINC00152 could be potential diagnostic and prognostic markers in patients with gastric cancer. Also, the impact of lncRNAs such as ecCEBPA, MLK7-AS1, TUG1, HOXA11-AS, GAPLINC, LEIGC, multidrug resistance-related and upregulated lncRNA, PVT1 on gastric cancer epigenetic and drug resistance as well as their potential as therapeutic targets for personalized medicine was discussed.     

CTNNBIP1 downregulation is associated with tumor grade and viral infections in gastric adenocarcinoma

Gastric cancer is a life-threatening disease; resulting from interaction among genetic, epigenetic, and environmental factors. Aberrant dysregulation and methylation changes in Wnt/β-catenin signaling downstream elements are a prevalent phenomenon encountered in gastric tumorigenesis. Also, viral infections play a role in gastric cancer development. CTNNBIP1 (β-catenin interacting protein 1) gene is an antagonist of Wnt signaling which binds to the β-catenin molecules. The CTNNBIP1 function as tumor suppressor gene or oncogene in different types of cancer is controversial. Moreover, its function and regulatory mechanisms in gastric cancer progression is unknown. In the present study, we examined CTNNBIP1 gene expression, the methylation status of the regulatory region of the gene, and their association with Epstein–Barr virus (EBV), and cytomegalovirus (CMV) and Helicobacter pylori infections in human gastric adenocarcinoma tissues in comparison with their adjacent nontumoral tissues. Our data revealed a significant downregulation of CTNNBIP1 in gastric tumors. Female patients showed lower level of CTNNBIP1 than males (p < 0.05). Also, decreased expression of CTNNBIP1 was markedly associated with well-differentiated tumor grades (p < 0.05). No methylation change was observed between tumoral and nontumoral tissues. Additionally, CTNNBIP1 down regulation was significantly associated with CMV infection (p < 0.05). In the absence of EBV infection, lower expression of CTNNBIP1 was observed. There was no association between H. pylori infection and CTNNBIP1 expression. Our findings revealed the tumor suppressor role for CTNNBIP1 in gastric adenocarcinoma. Interestingly, EBV and CMV infections modulate CTNNBIP1 expression.     

Microtubule cytoskeleton and morphogenesis in the amoebae of the myxomycete Physarum polycephalum

Summary— The amoebae of the myxomycete Physarum polycephalum are of interest in order to analyze the morphogenesis of the microtubule and microfilament cytoskeleton during cell cycle and flagellation. The amoebal interphase microtubule cytoskeleton consists of 2 distinct levels of organization, which correspond to different physiological roles. The first level is composed of the 2 kinetosomes or centrioles and their associated structures. The anterior and posterior kinetosomes forming the anterior and posterior flagella are morphologically distinguishable. Each centriole plays a role in the morphogenesis of its associated satellites and specific microtubule arrays. The 2 distinct centrioles correspond to the 2 successive maturation stages of the pro-centrioles which are built during prophase. The second level of organization consists of a prominent microtubule organizing center (mtoc 1) to which the anterior centriole is attached at least during interphase. This mtoc plays a role in the formation of the mitotic pole. These observations based on ultrastructural and physiological analyses of the amoebal cystoskeleton are now being extended to the biochemical level. The complex formed by the 2 centrioles and the mtoc 1 has been purified without modifying the microtubule-nucleating activity of the mtoc 1. Several microtubule-associated proteins have been characterized by their ability to bind taxol-stabilized microtubules. Their functions (e.g., microtubule assembly, protection of microtubules against dilution or cold treatment, phosphorylating and ATPase activities) are under investigation. These biochemical approaches could allow in vitro analysis of the morphogenesis of the amoebal microtubule cytoskeleton.     

Perception of Antiretroviral Generic Medicines: One-Day Survey of HIV-Infected Patients and Their Physicians in France

BackgroundIn the interest of cost effectiveness, switching antiretroviral brand name medications to generics is recommended in France since 2013. The study objective was to evaluate the perception of generics per se and antiretroviral generics in HIV-infected patients and their hospital physiciansConclusionsAcceptability of antiretroviral generics in this French population was mostly dictated by the patient’s and physician’s knowledge and use of generics overall. It should be improved with an efficient information of both patients and physicians.     

Reduced frequency of circulating regulatory T cells and their related immunosuppressive mediators in treated celiac patients

Background

Regulatory T cells (Tregs) have an important role in the control of the immune responses. This study aimed to compare the frequency of peripheral blood (PB) CD4+?CD25+?FoxP3+?Treg cells and PB and duodenal expression levels of pro- and anti-inflammatory mediators in treated celiac disease (CD) patients and healthy controls.

Methods and results

Duodenal biopsy specimens and PB samples were collected from 60 treated CD patients and 60 controls. Flow cytometry analysis was conducted on peripheral blood mononuclear cell (PBMC) specimens and relative PB and duodenal mRNA expression levels of CD25, forkhead box P3 (Foxp3), interleukin (IL)-10 and granzyme B (GrzB) were evaluated using quantitative real-time PCR. The levels of serum IL-10 and IL-6 were tested with sandwich enzyme-linked immunosorbent assay kits. p values?<?0.05 were considered significant. Flow cytometry analysis showed a significant decrease in the number of Tregs in CD patients’ PBMC specimens (p?=?0.012). CD25 and Foxp3 PB mRNA expressions were also lower in CD patients without reaching the significance level (p?>?0.05). IL-10 PB mRNA and protein expression did not differ between the groups (p?>?0.05), and GrzB PB expression was significantly reduced in CD patients (p?=?0.001). In duodenal specimens of CD patients, while significantly increased CD25, Foxp3 mRNA expression (p?=?0.01 and 0.001, respectively) and decreased IL-10 mRNA expression (p?=?0.02) were observed, GrzB mRNA expression did not differ between groups (p?>?0.05). Moreover, a high serum level of IL-6 was observed in CD patients (p?=?0.001).

Conclusions

Despite following the gluten free diet, there may still be residual inflammation in the intestine of CD patients. Accordingly, finding a therapeutic approach based on strengthening the function of Treg cells in CD might be helpful.

     

SurvJamda: an R package to predict patients' survival and risk assessment using joint analysis of microarray gene expression data

SurvJamda (Survival prediction by joint analysis of microarray data) is an R package that utilizes joint analysis of microarray gene expression data to predict patients' survival and risk assessment. Joint analysis can be performed by merging datasets or meta-analysis to increase the sample size and to improve survival prognosis. The prognosis performance derived from the combined datasets can be assessed to determine which feature selection approach, joint analysis method and bias estimation provide the most robust prognosis for a given set of datasets. AVAILABILITY: The survJamda package is available at the Comprehensive R Archive Network, http://cran.r-project.org. CONTACT: hyasrebi@yahoo.com.     

Vascular endothelial growth factor (VEGF) +405 C/G polymorphism is associated with essential hypertension in a population from Tehran of Iran

Vascular endothelial growth factor (VEGF) has long been recognized as a hypotensive mediator. Little is known regarding the contribution of polymorphisms in VEGF gene to essential hypertension (EH), however. We aimed to investigate the association between +405 VEGF C/G single nucleotide polymorphism (SNP) and occurrence of EH in a sample of patients with diabetes. A study population of 474 subjects with diabetes of which 45.6% (216) had EH was enrolled in this study. Interviews and physical examinations were performed in a clinical setting. Subjects were matched in baseline anthropometric and biochemical characteristics except for total cholesterol. Genotyping of +405 VEGF C/G (rs2010963) SNP was carried out using polymerase chain reaction–restriction fragment length polymorphism. The allelic distribution of the sample did not violate Hardy–Weinberg equilibrium. Subjects with EH had a higher frequency of G allele (P = 0.005). Additionally, those with EH had a significantly higher frequency of GG genotype (P = 0.015). In multivariate logistic regression models controlling for possible confounders, having GG against CC genotype was associated with an odds ratio of 2.51 (95% CI: 1.44–4.38; P = 0.001). Moreover, presence of each G allele was linked to a 1.58-fold increase in risk of having EH (95% CI: 1.200–2.086; P = 0.001). In conclusion, +405 VEGF C/G SNP is associated with EH in patients with diabetes, suggesting presence of G allele and GG or CG genotype confer susceptibility towards EH.     

Lack of association between cyclooxygenase 2−765G/C gene polymorphism and breast cancer risk in Ahvaz, west-south Iran

Cyclooxygenases are key enzymes in conversion of arachidonic acid into prostaglandin H2. Cyclooxygenase-2 (COX-2) increases prostaglandins in neoplastic tissue. COX-2 has important roles in cell proliferation cancers, angiogenesis, and alzheimer. COX-2 is up-regulated in several types of cancer, and it is hypothesized that COX-2 expression may be genetically influenced. Our main objective was to evaluated the association of polymorphism COX-2 with risk of breast cancer in khouzestan province, and the second objective of the study was to evaluate the association with biochemistry parameters. This study consisting of 150 patients with breast cancer and 120 normal DNA was extracted from the white blood cells. Polymorphism cox2 gene was detected by polymerase chain reaction according to the standard methods. The profile lipids and estrogen were measured in two groups by standard methods. Chi square analysis showed that there was no association between breast cancer risk and COX-2 ?765G>C genotype and alleles. Also, no association were observed between ?765G>C polymorphism and biochemistry parameters. A multiple logistic regression model with cox2 genotypes and LDL and HDL as covariates revealed that there is no significant association between cox2 genotypes and risk of breast cancer, but higher values of LDL and HDL significantly increase risk of breast cancer.     

Isolation and characterization of halophilic bacteria from Urmia Lake in Iran

Urmia Lake is one of the most permanent hypersaline lakes in the world which is threatened by hypersalinity and serious dryness. In spite of its importance no paper has been published regarding bacterial community of this lake. Accordingly, the present study aimed to investigate the halophilic bacteria in the aforementioned lake. In so doing, thirty seven strains were isolated on six different culture media. The isolated strains were characterized using phenotypic and genotypic methods. Growth of the strains occurred at 25–35°C, pH 6–9 and 7 to 20% (w/v) NaCl indicating that most of the isolates were moderately halophiles. Catalase, oxidase and urease activities were found to be positive for the majority of the isolates. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolated bacteria belonged to two major taxa: Gammaproteobacteria (92%, including Salicola [46%], Pseudomonas [13.5%], Marinobacter [11%], Idiomarina [11%], and Halomonas [8%]) and Firmicutes (8%, including Bacillus [5%] and Halobacillus [3%]). In addition, a novel bacterium whose 16S rRNA gene sequence showed almost 98% sequence identity with the taxonomically troubled DSM 3050^T, Halovibrio denitrificans HGD 3^T and Halospina denitriflcans HGD 1–3, each, was isolated. 16S rRNA gene similarity levels along with phenotypic characteristics suggest that some of the isolated strains could be regarded as potential type strain for novel species, on which further studies are recommended.