Diagnostic and Prognostic Value of miR-451 Expression in Colorectal Cancer: A Meta-Analysis.

BACKGROUND: The miR-451 has been reported to play an important role in colorectal cancer (CRC) pathogenesis and can be a pivotal diagnosis biomarker of CRC. Given the contradictions in the diagnosis value of the miR-451 in patients with CRC, deciphering the diagnostic/prognostic role of this miRNA in CRC will support the identification of a novel therapeutic target for CRC. Therefore, in the present meta-analysis, we evaluated the diagnostic value of miR-451 in CRC patients. MATERIALS AND METHODS: The electronic databases of Embase, PubMed, ISI Web of Science, and Scopus systematically searched for relevant studies. The odds ratio (OR) with a 95% confidence interval (CI) was calculated to evaluate the association between miR-451 family expression and diagnosis of colorectal cancer. The parameters including sensitivity, specificity, and area under the curve (AUC) were obtained. The quality of evidence was evaluated using the Newcastle-Ottava Scale (NOS). RESULTS: This study involved 510 patients (45% female and 55% male) with CRC. The pooled analysis of the studies showed a significant association between low expression levels of miR-451 in patients with CRC (OR = 7.59; 95% CI 2.39 - 24.07; p = 0.001). The overall sensitivity and specificity were 0.95 (0.61 - 1) and 0.83 (0.43 - 0.99), respectively. The pooled AUC was 0.97 (0.88 - 1; p < 0.006). Results showed if the pre-test probability is 50% for a patient, the post-test probability will be 85%. The indices demonstrated the high potency of miR-451 as a diagnostic biomarker in patients with CRC. No publication bias was observed using the Begg's (p=0.85) and Egger's tests (p=0.45). CONCLUSION: A strong relationship between the low expression levels of miR-451 and CRC progression was observed. This finding suggests the miR-451 family may be helpful as a potential biomarker for the earlier diagnosis of colorectal cancer.

Comprehensive Analysis of the Expression, Prognosis, and Immune Infiltrates for Chromodomain-Helicase-DNA-Binding Proteins in Breast Tumor.

BACKGROUND: Several recent studies suggest that chromodomain-helicase -DNA-binding domains (CHDs) are linked with cancers. We explored the association between chromodomain-Helicase-DNA-binding domain proteins and breast cancer (BrCa) and introduced potential prognostic markers using various databases. MATERIALS AND METHODS: We analyzed the expression of the CHD family and their prognostic value in BrCa by mining UALCAN, TIMER, and Kaplan-Meier plotter databases. The association of CHD expression and immune infiltrating abundance was studied via the TIMER database. In addition, microRNAs related to the CHD family were identified by using the MirTarBase online database. RESULTS: The present study indicated that compared to normal tissues, BrCa tissues showed increased mRNA levels of CHD3/4/7 but decreased CHD2/5/9 expression. Interestingly, We also found a positive correlation between CHD gene expression and the infiltration of macrophage, neutrophil, and dendritic cells in BrCa, except CHD3/5. The Kaplan-Meier Plotter analysis suggested that high expression levels of CHD1/2/3/4/6/8/9 were significantly related to shorter relapse-free survival (RFS), while higher mRNA expression of CHD1, CHD2, CHD8, and CHD9 was significantly associated with longer overall survival of BrCa patients. The miRNAs of hsa-miR-615-3p and hsa-let-7b-5p were identified as being more correlated with the CHD family. CONCLUSION: The altered expression of some CHD members was significantly related to clinical cancer outcomes, and CHD1/2/8/9 could serve as potential prognostic biomarkers to improve the survival of BrCa patients. However, to evaluate the studied CHD members in detail are needed further investigations including experimental validation.

Integrated Bioinformatics Analysis of mRNAs and miRNAs Identified Potential Biomarkers of Oral Squamous Cell Carcinoma.

Background: Oral cancer is a frequently encountered neoplasm of the head and neck region, being the eighth most common type of human malignancy worldwide. Despite improvement in its control, morbidity and mortality, rates have improved little in the past decades. The present investigations about gene interaction and pathways still could not clear the appearance and development of oral squamous cell carcinoma (OSCC), completely. The aim of this study is to investigate the key genes and microRNAs interaction in OSCC. Materials and Methods: The microarray datasets GSE13601 and GSE98463, including mRNA and miRNA profiles, were extracted from the GEO database and were analyzed using GEO2R. Functional and pathway enrichment analyses were performed by using the DAVID database. The protein-protein interaction (PPI) network was constructed and analyzed using STRING database and Cytoscape software, respectively. Finally, miRDB was applied to predict the targets of the differentially expressed miRNAs (DEMs). Results: Totally, 97 differentially expressed genes (DEGs) were found in OSCC, including 66 up-regulated and 31 down-regulated genes. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that up-regulated genes were significantly enriched in movement of cell or subcellular component, cell adhesion, biological adhesion, cellular localization, apoptotic signaling pathway, while the downregulated genes were enriched in muscle system process and oxidation-reduction process. From the PPI network, the top 10 nodes with the highest degree were detected as hub genes. In addition, 18 DEMs were screened, which included 7 up-regulated and 11 down-regulated miRNAs. STAT1 was potentially targeted by three miRNAs, including has-miR- 6825-5P, has-miR-4495, and has-miR-5580-3P. Conclusion: The roles of DEMs such as hsa-mir-5580-3p in OSCC through interactions with DEGs CD44, ACLY, ACTR3, STAT1, LAMC2 and YWHAZ may offer a suitable candidate biomarker pattern for diagnosis, prognosis and treatment processes in OSCC.

Protein-Protein Interaction Network Analysis of Salivary Proteomic Data in Oral Cancer Cases

Background: Oral cancer is a frequently encountered neoplasm of the head and neck region, being the eight most common type of human malignancy worldwide. Despite improvement in its control, morbidity and mortality rates have improved little in the past decades. Therefore, prevention and/or early detection are a high priority. Proteomics with network analysis have emerged as a powerful tool to identify important proteins associated with cancer development and progression that can be potential targets for early diagnosis. In the present study, network- based protein- protein interactions (PPI) for oral cancer were identified and then analyzed for use as key proteins/potential biomarkers. Material and Methods: Gene expression data in articles which focused on saliva proteomics of oral cancer were collected and 74 candidate genes or proteins were extracted. Related protein networks of differentially expressed proteins were explored and visualized using cytoscape software. Further PPI analysis was performed by Molecular Complex Detection (MCODE) and BiNGO methods. Results: Network analysis of genes/proteins related to oral cancer identified kininogen-1, angiotensinogen, annexin A1, IL-8, IgG heavy variable and constant chains, CRP, collagen alpha-1 and fibronectin as 9 hub-bottleneck proteins. In addition, based on clustering with the MCODE tool, vitronectin, collagen alpha-2, IL-8 and integrin alpha-v were established as 5 distinct seed proteins. Conclusion: A hub-bottleneck protein panel may offer a potential /candidate biomarker pattern for diagnosis and treatment of oral cancer disease. Further investigation and validation of these proteins are warranted.

Proteome evaluation of human cystic echinococcosis sera using two dimensional gel electrophoresis.

AIM: Detection of protein expression changes in human cystic echinococcosis sera by 2D gel electrophoresis. BACKGROUND: Diagnosis and successful treatment of cystic echinococcosis (CE) is a major challenge, up to now. Identification of related expressed proteins using proteomics tools and bioinformatics analysis of patients' sera have not been investigated, so far. METHODS: Sera from eight confirmed CE patients and three healthy controls were collected, tested by 2-DE for total protein separation of serum and analyzed using proteomics and bioinformatics methods. The gels were stained by Coomassie blue followed by scan imaging of the gels. The protein spots in each gel were analyzed using progenesis same spots software. Proteins names were obtained from TagIdent server. RESULTS: A total of 263 protein spots with different expression were detected in both normal and diseased samples. Comparison between diseased and normal gels showed the expression of 45 up-regulated protein spots with fold≥2 in diseased gel of which 10 were new proteins with statistical difference by normal gel (p-value<0.05). On the other hand, the expression of 50 down-regulated protein spots were observed of which 11 proteins have been suppressed. Clustering of all detected sera proteins (263) using correlation analysis, divided the proteins into 2 clusters based on up-regulated and down-regulated expression of proteins. Clustering results were approved by principal component analysis (PCA). CONCLUSION: Significant protein expression changes in human CE sera which is demonstrable by application of proteomics and bioinformatics analysis makes it an impressing tool for diagnosis of CE patients.

Prevalence of pterygium in Iran: a systematic review and meta-analysis study.

BACKGROUND AND AIM: Pterygium is one of the most prevalent pathologies involving the cornea, which can lead to various vision signs and even reduction in eyesight. No accurate estimate has been reported about the prevalence of pterygium in Iran. Hence, this study aimed to determine the pterygium prevalence in Iran by meta-analysis method. METHODS: Searching for data of the last eleven years (from 2004 to 2015) was conducted using the keywords of pterygium, eye, and Iran in International and domestic indexing services and databases including Iranmedex, Scientific Information Database (SID), Magiran, Irandoc, Medlib, IranPsych, Science Direct, Web of Science (Thomson Reuters), PubMed, and Scopus. The data were analyzed using the meta-analysis method (the random effects model). The disharmony of the studies was investigated using the I2 index. The data were analyzed by STATA Ver.11 software. RESULTS: In 5 studies conducted in Iran, with a sample size of 10,838 people between 2004 and 2015, the extent of the prevalence was estimated to be 11% (95% CI: 3 to 18%). Also, the prevalence of pterygium in women and men was 18% and 13%, respectively. CONCLUSION: According to the published reports from Iran and its comparison with other points in the world, the prevalence of pterygium in Iran is high, especially among women.

Impact of HIV infection in patients infected with chronic HCV (genotypes 1a and 3a): virological and clinical changes.

BACKGROUND: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection has become a serious public health problem. The influence of HIV/HCV coinfection on plasma HCV RNA loads and clinical criteria which are usually regarded as a predictor of the progress of liver disease have not been reliably evaluated. OBJECTIVES: This study investigated the impact of HIV infection on HCV RNA load and clinical indexes in Yazd and Tehran. MATERIALS AND METHODS: HCV/HIV-coinfected patients and HCV-monoinfected controls were examined and compared for plasma HCV RNA and related risk factors such as HCV genotypes, liver enzymes, and transmission routes. RESULTS: A total of 54 HCV/HIV-coinfected patients and 88 HCV-monoinfected controls were studied. The HCV RNA load mean was significantly higher in HCV/HIV-coinfected patients than in HCV-monoinfected patients (p < 0.001). HCV RNA load mean in patients infected with HCV without anti-HCV therapy was lower than HIV/HCV patients with and without highly active antiretroviral therapy that this difference was significant (p < 0.001). The HCV RNA levels were significantly higher in HIV/HCV genotype 3a coinfected patients than in genotype 3a monoinfected patients (p < 0.001). HIV RNA levels were lower in genotype 1a infected patients than in genotype 3a infected patients, but this difference was not significant statistically. The ALT mean levels were significantly higher in genotype 3a HIV/HCV-coinfected patients than in genotype 3a HCV-monoinfected patients (p < 0.001). CONCLUSIONS: HIV/HCV coinfection leads to a significant increase in plasma HCV RNA. Further evaluations of the effects of ART and HIV infection on the course of HCV infection and the response to treatment against HCV infection in other and different genotypes are also needed. Moreover, HIV-infected patients should be screened regularly for HCV coinfection, particularly if they are in high-risk groups such as IDUs and recipients of blood transfusions.

Evaluating Effect of Albendazole on Trichuris trichiura Infection: A Systematic Review Article.

BACKGROUND: The aim of the study was assessment of defaults and conducted meta-analysis of the efficacy of single-dose oral albendazole against T. trichiura infection. METHODS: We searched PubMed, ISI Web of Science, Science Direct, the Cochrane Central Register of Controlled Trials, and WHO library databases between 1983 and 2014. Data from 13 clinical trial articles were used. Each article was included the effect of single oral dose (400 mg) albendazole and placebo in treating two groups of patients with T. trichiura infection. For both groups in each article, sample size, the number of those with T. trichiura infection, and the number of those recovered following the intake of albendazole were identified and recorded. The relative risk and variance were computed. Funnel plot, Beggs and Eggers tests were used for assessment of publication bias. The random effect variance shift outlier model and likelihood ratio test were applied for detecting outliers. In order to detect influence, DFFITS values, Cook's distances and COVRATIO were used. Data were analyzed using STATA and R software. RESULTS: The article number 13 and 9 were outlier and influence, respectively. Outlier is diagnosed by variance shift of target study in inferential method and by RR value in graphical method. Funnel plot and Beggs test did not show the publication bias (P=0.272). However, the Eggers test confirmed it (P=0.034). Meta-analysis after removal of article 13 showed that relative risk was 1.99 (CI 95% 1.71 - 2.31). CONCLUSION: The estimated RR and our meta-analyses show that treatment of T. trichiura with single oral doses of albendazole is unsatisfactory. New anthelminthics are urgently needed.

Distribution of IL-28B genotypes in patients with hepatitis C and healthy individuals in Jahrom city.

AIM: The purpose of this study was to compare the distribution of interleukin (IL)-28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C based on the genotype. BACKGROUND: Polymorphisms in the region of IL-28B gene have been identified as the strongest genetic pretreatment predictor of sustained virological response (SVR) in hepatitis C infection. PATIENTS AND METHODS: In this study, 147 patients with chronic hepatitis C and 80 healthy individuals were included. The IL-28B rs12979860 and rs8099917 polymorphisms were genotyped by PCR-RFLP method and the frequency of IL-28B polymorphisms with respect to HCV genotypes was also determined. RESULTS: The frequencies of rs12979860 TT, CC and CT genotypes in the chronic hepatitis C patients and healthy individuals were as follows: 10.8% vs. 11.3%, 38.7% vs. 46.2% and 50.3% vs. 42.5%. Also, the frequencies of rs8099917 TT, GG and GT genotypes in the chronic hepatitis C patients was 61.9%, 6.1% and 32% and in controls was 47.5%, 11.2% and 41.3%. The differences in the distribution of rs12979860 genotypes and alleles between HCV genotype 1 and HCV genotype 3a infected patients were statistically significant. CONCLUSION: The rs12979860 C allele is the favorable allele for the spontaneous clearance of HCV. It seems that the impact of IL-28B polymorphism on the spontaneous clearance of HCV genotype 3 is more prominent than HCV genotype 1, which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.

Analytical assessment of interleukin - 23 and -27 cytokines in healthy people and patients with hepatitis C virus infection (genotypes 1 and 3a).

BACKGROUND: The immune system plays important roles in determining the outcomes of hepatitis C virus (HCV) infection. Interleukin-23 and -27 (IL-23 and IL-27) are two novel IL-12 cytokine family members known to enhance the T-lymphocyte response, but their precise involvement in HCV infection is not well known. OBJECTIVES: We investigated the serum IL-27 and IL-23 levels in patients with HCV infection and in healthy individuals. PATIENTS AND METHODS: In this case-control study, we assessed IL-23 and IL-27 levels in serum of 37 healthy individuals and 64 patients with chronic HCV using Enzyme-linked immunosorbent assay (ELISA). The relationship of cytokines level with liver enzymes (ALT, AST, and ALP), HCV genotype and viral load were analyzed. The differences of these cytokine levels in the groups of treatment and no treatment was compared. HCV genotypes were classified by HCV-specific primers methods. HCV RNA loads were determined by fluorescence quantitative PCR. RESULTS: Serum level of IL-23 was higher in HCV infected patients compared to control group (P = 0.005). However, no significant difference was seen in IL-27 serum level between patients compared to the control group (P = 0.65). There was no significant difference in IL-23 and IL-27 level between genotype 1 HCV-infected- and 3a HCV-infected- patients. Positive moderate correlation between IL-23 and IL-27 with viral load was found in type 3a and 1 HCV-infected patient. Positive relative correlation was seen between ALT and IL-23 in 1a HCV-infected patients, which was higher than 3a HCV-infected patients; but there were no significant difference between serums liver enzymes with IL-23 and IL-27 in respect to genotype 3a and 1a HCV-infected patients. CONCLUSIONS: These findings may reflect a vigorous pro-inflammatory reaction orchestrated by the host immune system against chronic HCV. Also, a better understanding of the involvement mechanism considering the correlation between other genotypes with inflammatory cytokines in various stages of disease can be obtained.

WITHDRAWN: An overview of the present status of hospital waste management in Kerman, Iran.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Molecular epidemiology of different hepatitis C genotypes in serum and peripheral blood mononuclear cells in jahrom city of iran.

BACKGROUND: The Hepatitis C Virus (HCV) is considered essentially hepatotropic, yet the virus compartments have also been found in important extra hepatic sites. Detection of HCV RNA in extra hepatic reservoirs such as peripheral blood mononuclear cells (PBMCs) is important for determining disease progression and treatment effectiveness. OBJECTIVES: The present study aimed to determine different HCV genotypes in patients' plasma and PBMC specimens, in Jahrom city of Iran. PATIENTS AND METHODS: Blood samples of 137 patients with established HCV were collected at the Honari clinic. These patients were anti-HCV and plasma HCV RNA positive. After plasma RNA extraction and obtaining a pellet of approximately 3-5 × 10(6) PBMCs, Real-time PCR was performed, using specific-genotype primers. Finally, data analysis was done by the Statistical Package for Social Sciences (SPSS) software. RESULTS: Subtype 3 was the most common genotype in plasma (57.7%) and PBMCs (51.1%). Subtype 1a was detected in 36.5% and 30.7% of plasma samples and PBMCs, respectively whereas subtype 4 was not detected in any of the cases. There was a genotype difference between plasma and PBMCs of 12.4% of patients. In four patients no genotype was detected in their plasma but genotype 3 was detected in the PBMCs. CONCLUSIONS: It is suggested that determination of the target genotype by plasma subtyping for choosing the proper antiviral therapy is essential but may result in therapy failure. HCV genotyping in PBMC samples, along with plasma specimens, might be more beneficial. Therefore determining the HCV genotype in PBMCs, before beginning the therapy is useful due to the possibility of occult infection detection.

A field evaluation of formalin-gasoline technique in the concentration of stool for detection of intestinal parasites.

A field evaluation of the formalin-gasoline procedure to detect parasite ova, cysts, or larvae from 470 fecal specimens (comprising both fresh and formalin-preserved stool samples) was compared with that of the formalin-ether sedimentation technique. Parallel concentrates with diethyl ether and gasoline were prepared for each specimen, and the species and appearance of recovered parasite species were determined. Of 470 total specimens, 206 (43.83%) were found to be positive for parasites in one or both concentration techniques. Gasoline was comparable to diethyl ether in the recovery of parasite eggs, cysts, and larvae, so that the formalin-gasoline and the formalin-diethyl ether sedimentation techniques detected 165 and 156 positive of total specimens, respectively. In this study, gasoline proved to be as good as diethyl ether in concentrating parasite eggs and cysts, as well as in maintaining characteristic morphology. However, gasoline was considerably superior to diethyl ether in detecting larvae of Strongyloides stercoralis. Parallel examination of total stool samples by the routine formalin-ether (original) and by the formalin-gasoline techniques resulted in identical distribution of positive slides and morphology of recovered parasite species. However, the easy availability of gasoline (wherever gas stations are present) and its low cost in comparison to ether makes gasoline superior to ether for use in concentration of stools by the sedimentation method in laboratories, including laboratories with limited material resources and also laboratories present in small cities and rural health centers.