Anti-inflammatory effects of extracellular vesicles and cell-free supernatant derived from Lactobacillus crispatus strain RIGLD-1 on Helicobacter pylori-induced inflammatory response in gastric epithelial cells in vitro.

Helicobacter pylori infection is the major risk factor associated with the development of gastric cancer. Currently, administration of standard antibiotic therapy combined with probiotics and postbiotics has gained significant attention in the management of H. pylori infection. In this work, the immunomodulatory effects of Lactobacillus crispatus-derived extracellular vesicles (EVs) and cell-free supernatant (CFS) were investigated on H. pylori-induced inflammatory response in human gastric adenocarcinoma (AGS) cells. L. crispatus-derived EVs were isolated by ultracentrifugation and physically characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Furthermore, the protein content of L. crispatus-derived EVs was also evaluated by SDS-PAGE. Cell viability of AGS cells exposed to varying concentrations of EVs and CFS was assessed by MTT assay. The mRNA expression of IL-1ß, IL-6, IL-8, TNF-α, IL-10, and TGF-ß genes was determined by RT-qPCR. ELISA was used for the measurement of IL-8 production in AGS cells. In addition, EVs (50 µg/mL) and CFS modulated the H. pylori-induced inflammation by downregulating the mRNA expression of IL-1ß, IL-6, IL-8, and TNF-α, and upregulating the expression of IL-10, and TGF-ß genes in AGS cells. Furthermore, H. pylori-induced IL-8 production was dramatically decreased after treatment with L. crispatus-derived EVs and CFS. In conclusion, our observation suggests for the first time that EVs released by L. crispatus strain RIGLD-1 and its CFS could be recommended as potential therapeutic agents against H. pylori-triggered inflammation.

Characterization of vaginal Lactobacillus species as a predictor of fertility among Iranian women with unexplained recurrent miscarriage and fertile women without miscarriage history using machine learning modeling.

BACKGROUND: Lactobacillus spp. are the predominant bacteria of the vaginal tract, the alteration of which has been previously linked to miscarriage. Here, we investigated differences between selected vaginal Lactobacillus species of women with a history of recurrent miscarriages and fertile women without a history of miscarriage in Iran. METHODS AND RESULTS: Vaginal swabs were taken from 29 fertile and 24 infertile women and quantitative real-time PCR (qPCR) assay was used to determine a selection of vaginal Lactobacillus species in both groups. The logistic regression (LR) model, Naive Bayes (NB) model, support vector machine model (SVM), and neural network model (NN) were developed to predict disease outcome by selected variables. LR analysis was used to construct a nomogram indicating predictions of the risk of miscarriage. The most abundant species among the patients were L. rhamnosus, L. ruminis, and L. acidophilus, while L. gasseri, L. vaginalis, L. fermentum, and L. iners were more abundant in healthy subjects. The distribution of L. ruminis, L. iners, and L. rhamnosus was higher in patients, while L. acidophilus, L. gasseri, and L. fermentum were highly distributed among healthy subjects. Higher AUC in predicting the disease outcome was observed for L. gasseri, L. rhamnosus, L. fermentum, and L. plantarum. CONCLUSION: Our findings provide experimental evidence of vaginal Lactobacillus imbalance in infertile women and a suitable predictor for miscarriage based on the AUC algorithms. Further studies with larger sample size and using high-throughput technologies are needed to boost our understanding of the role of lactobacilli in miscarriage.

Immunomodulatory effects of live and pasteurized Lactobacillus crispatus strain RIGLD-1 on Helicobacter pylori-triggered inflammation in gastric epithelial cells in vitro.

BACKGROUND: Helicobacter pylori infection is considered as the major risk factor for gastric adenocarcinoma. Today, the increasing emergence of antibiotic-resistant strains has drastically decreased the eradication rate of H. pylori infection. This study was aimed to investigate the inhibitory and modulatory effects of live and pasteurized Lactobacillus crispatus strain RIGLD-1 on H. pylori adhesion, invasion, and inflammatory response in AGS cell line. METHODS AND RESULTS: The probiotic potential and properties of L. crispatus were evaluated using several functional and safety tests. Cell viability of AGS cells exposed to varying concentrations of live and pasteurized L. crispatus was assessed by MTT assay. The adhesion and invasion abilities of H. pylori exposed to either live or pasteurized L. crispatus were examined by gentamycin protection assay. The mRNA expression of IL-1ß, IL-6, IL-8, TNF-α, IL-10, and TGF-ß genes was determined by RT-qPCR from coinfected AGS cells. ELISA was used for the detection of IL-8 secretion from treated cells. Both live and pasteurized L. crispatus significantly decreased H. pylori adhesion/invasion to AGS cells. In addition, both live and pasteurized L. crispatus modulated H. pylori-induced inflammation by downregulating the mRNA expression of IL-1ß, IL-6, IL-8, and TNF-α and upregulating the expression of IL-10, and TGF-ß cytokines in AGS cells. Furthermore, H. pylori-induced IL-8 production was dramatically decreased after treatment with live and pasteurized L. crispatus. CONCLUSIONS: In conclusion, our findings demonstrated that live and pasteurized L. crispatus strain RIGLD-1 are safe, and could be suggested as a potential probiotic candidate against H. pylori colonization and inflammation.

Upregulation of VDR-associated lncRNAs in Schizophrenia.

Vitamin D receptor (VDR) signaling has been found to contribute to the pathology of numerous neuropsychiatric diseases including schizophrenia. Notably, VDR signaling has a functional relationship with many long non-coding RNAs (lncRNAs) such as SNHG6, LINC00346 and LINC00511. We calculated expression of these lncRNAs in the venous blood of patients with schizophrenia versus healthy individuals. Expression of SNHG6 was significantly higher in cases versus controls (posterior beta = 0.552, adjusted P value < 0.0001). This pattern of expression was detected in both men (posterior beta = 0.556, adjusted P value < 0.0001) and women (posterior beta = 0.31, adjusted P value = 0.005). Expression of LINC00346 was also higher in cases versus controls (posterior beta = 0.497, adjusted P value < 0.0001) and in distinct sex-based comparisons (posterior beta = 0.451, adjusted P value = 0.009 among men and posterior beta = 0.214, P value = 0.004 among women). Expression of LINC00511 was higher in cases versus controls (posterior beta = 0.318, adjusted P value = 0.01). While sex-based comparisons revealed significant difference in expression of LINC00511 among female subgroups (posterior beta = 0.424, adjusted P value = 0.016), such comparison showed no difference among male cases and male controls (adjusted P value = 0.295). The expression levels of SNHG6 distinguished patients with schizophrenia from controls, with AUC = 0.932. LINC00346 and LINC00511 distinguished between the two groups with AUC values of 0.795 and 0.706, respectively. Therefore, these lncRNAs might be used as markers for schizophrenia.

The role of long noncoding RNAs in patients with Luminal A invasive breast ductal carcinoma.

Breast cancer is the most common form of cancer in women around the world. The molecular mechanisms of this heterogeneous disease have been extensively investigated; but yet; It requires a lot of sensitive and specific markers for prognosis and early detection approaches. Non-protein coding RNAs known as lncRNAs have been reported in tumorigenic involvement so they can be used for therapeutic purposes. In the present study, the expression levels of CCAT1, PDCD4, PDCD4-AS1, and MEG3 LncRNA in adjacent tumor and breast tissue in 88 Iranian patients were evaluated by quantitative real-time PCR. CCAT1 was significantly expressed and PDCD4-AS1 decreased in tumor samples, PDCD4 and PDCD4-AS1 showed a positive correlation with each other, higher levels of PDCD4-AS1 were associated with better survival, tumor samples showed lower levels of PDCD4 in Showed comparisons with normal tissue. Our findings suggest that lncRNAs play an important role in controlling gene expression after transcription of major tumor suppressors or carcinogenic genes, leading to the development of triple-negative breast cancer (TNBC). In conclusion, this study investigated the prognostic role of lncRNA in breast cancer patients.

Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues.

Breast cancer is the most common neoplasm among females. Estrogen receptor (ESR) signaling has a prominent impact in the pathogenesis of breast cancer. Among the transcription factors associated with ESR signaling, FOXM1, GATA3, FOXA1 and ESR1 have been suggested as a candidate in the pathogenesis of this neoplasm. In the current project, we have designed an in silico approach to find long non-coding RNAs (lncRNAs) that regulate these transcription factors. Then, we used clinical samples to carry out validation of our in silico findings. Our systems biology method led to the identification of APTR, AC144450.1, linc00663, ZNF337.AS1, and RAMP2.AS1 lncRNAs. Subsequently, we assessed the expression of these genes in breast cancer tissues compared with the adjacent non-cancerous tissues (ANCTs). Expression of GATA3 was significantly higher in breast cancer tissues compared with ANCTs (Ratio of mean expressions (RME) = 4.99, P value = 3.12E-04). Moreover, expression levels of APTR, AC144450.1, and ZNF337.AS1 were elevated in breast cancer tissues compared with control tissues (RME = 2.27, P value = 5.40E-03; Ratio of mean expressions = 615.95, P value = 7.39E-19 and RME = 1.78, P value = 3.40E-02, respectively). On the other hand, the expression of RAMP2.AS1 was lower in breast cancer tissues than controls (RME = 0.31, P value = 1.87E-03). Expression levels of FOXA1, ESR1, and FOXM1 and linc00663 were not significantly different between the two sets of samples. Expression of GATA3 was significantly associated with stage (P value = 4.77E-02). Moreover, expressions of FOXA1 and RAMP2.AS1 were associated with the mitotic rate (P values = 2.18E-02 and 1.77E-02, respectively). Finally, expressions of FOXM1 and ZNF337.AS1 were associated with breastfeeding duration (P values = 3.88E-02 and 4.33E-02, respectively). Based on the area under receiver operating characteristics curves, AC144450.1 had the optimal diagnostic power in differentiating between cancerous and non-cancerous tissues (AUC = 0.95, Sensitivity = 0.90, Specificity = 0.96). The combination of expression levels of all genes slightly increased the diagnostic power (AUC = 0.96). While there were several significant pairwise correlations between expression levels of genes in non-tumoral tissues, the most robust correlation was identified between linc00663 and RAMP2.AS1 (r = 0.61, P value = 3.08E-8). In the breast cancer tissues, the strongest correlations were reported between FOXM1/ZNF337.AS1 and FOXM1/RAMP2.AS1 pairs (r = 0.51, P value = 4.79E-5 and r = 0.51, P value = 6.39E-5, respectively). The current investigation suggests future assessment of the functional role of APTR, AC144450.1 and ZNF337.AS1 in the development of breast neoplasms.

Infertility cell therapy and epigenetic insights.

Recent advances in assisted reproductive technology (ART) have allowed couples with severe infertility to conceive, but the methods are not effective for all cases. Stem cells as undifferentiated cells which are found in different stages of embryonic, fetal and adult life are known to be capable of forming different cell types, tissues, and organs. Due to their unlimited resources and the incredible power of differentiation are considered as potential new therapeutic biological tools for treatment of infertility. For reproductive medicine, stem cells are stimulated in vitro to develop various specialized functional cells including male and female gametes. The epigenetic patterns can be modified in the genome under certain drugs exposure or lifestyle alterations. Therefore, epigenetics-related disorders may be treated if the nature of the modifications is completely admissible. It is proved that our understanding of epigenetic processes and its association with infertility would help us not only to understand the etiological factors but also to treat some type of male infertilities. Exploration of both genetic and epigenetic variations in the disease development could help in the identification of the interaction patterns between these two phenomena and possible improvement of therapeutic methods.

Altered expression of lncRNAs in autism spectrum disorder.

Long non-coding RNAs (lncRNAs) have been recognized as an important epigenetic factor in the evolution of neuropsychiatric conditions. We have selected five lncRNAs (DISC2, PRKAR2A-AS1, LOC105375675, LRRC2-AS1, and LOC101928237) to measure their expression in blood samples of children with autism spectrum disorder (ASD) versus children with normal development. Expressions of DISC2, PRKAR2A-AS1 and LOC101928237 have been enhanced in ASD cases compared with healthy children (Posterior Beta = 2.508, P value<0.0001; Posterior Beta = 2.793, P value = 0.014 and Posterior Beta = 1.646, P value <0.0001, respectively). On the other hand, expression of LRRC2-AS1 has been lower in ASD patients compared with controls (Posterior Beta = -3.781, P value<0.0001). Remarkably, expression of DISC2 and PRKAR2A-AS1 have been lower in girls compared with boys (Posterior Beta = -0.982, P value<0.0001 and Posterior Beta = -0.135, P value<0.0001, respectively). In addition, expression of DISC2 has been lower in ASD cases aged more than 6 compared with those aged less than 6 years (Posterior Beta = -0.876, P value = 0.003). DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 had the area under curve (AUC) values of 0.76, 0.90, 0.92, and 0.79 in distinguishing between ASD and healthy children. Expression levels of none of DISC2, LOC101928237, LOC105375675, LRRC2-AS1, and PRKAR2A-AS1 were correlated with age of ASD cases or healthy controls. A significant correlation was detected between expressions of DISC2 and PRKAR2A-AS1. There were inverse correlations between the following pairs of lncRNAs: DISC2/LRRC2-AS1, DISC2/LOC101928237, LRRC2-AS1/PRKAR2A-AS1, LOC101928237/LRRC2-AS1, and LOC101928237 /LOC105375675. We conclude that DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 might be used as potential markers for this condition.

Expression of BDNF-Associated lncRNAs in Treatment-Resistant Schizophrenia Patients.

Long non-coding RNAs (lncRNAs) play a decisive role in the development of the central nervous system and modulation, differentiation, and function of neurons. Thus, any abnormal pattern of expression of these transcripts might alter normal development leading to neuropsychiatric disorders. In this regard, transcripts of brain-derived neurotrophic factor (BDNF) and four BDNF-associated lncRNAs (BDNF-AS, MIR137HG, MIAT, and PNKY) were evaluated in the peripheral blood of schizophrenia (SCZ) patients as well as normal subjects. The results indicated that the relative expression (RE) of PNKY was higher in SCZ patients as compared with controls (posterior beta of RE = 2.605, P value = 0.006) and in female patients compared with female controls (posterior beta of RE = 2.831, P value < 0.0001). BDNF expression was also higher in SCZ patients when compared with controls (posterior beta of RE = 0.64, P value < 0.036). Finally, a correlation was detected between the disease status and gender in terms of BDNF-AS expression (P value = 0.026). An inverse correlation was also found between levels of PNKY and age in the control group (r = - 0.30, P value < 0.0001). Expressions of BDNF and all lncRNAs were correlated with each other in both patients and controls. PNKY had the best diagnostic power among all assessed genes in the identification of disease status (area under curve = 0.78). BDNF, BDNF-AS, MIR137HG, and MIAT genes could discriminate SCZ patients from normal subjects with diagnostic power of 71%, 72%, 67%, and 68%, respectively. The current investigation suggests the possibility of the application of transcript levels of lncRNAs as an SCZ diagnostic marker. However, it warrants further studies in larger sample sizes.

Association of the MTHFR 677C>T and 1298A>C polymorphisms and male infertility risk: a meta-analysis.

BACKGROUND AND OBJECTIVES: One of the possible male sterility risk factors are polymorphisms of Methylenetetrahydrofolate reductase (MTHFR). However, the epidemiologic investigations described inconsistent results regarding MTHFR polymorphism and the risk of male infertility. For that reason, we carried out a meta-analysis of published case-control studies to re-examine the controversy. METHODS: Electronic searches of Cochrane, EMBASE, Google Scholar, and PubMed were conducted to select eligible studies for this meta-analysis (updated to May 2019). According to our exclusion and inclusion criteria, only high-quality studies that remarked the association between MTHFR polymorphisms and male infertility risk were included. The Crude odds ratio (OR) with a confidence interval of 95% (CI) was used to assess the relationship between MTHFR polymorphism and male infertility risk. RESULTS: Thirty-four case-control studies with 9662 cases and 9154 controls concerning 677C/T polymorphism and 22 case-control studies with 5893 cases and 6303 controls concerning 1298A/C polymorphism were recruited. Both MTHFR polymorphisms had significant associations with male infertility risk (CT + TT vs. CC: OR = 1.37, 95% CI: 1.21-1.55, P = 0.00, I2 = 41.9%); (CC vs. CA + AA: OR = 0.82, 95% CI: 0.52-1.30, P = 0.04, I2 = 50.1%). Further, when stratified by ethnicity, the significant association results were observed in Asians and Caucasians for 677C/T and just Asians for 1298A/C. CONCLUSIONS: Some of MTHFR polymorphisms like MTHFR 677C > T are associated with an elevated male infertility risk. To confirm our conclusion and to provide more accurate and complete gene-environment communication with male infertility risk, more analytical studies are needed.

Investigating the relationship between ccfDNA concentration, its integrity, and some individual factors in an Iranian population.

INTRODUCTION: Circulating cell-free DNA (ccfDNA) increases in some pathologic conditions like cancer. We aimed to investigate the correlation between some individual factors and the ccfDNA level in peripheral blood of Iranian in relation to prostate cancer. MATERIAL AND METHOD: 30 patients with prostate cancer (PCa), 40 with benign prostate hyperplasia (BPH), and 30 controls were studied. Personal information, ccfDNA concentration, and the integrity index were assessed for the correlation between the disease and different factors. The results were statistically analyzed using SPSS software. RESULTS: In PCa group, no association was found between total ccfDNA, BMI, BPH background, non-cancerous diseases, medications, PCa length, and job (p-value > 0.05). But, total ccfDNA had statistical associations with weight, family history of cancer, and location (p-value < 0.05). No association was between the integrity of ccfDNA, weight, the background of BPH, and family history of cancer. But, the integrity of ccfDNA was significantly associated with BMI and PCa length (p-value < 0.05).In BPH group, no association between total ccfDNA or the integrity of ccfDNA and the assessed factors was obtained (p-value > 0.05). In the normal group, neither statistical association was found between total ccfDNA, weight, BMI, and job, nor between the integrity of ccfDNA, weight, BMI, non-cancerous disease, drug, job, and location (p-value > 0.05). But, a statistical association was found between the integrity of ccfDNA and family history of cancer in the recent group (Based on 95% CI and P-value less than 0.05). CONCLUSION: ccfDNA and its integrity as possible prostate cancer biomarkers under the influence of individuals' physiological status are prone to the pathologic changes toward the disease. Further simultaneous study of the target groups could clarify this matter.

Investigation of GSTP1 and epigenetic regulators expression pattern in a population of Iranian patients with prostate cancer.

BACKGROUND AND AIM: Prostate cancer is the leading cause of death in many countries. It is important to diagnose the disease in the early stages. Current methods detect the disease with low specificity. Examining the expression of genes responsible for disease and their epigenetic regulators are good tools in this regard. MATERIAL AND METHODS: In this prospective case-control study, 40 Iranian patients with cancer, 40 Iranian patients with prostate hyperplasia, and 40 control samples were examined. After blood sampling from each individual, RNA extraction and cDNA synthesis, GSTP1, HDAC, DNMT3A, and DNMT3B expressions were measured in three understudy groups using specific primers and Real-Time PCR method. RESULTS: A reverse correlation was identified between loss of GSTP1 expression and overexpression of HDAC, DNMT3A, and DNMT3B (P value < 0.0001) with a beneficial pattern of cancer development with high efficiency. The significant decrease of GSTP1 expression in patients in comparison to the healthy controls and the elevated expression levels of the studied epigenetic regulators in PCA and BPH samples indicate the impact of the regulators on GSTP1 expression activity. CONCLUSION: This study showed that the measurement of combined GSTP1 and its epigenetic regulators' expression could be used as suitable genetic markers for the detection and separation of healthy individuals from prostatic patient groups in the Iranian population. However, a similar study in a larger population of case and control could help us to distinguish between normal, benign, and malignant conditions.

The roles of miRNAs' clinical efficiencies in the colorectal cancer pathobiology: A review article.

MiRNAs (microRNAs) are defined as micro directors and regulators of gene expression. Since altered miRNA expression is signified in the pathobiology of diverse cancers such as colorectal cancers (CRCs), these molecules are described as therapeutic targets, either. Manipulation of miRNAs could lead to further therapy for chemo and radio-resistant CRCs. The usage of microRNAs has indicated prominent promise in the prognosis and diagnosis of CRC, because of their unique expression pattern associated with cancer types and malignancies. Nowadays, many researchers are analyzing the correlation between miRNA polymorphisms and cancer risk. With continuous incompatibility in colorectal cancer (CRC) miRNAs expression data, it is critical to move toward the content of a "pre-laboratory" analysis to speed up efficient accuracy medicine and translational study. Pathway study for the highest expressed miRNAs- regulated target genes resulted in the identification of a considerable number of genes associated with CRC pathway including PI3K, TGFß, and APC. In this review, we aimed to collect fruitful information about miRNAs and their potential roles in CRC, and provide a meta-analysis of the most frequently studied miRNAs in association with the disease.

Prognostic impact of ABO blood group on type I endometrial cancer in a population of Iranian patients.

BACKGROUND: Inherited ABO blood group has been shown to play an important role in the pathogenesis of various gynecological cancers including endometrial carcinoma (EC). OBJECTIVE: Our study aimed to determine the prevalence of ABO blood groups in Iranian patients with EC and to investigate the relationship between the blood group and several clinicopathologic parameters in Imam Hossein Hospital. METHODS: One hundred and seventy-five EC patients were selected and analyzed for their clinicopathologic details including ABO blood group, age, menopausal status, body mass index (BMI), tumor grade, and stage of the International Federation of Obstetrics and Gynecology (FIGO). RESULTS: Endometrioid carcinoma was the most common histological type in this case study. Early stages (I and II) were present in 135 individuals (77.1%) and advanced stages (III and IV) appeared in 40 (22.9%) patients. Blood group A was prominent in patients with EC. There was a significant relationship between blood group A and cancer grade (P= 0.024). 23.1% of group A had grade III EC, while this grade appeared in 35.2% of the non-A blood group. There was no significant association between ABO blood groups and other EC clinic-pathological results (P> 0.05). CONCLUSION: Although there was no significant relationship between the ABO blood group and the patients' clinicopathological characteristics, more studies could provide extensive information about any possible relation between the blood group, especially blood group A, EC, and the grade of the tumor.

The Effect of Hormone Therapy on the Expression of Prostate Cancer and Multi-Epigenetic Marker Genes in a Population of Iranian Patients.

BACKGROUND AND AIM: Many recent studies have shown a direct relationship between the decrease in the expression of GSTP1 and RASSF1 with the incidence and progression of prostate cancer. Moreover, the expression level of these genes is greatly affected by epigenetic factors and their methylation pattern. Given the prevalence of prostate cancer and the importance of choosing the best method to inhibit the progression of the disease and provide specific treatment, it is important to evaluate the effect of hormone therapy on the expression of effective prostate cancer genes and epigenetic markers. PATIENTS AND METHODS: In this case-control study, 35 prostate cancer samples were examined before and after hormone therapy. Following the blood sampling, RNA extraction, and cDNA synthesis, the expression of GSTP1, RASSF1, HDAC, DNMT3A, and DNMT3B was assessed by real-time PCR. RESULTS: The results analysis showed that the expression of GSTP1, RASSF1, and DNMT3B was significantly increased, DNMT3A was significantly decreased (P value<0.05) and HDAC expression did not change significantly (P value=0.19) after hormone therapy. DISCUSSION: Significant changes in the expression of GSTP1, RASSF1, DNMT3B and DNMT3A in the studied samples indicate that these genes are susceptible targets for cancer hormone therapy in Iranian men like in the other populations. Evaluation of gene activity in a larger population of patients may support these findings.

The Importance of Small Non-Coding RNAs in Human Reproduction: A Review Article.

BACKGROUND: MicroRNAs (miRNA) play a key role in the regulation of gene expression through the translational suppression and control of post-transcriptional modifications. AIM: Previous studies demonstrated that miRNAs conduct the pathways involved in human reproduction including maintenance of primordial germ cells (PGCs), spermatogenesis, oocyte maturation, folliculogenesis and corpus luteum function. The association of miRNA expression with infertility, polycystic ovary syndrome (PCOS), premature ovarian failure (POF), and repeated implantation failure (RIF) was previously revealed. Furthermore, there are evidences of the importance of miRNAs in embryonic development and implantation. Piwi-interacting RNAs (piRNAs) and miRNAs play an important role in the post-transcriptional regulatory processes of germ cells. Indeed, the investigation of small RNAs including miRNAs and piRNAs increase our understanding of the mechanisms involved in fertility. In this review, the current knowledge of microRNAs in embryogenesis and fertility is discussed. CONCLUSION: Further research is necessary to provide new insights into the application of small RNAs in the diagnosis and therapeutic approaches to infertility.

Association between tumor necrosis factor-alpha gene rs1800629 (-308G/A) and rs361525 (-238G > A) polymorphisms and prostate cancer risk in an Iranian cohort.

BACKGROUND: Prostate cancer (PCa) as the first men's common cancer in the world and the third cancer in Iranian men is a heterogeneous disorder which sometimes several biopsies are needed for its diagnosis. OBJECTIVES: The aim of current study is finding new biomarkers in order to diagnose of PCa at the earliest possible stage. Hence, the relationship between rs1800629 and rs361525 polymorphisms of TNF-α gene with PCa was investigated. MATERIALS AND METHODS: Blood DNA samples were collected from 100 patients with PCa, 110 with BPH, and 110 controls. Collected samples were examined using PCR-RFLP and Tetra-ARMS-PCR techniques to detect the desired polymorphisms. RESULTS: The frequency of rs1800629 genotypes in smokers was significantly different from non-smokers with PCa (p= 0.001). Logistic regression analysis results showed that GA heterozygotes in comparison to GG homozygotes had higher risk of developing Benign Prostatic Hyperplasia (BPH) or prostate cancer. However, no significant correlation was considered between the risk of PCa and the TNF-α gene polymorphisms (rs1800629 and rs361525). CONCLUSIONS: Although, the achieved results of this investigation demonstrated that the two examined genetic variants do not seem to be suitable markers for early diagnosis of prostate cancer in this pilot study; however increased risk for the disease is shown in GA heterozygotes and smokers which is indicative of some epigenetic factors influence on prostate cancer etiology.

Association between expression of long noncoding RNAs in placenta and pregnancy features.

Aim: The contribution of long noncoding RNAs (lncRNAs) has been highlighted in a variety of human disorders including cancer and placenta-associated conditions. Methods: We evaluated expression of CCAT2, UCA1, FAS-AS1 and OIP5-AS1 lncRNAs in placenta samples obtained from normal and intrauterine growth restriction pregnancies. Results: There was no significant difference in expression of these lncRNAs between cases and controls. A significant association was found between CCAT2 expression and gravidity/parity. CCAT2 expression was higher in cases with abortion history. Cases who received folic acid had lower expression of this lncRNA. Conclusion: The current study provides evidences for association between expression of CCAT2 and clinical determinants of placenta function. Future studies are needed to elaborate the underlying mechanism.

Expression of Long Non-Coding RNAs in Placentas of Intrauterine Growth Restriction (IUGR) Pregnancies.

BACKGROUND: Intrauterine growth restriction (IUGR), a pathologic diminution of the rate of fetal growth, has been associated with alterations in expression of several genes. However, the role of long non-coding RNAs (lncRNAs) in its pathogenesis has not been studied. METHODS: In this study we evaluated the expression of four lncRNAs namely, nuclear paraspeckle assembly transcript (NEAT1), taurine up-regulated 1 (TUG1), p21-associated ncRNA DNA damage-activated (PANDA), and metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) in placenta samples obtained from IUGR and normal pregnancies to determine their possible contributions in the pathogenesis of IUGR. RESULTS: We found no significant differences in expression levels between cases and controls. We also found no correlation between expression and clinical data of study participants; however, we found significant correlations between expression levels of all the assessed lncRNAs in both cases and controls. CONCLUSION: These results imply the existence of a possible shared regulatory mechanism for the expression of these transcripts in placenta. Future studies are needed to perform such evaluations in larger sample sizes or in animal models in earlier stages of pregnancy.