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Obsessive–compulsive disorder (OCD) is an important neuropsychiatric disorder worldwide. Common treatments of OCD include serotonergic antidepressants, which can cause potentially serious side effects. We assessed the effects of Lactobacillus casei (L. casei) Shirota consumption in an animal model of OCD. OCD-like symptoms were induced in rats by the chronic injection of the D2/D3 dopamine agonist quinpirole hydrochloride. Rats were classified into five groups of 6 rats. Four groups were injected chronically with quinpirole (0.5 mg/kg, twice weekly for 5 weeks). They were fed with L. casei Shirota (109 CF/g, daily for 4 weeks) (group 1), fluoxetine (10 mg/kg, daily for 4 weeks) (group 2), combination of L. casei Shirota and fluoxetine (group 3), and normal saline (positive control group). The last group did not receive dopamine agonist and was only injected with saline (negative control group). Expression levels of brain-derived neurotrophic factor (Bdnf), solute carrier family 6 member 4 (Slc6a4), and 5-hydroxytryptamine receptor type 2A (Htr2a) were assessed in orbitofrontal cortex tissues of all rats. Behavioral tests showed improvement of OCD signs in rats treated with L. casei Shirota, fluoxetine, and a combination of drugs. Quantitative PCR analysis showed a remarkable decrease in the expression of Bdnf and an increase in the expression of Htr2a in quinpirole-treated rats. After treatment with L. casei Shirota and fluoxetine, the expression level of Bdnf was increased remarkably, whereas Htr2a expression was decreased. The current study showed the effectiveness of L. casei Shirota in the treatment of OCD in a rat model. The beneficial effects of this probiotic are possibly exerted through the modulation of serotonin-related genes expression.

Background Bladder cancer (BC) is a frequent cancer with high morbidity and mortality. Method We assessed expression of NMP22, BAG3, BCL2 and BAX in BC samples, adjacent non-neoplastic tissues (ANNTs), urinary cell pellets (UCP) of the same patients and non-malignant conditions (NM). Results NMP22 was up-regulated in tumoral tissues compared with ANNTs and in UCP of BC patients compared with UCP of NM. BCL2 and BAX were down-regulated in BC tissues compared with ANNTs. BAG3 and BAX were down-regulated in UCP of BC compared with NM. The combination of all four genes had 100% sensitivity and specificity for detection of BC in urine. Conclusion Expression analysis of these genes in tumor or urine is a tool for detection of BC.

Aim: Cancer-testis antigens (CTAs) have specific expression in gametogenic tissues and aberrant expression in cancers. Materials & methods: We assessed expression of five testis-specific genes namely KIF2B, CST8, TMEM225, RBM46, OAZ3 in bladder cancer tissues, adjacent non-neoplastic tissues and urinary cell pellets (UCPs) of bladder cancer patients compared with nonmalignant conditions.Results: Expressions of all CTAs were higher in UCPs of bladder cancer patients compared with nonmalignant conditions. RBM46 expression in UCPs was higher in patients with recurrent tumors compared with primary tumors and in patients without hematuria compared with those having hematuria. TMEM225 expression in tumoral tissues was higher in high-grade tumors compared with low-grade tumors. Conclusion: Expression analysis of CTAs in UCP might provide diagnostic information about bladder cancer.

Fatemeh Yazarlou,1 Mohammad Hossein Modarressi,1 Seyed Javad Mowla,2 Vahid Kholghi Oskooei,3 Elahe Motevaseli,4 Leila Farhady Tooli,5 Leila Nekoohesh,6 Maryam Eghbali,1 Soudeh Ghafouri-Fard,3 Mandana Afsharpad7 1Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2Faculty of Biological Sciences, Department of Genetics, Tarbiat Modares University, Tehran, Iran; 3Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Microbiology, School of Biology, College of Science, Tehran University, Tehran, Iran; 6Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 7Cancer Control Research Center, Cancer Control Foundation, Iran University of Medical Sciences, Tehran, Iran Background: Long non-coding RNAs (lncRNAs) and exosomes have been regarded as components of cell signal transmission that modulate indigenous cellular microenvironments. Exosomes also participate in relocation of functional lncRNAs between cells. Methods: In the present study, we evaluated expression of LINC00355, LINC00958, UCA1-201, UCA1-203, and MALAT1 lncRNAs in urinary exosomes isolated from transitional cell carcinoma (TCC) of bladder, non-malignant urinary disorders, and normal subjects. Results: LINC00355, UCA1-203, and MALAT1 expression was significantly higher in TCC patients compared to controls (non-malignant or normal samples). However, UCA1-201 expression was significantly decreased in TCC patients compared with controls. LINC00355 and MALAT1 expression was significantly lower in cigarette smokers and opium-addicted TCC patients, respectively. On the other hand, LINC00355 expression tended to be higher in opium-addicted TCC patients. The proposed panel of lncRNAs (composed of UCA1-201, UCA1-203, MALAT1, and LINC00355) had 92% sensitivity and 91.7% specificity for diagnosis of bladder cancer from normal samples. Conclusion: Transcript levels of lncRNAs in urinary exosomes are potential diagnostic biomarkers in bladder cancer. Keywords: lncRNA, exosome, bladder cancer

Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare autosomal recessive disease characterized by pain insensitivity, frequent intermittent fevers, anhidrosis, self-mutilating actions and mental retardation. Germline mutations in NTRK1 gene have been associated with CIPA. In the current study, we describe the first reported case from Iran. The patient was a 10 month old girl born to a healthy consanguineous Iranian parent with family history of CIPA. Unexpectedly, the cases had normal sweating. Whole exome sequencing revealed a new likely pathogenic mutation in the exon 13 of NTRK1 gene (NM_002529.3) in the proband in homozygote state (c.1524_1531dupGGACATCG, p.Val511Glyfs*39). The frameshift mutation leads to early termination of the coding sequence, which is anticipated to affect the protein function. Sanger sequencing confirmed the results in the proband and other affected members of the family. In addition, Sanger sequencing showed that parents carry the same mutation in heterozygote state. The current study shows a different phenotypic variant of CIPA in Iranian population and adds to the repository NTRK1 mutations.

Fatemeh Yazarlou,1 Seyed Javad Mowla,2 Vahid Kholghi Oskooei,3 Elahe Motevaseli,4 Leila Farhady Tooli,5 Mandana Afsharpad,6 Leila Nekoohesh,7 Nafiseh Sadat Sanikhani,4 Soudeh Ghafouri-Fard,3 Mohammad Hossein Modarressi1 1Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2Faculty of Biological Sciences, Department of Genetics, Tarbiat Modares University, Tehran, Iran; 3Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Microbiology, School of Biology, College of Science, Tehran University, Tehran, Iran; 6Cancer Control Research Center, Cancer Control Foundation, Iran University of Medical Sciences, Tehran, Iran; 7Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Background: Exosomes have been regarded as emerging tools for cancer diagnosis. Tumor-derived exosomes contain molecules that enhance cancer progression and affect immune responses. Material and methods: In the present study, we evaluated expression of seven cancer-testis antigens (CTAs) that are regarded as putative biomarkers and immunotherapeutic targets along with NMP22 in urinary exosomes of bladder cancer patients, healthy subjects and patients affected with nonmalignant urinary disorders. Results: Exosomal expression of MAGE-B4 was significantly higher in bladder cancer patients compared with normal samples (expression ratio=2.68, P=0.01). However, its expression was lower in bladder cancer patients compared with benign prostate hyperplasia (BPH) patients (expression ratio=0.17, P=0.01). Exosomal expression of NMP22 was significantly higher in bladder cancer patients compared with BPH patients (expression ratio=9.22, P=0.02). Expressions of other genes were not significantly different between bladder cancer patients and normal/nonmalignant samples. We found significant correlation between MAGE-A3 and MAGE-B4 expressions in exosomes obtained from controls. In addition, TSGA10 expression was correlated with expression of NMP22 in both cancer patients and controls. Conclusion: The present study provides evidences for differential expression of CTAs in urinary exosomes of bladder cancer patients and urogenital disorders and warrants further studies for assessment of their significance in cancer diagnosis and immunotherapeutic approaches. Keywords: cancer-testis antigen, bladder cancer, exosome

Deregulation of key signaling pathways is one of the primary phenomena in carcinogenesis. DAB2IP and SPRY2 are regulatory elements, which act as feedback inhibitors of receptor tyrosine kinases signaling in mitogen-activated protein kinase pathway. These elements have also been implicated in the pathophysiology of cancer. Therefore, this study is aimed to investigate the expression of all known splice variants of DAB2IP and SPRY2 in prostate tissue. Fresh Prostate tissue samples (50 prostate cancer/ matched normal tissue and 30 BPH) were collected and total RNA was extracted followed by cDNA synthesis. The expression of DAB2IP and SPRY2 transcript variants were evaluated using RT-PCR and quantitative Real-time PCR. The results indicated significant down-regulation of DAB2IP transcript variant 1 in cancerous tissues compared to paired normal tissues (P = 0.001) as well as SPRY2 transcript variant 2 in cancerous tissues in comparison with the normal counterparts and BPH (P = 0.008 and P = 0.025, respectively). In addition, there was a significant negative correlation between DAB2IP.1 and SPRY2.2 expression with PSA levels in prostate cancer (P = 0.039 ρ =−0.24 and P = 0.045 ρ =−0.3, respectively). Interestingly, the down-regulation of DAB2IP.1 mRNA and SPRY2.2 mRNA was positively correlated in tumor samples (P = 0.002 ρ = 0.434). For the first time, this experiment highlights the deregulation of DAB2IP and SPRY2 transcript variants in human prostate cancer. The present study confirms and extends the previous reports through indicating transcript-specific down-regulation and significant association of DAB2IP and SPRY2 in prostate tumorigenesis.

Testis specific protein 10 (TSGA10) is expressed in normal adult testis and has been suggested to be involved in the normal function of sperms. Tsga10 expression has a role in the protection of spermatozoa and enhancement of male fertility. This gene has a number of single nucleotide polymorphisms (SNPs). In the current study, we genotyped rs3811553, rs200902126 and rs17852533 in 156 fertile men, 150 oligospermic and 150 azoospermic men using PCR-RFLP method. The genotyping showed that all assessed individuals were homozygote for wild type allele of both rs3811553 and rs200902126. In the case of the rs17852533, although we found the three genotypes in the studied individuals, there was no significant difference in distribution of these genotypes between the study groups. The current study shows insignificance of these SNPs in male infertility. However, future studies in larger sample sizes are needed to reach conclusive results.