Introduction: Effects of cimetidine (CIM) on locomotor is controversial. This study was designed to evaluate the effects of CIM on motor activity and possible roles of opioid RECEPTORs in CIM-induced decrement in locomotor activity in mice.Materials & Methods: Thirty-six male mice (25-30gr) were divided into six groups in this study. Locomotor activity was evaluated using an automated activity monitor system. CIM (50 mg\kg, i.p.) was injected 25 min before testing in presence or absence naloxone (2 mg/kg, sc). Morphine (5 mg/kg, i.p) was injected 25 min before testing in the presence or absence CIM. Decreased motor activity significantly. Pretreatment of or morphine did not change CIM - induced response significantly.Results: The results showed that CIM significantly decreased motor activity in mice (P=0.000). Pretreatment of nalxone did not change CIM-induced response significantly. Morphine alone did not change motor activity. Pretreatment of ClM did not change morphine-induced response.Conclusion: Data indicated that cimetidine can reduce motor activity independence from interaction with opioid RECEPTORs.

Introduction: Peroxisome proliferator-activated RECEPTOR gamma (PPARg) is a ligand-dependent transcription factor involved in various disease processes including inflammation and carcinogenesis. This study aimed to determine polymorphism of PPARg gene and its association with Helicobacter pylori infection and gastrointestinal diseases in patients.Materials and Methods: Two hundred patients with helicobacter pylori infection were examined. H. pylori infection was diagnosed by histology, rapid urease test (RUT), culture, ELISA and PCR. PPARg polymorphism was analyzed by PCR-based restriction fragment length polymorphism.Results: In total 200 patients (4 gastric cancers, 141 gastritis, 35 peptic ulcers, 18 duodenal ulcers, 2 peptic ulcer and duodenal ulcer) with Helicobacter pylori infection were enrolled. The frequency of PPARg G (Ala12) allele (5%) showed a significant association with gastric cancer (P=0.004) or gastritis (P=0.007).PPARg GC (Pro12Ala) allele (35%) showed a significant association with duodenal ulcer (P=0.03) or gastritis (P=0.002).Conclusion: Pro12Ala PPARg polymorphism is associated with gastric cancer and gastritis and is a potential marker for genetic susceptibility to these two diseases in the presence of H. pylori infection.Finally, our study suggests the potential association between PPARg polymorphism and H. pylori infection in the development of gastric cancer and peptic ulcer and gastritis.

Aim: b-Catenin is a known proto-oncoprotein which its upregulation is involved in tumorigenesis of several human cancers including colorectal cancer, melanoma, pancreatic, ovarian and many other human malignancies. It is believed that this protein is a very potential target for cancer prevention and therapy. Although b-Catenin was originally identified as a component of the canonical Wnt signaling, there are many reports that this protein can also be regulated by several other signaling pathways including those through RECEPTOR tyrosine kinases, PI3-kinses and heterotrimeric G-proteins. It is quite likely that regulation of b-Catenin by multiple signaling pathways is a result of the cross-talk among these pathways. We and others have already provided evidence that activation of almost all members of the Ga subunits of heteritrimeric G-proteins can regulate b-Catenin via different mechanisms. For example, by using several cell systems, we have shown that activation of the Gaq class of Ga proteins leads to inhibition of GSK-3b and cellular accumulation of b-Catenin, suggesting that Gaq signaling may somehow positively regulate the canonical Wnt signaling. We have also confirmed the positive role of Gaq on b-Catenin-mediated signaling by using a couple of specific Gaq blocking peptides. RECEPTORs for G-proteins (G protein-coupled RECEPTORs, GPCRs) are the most diverse family of proteins in mammals which are involved in many critical cellular processes. Around one thousand different GPCRs are encoded by human genome and more than 30% of the approved therapeutic drugs, target these RECEPTORs. Calcitonin RECEPTOR (CTR) is a member of the GPCR family (B1 subfamily) which is shown to couple to Gaq or Gas containing trimeric G proteins involved in primarily activation of phospholipase Cb1 and adenylate cyclase respectively. The known ligand for Calcitonin RECEPTOR is a 32 amino acid peptide called Calcitonin which is produced by several tissues in the body including thyroid, prostate, and central nervous system. CTR-mediated signaling has very important biological roles in many tissues including bones in which this signaling pathway is involved in maturation of osteoclasts and bone homeostasis. Calcitonin RECEPTOR is a GPCR family member which functions through activation of Gs and Gq trimeric G proteins and therefore, in this study we have examined whether activation of this RECEPTOR has any effect on b-Catenin transcriptional activity by measuring the expression of several b-Catenin-target genes including a reporter luciferase gene harboring several b-Catenin/T-cell factor recognition elements.Material and Methods: HEK293T cell culture and transfection with appropriate genetic constructs plus gene expression assays at the level of transcription including quantitative RT-PCR and real-time PCR have been used in this study.Results: The results showed that cellular activation of Calcitonin RECEPTOR increases the expression of several b-Catenin-responsive genes. Expression of the reporter luciferase, CCND1 (the Cyclin D1 encoding gene), c-MYC, and FGF-20 (Fibroblast growth factor-20) was increased upon the expression of Calcitonin RECEPTOR in HEK293T cells or treatment of these cells with Calcitonin.Conclusion: The Calcitonin RECEPTOR-mediated signaling may activate b-Catenin and (or) the Wnt/b-Catenin pathway. Further investigations are required to find out the exact mechanism of regulation of the Wnt/b-Catenin pathway by Calcitonin RECEPTOR-mediated signaling. Since b-Catenin is a potential oncogene in human cancers, Calcitonin RECEPTOR and its signaling partners can be considered for clinical studies.

Background: The major issue to address in endometriosis etiology is to identify the genetic changes in the disease and their occurrence in different populations. Uncovering these genetic changes may be important in developing potential biomarkers for early diagnosis and prognosis of endometriosis. Among all endometriosis susceptibility genes studied before, convincing association has been found with variants in the estrogen RECEPTOR alpha (ESR1) gene and this disease; however, the contributions of these genetic variants in different populations and ethnic groups are not similar. Accordingly, this study was carried out to replicate the previous findings to assess whether this polymorphism is associated with endometriosis in Iranian women.Methods: A case-control study was designed to determine the possible association between ESR1-351A>G variant and occurrence of endometriosis. The study group consisted of 100 subjects diagnosed with endometriosis as case group and 100 fertile women without endometriosis as controls recruited from subjects referred to the Tehran Women’s General Hospital between January to September 2013. All subjects were genotyped for this marker using amplification refractory mutation system- polymerase chain reaction (ARMS-PCR). Association of risk allele (G) with endometriosis was assessed using PLINK software after age adjustment.Results: The results showed that the genotype frequencies were in Hardy-Weinberg Equilibrium (HWE) in both case (F=0.04, P: 0.67) and control (F=0.02, P: 0.83) groups.In addition, there were no significant differences between case and control groups in terms of genotype frequencies (P=0.17). Moreover, the results indicated that the presence of risk allele (G) did not significantly increase risk of endometriosis (OR: 1.43, 95%CI: 0.96-2.13, P=0.07).Conclusion: The results do not support the previous findings of an association between -351A>G genetic polymorphism in ESR1 gene and endometriosis. Therefore, comprehensive genetic approaches including linkage analyses and family-based tests, together with a number of replication studies with large sample size, are needed to make conclusive claims about the role of this genetic polymorphism in susceptibility to endometriosis.