Shahid Beheshti
University of Medical Sciences


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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 mens 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.

KEYWORDS: Prostate cancer; TNF-α polymorphism; benign prostate hyperplasia


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Does in vitro fertilization affect the expression of miRNAs and their biogenesis pathway in preimplantation mouse embryos?



In vitro fertilization (IVF) is a well-accepted procedure which has been utilized for the treatment of infertile patients. As embryos at early stages of development are very vulnerable, the IVF conditions may influence genetic and epigenetic regulation of preimplantation mouse embryo.


We assessed the effect of IVF on the expression of developmental and implantation related miRNAs (miR-21, miR-93, miR-24, and let-7a), their common presumptive target (Stat3), and miRNA biogenesis pathway genes (Drosha, Dgcr8, Exportin-5, Dicer, and Ago2). in vivo 8-cell and blastocysts were compared to IVF embryos. Expression levels of miRNAs, Stat3, and miRNA biogenesis pathway genes were evaluated by qRT-PCR in in vivo (n = 8) and IVF (n = 4) embryos.


The expression levels of let-7a and Stat3 were significantly reduced in IVF blastocyst when compared with in vivo (p = .004 and p = .009, respectively). Nevertheless, the IVF procedure did not influence the expression levels of miRNA biogenesis pathway components in 8-cell and blastocyst embryos.


Downregulation of let-7a and developmental related transcription factor, Stat3, in IVF mouse blastocysts may affect preimplantation development and implantation of embryos. Moreover, the genes of the miRNA biogenesis pathway were not changed in preimplantation mouse embryos through the IVF procedure.


embryo development; in vitro fertilization; microRNA biogenesis; microRNA expression; preimplantation mouse embryo


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Boomerang Technique, The Buccal Mucosal Grafting Harvesting Model for Long Urethral Stricture Urethroplasty; A Case Series




Currently, three methods are implicated in cases of long urethral stricture including harvesting buccal mucosa of inner cheeks, harvesting lip mucosa and finally lingual mucosal graft. This study evaluated the feasibility, safety and morbidity of our "Boomerang shape" technique used for graft retrieval from the inner cheeks to repair long urethral defect cases which are usually 12-15 cm in length and 2.5 cm in width.


The Kilner-Doughty mouth retractor is inserted to give access to the donor site. Initially, the internal surface of the right/left cheek is cleaned with a solution containing 10% povidone-iodine. Then, Stensens duct, located at the level of the second molar is identified and the desired size of the graft is measured and marked in a boomerang shape, 1.5 cm from the Stensens duct and 1.5 cm from the edge of the cheek. To decrease submucosal bleeding from the harvest site, 1% lidocaine combined with a 1:100,000 epinephrine solution is injected using a 25-gauge long needle. The outlines of the graft are drawn by using a scalpel through the mucosa. Then, the outlined graft is sharply dissected and removed, leaving the muscle intact. A 5-0 polyglactin continuous suture is used for the closure of the harvest site. The standard graft harvested from the cheek should be 12-15 cm in length and 2.5 cm in width.


Between 2017-2019, five adults have had their mucosal grafts harvested by the "Boomerang shape" technique in our center. No donor site complications were observed. Moreover, no urethral strictures or diverticulum occurred and the functional outcomes were satisfactory in all patients.


Our routine technique of harvesting the buccal mucosa from the cheek is secure and easily performable by any surgeon. It has minimal incidence of intra and post-operative complications.


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Skin Metastasis of Laryngeal Carcinoma Presenting as Multiple Eruptive Nodules


Metastasis of head and neck squamous cell carcinoma (SCC) to the skin of this region is extremely rare and reported in 1-2% of cases. The cutaneous metastases of head and neck cancers often present as multiple papulonodular lesions; however, sporadic cases of solitary or multiple keratoacanthoma-like lesions are reported. We describe a rare case of cutaneous metastases of laryngeal SCC presenting as multiple eruptive keratoacanthoma-like lesions with concomitant scrofuloderma in an area of previous radiotherapy.


Laryngeal neoplasms; Neoplasm metastasis; Scrofuloderma


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Pyrvinium pamoate inhibits proliferation and invasion of human endometriotic stromal cells



Endometriosis is characterized by the presence of functional endometrial tissue in other pelvic organs. This gynecologic problem occurs in 35-50% of women with pain and infertility. Endometriotic cells share some characteristics such as proliferation, migration, and invasion with tumor cells. Pyrvinium pamoate, an anthelmintic drug approved by the Food and Drug Administration, could inhibit the Wnt/β-catenin signaling pathway and its anticancer effects were examined by several researchers. In this study, 12 ectopic and eutopic endometrial biopsies from females with ovarian endometrioma and 12 endometrial biopsies from nonendometriotic females were obtained. Ectopic (EESCs), eutopic (EuESCs), and control (CESCs) endometrial stromal cells were isolated. Then, the effect of pyrvinium pamoate on the proliferation and invasiveness of in vitro cultured cells was evaluated. The proliferation of CESCs, EuESCs, and EESCs was significantly decreased after treatment with pyrvinium pamoate. In addition, treatment with pyrvinium pamoate significantly inhibited the invasiveness of CESCs, EuESCs, and EESCs compared to nontreated groups. The results of the present research showed that pyrvinium pamoate inhibits the proliferation and invasion of human endometriotic stromal cells in vitro, further investigations on the therapeutic potential of this compound in endometriosis are required.


Endometriosis; Wnt signaling pathway; cell proliferation; pyrvinium pamoate; stromal cells


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Post Intensity-Modulated Radiation Therapy Urinary Function for Prostate Cancer; A Prospective Study



Background: At present, there is a lack of evidence concerning urinary complications caused by intensity-modulated radiation therapy (IMRT) used for the management of prostate cancer (PCa).
Objectives: This study aimed at identifying the nature and severity of post-IMRT urinary symptoms in patients with PCa.
Methods: This prospective study was performed with consecutive patients, who had clinically localized PCa (cT1c-cT2c) and had undergone IMRT treatment from 2016 to 2019. At 1, 6, and 12 months of follow-up, medical history, physical information, prostate-specific antigen values, International Prostate Symptom Score (IPSS), medication use, Radiation Therapy Oncology Group (RTOG), acute and late toxicity, and Q max were collected.
Results: A total of 127 patients with a mean age of 71.04 ± 7.1 years received IMRT and underwent 12 months of follow-up. The mean IPSSs at baseline versus those at 1, 6, and 12 months after IMRT was 14.5 ± 6.8 versus 13.3 ± 6.1, 12.3 ± 5.3, and 10.4 ± 4.2, respectively (P < 0.000). The mean prostate volume was 38.2 ± 12.1 cc. At the last follow-up, 31 patients (24.4%) took genitourinary (GU) medications.


Conclusions: This study showed that the majority of GU side effects caused by primary IMRT for PCa treatment are transient. Treatment triggered an acute increase in obstructive urinary symptoms, which peaked during the first month after IMRT. In most patients, in the course of 6 months, symptoms returned to baseline.


Quality of Life; Prostate Cancer; IPSS; Intensity-Modulated Radiation Therapy; Genitourinary Toxicities.
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Basal characterization and in vitro differentiation of putative stem cells derived from the adult mouse ovary



Lately, stem cell approaches have provided new information on reproductive organ function and additionally recommended novel treatment possibilities. The type(s) and differentiation potential of stem cells present in the mammalian ovary are largely unknown; while oogonial stem cells have been reported, we explored the possibility that multipotent stem cells may reside in the ovary and have wide differentiation potential. In this experimental study, homogenates of whole mouse ovaries were sorted using the stem cell surface markers stem cell antigen-1 and stage specific embryonic antigen-1/CD15. Viable double-positive cells 3–10 μm in diameter were evaluated immediately after sorting and after culture using differentiation conditions. Ovarian-derived stem cells were differentiated into the three main cell types: adipocytes, chondrocytes, or osteocytes. The subsequent culture was performed in media containing bone morphogenetic protein 4 (BMP-4) and/or retinoic acid (RA). RA, BMP-4 or the two agents in combination, consistently stimulated germ cell gene expression. RA treatment strongly stimulated germline gene expression and also the development of cells that were morphologically reminiscent of oocytes. The germ cell genes Dazl, Ddx4, Figla, Gdf-9, Nobox, Prdm9, and Sycp-1 were all detected at low levels. Remarkably, treatment with BMP-4 alone significantly increased protein expression of the granulosa cell product anti-Müllerian hormone (AMH). We have shown that an inclusive isolation protocol results in the consistent derivation of multipotent stem cells from the adult ovary; these cells can be differentiated towards the germ cell fate (RA alone), somatic ovarian cell fate as indicated by AMH production (BMP-4 alone), or classical mesenchymal cell types. Taken together, these data suggest the presence of multipotent mesenchymal stem cells in the murine ovary.
Keywords: Stem cells; Ovary; BMP-4; Retinoic acid; Multipotent
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The roles of miRNAs’ clinical efficiencies in the colorectal cancer pathobiology: A review article


Comparing the effect of sitagliptin and metformin on the oocyte and embryo quality in classic PCOS patients undergoing ICSI


Background: Insulin resistance plays a major role in the pathogenesis of polycystic ovary syndrome (PCOS). Therefore, there is a growing interest in the use of insulin sensitizer drugs in the treatment of PCOS. Research in recent years has shown that sitagliptin has been reported to improve ovarian cycles and ovulation in PCOS patients.

Aims: We aimed to compare the effects of metformin and sitagliptin on PCOS individuals undergoing ICSI.

Methods: Sixty PCOS patients were divided into 3 groups: metformin, sitagliptin, and placebo group. Treatment was carried out 2 months before the start of the ovulation cycle and continued until the day of oocyte aspiration. The serum levels of total testosterone, estradiol, and fasting insulin along with the total number of retrieved, normal and abnormal MII, and fertilized oocytes, the number of transferred embryos (grades I, II and III), and biochemical and clinical pregnancy rates as well as the ovarian hyperstimulation syndrome (OHSS) were evaluated.

Results: There was a significant reduction in the serum levels of Insulin and total testosterone in the treated groups compared with the placebo. The number of mature and normal MII oocytes increased significantly in the treated groups compared with the placebo. Moreover, the number of immature oocytes decreased significantly and the number of grade I embryos increases significantly in the sitagliptin group compared with the placebo group.

Conclusion: We conclude that sitagliptin can improve the maturation of oocytes and embryos quality more effectively than metformin, in PCOS patients undergoing ICSI.

Trial registration: Trial registration is NCT04268563 ( ).


Keywords: GnRH antagonist; ICSI; Metformin; PCOS; Sitagliptin.

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



Potential of Auraptene in Improvement of Oocyte Maturation, Fertilization Rate, and Inflammation in Polycystic Ovary Syndrome Mouse Model


Polycystic ovary with poor-quality oocytes has remained problematic in polycystic ovary syndrome (PCOS) patients. It is well documented that the inflammation and production of reactive oxygen species (ROS) in PCOS ovaries are significantly higher than normal voluntaries. In this study, we hypothesized that auraptene (AUR), as a coumarin derivative with anti-inflammatory properties, may be effective in improvement of oocyte maturation and fertilization rate in PCOS patients. For this purpose, PCOS model was induced in NMRI mice and confirmed by ovarian histopathology observations and hormonal assays. PCOS-induced mice were administrated with AUR (PCOS-AUR) and metformin (PCOS-MET), and their effects on inflammation, apoptosis rate, oocyte maturation, and in vitro fertilization capacity were determined and compared with those normal and PCOS animals treated with sesame oil (PCOS-sesame oil) and no treatment (PCOS). Treatment with AUR and MET decreased the inflammation and apoptosis rates in PCOS mice compared with PCOS animals with no treatment. PCOS-AUR and PCOS-MET oocytes also showed higher intracellular glutathione and lower ROS concentrations compared with PCOS mice, indicating improved oocyte maturation rate. PCOS-AUR and PCOS-MET groups showed higher percentages of expansion rate and MII stage oocytes, and lower rate of abnormal oocytes compared with PCOS with no treatment. The rate of fertilization in the oocytes isolated from PCOS-AUR and PCOS-MET groups was higher than PCOS-sesame oil and PCOS groups. Our findings suggest that AUR can be considered as a potential candidate for improvement of oocyte maturation and fertilization capacity in PCOS patients, comparable to MET.
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  Investigation of GSTP1 and epigenetic regulators expression pattern in a population of Iranian patient with prostate cancer



Keywords: DNMT3A; DNMT3B; GSTP1; HDAC; benign prostatic hyperplasia; prognosis; prostate cancer; quantitative Real-time PCR.
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Men's Health and Reproductive Health Research Center

Shahid Beheshti University of Medical Sciences


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