Caffeic Acid Phenethyl Ester Reduces the Adverse Effects of Nicotine on the Endometrium.

Background: Tobacco smoke contains various toxins that negatively affect the human reproductive system. Caffeic acid phenethyl ester (CAPE), a potent antioxidant, has protective effects on the reproductive system against oxygen-free radicals, methotrexate, and pesticides. Herein, the effect of CAPE on some key markers of endometrial receptivity has been evaluated. Methods: A cross-sectional study was conducted during 2018-2019 in the Department of Clinical Biochemistry, School of Medicine, Fasa University of Medical Sciences (Fasa, Iran). Primary endometrial cells were divided into five groups, namely control, nicotine, CAPE, vehicle, and nicotine+CAPE. Real-time polymerase chain reaction (PCR) and methylation-specific PCR were performed to evaluate gene expressions and methylation, respectively. Appropriate doses of CAPE and nicotine were determined using the MTT assay. Data were analyzed using SPSS software (version 16.0) with a one-way analysis of variance. P<0.01 was considered statistically significant. The fold change was calculated using the 2-∆ΔCT method. Results: Treatment of cells with nicotine significantly reduced the expression of C-X-C motif chemokine ligand 12 (CXCL12), fibroblast growth factor 2 (FGF2), and vascular endothelial growth factor A (VEGF-A) genes (P<0.0001). However, the expression levels increased significantly when treated with nicotine+CAPE (P<0.0001). Despite the reduced CXCL12 gene expression in cells treated with nicotine, CXCL12 was unmethylated in all study groups, indicating that the methylation status of the CXCL12 gene was not affected by nicotine or CAPE. Conclusion: CAPE can be a suitable agent to protect female smokers from the harmful effects of nicotine. This manuscript is available as a preprint on the Research Gate website.

Insilco prediction of the role of the FriZZled5 gene in colorectal cancer.

INTRODUCTION: In this study, we aimed to elucidate the crosstalk between the Wnt/ß-catenin signaling pathway and colorectal cancer (CRC) associated with inflammatory bowel disease (IBD) using a bioinformatics analysis of putative common biomarkers and a systems biology approach. MATERIALS AND METHODS: The following criteria were used to search the GEO and ArrayExpress databases for terms related to CRC and IBD: 1. The dataset containing the transcriptomic data, and 2. Untreated samples by medications or drugs. A total of 42 datasets were selected for additional analysis. The GEO2R identified the differentially expressed genes. The genes involved in the Wnt signaling pathway were extracted from the KEGG database. Enrichment analysis and miRNA target prediction were conducted through the ToppGene online tool. RESULTS: In CRC datasets, there were 1168 up- and 998 down-regulated probes, whereas, in IBD datasets, there were 256 up- and 200 down-regulated probes. There were 65 upregulated and 57 downregulated genes shared by CRC and IBD. According to KEGG, there were 166 genes in the Wnt pathway. FriZZled5 (FZD5) was a down-regulated gene in both CRC and IBD, as determined by the intersection of CRC- and IBD-related DEGs with the Wnt pathway. It was also demonstrated that miR-191, miR-885-5p, miR-378a-3p, and miR-396-3p affect the FriZZled5 gene expression. CONCLUSION: It is possible that increased expression of miR-191 and miR-885-5p, or decreased expression of miR-378a -3p and miR396-3, in IBD and CRC results in decreased expression of the FZD5 gene. Based on the function of this gene, FZD5 may be a potential therapeutic target in IBD that progresses to CRC.

The role of vitamin D receptor and IL-6 in COVID-19.

BACKGROUND: Vitamin D (Vit.D) has an important role in protecting COVID-19 patients. This study investigated the changes in vitamin D receptor (VDR) expression and interleukin 6 levels in patients with COVID-19. MATERIALS AND METHODS: 120 hospitalized patients and 120 healthy people participated in this study, both group adjusted by sex and age. Vit.D was measured with HPLC, the expression of VDR gene was done with Real-time PCR, and IL-6 was measured with ELISA assay. RESULTS: Our findings showed no significant difference in the case of Vit.D (25-OH-D3) between the two studied groups, interestingly the expression of VDR was statistically lower in the patients with COVID-19, p-value = 0.003. VDR expression was lower in the patient with diabetes, hypertension and cardiovascular disease, significantly, p-value = 0.002. The level of IL-6 was statistically higher in the COVID-19 group, p-value = 0.003. CONCLUSION: Alongside the important role of 25-OH-D3 in COVID-19 patients, the quality and quantity of the VDR expression and its role in the level of IL-6 are the promising risk factors in the future. Further studies are needed to determine the factors increasing the expression level of VDR, especially in the patients with diabetes, hypertension and cardiovascular disease.

Up-regulated lncRNA-PVT1 expression in peripheral blood mononuclear cells of patients with coronary artery disease is correlated with decreased interleukin-10 production.

OBJECTIVES: Plasmacytoma variant translocation 1 (PVT1) is a newly discovered long non-coding RNA, which has not been previously studied in the inflammatory responses of the peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD). MATERIALS AND METHODS: This cross-sectional study was conducted on 15 CAD patients and 15 non-CAD (NCAD) individuals. The PVT1 expression was assessed in the PBMCs of the participants using a real-time polymerase chain reaction. Interleukin (IL)-10, IL-22, and matrix metalloproteinase-9 (MMP-9) were measured in the plasma and supernatant of cultured PBMCs in the presence or absence of lipopolysaccharide (LPS) using flow cytometry and enzyme-linked immunosorbent assay. RESULTS: An increased expression of PVT1 was observed in the untreated PBMCs of CAD patients, compared to the NCAD group. The PVT1 was significantly up-regulated after LPS treatment in the PBMCs of both groups. Plasma MMP-9 levels were found to be higher in CAD patients than in the control individuals. The level of IL-10 and IL-22 production by the non-treated PBMCs of CAD cases was significantly lower than the NCAD group. Overall, in the examined population, PVT1 expression was negatively correlated with IL-10 secretion. Moreover, the results showed a significant negative correlation between PVT1 expression and IL-10 production by untreated cells. CONCLUSIONS: The PVT1 expression augmented in the PBMCs of CAD patients, which could be associated with the decreased IL-10 generation by the PBMCs of these patients.

Scrotal leiomyoma a rare benign intra-scrotal mass could lead to unnecessary orchiectomy.

Leiomyoma is a benign tumor originating from smooth muscle cell, Mostly from uterus. However, in men is a very rare entity. Scrotal leiomyoma is a very rare tumor. Here we presented a case of scrotal leiomyoma in a 71-year-old man. He presented with a slowly growing, painless mass and heaviness in the left testis for 10 years. Due to huge size, testicular attachment and preoperational diagnosis of atypical leiomyoma/leiomyosarcoma, orchiectomy was performed. Pathology report diagnosed leiomyoma. We suggest frozen section diagnosis as a useful tool, to prevent unnecessary procedure.

Primary amelanotic melanoma of the male urethra: A rare entity and diagnostic challenge.

Malignant melanoma (melanoma) is a tumor of melanocytes that usually presents as cutaneous lesions. While melanoma can infrequently appear as a primary tumor elsewhere in the body, it is extremely rare in the urethra and even rarer as amelanotic malignant melanoma. We report the case of a 66-year-old male who presented with painless gross hematuria and lower urinary tract obstructive symptoms in the recent 2 weeks prior to his visit to our clinic. History and physical examination, including external genital examination, abdominopelvic sonography, and urine culture, were not conclusive. Cystourethroscopy revealed a creamy pink fragile mass located in the anterior proximal urethra that extended to the mid portion. Pathological examination of this lesion confirmed the diagnosis of amelanotic malignant melanoma using immunohistochemistry. Radical cystourethrectomy with ileal conduit was subsequently conducted. Although this tumor is extremely rare, urologists and pathologists should consider malignant melanoma as a diagnosis in patients with urethral tumor because of the likelihood of early metastasis and, consequently, poor prognosis. Complete surgical removal of the tumor and use of effective therapies can improve outcomes in these patients.

Quantitative analysis of expression level of estrogen and progesterone receptors and VEGF genes in human endometrial stromal cells after treatment with nicotine.

Cigarette smoke is a complex mixture of toxic chemicals, including nicotine, carbon monoxide, and several recognized carcinogens and mutagens. Nicotine has a direct disturbing influence on steroid hormones (estrogen and progesterone), which are essential components of the female reproductive system, but the effect of nicotine on the hormone receptors is not yet clear. The aim of this study was to elucidate the effect of nicotine on the expression of estrogen receptor (ER), progesterone receptor (PR), and vascular endothelial growth factor (VEGF) in endometrial stromal cells. Expression levels of PR, ER, and VEGF in human endometrial stromal primary cells treated with nicotine (0, 10-11, 10-8, and 10-6 µM) for 24 h were measured by quantitative real-time PCR. MTT assay demonstrated that nicotine decreased cell viability in a dose-dependent manner. Real-time PCR data showed that despite decrease in ER expression in the nicotine-treated groups compared with the control, nicotine exerted an increased inhibitory effect on PR expression compared to that on ER expression. VEGF mRNA expression in nicotine-treated endometrial stromal cells was increased. The results from this study provide novel evidence for inhibitory effects of nicotine on steroid hormones receptor expression in human primary endometrial cells. Also, our data suggest that nicotine might have angiogenesis effects on these cells.

Association of the colorectal cancer and MDR1 gene polymorphism in an Iranian population.

The human multidrug resistance (MDR1) gene product P-glycoprotein is highly expressed in intestinal epithelial cells, where it constitutes a barrier against xenobiotics, bacterial toxins, drugs and other biologically active compounds, possibly carcinogens. In this study, an association of MDR1 gene polymorphism and the occurrence of colorectal cancer were evaluated. In this case-control-designed 118 unrelated colorectal cancer and 137 sex-and-ages matched healthy controls were enrolled. The C3435T MDR1 gene polymorphism was identified using the polymerase chain reaction-restriction fragment length polymorphism method. Significantly increased frequencies of the 3435T allele and the 3435TT were observed in patients with colorectal cancer compared with controls (P = 0.03; OR, 95% CI; 1.46 for 3435T allele and P = 0.003; OR, 95% CI; 2.2 for 3435TT genotype). In contrast, frequency of genotype TT was significantly higher in controls compared to colorectal cancer (P = 0.006; OR, 95% CI; 0.49 for TC genotype). In this study suggest that C3435T MDR1 polymorphism has an association with colorectal cancer. The results support that the presence of allele C results in decreased susceptibility to colorectal cancer.