Investigating the role of Epstein-Barr virus and human papillomavirus types 16 and 18 co-infections in cervical disease of Iranian women.

Introduction: High-risk human papillomaviruses (HR-HPVs) are known to contribute to cervical cancer (CC), but the role of Epstein-Barr virus (EBV) in this process remains unclear, despite EBV's widespread detection in premalignant and malignant cervical tissues. Methods: In this cross-sectional study of 258 cervical samples, including both formalin-fixed paraffin-embedded (FFPE) and fresh cervical tissues, the presence and viral load of HR-HPVs (HPV-16 and HPV-18) and EBV were evaluated in Iranian women with cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), and a cervicitis control group using real-time PCR. Results: The study revealed a significant correlation between disease severity and both increased HPV-16 positivity and HPV-16 and HPV-18 co-infection (p<0.001). Interestingly, the control group had a higher frequency of EBV-positive cases than SCC/CIN groups (p<0.001). HPV-16 DNA load increased with disease severity (P<0.001), while HPV-18 showed no significant difference (P=0.058). The control group had a higher EBV DNA load compared to SCC/CIN groups (P=0.033). HPV-16 increased the risk of CIN II, CIN III, and SCC, while HPV-18 increased the risk of CIN II and CIN III. Notably, EBV was associated with a lower risk of CIN groups and SCC. Conclusions: No significant difference in EBV co-infection with HPV-16/18 was found, failing to support the hypothesis that EBV is a cofactor in CC. However, high EBV viral load in the control group suggests a potential "hit and run hypothesis" role in CC progression. This hypothesis suggests that EBV may contribute briefly to the initiation of CC with an initial impact but then becomes less actively involved in its ongoing progression.

The Relationship Between Tumor Budding and Patient's Survival in Breast Cancer.

Introduction: Breast cancer is a severe life-threatening condition in which many women are involved yearly. One factor that has recently been noticed and investigated as a diagnostic predictor of this type of cancer is the number of tumor buds and the relation of this factor with a patient's survival rate. Materials and methods: This study includes 150 female patients over 18 years old with a mean age of 53.99 ± 12.56 years old with breast cancer, which was diagnosed at various medical centers, including Rouhani Hospital itself, and referred to Rouhani Hospital Medical Center, Babol, Iran. The number of intratumoral and peritumoral buds in patients' microscopic slides were archived and evaluated along with tumor microenvironment on hematoxylin and eosin (H&E) slides and compared to other clinicopathological findings. This article precisely investigated the relationship between the number of intratumoral and peritumoral buds with patients' 5-year survival rate. Also, the relationship between age, tumor stage, grade, size, the number of lymph nodes involved, and the presence of metastasis with the number of intratumoral and peritumoral buds was studied. Results and discussion: The result showed a significant statistical association between the number of intratumoral and peritumoral buds with tumor size, tumor stage, presence of metastasis, the number of lymph nodes involved, and 5-year survival rate. On the other hand, there is not a significant statistical association between the number of intratumoral and peritumoral buds with age and tumor grade. Conclusion: Our investigation revealed a significant statistical relationship between the number of tumor buds and patients' survival rate. So, this factor should be considered significant to help those patients increase their survival ratio.

Placental Mesenchymal Dysplasia Associated with Severe Intrauterine Growth Restriction: A Case Report.

Placental mesenchymal dysplasia (PMD) is an uncommon placental lesion, which may mimic molar pregnancy at gross and microscopic examination. PMD can be associated with fetal growth restriction, Beckwith-Wiedemann syndrome, intrauterine fetal death, and preterm delivery. Nonetheless, it may also be associated with a normal appearing fetus. We aimed to emphasize that clinicians, radiologists, and pathologists should be aware of PMD as one of the etiologies of intrauterine growth restriction (IUGR). We presented the case of a 27-year-old gravida 1, para 1 woman who was admitted to Ayatollah Rouhani hospital, in Babol, Iran, at 30 weeks of gestation due to severe IUGR and fetal tachycardia. Ultrasound examination showed uteroplacental insufficiency and increased resistive index (RI) of umbilical artery. At last, a normal female fetus (1320 g) with no definitive anomalies was delivered by cesarean section. Pathological examination revealed cystically dilated stem villi with peripherally located thick-walled muscular stem vessels, and also stromal fibroblasts overgrowth in some stem villi. None of the examined sections revealed trophoblastic proliferation or stromal trophoblastic inclusion. The findings confirmed the diagnosis of PMD. Careful radiological and pathological examination should be performed in the case of IUGR for ruling out the rare placental abnormalities, including PMD.

New Presentation of Inlet Patch with Polypoid Kissing Pattern: Case Report.

In the worldwide medical literature, only one case of inlet patch shows a kissing pattern on endoscopy. This article describes a 69-year-old female patient who came to the gastroenterology clinic, Rohani hospital, Babol University of Medical Sciences (Iran) for an examination for indigestion. Endoscopy showed two polyps in the background of a maroon patch just below the upper esophageal sphincter, oppositely positioned in view of the kissing pattern, and extending into muscular mucosa and regional lymph nodes. There was no A polyp biopsy was performed and, on histological evaluation, there was heterotopic cardiac gastric mucosa. Since heterotopic gastric mucosa can be found anywhere in the gastrointestinal tract, careful examination of the proximal esophagus increases the likelihood of detecting an inlet patch.

A Rare Case of Cardiac Metastasis from Colon Cancer.

It is very rare for colorectal neoplasms to metastasize to the heart in the worldwide medical literature; only a single case of well-documented colorectal cancer metastasis to the left atrium was found. The case of a 66-year-old man is explained in this paper, who was suffering from metastatic adenocarcinoma of the colon that included the left atrium. In transthoracic and transesophageal echocardiography, a large multilobulated mass was present in the left atrium. An accidental pulmonary mass was also seen in a lung spiral CT scan. The cardiac mass was taken out, and a biopsy was obtained from the pulmonary mass. Adenocarcinoma was seen in histological assessment. Immunohistochemical staining was carried out to examine the expression of cytokeratin 7, cytokeratin 20, and caudal-related homeobox transcription factor 2 (CDX2) to determine the origin of the adenocarcinoma. In addition, the expression of these proteins was linked to the attributes of the patient and tumor. Post-surgical transesophageal echocardiography showed normal left ventricle and right ventricle function with no evidence of left atrium mass. Therefore, we suggest that asymptomatic cancer patients with a history of colorectal cancer and who have developed cardiac symptoms should be immediately examined for potential cardiac metastasis.

Quantitative analysis of Merkel cell polyomavirus (MCPyV) genome in non-melanoma skin cancer and normal tumor margins.

Merkel cell polyomavirus (MCPyV) is the cause of approximately 80% of Merkel cell carcinomas (MCC). The common types of non-melanoma skin cancer (NMSC) including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are histologically similar to MCC. In the present study, 58 NMSC formalin-fixed paraffin-embedded tissue (FFPE) samples including 12 SCC, 46 BCC, and 58 FFPE samples of adjacent non-tumoral margins as the control were included. Determination of large tumor antigens (LTAg) copy number was performed by qReal-Time PCR as a viral copy number per cell to elucidate MCPyV carcinogenic role in non-melanoma skin cancer. Out of 58 samples, 36 (62%) cancerous and 22 (37.9%) normal tumor margins were positive for MCPyV LTAg. Median copy numbers of MCPyV LTAg among all NMSC samples and non-tumoral margins were 0.308×10-2 and 0.269×10-3 copies per cell respectively (P=0.001). In addition, although the viral load in the majority of samples was detected to be lower than one copy per cell, in 4 BCC samples, a viral load higher than one LTAg copy per cell was detected. The present study revealed that the detection of higher levels of MCPyV LTAg viral load in some BCC and SCC samples may be correlated with the role of MCPyV in some cases of BCC and SCC skin cancer.

Higher viral load of Epstein-Barr virus in gastric cancer compared with non-cancerous gastroduodenal tissues.

Introduction: Epstein-Barr Virus (EBV)-associated gastric cancer is a distinct molecular subtype of gastrointestinal carcinomas as defined by the Cancer Genome Atlas. Methods: In the present study 237 samples from Iranian patients diagnosed with gastric cancer and gastroduodenal disease were retrospectively examined for EBV infection by quantitative Real-Time PCR. Results: Of the 237 samples tested, EBV DNA was detected in 37 samples (15.6%), in 13 of the 81 gastric cancer cases (16%), and 24 of the 156 non-cancerous samples (15.4%). The EBV infection rate was found higher in patients with gastric ulcer (35%) and duodenal ulcer (21.9%) compared to patients with gastric cancer (16%) and gastritis (19.6%). The EBV-encoded small RNA (EBER) copy number in the gastric cancer group (mean = 2.14×10-1 with range of 2.14×10-2 to 4.10×10-1 copies/ cell) was higher than gastroduodenal diseases group (mean = 1.39×10-2 with range 1.11×10-3 to 2.35×10-2 copies/ cell), and this difference was statistically significant (P >0.001). Conclusion: The higher number of copies of EBV-EBER in the gastric cancer group compared to the non-cancer group confirmed the possible role of EBV in inducing cancer.

Quercetin ameliorates Di (2-ethylhexyl) phthalate-induced nephrotoxicity by inhibiting NF-κB signaling pathway.

This study aimed to evaluate the possible protective effects of quercetin, a natural flavonoid, against nephrotoxicity induced by Di (2-ethylhexyl) phthalate (DEHP) in kidney tissue of rats and human embryonic kidney (HEK) 293 cell line. The HEK-293 cells were treated with different concentrations of quercetin 24 h before treatment with monoethylhexyl phthalate (MEHP). Male rats were treated with 200-mg/kg DEHP, 200-mg/kg DEHP plus quercetin (50 and 100 mg/kg), and 200-mg/kg DEHP plus vitamin E (20 mg/kg) for 45 days by gavage. Quercetin treatment reduced cytotoxicity and oxidative damage inducing by MEHP in HEK-293 cells. The in vivo findings showed that 100-mg/kg quercetin significantly suppressed DEHP-induced kidney damage. For exploring the involved mechanisms, the expressions of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor kappa B (NFκB), and tumor necrosis factor alpha (TNFα) genes were determined via real-time Polymerase chain reaction (PCR) assay. High dose of quercetin significantly decreased the gene expressions of NF-κB and TNFα, whereas the alternations of Nrf2 and HO-1 gene expressions were not significant in quercetin groups in compared with DEHP group. These findings suggested that the suppression of DEHP-induced nephrotoxicity via quercetin is correlated, at least in part, with its potential to regulate NF-κB signaling pathway.

Evaluating the MicroRNA Expression of IL-35 and IL-37 in Helicobacter Pylori-infected Patients with Gastritis and Gastric Ulcer.

Interleukin (IL)-35 and IL-37 are two anti-inflammatory cytokines. IL-35 inhibits the development of T-effector cells such as Th1, and Th17; while increasing regulatory T cells (Tregs). IL-37 causes the suppression of inflammatory cytokines. Regarding the positive impact of Helicobacter pylori (H. pylori) infection on inflammation and considering the anti-inflammatory effects of IL-35 and IL-37, this study aimed to evaluate the expression of these two cytokines in H. pylori-infected patients with gastrointestinal problems. The case group consisted of H. pylori-infected individuals with gastric ulcer and/or gastritis (n=50) and the control group consisted of cases with gastric ulcer and/or gastritis non-H. pylori-infected (n=50). Sampling and classification of patients were based on pathology findings. A real-time polymerase chain reaction was performed for evaluating the IL-35 and IL-37 expression levels. pylori-infected gastritis patients showed lower expression of IL-35 and IL-37 than the non-infected group. There was a significant difference between the expression levels of IL-35 and IL-37 in patients with gastric ulcers and/or gastritis who were infected and non-infected by H. pylori. There were no significant differences in the expression level of IL-35 and IL-37 in H. pylori-infected patients with gastric ulcer or gastritis. Interleukins 37 and 35 were less expressed in patients with H. pylori-infection. In differentiation between patients with gastrointestinal symptoms who have H. pylori infection or with similar symptoms who do not have H. pylori-infection, mentioned interleukins can be used as diagnostic markers.

Atorvastatin Entrapped Noisome (Atrosome): Green Preparation Approach for Wound Healing.

The present study aimed to formulate atorvastatin niosome (Atrosome) through an ultrasonic technique and to determine its contribution to the extent of wound healing in an animal model. The optimized Atrosome formulation (Atrosome-2) was stable at 4 °C for 3 months. Differential scanning calorimetry (DSC), ATR-Fourier transform infrared spectroscopy (ATR-FTIR), and powder X-ray diffraction (PXRD) analysis revealed that atorvastatin (ATR) was well encapsulated within the niosomes either in a stabilized amorphous form or a molecularly dispersed state. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscope (AFM) confirmed the spherical nature of the Atrosomes. The optimized formulation showed polydispersity index, particle size, drug encapsulation efficiency (EE%), and zeta potential of 0.457 ± 0.05, 196.33 ± 6.45 nm, 86.15 ± 0.58 %, and - 20.73 ± 0.98 mV, respectively. ATR release from the Atrosome gel followed the first-order kinetic model and showed no cytotoxicity in the in vitro cytotoxicity test. Cell viability (human foreskin fibroblast cell line) was nearly 99%. An excision wound model was also applied in male Wistar rats to examine the in vivo efficacy of the optimized formulation, followed by investigating malondialdehyde (MDA, an end-product of lipid peroxidation), superoxide dismutase (SOD, an endogenous antioxidant), hydroxyproline levels, and glutathione peroxidase (GPx) in skin tissue samples. MDA significantly decreased in the Atrosome gel group after 21 days, while GPx, SOD, and hydroxyproline levels demonstrated an increase. According to histological results, rats receiving Atrosomes were treated effectively faster when compared to the other formulation used.

Ninety-six-hour starved peripheral blood mononuclear cell supernatant inhibited LA7 breast cancer stem cells induced tumor via reduction in angiogenesis and alternations in Gch1 and Spr expressions.

Introduction: The microenvironment of solid tumors such as breast cancer is heterogeneous and complex, containing different types of cell, namely, cancer stem cells and immune cells. We previously reported the immunoregulatory behavior of the human immune cell in a solid tumor microenvironment-like culture under serum starvation stress for 96 h. Here, we examined the effect of this culture-derived solution on breast cancer development in rats. Method: Ninety-six-hour starved PBMCs supernatant (96 h-SPS) was collected after culturing human PBMCs for 96 h under serum starvation condition. Breast cancer stem cells, LA7 cell line, was used for in vitro study by analyzing gene expression status and performing cytotoxicity, proliferation, scratch wound healing assays, followed by in vivo tumor induction in three groups of mature female Sprague Dawley rats. Animals were treated with 96 h-SPS or RPMI and normal saline as control, n = 6 for each group. After biochemical analysis of iron, lactate, and pH levels in the dissected tumors, Ki67 antigen expression, angiogenesis, and necrosis evaluation were carried out. Metabolic-related gene expression was assessed using RT-qPCR. Moreover, 96 h-SPS composition was discovered by Nano-LC-ESI-MS/MS. Results: 96 h-SPS solution reduced the LA7 cell viability, proliferation, and migration and Gch1 and Spr genes expression in vitro (p< 0.05), whereas stemness gene Oct4 was upregulated (p< 0.01). The intracellular lactate was significantly decreased in the 96 h-SPS treated group (p = 0.007). In this group, Gch1 and Spr were significantly downregulated (p< 0.05), whereas the Sox2 and Oct4 expression was not changed significantly. The number of vessels and mitosis (Ki67+ cells) in the 96 h-SPS-treated group was significantly reduced (p = 0.024). The increased rate of necrosis in this group was statistically significant (p = 0.04). Last, proteomics analysis revealed candidate effectors' components of 96 h-SPS solution. Conclusion: 96 h-SPS solution may help to prevent cancer stem cell mediated tumor development. This phenomenon could be mediated through direct cytotoxic effects, inhibition of cell proliferation and migration in association with reduction in Gch1 and Spr genes expression, angiogenesis and mitosis rate, and necrosis augmentation. The preliminary data obtained from the present study need to be investigated on a larger scale and can be used as a pilot for further studies on the biology of cancer development.

Evaluation of Serum Pentraxin-3 Level in Patients with Acute Myocardial Infarction Compared with Control Group.

BACKGROUND & OBJECTIVE: The aim of this study was to measure serum pentraxin 3 (PTX3) in patients with acute myocardial infarction (MI) and compare it with the control group. METHODS: In this case-control study, 60 patients with MI (±ST-segment elevation) were included in the case group , and those with symptoms suspicious for coronary artery disease (CAD) and with no abnormal findings in angiography and troponin I level less than 99th percentile of normal population were included as a control group (N=30). Serum PTX3 and troponin I were measured. RESULTS: In this study, 60 patients including 34 men and 26 women were included in the case group (mean age: 61.4±8.86 years in non-ST-segment elevation myocardial infarction [NSTEMI] subgroup and mean age: 57.9±9.49 years in ST-segment elevation myocardial infarction [STEMI] subgroup), as well as 13 men and 17 women as the control group (mean age: 55.47±10.09 years). PTX3 level was higher in MI cases (1128.4±1205 pg/mL) compared to controls (394.5±170.40 pg/mL) (P=0.001). There was no relationship between ejection fraction (EF) and PTX3 level in the MI group. The area under the ROC curve (AUC) of PTX3 in MI was presented by 0.828 (AUC=0.828) (P>0.001). We defined three different cutoffs for PTX in this study, in which the cutoff ≥400 pg/mL had the highest sensitivity (92%), and the cutoff ≥700 pg/mL had the highest specificity (97%). CONCLUSION: According to the results of this study, PTX3 as an inflammatory marker showed higher level in patients with MI, especially in STEMI cases. Therefore, combined evaluation of troponin I and PTX3 levels would be associated with more accuracy in diagnosis of MI.

LINC02688 and PP7080 as novel biomarkers in early diagnosis of gastric cancer.

Despite considerable progress in gastric cancer screening, prevention, and treatment, it remains a major cause of morbidity and mortality worldwide. Due to late diagnosis of the disease, early potential diagnostic biomarkers are needed. Accumulating evidence indicates that non-coding RNAs have potential applications as diagnostic and prognostic biomarkers in gastric cancer. Herein, we investigated the expression levels of two novel non-coding RNAs, long intergenic non-protein coding RNA 2688 (LINC02688) and LOC25845 (PP7080) by real-time PCR for the first time in 47 gastric cancer patients. We found significant downregulation of LINC02688 and LOC25845 (PP7080) with 3.44 and 2.2-fold decrease, respectively in tumoral tissues in comparison with their adjacent non-tumoral counterparts (P < 0.0001). Our data also indicates that more than 96% and 88% of patients showed unchanged or decreased expression of LINC02688 and LOC25845 (PP7080), respectively. As most gastric cancer patients showed lower expression of these two lncRNAs, no significant association between clinicopathological features of the patients and the level of LINC02688 and LOC25845 (PP7080) expression could be detected. Furthermore, ROC curve analysis indicated that LINC02688 and PP7080 can serve as good predictive biomarkers for distinguishing tumoral tissues from their adjacent non-tumoral counterparts. Taken together, our findings suggested that these two novel tumor suppressor non-coding RNAs may act as novel diagnostic biomarkers for diagnosis of carcinogenesis event even at earlier stages of gastric adenocarcinoma.

RNA Sequencing of Early-Stage Gastric Adenocarcinoma Reveals Multiple Activated Pathways and Novel Long Non-Coding RNAs in Patient Tissue Samples.

BACKGROUND: Gastric cancer is among the most common cancers worldwide that currently lacks effective diagnostic biomarkers and therapeutic targets. Next-generation RNA sequencing is a powerful tool that allows rapid and accurate transcriptome-wide profiling to detect differentially expressed transcripts involved in normal biological and pathological processes. Given the function of this technique, it has the potential to identify new molecular targets for the early diagnosis of disease, particularly in gastric adenocarcinoma. METHODS: In this study, whole-transcriptome analysis was performed with RNA sequencing on tumoral and non-tumoral tissue samples from patients with early-stage gastric cancer. Gene ontology and pathway enrichment analysis were used to determine the main function of the specific genes and pathways present in tissue samples. RESULTS: Analysis of the differentially expressed genes revealed 5 upregulated and 234 downregulated genes in gastric cancer tissues. Pathway enrichment analysis revealed significantly dysregulated signalling pathways, including those involved in gastric acid secretion, drug metabolism and transporters, molecular toxicology, O-linked glycosylation of mucins, immunotoxicity, metabolism of xenobiotics by cytochrome P450, and glycosylation. We also found novel downregulated non-coding RNAs present in gastric cancer tissues, including GATA6 antisense RNA 1, antisense to LYZ, antisense P4HB, overlapping ACER2, long intergenic non-protein coding RNA 2688 (LINC02688) and uncharacterized LOC25845 (PP7080). CONCLUSION: The transcriptomic data found in this study illustrates the power of RNA-sequencing in discovering novel genes and tumorigenic pathways involved in human carcinogenesis. The anomalies present in these genes may serve as promising tools for the development of accurate diagnostic biomarkers for the detection of early-stage gastric cancer.

Two Rare Cases of Uterine Leiomyosarcomas Originating from Submucosal Leiomyomas Proved by Their Immunohistochemistry Profiles.

The most common mesenchymal tumours of the uterine corpus originate from smooth muscle cells. Leiomyomas are commonly found in women of child bearing age; however, leiomyosarcomas occur later in life (50-55 years of age). Most uterine leiomyosarcomas occur de novo, but rare cases of leiomyosarcomas that arise from leiomyomas have been reported. We present two cases of fertile women with submucosal leiomyomas that became malignant and discuss their pathologic features and immunohistochemistry studies for P16, P53 and Ki67.

Presence of JC Polyomavirus in Nonneoplastic Inflamed Colon Mucosa and Primary and Metastatic Colorectal Cancer.

BACKGROUND: Despite decades of epidemiologic and histopathologic investigations, the association between JC polyomavirus (JCPyV) infection and colorectal cancer (CRC) remains controversial. OBJECTIVE: This study tested the presence of JCPyV sequences and determined the viral load in a series of colorectal samples from Iranian patients. In total, 223 formalin-fixed paraffin-embedded samples from patients diagnosed with primary and metastatic CRC as well as with nonneoplastic inflamed colon mucosa were analyzed by quantitative real-time PCR for the presence of JCPyV large tumor antigen (LT-Ag) sequences. RESULTS: JCPyV LT-Ag sequences were detected in 18.6% of the CRC tissues and in 15.5% of the nonneoplastic control group. Viral LT-Ag was quantified in 18/100 primary colon adenocarcinomas, 2/10 metastatic adenocarcinomas, and 1/3 primary adenocarcinomas of the rectum. Two JCPyV-positive metastatic tumors presented a negative test result for JCPyV in the corresponding primary tumor. The median JCPyV LT-Ag copy number was 64 × 10-2 per cell and 14 × 10-2 per cell in the CRC cases and the nonneoplastic samples, respectively. There was no statistically significant difference between the two study groups regarding median LT-Ag DNA load (p = 0.059). Among the JCPyV-positive samples, the LT-Ag DNA load was higher in 2 metastatic tumors (from a patient with lung metastasis: 232 × 10-2 copies per cell; from a patient with liver metastasis: 121 × 10-2 copies per cell). CONCLUSIONS: The detection of JCPyV DNA at low copy numbers (lower than 1 viral copy per cell equivalent) and the absence of viral sequences in the corresponding primary tumors of the JCPyV-positive metastatic samples weaken the hypothesis of an etiological role of JCPyV in primary CRC induction.

The implication of mitochondrial dysfunction and mitochondrial oxidative damage in di (2-ethylhexyl) phthalate induced nephrotoxicity in both in vivo and in vitro models.

Di-(2-ethylhexyl) phthalate (DEHP) and its main metabolite, monoethylhexyl phthalic acid (MEHP), are a serious threat to human and animals' health in the current century. However, their exact mechanism to induce nephrotoxicity is not clear. In the current study, we addressed toxic effects of MEHP and DEHP on embryonic human kidney cells (HEK-293 cell line) and kidney tissue of rats, respectively. In the HEK-293, MTT assay and oxidative stress parameters were measured after treatment with different concentrations of MEHP. For in vivo study, rats were treated with different doses of DEHP (50, 100, 200, 400 mg/kg) via gavage administration for 45 days. The renal function biomarkers (BUN and creatinine) were determined in serum of rats. Mitochondrial toxic parameters including MTT, mitochondrial membrane potential (MMP), mitochondrial swelling, and also oxidative stress parameters were measured in isolated kidney mitochondria. Histopathological effects of DEHP were also evaluated in rats' kidneys. We demonstrated that MEHP induced oxidative stress and cytotoxicity in HEK-293 cells in a concentration dependent manner. The administration of DEHP led to histopathological changes in kidney tissue, which concurred with BUN and creatinine alternations in serum of rats. The results of present study showed a significant mitochondrial dysfunction and oxidative stress confirmed by enhancement of mitochondrial swelling, mitochondrial reactive oxygen species (ROS) and malondialdehyde (MDA), and reduction of MMP and mitochondrial glutathione (GSH). Taken together, this study showed that DEHP/MEHP resulted in mitochondrial dysfunction and oxidative damage, which suggest a vital role of mitochondria in DEHP/MEHP-induced nephrotoxicity.

Concurrent bilateral testicular tumors with different histopathology: A case report.

BACKGROUND: Bilateral synchronous testis germ cell tumors with different histopathology are not common. CASE PRESENTATION: Here, a case of 27-year-old male who is reported presented with bilateral testicular swellings. There was a high α-fetoprotein level with bilateral lesions on scrotal Ultrasonography. Bilateral orchiectomy was performed. According to pathology report, there was a right testicular seminoma and left testicular mixed germ cell tumor composed of seminoma, yolk sac tumor and embryonal carcinoma. CONCLUSION: He received one cycle of chemotherapy with BEP regimens.

A rare case of primary malignant fibrous histiocytoma: a sarcoma of the kidney.

BACKGROUND: Primary malignant fibrous histiocytoma of the kidney (MFH) is an extremely rare tumor which is indistinguishable from its' mimics in particular renal cell carcinoma (RCC) by clinical features and preoperative imaging evaluation. Due to its high predilection to local recurrence and distant metastases, early diagnosis has great value. CASE PRESENTATION: Herein, we describe a 62 year-old man with a 3-month history of abdominal discomfort and a palpable right loin mass whom computerized tomography (CT) showed a large heterogeneous solid mass in the right kidney. With the suspicious to RCC; the patient underwent radical nephrectomy. However, histopathological report revealed pleomorphic-storiform malignant fibrous histiocytoma. Immunohistochemistry study was also confirmed the diagnosis of MFH. Six month follow up showed no evidence of any recurrence. CONCLUSIONS: The therapeutic options for MFH differ from other renal tumors, hence histopathology and immunohistochemistry studies are required to establish a definite diagnosis of the disease. Despite of progress made in clinical studies and advances in diagnostic modalities, early diagnosis of MFH has not achieved yet. Further studies and accumulated experience with renal MFH are required to determine the approach to prolong survival in selected cases along with management and prognostic factors of such tumors.

Epigenetic alterations of CYLD promoter modulate its expression in gastric adenocarcinoma: A footprint of infections.

Gastric cancer (GC) is one of the most common causes of cancer-related death in the world, with multiple genetic and epigenetic alterations involved in disease development. CYLD tumor suppressor gene encodes a multifunctional deubiquitinase which negatively regulates various signaling pathways. Deregulation of this gene has been found in different types of cancer. This study aimed to evaluate for the first time the CpG island methylation pattern of CYLD gene promoter, and its expression level in gastric adenocarcinoma. CYLD messenger RNA expression and promoter methylation in 53 tumoral and their non-neoplastic counterpart tissues were assessed using quantitative polymerase chain reaction and bisulfite sequencing. Also, we investigated the impacts of the infectious agents including Helicobacter pylori (H. pylori), EBV, and CMV on CYLD expression and promoter methylation in GC. Results showed that the expression level of CYLD was downregulated in GC, and was significantly associated with gender (female), patient's age (<60), high grade, and no lymph-node metastasis (p = 0.001, 0.002, 0.03, and 0.003, respectively). Among the 31 analyzed CpG sites located in about 600 bp region within the promoter, two CpG sites were hypermethylated in GC tissues. We also found a significant inverse association between DNA promoter methylation and CYLD expression (p = 0.02). Furthermore, a direct association between H. pylori, EBV, and CMV infections with hypermethylation and reduced CYLD expression was observed (p = 0.04, 0.03, and 0.03, respectively). Our findings indicate that CYLD is downregulated in GC. Infectious agents may influence CYLD expression.