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جستجوی مقالات مرتبط با کلیدواژه « epstein–barr virus » در نشریات گروه « پزشکی »

  • Mohsen Danaeifar*
    Introduction

    MicroRNAs play important roles in regulating gene expression in animals and plants. Many studies used these genetic elements to up- or down-regulate human gene expression. It has been shown that viral miRNAs can target and regulate not only viral genes but also host genes. To date, 48 miRNAs have been identified in Epstein-Barr virus (human gamma-herpesvirus 4). This virus can invade and reside in many human tissues such as epithelial or immune system cells. In this study, we evaluated a novel method of finding miRNAs in the Epstein-Barr virus (EBV).

    Materials and Methods

    The entire genome content of human gamma-herpesvirus 4 (EBV) was searched using ab initio prediction algorithm by miRNAFold. Selected sequences screened by homology algorithm of miRBase web server.

    Results

    Among the identified 12 sequences, two putative miRNAs were selected and their properties were further investigated. The main human gene target of the putative miRNA-1 was BCL11A gene that is related to the B-cell lymphoma, and that of putative miRNA-2 was ZBTB18 gene which is mainly related to the mental retardation.
    Previous studies used known EBV miRNAs incorporated in delivering vectors such as lentiviral vectors to target various human genes. The introduced two miRNAs can target genes in some malignancies and other types of disorders.

    Conclusion

    Because of the high stability of the proposed putative miRNAs, they can be used experimentally to regulate human genes.

    Keywords: Epstein - barr virus, Hairpins, miRNA, RNA folding}
  • Maryam Abolhasani, Ata Ollah Mohseni, Ramin Shakeri, Ali Khavanin, Mehrdad Khajehei, Abbasali Omidi, Bita Geramizadeh, Ensieh Shafigh, Farshad Naghshvar, Payam Fathizadeh, Leyla Taghizadehgan, Atoosa Gharib, Margaret L. Gulley, Sanford M. Dawsey, Reza Malekzadeh, Charles S. Rabkin *, Mohammad Vasei
    Background

     Gastric cancer is the fourth leading cause of cancer-related deaths in the world. The identification of gastric cancer subtypes related to recognizable microbial agents may play a pivotal role in the targeted prevention and treatment of this cancer. The current study is conducted to define the frequency of Epstein-Barr virus (EBV) infection in gastric cancers of four major provinces, with different incidence rates of gastric cancers, in Iran.

    Methods

     Paraffin blocks of 682 cases of various types of gastric cancer from Tehran, South and North areas of Iran were collected. Twelve tissue microarray (TMA) blocks were constructed from these blocks. Localization of EBV in tumors was assessed by in situ hybridization (ISH) for EBV-encoded RNA (EBER). Chi-squared test was used to evaluate the statistical significance between EBV-associated gastric cancer (EBVaGC) and clinicopathologic tumor characteristics.

    Results

     Fourteen out of 682 cases (2.1%) of gastric adenocarcinoma were EBER-positive. EBER was positive in 8 out of 22 (36.4%) of medullary carcinomas and 6 out of 660 (0.9%) of non-medullary type, which was a statistically significant difference (P<0.001). The EBVaGCs were more frequent in younger age (P=0.009) and also showed a trend toward the lower stage of the tumor (P=0.075).

    Conclusion

     EBV-associated gastric adenocarcinoma has a low prevalence in Iran. This finding can be due to epidemiologic differences in risk factors and exposures, and the low number of gastric medullary carcinomas in the population. It may also be related to gastric tumor heterogeneity not detected with the TMA technique.

    Keywords: Gastric Cancer, Epstein-Barr Virus, Iran, Tissue Microarray}
  • امیرحسین علی پور، حمیده نجفی، زهرا ضیافتی کافی، سید محمد علی هاشمی، جمال سروری، آرش قلیانچی لنگرودی*
    زمینه و اهداف

      عفونت با ویروس اپشتین بار یکی از مهم ترین عوامل خطر مرتبط با گلیوبلاستوما است. در بطن این رابطه پیچیده، پروتئین آنتی ژن-1 هسته ای ویروس اپشتین بار (EBNA1) قرار دارد، یک پروتئین مهم با توانایی قابل توجه برای تنظیم بیان ژن های سلولی و ویروسی. این تحقیق به بررسی تاثیر EBNA1 بر الگوهای بیان چهار ژن سلولی - MDMX، MDM2، MYC و BIRC5 در رده سلولی U87MG می پردازد.

    مواد و روش کار

      سلول های U87MG را به دو گروه مجزا تقسیم شدند. گروه اول شامل سلول هایی بود که با پلاسمید حاوی ژن EBNA1 ترانسفکت شده بودند، در حالی که گروه دوم شامل سلول هایی بود که با پلاسمید کنترل ترانسفکت شده بودند. برای ارزیابی فعالیت رونویسی ژن های MDMX، MDM2، MYC و BIRC5 در هر دو مجموعه سلول، از تکنیک Real-time PCR استفاده کردیم. هر گونه تفاوت مشاهده شده از نظر آماری معنی دار در نظر گرفته شد در صورتی که مقادیر p-value کمتر از 0.05 باشد.

    یافته ها

      یافته های ما افزایش سه برابری قابل توجهی را در بیان ژن MDMX هنگامی که سلول های U87MG با پلاسمید EBNA1 ترانسفکت شدند نشان داد (02/0=p). اگرچه سلول های ترانسفکت شده با پلاسمید EBNA1 به ترتیب افزایش دو، سه برابر و پنج برابری در سطوح بیان ژن های MDM2، MYC و BIRC5 را نشان دادند، اما این تغییرات از نظر آماری معنی دار نبودند.

    نتیجه گیری

      نتایج این تحقیق نشان داد که EBNA1 توانایی تحریک بیان چهار ژن سلولی حیاتی در سلول های آستروسیتومای گلیوبلاستوما را دارد. این امر بر تاثیر بالقوه EBNA1 بر پیشرفت گلیوبلاستوما، به ویژه در افرادی که آلوده به ویروس اپشتین بار هستند تاکید می کند.

    کلید واژگان: گلیوبلاستوما, ویروس اپشتین بار, EBNA1, MDMX, MDM2, MYC, BIRC5}
    Amir Hossein Alipour, Hamideh Najafi, Zahra Ziafati Kafi, Seyed Mohammad Ali Hashemi, Jamal Sarvari, Arash Ghalyanchi Langeroudi*
    Background and Aim

     Infection with Epstein-Barr virus (EBV) ranks as one of the most substantial risk factors associated with Glioblastoma multiforme (GBM). At the core of this intricate relationship lies the EBV nuclear antigen-1 (EBNA1) protein, a central figure with a remarkable ability to regulate the expression of both cellular and viral genes. This research delves into the impact of EBNA1 on the expression patterns of four cellular genes - MDMX, MDM2, MYC, and BIRC5 in the U87MG cell line.

    Materials and Methods

     We divided U87MG cells into two distinct groups. The first group involved cells that were transfected with a plasmid containing the EBNA1 gene, while the second group consisted of cells that were transfected with a control plasmid. To evaluate the transcriptional activity of MDMX, MDM2, MYC, and BIRC5 genes in both sets of cells, we employed a real-time PCR technique. Any observed differences were considered statistically significant if the associated P-values were less than 0.05.

    Results

     Our findings demonstrated a substantial three-fold increase in the expression of the MDMX gene when U87MG cells were transfected with EBNA1 plasmid (P=0.02). Although the cells transfected with EBNA1 plasmid displayed great elevations in the expression levels of MDM2, MYC, and BIRC5 genes, these alterations were not statistically significant.

    Conclusion

     The outcomes of this investigation have unveiled that EBNA1 has the ability to trigger the expression of four crucial cellular genes, which wield substantial influence in the genesis of GBM within glioblastoma astrocytoma cells. This underscores the potential impact of EBNA1 on the evolution of GBM, particularly in individuals harboring EBV.

    Keywords: BIRC5, EBNA1, Epstein–Barr virus, Glioblastoma, MDMX, MDM2, MYC}
  • احمد تفقد، سمانه سجادی، محمدحسین طاهری نژاد، حسن مهراد مجد، سحر روانشاد*
    مقدمه

    سرطان پستان، یکی از شایع ترین سرطان ها در جهان است که در دهه اخیر افزایش چشم گیری در میزان بروز آن رخ داده است. اگرچه عوامل خطر و علل سرطان پستان به طور کامل شناخته نشده است، اما مطالعاتی در مورد ارتباط بین سرطان پستان و عوامل ویروسی از جمله ویروس اپشتین- بار (EBV) گزارش شده است، لذا مطالعه حاضر با هدف بررسی ارتباط بین EBV و سرطان پستان انجام شد.

    روش کار

    در این مطالعه مقطعی که بر روی نمونه های پاتولوژی بافت پستان بین سال های 1401-1396 در بیمارستان های مشهد صورت گرفت، 30 نمونه پارافینه از بیماران مبتلا به سرطان پستان و 33 نمونه پارافینه به عنوان گروه کنترل از بیماری های خوش خیم پستان جمع آوری شد. بعد از فرآیندهای استخراج DNA، بررسی از نظر ویروس EBV با روش واکنش زنجیره ای پلیمراز (PCR) انجام گرفت. تجزیه و تحلیل داده ها با استفاده از نرم افزار آماری SPSS (نسخه 20) و آزمون های کای دو، دقیق فیشر و تی تست انجام شد. میزانp  کمتر از 05/0 معنی دار در نظر گرفته شد.

    یافته ها

    بر اساس نتایج به دست آمده، از PCR 63 نمونه بیوپسی بافتی انجام شده، هیچ یک از نمونه های گروه بدخیم و کنترل از نظر EBV مثبت نبودند.

    نتیجه گیری

    حضور ژن ویروس EBV در یک گروه قابل توجه از زنان مبتلا به سرطان پستان در شهر مشهد تایید نشد. با این حال مطالعات بیشتر با حجم نمونه بزرگ تر برای اعتبارسنجی نتایج ضرورت دارد.

    کلید واژگان: سرطان پستان, واکنش زنجیره ای پلیمراز, ویروس ابشتین بار}
    Ahmad Tafaghod, Samaneh Sajjadi, Mohammadhossein Taherynejad, Hassan Mehrad- Majd, Sahar Ravanshad *
    Introduction

    Breast cancer is one of the most common cancers in the world that its incidence rate has increased over the last decade. Although the causes and risk factors of breast cancer are not fully known, studies have been reported on the relationship between breast cancer and viral agents, including the Epstein-Barr virus (EBV). Therefore, the present study was performed with aim to explore the correlation between EBV and breast cancer.

    Methods

    In this cross-sectional study which was conducted using breast tissue pathology samples collected from Mashhad hospitals between 2017 and 2022, 30 paraffin tissue samples from breast cancer patients and 33 paraffin tissue samples as a control group from benign breast diseases were collected. After the DNA extraction processes, the EBV virus was tested by polymerase chain reaction (PCR). Data analysis was done using SPSS software (version 20) and Chi-square, Fisher's exact and t-test. P<0.05 was considered statistically significant.

    Results

    According to the PCR results of 63 tissue biopsy samples, none of the malignant and control group samples were EBV-positive.

    Conclusion

    The presence of the EBV virus gene was not confirmed in a group of women with breast cancer in Mashhad. However, further studies with a larger sample size are needed to validate the results.

    Keywords: Breast Cancer, Epstein-Barr virus, Polymerase chain reaction}
  • پریسا حسن زاده، مهناز محمدی*، صبا طاهری
    مقدمه

    افرادی که سیستم ایمنی ضعیفی دارند سریع تر به عفونت های فرصت طلب (OIs) مبتلا  می شوند. یافتن ارتباط ویروس ها و مسیر های سیگنالی مرتبط با عفونت های این ویروس ها مثل اپشتین بار ویروس (EBV) و سایتو مگالو ویروس (CMV) نقش قابل ملاحظه ای در بررسی ارتباط آن ها با سلول های لنفوسیت T کمکی دارند. در این مطالعه با استفاده از آنالیز بیوانفورماتیک به بررسی و کاندید نمودن ژن های موجود در مسیرهای وابسته به عفونت ویروس های فرصت طلب با سلول های لنفوسیت  T کمکی پرداخته شد.

    روش

    در این مطالعه با مراجعه به پایگاه داده GEO دیتاست مناسب برای آنالیز انتخاب گردید. این دیتاست شامل پروفایل بیان ژنی در عفونت ویروس های EBV و  CMVبود. کلاسترهای ژنی با بیان بالا و پایین دسته بندی شدند. برای ارزیابی دقیق تر داده از پایگاه های داده غنی همچون Enrichr، STRING و Networkanalyst استفاده شد. در نهایت ژن های کاندید شده جدا و ارتباط پروتیینی آن ها نیز سنجیده شد.

    نتایج

    964 ژن با بیان بالا و 837 ژن با بیان پایین در مسیرهای پیشرفت عفونت ویروسی های فرصت طلب با لنفوسیت ها نقش دارند. مسیر های چرخه سلولی، استرس اکسیداتیو، سنتز RNA و TGFB به صورت بارزی مشاهده شدند.

    نتیجه گیری

    مطالعه حاضر نشان داد که پروتیین ها و ژن های مهمی در تقویت التهاب ویروس های فرصت طلب همچون اپشتین بار و سایتومگالو ویروس نقش عمده ای داشته که از میان آن ها CDK2, CCNB1, GSK3B, SRC و SMAD3 نقش بارزتری را نشان دادند.

    کلید واژگان: اپشتین بار ویروس, پروفایل بیان ژن, آنالیز بیوانفورماتیک, سایتو مگالو ویروس, ویروس های فرصت طلب}
    Parisa Hassanzadeh, Mahnaz Mohammadi*, Saba Taheri
    Introduction

    People with weakened immune system are more prone to opportunistic infections (OIs). Finding the association of these viruses and the transmission pathways associated with these viruses, such as EBV and CMV, play a significant role in investigating their association with helper T lymphocytes. In this study, bioinformatics analysis was used to examine and candidate genes in pathways associated with opportunistic viruses with helper T lymphocytes.

    Method

    In this study, by referring to the GEO database, a suitable database was selected for analysis. This dataset included gene expression profiles in EBV and CMV virus infections. Gene clusters were classified into high and low expression. Rich databases such as Enrichr, STRING, and Networkanalyst were used to evaluate the data more accurately. Finally, the candidate genes were isolated and their protein binding was measured.

    Results

    964 high-expression genes and 837 low-expression genes are involved in the progression of opportunistic viral infections with lymphocytes. Cell cycle pathways, oxidative stress, RNA synthesis and TGFB were significantly observed.

    Conclusion

    The present study showed that important proteins and genes played a major role in enhancing the inflammation of opportunistic viruses such as Epstein-Barr and Cytomegalovirus, among which CDK2, CCNB1, GSK3B, SRC, and SMAD3 showed a more prominent role in this pathway.

    Keywords: Epstein Barr Virus, Gene Expression Profile, Bioinformatics Analysis, Cytomegalovirus, Opportunistic Viruses}
  • Shokouh Yasaie, Atousa Ferdousi, Seyed Dawood Mousavi Nasab, Hooman Kaghazian, Saeed Shams*
    Background

    Gastroenteritis is the second leading cause of death worldwide, with a high prevalence in children. Among pathogenic microorganisms, viruses are one of the main causes of this disease. Thus, the aim of this research was to investigate the prevalence of diarrhea caused by human adenovirus (HAdV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in children with hematological diseases for the first time in Iran.

    Materials & Methods

    This study was conducted on 120 stool samples stored in the clinical sample bank of the Cellular and Molecular Research Center of Qom University of Medical Sciences. These samples were obtained from immunocompromised children with gastrointestinal symptoms, who referred to one of the children's hospitals in Qom during 2018 to 2019. Genomes were extracted from the stool samples and evaluated using the polymerase chain reaction (PCR) method.

    Findings

    The prevalence of HAdV and EBV was reported in seven (5.8%) and one (0.8%) cases, respectively, and CMV was detected in none of the samples. No cases of co-infection were observed.

    Conclusion

    This study results show that there are diarrhea-causing viruses among patients in the study area. Fortunately, the prevalence of these infectious agents in patients with underlying conditions was relatively low. However, monitoring of these viruses in the feces of all patients, especially immunocompromised patients, is recommended.

    Keywords: Adenoviruses, Epstein-Barr Virus, Cytomegalovirus, Hematologic Diseases, Polymerase Chain Reaction, Children}
  • Tayebeh Latifi, Majid Teymoori-Rad, Ahmad Nejati, Shohreh Shahmahmoodi, Farhad Rezaei, Sayed Mahdi Marashi*
    Background

    HERV-K env is associated with several neurological disorders, including MS. Clinical studies have demonstrated a plausible interaction between HERV-K env and other MS risk factors. The present study aimed to investigate the possible association between HERV-K18 env and TGF-β. We further assessed the in vitro effect of EBV infection on HERV-K18 env expression in the presence and absence of vitamin D in MS patients.

    Methods

    PBMCs from 20 MS patients and 20 healthy controls were infected with the B95.8 EBV, seeded into 24-well plates and incubated in the presence or absence of 100 nM of 1,25(OH)D3. The expression levels of HERV-K18 env and TGF-β were measured using real-time PCR.

    Results

    While the expression level of HERV-K18 env was significantly higher in MS patients than the healthy controls, this trend for TGF-β was significantly reverse. Interestingly, an inverse correlation was found between HERV-K18 env and TGF-β expression in MS patients, although the in vitro stimulation of PBMCs with EBV and vitamin D showed no significant differences in terms of HERV-K18 expression.

    Conclusion

    Our findings highlight the potential role of HERV-K18 env in MS patients.

    Keywords: Multiple Sclerosis, HERV-K18, Transforming growth factor beta, Epstein–Barr virus, Vitamin D}
  • Miao Zhu, Jun Zhang, Qingqing Shi, Xing Sun, Haibo Wang, Mei Sun, Yanqing Liu *

    Hemophagocytic lymphohistiocytosis (HLH) is a fatal clinical syndrome. The most common cause of secondary HLH is Epstein-Barr virus (EBV) infection. EBV-HLH is a common clinical disease with high mortality, easy relapse, and poor prognosis. Therefore, treating EBV-HLH with T and B lymphocyte involvement is challenging, and selecting an appropriate treatment regimen is critical. Moreover, research on how to evaluate the recurrence index after remission is scarce. In this study, we reported a case of EBV-HLH successfully treated with programmed cell death protein-1 (PD-1) inhibitor in combination with rituximab. The regimen had a good curative effect, and we successfully detected the trend of early recurrence. Our findings indicated that PD-1 inhibitor in combination with rituximab may help to treat EBV-HLH and maintain EBV-infected T and B whole-line lymphocytes.

    Keywords: CD20 Monoclonal Antibody, Epstein-Barr virus, Hemophagocytic lymphohistiocytosis, Programmed Cell Death Protein-1, Salvage Therapy}
  • AmirHossein Alipour, Seyed MohammadAli Hashemi, Afagh Moattari, Ali Farhadi, Jamal Sarvari*

    Epstein-Barr virus (EBV) represents one of the most important viral carcinogens. EBV nuclear antigen-1 (EBNA1) can induce the expression of different cellular and viral genes. In this study, we evaluated the EBNA1 effects on the expression patterns of human papillomavirus type 18 (HPV-18) E6 and E7 oncogenes and three cellular genes, including BIRC5, c-MYC, and STMN1, in a cervical adenocarcinoma cell line. HeLa cells were divided into three groups: one transfected with a plasmid containing the EBNA1 gene, one transfected with a control plasmid, and one without transfection. In all three groups, the expression levels of E6, E7, BIRC5, c-MYC, and STMN1 genes were checked using real-time PCR. Pathological staining was used to examine changes in cell morphology. Real-time PCR results showed that the expression level of HPV-18 E6 (P=0.02) and E7 (P=0.02) oncogenes significantly increased in HeLa cells transfected with the EBNA1 plasmid compared to cells transfected with control plasmid. Also, the presence of EBNA1 induced the expression of BIRC5 and c-MYC, which increased tenfold (P=0.03) and threefold (P=0.02), respectively. Regarding the STMN1 cellular gene, although the expression level in HeLa cells transfected with EBNA1 plasmid showed a twofold increase, this change was insignificant (P=0.11). Also, EBNA1 expression caused the creation of large HeLa cells with abundant cytoplasm and numerous nuclei. The EBV-EBNA1 could increase the expression levels of HPV-18 E6 and E7 viral oncogenes as well as c-MYC and BIRC5 cellular genes in the HeLa cell line. These findings indicate that the simultaneous infection of cervical cells with HPV-18 and EBV might accelerate the progression of cervical cancer.

    Keywords: Cervical carcinoma, human Papillomavirus, Epstein–Barr Virus, EBNA1}
  • Mahboobeh Cheragh, Majid Sadeghizadeh, Mohammad Hasan Pouriayevali, Masoud Parsania *
    Objective(s)
    Targeting the lytic cycle of the Epstein-Barr virus (EBV) has been considered a new treatment strategy for malignancies caused by this virus.  This study aimed to investigate the effect of Dendrosomal NanoCurcumin (DNC) to prevent cell transformation and inhibit the expression of viral lytic gene expression in the generation of lymphoblastoid cell line (LCL).
    Materials and Methods
    Cell viability of LCLs and PBMCs was performed by MTT assay, and flow cytometry (Annexin/PI) was used for evaluation of apoptosis. CD markers on the surface of generated LCL (CD19) cells were examined for cell validation. The effect of DNC on transformation was evaluated by examining cell morphology and determining the expression level of lytic genes BZLF1, Zta, BHRF1, and BRLF1 of EBV using Real-time PCR. Student’s t-test was used for statistical analysis.
    Results
    The MTT assay showed that DNC can inhibit the proliferation of LCL in a dose-dependent manner. The 50% cytotoxic concentration (CC50) of DNC and curcumin for LCL was determined 38.8 µg/ml and 75 µg/ml, respectively after 72 hr. Also, Real-time PCR data analysis showed that DNC in 30 µg/ml concentration significantly inhibited cell transformation in the LCL and significantly reduced viral lytic genes such as BZLF1, Zta, BHRF1, and BRLF1expression compared to control.
    Conclusion
    Overall, these findings show that DNC reduces the expression of the viral lytic cycle genes and also the induction of cell apoptosis and finally prevents the generation of LCL.
    Keywords: Cell transformation, Curcumin, Epstein-Barr virus, Lymphoma, Viral genes}
  • Javad Hosseni Nejad, Seyed Mohammad Javad Hosseini, Leila Darabi, Mohamad Javad Soltanpour, Fakhri Alahyari *

    Usual neurological complications of Epstein-Barr virus infection are aseptic meningitis, encephalitis, transverse Usual neurological complications of Epstein-Barr virus infection are aseptic meningitis, encephalitis, transverse myelitis, cerebellitis, Guillain-Barre syndrome, and cranial or peripheral neuritis most commonly in immunocompromised patients. These clinical manifestations may occur alone or accompanied by infectious mononucleosis. Usually, EBV encephalitis occurs infrequently and with non-specific symptoms. Herein, we report two patients: a 24-year-old female with generalized tonic-clonic fever and seizures for ten days. The other was a 28-year-old male with repeated fever, headache, 4-day amnesia, and symptoms of meningeal irritation. Since the physical examination results were not very helpful, the definite diagnosis was achieved by sampling, analysis, and polymerase chain reaction for the cerebrospinal fluid. Our patients had a direct EBV invasion of the CNS and were affected by Epstein-Barr virus encephalitis, confirmed by their clinical test results as a positive polymerase chain reaction of cerebrospinal fluid. The PCR results were negative for a panel of microorganisms that cause bacterial meningitis in the CSF, but positive for EBV. Image findings also did not show any significant results. Patients treated with acyclovir and precision control at the relative center with favorable outcomes. Acyclovir possibly will lessen viral replication. Finally, despite obtaining negative test results of EBV infection, every therapeutic effort should be undertaken and maintained continuous attention.

    Keywords: Meningoencephalitis, Meningitis, Epstein-Barr Virus, Meningeal Irritation, Infection, Antiviral agents}
  • Fatemeh Hoseini Tabatabaie, Seyed Younes Hosseini, Seyed MohammadAli Hashemi, Akbar Safaie, Jamal Sarvari *
    Background & Objective

    Epstein-Barr virus nuclear antigen-1 (EBNA1) is one of the most important proteins of Epstein-Barr virus (EBV) that might be mutated in various related cancers. The purpose of this study was to compare EBNA1 mutations in the C-terminal region between patients with cervical and ovarian cancer and healthy individuals.

    Methods

    As test and control groups, 18 EBV-positive paraffin-embedded samples of cervical and ovarian cancer and 10 age- and gender-matched healthy volunteers who did not have cancer but were EBV-positive were both used. Utilizing a commercial DNA extraction kit, total DNA was extracted following deparaffinization. The entire C-terminal region of the EBNA1 sequence was amplified using an in-house nested PCR. Phylogenetic analysis and Sanger sequencing were used to analyze the sequences using MEGA 7 software and through NJ method.

    Results

    Sequence analysis revealed that the P-Ala subtype of EBNA1 was present in all samples. In two and one samples, respectively, of cervical cancer patients, the mutations A1887G and G1891A were found. The G1595T mutation was also detected in four sequences taken from ovarian cancer patients. No statistically significant difference could be found between the frequency of mutations in patients and controls (P>0.05). No known amino acid substitutions were found in the USP7-binding region and the DBD/DD domain.

    Conclusion

    The findings showed that P-Ala is the predominant EBV subtype across all samples. Additionally, as the sequence of EBNA1's C-terminal region is so stable, it's possible that it had little impact on the pathogenesis of ovarian and cervical malignancies. It is advised to conduct additional research to verify these findings.

    Keywords: cervical cancer, EBNA1, Epstein-Barr virus, Mutation, Ovarian Cancer}
  • Seyed MohammadAli Hashemi, Abdolvahab Moradi, Seyed Younes Hosseini, Hadi Razavi Nikoo, Taravat Bamdad, Mahboobeh Razmkhah, Jamal Sarvari*, Alijan Tabarraei*
    Background

    Suppression of p53 is an important mechanism in Epstein-Barr virus associate-tumors and described as EBNA1-USP7 which is a key axis in p53 suppression. Thus, in this study, we aimed to evaluate the function of EBNA1 on the expression of p53-inhibiting genes including HDAC-1, MDM2, MDM4, Sirt-3, and PSMD10 and the influence of USP7 inhibition using GNE-6776 on p53 at protein/mRNA level.

    Methods

      The electroporation method was used to transfect the BL28 cell line with EBNA1. Cells with stable EBNA1 expression were selected by Hygromycin B treatment. The expression of seven genes, including PSMD10, HDAC-1, USP7, MDM2, P53, Sirt-3, and MDM4, was evaluated using a real-time PCR assay. For evaluating the effects of USP7 inhibition, the cells were treated with GNE-6776; after 24 hours and 4 days, the cells were collected and again expression of interest genes was evaluated.

    Results

    MDM2 (P=0.028), MDM4 (P=0.028), USP7 (P=0.028), and HDAC1 (P=0.015) all showed significantly higher expression in EBNA1-harboring cells compared to control plasmid transfected cells, while p53 mRNA expression was only marginally downregulated in EBNA1 harboring cells (P=0.685). Four-day after treatment, none of the studied genes was significantly changed. Also, in the first 24-hour after treatment, mRNA expression of p53 was downregulated (P=0.685), but after 4 days it was upregulated (P=0.7) insignificantly.

    Conclusions

    It seems that EBNA1 could strongly upregulate p53-inhibiting genes including HDAC1, MDM2, MDM4, and USP7. Moreover, it appears that the effects of USP7 suppression on p53 at protein/mRNA level depend on the cell nature; however, further research is needed.

    Keywords: Epstein-Barr virus, EBNA1, P53, USP7, P53-inhibiting Genes}
  • Mahboobeh Cheragh, Majid Sadeghizadeh, MohammadHassan Pouriayevali, Masoud Parsania*
    Background

    During research on lymphoma and its malignancies, scientists have traced the role of the angiogenesis index in patient survival. Epstein-Barr virus (EBV) is a human tumor-causing virus that targets B lymphocytes and causes persistent infection. This virus is also associated with malignancies, such as Burkitt's lymphoma. Using herbal medicines to treat cancer and angiogenesis has been considered, due to the side effects of chemical drugs. This experimentation aimed to research the antiviral impact of nano-curcumin on the Daudi cell line (which belongs to Burkitt's lymphoma) and to evaluate the expression of the vascular endothelial growth factor (VEGF) gene.

    Materials and Methods

    The cytotoxicity of nano curcumin, curcumin, and dendrosome on Daudi cells and normal human lymphocytes was evaluated using an MTT assay. Cellular apoptosis was assessed by Annexin / PI flow cytometry. The VEGF angiogenesis gene expression was performed by real-time PCR.

    Results

    The 50% cytotoxic concentration (CC50) was determined 30 μg/ml for dendrosomal nano-curcumin, 50 μg/ml for curcumin, and 987 μg/ml for dendrosome in the Daudi cell line.Dendrosomal nano curcumin (DNC) caused time and dose-dependent death in Daudi cancer cells compared to curcumin. Dendrosome did not show toxicity on control cells. The results of Flow cytometry are constant with the results of the MTT test. The data obtained from the real-time PCR showed a significant decrease in the expression of the VEGF gene (P <0.01).

    Conclusion

    The dendrosomal nano curcumin is involved in angiogenesis by reducing the expression of the VEGF gene, and can be a good candidate as a supplement drug in the chemotherapy treatment of Burkitt's lymphoma.

    Keywords: Dendrosomal nano curcumin, Epstein-Barr virus, Daudi cell line, Anti-angiogenesis}
  • Arjola Agolli*, Angela Ishak, Mahima Viswanathan, Edzel Lorraine, Jeevan Shivakumar, Olsi Agolli
    Background

    The prevalence of breast cancer has increased and has currently become one of the most common cancers. Although the majority of the world’s population is infected with Epstein Barr Virus (EBV) during their lives, the severity of symptoms varies and not everyone infected with EBV is diagnosed with cancer. EBV might increase the risk for breast cancer either by activating the HER2/HER3 signaling cascades or by creating a state of prolonged immune stimulation.

    Materials and Methods

    A systematic search of several electronic databases including PubMed, ScienceDirect, Cochrane, EBSCOhost, JSTOR, and Scopus, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. The primary outcome of this review was to assess the prevalence of people with breast cancer that had a prior EBV infection.

    Results

    For this review, 24 case-control studies were accepted. Our analyses included 1.989 breast cancer cases versus 1.034 control cases. EBV was found to be present in 27.9% of breast cancer cases versus 8.02% found in the normal breast tissue of controls. All affected people were women with a mean age was 48.19 years. The most common type of breast cancer found in EBV-infected tissues was invasive breast cancer. Cases were reported sporadically in a wide geographical distribution, and the prevalence varied from 4.6% - 64.1%.

    Conclusions

    A previous EBV infection might be associated with a higher risk for breast malignancy. The most common type is invasive cancer. It mainly affects women and geographical variances are observed. More studies are necessary to elucidate the role of EBV in the mechanisms of breast cancer. Also, it is crucial to improve the prevention and treatment strategies.

    Keywords: Epstein - Barr virus (EBV), Systematic review, Breast carcinoma, Breast cancer, Epstein–Barr virus}
  • پریا احمدی صید محمدی، زهره شریفی، آرزو اودی، سعیده میلانی *
    سابقه و هدف

    آلوایمیونیزاسیون به علت مواجهه لنفوسیت‌های B با آنتی‌ژن بیگانه به دنبال تزریق خون ناسازگار ایجاد می‌شود. یکی از راه‌های شناسایی آنتی‌ژن‌های گروه‌های خونی، استفاده از آنتی‌بادی‌های مونوکلونال می‌باشد. هدف از مطالعه حاضر، ترانسفورماسیون سلول‌های آلوایمن شده ضد آنتی‌ژن Kell در افراد تالاسمی به کمک ویروس اپشتاین بار و تولید سلول‌های لنفوبلاستوئید تولیدکننده آنتی بادی ضد Kell می‌باشد.

    مواد و روش‌ها

    در یک مطالعه تجربی، سلول‌های تک هسته‌ای خون محیطی(PBMC) از 10بیمار تالاسمی ایمن شده علیه آنتی‌ژن KELL به روش گرادیان غلظتی فایکول جدا و با سوپ ویروسی اپشتاین بار به دست آمده از محیط کشت خط سلولی B95-8 به مدت 4 ساعت مواجه شد. پس از گذشت یک تا سه هفته، تولید کلون‌های لنفوبلاستوئیدی تولیدکننده آنتی‌بادی و اختصاصیت آنتی‌بادی تولیدی به ترتیب با مشاهده میکروسکوپی، الایزا و روش میکرو هماگلوتیناسیون بررسی شد.

    یافته‌ها

    نتایج به دست آمده نشان داد که مواجهه سلول‌های PBMC بیماران تالاسمی ایمن شده علیه آنتی‌ژن KELL با سوپ ویروسی EBV سبب ایجاد کلون‌های لنفوبلاستوئیدی می‌گردد. بررسی سوپ سلولی کلون‌های تولیدی نشان داد که آنتی بادی تولیدی توسط این سلول‌ها قادر به شناسایی گلبول‌های قرمز حاوی آنتی‌ژن KELL و آگلوتیناسیون آن‌ها با آزمایش میکروهماگلوتیناسیون می‌باشد.

    نتیجه گیری

    براساس یافته‌های به دست آمده ترانسفورماسیون PBMC بیماران تالاسمی ایمن شده علیه آنتی‌ژن KELL باعث ایجاد سلول‌های لنفوبلاستوئیدی تولیدکننده آنتی‌بادی ضد این آنتی‌ژن می‌گردد.

    کلید واژگان: آلوایمیونیزاسیون, ویروس اپشتاین بار, لنفوسیت های B}
    P. Ahmadi Sead Mohammadi, Z. Sharifi, A. Oodi, S. Milani *
    Background and Objectives

    Alloimmunization is caused by exposure of B lymphocytes to foreign antigens following incompatible blood transfusions and is associated with many hemolytic complications. One of the ways to detect blood group antigens is monoclonal antibodies. The aim of the present study is transforming of alloimmunized cells against KELL antigen in thalassemia patients by EBV-Transformation method and to produce lymphoblastoid cell line producing anti-KELL antibody.

    Materials and Methods

    In an experimental study, peripheral blood mononuclear cells (PBMCs) of 10 thalassemia patients immunized against KELL antigen were isolated by ficoll hypaque method and exposed to EBV-containing supernatant of B95-8 cell line for 4 hours. After one to three weeks, the production of antibody-producing lymphoblastoid clones and the specificity of the antibody were examined by microscopic observation and microhemagglutination method, respectively.

    Results

    The results showed that exposure of PBMCs of thalassemia patients immunized against KELL antigen with EBV viral soup caused the formation of lymphoblastoid clones. Examination of the supernatant of culture of produced clones showed that the antibody produced by these cells were able to identify red blood cells containing KELL antigen and agglutinate them by micro hemagglutination test.

    Conclusions

    Based on the findings, there is a possibility of PBMC transformation in thalassemia patients immunized against KELL antigen and antibody production.

    Keywords: Alloimmunization, Epstein-Barr Virus, B Lymphocytes}
  • Dahmani Bouchra*, Boublenza Lamia, Behar Dalale, Belatbi Kacem, Breik Ikram, Benfoula Amel, Chabni Nafissa, Hassaine Hafida
    Background

    Environmental factors may play a role in colon cancer. In this view, several studies investigated tumor samples for the presence of various viral DNA with conflicting results. The purpose of this study is to investigate the prevalence of Human papillomaviruses (HPVs) and Epstein-Barr virus (EBV) in patients with colorectal carcinomas.

    Materials and Methods

    In this study, we collected 74 tumorous paraffin-embedded tissues (Mean±SD age: 66.3±14.98) from the Pathology Department of a hospital in AinTemouchent and laboratories of pathological anatomy in western Algeria. DNA from each tissue was extracted and the presence of HPV and EBV was investigated using PCR.

    Results

    None of our samples were HPV or EBV positive, and we failed to find an obvious correlation between EBV and HPV infections and this type of cancer.

    Conclusion

    The results suggested that EBV and HPV infection is not common in patients with colorectal cancer in our population. However, the findings merit more investigations on a large number of cases.

    Keywords: Human papillomavirus, Epstein–Barr virus, colorectal cancer, Algeria, pcr}
  • Fatemeh Estaji, Bahram Nasr Esfahani, Saeed Zibaee, MohammadHossein Sanei, Sharareh Moghim
    Background and Objectives

    Among the various factors involved in the development of gastric cancer (GC), infectious agents are one of the most important causative inducers. This study aimed to investigate the possible role of EBV gene expression on SHP1 methylation in co-infection with Helicobacter pylori in patients with GC.

    Materials and Methods

    Formalin-fixed paraffin-embedded samples were obtained from 150 patients with gastrointestinal disorders. The presence of the H. pylori and EBV genome were examined by PCR. The expression level of viral gene transcripts and methylation status of the SHP1 cellular gene was assessed by quantitative real-time PCR and methyl-specific PCR.

    Results

    EBV and H. pylori coinfection were reported in 5.6% of patients. The mean DNA viral load was significant in patients coinfected with cagA-positive H. pylori (P= 0.02). The expression of BZLF1 and EBER was associated with GC. Also, the expression level of BZLF1in GC tissues was significantly higher in coinfection (P = 0.01). SHP1 methylation frequency was higher in the GC group than in the control group (P = 0.04). The correlation between the methylation rate and the H. pylori infection was highly significant (P<0.0001). The strongest positive correlation was observed in GC specimens between SHP1 methylation and H. pylori cagA-positive strains (p= 0.003).

    Conclusion

    Our results suggested that cagA might involve in the elevation of EBV lytic gene expression and SHP1 methylation, and the development of gastric cancer. Understanding the mechanism of EBV H. pylori - cagA + coinfection, as well as host epigenetic changes, can play an important role in diagnosing and preventing gastric cancer.

    Keywords: Epstein-barr virus, Helicobacter pylori coinfection, Viral gene expression, SHP1 methylation, Gastric cancer}
  • رضا طاهرخانی، محمدرضا فرزانه، سکینه طاهرخانی، اعظم امینی، فائزه کشتکار، مریم آقاسی پور، آرزو بدری، زهرا عنایی، فاطمه فرشادپور*
    زمینه

    سرطان مثانه ششمین سرطان شایع در مردان و دهمین نوع سرطان در زنان است. نقش عفونت های ویروسی در ایجاد سرطان مثانه در سال های اخیر بسیار مورد بحث قرار گرفته است. نقش ویروس اپشتن بار (EBV) به عنوان کوکارسینوژن در برخی از سرطان های انسانی اثبات شده است. لذا هدف این پژوهش، بررسی مولکولی EBV در تومورهای مثانه در استان بوشهر می باشد.

    مواد و روش ها

    پژوهش حاضر یک مطالعه توصیفی- تحلیلی است. جمعیت مورد مطالعه شامل بیوپسی های بافت مثانه افراد مبتلا به سرطان مثانه مراجعه کننده به بیمارستان شهدای خلیج فارس بوشهر می باشد. بافت بیوپسی مثانه پارافینه مربوط به 181 بیمار مبتلا به سرطان مثانه با میانگین سنی 13/78± 64/52 و همچنین تعداد 30 نمونه بافت مثانه غیرسرطانی به عنوان گروه کنترل، بعد از پارافین زدایی و تخلیص اسیدنوکلییک، جهت آزمون های مولکولی مورد بررسی قرار گرفتند. به منظور اطمینان از عدم حضور مهارکننده های PCR ابتدا شناسایی ژن بتاگلوبین انسانی به عنوان کنترل داخلی و سپس شناسایی ژن BKRF1 ویروس EBV با روش nested PCR انجام گردید. در پایان از نرم افزار SPSS ویرایش 26 جهت تجزیه تحلیل داده ها و آزمون های آماری استفاده شد.

    یافته ها

    از 181 بافت کارسینوم مثانه مورد مطالعه، 7 مورد (3/9 درصد) با ویروسEBV  آلوده بودند، ولی رابطه آماری معناداری میان سن، جنس، مرحله و درجه تومور با مثبت شدن نمونه از نظر ویروسEBV مشاهده نگردید (0/05<p). همچنین در هیچ کدام از نمونه های غیرسرطانی به عنوان گروه کنترل ویروس EBV شناسایی نشد، با این وجود، اختلاف شیوع EBV بین گروه بیماران سرطان مثانه و گروه کنترل از نظر آماری معنی دار نبود (0/33=p). همچنین نتایج توالی یابی محصولات nested-PCR ژن BKRF1 و رسم درخت فیلوژنیک بیانگر وجود ویروس EBV تایپ 1 در نمونه های مثبت می باشد.

    کلید واژگان: سرطان مثانه, ویروس اپشتن بار, nested PCR, استان بوشهر}
    Reza Taherkhani, Mohammad Reza Farzaneh, Sakineh Taherkhani, Azam Amini, Faeazeh Keshtkar, Maryam Aghasipour, Arezoo Badri, Zahra Anaei, Fatemeh Farshadpour*
    Background

    Bladder cancer is the sixth most common cancer in men and the tenth most common cancer in women. The role of viral infections in the development of urinary bladder cancer has been discussed a lot in recent years. The role of Epstein-Barr Virus (EBV) as a cocarcinogen has been proven in some human cancers. Therefore, the aim of this research is the molecular investigation of EBV in bladder masses in Bushehr province.

    Materials and Methods

    The current research is a descriptive-analytical study. The study population includes bladder tissue biopsies of people diagnosed with bladder cancer referred to Persian Gulf Martyrs Hospital in Bushehr. The paraffin-embedded bladder biopsy tissue of 181 patients with bladder cancer with an average age of 64.52±13.78 as well as 30 non-cancerous bladder tissue samples as the control group were examined for molecular tests after deparaffinization and nucleic acid purification. In order to ensure the absence of PCR inhibitors, human beta globin gene was first detected as an internal control, and then the BKRF1 gene of EBV was detected by nested PCR method. Finally, SPSS software version 26 was used to analyze the data and perform statistical tests.

    Results

    Out of 181 bladder carcinoma samples, 7 cases (3.9%) were infected with EBV, but no statistically significant relationship was found for age, sex, and stage and grade of tumor with EBV positive samples (P>0.05). In addition, EBV was not detected in any of the non-cancerous control samples; however, the difference in the prevalence of EBV between the bladder cancer patients' group and the control group was not statistically significant (P=0.33). In addition, the sequencing of the nested PCR products of the BKRF1 gene and the phylogenetic analysis indicate the presence of EBV type 1 in the positive samples.

    Conclusion

    Based on the findings of the present study and despite the fact that the percentage of EBV infection in cancerous samples was higher than in non-cancerous samples, it is unlikely that EBV is an effective factor in causing bladder cancer in Bushehr province, and other risk factors are probably involved in the etiology of bladder tumors in our study population, such as increasing air pollution in this region of the country, high-risk occupations, smoking, and other carcinogenic viral factors.

    Keywords: Bladder Cancer, Epstein-Barr Virus, Nested PCR, Bushehr Province}
  • Arezoo Marjani, Khashayar Hesamizadeh, Farah Bokharaei-Salim, Khadijeh Khanaliha, MohammadHadi Karbalaie Niya, Zahra Habib, Maryam Esghaei*
    Background and Aims

    Among Human Immunodeficiency Virus (HIV)-infected individuals, Epstein-Barr virus (EBV) and Human Herpesvirus (HHV)-8 could cause significant illness as opportunistic infections. The purpose of the present study was to evaluate the prevalence of EBV and HHV-8 in saliva specimens obtained from HIV-1 infected Iranian individuals under the Highly Active Antiviral Therapy (HAART) regimen compared with naïve patients.

    Materials and Methods

    A cross-sectional study was conducted on 103 HIV-1 positive patients who attended the hospitals affiliated with the Iran University of Medical Sciences, in Tehran, Iran, from 2018 to 2019. Enzyme-linked immunosorbent assay (ELISA) test was performed to evaluate HHV-8 and EBV antibodies. A conventional polymerase chain reaction (PCR) was carried out on saliva samples to detect EBV infection and a nested-PCR assay for HHV-8 infection. SPSS (version 20) was used for statistical analysis.

    Results

    Patients' mean age ± SD was 43.9 ± 16 (range 18-82 years), and from among 103 participants, 59 (57.3%) were male. The results of PCR showed that HHV-8 infection was found in 19 (18.4%), and EBV infection was found in 61 (59.2%) participants. Also, HHV-8 antibody was detected in 73 (70.9%), and EBV antibody in 97 (94.2%) patients. A significant association was observed between patients under treatment with HAART and HHV-8 DNA or EBV DNA infection in saliva.

    Conclusions

    HIV-infected patients demonstrated a remarkable rate of EBV and HHV-8 in saliva, which could have a great role in the shedding of viruses. Also, they may contribute to the establishment of further opportunistic infections and devastating complications.

    Keywords: Epstein-Barr Virus, HIV, Human Herpesvirus 8, Opportunistic infections}
نکته
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