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Introduction: Central nervous system tumors are a diverse group of tumors that account for 2% of all adult cancers and 17% of childhood malignancies. Several internal and external risk factors are involved in the development of this cancer such as viral infections. The aim of this study was to the determination of the EBV infection frequency and the expression level of miR-122 and miR-BART in CNS tumors samples., Methods: One hundred and thirty-eight  fresh tissue sample (106 case and 32 control) was collected from CNS specimens. The presence of Epstein-Barr virus (EBV) DNA was examined by PCR assay and the expression level of miR-122 and miR-BART were evaluated by using real-time PCR assay in CNS tissue samples., Results: EBV DNA was detected in 17% (18 of 106) of tumors tissue samples and 6.4% (2 of 32) of control samples. according to results, there was a significant relationship between the presence of EBV-DNA with CNS tumors. Additionally, the expression level of miR-122 was significantly downregulated in the EBV-positive sample compared to that of the EBV-negative sample. Also, the level of EBV-BART1-3p expression was significantly higher in EBV-positive tumors samples than EBV-positive normal samples., Conclusion: The results of this study suggest that the EBV could change the condition of cancer cells by altering the expression of miR-122 and EBV-BART1-3p and maybe contribute to the development of cancer cells. However, the role of viral infections in CNS cancer requires further studies. , .

Autoimmune hepatitis (AIH) is recognized as a serious disease in which the body's immune system attacks liver cells so untreated patients may consequently suffer from liver cirrhosis, hepatocellular carcinoma (HCC) and liver failure. The role of viral infection may be involved in AIH. Presence of anti-HBc alone is a predictive signal of potential OBI. Thus, this study was conducted to evaluate the rate OBI among the patients with AIH., Methods: The sera of 20 consecutive  patients with AIH were collected and tested for LFT (ALT, AST, ALP elevation), Immunoglobulin (IgG) level, bilirubin, anti -LKM-1, ASMA, ANA in titer, HBsAg, HBcIgG. The patients' sera were also tested for HBV DNA by nested PCR and Real-time PCR., Results: Out of 20 patients, 10 (50%) were males and 10 (50%) females. The patients' ages ranged from 25 to 71 years with the mean age of 44.5±13.4. All patients' had elevated abnormal ALT and AST but their level of alkaline phosphatase was normal among the patients. All patients had IgG level>1.5 times upper than the normal limit. The patients' sera were negative for HBsAg and HBV DNA (by nested PCR and real- time PCR). Only 2 (10%) females with AHI type 1 (positive  ANA, ASMA in titers >1:100 were positive for HBcIgG while no OBI detection was found among the males (p=0.005)). All diagnosis of the AHI was confirmed by pathologist. The level of ALT, AST among the cases with positive and negative OBI were (p=0.000) and (p=0.003), respectively., Conclusion: In the present study, two OBI female patients with type 1 AIH were positive for anti-HBc but negative for HBsAg and HBV DNA. With regard to the consequences of OBI, prior to prophylactic treatment, it is recommended to screen HBV markers including anti-HBc in all diagnosed patients with AIH., .

Background: Colorectal cancer (CRC) as a worldwide human health concern is identified being a multifactorial subject that infection with specific viral particles such as oncogenic viruses is research interest. Human bocavirus (HBoV) as a recent isolated virus has been investigated in many respiratory and enteric diseases but rare studies evaluates it in tissue specimens especially in cancerous sections. The aim of this study was to detect the presence of HBoV genome and its genotyping in CRC patient’s tissue and compare the result with matched healthy control group tissue. Method: in this retrospective case-control study, CRC cases were sporadic and non-familial cancerous while control subjects had healthy or non-malignant lesions in colon tissue. A conventional-PCR performed by specific primers for HBoV VP1 gene. After sequencing of positive PCR products, raw data used for trimming and alignment by bioinformatics software CLC Main Workbench 5 and MEGA5. SPSS v.22 used for statistical calculations. Result: a total of 157 subjects were participated that 66 were diagnosed as CRC cases and 91 were non-CRC colon tissue as control group that matched by the cases. The mean age (y) ± standard deviation of each case and control groups were 59.35±14.48 and 57.21±14.66, respectively. PCR results showed there were 1.3% (2/157) HBoV positive (of each groups one was positive). Sequencing analysis showed all were HBoV-1 genotype. Conclusion: our study showed there are low rate of HBoV genome in Iranian CRC and non-CRC colon tissue. Furthermore, the predominant genotype in our studied subsets were HBoV-1 according to phylogenetic analysis., (Creative Commons Attribution License)

Background: Head and neck squamous cell carcinomas (HNSCC) are a major health issue in many parts of the world. Recently, attention has focused on the human papilloma virus (HPV) as a potential causative agent for HNSCC. This study aimed to survey HPV occurrence in HNSCCs as part of a comprehensive molecular epidemiology approach. Methods: In this retrospective study, patients were recruited from hospitals affiliated to the Iran University of Medical Sciences, Tehran, Iran. Formalin-fixed paraffin-embedded (FFPE) blocks were subjected to DNA isolation by QIAamp® DNA FFPE Tissue Kit and nested PCR, HPV-16 specific conventional PCR, and extra INNO-LiPA HPV genotyping assays were subsequently performed. PCR products were purified with a High Pure PCR Product Purification Kit and sequenced with an ABI 3730 XL sequencer. CLC Main Workbench 5 and MEGA5 bioinformatics software was used to analyze the raw data and to create the phylogenetic tree. SPSS v.20 was applied for statistical analysis. Results: A total of 156 FFPE blocks were collected from 2011 to 2017. Total mean age (y) of participants was 60.5 ± 12.6; 77.6 % (121/156) being men and 22.4% (35/156) e women. Overall, 5/156 (3.2%) patients (3 females and 2 males) were found to be HPV positive using the three methods. HPV genotyping revealed HPV types 16, 2, 27, and 43 in these malignancies. Tumor location and lymph node involvement indicated significant differences between the sexes. Conclusion: Although high risk HPV genotypes have been associated with HNSCCs, our findings indicate a potential of low risk HPV types to also contribute to such malignancies., (Creative Commons Attribution License)

Background: Human tissue-type plasminogen activator (t-PA) is a key protease of the trypsin family. It catalyzes the activation of zymogen plasminogen to the fibrin-degrading proteinase, plasmin, leading to digestion of fibrin clots. The recombinant enzyme produced by recombinant technology issued to dissolve blood clots in treatment of various human diseases such as coronary artery thrombosis, pulmonary embolism, acute ischemic stroke (AIS). Pichia pastoris expression system is a unique system for the production of high level of recombinant proteins. GS115 and KM71H are two kinds of Pichia pastoris strains whilst production of recombinant proteins in these strains is not predictable. The aim of the study was evaluation of t-PA expression in KM71H strains. Methods: In this study, the cDNA of the t-PA gene was amplified by PCR, sequenced and cloned into Pichia pastoris KM71H host strain using pPICZalphaA expression vector that allows methanol-induced expression and secretion of the protein. Results: Dot blotting results confirmed the presence oft-PA in the cell supernatant. Western blotting test revealed the approximate size of 70 KDa for recombinant t-PA. Quantitative ELISA experiment showed 810 μg/L of t-PA in the supernatant samples. Zymography analysis confirmed the proteolytic activity and biological function of the expressed recombinant t-PA. Conclusions: Correspondingly, Pichia pastoris KM71H is an appropriate strain for production of active recombinant protein., (Creative Commons Attribution License)

Background: Currently, recurrent respiratory papillomatosis (RRP), common laryngeal warts in the upper airway systems of children and adults are on the increase. Human papillomaviruses (HPVs) are suspected as causative agents. This study concerned HPV incidence and genotype distribution in Iranian RRP patients. Methods: Specimens were collected from RRP patients referred to hospitals affiliated with Iran University of Medical Sciences, Tehran, Iran, from Dec 2014 to Feb 2016 in a cross sectional study. After DNA extraction with an QIAamp® DNA FFPE Tissue Kit, conventional PCR was performed and products were sequenced. INNO-LiPA HPV Genotyping Extra assays as another method for genotyping were conducted. CLC Main Workbench 5 and MEGA6 software as well as SPSS v.20 were used for further analysis. Results: Of the total of 12 patients, 6 (50%) were male. Total mean age (y) ± SD was 9.8±6.3. All RRP patients suffered from HPV infection, with HPV-6 found in 75% (9/12) and HPV-11 in 16.7% (2/12) and one co-infection by both HPV-6 and 11. Statistically, there were no correlations between demographic variables and HPV infection. Conclusion: The major cause of RRP is HPV genotypes 6 and 11 increasing the risk of a requirement for medical interventions. Broader studies are needed to clarify the major risk factors in RRP patients., (Creative Commons Attribution License)

HPV 16 intratypic sequence variations has been recognized in association with oncogenic potential diverge and geographic distribution. This study aimed to investigate nucleotide modifications and optimization of HPV 16 E7 regions from Iranian infected women. Cervical biopsies from 79/163 HPV 16 positive cancer patients detected in our study were analyzed by PCR in a couple of cloning of a complete ORF of the E7 gene, and sequencing. The most frequently observed variant was C196T in E7 which led to an amino acid change of R66W. In addition, only one common variant T234G was identified from all specimens, but it did not lead to any amino acid change. We also detected nucleotide variations A86G, and C188T in samples. Among 99 codons in E7 gene, 56 codons were improved for Lactococcus lactis subsp. cremoris MG1363 resulting in a reduced G+C content from 43.1% to 34.0%. Also, the AT%, ENC, and CAI values were 66, 20±1.1, and 1.000 instead of 56.90, 60 ±1.1, and 0.406 respectively. Finally we constructed expression vector pNZ8148 encoding optimized E7 oncoprotein of HPV 16. This study declared for the first time, the genetic variations of HPV 16 E7 in IRAN. We conclude that plasmid pNZ8148-HPV 16-opti E7 can be potential vaccine candidates in the future., (Creative Commons Attribution License)

Background: A recent genome-wide association study (GWAS) on patients with chronic hepatitis C (CHC) treated with peginterferon and ribavirin (pegIFN-α/RBV) identified a single nucleotide polymorphism (SNP) on chromosome 19 (rs12979860) which was strongly associated with a sustained virological response (SVR). The aim of this study was twofold: to study the relationship between IL28B rs12979860 and sustained virological response (SVR) to pegIFN-α/RVB therapy among CHC patients and to detect the rs12979860 polymorphism by high resolution melting curve (HRM) assay as a simple, fast, sensitive, and inexpensive method., Materials and Methods: The study examined outcomes in 100 patients with chronic hepatitis C in 2 provinces of Iran from December 2011 to June 2013. Two methods were applied to detect IL28B polymorphisms: PCR-sequencing as a gold standard method and HRM as a simple, fast, sensitive, and inexpensive method., Results: The frequencies of IL28B rs12979860 CC, CT, and TT alleles in chronic hepatitis C genotype 1a patients were 10% (10/100), 35% (35/100), and 6% (6/100) and in genotype 3a were 13% (13/100), 31% (31/100), and 5% (5/100), respectively. In genotype 3a infected patients, rs12979860 (CC and CT alleles) and in genotype 1a infected patients (CC allele) were significantly associated with a sustained virological response (SVR). The SVR rates for CC, CT and TT (IL28B rs12979860) were 18%, 34% and 4%, respectively. Multiple logistic regression analysis identified two independent factors that were significantly associated with SVR: IL-28B genotype (rs 12979860 CC vs TT and CT; odds ratio [ORs], 7.86 and 4.084, respectively), and HCV subtype 1a (OR, 7.46). In the present study, an association between SVR rates and IL28B polymorphisms was observed., Conclusions: The HRM assay described herein is rapid, inexpensive, sensitive and accurate for detecting rs12979860 alleles in CHC patients. This method can be readily adopted by any molecular diagnostic laboratory with HRM capability and will be clinically beneficial in predicting treatment response in HCV genotype 1 and 3 infected patients. In addition, it was demonstrated that CC and CT alleles in HCV-3a and the CC allele in HCV-1a were significantly associated with response to pegIFN-α/RBV treatment. The present results may help identify subjects for whom the therapy might be successful.

Background: In chronic hepatitis B (CHB), the presence of hepatic steatosis (HS) seems to be associated with known host and viral factors which may influence the long-term prognosis of chronic hepatitis B (CHB), probably leading to cirrhosis and hepatocellular carcinoma (HCC). Different from chronic hepatitis C (CHC), factors associated with HS in CHB are not clearly explored., Materials and Methods: 160 CHB patients were divided into two groups depending on the results of liver biopsy. Group I consisted of 71 patients with confirmed steatosis. Group II comprised 89 patients without steatosis. The groups were compared in terms of basal characteristics, body mass index (BMI), liver enzymes (ALT, AST, ALP), serum fasting blood sugar (FBS) and lipids, hepatitis B e antigen (HBeAg), viral load, and histological findings., Results: In terms of host factors, male gender, older age, BMI, high serum FBS and lipid levels were associated with HS. On the other hand, ALT levels, the HAI scores of necroinflammation and stage of fibrosis did not associate with HS. On multivariate analysis, parameters of sex, BMI, cholesterol and FBS levels were independently associated with HS. Regarding viral factors, HBeAg negativity was significantly associated with HS (81.7%, p value 0.006), but not HBV DNA level (p value 0.520)., Conclusions: HS in CHB appears to be unrelated to the status of HBV replication. However, fibrosis progression in CHB is related to variable host factors. HS may be enhanced through these factors in HBV chronic patients.

Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection.