Publications by authors named "Fahimeh Safarnezhad Tameshkel"

27 Publications

  • Page 1 of 1

The Ability of the Framingham Steatosis Index (FSI) to Predict Non-alcoholic Fatty Liver Disease (NAFLD): A Cohort Study.

Clin Res Hepatol Gastroenterol 2021 Mar 9;45(6):101567. Epub 2021 Mar 9.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The utilization of indexes for the diagnosis of non-alcoholic fatty liver disease (NAFLD) can be valuable. This study was conducted to determine the ability of the Framingham steatosis index (FSI) to distinguish between people with NAFLD and those without and to predict people at risk of NAFLD to establish the need for lifestyle modifications in such individuals.

Methods: Our study was conducted in two phases from 2009-2010 (phase I) to 2016-2017 (phase II). A total of 4670 people in northern Iran were included. NAFLD was diagnosed by ultrasound. The FSI was calculated based on age, sex, hypertension, diabetes mellitus status, liver enzyme levels and triglyceride levels. Receiver operating characteristic (ROC) analysis was conducted to determine the discriminatory and predictive abilities of the FSI. To remove the confounding effects of potential mediators, logistic regression was performed in which NAFLD was considered the outcome and the FSI as the predictor.

Results: The odds ratios of the FSI when the outcome was the prevalence of NAFLD in phase I and when the outcome was new cases of NAFLD from 2009-2010 to 2016-2017 were 4.909 (4.243-5.681) and 2.453 (2.024-2.972), respectively (P<0.001). The areas under the curve (AUCs) for the discriminatory and predictive abilities of the FSI were 0.8421 (95% CI: 0.8314-0.8527) and 0.7093 (95% CI: 0.6863-0.7322), respectively.

Conclusion: The FSI has a strong ability to diagnose NAFLD while it has an acceptable ability to predict the occurrence of new cases of NAFLD.
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http://dx.doi.org/10.1016/j.clinre.2020.10.011DOI Listing
March 2021

Molecular epidemiology of human respiratory syncytial virus (HRSV) in Iranian military trainees with acute respiratory symptoms in 2017.

Iran J Microbiol 2020 Oct;12(5):495-502

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background And Objectives: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in many populations, including military recruits receiving basic training. Therefore, this study was set out to determine the molecular epidemiology, genotype and phylogenetic features of RSVs in patients with respiratory infection as a case study.

Materials And Methods: In this study, military barracks of Tehran, Iran, between January to March 2017 exposed to respiratory diseases were used for sampling. Throat swabs were taken, a reverse transcriptase-polymerase chain reaction (RTPCR) assay was performed to identify RSV and then the genotyping and phylogenetic analyses of RSVs in patients with a respiratory infection.

Results: Among 400 Iranian military trainees with respiratory symptoms, RSV infection was identified in 2.75% (11/400) using RT-PCR. Sequencing showed the incidence of type A (2.5%, n=10) to be much higher than type B (0.25%, n=1); Sore throat was the most common symptom among RSV patients. Phylogenetic analysis revealed that the majority of strains from the studied samples were more consistent with those from the Philippines and the US strains.

Conclusion: This study is the first to document RSV as a major cause of acute respiratory illness among military trainees in Iran. The prevalence of RSV is substantial in the cold season and the prevalence of genotype A is dominant in the country, leading to take essential steps in preparing a preventive vaccine against this viral infection.
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http://dx.doi.org/10.18502/ijm.v12i5.4612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867691PMC
October 2020

Angiotensin Converting Enzyme Inhibitors, A Risk Factor of Poor Outcome in Diabetic Patients with COVID-19 Infection.

Iran J Kidney Dis 2020 12 5;14(6):482-487. Epub 2020 Dec 5.

Firoozgar Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran.

Introduction: Diabetes mellitus and hypertension are described as the most common comorbidities among COVID-19 patients. We investigated the adverse effect of ACEIs in diabetic and nondiabetic patients with COVID-19.

Methods: This prospective study consisted of 617 RT-PCR-confirmed COVID-19 inpatients. Demographic and baseline characteristics, underlying comorbid diseases, and antihypertensive drugs were evaluated. Study outcome (in-hospital death) was evaluated with the Kaplan-Meyer method and Cox regression model. Statistical analyses were performed with SPSS software for Windows. P values < .05 were considered significant.

Results: Mean ± SD age was 58.49 ± 15.80 (range: 18 to 94) years old. Cox regression analysis revealed that age (adjusted hazard ratio [HR] = 1.04, 95% CI: 1.03 to 1.06), diabetes mellitus (adjusted HR = 2.07, 95% CI: 1.32 to 3.26), immunocompromised patients (adjusted HR = 2.33, 95% CI: 1.29 to 4.21), acute kidney injury (AKI) (adjusted HR = 3.23, 95% CI: 2.01 to 5.19), ICU admission (adjusted HR = 2.48, 95% CI: 1.46 to 4.21), Asthma and COPD (adjusted HR = 2.13, CI:1.6 to 4.28) and ACEI (adjusted HR = 3.08, 95% CI: 1.56 to 6.06), respectively were associated with in-hospital death. Among diabetic patients, ACEI (adjusted HR = 3.51, 95% CI: 1.59 to 7.75), AKI (adjusted HR = 3.32, 95% CI: 1.76 to 6.45) and ICU admission (adjusted HR = 3.64, 95% CI: 1.530 to 8.65) were associated with increased mortality. The Kaplan-Meier survival curve showed a lower survival rate in diabetic patients with ACE inhibitor (adjusted HR = 3.36, 95% CI: 2.25 to 7.71).

Conclusion: ACEIs may harm the diabetic patient's outcome with COVID-19. Further studies can confirm if ACE inhibitors have an adverse effect on COVID-19 diabetic patient's mortality.
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December 2020

Evolutionary study of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emerging coronavirus: Phylogenetic analysis and literature review.

Vet Med Sci 2021 03 18;7(2):559-571. Epub 2020 Nov 18.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.

Since emerging coronaviruses have always become a human health concern globally especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV) and Middle East respiratory syndrome coronavirus and a novel coronavirus was introduced in Wuhan, China, in December 2019 (called SARS-CoV-2), many researchers focused on its epidemics, virological and clinical features. SARS-CoV-2 is classified as Betacoronaviruses genus and Sarbecovirus subgenus (lineage B). The virus shows a great similarity with SARS-CoV and bat SARS-like coronaviruses. In this study, we evaluate SARS-CoV-2 virus phylogeny and evolution by using current virus and related sequences.
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http://dx.doi.org/10.1002/vms3.394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753621PMC
March 2021

Signal transduction pathway mutations in gastrointestinal (GI) cancers: a systematic review and meta-analysis.

Sci Rep 2020 10 30;10(1):18713. Epub 2020 Oct 30.

Gastrointestinal and Liver Disease Research Center, Iran University of Medical Sciences, Tehran, Iran.

The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and meta-analysis study. The study was performed based on the PRISMA criteria. Random models by confidence interval (CI: 95%) were used to calculate the pooled estimate of prevalence via Metaprop command. The pooled prevalence indices of signal transduction pathway mutations in gastric cancer, liver cancer, colorectal cancer, and pancreatic cancer were 5% (95% CI: 3-8%), 12% (95% CI: 8-18%), 17% (95% CI: 14-20%), and 20% (95% CI: 5-41%), respectively. Also, the mutation rates for Wnt pathway and MAPK pathway were calculated to be 23% (95% CI, 14-33%) and 20% (95% CI, 17-24%), respectively. Moreover, the most popular genes were APC (in Wnt pathway), KRAS (in MAPK pathway) and PIK3CA (in PI3K pathway) in the colorectal cancer, pancreatic cancer, and gastric cancer while they were beta-catenin and CTNNB1 in liver cancer. The most altered pathway was Wnt pathway followed by the MAPK pathway. In addition, pancreatic cancer was found to be higher under the pressure of mutation compared with others based on pooled prevalence analysis. Finally, APC mutations in colorectal cancer, KRAS in gastric cancer, and pancreatic cancer were mostly associated gene alterations.
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http://dx.doi.org/10.1038/s41598-020-73770-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599243PMC
October 2020

Non-alcoholic fatty liver disease is not independent risk factor for cardiovascular disease event: A cohort study.

World J Hepatol 2020 Jun;12(6):323-331

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran.

Background: There are no consistent results between previous studies for an independent association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) events.

Aim: To determine if there is an independent association between NAFLD and CVD events.

Methods: In the present study, valid outcome data of 4808 subjects were available for phase 2 of our cohort study. These subjects had been followed up for seven years from phase 1, beginning in 2009-2010 to phase 2 during 2016-2017. Simple and multiple Cox proportional models were used to determine the association between NAFLD in the primary phase of the cohort and subsequent fatal and non-fatal CVD events during follow-up.

Results: The incidence of non-fatal CVD events in males with NAFLD was significantly higher ( = 0.004) than in males without NAFLD. A positive association was demonstrated between NAFLD and non-fatal CVD events in males (Hazard ratio = 1.606; 95%CI: 1.166-2.212; = 0.004) by the simple Cox proportional hazard model, but no independent association was detected between these in the multiple Cox models.

Conclusion: No independent association was detected between NAFLD and CVD. It is likely that diabetes mellitus and age may be the principle mediators in this regard.
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http://dx.doi.org/10.4254/wjh.v12.i6.323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364326PMC
June 2020

Resistance-associated substitutions (RASs) to HCV direct-acting antivirals (DAAs) at baseline of treatment in thalassemia patients: a referral center study.

Arch Virol 2020 Oct 8;165(10):2193-2203. Epub 2020 Jul 8.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.

Patients with thalassemia major are at high risk of hepatitis C through blood transfusion from donors infected by hepatitis C virus (HCV). The use of direct-acting antiviral (DAA) therapy against such HCV infections has increased in different populations. However, resistant viral variants can affect treatment outcomes, and therefore improved surveillance strategies are needed. Accordingly, we aimed to evaluate resistance-associated substitutions (RASs) to HCV DAAs at the baseline of treatment in thalassemia patients in a referral center. Out of 89 thalassemia patients who suffered from HCV infection and were referred to our center between 2016 and 2017, 43 underwent further analysis of the HCV nonstructural proteins NS5A and NS5B using polymerase chain reaction (PCR) sequencing methods. Unique primers were designed using bioinformatics software for separate detection of HCV subtypes 1a, 3a, and 1b. Detection of RASs was performed based on previously published literature. Statistical analysis was carried out using SPSS version 19. The participants, 60.4% (26/43) of whom were male, had a mean age ± standard deviation (SD) of 33.0 ± 5.0 years. HCV subtype 1a was found in 27 cases, 3a in 13, and 1b in three. In HCV subtype 1a there were 163 mutations in NS5A and 212 mutations in NS5B. The frequency of RASs was 20.9% (8 RASs in 9 patients), including M28V and H58P in subtype 1a, L28M, R30Q, C316N, and C316S in subtype 1b, and S24F in subtype 3a. Statistically, the subtype 1b and a higher mutation rate in NS5A were associated with RASs (p-value < 0.05). The emergence of natural RASs to HCV DAAs serves as a warning of the risk of drug resistance in response to the broad usage of antivirals. However, relapses in these DAA-treated HCV-infected thalassemia patients are rarely reported. Our findings indicate that the prevalence of RASs prevalence at baseline was 20.9% in these patients, and this calls for extrapolation to a larger population study, as highlighted in other studies, with larger sample sizes, high-throughput methods, and follow-up in order to fully evaluate treatment outcomes in RASs-detected individuals. Optimized therapeutic strategies, particularly in complex, difficult-to-cure patients, can effectively prevent DAA treatment failure as a result of selection for RASs.
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http://dx.doi.org/10.1007/s00705-020-04728-xDOI Listing
October 2020

Investigation of gene mutations and expression in hepatocellular carcinoma and cirrhosis in association with hepatitis B virus infection.

Infect Agent Cancer 2020 3;15:37. Epub 2020 Jun 3.

Department of Virology, Iran University of Medical Sciences, Tehran, Iran.

Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including , promoting the neoplastic process. The present study evaluated the mutational profile of the gene and expression levels of and genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and genes was assessed using real-time PCR. Among the HCC cases, 18.1% showed missense point mutation in exon 3 of , more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4%) rather than HBV-related cases (12.7%,  = 0.021). The expression of β-catenin and genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC.
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http://dx.doi.org/10.1186/s13027-020-00297-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268324PMC
June 2020

10-year risk of cardiovascular disease and body mass index in association with the obesity paradox.

ARYA Atheroscler 2020 Jan;16(1):16-23

Assistant Professor, Department of Cardiology, Iran University of Medical Sciences, Tehran, Iran.

Background: Some recent studies reported an inverse association between obesity and risk of cardiovascular diseases (CVD), heart failure related mortality rate, outcomes of myocardial infarction (MI), and the consequences of cardiovascular events interventions; this inverse association was named the obesity paradox. The present study was conducted with the aim to determine whether the obesity paradox will be detectable when the 10-year risk of CVD is estimated using CVD risk assessment tools.

Methods: The related data of 2910 subjects aged 40-74 years obtained in our cohort study that was carried out among 6140 subjects in Amol, in northern Iran, was included in this study. CVD risk assessment tools were used to estimate the 10-year risk of CVD. Obesity was evaluated using 4 indices, including waist circumference (WC), waist to height ratio (WHtR), waist to hip ratio (WHR), and body mass index (BMI). The receiver operating characteristic (ROC) curve analysis was utilized to evaluate the discriminatory power of obesity indices for 10-year risk of CVD.

Results: Categorizing the participants to with and without obesity according to BMI showed that a significantly higher proportion of men with obesity had a 10-year risk of CVD ≥ 7.5% and ≥ 10% according to American College of Cardiology/American Heart Association (ACC/AHA) and the Framingham approaches, respectively. A higher proportion of women without obesity had a 10-year risk of CVD ≥ 7.5% than women with obesity based on the ACC/AHA equation (28.54% vs. 24.15%; P = 0.0707). BMI had a non-significant AUC (< 0.5) according to the the ACC/AHA equation.

Conclusion: BMI showed a weak and non-significant inverse association with 10-year risk of CVD estimated using pooled cohort equations of ACC/AHA in women. However, this result cannot directly provide enough evidence for the obesity paradox.
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http://dx.doi.org/10.22122/arya.v16i1.1581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244790PMC
January 2020

SARS-CoV-2 Molecular and Phylogenetic analysis in COVID-19 patients: A preliminary report from Iran.

Infect Genet Evol 2020 10 30;84:104387. Epub 2020 May 30.

Department of Virology, Iran University of Medical Sciences, Tehran, Iran; Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The aim of the current study was to investigate and track the SARS-CoV-2 in Iranian Coronavirus Disease 2019 (COVID-19) patients using molecular and phylogenetic methods.

Methods: We enrolled seven confirmed cases of COVID-19 patients for the phylogenetic assessment of the SARS-CoV-2 in Iran. The nsp-2, nsp-12, and S genes were amplified using one-step RT-PCR and sequenced using Sanger sequencing method. Popular bioinformatics software were used for sequences alignment and analysis as well as phylogenetic construction.

Results: The mean age of the patients in the present study was 60.42 ± 9.94 years and 57.1% (4/7) were male. The results indicated high similarity between Iranian and Chinese strains. We could not find any particular polymorphisms in the assessed regions of the three genes. Phylogenetic trees by neighbor-joining and maximum likelihood method of nsp-2, nsp-12, and S genes showed that there are not any differences between Iranian isolates and those of other countries.

Conclusion: As a preliminary phylogenetic study in Iranian SARS-CoV-2 isolates, we found that these isolates are closely related to the Chinese and reference sequences. Also, no sensible differences were observed between Iranian isolates and those of other countries. Further investigations are recommended using more comprehensive methods and larger sample sizes.
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http://dx.doi.org/10.1016/j.meegid.2020.104387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832360PMC
October 2020

COVID-19 in the endoscopy ward: A potential risk for gastroenterologists.

Infect Control Hosp Epidemiol 2020 10 23;41(10):1242-1243. Epub 2020 Apr 23.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1017/ice.2020.160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200836PMC
October 2020

Epstein-Barr virus molecular epidemiology and variants identification in head and neck squamous cell carcinoma.

Eur J Cancer Prev 2020 11;29(6):523-530

Department of Virology, Iran University of Medical Sciences, Tehran, Iran.

Epstein-Barr virus (EBV) is known as one of the most widespread oncogenic viruses. Head and neck squamous cell carcinoma (HNSCC) is triggered by various risk factors. The aim of the present study was to determine the EBV infection rate, genotyping and variants frequency in HNSCC patients. In this cross-sectional study, 156 patients with HNSCC were enrolled. Formalin fixed paraffin embedded (FFPE) tissue samples were selected from hospitals affiliated to Iran University of Medical Sciences, Tehran, Iran. The EBV EBNA-3C, EBNA-1 and LMP-1 genes were amplified by PCR and then analyzed and confirmed by nucleotide sequencing. CLC work bench 5, MEGA6 and SPSS v.21 software were used for analysis the raw data. The mean age ± SD (years) of the all patients (n = 156) was 60.5 ± 12.6, in which of 121(77.6%) males it was 60.7 ± 11.9 and of 35 (22.4%) females it was 59.7 ± 14.9. Totally, 20 samples (12.8%) were found to be infected with EBV genome. The EBV genotypes 1 and 2 were calculated 90% (18/20) and 10% (2/20), respectively. vLMP-1 found in 40% (4/10) of all LMP-1 tested samples. Furthermore, the EBNA-1 predominant variants were P-ala followed by P-thr and also there were three P-ala-v2 sub variants. Statistics could not find any significant associations although there were some potentials. By our preliminary study in Iran, it revealed that EBV-1 is the predominant Epstein-Barr virus genotype in head and neck squamous cell carcinoma patients. vLMP-1 isolates showed lower survival rate than others. EBNA-1 variants had no significant association with any specific disease complication.
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http://dx.doi.org/10.1097/CEJ.0000000000000554DOI Listing
November 2020

The Comparison of the Plasma Levels of the Lead Element in Patients with Gastrointestinal Cancers and Healthy Individuals.

Asian Pac J Cancer Prev 2019 09 1;20(9):2639-2644. Epub 2019 Sep 1.

Gastrointestinal and Liver Diseases Research Center (GILDRC), Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran. Email:

Back ground and Aim: Heavy metals are considered as risk factors in the development of some types of cancers. In this context, the lead (Pb) along with its biological impacts on the human body has raised significant concerns in public health. The aim of this study was to compare the plasma levels of the lead element in patients with gastrointestinal (GI) cancer and healthy subjects to examine whether this element has a role in the susceptibility of cancer. Methods: In a case-control study conducted between March 2016 to February 2017, the plasma levels of the lead were assessed. One-hundred patients with upper and lower GI cancers, as well as one-hundered healthy subjects who were age- and sex-matched participated in our study. A classic flame atomic absorption spectroscopy (FAAS) method was employed for the determination of the lead element in plasma levels of all subjects. Results: The mean age of patients was 53.8±10.6 years old. The patient group consisted of 51 male and 49 female patients. The results showed that the concentrations of Pb were lower than the defined toxic levels. The comparison of the mean levels of Pb between the case and control groups revealed that there was no statistically significant difference even when the gender, age, and history of smoking were included in the statistical analysis. Our findings showed that the concentration of Pb is significantly associated with the type of cancer (p<0.003) and the location of the tumor (whether upper or lower tract was affected) (p<0.003). Conclusion: Lead may contributes to the pathology and progression of GI cancers but we can not conclude that it involved in the causation or susceptibility of healthy individuals to develop GI cancer.
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http://dx.doi.org/10.31557/APJCP.2019.20.9.2639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976846PMC
September 2019

Fatty liver index (FLI) and prediction of new cases of non-alcoholic fatty liver disease: A population-based study of northern Iran.

Clin Nutr 2020 02 18;39(2):468-474. Epub 2019 Mar 18.

Gastrointestinal and Liver Disease Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background And Aims: Non-alcoholic fatty liver disease is considered a major public health concern. The prediction of individuals who can acquire this disease would be valuable. The fatty liver index (FLI) is a non-invasive approach that has shown a good capability for discriminating individuals with non-alcoholic fatty liver disease (NAFLD) from those without it. Thus, this study evaluated the ability of the FLI to predict new cases of NAFLD following a 7-year follow up.

Materials And Methods: This study was based on the results of follow-up on individuals who did not have NAFLD in 2009-2010, but acquired the disease by 2016-2017. A total of 2241 people who did not have NAFLD in 2009-2010 were evaluated 7 years later by ultrasound so as to diagnose new cases of NAFLD. The FLI was calculated based on data from phase 1 (performed in 2009-2010) of the cohort study. ROC analyses were performed to estimate the predictive ability of the FLI in the diagnosis of new cases of NAFLD. Logistic regression analysis was performed, in which the FLI was considered the predictor and new cases of NAFLD was the outcome.

Results: The related AUCs for the FLI in men and women were 0.712 (95% CI = 0.675-0.749) and 0.721 (95% CI = 0.683-0.759), respectively. Based on the current findings, the FLI showed a significant association with NAFLD in multiple logistic regression analyses in both men and women (OR (95% CI) = 1.038 (1.029-1.047), p-value <0.001 in men and OR (95% CI) = 1.032 (1.023-1.041), p-value <0.001 in women in multiple logistic analyses).

Conclusion: In this study, the FLI was shown to have an acceptable capability of predicting the occurrence of new cases of NAFLD.
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http://dx.doi.org/10.1016/j.clnu.2019.02.024DOI Listing
February 2020

The Molecular Detection of Human Bocavirus (HBoV) in Colorectal Tissue with Malignant and Non-Malignant Lesions

Asian Pac J Cancer Prev 2018 Nov 29;19(11):3295-3299. Epub 2018 Nov 29.

Institute of Immunology and Infectious Diseases, Iran University of medical sciences, Tehran, Iran. Email:

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.
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http://dx.doi.org/10.31557/APJCP.2018.19.11.3295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318405PMC
November 2018

A Survey on Human T-cell Lymphotropic Virus Type 1 (HTLV-1) and Xenotropic Murine Leukemia Virus-Related Virus (XMRV) Coinfection in Tehran, Iran.

J Pharm Bioallied Sci 2018 Jul-Sep;10(3):166-171

Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Xenotropic murine leukemia virus-related virus (XMRV) is a gamma retrovirus, which has been detected in patients with prostate cancer, chronic fatigue syndrome, and general population with a number of acquired infections such as infection with human T-cell lymphotropic virus (HTLV) and human immunodeficiency virus (HIV). The aim of this study was to determine the HTLV-1 and XMRV coinfection for the first time in Iranian patients who were admitted to the Tehran hospitals.

Materials And Methods: Two hundred and ninety one patients suspected with HTLV-1 were referred to the hospitals affiliated to the Iran University of Medical Sciences, Tehran, Iran from April 2012 to October 2016. Genomic deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) from peripheral blood mononuclear cells/cerebrospinal fluids was extracted by High Pure Viral Nucleic Acid Kit (Roche, Germany). After complementary DNA synthesis, conventional reverse transcriptase polymerase chain reaction was used for the detection of HTLV-1 or XMRV-infected patients. Statistical Package for Social Sciences (SPSS) software, version 16 (SPSS, Chicago, IL, USA) was used for statistical analyses.

Results: Of the 291 patients suspected of HTLV infection, 123 (42.3%) were male with a mean age of 38±15 years. HTLV-1 RNA was found in 93 (31.9%) specimens comprising 40 men (41.3%) and 53 women (56.9%). Of the 93 patients who were HTLV-1 positive, one sample (1%) was positive for XMRV gene.

Conclusion: These findings suggest that the lack of significant detection of XMRV in patients who were HTLV-1 positive could not be associated with complications of HTLV-1. Although this is a preliminary report from Iranian patients with HTLV-1, further studies are needed to show the actual prevalence of XMRV infection by geographical distribution and various populations.
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http://dx.doi.org/10.4103/jpbs.JPBS_25_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142885PMC
September 2018

The effectiveness of sofosbuvir and daclatasvir in the treatment of hepatitis C in thalassaemia major patients and their effect on haematological factors.

Indian J Med Microbiol 2018 Apr-Jun;36(2):224-229

Gastrointestinal and Liver Disease Research Center, Iran University of Medical Sciences, Tehran; Gastroenterology and Hepatology Disease Research Center, Qom University of Medical Sciences, Qom, Iran.

Context: Patients with thalassaemia are at risk of infections such as hepatitis C virus (HCV) due to their repeated blood transfusions; meanwhile, the treatment of thalassaemia patients who had developed HCV infection is a controversial issue.

Aims: Although the effectiveness of direct-acting antivirals on HCV infection has been confirmed, their side-effects as well as effects on haematological factors due to the resultant need for blood transfusion remain to be further understood.

Materials And Methods: In this study, 61 patients with major beta thalassaemia and HCV infection, and who had a history of interferon treatment failure were examined. The patients underwent a 24-week treatment with sofosbuvir (SOF) and daclatasvir (DAC). Sustained virological response 12 was used to assess response to treatment. At the end of the study, the need for blood transfusion and serum ferritin was evaluated.

Results: About 98.4% of the patients responded to the treatment, and only one patient with genotype 1b did not respond positively. No significant complications necessitating treatment cessation were observed, and all the patients tolerated the treatment well. The level of liver enzymes showed a significant reduction 12 weeks after the treatment. The need for blood transfusions in patients before treatment was averagely 1.595 ± 0.65 bag per month, in which 1.593 ± 0.64 bags were received after treatment (P = 0.9). This regimen did not affect the amount of anaemia in patients and did not differentiate the need for blood transfusions. The rate of haemoglobin before treatment was 9.5 ± 1.42 g/dl, which reached 9.6 ± 1.6 g/dl after treatment (P = 0.54). Ferritin levels decreased significantly (from 1948.08 ± 1539.54 to 1315.73 ± 1207.67 ng/ml) (P = 0.001) in the patients after the treatment.

Conclusion: Combination of SOF and DAC is an effective and tolerable treatment regimen without affect on the amount of anaemia in patients and did not differentiate the need for blood transfusions.
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http://dx.doi.org/10.4103/ijmm.IJMM_18_90DOI Listing
December 2018

The Evaluation of Diagnostic and Predictive Values of Stool Antigen Test in Iranian Patients with Dyspepsia.

Iran J Pathol 2018 ;13(1):38-44

Dept. of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background And Objectives: Iran, as a developing country, is experiencing high burdens of (Hp)-associated non-communicable diseases. Hp stool antigen test (HpSA) is widely used as an inexpensive and feasible noninvasive method to diagnose Hp infection, instead of invasive approaches. The current study aimed at evaluating the diagnostic and predictive values of HpSA test for Hp infection in Iranian patients with dyspepsia.

Methods: The current cross sectional study was performed on 100 patients with dyspepsia. Gastric mucosal specimens were taken, processed, and examined according to the standard protocols. Simultaneously, stool samples were obtained and sent to laboratory for further analyses. Hp stool antigen titers were assessed using enzyme-linked immunosorbent assay (ELISA) technique.

Results: Stool antigen titers were not associated with gender (-value=0.284), but correlated to age (r=0.213, -value=0.034). Considering 0.385 as a cutoff point, the HpSA test had 80.4% sensitivity and 85.7% specificity.

Conclusion: Based on cost-effectiveness of HpSA test, the current study findings corroborated the use of HpSA test to detect and follow-up patients with Hp infection, as an alternative method to detect Hp rather than invasive procedures.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929387PMC
January 2018

Human Papillomavirus Type 16 Integration Analysis by Real-time PCR Assay in Associated Cancers.

Transl Oncol 2018 Jun 13;11(3):593-598. Epub 2018 Mar 13.

Department of Virology, Iran University of Medical Sciences, Tehran, Iran.

Human papillomavirus (HPV) is a common viral infection worldwide associated with a variety of cancers. The integration of the HPV genome in these patients causes chromosomal instability and triggers carcinogenesis. The aim of this study was to investigate the HPV-16 genome physical status in four major cancers related to HPV infection. Formalin-fixed paraffin-embedded blocks from our previous projects on head and neck, colorectal, penile, and cervical cancers were collected, and HPV-16-positive specimens were used for further analysis. The DNA extraction copy number of E2 and E7 genes was calculated by qualitative real-time PCR method. Serially diluted standards that were cloned in PUC57 plasmid were used. Standard curve and melting curve analysis was used for quantification. Of the 672 specimens studied, 76 (11.3%) were HPV-16 positive. We found that 35.6% (16/45) were integrated. Statistical analysis showed that there were significant correlations between integration of HPV-16 and cervical cancer end-stage carcinogenesis (P < .0001), episomal form, and ASCUS lesions (P = .045). Significant correlation in penile cancer patients was seen between the episomal form and high-grade cancer stage (P = .037). Integration is a major factor in the carcinogenesis mechanism of HPV and has different prevalence in various cancers with a higher rate in progression except in penile cancer.
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http://dx.doi.org/10.1016/j.tranon.2018.02.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854915PMC
June 2018

Clinical Manifestations and Diagnosis of Nonalcoholic Fatty Liver Disease.

Iran J Pathol 2017 1;12(2):99-105. Epub 2017 Apr 1.

Gastrointestinal and Liver Disease Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background & Objective: Nonalcoholic fatty liver diseases (NAFLD) is the major cause of hepatocellular carcinoma and increases the risk of mortality. Understanding the trends of its clinical and biochemical changes is essential to identify patients with NAFLD that are at the greatest risk of nonalcoholic steatohepatitis (NASH) and cirrhosis in Iran.

Methods: Patients with NAFLD confirmed by ultrasonography were enrolled into the current study. They had negative serologic markers of viral or autoimmune hepatitis, no findings in favor of metabolic liver disease, and had not received medications that affect liver, such as silymarin and Ursobil. Biochemical and clinical symptoms and histological variables were evaluated for each patient. Descriptive statistics were used to compute all variables.

Results: A total of 206 patients, including 109 male and 97 female, with the mean age of 41.2 years were enrolled. The number of patients without obesity and diabetes were 34 (16.4%) and 48 (23.1%), respectively. Sleep disorder, delayed sleep, daytime sleepiness, and late dinner were noticeably common in patients with NAFLD. Furthermore, anxiety, thirst sensation, bloating, warming sensation, defecation disturbances, and upper abdominal pain were common among patients with NAFLD.

Conclusion: NAFLD is a heterogeneous disorder with vast clinical presentations. It seems that anxiety and gastrointestinal problem are common among such patients. Moreover, inadvertent sleep could have a considerable effect on developing NAFLD. Patients with diabetes have more severe NAFLD, based on clinical and histological findings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831064PMC
April 2017

Human Papillomavirus Investigation in Head and Neck Squamous Cell Carcinoma: Initial Report from the Low Risk HPV Types Associations

Asian Pac J Cancer Prev 2017 09 27;18(9):2573-2579. Epub 2017 Sep 27.

Department of Virology, Iran University of Medical Sciences, Tehran, Iran. Email:

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.
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http://dx.doi.org/10.22034/APJCP.2017.18.9.2573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720669PMC
September 2017

Hirschsprung Disease Diagnosis: Calretinin Marker Role in Determining the Presence or Absence of Ganglion Cells.

Iran J Pathol 2016 ;11(4):409-415

Gastrointestinal and Liver Diseases Research Center, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.

Background: Hirschsprung disease is a complex genetic disorder of the enteric nervous system (ENS), often called congenital aganglionic megacolon and characterized by the absence of enteric neurons along a variable length of the intestine. The definitive diagnosis of Hirschsprung disease relies on histologic and/or histochemical staining of sections from suction rectal biopsies. Calretinin immunohistochemistry (IHC) may be a useful in its diagnosis. This study aimed to proof the usefulness of immunohistochemical staining for calretinin in rule out of Hirschsprung disease.

Methods: Paraffin blocks and slides were retrieved from the pathology archives of Ali Asghar Hospital, Tehran, Iran from 2007 to 2011 with pathology report based on the presence (14 patients) or absence (70 patients) of ganglion cells and transitional zone anatomical region (10 patients). Slides were stained with hematoxylin and eosin method to confirm the initial diagnosis was verification again. After preparing the slides, they were stained by IHC for calretinin. Then, the results were analyzed using SPSS software.

Results: In most patients, IHC for calretinin provided highly compatible results with hematoxylin-eosin findings in diagnosis of Hirschsprung disease. The values of specificity and accuracy between calretinin and standard histology (H&E) compared by the Fisher exact test declared calretinin presented significantly higher specificity and accuracy values than H&E staining ( <0.0001).

Conclusion: Calretinin IHC overcomes most of the difficulties encountered using the histology hematoxylin-eosin. Then, IHC for calretinin is a good ancillary method used by pathologists in diagnosis of Hirschsprung disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563939PMC
January 2016

Sensitive High-Resolution Melting Analysis for Screening of KRAS and BRAF Mutations in Iranian Human Metastatic Colorectal Cancers

Asian Pac J Cancer Prev 2016 12 1;17(12):5147-5152. Epub 2016 Dec 1.

Department of Virology, Faculty of Medicine,Shahid Beheshti University of Medical Sciences, Tehran, Iran. Email:

Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes.
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http://dx.doi.org/10.22034/APJCP.2016.17.12.5147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454650PMC
December 2016

Polymorphism of IL-28B Gene (rs12979860) in HCV Genotype 1Patients Treated by Pegylated Interferon and Ribavirin.

Iran J Pathol 2016 ;11(3):216-221

Gastrointestinal & Liver Disease Research Center (GILDRC), Iran University of Medical Sciences, Tehran, Iran; Department of Pathology, Iran University of Medical Sciences, Tehran, Iran.

Background: Nowadays, the immune response to hepatitis C (HCV) treatment has become a crucial issue mostly due to the interleukin 28B (IL-28B) polymorphism effects in chronic HCV patients. The aim of this study was to detect the polymorphism of IL-28B gene (rs12979860) in HCV genotype 1 patients treated with pegylated Interferon and Ribavirin.

Methods: From the 2010 to 2012, a total of 115 peripheral blood mononuclear cells (PBMCs) of HCV patients who presented to Gastrointestinal & Liver Disease Research Center (GILDRC), Firoozgar Hospital, Tehran, Iran were enrolled in this retrospective cross sectional study. Samples were then categorized based on the presence of sustained virologic response (SVR and no-SVR). Variables including age, gender, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of the two groups were investigated based on different IL-28B genotypes.

Results: Analysis by the variables of age and gender showed a mean age ± SD of 42.1±14.0 and gender variability of 44 females (38.2%) and 71 males (61.8%). Adding up these results, the analysis of ALT levels revealed that there was between 293 and 14 mg/ml; AST levels ranged between 217 and 17 mg/ml; the viral load (HCV RNA) ranged between 7,822,000 and 50 IU/ml; the prevalence of CC, CT and TT genotypes were 90.9%, 54% and 25.0%.

Conclusion: IL-28B polymorphism has an effective impact on the therapeutic response to ribavirin and peginterferon combination therapy in chronic HCV patients infected by different genotypes. This polymorphism is crucial in natural clearance.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079454PMC
January 2016

Mutation Analysis of KRAS and BRAF Genes in Metastatic Colorectal Cancer: a First Large Scale Study from Iran.

Asian Pac J Cancer Prev 2016 ;17(2):603-8

Gastrointestinal and Liver Diseases Research Center, Firoozgar Hospital, Iran University Of Medical Sciences, Tehran, Iran E-mail :

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features.

Materials And Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these.

Results: KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics.

Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.
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http://dx.doi.org/10.7314/apjcp.2016.17.2.603DOI Listing
January 2017

Enzymatic Digestion Pattern of Varicella Zoster Virus ORF38 and ORF54 in Chickenpox Patients Using RFLP Technique.

Iran J Pathol 2016 ;11(1):35-40

Dept. of Virology, Iran University of Medical Sciences, Tehran, Iran.

Background: Varicella zoster virus (VZV) causes chickenpox in children and zoster (zona) in the elderly. Using RFLP-PCR method for detection of VZV specific SNPs ORF38, 54 and 62 could distinguish the profile of VZV isolates. The aim of this study was to investigate enzymatic digestion pattern of VZV ORF38 and ORF54 in chickenpox patients using RFLP technique.

Methods: Thirty-eight chickenpox patients, who referred to the hospitals of Iran University of Medical Sciences in Tehran from May 2010 to June 2015 were enrolled in this cross sectional study. After the DNA extraction, PCR amplification of 38 VZV isolates performed by specific primers of ORFs 38 and 54, then RFLP assay and digestion carried out by PstI (for ORF38) and BglI (for ORF54) restriction enzymes.

Results: Of 38 positive VZV DNA, the mean age (yr)±SD was 34.4±23.3 (range: 7-89). 22 (57.9%) were female and 16 (42.1%) were male. The predominant VZV profile of BglI(+) PstI(+) were 89.5% (34/38) followed by 10.5% (4/38) PstI(+) BglI‾. Statistical analysis showed that there was no significant relationship between genotype, age, sex, and year of infection variables (P value> 0.05). The common VZV genotype among Iranian patients with chickenpox and zona infection is genotype BglI(+) PstI(+) followed by PstI(+) BglI‾.

Conclusion: There are different VZV circulating genotypes that call for for more research on this field by widely population and other methods such as nucleotide sequencing to justify the accurate VZV genotype prevalence in Iran.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749193PMC
February 2016

Designing a recombinant Bacmid construct of HCV core+1 in Baculovirus expression system.

Iran J Microbiol 2015 Aug;7(4):221-5

Department of Biology, Islamic Azad University, Tonekabon branch, Tonekabon, IR Iran.

Background And Objectives: Hepatitis C virus (HCV) chronically infects around 200 million people worldwide and frequently causes liver cirrhosis and hepatocellular carcinoma. Rapid detection of this virus results in decreasing the distance between infection and initiation the anti-viral treatment, and may prevent most of the undesirable consequences. The new detected HCV protein "Core+1" made from the ribosomal frame shift in Core region is an important candidate for diagnostic tools. This study was conducted to design a recombinant Bacmid plasmid expressing the HCV 1a Core+1 sequence in the Baculovirus expression system for further diagnostic applications.

Materials And Methods: The HCV Core +1 gene was amplified by PCR using the pcDNA-HAF recombinant vector that contained the Core+1 sequence from HCV genotype 1a as a template, and the specific primers with 2 restriction sites for Nco I and Xba I restriction enzymes. The PCR product was cloned in XbaI/NcoI restriction sites of the linearized pFastBac-HTB vector and evaluated by using those restriction enzymes and sequencing. Then the recombinant pFastBac-HTB vector was transformed in DH10Bac and the result was screened and confirmed by X-Gal discrimination and PCR.

Results: The HCV 1a Core+1 was successfully amplified and the PCR product was confirmed by using the related restriction enzymes and sequencing. Cloning of pFastBac vector with the purified PCR product of HCV Core+1 was confirmed. Finally, the recombinant Bacmid was successfully transformed in DH10Bac.

Conclusion: The recombinant Bac-Core+1 expression vector is considered as an important tool to transfect the sf9 cell line and expression the Core+1 protein.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685167PMC
August 2015