12 research outputs found

    The decrease in NKG2D+ Natural Killer cells in peripheral blood of patients with metastatic colorectal cancer

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    Background: Natural killer (NK) cells play important roles in the immune defense against tumors such as colorectal cancer. In humans, NKG2D is an activating immune receptor constitutively expressed in most cytotoxic lymphocytes including NK and CD8+ T cells. In this study, the expression of NKG2D molecule was investigated in peripheral blood NK cells from colorectal cancer patients and compared with healthy subjects. Methods: We studied 21 non-metastatic (low-grade), 17 non-metastatic (high-grade), 16 metastatic colorectal cancer patients, and 24 healthy controls. Peripheral blood samples were obtained to isolate peripheral blood mononuclear cells (PBMCs) and the percentage of peripheral blood NKG2D+CD3-CD56+ NK cells was analyzed by flow cytometry. The expression of NKG2D at mRNA level was also measured by real-time PCR in both, patients and control subjects. Results: The results showed a significant reduction in the percentage of NKG2D+NK cells as well as NKG2D mRNA expression in peripheral blood of metastatic colon cancer patients. Conclusion: This result suggests that decreased expression of activating NKG2D receptor in metastatic colorectal cancer might compromise NK cell function and allow tumor to evade immunity (Tab. 3, Fig. 4, Ref. 33). Text in PDF www.elis.sk

    Drug-related mutational patterns in hepatitis B virus (HBV) reverse transcriptase proteins from Iranian treatment-Naïve chronic HBV patients

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    Background: Immunomodulators and Nucleotide analogues have been used globally for the dealing of chronic hepatitis B virus (HBV) infection. However, the development of drug resistance is a major limitation to their long-term effectiveness. Objectives: The aim of this study was to characterize the hepatitis B virus reverse transcriptase (RT) protein variations among Iranian chronic HBV carriers who did not receive any antiviral treatments. Materials and Methods: Hepatitis B virus partial RT genes from 325 chronic in active carrier patients were amplified and directly sequenced. Nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database. Results: All strains belonging to genotype D.365 amino-acid substitutions were found. Mutations related to lamivudine, adefovir, telbivudine, and entecavir occurred in (YMDD) 4% (n = 13), (SVQ) 17.23% (n = 56), (M204I/V + L180M) 2.45% (n = 8) and (M204I) 2.76% (n = 9) of patients, respectively. Conclusions: RT mutants do occur naturally and could be found in HBV carriers who have never received antiviral therapy. However, mutations related to drug resistance in Iranian treatment-naïve chronic HBV patients were found to be higher than other studies published formerly. Chronic HBV patients should be monitored closely prior the commencement of therapy to achieve the best regimen option. © 2013, KOWSAR Corp

    Evolution of hepatitis B virus surface gene and protein among Iranian chronic carriers from different provinces

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    Background and Objectives: Iranian chronic HBV carrier�s population has shown a unique pattern of genotype D distribution all around the country. The aim of this study was to explore more details of evolutionary history of carriers based on structural surface proteins from different provinces. Materials and Methods: Sera obtained from 360 isolates from 12 Different regions of country were used for amplification and sequencing of surface proteins. A detailed mutational analysis was undertaken. Results: The total ratio for Missense/Silent nucleotide substitutions was 0.96. Sistan and Kermanshah showed the lowest rate of evolution between provinces (P = 0.055). On the other hand, Khorasan Razavi and Khoozestan contained the highest ratio (P = 0.055). The rest of regions were laid between these two extremes. Azarbayjan and Guilan showed the highest proportion of immune epitope distribution (91.3 and 96, respectively). Conversely, Sistan and Tehran harbored the least percentage (66.6 and 68.8, respectively). Kermanshah province contained only 5.2, whereas Isfahan had 54.5 of B cell epitope distribution. In terms of T helper epitopes, all provinces showed a somehow homogeneity: 22.58 (Fars) to 46.6 (Khuzestan). On the other hand, distribution of substitutions within the CTL epitopes showed a wide range of variation between 6.6 (Khuzestan) and 63 (Kermanshah). Conclusion: Further to low selection pressure found in Iranian population, the variations between different regions designate random genetic drift within the surface proteins. These finding would have some applications in terms of specific antiviral regimen, design of more efficient vaccine and public health issues. © 2015, Tehran University of Medical Science. All rights reserved

    Hepatitis B virus genotype D is the only genotype circulating in Iranian chronic carriers, the unique pattern of genotypic homogeneity

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    Aim: To characterize the hepatitis B virus surface protein genotypes and sequence variations among HBsAg positive chronic Iranian patients from different ethnic groups. Method: The surface genes from 312 patients were amplified and directly sequenced. Results: All strains (100) belonged to genotype D and subtypes ayw2. The average nucleotide mutation frequency was 0.91 (dN/dS < 1.0), indicated negative selection. There was no significant correlation between HBV DNA and ALT levels and the occurrence of amino acid substitutions. However, in terms of HBeAg/Anti-HBe status, the association between both groups for silent nucleotide mutation was strong, indicating selection bias on missense mutations. A higher number of amino acid mutations was found in anti-HBe positive versus HBeAg positive patients.Conclusion: The uniqueness pattern of HBV genetics hemogeniety together with the low mutational frequency indicated that HBV has introduced to Iran recently and isolation of people in the absence of intermixing with other genotypes led to a homologous pattern. © 2014 ACT

    Molecular detection of TEM and AmpC (Dha, mox) broad spectrum β-lactamase in clinical isolates of Escherichia coli

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    Background: Beta- lactamase enzymes are the most important resistant factors to beta lactam antibiotics among gram negative bacteria. Nowadays, the prevalence of betalactamase infection is increasing worldwide and drawn the scientists attention as an important subject. Due to high prevalence of bacteria contained TEM beta lactamase and AmpC enzymes, using molecular methods especially designing universal primers could be valuable to detect all of them. The aim of this study was to determine the prevalence of TEM and AmpC (Dha and MOX) beta- lactamase genes using universal primers. Methods: A total of 500 clinical specimens from various Hospitals in Tehran, Iran were collected and analyzed for E. coli based on biochemical tests. These clinical specimens were also screened by Disk diffusion agar, combined disk method and PCR to detect the samples producing extended- spectrum beta- lactamase. Results: Overall 200 isolates of Escherichia coli were collected from the 500 clinical specimens out of which 128(64) isolates were positive by PCR assay and showed bla-TEM, bla- AmpC (Dha, MOX) genes, 74(57.8) and 5(3.9) to have bla- TEM and bla Dha, respectively. Mox gene was not detected in any of the specimens. Conclusions: Our results revealed that using the molecular methods with phenotype methods is very essential for complete detection of Beta- lactamases. There is the need for updating the treatment protocol because the prevalence of this resistance is increasing

    Molecular evolution and phylodynamics of hepatitis B virus infection circulating in Iran

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    Previous local and national Iranian publications indicate that all Iranian hepatitis B virus (HBV) strains belong to HBV genotype D. The aim of this study was to analyze the evolutionary history of HBV infection in Iran for the first time, based on an intensive phylodynamic study. The evolutionary parameters, time to most recent common ancestor (tMRCA), and the population dynamics of infections were investigated using the Bayesian Monte Carlo Markov chain (BMCMC). The effective sample size (ESS) and sampling convergence were then monitored. After sampling from the posterior distribution of the nucleotide substitution rate and other evolutionary parameters, the point estimations (median) of these parameters were obtained. All Iranian HBV isolates were of genotype D, sub-type ayw2. The origin of HBV is regarded as having evolved first on the eastern border, before moving westward, where Isfahan province then hosted the virus. Afterwards, the virus moved to the south and west of the country. The tMRCA of HBV in Iran was estimated to be around 1894, with a 95 credible interval between the years 1701 and 1957. The effective number of infections increased exponentially from around 1925 to 1960. Conversely, from around 1992 onwards, the effective number of HBV infections has decreased at a very high rate. Phylodynamic inference clearly demonstrates a unique homogenous pattern of HBV genotype D compatible with a steady configuration of the decreased effective number of infections in the population in recent years, possibly due to the implementation of blood donation screening and vaccination programs. Adequate molecular epidemiology databases for HBV are crucial for infection prevention and treatment programs. © 2018, Springer-Verlag GmbH Austria, part of Springer Nature

    Molecular evolution and phylodynamics of hepatitis B virus infection circulating in Iran

    No full text
    Previous local and national Iranian publications indicate that all Iranian hepatitis B virus (HBV) strains belong to HBV genotype D. The aim of this study was to analyze the evolutionary history of HBV infection in Iran for the first time, based on an intensive phylodynamic study. The evolutionary parameters, time to most recent common ancestor (tMRCA), and the population dynamics of infections were investigated using the Bayesian Monte Carlo Markov chain (BMCMC). The effective sample size (ESS) and sampling convergence were then monitored. After sampling from the posterior distribution of the nucleotide substitution rate and other evolutionary parameters, the point estimations (median) of these parameters were obtained. All Iranian HBV isolates were of genotype D, sub-type ayw2. The origin of HBV is regarded as having evolved first on the eastern border, before moving westward, where Isfahan province then hosted the virus. Afterwards, the virus moved to the south and west of the country. The tMRCA of HBV in Iran was estimated to be around 1894, with a 95 credible interval between the years 1701 and 1957. The effective number of infections increased exponentially from around 1925 to 1960. Conversely, from around 1992 onwards, the effective number of HBV infections has decreased at a very high rate. Phylodynamic inference clearly demonstrates a unique homogenous pattern of HBV genotype D compatible with a steady configuration of the decreased effective number of infections in the population in recent years, possibly due to the implementation of blood donation screening and vaccination programs. Adequate molecular epidemiology databases for HBV are crucial for infection prevention and treatment programs. © 2018, Springer-Verlag GmbH Austria, part of Springer Nature
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