In vitro cytotoxic and anti-cancer effects of body wall for sea cucumber (Holothuria leucospilota)

In recent years efforts to find bioactive compounds from live organisms especially marine animals have been increased. In the present study, the anticancer and cytotoxic effects of sea cucumber body walls (Holothuria leucospilota) were investigated. For this purpose, sea cucumbers were collected from Larak Island at depths of 10 to 30 m and extraction process was done with methanol and diethyl ether solvent which then concentrated by rotary evaporator (40℃) following lyophilization with vacuum freeze dryer. XTT method was used to investigate anticancer and cytotoxic effects of body wall extracts. The results showed that the methanolic extract could prevent proliferation of human oral epidermoid carcinoma cells (KB) at concentrations of 100 and 500 μg/ml. The diethyl etheric extract also could prevent proliferation of KB at 500 μg/ml concentration. Overall result showed that sea cucumber body wall had a strong cytotoxic effect on normal cell line (Human embryonic kidney cell [HEK]) which can be used as potent cytotoxic material. However these extracts did not show significant therapeutic value against KB cells

High resolution melting curve assay for detecting rs12979860 IL28B polymorphisms involved in response of iranian patients to chronic hepatitis C treatment

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

Preparation and Evaluation of a New Lipopolysaccharide-based Conjugate as a Vaccine Candidate for Brucellosis

Objectives: Development of an efficacious vaccine against brucellosis has been a challenge for scientists for many years. At present, there is no licensed vaccine against human brucellosis. To overcome this problem, currently, antigenic determinants of Brucella cell wall such as Lipopolysaccharide (LPS) are considered as potential candidates to develop subunit vaccines. Methods: In this study, Brucella abortus LPS was used for conjugation to Neisseria meningitidis serogroup B outer membrane vesicle (OMV) as carrier protein using carbodiimide and adipic acid-mediated coupling and linking, respectively. Groups of eight BALB/c mice were injected subcutaneously with 10μg LPS alone, combined LPS+OMV and conjugated LPS-OMV on 0 days, 14 days, 28 days and 42 days. Anti-LPS IgG was measured in serum. Results: The yield of LPS to OMV in LPS-OMV conjugate was 46.55, on the basis of carbohydrate content. The ratio for LPS to OMV was 4.07. The LPS-OMV conjugate was the most immunogenic compound that stimulated following the first injection with increased IgG titer of ~5-fold and ~1.3-fold higher than that produced against LPS and LPS in noncovalent complex to OMV (LPS+OMV), respectively. The highest anti-LPS IgG titer was detected 2 weeks after the third injection (Day 42) of LPS-OMV conjugate. The conjugated compound elicited higher titers of IgG than LPS+OMV, that showed a 100-120-fold rise of anti-LPS IgG in mice. Conclusion: These results indicate that our conjugated LPS-OMV can be used as a brucellosis vaccine, but further investigation is required. © 2014

Design, modeling, expression, and chemoselective PEGylation of a new nanosize cysteine analog of erythropoietin

Reza Ahangari Cohan1, Armin Madadkar-Sobhani2,3, Hossein Khanahmad1, Farzin Roohvand4, Mohammad Reza Aghasadeghi4, Mohammad Hossein Hedayati5, Zahra Barghi5, Mehdi Shafiee Ardestani4, Davoud Nouri Inanlou1, Dariush Norouzian11Research and Development Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran; 2Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; 3Department of Life Sciences, Barcelona Supercomputing Center, Barcelona, Spain; 4Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Iran; 5Quality Control Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, IranBackground: Recombinant human erythropoietin (rhEPO) is considered to be one of the most pivotal pharmaceutical drugs in the market because of its clinical application in the treatment of anemia-associated disorders worldwide. However, like other therapeutic proteins, it does not have suitable pharmacokinetic properties for it to be administrated at least two to three times per week. Chemoselective cysteine PEGylation, employing molecular dynamics and graphics in in silico studies, can be considered to overcome such a problem.Methods: A special kind of EPO analog was elicited based on a literature review, homology modeling, molecular dynamic simulation, and factors affecting the PEGylation reaction. Then, cDNA of the selected analog was generated by site-directed mutagenesis and subsequently cloned into the expression vector. The construct was transfected to Chinese hamster ovary/dhfr- cells, and highly expressed clones were selected via methotrexate amplification. Ion-immobilized affinity and size exclusion (SE) chromatography techniques were used to purify the expressed analog. Thereafter, chemoselective PEGylation was performed and a nanosize PEGylated EPO was obtained through dialysis. The in vitro biologic assay and in vivo pharmacokinetic parameters were studied. Finally, E31C analog Fourier transform infrared, analytical SE-high-performance liquid chromatography, zeta potential, and size before and after PEGylation were characterized.Results: The findings indicate that a novel nanosize EPO31-PEG has a five-fold longer terminal half-life in rats with similar biologic activity compared with unmodified rhEPO in proliferation cell assay. The results also show that EPO31-PEG size and charge versus unmodified protein was increased in a nanospectrum, and this may be one criterion of EPO biologic potency enhancement.Discussion: This kind of novel engineered nanosize PEGylated EPO has remarkable advantages over rhEPO.Keywords: nanoPEGylated EPO, cysteine PEGylation, pharmacokinetic propert

Prevalence of Merkel cell polyomavirus in Tehran: An age-specific serological study

Background: Several new types of polyomavirus have been discovered in recent years mainly because of the recent state-of-the-art detection technologies. Among the polyomaviruses, Merkel cell polyomavirus (MCPyV) has attracted the most attention because of its possible role in the etiology of Merkel cell carcinoma, a rare but lethal form of skin cancer. Objectives: This study aimed to determine age-specific seroprevalence of MCPyV in Tehran. Patients and Methods: In this cross-sectional study, we collected 440 serum samples from healthy individuals 2 to 78 years of age who visited the Pasteur Institute�s clinic in Tehran, Iran, using a convenience sampling strategy. We developed a virus-like particle-based enzyme-linked immunosorbent assay that uses VP1, the major capsid protein of MCPyV, to detect and quantitate serum antibodies to MCPyV. We compared the prevalence of MCPyV between males and females and across eight age groups. Results: A total of 255 (57.9) of the serum samples were MCPyV positive. The seroprevalence in children under 10 years of age was 25. The seroprevalence increased to 56 over the next decade of life (10 - 19 years of age). The seroprevalence rate in males and females was 56.1 and 59.7 respectively, and a binary logistic regression showed no significant difference between males and females (P = 0.77). However, the prevalence of MCPyV increased with age (P = 0.012). Conclusions: Our results suggest that human exposure to MCPyV occurs throughout life. The MCPyV antibody levels remained high among older adults in our population, consistent with reports from other populations. © 2016, Iranian Red Crescent Medical Journal

Comparison of the cost-effectiveness of transesophgeal and transthoracic echocardiographies to detect cardioembolic causes of stroke in non-selected patients

Background: Both Transthoracic Echocardiography (TTE) and Transesophgeal Echocardiography (TEE) are effective investigation tools to detect cardioaortic sources of embolism in ischemic stroke. Nevertheless, there are still uncertainties about the cost-effectiveness of these methods in non-selected patients with acute stroke. Objectives: This study aimed to investigate the cost-effectiveness of TTE and TEE using a decision analytic model in non-selected patients with acute ischemic stroke with or without clinical and radiological signs of embolic pattern. Patients and Methods: This cross-sectional cost-effectiveness study was performed in Nemazee hospital affiliated to Shiraz University of Medical Sciences from January 2014 to April 2014. TTE and TEE were performed for all 65 consecutive patients with ischemic stroke (51.3 male, mean age of 69.7 ± 17.9 years). The required data were direct costs related to performance of TTE and TEE, which were obtained from the patients� bills in their charts. A decision analytic model was implemented to assess the cost-effectiveness of these two methods, which demonstrated an Incremental Cost-Ef-fectiveness Ratio (ICER). Effectiveness was determined based on the number of disorders diagnosed using each of the two echoes confirmed by two cardiologists. All analyses were done using Tree Age Pro 2011. Results: The results showed that TEE was more expensive than TTE in non-selected patients. Performing TEE increased the cost by 1494 USD and the effectiveness by 7. As per ICER equation, for each increment unit in the effectiveness, performing TEE would increase the cost by 213.4 USD compared to TTE. TEE was cost-effective in comparison to TTE regardless of age factor considering the cutoff of Gross Domestic Product (GDP) by three for ICER. Moreover, TTE was cost-effective in 41-60-and 61-80-year-old age groups, while TEE was cost-effective in the 41-60-year-old age group. However, none of the techniques was cost-effective in patients above 81 years old. Conclusions: The results of this study can help reduce the unnecessary use of echocardiography by considering the age group and their corresponding risk factors for developing ischemic stroke. © 2018, Iranian Cardiovascular Research Journal. All rights reserved

Comparison of the cost-effectiveness of transesophgeal and transthoracic echocardiographies to detect cardioembolic causes of stroke in non-selected patients

Background: Both Transthoracic Echocardiography (TTE) and Transesophgeal Echocardiography (TEE) are effective investigation tools to detect cardioaortic sources of embolism in ischemic stroke. Nevertheless, there are still uncertainties about the cost-effectiveness of these methods in non-selected patients with acute stroke. Objectives: This study aimed to investigate the cost-effectiveness of TTE and TEE using a decision analytic model in non-selected patients with acute ischemic stroke with or without clinical and radiological signs of embolic pattern. Patients and Methods: This cross-sectional cost-effectiveness study was performed in Nemazee hospital affiliated to Shiraz University of Medical Sciences from January 2014 to April 2014. TTE and TEE were performed for all 65 consecutive patients with ischemic stroke (51.3 male, mean age of 69.7 ± 17.9 years). The required data were direct costs related to performance of TTE and TEE, which were obtained from the patients� bills in their charts. A decision analytic model was implemented to assess the cost-effectiveness of these two methods, which demonstrated an Incremental Cost-Ef-fectiveness Ratio (ICER). Effectiveness was determined based on the number of disorders diagnosed using each of the two echoes confirmed by two cardiologists. All analyses were done using Tree Age Pro 2011. Results: The results showed that TEE was more expensive than TTE in non-selected patients. Performing TEE increased the cost by 1494 USD and the effectiveness by 7. As per ICER equation, for each increment unit in the effectiveness, performing TEE would increase the cost by 213.4 USD compared to TTE. TEE was cost-effective in comparison to TTE regardless of age factor considering the cutoff of Gross Domestic Product (GDP) by three for ICER. Moreover, TTE was cost-effective in 41-60-and 61-80-year-old age groups, while TEE was cost-effective in the 41-60-year-old age group. However, none of the techniques was cost-effective in patients above 81 years old. Conclusions: The results of this study can help reduce the unnecessary use of echocardiography by considering the age group and their corresponding risk factors for developing ischemic stroke. © 2018, Iranian Cardiovascular Research Journal. All rights reserved

Prevalence and risk factors for HBV and HCV in prisoners in Iran: a national bio-behavioural surveillance survey in 2015

Objectives: To provide more accurate estimates of the prevalence of Hepatitis B (HBV) and Hepatitis C (HCV) and their contributing factors among prisoners in Iran. Methods: Cross-sectional study of 6200 Iranian prisoners in 2015. Data were collected through questionnaires and interviews. HBV infection and HCV exposure status of the participants was determined by HBsAg and HCV antibodies blood tests using enzyme-linked immunosorbent assay (ELISA). Data were analysed in STATA-12. Result: Prevalence of HCV exposure was 9.48 (95 CI: 8.73�10.27), and prevalence of HBV was 2.48 (95 CI: 2.07�2.89) in the general prison population. In multivariate analysis, the most important risk factor for HBV was a history of drug use in lifetime (adjusted odds ratio, AOR: 1.8, 95 CI: 1.17�3.02). The main risk factors for HCV exposure were a history of drug use in lifetime (AOR: 4.08, CI: 2.56�6.27), age over 30 (AOR: 2.68, CI: 2.01�3.56), and having tattoos (AOR = 1.67, CI: 1.35�2.07). Conclusion: Although vaccination is used to control HBV among prisoners, prevalence of HCV exposure is alarming in the prison population of Iran, especially among people who inject drugs. Eliminating viral hepatitis in Iran by 2030 requires a national commitment and rapid measures for targeting this high-risk group. Given the increased efficiency of HCV treatment in recent years, prisons provide an opportunity to access patients for treatment. © 2018 John Wiley & Sons Lt

Prevalence and risk factors for HBV and HCV in prisoners in Iran: a national bio-behavioural surveillance survey in 2015

Objectives: To provide more accurate estimates of the prevalence of Hepatitis B (HBV) and Hepatitis C (HCV) and their contributing factors among prisoners in Iran. Methods: Cross-sectional study of 6200 Iranian prisoners in 2015. Data were collected through questionnaires and interviews. HBV infection and HCV exposure status of the participants was determined by HBsAg and HCV antibodies blood tests using enzyme-linked immunosorbent assay (ELISA). Data were analysed in STATA-12. Result: Prevalence of HCV exposure was 9.48 (95 CI: 8.73�10.27), and prevalence of HBV was 2.48 (95 CI: 2.07�2.89) in the general prison population. In multivariate analysis, the most important risk factor for HBV was a history of drug use in lifetime (adjusted odds ratio, AOR: 1.8, 95 CI: 1.17�3.02). The main risk factors for HCV exposure were a history of drug use in lifetime (AOR: 4.08, CI: 2.56�6.27), age over 30 (AOR: 2.68, CI: 2.01�3.56), and having tattoos (AOR = 1.67, CI: 1.35�2.07). Conclusion: Although vaccination is used to control HBV among prisoners, prevalence of HCV exposure is alarming in the prison population of Iran, especially among people who inject drugs. Eliminating viral hepatitis in Iran by 2030 requires a national commitment and rapid measures for targeting this high-risk group. Given the increased efficiency of HCV treatment in recent years, prisons provide an opportunity to access patients for treatment. © 2018 John Wiley & Sons Lt