Publications by authors named "Ahad Alizadeh"

48 Publications

Improved risk assessment of coronary artery disease by substituting paraoxonase 1 activity for HDL-C: Novel cardiometabolic biomarkers based on HDL functionality.

Nutr Metab Cardiovasc Dis 2021 Jan 1. Epub 2021 Jan 1.

Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background And Aims: Developing laboratory assays to evaluate HDL functions and improve cardiovascular disease (CVD) risk assessment has recently emerged as a challenge. The present study was conducted to help predict the risk of coronary artery disease (CAD) by investigating new cardiometabolic risk factors based on substituting paraoxonase 1 (PON1) as a critical enzyme in the functionality of HDL for that of HDL-C.

Methods And Results: The present study recruited 274 subjects undergoing diagnostic coronary angiography, 92 without significant CAD (non-CAD), and 182 with a severe CAD. The diagnostic accuracy of the new biomarkers in non-CAD versus multi-vessel disease was obtained in descending order of AUC as 0.72 (P < 0.001) for log (TG/PON1), 0.70 (P < 0.001) for nonHDL-C/PON1, and 0.67 (P < 0.001) for LDL-C/PON1. After performing a multivariate adjustment for age, gender, BMI, statin therapy, and diabetes mellitus, the increased odds of CAD remained significant for the new cardiometabolic ratios as independent variables [adjusted OR = 1.47 (1.15-1.88), p = 0.002 for LDL-C/PON1; adjusted OR = 2.15 (1.41-3.5), p = 0.009 for nonHDL-C/PON1; adjusted OR = 5.03 (2.14-13.02), p = 0.004 for log (TG/PON1)]. CAD was diagnosed with an optimal discriminating cutoff of 1.84 for LDL-C/PON1, 2.8 for nonHDL-C/PON1, and 0.48 for log (TG/PON1).

Conclusions: To improve CAD's risk assessment, the PON1 activity was proposed as an alternative to HDL-C in the commonly used atherogenic lipid ratios. Substituting the PON1 activity for the HDL-C concentration can provide an index of the HDL activity. The present study sought to exploit the lipoprotein-related risk factors of CAD from a more effective perspective.
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http://dx.doi.org/10.1016/j.numecd.2020.12.026DOI Listing
January 2021

The marginal causal effect of opium consumption on the upper gastrointestinal cancer death using parametric g-formula: An analysis of 49,946 cases in the Golestan Cohort Study, Iran.

PLoS One 2021 25;16(1):e0246004. Epub 2021 Jan 25.

Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Upper gastrointestinal (UGI) cancer, including esophageal and gastric, is one of the most common cancers in the world. Hence, the determination of risk factors of UGI helps to reduce the economic and social burden of this cancer in communities. In Iran, the consumption of opium because of its neighborhood with Afghanistan are considerable. In this study, we examine the causal effect of opium use on the time to UGI cancer death. Based on the Golestan Cohort Study (GCS) in northeastern of Iran, about 50000 adults were enrolled to the study for four years (2004-2008) and followed annually until July 2018. We used "parametric g-formula" to study the causal effect of opium use on the time to death due to UGI. In this study, the information of 49946 individuals due to missingness were analyzed. So the median of follow-up time was 144 months and the prevalence of opium use was 17% (about 8489 persons). During the follow-up period, 593 (1.2%) death from upper gastrointestinal cancer were reported. The study showed that the effect of opium use on the time to UGI death was statistically significant (adjusted risk-ratio based on parametric g-formula = 1.31, 95% CI: [1.04, 1.65]). Additionally, the Population Attributable Fraction (PAF) in UGI cancer deaths of opium use was estimated 5.3% (95% CI: [0.6%, 11.3%]). Our results showed a causal effect of opium use on the intensity of upper gastrointestinal cancer death.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246004PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833230PMC
January 2021

Comprehensive Survey of Plagiarism in Iran.

Pak J Med Sci 2020 Nov-Dec;36(7):1441-1448

Ladan Rokni, PhD, Asia Contents Institute, Konkuk University, Seoul, South Korea.

Background And Objective: We conducted this study to assess the prevalence of plagiarism and to shed light on some dark aspects of this issue. The main objectives included to find out the etiology, prevalence, and detection of various forms plagiarism.

Methods: In this Cross-sectional study we used a questionnaire, face-to-face interview, analyzing the present notifications and codes, websites, and literature review. The current study was conducted throughout Iran from 2017-2018. Those associated with scientific journalism, academic staffs, and authors were interviewed or asked to fill out a prepared questionnaire.

Results: Nine hundred seventy nine questionnaires were circulated. Out of this 706 (72.1%) were completed and returned. Those with a master degree were most cooperative in filling out the questionnaires (36.4%); followed by Assistant Professors (29.6%). About 74.1% of respondents, had not participated in any educational workshops on plagiarism (<0.001) while 10.8% had not heard anything about plagiarism (<0.001). As regards correct reply as for definition and detecting plagiarism; 91.1%, 40.8%, 48.4% and 57.9% could reply correctly (<0.001). Forty-one-point one percent of the participants believed that reprimand would be the best punishment. The percentage of plagiarism as per people associated in journal administration, was 22.9%; based on experts' opinions, it was 30.0%; and based on analysis of some journals published in Iran, it was 25.5%.

Conclusion: We found a noticeable prevalence of plagiarism in Iran. Many factors are involved in this misconduct; most important being the need for academic staff and students to publish e more papers regardless of their quality to meet some of the academic requirements. Considering the high rank of Iran in terms of scientific growth worldwide, it is expected from the regulatory authorities to monitor all aspects of scientific misconducts in medical journalism.
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http://dx.doi.org/10.12669/pjms.36.7.3456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674871PMC
November 2020

Association between prostate-specific antigen change over time and prostate cancer recurrence risk: A joint model.

Caspian J Intern Med 2020 May;11(3):324-328

Department of Urology, Babol University of Medical Sciences, Babol, Iran.

Background: Prostate specific antigen (PSA) is an important biomarker to monitor patients after treated with radiation therapy (RT). The aim of this study is to evaluate the relationship between the PSA data and prostate cancer recurrence using the joint modeling.

Methods: This historical cohort study was performed on 422 prostate cancer patients. Inclusion criteria included: patients with localized prostate cancer referring to Cancer Institute in Tehran (Iran) from 2007 to 2012, and under radiation therapy. Joint model has two components or sub-models. We showed the results by parameter estimating the longitudinal sub-model and survival sub-model. EM algorithm, Newton-Gauss and Gauss-Hermit law were used for final model parameters. R software version 3.2 was used for statistical analysis.

Results: In this study, considering the inclusion and exclusion criteria, out of 422 patients, the data on 314 cases were selected for analysis and the main result of joint model was obtained. PSA directly and significantly was associated with recurrence risk, therefore increasing 2.6 ml/lit PSA (one unit in transformed PSA) increases 39% recurrence risk (95% CI for RR: 1.09-1.77). Also, slope of PSA trend has significant association with prostate cancer recurrence risk (95% CI for RR: 1.05-1.41).

Conclusion: This study showed a significant relationship between PSA, and its slope with the recurrence risk by joint model, with regard to the pathological, demographic and clinical features in the Iranian population.
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http://dx.doi.org/10.22088/cjim.11.3.324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442453PMC
May 2020

Presence of JC Polyomavirus in Nonneoplastic Inflamed Colon Mucosa and Primary and Metastatic Colorectal Cancer.

Gastrointest Tumors 2020 Apr 18;7(1-2):30-40. Epub 2019 Nov 18.

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

Background: Despite decades of epidemiologic and histopathologic investigations, the association between JC polyomavirus (JCPyV) infection and colorectal cancer (CRC) remains controversial.

Objective: This study tested the presence of JCPyV sequences and determined the viral load in a series of colorectal samples from Iranian patients. In total, 223 formalin-fixed paraffin-embedded samples from patients diagnosed with primary and metastatic CRC as well as with nonneoplastic inflamed colon mucosa were analyzed by quantitative real-time PCR for the presence of JCPyV large tumor antigen (LT-Ag) sequences.

Results: JCPyV LT-Ag sequences were detected in 18.6% of the CRC tissues and in 15.5% of the nonneoplastic control group. Viral LT-Ag was quantified in 18/100 primary colon adenocarcinomas, 2/10 metastatic adenocarcinomas, and 1/3 primary adenocarcinomas of the rectum. Two JCPyV-positive metastatic tumors presented a negative test result for JCPyV in the corresponding primary tumor. The median JCPyV LT-Ag copy number was 64 × 10-2 per cell and 14 × 10-2 per cell in the CRC cases and the nonneoplastic samples, respectively. There was no statistically significant difference between the two study groups regarding median LT-Ag DNA load ( = 0.059). Among the JCPyV-positive samples, the LT-Ag DNA load was higher in 2 metastatic tumors (from a patient with lung metastasis: 232 × 10-2 copies per cell; from a patient with liver metastasis: 121 × 10-2 copies per cell).

Conclusions: The detection of JCPyV DNA at low copy numbers (lower than 1 viral copy per cell equivalent) and the absence of viral sequences in the corresponding primary tumors of the JCPyV-positive metastatic samples weaken the hypothesis of an etiological role of JCPyV in primary CRC induction.
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http://dx.doi.org/10.1159/000504293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206609PMC
April 2020

Long-Term Follow-up of Autologous Fibroblast Transplantation for Facial Contour Deformities, A Non-Randomized Phase IIa Clinical Trial.

Cell J 2020 Apr 8;22(1):75-84. Epub 2019 Sep 8.

Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic Address:

Objective: Recently, the promising potential of fibroblast transplantation has become a novel modality for skin rejuvenation. We investigated the long-term safety and efficacy of autologous fibroblast transplantation for participants with mild to severe facial contour deformities.

Materials And Methods: In this open-label, single-arm phase IIa clinical trial, a total of 57 participants with wrinkles (n=37, 132 treatment sites) or acne scars (n=20, 36 treatment sites) who had an evaluator's assessment score of at least 2 out 7 (based on a standard photo-guide scoring) received 3 injections of autologous cultured fibroblasts administered at 4-6 week intervals. Efficacy evaluations were performed at 2, 6, 12, and 24 months after the final injection based on evaluator and patient's assessment scores.

Results: Our study showed a mean improvement of 2 scores in the wrinkle and acne scar treatment sites. At sixth months after transplantation, 90.1% of the wrinkle sites and 86.1% of the acne scar sites showed at least a one grade improvement on evaluator assessments. We also observed at least a 2-grade improvement in 56.1% of the wrinkle sites and 63.9% of the acne scar sites. A total of 70.5% of wrinkle sites and 72.2% of acne scar sites were scored as good or excellent on patient assessments. The efficacy outcomes remained stable up to 24-month. We did not observe any serious adverse events during the study.

Conclusion: These results have shown that autologous fibroblast transplantation could be a promising remodeling modality with long-term corrective ability and minimal adverse events (Registration Number: NCT01115634).
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http://dx.doi.org/10.22074/cellj.2020.6340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791067PMC
April 2020

Risk of gestational diabetes mellitus following assisted reproductive technology: systematic review and meta-analysis of 59 cohort studies.

J Matern Fetal Neonatal Med 2019 Oct 1:1-10. Epub 2019 Oct 1.

Department of Medical Ethics and Law, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR , Tehran , Iran.

The use of assisted reproductive technology (ART) has been associated with an increased risk of gestational diabetes mellitus (GDM) in previous studies, but its risk has not been consistent. Therefore, we aimed to estimate the risk of GDM in women who conceived with ART via a systematic review and meta-analysis of cohort studies. ISI Web of Knowledge, Medline/PubMed, Scopus, and Embase databases were searched to identify studies that evaluated the risk of GDM through May 2017 using the relevant keywords. Two reviewers independently performed the screening, data extraction, and quality assessment. Meta-analysis was performed with a random effects model. The search yielded 957 records relating to GDM and use of ART, from which 59 eligible cohorts were selected for meta-analysis ( = 96,785). There was evidence of substantial heterogeneity among these studies ( = 3072.34,  < .001; =98.1%). The pooled estimate of GDM risk using the random effects model was 9.00% (95% CI: 7.90-10.20). Visual inspection of the funnel plot indicated the presence of low publication bias, but Egger's test did not reveal publication bias. The findings revealed that the risk of GDM was very high among women who conceived with ART treatment. GDM screening, management, and improved care are vital in ART pregnancy.
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http://dx.doi.org/10.1080/14767058.2019.1670790DOI Listing
October 2019

The Ability of Polyuria in Prediction of Weaning Outcome in Critically Ill Mechanically Ventilated Patients.

Tanaffos 2019 Jan;18(1):74-78

Internal Medicine Department, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Fluid balance and oliguria influence outcome in critically ill patients. Although, osmotic dieresis with hypernatraemia is a predictor of mortality in critically ill patients, the purpose of this study was to demonstrate the effect of polyuria as an independent predictor on weaning outcome in mechanically ventilated patients.

Materials And Methods: This retrospective, single center, cohort study was carried out at Imam Teaching Hospital Intensive Care Unit (ICU) on 263 adult mechanically ventilated patients. We collected data of these patients during the mean seven consecutive days before weaning from mechanical ventilator. Patients with polyuria (sustained urine output greater than 3000 ml/day) were compared with patients without polyuria. The primary endpoint was successful weaning and the secondary endpoints were the mechanical ventilation duration, post weaning length of ICU stay, post weaning length of hospitalization and rate of mortality.

Results: In 93 patients with polyuria, the mean age was 45.14±19.47 years in comparison of 170 patients without polyuria with mean age of 52.9±21.37 years (P=0.004). Fluid intake, urine output and temperature were significantly higher in patients with polyuria, but there were no statistical differences in systolic and diastolic blood pressure, serum electrolytes, urea and creatinine. No significant differences were found in primary and secondary endpoints including successful weaning, post weaning length of ICU stay, post weaning hospital duration and mortality, except for duration of mechanical ventilation (P=0.014). The area under the ROC curve for variables showed only seven days mean creatinine level before weaning which may act as a predictor of successful weaning (ROCAUC=0.67, 95% CI 0.61-0.73, P=0.0002). Serum creatinine level of 0.8 provided best overall combination of sensitivity and specificity for successful weaning (sensitivity 72.22%, 95% CI 54.8-85.8; specificity 61.19%, 95% CI 54.1-68.0).

Conclusion: Polyuria cannot predict weaning outcome but maybe considered as a predictor of longer duration of mechanical ventilation and is probably associated with a subclinical renal dysfunction.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690324PMC
January 2019

Radiation dose-response (a Bayesian model) in the radiotherapy of the localized prostatic adenocarcinoma: the reliability of PSA slope changes as a response surrogate endpoint.

PeerJ 2019 1;7:e7172. Epub 2019 Jul 1.

Department of Radiation Oncology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.

Purpose: One of the characteristics of Prostate-Specific Antigen (PSA) is PSA slope. It is the rate of diminishing PSA marker over time after radiotherapy (RT) in prostate cancer (PC) patients. The purpose of this study was to evaluate the relationship between increasing RT doses and PSA slope as a potential surrogate for PC recurrence.

Patients And Methods: This retrospective study was conducted on PC patients who were treated by radiotherapy in the Cancer Institute of Iran during 2007-2012. By reviewing the records of these patients, the baseline PSA measurement before treatment (iPSA), Gleason score (GS), clinical T stage (T. stage), and periodic PSA measurements after RT and the total radiation dose received were extracted for each patient separately. We used a Bayesian dose-response model, analysis of variance, Kruskal-Wallis test, Kaplan-Meier product-limit method for analysis. Probability values less 0.05 were considered statistically significant.

Results: Based on the D'Amico risk assessment system, 13.34% of patients were classified as "Low Risk", 51.79% were "Intermediate Risk", and 34.87% were "High Risk". In terms of radiation doses, 12.31% of the patients received fewer than 50 Gy, 15.38% received 50 to 69 Gy, 61.03% received 70 Gy, and 11.28% received more than 70 Gy. The PSA values decreased after RT for all dose levels. The slope of PSA changes was negative for 176 of 195 patients. By increasing the dosage of radiation, the PSA decreased but these changes were not statistically significant ( = 0.701) and PSA slope as a surrogate end point cannot met the Prentice's criteria for PC recurrence.

Conclusion: Significant changes in the dose-response relationship were not observed when the PSA slope was considered as the response criterion. Therefore, although the absolute value of the PSA decreased with increasing doses of RT, the relationship between PSA slope changes and increasing doses was not clear and cannot be used as a reliable response surrogate endpoint.
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http://dx.doi.org/10.7717/peerj.7172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610535PMC
July 2019

A Comprehensive, Epidemiological and Ecological Descriptive Study on Vitamin D Status in Iran (308005 People, from 2009-2018).

Iran J Public Health 2019 Apr;48(4):644-654

Payvand Teb va Narmafzar Company (PTN), Tehran, Iran.

Background: Vitamin D is an essential substance for absorption of calcium and phosphorus from intestine so it is vital for muscles and skeletal development. Deficiency of this vitamin is pandemic. The vitamin D status depends on the different factors such as UV exposure, diet, and ecological features of living location, age and gender. The aim of this study was to describe the vitamin D level in different provinces of Iran and to investigate the association between vitamin D status and multiple variables.

Methods: We collected the serum 25(OH)D (Vitamin D) level data of 308,005 people referred to different laboratories from 30 provinces of Iran and organized them by each province, year, age, gender, precipitation, latitude and longitude, and humidity over 10 yr (2009-2018). Data were analyzed to find out the correlation between age, gender, longitude and latitude, humidity and sum of precipitation.

Results: West Azerbaijan had the highest level of vitamin D with a mean level of 33.24 and a standard deviation of 32.001, and North Khorasan had the lowest level with a mean level of 14.46 and a standard deviation of 8.980 among 30 provinces of Iran. The correlation between all studied variables (age, and gender, latitude and longitude, humidity, the sum of precipitation) was significant (<0.001).

Conclusion: The average total vitamin D level in Iran is 25.41 ng/ml, which is within the area of deficiency. Vitamin D is associated with age, and gender, latitude and longitude, humidity, the sum of precipitation. So changes in any of these variables can lead to vitamin D alteration.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500541PMC
April 2019

Assisted reproductive technology and the risk of preeclampsia: an updated systematic review and meta-analysis.

BMC Pregnancy Childbirth 2019 May 2;19(1):149. Epub 2019 May 2.

School of Nursing and Midwifery, Guilan University of Medical Sciences, Rasht, Iran.

Background: The objective of this systematic review and meta-analyses was to assess the risk of preeclampsia among women who conceived with assisted reproductive technology (ART).

Methods: We searched the ISI Web of Knowledge, Medline/PubMed, Scopus, and Embase (from inception to May 2017) for English language articles using a list of key words. In addition, reference lists from identified studies and relevant review articles were also searched. Data extraction was performed by two authors, and the study quality was assessed using the Newcastle-Ottawa Scale. Random-effects model meta-analysis was applied to pool the relative risks (RR) across studies.

Results: A total of 48 studies (5 case-control studies and 43 cohort studies) were included in this meta-analysis. The Cochran Q test and I statistics revealed substantial heterogeneity (Q = 26,313.92, d.f. = 47, p < 0.001 and I = 99.8%). Meta-analysis showed a significant increase in preeclampsia in women who conceived by ART compared with those who conceived spontaneously (RR = 1.71, 95% CI = 1.11-2.62, p = 0.015).

Conclusions: The findings of this systematic review indicate that the use of ART treatment is associated with a 1.71-fold increase in preeclampsia.
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http://dx.doi.org/10.1186/s12884-019-2291-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498659PMC
May 2019

The myo-inositol effect on the oocyte quality and fertilization rate among women with polycystic ovary syndrome undergoing assisted reproductive technology cycles: a randomized clinical trial.

Arch Gynecol Obstet 2019 06 27;299(6):1701-1707. Epub 2019 Mar 27.

Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), Iran University of Medical Sciences, PO Box: 15875-1454, 1168743514, Tehran, Iran.

Purpose: The aim of the present study was to evaluate the effect of myo-Inositol administration on oocyte quality, fertilization rate and embryo quality in patients with PCOS during assisted reproductive technology (ART) cycles.

Methods: Fifty infertile PCOS patients were randomly designated in two groups. In the study group, patients received daily doses of 4 g myo-Inositol combined with 400 mg folic acid and in the control group patients received only 400 mg folic acid from 1 month before starting the antagonist cycle until the day of ovum pick up. Oocyte and embryo qualities were assessed according to European Society of Human Reproduction and Embryology (ESHRE) guidelines. The gene expression of PGK1, RGS2 and CDC42 as a factor of oocyte quality in granulosa cells was analyzed using real-time RT-PCR. Levels of total antioxidant capacity (TAC) and reactive oxygen species (ROS) were evaluated by chemiluminescence assay in follicular fluid.

Results: The percentage of metaphase II oocyte, fertilization rate and embryo quality significantly improved in the study group (p < 0.05), but the number of retrieved oocytes and follicle count were not statistically different between groups. Furthermore, the gene expression of PGK1, RGS2 and CDC42 was significantly higher in the study group (p < 0.05) but no differences were found between two groups in terms of TAC and ROS levels.

Conclusions: The present study findings suggest that myo-Inositol alters the gene expression in granulosa cells and improves oocyte and embryo quality among PCOS patients undergoing ART.
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http://dx.doi.org/10.1007/s00404-019-05111-1DOI Listing
June 2019

Paraoxonase-2 variants potentially influence insulin resistance, beta-cell function, and their interrelationships with alanine aminotransferase in type 2 diabetes.

J Res Med Sci 2018 28;23:107. Epub 2018 Dec 28.

Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: The aim of this study was to determine whether insulin resistance, beta-cell function, and their associations with alanine aminotransferase (ALT) are affected by the functional variants of paraoxonase-2 (PON2) as an intracellular antioxidant in patients with type 2 diabetes (T2D).

Materials And Methods: Quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment for beta-cell function (HOMA-BCF) were assessed in T2D patients. Insulin levels were determined using ELISA. The variants PON2-A148G and PON2-S311C were genotyped using polymerase chain reaction-based restriction fragment length polymorphism.

Results: According to the PON2-G148A variant, ALT was found to be significantly correlated with QUICKI ( = -0.616, = 0.005) and HOMA-BCF ( = 0.573, = 0.01) in the GA + GG group; however, the correlations were not statistically significant in the AA genotypes. Based on the genotypes of PON2-S311C, there was a significant correlation between ALT with QUICKI ( = -0.540, = 0.031) and HOMA-BCF ( = 0.567, = 0.022) in the SC + CC group. In the multiple adjusted logistic regression analyses, considering the variants PON2-G148A and PON2-C311S as independent variables and QUICKI and HOMA-BCF as the dependent variables, both variants were significantly associated with the QUICKI ( = 0.019 for PON2-G148A and = 0.041 for PON2-C311S). Furthermore, PON2-C311S remained significantly associated with HOMA-BCF ( = 0.03).

Conclusion: These data implicate a role for the functional variants of PON2 in insulin resistance and beta-cell function as well as underscore the effective role of these variants in the associations between them and ALT. Our data contribute to our understanding of the important physiologic functions of PON2 in glucose metabolism and its related metabolic diseases.
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http://dx.doi.org/10.4103/jrms.JRMS_88_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327680PMC
December 2018

Measurement of peripheral dose to the pelvic region and the associated risk for cancer development after breast intraoperative electron radiation therapy.

J Radiol Prot 2019 Mar 11;39(1):278-291. Epub 2019 Jan 11.

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

This study aimed to measure the received dose to the pelvic region of patients during breast intraoperative electron radiation therapy (IOERT). Furthermore, we compared the findings with those of external beam radiation therapy. Finally, secondary ovarian and uterus cancer risks following breast IOERT were estimated. In the current study, the received dose to the pelvic surface of 18 female patients during breast IOERT boosts were measured by thermoluminescent dosimeter (TLD-100) chips. All patients were treated with 12 Gy given in a single fraction. To estimate the dose to the ovary and uterus of the patients, conversion coefficients for depth from the surface dose were obtained in a Rando phantom. Given the received dose to the pelvic region of the patients, secondary ovarian and uterus cancer risks following breast IOERT were estimated. The received doses to the ovary and uterus surface of the patients were 0.260 ± 0.155 mGy to 31.460 ± 6.020 mGy and 0.485 ± 0.122 mGy to 22.387 ± 15.476 mGy, respectively. Corresponding intra-pelvic (ovary and uterus) regional doses were 0.012 ± 0.007 mGy to 1.479 ± 0.283 mGy and 0.027 ± 0.001 mGy to 1.164 ± 0.805 mGy, respectively. Findings demonstrated that the ratio of the received dose by the pelvic surface to the regional dose during breast IOERT was much less than external beam radiation therapy. The mean of the secondary cancer risks for the ovary in 8 and 10 MeV electron beam energies were 135.722 ± 117.331 × 10 and 69.958 ± 28.072 × 10, and for the uterus were 17.342 ± 10.583 × 10 and 2.971 ± 3.604 × 10, respectively. According to our findings, the use of breast IOERT in pregnant patients can be considered as a safe radiotherapeutic technique, because the received dose to the fetus was lower than 50 mGy. Furthermore, IOERT can efficiently reduce the unnecessary dose to the pelvic region and lowers the risk of secondary ovarian and uterus cancer following breast irradiation.
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http://dx.doi.org/10.1088/1361-6498/aafdc8DOI Listing
March 2019

Risk of preeclampsia following assisted reproductive technology: systematic review and meta-analysis of 72 cohort studies.

J Matern Fetal Neonatal Med 2020 Aug 7;33(16):2826-2840. Epub 2019 Jan 7.

Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Previous studies have indicated that women with assisted reproductive technology (ART) pregnancy have an increased risk of preeclampsia. The aim of this current study was to estimate, through a systematic review and meta-analysis of cohort studies, the risk of preeclampsia in women who conceived with ART. We searched ISI Web of Knowledge, Medline/PubMed, Scopus and Embase up to August 2017 for English-language articles pertaining to risk of preeclampsia in ART pregnancy using standard keywords. Data extraction was conducted by two authors and quality of the studies was assessed using the Newcastle-Ottawa Scale. A random-effects model was used for the meta-analysis. In total, 72 cohort studies ( = 164 870) were included. The results of Cochran test and statistic indicated considerable heterogeneity among studies (Q = 15 415.61, df = 71,  < .001, =99.5%). The pooled estimate of preeclampsia risk using the random effects model was 10.8% (95% CI: 9.10-12.5). Furthermore, the funnel plot and Begg's test showed evidence of publication bias. We found that the risk of preeclampsia was very high among women who conceived with ART. Women should be counseled carefully before undergoing ART treatment.
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http://dx.doi.org/10.1080/14767058.2018.1560406DOI Listing
August 2020

A randomized, double-blind, phase I clinical trial of fetal cell-based skin substitutes on healing of donor sites in burn patients.

Burns 2019 06 14;45(4):914-922. Epub 2018 Dec 14.

Burn Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Due to limited graft donor sites in extensive burns, re-harvesting of a single donor area is very common. Given the importance of fetal fibroblasts in accelerating fetal wound healing, fetal cell-based skin substitutes have emerged as a novel therapeutic modality for regenerating damaged skin. In this trial, we aimed to evaluate the safety, feasibility and potential efficacy of application of amniotic membranes seeded with fetal fibroblasts for accelerating donor sites healing in burn patients.

Methods: In this randomized, double-blind, phase I clinical trial, 10 patients with total burn surface area of 10-55% were enrolled. Three equal parts (10×10cm) were selected in donor site of each patient and covered by Vaseline gauze (control group), amniotic membrane (AM group), or amniotic membrane seeded with fetal fibroblasts (AM-F group). Adverse events, pain intensity scores, and wound sizes were recorded on days 4, 8, 11, 14, and 20 post-treatment. Also, histological assessments were done on days 0 and 14 after the surgery.

Results: All patients underwent surgery, and no adverse events occurred during the procedure and follow-up period. Significantly lower pain intensity and higher healing rates were observed in AM-F and AM groups compared to the control group. Moreover, mean complete re-epithelializatin in AM-F and AM groups were 10.1±2.4 and 11.3±2.9 days, showing that the healing process was significantly accelerated compared to the control group with mean closure time of 14.8±1.6 days. Histological assessment showed lower inflammatory cells infiltration in AM-F and AM groups compared to control group.

Conclusions: This study indicated the safety of transplantation of amniotic membrane seeded with fetal fibroblasts for treatment of donor sites in burn patients; however, preliminary assessments showed no benefits for this therapeutic modality over amniotic membrane alone. Thus, to draw accurate conclusions, further trials in larger populations should be conducted.

Level Of Evidence: This study is assigned as level I.
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http://dx.doi.org/10.1016/j.burns.2018.10.016DOI Listing
June 2019

Prevalence and association of human papillomavirus, Epstein-Barr virus and Merkel Cell polyomavirus with neoplastic esophageal lesions in northern Iran.

Caspian J Intern Med 2018 ;9(4):353-360

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

Background: Studies concerning on esophageal squamous cell carcinoma (ESCC) etiological factors have been done for several decades, however, results reported from various investigations were not consistent. The present investigation aimed to explore the presence of 3 oncogenic viruses, human papilloma virus (HPV), Epstein-Barr virus (EBV) and Merkel cell polyomavirus (MCPyV) in the neoplastic and non- neoplastic esophageal lesions collected from Mazandaran, a high risk area of Iran.

Methods: In total, 168 esophageal specimens (100 with ESCC confirmed diagnosis and 68 without esophageal malignancy) were analyzed for HPV, EBV and MCPyV by Real Time PCR.

Results: HPV DNA was detected in 27 out of the 100 neoplastic esophageal lesions (27.0%) and 28 out of the 68 samples from non-neoplastic group (41.2%). EBV DNA was detected in esophageal specimens of 10 out of the 100 neoplastic cases (10%) and 3 out of the 68 samples in non- neoplastic group (4.4%). MCPyV DNA was detected in esophageal specimens of 30 out of the 100 neoplastic cases (30.0%) and 24 out of the 68 samples in non- neoplastic group (35.3%). There was no statistically significant difference in HPV (p=0.066), EBV (p=0.143) and MCPyV (p=0.471) DNA positivity between neoplastic and non-neoplastic groups.

Conclusions: This study showed that HPV, EBV and MCPyV can be detected in both neoplastic and non-neoplastic esophageal tissues and weakens the hypothesis of the pathogenic role of these viruses in esophageal malignant transformation.
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http://dx.doi.org/10.22088/cjim.9.4.353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230459PMC
January 2018

The combined utility of myeloperoxidase (MPO) and paraoxonase 1 (PON1) as two important HDL-associated enzymes in coronary artery disease: Which has a stronger predictive role?

Atherosclerosis 2019 01 8;280:7-13. Epub 2018 Nov 8.

Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

Background And Aims: Serum paraoxonase 1 (PON1) and myeloperoxidase (MPO) are HDL-associated enzymes that contribute significantly to the formation of dysfunctional HDL. The present study thus seeks to comparatively analyze the predictive role of PON1, MPO and the MPO/PON1 ratio and to also evaluate which one has a stronger predictive role in their combined utility as an MPO/PON1 ratio in coronary artery disease (CAD).

Methods: PON1 activity and MPO concentrations were determined in patients with established CAD and those without significant CAD. Receiver operating characteristic (ROC) curves were drawn by plotting true positivity versus false positivity.

Results: The ROC curve analyses showed that PON1 (AUC = 61%, p = 0.003) and MPO/PON1 (AUC = 60%, p = 0.01) have a better diagnostic performance than MPO (AUC = 50%, p = 0.42) in detecting patients with CAD. PON1 and MPO/PON1 were found to have a significantly stronger discriminatory power for the age range ≥52 and < 60 years (AUC = 69%, p = 0.008 for PON1; AUC = 66%, p = 0.022 for MPO/PON1). The multivariate analysis revealed PON1 as an independent variable that was significantly associated with the multi-vessel disease [odds ratio (OR) = 0.98; p = 0.017]. At the cutoff point of 30 μmol/mL/min for PON1 and 1.85 for MPO/PON1, specificities were 97% and 73% and sensitivities 30% and 54% for discriminating patients with single-vessel disease from non-CAD subjects.

Conclusions: The diagnostic performance of PON1 alone was comparable to that of the MPO/PON1 ratio for CAD risk assessment; however, MPO may increase the true positive rate. A larger number of blocked vessels seems to be associated with an increased predictive power for both PON1 and MPO/PON1. Recent data support the fact that PON1 and MPO may potentially be appropriate therapeutic targets for preventing CAD.
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http://dx.doi.org/10.1016/j.atherosclerosis.2018.11.004DOI Listing
January 2019

Frequency and Geographic Distribution of Mutations in Patients With Severe Fungal Infections.

Front Microbiol 2018 12;9:2434. Epub 2018 Oct 12.

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Autosomal recessive deficiency in the caspase recruitment domain containing protein 9 (CARD9) results in susceptibility to fungal infections. In the last decade, infections associated with CARD9 deficiency are more reported due to the advent of genome sequencing. The aim of this study was to evaluate the frequency, geographic distribution and nature of mutations in patients with CARD9 deficiency. We identified 60 patients with 24 mutations and different fungal infections. The presence of the homozygous (HMZ) p.Q295X (c.883C > T) and HMZ p.Q289X (c.865C > T) mutations were associated with an elevated risk of candidiasis (OR: 1.6; 95% CI: 1.18-2.15; = 0.004) and dermatophytosis (OR: 1.85; 95% CI: 1.47-2.37; < 0.001), respectively. The geographical distribution differed, showing that the main mutations in African patients were different Asian patients; HMZ p.Q289X (c.865C > T) and HMZ p.Q295X (c.865C > T) accounted for 75% and 37.9% of the African and Asian cases, respectively. The spectrum of mutations in Asian patients was higher than in African. Asia is the most populous continent in the world and may have a greater genetic burden resulting in more patients with severe fungal infections. The presence of a high diversity of mutations revealing 24 distinct variations among 60 patients emphasize that the unique genetic alteration in gene may be associated with certain geographical areas.
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http://dx.doi.org/10.3389/fmicb.2018.02434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195074PMC
October 2018

The role of minocycline in alleviating aluminum phosphide-induced cardiac hemodynamic and renal toxicity.

Environ Toxicol Pharmacol 2018 Dec 2;64:26-40. Epub 2018 Oct 2.

Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Poisoning with aluminum phosphide (AlP) has been attributed to the high rate of mortality among many Asian countries. It affects several organs, mainly heart and kidney. Numerous literature demonstrated the valuable effect of minocycline in mitigating pathological symptoms of heart and kidney disease. The aim of the present study was to evaluate the probable protective effect of minocycline on cardiac hemodynamic parameters abnormalities and renal toxicity induced by AlP-poisoning in the rat model. AlP was administered by gavage at 12 mg/kg body weight followed by injection of minocycline for two interval times of 12 and 24 h, at 40, 80, 120 mg/kg body weight. Electrocardiographic (ECG) parameters were monitored, 30 min after AlP gavage for 6 h using an electronic cardiovascular monitoring device. Kidney tissue and serum were collected for the study of histology, mitochondrial complexes I, II, IV, lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity, ADP/ATP ratio, mitochondrial cytochrome c release, apoptosis, lactate, BUN, and Cr levels. The results demonstrated that AlP induces ECG abnormalities, and failure of heart rate and blood pressure, which improved significantly by minocycline. Minocycline treatment significantly improved complexes I, IV, MPO and LDH activities, and also reduced the ADP/ATP ratio, lactate level, release of cytochrome c, and apoptosis in the kidney following AlP-poisoning. Also, the histological results showed an improvement of kidney injury in minocycline treated groups. In conclusion, the findings of this study showed that minocycline could improve cardiac hemodynamic abnormalities and kidney injury following AlP-poisoning, suggesting minocycline might be a possible candidate for the treatment of AlP-poisoning.
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http://dx.doi.org/10.1016/j.etap.2018.09.008DOI Listing
December 2018

Genotype and phenotype of salt-stimulated paraoxonase 1 (PON1) is associated with atherogenic indices in type 2 diabetes.

J Diabetes Metab Disord 2018 Jun 26;17(1):1-10. Epub 2018 Mar 26.

4Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Km 17 Khazarabad Road, Sari, Iran.

Background: Paraoxonase 1 (PON1) and lipid abnormalities contribute to the development of cardiovascular disease, which is the principal cause of mortality in patients with type 2 diabetes (T2D). Data are not available on the potential association between salt-stimulated activity of PON1 (PON1-salt) and the atherogenic indices in T2D, therefore, we focused on these associations and evaluated whether the functional variants PON1-Q192R and PON1-L55M influence the associations.

Methods: Paraoxonase activity (PON1-para), arylesterase activity (PON1-aryl) and salt-stimulated activity (PON1-salt) were measured by spectrophotometric assays. The atherogenic index of plasma (AIP) was calculated from the log (TG/HDL-C). The genetic analyses were made by the restricted fragment length polymorphism after PCR amplification.

Results: We observed that PON1-salt was negatively correlated with total cholesterol (TC)/HDL-C ( = -0.441, = 0.006), LDL-C/HDL-C ( = -0.415,  = 0.011), and AIP ( = -0.422,  = 0.009). Correlations between PON1-salt and all three atherogenic indices were significantly affected by PON1-L55M and PON1-Q192R. Linear regression showed that AIP ( = 0.002), LDL-C/HDL-C ( = 0.005), and TC/HDL-C (p = 0.002) were independently associated with PON1-salt. Based on Ridge regression, the standardized coefficients -0.358, -0.297, and - 0.044 were obtained for AIP, LDL-C/HDL-C, and TC/HDL-C, respectively, and this shows that AIP could have more negative effect on PON1-salt than the others.

Conclusions: The decreased PON1-salt may be considered as a risk factor for atherosclerosis in T2D, therefore, understanding the associations between PON1-salt as an important although neglected property and atherogenic indices may be valuable in T2D. Accordingly, detection of PON1-salt status (phenotype and genotype) together with the atherogenic indices particularly AIP could be beneficial in identifying the increased atherogenicity in T2D.
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http://dx.doi.org/10.1007/s40200-018-0332-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154515PMC
June 2018

Investigation of CCR7 Marker Expression Using Immunohistochemical Method and Its Association with Clinicopathologic Properties in Patients with Breast Cancer.

Int J Hematol Oncol Stem Cell Res 2018 Apr;12(2):103-110

Research and Development Unit of Referral Laboratory, Deputy of Health Management, Mazandaran University of Medical Sciences, Sari, Iran.

Breast cancer is one of the most common cancers among women in the world, especially in Iran. There are large numbers of molecular and genomic factors causing breast cancer as well as many markers associated with tumor invasion. Chemokines are small proteins that primarily regulate leukocyte trafficking in the homeostatic conditions and specific immune responses. Chemokine receptor 7 (CCR7) belongs a class A subtype 7-span transmembrane G-protein coupled receptor. CCR7 plays a role in the migration of tumor cells such as immune cells into lymphoid organs through binding to its only two ligands CCL19/CCL21. High expression of this marker has been observed in breast cancer. However, there have been limited and contradictory data in studies conducted on the relationship between the increasing expression of this marker with various clinical and pathological factors. This case-control practical study was carried out on total mastectomy samples from 70 patients with breast cancer and tumor-adjacent normal tissue using immunohistochemistry technique to assess the expression of CCR7 marker. The relationship among the marker expression with different clinical and pathological tumor factors such as age, tumor size, microscopic grade, neurovascular invasion, lymph node metastasis and tumor stage were evaluated in all patients. Since the both groups were matched for age, so McNemar test, Chi-square test and Fisher's exact test were used to compare the expression of CCR7 marker in the case and control groups. Conditional logistic regression was employed to compare the effects of other variables regarding the age harmonization. CCR7 expression was observed in 63 (91.4%) out of 70 studied patients and in tumor-adjacent normal tissue of 55 patients (78.6%), while the marker expression intensity in normal tissue was lower than tumoral tissue (P<0.032) There was a significant relationship among the expression of CCR7 marker with disease stage (P<0.001), grade (P<0.035), lymph node metastasis (P<0.003), perineural invasion (P<0.037) and vascular invasion (P<0.01), but no significant relationship was found among CCR7 expression with other tumor clinicopathologic parameters such as age (P>0.19) and tumor size (P>0.105). Increased expression of CCR7 has a significant relationship with disease stage, grade, lymph node metastasis and neurovascular invasion of breast cancer but has no relationship with age of patients and tumor size. Therefore, this biomarker can be utilized as a predictive factor for tumor metastasis and survival of patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141431PMC
April 2018

Incidence and Mortality of Various Cancers in Iran and Compare to Other Countries: A Review Article.

Iran J Public Health 2018 Mar;47(3):309-316

Dept. of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Background: Iran in recent years had the rapid development of industrialization and modernity, and changes in the people's lifestyles and environment, these changes may affect epidemiological patterns of various types of cancers. In this review, incidence and mortality of various cancers (skin, gastric, esophageal, breast, and prostate) in Iran have been reported.

Methods: The related data about Iran and other countries were collected from databases such as Google Scholar, Scopus, PubMed, EMBASE, and Web of Science. All included studies were published before Jun 2017.

Results: There is an increment trend of incidence and mortality rate for most cancers in Iran.

Conclusion: The plan for control and prevention of cancers must be a high priority for health policy in Iran as well as it is suggested that earlier screening is need for high-risk population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971166PMC
March 2018

Paraoxonase 1 (PON1)-L55M among common variants in the coding region of the paraoxonase gene family may contribute to the glycemic control in type 2 diabetes.

Clin Chim Acta 2018 Sep 19;484:40-46. Epub 2018 May 19.

Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Electronic address:

Objective: Genome studies have shown that the genes encoding paraoxonase 1 (PON1) and PON2 are associated with glucose metabolism. The goal of this study was to simultaneously evaluate the association between functional variants in PON1 and PON2 genes and susceptibility for type 2 diabetes (T2D) and determine whether they can affect glycemic control.

Methods: We performed a case-control study with 145 newly diagnosed patients with T2D and 148 controls. The common variants including PON1-Q192R, PON1-L55M and PON2-S311C were genotyped by PCR-based RFLP. A mismatch-PCR/RFLP was applied for genotyping the PON2-A148G variant.

Results: The variant PON1-Q192R in males (OR = 2.55, 95%CI 1.16-5.69, p = 0.023) and PON2-A148G in females (OR = 1.56, 95%CI 1.00-2.44, p = 0.059) were associated with T2D. Compared with the LL genotypes of PON1-L55M, HbA1c levels were significantly lower in the LM genotypes (p = 0.01) and MM genotypes (p = 0.032) in patients. Multiple linear regression analyses showed that among the study variants only the PON1-L55M variant as an independent variable significantly associated with glycemic control. This variant significantly influenced glycemic control in patients with poor glycemic control so that it was better with the following order: LL < LM < MM. Based on gamma correlation, there was a significant inverse association between the number of M alleles of the PON1-L55M and HbA1c levels (r = -0.261, p = 0.001).

Conclusions: Sex should be considered a confounding variable in association studies on the variants PON1-Q192R and PON2-A148G in T2D. Patients sharing the 55 M allele were prone to having good glycemic control. Our findings provide genetic evidence that the PON1-L55M variant may be a factor contributing to glycemic control.
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http://dx.doi.org/10.1016/j.cca.2018.05.037DOI Listing
September 2018

Efficacy of green nanoparticles against cancerous and normal cell lines: a systematic review and meta-analysis.

IET Nanobiotechnol 2018 Jun;12(4):377-391

Department of Medical Microbiology and Immunology, Institute of Biomedical Sciences, College of Health Sciences, Mekelle University, 1871 Mekelle, Ethiopia.

This study aimed to perform a systematic review and meta-analysis of papers discussing the efficacy of microbial synthesised metallic nanoparticles (MNPs) against cancerous and normal cell lines by exploiting Bayesian generalised linear (BGL) model. Data was systematically collected from published papers via Cochrane library, Web of Science, PubMed, Science Direct, ProQuest, Scopus, and Embase. Impressively, most of the studies were carried out on HeLa and A549 cancer cell lines. Specifically, a hefty 65.67% of studies employed bacteria to biofabricate MNPs. Significantly, BGL meta-analysis represented highly valuable information. Hence, based on adjusted analysis, the MNPs with the size of 25-50 nm were found to be far less cytotoxic than the MNPs with the size of ≤25 nm (OR = 0.233,  ˂ 0.05) against either cancerous or normal cell lines. Interestingly, it was found that the odds of cytotoxicity in cancerous cell lines were practically nine times more than normal cell lines, representing the substantially more cytotoxicity of MNPs in cancerous cell lines (OR = 9.004,  ˂ 0.001). Green MNPs mentioned here may be developed as novel anti-cancer agents, which could lead to a revolution in the treatment of cancer.
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http://dx.doi.org/10.1049/iet-nbt.2017.0120DOI Listing
June 2018

Probabilistic risk assessment of exposure to fluoride in most consumed brands of tea in the Middle East.

Food Chem Toxicol 2018 May 19;115:267-272. Epub 2018 Mar 19.

Department of Environmental Health Engineering, Gonabad University of Medical Sciences, Gonabad, Iran. Electronic address:

The aim of this study was to evaluate the fluoride concentration in seven most consumed brands of tea in the Middle East which was imported to Iran through Zabol County. In the present study, the health risk of exposure to fluoride was estimated using a probabilistic approach. Monte Carlo simulation and sensitivity analysis were applied to quantify uncertainties in risk estimation. The highest mean and 95th percentile of chronic daily intake (CDI) was observed for children group. Iranian tea and Kenya tea had maximum CDI and target hazard quotient (THQ) values among studied brands of tea which followed by Green tea, Taksetare tea, Ceylan tea, Red tea, and White tea. These result indicated that there were significant risks of exposure to fluoride in most of studied brands of tea for children (THQ>1). Sensitivity analysis showed that fluoride concentration and daily intake were the most influential variables in three exposed populations. In conclusion, the fluoride concentration in some studied brands of tea is high and it put children at risk risks of exposure to fluoride.
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http://dx.doi.org/10.1016/j.fct.2018.03.023DOI Listing
May 2018

A single-arm open-label clinical trial of autologous epidermal cell transplantation for stable vitiligo: A 30-month follow-up.

J Dermatol Sci 2018 Jan 18;89(1):52-59. Epub 2017 Oct 18.

Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic address:

Background: Recently, we introduced intralesional injection of autologous epidermal cells as a safe and feasible approach for transplantation in patients with stable vitiligo. This approach resulted in less pain during and after the procedure, no scarring or cobblestone formation at the recipient site, and was more feasible to perform on curved surfaces such as joints, lips, eyelids, ears, and face.

Objective: In this study, we aimed to investigate the long-term efficacy and safety of this transplantation technique.

Methods: In this open-label and single-arm clinical trial, we enrolled 300 patients with stable vitiligo. We obtained a partial thickness normo-pigmented skin specimen from the patients' thigh-buttock junction with an area of one tenth to one third of the recipient site area. The epidermal cell suspension was prepared by processing the autologous skin specimen. We injected the cell suspension into 1060 vitiligo patches in 300 patients. Patients did not use any adjuvant phototherapy during the study. An experienced dermatologist and patients respectively defined the repigmentation score and self-assessment score at regular follow-up visits for up to 30 months after treatment. The scores represented the repigmentation percentage as follows: 0 (0), I (1%-24%), II (25%-49%), III (50%-74%), and IV (75%-100%).

Results: The mean repigmentation score at 3 months post-transplantation was 1.12±0.73. A significant upward trend existed in the mean repigmentation score until 9 months after cell transplantation, when the mean repigmentation score reached to 1.98±1.20. At 9 months after treatment, repigmentation of >50% was obtained in 32.2% of treated patches. Acquired repigmentation remained stable in 79.3% of treated patches during the follow-up period. The number of received cells per cm positively influenced the repigmentation score. Patches located on face, neck and trunk showed significantly higher response to the treatment.

Conclusion: The results of our study demonstrated efficacy and safety of autologus epidermal cell transplantation on repigmentation of vitiligo patches. The achieved repigmentation was stable in the majority of treated patches during the follow-up period.
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http://dx.doi.org/10.1016/j.jdermsci.2017.10.007DOI Listing
January 2018

Methodological and statistical issues related to analysis of survival.

Lancet HIV 2017 08;4(8):e330

Department of Epidemiology & Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Department of Epidemiology, School of Health, Arak University of Medical Sciences, Arak, Iran. Electronic address:

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http://dx.doi.org/10.1016/S2352-3018(17)30134-0DOI Listing
August 2017

Sperm Retrieval in Patients with Klinefelter Syndrome: A Skewed Regression Model Analysis.

Int J Fertil Steril 2017 Jul-Sep;11(2):117-122. Epub 2017 Feb 16.

Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Background: The most common chromosomal abnormality due to non-obstructive azoospermia (NOA) is Klinefelter syndrome (KS) which occurs in 1-1.72 out of 500-1000 male infants. The probability of retrieving sperm as the outcome could be asymmetrically different between patients with and without KS, therefore logistic regression analysis is not a well-qualified test for this type of data. This study has been designed to evaluate skewed regression model analysis for data collected from microsurgical testicular sperm extraction (micro-TESE) among azoospermic patients with and without non-mosaic KS syndrome.

Materials And Methods: This cohort study compared the micro-TESE outcome between 134 men with classic KS and 537 men with NOA and normal karyotype who were referred to Royan Institute between 2009 and 2011. In addition to our main outcome, which was sperm retrieval, we also used logistic and skewed regression analyses to compare the following demographic and hormonal factors: age, level of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone between the two groups.

Results: A comparison of the micro-TESE between the KS and control groups showed a success rate of 28.4% (38/134) for the KS group and 22.2% (119/537) for the control group. In the KS group, a significantly difference (P<0.001) existed between testosterone levels for the successful sperm retrieval group (3.4 ± 0.48 mg/mL) compared to the unsuccessful sperm retrieval group (2.33 ± 0.23 mg/mL). The index for quasi Akaike information criterion (QAIC) had a goodness of fit of 74 for the skewed model which was lower than logistic regression (QAIC=85).

Conclusion: According to the results, skewed regression is more efficient in estimating sperm retrieval success when the data from patients with KS are analyzed. This finding should be investigated by conducting additional studies with different data structures.
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http://dx.doi.org/10.22074/ijfs.2017.4702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347449PMC
February 2017

Polymorphic Variants rs3088442 and rs2292334 in the Organic Cation Transporter 3 (OCT3) Gene and Susceptibility Against Type 2 Diabetes: Role of their Interaction.

Arch Med Res 2017 Feb;48(2):162-168

Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Aims: In this study, we investigated whether two common variants (rs3088442G>A and rs2292334G>A) in the organic cation transporter 3 (OCT3) gene, a high-capacity transporter widely expressed in various tissues, affect susceptibility to type 2 diabetes (T2D) in patients newly diagnosed with T2D.

Methods: We performed a study with 150 newly diagnosed patients with T2D and 152 controls. The genetic analyses were performed using the restricted fragment length polymorphism (RFLP) after PCR amplification.

Results: For the rs3088442G>A variant, A allele carriers had a significantly lower odds ratio (OR) vs. GG homozygotes in the BMI <30 kg/m group (OR = 0.23, p <0.001) compared with the BMI ≥30 kg/m group (OR = 0.67, p = 0.34). When ORs were adjusted for BMI, age, sex, and blood pressure, our findings showed that the overexpression of the A allele of the rs3088442G>A variant was associated with a decreased risk of T2D (OR = 0.016, p <0.001). A Bayesian logistic model revealed that the interaction of two variants studied were significantly associated with a decreased risk of T2D (OR = 0.61, p = 0.03).

Conclusions: The present study has identified the protective effect of the variant rs3088442G>A in the 3'-untranslated region of the OCT3 gene in susceptibility to T2D, and that the protective role is maintained in the presence of risky alleles of the variant rs2292334G>A. The association of the A allele of rs3088442G>A with T2D become weaker in obese people than that of non-obese. If confirmed in other populations, the rs3088442G>A variant as a genetic marker may potentially assist in the identification of individuals at an increased risk of T2D.
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http://dx.doi.org/10.1016/j.arcmed.2017.03.010DOI Listing
February 2017