Publications by authors named "Mojtaba Fathi"

24 Publications

  • Page 1 of 1

Clinicopathological, Immunohistochemical, and Gene Expression Profiling of Patients with Sporadic Colorectal Cancer.

Arch Iran Med 2021 Feb 1;24(2):86-93. Epub 2021 Feb 1.

Department of Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

Background: The DNA mismatch repair (MMR) system is one of the molecular pathways involved in colorectal cancer (CRC) carcinogenesis that consists of several genes, including (MutL homolog 1), (MutS homolog 6), (MutS homolog 2), and (MutS homolog 3). The protein encoded by (post-meiotic segregation 2) is also essential for MMR. Here, we address the correlation between immunohistochemical and transcriptional expression of PMS2 with the tumor grade and clinical stage of non-hereditary/sporadic CRC disease.

Methods: This study retrospectively analyzed 67 colorectal resections performed for 38 male and 29 female patients. Random biopsies were taken by a gastroenterologist from patients referring to three hospitals in the cities of Zanjan, Urmia and Qazvin (Iran) during 2017-2019. All specimens were examined and classified for localization of tumor, pathological stage and grade. The PMS2 protein expression was studied immunohistochemically and analysis of mRNA expression was performed in the same tissue sections.

Results: Immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analysis showed a decrease in PMS2 expression compared with paracancerous tissue (<0.001), which correlated with tumor stage. In addition, reduced PMS2 expression was correlated with the tumor differentiation grade, underlining a connection between downregulation of PMS2 and progression of CRC. Comparing the PMS2 mRNA levels in different groups showed the following results: 0.92 ± 0.18 in patients with Stage I CRC tumor, 0.86 ± 0.38 in Stage Ⅱ, 0.50 ± 0.29 in Stage Ⅲ, and 0.47 ± 0.23 in Stage Ⅳ.

Conclusion: These findings suggest that may provide a potential reliable biomarker for CRC classification by combined immunohistochemical and mRNA analysis.
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http://dx.doi.org/10.34172/aim.2021.13DOI Listing
February 2021

Modeling and Reducing the Effect of Geometric Uncertainties in Intracranial Aneurysms with Polynomial Chaos Expansion, Data Decomposition, and 4D-Flow MRI.

Cardiovasc Eng Technol 2021 Jan 7. Epub 2021 Jan 7.

Department of Mechanical Engineering, University of Wisconsin-Milwaukee, Milwaukee, WI, 53211, USA.

Purpose: Variations in the vessel radius of segmented surfaces of intracranial aneurysms significantly influence the fluid velocities given by computer simulations. It is important to generate models that capture the effect of these variations in order to have a better interpretation of the numerically predicted hemodynamics. Also, it is highly relevant to develop methods that combine experimental observations with uncertainty modeling to get a closer approximation to the blood flow behavior.

Methods: This work applies polynomial chaos expansion to model the effect of geometric uncertainties on the simulated fluid velocities of intracranial aneurysms. The radius of the vessel is defined as the uncertainty variable. Proper orthogonal decomposition is applied to characterize the solution space of fluid velocities. Next, a process of projecting the 4D-Flow MRI velocities on the basis vectors followed by coefficient mapping using generalized dynamic mode decomposition enables the merging of 4D-Flow MRI with the uncertainty propagated fluid velocities.

Results: Polynomial chaos expansion propagates the fluid velocities with an error of 2% in velocity magnitude relative to computer simulations. Also, the bifurcation region (or impingement location) shows a standard deviation of 0.17 m/s (since an available reported variance in the vessel radius is adopted to model the uncertainty, the expected standard deviation may be different). Numerical phantom experiments indicate that the proposed approach reconstructs the fluid velocities with 0.3% relative error in presence of geometric uncertainties.

Conclusion: Polynomial chaos expansion is an effective approach to propagate the effect of the uncertainty variable in the blood flow velocities of intracranial aneurysms. Merging 4D-Flow MRI and uncertainty propagated fluid velocities leads to more realistic flow trends relative to ignoring the uncertainty in the vessel radius.
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http://dx.doi.org/10.1007/s13239-020-00511-wDOI Listing
January 2021

Application of decoy oligodeoxynucleotides strategy for inhibition of cell growth and reduction of metastatic properties in nonresistant and erlotinib-resistant SW480 cell line.

Cell Biol Int 2020 Dec 30. Epub 2020 Dec 30.

Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

Signal transducer and activator of transcription 3 (STAT3) is a critical regulator for angiogenesis, cell cycle progression, apoptosis, and drug resistance. Resistance toward EGF receptor (EGFR) inhibitors is a significant clinical concern for metastatic colon cancer patients. The present study aimed to evaluate the blocking influences of STAT3 decoy oligodeoxynucleotides (ODNs) on the STAT3 survival signaling pathway in nonresistant and erlotinib-resistant SW480 colon cancer cells. First, STAT3 decoy and scramble ODNs were designed according to STAT3 elements in the promoter region of MYCT1 gene and tested for the interaction of STAT3 protein with designed ODNs via in silico molecular docking study. Then, the efficiency of transfection and subcellular localization of ODNs were assessed using flow cytometry and fluorescence microscopy, respectively. Cell viability, cell cycle, and apoptosis tests, scratch and colony formation assays, and real-time PCR were also used to study the cancerous properties of cells. A considerable decrease in proliferation of colon cancer cells was observed with blockade of STAT3 signaling due to cell cycle arrest and induced apoptosis via downregulation of cyclin D1 and Bcl-XL, respectively. Furthermore, upon transfecting STAT3 decoy ODNs, colony formation potential and migration activity in both SW480 colon cancer cell lines were decreased compared to the control groups. From this study, it could be concluded that STAT3 is critical for cell growth inhibition and metastatic properties reduction of resistant SW480 colon cancer cells; therefore, STAT3 decoy ODNs could be considered as potential therapeutics along with current remedies for treating drug-resistant colon cancer.
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http://dx.doi.org/10.1002/cbin.11543DOI Listing
December 2020

Oxidative toxic stress and p53 level in healthy subjects occupationally exposed to outdoor air Pollution - a cross-sectional study in Iran.

Ann Agric Environ Med 2020 Dec 4;27(4):585-590. Epub 2020 Sep 4.

Department of Biochemistry and Genetics, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.

Introduction: It is suggested that air pollution exposure induces oxidative stress in the body and causes diseases. However, current evidence regarding the association of outdoor air pollution with some oxidative toxic stress (OTS) biomarkers in areas with different pollutant concentrations is equivocal.

Objective: The aim of study was to investigate the adverse effects of outdoor air pollution on human health, by evaluating potential oxidative and anti-oxidative biomarkers and p53 protein levels in subjects exposed to different outdoor air pollution from two polluted and less polluted cities of Iran.

Material And Methods: In this cross-sectional study, a total of 203 healthy working men were selected from two cities. The activities of superoxide dismutase (SOD), catalase (CAT) and γ-glutamyltransferase (GGT) and the levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS), were measured by the colorimetric method. The levels of p53 were measured by an ELISA method.

Results: The results showed a significant increase in the levels of p53 and MDA in the exposure group compared to the control group, while the activity of SOD and TAC was significantly decreased in the exposure group. No significant differences were found in activities of CAT and GGT, and levels of TOS between the two groups.

Conclusions: The findings obtained confirmed the implication of air pollution in the development of OTS, and suggested useful biomarkers to evaluate the air pollution-induced harmful effects on human health in the polluted areas.
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http://dx.doi.org/10.26444/aaem/126313DOI Listing
December 2020

Determination of carcinoembryonic antigen as a tumor marker using a novel graphene-based label-free electrochemical immunosensor.

Anal Biochem 2021 01 17;613:114017. Epub 2020 Nov 17.

Department of Mechanical and Industrial Engineering, Tallinn University of Technology (TalTech), Ehitajate tee 5, 19086, Tallinn, Estonia.

In this work, a simple label-free electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA) was developed. At first, the GC electrode was coated with partially reduced graphene oxide (rGO) to form a platform to bind the antibody. After activating the carboxyl groups of rGO through the EDC/NHS linker, the electrode surface was covered with the antibody. Then, the electrochemical behavior of the antibody-modified electrode and the parameters of the interactions of antibody-antigen immune complexes were investigated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). This immune-complex layer was found to attenuate the electrochemical current which can be used as a good signal to determine the antigen concentration. The proposed immunosensor exhibited a good amperometric response to CEA within a concentration range of 0.1-5 ng mL with a detection limit of 0.05 ng ml. Furthermore, the developed method was evaluated for the detection of CEA in the real sample (human blood serum), and the results were comparable with the reference values obtained by the standard enzyme-linked immunosorbent assay (ELISA). Our findings suggest the present immunosensor as a good candidate for application in clinical screening.
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http://dx.doi.org/10.1016/j.ab.2020.114017DOI Listing
January 2021

Circulating Irisin Levels and Redox Status Markers in Patients with Gastric Cancer: A Case-Control Study.

Asian Pac J Cancer Prev 2020 Oct 1;21(10):2847-2851. Epub 2020 Oct 1.

Department of Biochemistry. School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

Objective: Irisin, mostly known as an exercise-induced fat browning myokine, has been recently detected in several cancer cells, and its potential for being utilized as a biomarker for early diagnosis of some cancers, such as Gastric cancer (GC), is the subject of speculation. The present study aims to compare serum irisin levels in GC patients and healthy controls and assess the interrelation between irisin and oxidative stress markers.

Methods: In this case-control study, 22 newly diagnosed GC patients and 29 healthy controls were recruited based on the inclusion criteria. Serum levels of irisin were quantified in duplicates by ELISA. Oxidative stress indices, including total antioxidant power in sera, thiol group, malondialdehyde, and superoxide dismutase concentrations, were also measured in both groups. An independent-sample t-test was used to compare the means between the two studied groups.

Results: Serum levels of irisin were significantly higher in the GC group compared with those of their healthy counterparts (p =0.032). No significant differences were observed between the two groups in terms of the serum total antioxidant power or the oxidative stress marker, including MDA, thiol groups, and SOD concentration in sera. Furthermore, there was no significant association between irisin, FRAP, the Thiol group, and the SOD activity.

Conclusion: According to the finding, the increased serum levels of irisin in GC patients can play a potential role in the early diagnosis of the GC patients; hence, this peptide can be employed as a new diagnostic indicator of GC.
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http://dx.doi.org/10.31557/APJCP.2020.21.10.2847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798161PMC
October 2020

Super-resolution and denoising of 4D-Flow MRI using physics-Informed deep neural nets.

Comput Methods Programs Biomed 2020 Dec 15;197:105729. Epub 2020 Sep 15.

Dept. of Mechanical Engineering, University of Wisconsin-Milwaukee, Milwaukee, WI, USA. Electronic address:

Background And Objective: Time resolved three-dimensional phase contrast magnetic resonance imaging (4D-Flow MRI) has been used to non-invasively measure blood velocities in the human vascular system. However, issues such as low spatio-temporal resolution, acquisition noise, velocity aliasing, and phase-offset artifacts have hampered its clinical application. In this research, we developed a purely data-driven method for super-resolution and denoising of 4D-Flow MRI.

Methods: The flow velocities, pressure, and the MRI image magnitude are modeled as a patient-specific deep neural net (DNN). For training, 4D-Flow MRI images in the complex Cartesian space are used to impose data-fidelity. Physics of fluid flow is imposed through regularization. Creative loss function terms have been introduced to handle noise and super-resolution. The trained patient-specific DNN can be sampled to generate noise-free high-resolution flow images. The proposed method has been implemented using the TensorFlow DNN library and tested on numerical phantoms and validated in-vitro using high-resolution particle image velocitmetry (PIV) and 4D-Flow MRI experiments on transparent models subjected to pulsatile flow conditions.

Results: In case of numerical phantoms, we were able to increase spatial resolution by a factor of 100 and temporal resolution by a factor of 5 compared to the simulated 4D-Flow MRI. There is an order of magnitude reduction of velocity normalized root mean square error (vNRMSE). In case of the in-vitro validation tests with PIV as reference, there is similar improvement in spatio-temporal resolution. Although the vNRMSE is reduced by 50%, the method is unable to negate a systematic bias with respect to the reference PIV that is introduced by the 4D-Flow MRI measurement.

Conclusions: This work has demonstrated the feasibility of using the readily available machinery of deep learning to enhance 4D-Flow MRI using a purely data-driven method. Unlike current state-of-the-art methods, the proposed method is agnostic to geometry and boundary conditions and therefore eliminates the need for tedious tasks such as accurate image segmentation for geometry, image registration, and estimation of boundary flow conditions. Arbitrary regions of interest can be selected for processing. This work will lead to user-friendly analysis tools that will enable quantitative hemodynamic analysis of vascular diseases in a clinical setting.
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http://dx.doi.org/10.1016/j.cmpb.2020.105729DOI Listing
December 2020

Towards multi-modal data fusion for super-resolution and denoising of 4D-Flow MRI.

Int J Numer Method Biomed Eng 2020 09 13;36(9):e3381. Epub 2020 Aug 13.

Department of Mechanical Engineering, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.

4D-Flow magnetic resonance imaging (MRI) has enabled in vivo time-resolved measurement of three-dimensional blood flow velocities in the human vascular system. However, its clinical use has been hampered by two main issues, namely, low spatio-temporal resolution and acquisition noise. While patient-specific computational fluid dynamics (CFD) simulations can address the resolution and noise issues, its fidelity is impacted by accuracy of estimation of boundary conditions, model parameters, vascular geometry, and flow model assumptions. In this paper a scheme to address limitations of both modalities through data-fusion is presented. The solutions of the patient-specific CFD simulation are characterized using proper orthogonal decomposition (POD). Next, a process of projecting the 4D-Flow MRI data onto the POD basis and projection coefficient mapping using generalized dynamic mode decomposition (DMD) enables simultaneous super-resolution and denoising of 4D-Flow MRI. The method has been tested using numerical phantoms derived from patient-specific aneurysmal geometries and applied to in vivo 4D-Flow MRI data.
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http://dx.doi.org/10.1002/cnm.3381DOI Listing
September 2020

Crosstalk between Epidermal Growth Factor Receptors (EGFR) and integrins in resistance to EGFR tyrosine kinase inhibitors (TKIs) in solid tumors.

Eur J Cell Biol 2020 May 28;99(4):151083. Epub 2020 Apr 28.

Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran; Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran. Electronic address:

Cell adhesion to the extracellular matrix (ECM) is important in a variety of physiological and pathologic processes, including development, tumor invasion, and metastasis. Integrin-mediated attachment to ECM proteins has emerged to cue events primitively important for the transformed phenotype of human cancer cells. Cross-talk between integrins and growth factor receptors takes an increasingly prominent role in defining adhesion, motility, and cell growth. This functional interaction has expanded beyond to link integrins with resistance to Tyrosine kinase inhibitors (TKIs) of Epidermal Growth Factor Receptors (EGFRs). In this regard, integrin-mediated adhesion has two separate functions one as a clear collaborator with growth factor receptor signaling and the second as a basic mechanism contributing in Epithelial to Mesenchymal Transition (EMT) which affects response to chemotherapy. This review provides an overview of these mechanisms and describes treatment options for selectively targeting and disrupting integrin interaction to EGFR for cancer therapy.
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http://dx.doi.org/10.1016/j.ejcb.2020.151083DOI Listing
May 2020

The effect of resveratrol supplementation on C-reactive protein (CRP) in type 2 diabetic patients: Results from a systematic review and meta-analysis of randomized controlled trials.

Complement Ther Med 2020 Mar 8;49:102251. Epub 2020 Jan 8.

Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objective: C-reactive protein (CRP) is considered to be an inflammatory marker in type 2 diabetes (T2D) and it is produced by liver cells. The evidence has suggested that resveratrol has anti-inflammatory effect. This study aimed to evaluate the effect of resveratrol supplementation on CRP level in patients with T2D using a systematic review and meta-analysis of randomized controlled trials.

Methods: Electronic databases were completely searched using Medline, ISI Web of Science, EMBASE and Cochrane Library and Scopus until October 2019. Meta-analysis was performed using random-effects model and inverse variance method. Heterogeneity and publication bias were evaluated in selected studies. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity. Meta-regression was performed to assess the effect of potential confounders on the estimated effect sizes.

Results: Six trials comprising a total of 491 subjects were included in this meta-analysis. The results showed significant reduction in the level of CRP [SMD (-0.34 mg/l) (95 % CI, -0.52, to -0.16) p < 0.05] in participants with T2D following supplementation with resveratrol. No significant publication bias was observed in the meta-analysis. Subgroup and sensitivity analyses indicated that the pooled effects of resveratrol supplementation on CRP level in T2D patients were affected by resveratrol dose and duration of resveratrol. Random-effects meta-regression did not indicate any significant association of CRP level with potential confounders including resveratrol dose, duration of treatment, age and gender of type 2 diabetic patients.

Conclusion: We found a significant reduction in CRP level in patients with type 2 diabetes, who received resveratrol supplementation.
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http://dx.doi.org/10.1016/j.ctim.2019.102251DOI Listing
March 2020

Capturing Upper Limb Gross Motor Categories Using the Kinect® Sensor.

Am J Occup Ther 2019 Jul/Aug;73(4):7304205090p1-7304205090p10

Michelle L. Woodbury, PhD, OTR/L, is Associate Professor, Division of Occupational Therapy, Department of Health Professions, and Associate Professor, Department of Health Science and Research, Medical University of South Carolina, Charleston.

Importance: Along with growth in telerehabilitation, a concurrent need has arisen for standardized methods of tele-evaluation.

Objective: To examine the feasibility of using the Kinect sensor in an objective, computerized clinical assessment of upper limb motor categories.

Design: We developed a computerized Mallet classification using the Kinect sensor. Accuracy of computer scoring was assessed on the basis of reference scores determined collaboratively by multiple evaluators from reviewing video recording of movements. In addition, using the reference score, we assessed the accuracy of the typical clinical procedure in which scores were determined immediately on the basis of visual observation. The accuracy of the computer scores was compared with that of the typical clinical procedure.

Setting: Research laboratory.

Participants: Seven patients with stroke and 10 healthy adult participants. Healthy participants intentionally achieved predetermined scores.

Outcomes And Measures: Accuracy of the computer scores in comparison with accuracy of the typical clinical procedure (immediate visual assessment).

Results: The computerized assessment placed participants' upper limb movements in motor categories as accurately as did typical clinical procedures.

Conclusions And Relevance: Computerized clinical assessment using the Kinect sensor promises to facilitate tele-evaluation and complement telehealth applications.

What This Article Adds: Computerized clinical assessment can enable patients to conduct evaluations remotely in their homes without therapists present.
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http://dx.doi.org/10.5014/ajot.2019.031682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638702PMC
July 2019

Denoising and spatial resolution enhancement of 4D flow MRI using proper orthogonal decomposition and lasso regularization.

Comput Med Imaging Graph 2018 12 7;70:165-172. Epub 2018 Aug 7.

Department of Mechanical Engineering, University of Wisconsin-Milwaukee, United States. Electronic address:

4D-Flow MRI has emerged as a powerful tool to non-invasively image blood velocity profiles in the human cardio-vascular system. However, it is plagued by issues such as velocity aliasing, phase offsets, acquisition noise, and low spatial and temporal resolution. In imaging small blood vessel malformations such as intra-cranial aneurysms, the spatial resolution of 4D-Flow is often inadequate to resolve fine flow features. In this paper, we address the problem of low spatial resolution and noise by combining 4D-Flow MRI and patient specific computational fluid dynamics using Least Absolute Shrinkage and Selection Operator. Extensive experiments using numerical phantoms of two actual intra-cranial aneurysms geometries show the applicability of the proposed method in recovering the flow profile. Comparisons with the state-of-the-art denoising methods for 4D-Flow show lower error metrics. This method can enable more accurate computation of flow derived patho-physiological parameters such as wall shear stresses, pressure gradients, and viscous dissipation.
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http://dx.doi.org/10.1016/j.compmedimag.2018.07.003DOI Listing
December 2018

ALOX12 gene polymorphisms and serum selenium status in elderly osteoporotic patients.

Adv Clin Exp Med 2018 Dec;27(12):1717-1722

Department of Biochemistry, School of Medicine, Babol University of Medical Sciences, Iran.

Background: Osteoporosis is a systemic bone disease which leads to a reduction in bone mass. Many studies have shown that up to 80% of bone mineral density (BMD) variations are attributed to genetic factors. Arachidonate 12-lipoxygenase enzyme, encoded by the ALOX12 gene, produces lipid peroxides as reactive oxygen species (ROS), leading to oxidative stress and the development of osteoporosis. Selenium (Se) is incorporated into selenoproteins, which may reduce the risk of osteoporosis.

Objectives: We aimed to investigate the association of 2 ALOX12 single nucleotide polymorphisms (SNPs) and serum Se level with lumbar spine and femoral neck BMD among elderly individuals living in Amirkola, Iran.

Material And Methods: The study consisted of 180 individuals aged ≥60 years (90 healthy and 90 osteoporotic patients). We examined the effect of 2 ALOX12 SNPs (rs2292350 and rs9897850), using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) on both BMD regions measured by dual energy X-ray absorptiometry (DXA). Serum Se level was measured using an atomic absorption spectrophotometer PGG990 AAS (PG Instruments Ltd., Luterworth, USA).

Results: The rs2292350 SNP showed a significant association with femoral neck BMD (p = 0.04). Moreover, in terms of serum Se level, a significant difference was found between the patient group (57.58 ±25.54 μg/L) and the control group (81.09 ±25.58 μg/L) (p < 0.001). In addition, individuals with higher serum Se levels also had higher BMD of the lumbar spine (r2 = 0.392; p < 0.001) and the femoral neck (r2 = 0.478; p < 0.001).

Conclusions: The results suggested that genetic variation in ALOX12 might influence BMD variations in our recruited participants. As for the patients with lower serum Se levels, it was observed that serum Se deficiency was accompanied by some ALOX12 variation, contributing to the development of osteoporosis.
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http://dx.doi.org/10.17219/acem/75689DOI Listing
December 2018

Preliminary study showing no association between G238A (rs361525) tumor necrosis factor-α (TNF-α) gene polymorphism and its serum level, hormonal and biochemical aspects of polycystic ovary syndrome.

BMC Med Genet 2018 08 22;19(1):149. Epub 2018 Aug 22.

Department of Biochemistry and Nutrition, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

Background: Polycystic ovary syndrome (PCOS) is the main cause of female infertility. Interactions among genetic, biochemical, and immunological factors can affect the pathogenesis of PCOS. As a proinflammatory cytokine, tumor necrosis factor-α (TNF-α) plays an important role in this regard. The present study aimed to evaluate the association of the rs361525 gene single-nucleotide polymorphism (SNP) and TNF-α serum levels with the hormonal and biochemical characteristics of PCOS in Iranian individuals.

Methods: The SNP rs361525 in the TNF-α gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a total of 111 PCOS patients and 105 healthy females. Serum levels of TNF-α, lipid and hormone profiles, and biochemical factors were measured using enzyme-linked immunosorbent assay (ELISA) and calorimetric methods, as appropriate.

Results: The TNF-α serum level was higher in women with PCOS compared with the control group (p <  0.0001), and it was significantly correlated with the homeostasis model assessment (HOMA) factor (r = 0.138, p <  0.05). No significant differences were found in the genotype and allelic frequencies between the two groups (p >  0.05). Higher levels and significant differences were found for the HOMA factor, luteinizing hormone/follicle-stimulating hormone (LH/FSH), testosterone, and body mass index (BMI) in the PCOS group compared with the control group (p <  0.0001). High LH/FSH ratios (odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.20-3.28, p <  0.01), and high HOMA factor (OR = 5.04, 95% CI = 2.82-9.01, p <  0.001) were significantly associated with an increased risk of PCOS.

Conclusions: Despite the lack of significant difference between rs361525 polymorphism of the TNF-α gene and PCOS, the serum level of TNF-α was increased in PCOS patients and positively correlated with the HOMA factor. Elevation of the LH/FSH ratio and HOMA for insulin resistance (HOMA-IR) increased the risk of PCOS. Therefore, TNF-α could indirectly contribute to PCOS progression.
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http://dx.doi.org/10.1186/s12881-018-0662-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106732PMC
August 2018

The assessment of metabolite alteration induced by -OH functionalized multi-walled carbon nanotubes in mice using NMR-based metabonomics.

Bioimpacts 2018 6;8(2):107-116. Epub 2017 Dec 6.

Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

There is a fundamental need to characterize multiwalled carbon nanotubes (MWCNTs) toxicity to guarantee their safe application. Functionalized MWCNTs have recently attracted special interest in order to enhance biocompatibility. The aim of the current work was to study the underlying toxicity mechanism of the -OH-functionalized MWCNTs (MWCNTs-OH), using the powerful NMR-based metabonomics technique. Following intraperitoneal single-injection of mice with 3 doses of MWCNTs-OH and one control, samples were collected at four time points during 22-days for NMR, biochemistry, and histopathology analysis. Metabolome profiling and pathway analysis were implemented by chemometrics tools and metabolome databases. Based on the H-NMR data, metabolic perturbation induced by MWCNTs-OH were characterized by altered levels of steroid hormones, including elevated androgens, estrogens, corticosterone, and aldosterone. Moreover, increased L-lysine, aminoadipate, taurine and taurocholic acid and decreased biotin were observed in the high-dose group (1 mg.kg B.W.) compared to the control. The findings also indicated that steroid hormone biosynthesis, lysine biosynthesis, and biotin metabolism are the most affected pathways by MWCNTs-OH. These pathways can reflect perturbation of energy, amino acids, and fat metabolism, as well as oxidative stress. The data obtained by biochemistry, metabonomics, and histopathology were in good agreement, proving that MWCNTs-OH was excreted within 24 h, through the biliary pathway.
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http://dx.doi.org/10.15171/bi.2018.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026527PMC
December 2017

Curvelet Transform-based volume fusion for correcting signal loss artifacts in Time-of-Flight Magnetic Resonance Angiography data.

Comput Biol Med 2018 08 15;99:142-153. Epub 2018 Jun 15.

Weldon School of Biomedical Engineering, Purdue University, United States.

Flow fields in cerebral aneurysms can be measured in vivo with phase-contrast MRI (4D Flow MRI), providing 3D anatomical magnitude images as well as 3-directional velocities through the cardiac cycle. The low spatial resolution of the 4D Flow MRI data, however, requires the images to be co-registered with higher resolution angiographic data for better segmentation of the blood vessel geometries to adequately quantify relevant flow descriptors such as wall shear stress or flow residence time. Time-of-Flight Magnetic Resonance Angiography (TOF MRA) is a non-invasive technique for visualizing blood vessels without the need to administer contrast agent. Instead TOF uses the blood flow-related enhancement of unsaturated spins entering into an imaging slice as means to generate contrast between the stationary tissue and the moving blood. Because of the higher resolutions, TOF data are often used to assist with the segmentation process needed for the flow analysis and Computational Fluid Dynamics (CFD) modeling. However, presence of slow moving and recirculating blood flow such as in brain aneurysms, especially regions where the blood flow is not perpendicular to the image plane, causes signal loss in these regions. In this work a 3D Curvelet Transform-based image fusion approach is proposed for signal loss artifact reduction of TOF volume data. Experiments show the superiority of the proposed approach in comparison to other multi-resolution 3D Wavelet-based image fusion methodologies. The proposed approach can further facilitate model-based fluid analysis and pre/post-operative treatment of patients with brain aneurysms.
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http://dx.doi.org/10.1016/j.compbiomed.2018.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077095PMC
August 2018

Curcumin mediated down-regulation of α β integrin and up-regulation of pyruvate dehydrogenase kinase 4 (PDK4) in Erlotinib resistant SW480 colon cancer cells.

Phytother Res 2018 Feb 23;32(2):355-364. Epub 2017 Nov 23.

Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

Erlotinib is a potent, selective, and orally active inhibitor of the epidermal growth factor receptor, but the development of erlotinib resistance during chemotherapy can lead to treatment failure. To shed light on the erlotinib-resistant pathway, this study investigated the effect of combination therapy using curcumin- and erlotinib-loaded nanoparticles on the expression of α β integrin and pyruvate dehydrogenase kinase 4 (PDK4) in an erlotinib-resistant SW480 colon cancer cell line. An erlotinib-resistant SW480 colon cancer cell line was produced by long-term exposure to erlotinib. Curcumin-loaded Methoxy poly ethylene glycol Poly caprolactone (cur/mPEG-PCL) and erlotinib-loaded mPEG-PCL (erl/mPEG-PCL) micelles were provided using a single step nanoprecipitation method and used as combination therapy of resistant SW480 cancer cells. After that, gene expression levels of PDK4, αv, and β3 mRNA were determined by the semiquantitative reverse transcription-polymerase chain reaction. Protein levels of whole α β integrin were evaluated using the enzyme-linked immunosorbent assay method. In SW480 cell line, the IC50 of nonresistant and resistant cells was 87.6 ± 1.2 nM and 19.1 ± 0.14 μM, for erlotinib and it was about 21.8 and 30 μM for curcumin, respectively. Although PDK4 expression was not significantly different in resistant and nonresistant cells, its expression was up regulated (1.4 fold) in resistant cells by a combination therapy of cur/mPEG-PCL at a dose of 3 μM and erl/mPEG-PCL at a dose of 5 μM. β mRNA and the protein level of whole α β integrin was significantly higher in resistant SW480 cells as compared with those in nonresistant cells. In terms of treatment, a combination of 6-μM cur/mPEG-PCL and 5-μM erl/mPEG-PCL down regulated β gene expression 6.6-fold in resistant cells as compared with nonresistant cells. At the protein level, a combination of 3-μM-cur/mPEG-PCL and 10-μM erl/mPEG-PCL reduced α β protein in resistant cells. The results indicated that combination therapy using cur/mPEG-PCL and erl/mPEG-PCL could decrease α β integrin expression and increase PDK4 gene expression in resistant colon cancer cells, which may have effects on drug resistance signaling pathways.
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http://dx.doi.org/10.1002/ptr.5984DOI Listing
February 2018

Evaluation of the Level of Zinc and Malondialdehyde in Basal Cell Carcinoma.

Iran J Public Health 2017 Aug;46(8):1104-1109

Dept. of Clinical Biochemistry, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

Background: Basal Cell Carcinoma (BCC) is one of the most common skin cancers in the world and that use to lifestyle, increasing chemical pollutions, environmental factors and poor nutrition. The most important cause of this cancer is oxidative stress and free radicals so antioxidant activities for the body are so important. The aim of this study was to determine the variation of zinc and (Malondialdehyde) MDA in BCC patients.

Methods: This study has been performed on case and control patients from 2013 to 2014. The samples were collected from cell carcinoma patients at Razi Hospital in Tehran, Iran. We evaluated the level of zinc with the use of Atomic Absorption Spectroscopy (AAS) method. Besides, we evaluated MDA with colorimetric assay.

Results: The concentration of MDA was significantly higher in case group in comparison to control group (=0.001). In addition, case group had lower concentration of zinc than the control group (=0.000). There was no correlation between MDA and body mass index (BMI) and between zinc and BMI.

Conclusion: All the patients with BCC showed a significant MDA serum in comparison with control group. However, significant decrease in zinc serum of the patients was seen that is because of consuming zinc during oxidative stress process so topical use of zinc in the form of 2+ ions could be effective on antioxidant protection against the sun UV radiation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575390PMC
August 2017

Evaluation of hypoxia inducible factor-1 alpha gene expression in colorectal cancer stages of Iranian patients.

J Cancer Res Ther 2016 Oct-Dec;12(4):1313-1317

National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

Aim Of Study: Colorectal cancer (CRC) is the fourth most prevalent cancer globally. Several factors have roles in cancer establishment. One of the most important factors is hypoxia that induces hypoxia inducible factor-1 (HIF-1). The HIF-1 alpha overexpressed in hypoxia conditions and plays a pivotal role in carcinogenesis features. In this study, we aimed to examine the efficiency of HIF-1 alpha gene expression at mRNA and protein's level for CRC diagnosing and staging.

Materials And Methods: In this study, the cases included into 75 cancer specimens in different stages (Group 2 = Stage 1, Group 3 = Stage 2, and Group 4 = Stage 3, 4) and ten normal specimens as control (Group 1). Real-time reverse transcription-polymerase chain reaction and immunohistochemistry (IHC) were performed for measuring gene expression at RNA and protein's level, respectively. The raw data were analyzed in the SPSS20 software.

Results: HIF-1 alpha gene expression rate (2-ΔΔCT) and ΔCT values were significantly higher increased in Group 4 in compare to control (P < 0.001). Other cancer groups (2 and 3) had greater ΔCT values than control, but it was not statistically significant. Moreover, the rate of HIF-1 alpha gene expression (2-ΔΔCT) was increased with cancer stages. According to the IHC results, there was a positive relationship between CRC stages and HIF-1 alpha protein expression (P < 0.05).

Conclusions: HIF-1 alpha gene expression increased in earlier up to metastasis stages of CRC, but the assessment of HIF-1 alpha gene expression has not important role in the diagnosis of cancer in early stages and classification of carcinoma because the increasing of HIF-1 alpha gene expression is not significant in early cancer stages.
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http://dx.doi.org/10.4103/0973-1482.199542DOI Listing
March 2017

Modifying Kinect placement to improve upper limb joint angle measurement accuracy.

J Hand Ther 2016 Oct - Dec;29(4):465-473. Epub 2016 Oct 18.

The Melbourne School of Engineering, The University of Melbourne, Melbourne, Victoria, Australia.

Study Design: Repeated measures.

Introduction: The Kinect (Microsoft, Redmond, WA) is widely used for telerehabilitation applications including rehabilitation games and assessment.

Purpose Of The Study: To determine effects of the Kinect location relative to a person on measurement accuracy of upper limb joint angles.

Methods: Kinect error was computed as difference in the upper limb joint range of motion (ROM) during target reaching motion, from the Kinect vs 3D Investigator Motion Capture System (NDI, Waterloo, Ontario, Canada), and compared across 9 Kinect locations.

Results: The ROM error was the least when the Kinect was elevated 45° in front of the subject, tilted toward the subject. This error was 54% less than the conventional location in front of a person without elevation and tilting. The ROM error was the largest when the Kinect was located 60° contralateral to the moving arm, at the shoulder height, facing the subject. The ROM error was the least for the shoulder elevation and largest for the wrist angle.

Discussion: Accuracy of the Kinect sensor for detecting upper limb joint ROM depends on its location relative to a person.

Conclusion: This information facilitates implementation of Kinect-based upper limb rehabilitation applications with adequate accuracy.

Level Of Evidence: 3b.
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http://dx.doi.org/10.1016/j.jht.2016.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701865PMC
November 2017

Toxic effects of magnesium oxide nanoparticles on early developmental and larval stages of zebrafish (Danio rerio).

Ecotoxicol Environ Saf 2015 Dec 20;122:260-7. Epub 2015 Sep 20.

Department of Biological Sciences, Shahid Beheshti University, Tehran, Iran.

Magnesium oxide nanoparticles (MgONPs) are used in medicine, manufacturing and food industries. Because of their extensive application in our daily lives, environmental exposure to these nanoparticles is inevitable. The present study examined the effects of MgONPs on zebrafish (Danio rerio) early developmental stages. The results showed that, at different concentrations, MgONPs induced cellular apoptosis and intracellular reactive oxygen species. The hatching rate and survival of embryos decreased in a dose dependent manner. The 96-h LC50 value of MgONPs on zebrafish survival was 428 mg/l and the 48-h EC50 value of MgONPs on zebrafish embryo hatching rate was 175 mg/l. Moreover different types of malformation were observed in exposed embryos. The results demonstrate the toxic effects of MgONPs on zebrafish embryos and emphasize the need for further studies.
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http://dx.doi.org/10.1016/j.ecoenv.2015.08.009DOI Listing
December 2015

Synthesis of a stabilized 177Lu-siRNA complex and evaluation of its stability and RNAi activity.

Nucl Med Commun 2015 Jun;36(6):636-45

aDepartment of Clinical Biochemistry, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan bDepartment of Radiochemistry, Nuclear Sciences and Technology Research Institute (NSTRI) cDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Purpose: Serum and intracellular instability limits the therapeutic applications of short interfering RNA (siRNA) as a radiopharmaceutical. Chemical modifications like phosphorothioate (PS) substitution and 2'-O-methoxy (2'-O-Me) modifications could eliminate such limitations. In this study, the effects of PS and 2'-O-Me modifications at the backbone of siRNA on serum stability and RNA interference activity were investigated.

Materials And Methods: Fully PS and 2'-O-Me-modified type 1 insulin-like growth factor receptor (IGF-1R) siRNA was radiolabeled with lutetium-177 ((177)Lu) through p-SCN-Bn-DTPA as a chelator. After purification with Vivaspin and PD-10 columns, the radiolabs were examined for stability in serum by instant thin-layer chromatography and polyacrylamide gel electrophoresis. The level of IGF-1R in response to the modified and labeled IGF-1R siRNA was examined using RT-PCR and ELISA assay in colon cancer cells. The effects of such siRNA on the prevention of proliferation of colon cancer cells and its apoptosis were investigated using MTT assay and Annexin-V/propidium iodide double staining, respectively. Cellular accumulation quantities of the labeled and modified IGF-1R siRNA were determined using a γ-counter by taking advantage of (177)Lu as a γ-emitter.

Results: Both the modified (177)Lu-siRNA complex and the modified nonlabeled siRNA showed significant stability in serum. The levels of IGF-1R mRNA and protein significantly decreased with both the labeled and nonlabeled IGF-1R siRNAs, but no such reduction in IGF-1R was observed with luciferase siRNA (P<0.01). Proliferation decreased significantly and apoptosis increased in the cells treated with modified (177)Lu-IGF-1R siRNA in comparison with either (177)Lu or labeled luciferase siRNA (P<0.001).

Conclusion: Uniform chemically modified siRNAs can form stable complexes with Lu that pronounce its cytotoxic effect through apoptosis in colon cancer cells.
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http://dx.doi.org/10.1097/MNM.0000000000000292DOI Listing
June 2015

Demonstration of dose dependent cytotoxic activity in SW480 colon cancer cells by ¹⁷⁷Lu-labeled siRNA targeting IGF-1R.

Nucl Med Biol 2013 May;40(4):529-36

Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.

Purpose: The radiolabeling of targeting biomolecules with gamma emitter radionuclides for tracing and beta emitters for therapy involves the conjugation of such biomolecules to the chelating agents to form complexes with the radionuclide of interest. In this study, radioconjugate of IGF-1R siRNA with lutetium-177 ((177)Lu) was produced, and the anti-proliferation and apoptosis effects elicited by this (177)Lu-siRNA complex in the SW480 colon cancer cells were evaluated.

Methods: IGF-1R and Luciferase siRNAs were conjugated with p-SCN-Bn-DTPA, and then radiolabeled with (177)Lu. The effects of labeled and non-labeled IGF-1R siRNAs on IGF-1R expression were assessed with RT-PCR analysis and ELISA assay. IGF-1R siRNAs induced cell death and apoptosis were investigated using MTT assay and Annexin-V/propidium iodide (PI) double staining, respectively.

Results: Combined purification using Vivaspin and PD-10 columns resulted in a radiochemical purity of 97.32% ± 1.97%. Knockdown effect of the labeled IGF-1R siRNA was not significantly different from the non-labeled duplex of the same sequence (P<0.05), but it was significant compared to the Luciferase siRNAs (P<0.001). Proliferation decreased significantly, but apoptosis increased in the cells treated with the (177)Lu-IGF-1R siRNA in comparison with either (177)Lu or IGF-1R siRNA (P<0.001).

Conclusion: Radioconjugate of IGF-1R siRNA, p-SCN-Bn-DTPA and (177)Lu was successfully produced and characterized as radiopharmaceutical. The present study demonstrates the involvement of (177)Lu-labeled IGF-1R siRNA in the inhibition of cell growth and induction of apoptosis in colon cancer cells.
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http://dx.doi.org/10.1016/j.nucmedbio.2012.05.001DOI Listing
May 2013

Adenosine induces cell cycle arrest and apoptosis via cyclinD1/Cdk4 and Bcl-2/Bax pathways in human ovarian cancer cell line OVCAR-3.

Tumour Biol 2013 Apr 24;34(2):1085-95. Epub 2013 Jan 24.

Department of Laboratory Sciences, Chalous Branch, Islamic Azad University, Chalous, Iran.

Adenosine is a regulatory molecule with widespread physiological effects in almost every cells and acts as a potent regulator of cell growth. Adenosine has been shown to inhibit cell growth and induce apoptosis in the several cancer cells via caspase activation and Bcl-2/Bax pathway. The present study was designed to understand the mechanism underlying adenosine-induced apoptosis in the OVCAR-3 human ovarian cancer cells. MTT viability, BrdU and cell counting assays were used to study the cell proliferation effect of adenosine in presence of adenosine deaminase inhibitor and the nucleoside transporter inhibitor. Cell cycle analysis, propidium iodide and annexin V staining, caspase-3 activity assay, cyclinD1, Cdk4, Bcl-2 and Bax protein expressions were assessed to detect apoptosis. Adenosine significantly inhibited cell proliferation in a concentration-dependent manner in OVCAR-3 cell line. Adenosine induced cell cycle arrest in G0/G1 phase via Cdk4/cyclinD1-mediated pathway. Adenosine induced apoptosis, which was determined by Annexin V-FITC staining and increased sub-G1 population. Moreover, down-regulation of Bcl-2 protein expression, up-regulation of Bax protein expression and activation of caspase-3 were observed in response to adenosine treatment. The results of this study suggest that extracellular adenosine induced G1 cell cycle arrest and apoptosis in ovarian cancer cells via cyclinD1/ Cdk4 and Bcl-2/Bax pathways and caspase-3 activation. These data might suggest that adenosine could be used as an agent for the treatment of ovarian cancer.
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http://dx.doi.org/10.1007/s13277-013-0650-1DOI Listing
April 2013