Publications by authors named "Ali Najafi"

92 Publications

Candidate Molecular Biomarkers for the Non- Invasive Detection of Colorectal Cancer using Gene Expression Profiling.

Iran J Pathol 2021 2;16(2):205-214. Epub 2021 Mar 2.

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

Background & Objective: olorectal Cancer (CRC) is the third most common cancer after prostate (breast in women) and lung cancer; it is also the third cause of cancer deaths reported in both men and women in 2020. Currently, the most commonly used diagnostic tools for CRC are colonoscopy, serological methods, and other imaging techniques. Despite the benefits and abilities of these methods, each of them has disadvantages that reduce its functionality and acceptance. The aim of this study was identifying specific and non-invasive genetic biomarkers to diagnose colorectal cancer.

Methods: In this study, changes in the expression of and genes were evaluated by Real Time PCR in blood and tissue samples of CRC patients. A total of 100 samples (50 Blood and 50 Tissue samples) were evaluated with a definite diagnosis of CRC in Firoozgar Hspital, Tehran, Iran, in 2018. The QPCR method was used to compare the expression of candidate genes between the patients group and control group in both samples. Sensitivity and specificity of the test were examined using ROC curve analysis.

Results: The results showed a significant down-regulation in the expression of both selected genes in tissue and peripheral blood in the various stages of the CRC. The sensitivity and specifity of both genes was about 80%.

Conclusion: The findings showed that the two candidate genes can be suggested as specific biomarkers for diagnosis of CRC using the peripheral blood as a non-invasive method. For a definite conclusion, more research is needed.
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http://dx.doi.org/10.30699/IJP.2021.132385.2475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085285PMC
March 2021

In silico design of novel aptamers utilizing a hybrid method of machine learning and genetic algorithm.

Mol Divers 2021 Feb 7. Epub 2021 Feb 7.

Department of Bioinformatics, Kish International Campus, University of Tehran, Kish Island, Iran.

Aptamers can be regarded as efficient substitutes for monoclonal antibodies in many diagnostic and therapeutic applications. Due to the tedious and prohibitive nature of SELEX (systematic evolution of ligands by exponential enrichment), the in silico methods have been developed to improve the enrichment processes rate. However, the majority of these methods did not show any effort in designing novel aptamers. Moreover, some target proteins may have not any binding RNA candidates in nature and a reductive mechanism is needed to generate novel aptamer pools among enormous possible combinations of nucleotide acids to be examined in vitro. We have applied a genetic algorithm (GA) with an embedded binding predictor fitness function to in silico design of RNA aptamers. As a case study of this research, all steps were accomplished to generate an aptamer pool against aminopeptidase N (CD13) biomarker. First, the model was developed based on sequential and structural features of known RNA-protein complexes. Then, utilizing RNA sequences involved in complexes with positive prediction results, as the first-generation, novel aptamers were designed and top-ranked sequences were selected. A 76-mer aptamer was identified with the highest fitness value with a 3 to 6 time higher score than parent oligonucleotides. The reliability of obtained sequences was confirmed utilizing docking and molecular dynamic simulation. The proposed method provides an important simplified contribution to the oligonucleotide-aptamer design process. Also, it can be an underlying ground to design novel aptamers against a wide range of biomarkers.
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http://dx.doi.org/10.1007/s11030-021-10192-9DOI Listing
February 2021

Real Clinical Practice and Therapeutic Management Following COVID-19 Crisis in two Hospitals in Iran: A Statistical and Conceptual View.

Tanaffos 2020 Nov;19(2):112-121

Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Background: The Coronavirus disease 2019 (COVID-19) outbreak quickly has spread and became a pandemic. However, no approved therapeutics or effective treatment is available for the treatment of these patients. The present study was done to retrospectively assess the treatment strategies (e.g., pharmaceutical care services) for COVID-19 patients in selected hospitals and highlight the importance of such services in the management of a pandemic.

Materials And Methods: Data from a series of COVID-19 patients (978 patients; 658 males [66.9%] and 324 females [33.1%]) admitted to the selected hospitals in Tehran from 20 February to 19 March 2020 were retrieved retrospectively from the Health Information System (HIS) of the hospitals. The statistical tests were used for analyzing the effect and correlation of the variables (drugs) with the average length of stay (ALOS) in the hospital.

Results: Diverse medication classes and old drugs with or without strong evidence of therapeutic effects against the novel coronavirus, some previously tried as a treatment for SARS-CoV and MERS-CoV, were mostly used for the treatment of patients in the hospitals. Many medications (broad-spectrum antibiotics and antivirals) or combination therapies are used without evidence of their therapeutic effects during pandemics.

Conclusion: Therefore, guidelines should be provided for the off-label use of these drugs by policymakers and stakeholders during a pandemic emergency due to high demands. Also, monitoring of the HIS data can play an important role in improving public health response to emerging diseases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680514PMC
November 2020

Immunoinformatic design of a COVID-19 subunit vaccine using entire structural immunogenic epitopes of SARS-CoV-2.

Sci Rep 2020 11 30;10(1):20864. Epub 2020 Nov 30.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Zakariya Razi Blvd., Kermanshah, Iran.

Coronavirus disease 2019 (COVID-19) is an acute pneumonic disease, with no prophylactic or specific therapeutical solution. Effective and rapid countermeasure against the spread of the disease's associated virus, SARS-CoV-2, requires to incorporate the computational approach. In this study, we employed various immunoinformatics tools to design a multi-epitope vaccine polypeptide with the highest potential for activating the human immune system against SARS-CoV-2. The initial epitope set was extracted from the whole set of viral structural proteins. Potential non-toxic and non-allergenic T-cell and B-cell binding and cytokine inducing epitopes were then identified through a priori prediction. Selected epitopes were bound to each other with appropriate linkers, followed by appending a suitable adjuvant to increase the immunogenicity of the vaccine polypeptide. Molecular modelling of the 3D structure of the vaccine construct, docking, molecular dynamics simulations and free energy calculations confirmed that the vaccine peptide had high affinity for Toll-like receptor 3 binding, and that the vaccine-receptor complex was highly stable. As our vaccine polypeptide design captures the advantages of structural epitopes and simultaneously integrates precautions to avoid relevant side effects, it is suggested to be promising for elicitation of an effective and safe immune response against SARS-CoV-2 in vivo.
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http://dx.doi.org/10.1038/s41598-020-77547-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704662PMC
November 2020

The effect of caring intervention (physical activity, diet and counseling) on gestational diabetes for pregnant women with metabolic syndrome.

J Matern Fetal Neonatal Med 2020 Nov 26:1-7. Epub 2020 Nov 26.

Department of Midwifery and Reproductive Health School of Nursing and Midwifery, Shahroud University of Medical Sciences, Shahroud, Iran.

Objective: Metabolic syndrome and its indexes is one of the critical health problems during pregnancy. This study aimed to examine the effects of a care intervention program on pregnancy outcome in pregnant women with Metabolic Syndrome during 2017-2018.

Methods: This randomized clinical trial study was conducted in 120 singleton pregnant women with metabolic syndrome. The participants were selected using purposive sampling method from pregnant women referred to two health centers of Babol. They were randomly divided in two control and intervention groups (60 samples in each group). Intervention group received one motivational interview session for 120 min, two consultation sessions with expert for nutritional recommendations based on Nutrition Guidelines of Ministry of Health for Pregnant Women. They were also theoretically and practically provided by three training sessions for physical activity and pregnancy exercises combining pelvic floor muscles, bodybuilding, muscle strengthening, stretching, and relaxation and walking activities. To follow up on the intervention, the researcher made a phone call with the participants in intervention group every 10 days to two weeks. Pregnancy outcomes were assessed using SPSS software.

Results: The obtained results showed that there was a significant difference between the two groups in maternal complications including gestational diabetes, hospitalization due to gestational diabetes, nutritional diet for gestational diabetes, pregnancy weight gain and 2-hour post-prandial blood glucose test ( ≤ .01). There was no significant difference in terms of demographic, midwifery and metabolic syndrome indices between the intervention and control groups.

Conclusion: The results of the study indicated that intervention program improved the maternal pregnancy outcome such as gestational diabetes and weight gain during the pregnancy in the intervention group. This program had no adverse effects for the mother who is consistent with pregnancy health objectives.
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http://dx.doi.org/10.1080/14767058.2020.1849088DOI Listing
November 2020

Wireless steerable vision for live insects and insect-scale robots.

Sci Robot 2020 07;5(44)

Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA, USA.

Vision serves as an essential sensory input for insects but consumes substantial energy resources. The cost to support sensitive photoreceptors has led many insects to develop high visual acuity in only small retinal regions and evolve to move their visual systems independent of their bodies through head motion. By understanding the trade-offs made by insect vision systems in nature, we can design better vision systems for insect-scale robotics in a way that balances energy, computation, and mass. Here, we report a fully wireless, power-autonomous, mechanically steerable vision system that imitates head motion in a form factor small enough to mount on the back of a live beetle or a similarly sized terrestrial robot. Our electronics and actuator weigh 248 milligrams and can steer the camera over 60° based on commands from a smartphone. The camera streams "first person" 160 pixels-by-120 pixels monochrome video at 1 to 5 frames per second (fps) to a Bluetooth radio from up to 120 meters away. We mounted this vision system on two species of freely walking live beetles, demonstrating that triggering image capture using an onboard accelerometer achieves operational times of up to 6 hours with a 10-milliamp hour battery. We also built a small, terrestrial robot (1.6 centimeters by 2 centimeters) that can move at up to 3.5 centimeters per second, support vision, and operate for 63 to 260 minutes. Our results demonstrate that steerable vision can enable object tracking and wide-angle views for 26 to 84 times lower energy than moving the whole robot.
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http://dx.doi.org/10.1126/scirobotics.abb0839DOI Listing
July 2020

An efficient hybrid feature selection method to identify potential biomarkers in common chronic lung inflammatory diseases.

Genomics 2020 09 12;112(5):3284-3293. Epub 2020 Jun 12.

Laboratory of Systems Biology and Bioinformatics (LBB), Department of Bioinformatics, Kish International Campus, University of Tehran, Kish Island, Iran; Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. Electronic address:

Asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are three serious lung inflammatory diseases. The understanding of the pathogenesis mechanism and the identification of potential prognostic biomarkers of these diseases can provide the patients with more efficient treatments. In this study, an efficient hybrid feature selection method was introduced in order to extract informative genes. We implemented an ontology-based ranking approach on differentially expressed genes following a wrapper method. The examination of the different gene ontologies and their combinations motivated us to propose a biological functional-based method to improve the performance of further wrapper methods. The results identified: TOM1L1, SRSF1, and GIT2 in asthma; CHCHD4, PAIP2, CRLF3, UBQLN4, TRAK1, PRELID1, VAMP4, CCM2, and APBB1IP in COPD; and TUFT1, GAB2, B4GALNT1, TNFRSF17, PRDM8, and SETDB2 in IPF as the potential biomarkers. The proposed method can be used to identify hub genes in other high-throughput datasets.
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http://dx.doi.org/10.1016/j.ygeno.2020.06.010DOI Listing
September 2020

RPINBASE: An online toolbox to extract features for predicting RNA-protein interactions.

Genomics 2020 05 21;112(3):2623-2632. Epub 2020 Feb 21.

Laboratory of Systems Biology and Bioinformatics (LBB), Department of Bioinformatics, Kish International Campus, University of Tehran, Kish Island, Iran; Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. Electronic address:

Feature extraction is one of the most important preprocessing steps in predicting the interactions between RNAs and proteins by applying machine learning approaches. Despite many efforts in this area, still, no suitable structural feature extraction tool has been designed. Therefore, an online toolbox, named RPINBASE which can be applied to different scopes of biological applications, is introduced in this paper. This toolbox employs efficient nested queries that enhance the speed of the requests and produces desired features in the form of positive and negative samples. To show the capabilities of the proposed toolbox, the developed toolbox was investigated in the aptamer design problem, and the obtained results are discussed. RPINBASE is an online toolbox and is accessible at http://rpinbase.com.
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http://dx.doi.org/10.1016/j.ygeno.2020.02.013DOI Listing
May 2020

PSSP: Protein splice site prediction algorithm using Bayesian approach.

J Bioinform Comput Biol 2019 12;17(6):1950034

Department of Animal Science, University College of Agriculture and Natural Resources, University of Tehran, Karaj, Islamic Republic of Iran.

This study aimed to introduce an algorithm and identify intein motif and blocks involved in protein splicing, and explore the underlying methods in the development of detection of protein motifs. Inteins are mobile protein splicing elements capable of self-splicing post-translationally. They exist in viruses and bacteriophage, notwithstanding this broad phylogenetic distribution, all inteins apportion common structural features. A method was developed to predict intein in a raw sequence, using a ranking and scoring scheme based on amino acid value tables. This method aided in the identification and assessment of patterns characterizing the intein sequences. New intein conserved properties are revealed and the known ones are described and localized. We have computed the value of each amino acid at block A positions to , block B positions to and block G positions 7 to for the three categories. The consensus amino acids thus found are listed at the end of each row. We gave statistics for the distance between the blocks, block A to B, block B to F, and block F to G with the average being 66.1, 294, and 10.2 amino acids, respectively. The actual blocks A, B, and G of the one intein found in vacuolar membrane ATPase subunit, a precursor protein, are ranked 1. The results indicate all of the block sequences that are found in nine proteins are ranked at top of the list. The intein sequence is used to search the databases for intein-like proteins. Understanding the functional, structural, and dynamical aspects of inteins is important for intein engineering and the betterment of intein database.
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http://dx.doi.org/10.1142/S0219720019500343DOI Listing
December 2019

Identification of biomarkers in common chronic lung diseases by co-expression networks and drug-target interactions analysis.

Mol Med 2020 01 17;26(1). Epub 2020 Jan 17.

Laboratory of Systems Biology and Bioinformatics (LBB), Department of Bioinformatics, Kish International Campus, University of Tehran, Kish Island, Iran.

Background: asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are three serious pulmonary diseases that contain common and unique characteristics. Therefore, the identification of biomarkers that differentiate these diseases is of importance for preventing misdiagnosis. In this regard, the present study aimed to identify the disorders at the early stages, based on lung transcriptomics data and drug-target interactions.

Methods: To this end, the differentially expressed genes were found in each disease. Then, WGCNA was utilized to find specific and consensus gene modules among the three diseases. Finally, the disease-disease similarity was analyzed, followed by determining candidate drug-target interactions.

Results: The results confirmed that the asthma lung transcriptome was more similar to COPD than IPF. In addition, the biomarkers were found in each disease and thus were proposed for further clinical validations. These genes included RBM42, STX5, and TRIM41 in asthma, CYP27A1, GM2A, LGALS9, SPI1, and NLRC4 in COPD, ATF3, PPP1R15A, ZFP36, SOCS3, NAMPT, and GADD45B in IPF, LRRC48 and CETN2 in asthma-COPD, COL15A1, GIMAP6, and JAM2 in asthma-IPF and LMO7, TSPAN13, LAMA3, and ANXA3 in COPD-IPF. Finally, analyzing drug-target networks suggested anti-inflammatory candidate drugs for treating the above mentioned diseases.

Conclusion: In general, the results revealed the unique and common biomarkers among three chronic lung diseases. Eventually, some drugs were suggested for treatment purposes.
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http://dx.doi.org/10.1186/s10020-019-0135-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969427PMC
January 2020

Role of dimethyl fumarate in the treatment of glioblastoma multiforme: A review article.

Iran J Neurol 2019 Jul;18(3):127-133

Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Glioblastoma multiforme (GBM), the most frequent malignant and aggressive primary brain tumor, is characterized by genetically unstable heterogeneous cells, diffused growth pattern, microvascular proliferation, and resistance to chemotherapy. Extensive investigations are being carried out to identify the molecular origin of resistance to chemo- and radio-therapy in GBM and find novel targets for therapy to improve overall survival rate. Dimethyl fumarate (DMF) has been shown to be a safe drug with limited short and long-term side effects, and fumaric acid esters (FAEs), including DMF, present both anti-oxidative and anti-inflammatory activity in different cell types and tissues. DMF has also anti-tumoral and neuroprotective effects and so it could be repurposed in the treatment of this invasive tumor in the future. Here, we have reviewed DMF pharmacokinetics and different mechanisms by which DMF could have therapeutic effects on GBM.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858600PMC
July 2019

Structural and functional evaluation of recombinant histidine phosphokinase NisK and response regulator NisR: in silico and experimental approach.

World J Microbiol Biotechnol 2019 Oct 25;35(11):169. Epub 2019 Oct 25.

Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

In the two-component system of NisRK from Lactococcus lactis, the production of nisin is affected by transmembrane NisK and activation of intracellular NisR. The transcription of nisin structural genes can be induced by derivatives of nisin. NisR activation leads to the activation of nisA/Z transcription, which encodes the nisin maturation machinery, nisin regulation and activation of the nisFEG operon to confer immunity. The aim of this study was to express the Lactococcus lactis histidine phosphokinase NisK and response regulator NisR in E. coli, and to perform activity assays and in silico analysis. In silico methods were applied to study the properties and structures of the NisK and NisR proteins, including prediction of physicochemical characteristics, secondary and tertiary structure, stability and ligand-receptor interactions.pET32a and pET28a vectors containing synthetic nisK and nisR genes were transformed into E. coli followed by IPTG induction. SDS-PAGE and western blotting methods were applied to confirm the presence and identity of the amplified proteins. Following purification, the proteins were dialyzed and then prepared for activity assay. The CAI index showed that the genes was compatible with the E. coli host and that the proteins have effective expression. Also, the mRNA prediction results suggest that there is enough mRNA stability for efficient translation in the new host. NisK and NisR recombinant proteins were expressed in E. coli with half - lives of around 10 h and were confirmed with molecular weights of 27 kDa and 69 kDa, respectively, by SDS-PAGE and western blotting. The secondary structure of the recombinant proteins as predicted by circular dichroism spectroscopy was similar to the in silico protein structures. Activity assay of recombinant NisK was performed by measuring the amount of consumed ATP according to the light produced by luciferase. Because NisK and NisR have a direct impact on each other, they have an essential role in increasing the production of nisin and they can be used in different research fields. Our results demonstrated that recombinant proteins NisK and NisR preserved their structure and function after expression.
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http://dx.doi.org/10.1007/s11274-019-2735-5DOI Listing
October 2019

Bullying and Victimization among Students Bears Relationship with Gender and Emotional and Behavioral Problems.

Iran J Psychiatry 2019 Jul;14(3):211-220

Department of Community Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Bullying and victimization are common and serious problems in schools resulting in development of emotional and behavioral disorders in adolescents. This study aimed at examining the prevalence of bullying behavior and some of its associated factors among students. This was a cross sectional analytic study involving junior high schoolers in grades seven, eight and nine. This study was part of an international study that used a questionnaire as a tool for data collection. The questionnaire investigated some of the characteristics and qualities possessed by most juveniles and some occasional problems which they may experience. Also, it was used to examine participants' experiences with bullying and victimization. This questionnaire comprised of 15 sections on demographic characteristics, individual health, family status and types of bullying experiences at school and outside of school, along with the Strengths and Difficulties Questionnaire (SDQ), which is an instrument for screening emotional and behavioral problems in children and adolescents. A multistage cluster sampling from five regions, consisting of the north, south, west, east, and central regions of Tehran, was conducted and 1456 questionnaires were completed by the students. According to the results of this study, prevalence rate for bullying and victimization was 17.4% and 25.8%, respectively. The results indicated that gender had a significant relationship with bullying and victimization, with boys being more likely to be bullies and also more prone to victimization than girls (p < 0.001). Other parameters such as emotional, behavioral, and environmental influence also had a significant relationship with bullying and victimization. Bullying is more prevalent in boys than in girls, and boys are more likely to be victimized as well. Emotional and behavioral problems are identified as risk factors, and future interventions should focus on these risk factors to develop preventive measures.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778606PMC
July 2019

Diagnostic Challenges in the Early Onset of Inflammatory Bowel Disease: A Case Report.

Int J Mol Cell Med 2018 28;7(4):251-257. Epub 2019 Feb 28.

Sanquin Blood Supply Organization, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

Inflammatory bowel disease (IBD) with very early onset manifestations (younger than six years of age) is an essential pediatric gastrointestinal disease that encompasses a group of diverse and rare genetic defects. It may be associated with chronicity, premalignant nature, and high morbidity and mortality during childhood. Because of overlapping phenotypes, the definitive diagnosis based on conventional strategies is frequently a challenge. However, many patients with different molecular pathologies are treated with the same therapeutic strategy. In this context, it is essential to define a more reliable method to provide an opportunity for a rapid and accurate diagnosis. Here we report a novel homozygous exonic variant in a patient with an IBD-like lesion in the colon during the infancy period. A 7 months old boy who was born of a consanguineous marriage developed gastrointestinal disorders early in life. After complete diagnostic workups, this case underwent conventional therapy of IBD for five months; but clinical remission was not achieved. We identified a novel homozygous mutation (c.684C>T p(=)) in exon 7 of gene that studies indicated its significance in the splicing process. At the 14 month of age, this case died. Our finding reveals the importance of genetic screening as an early diagnostic tool in the identification of the underlying causes of IBD with very early onset manifestations, particularly infantile (< 2 years of age) IBD. This strategy makes an opportunity in prompt diagnosis and targeted therapy.
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http://dx.doi.org/10.22088/IJMCM.BUMS.7.4.251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709932PMC
February 2019

Dynamics near planar walls for various model self-phoretic particles.

Soft Matter 2019 Jul;15(28):5644-5672

Department of Physics, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45137-66731, Iran. and Research Center for Basic Sciences & Modern Technologies (RBST), Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45137-66731, Iran.

For chemically active particles suspended in a liquid solution and moving by self-phoresis, the dynamics near chemically inert, planar walls is studied theoretically by employing various choices for the activity function, i.e., the spatial distribution of the sites where various chemical reactions take place. We focus on the case of solutions composed of electrically neutral species. This analysis extends previous studies of the case that the chemical activity can be modeled effectively as the release of a "product" molecular species from parts of the surface of the particle by accounting for annihilation of the product molecules by chemical reactions, either on the rest of the surface of the particle or in the volume of the surrounding solution. We show that, for the models considered here, the emergence of "sliding" and "hovering" wall-bound states is a generic, robust feature. However, the details of these states, such as the range of parameters within which they occur, depend on the specific model for the activity function. Additionally, in certain cases there is a reversal of the direction of the motion compared to the one observed if the particle is far away from the wall. We have also studied the changes of the dynamics induced by a direct interaction between the particle and the wall by including a short-ranged repulsive component to the interaction in addition to the steric one (a procedure often employed in numerical simulations of active colloids). Upon increasing the strength of this additional component, while keeping its range fixed, significant qualitative changes occur in the phase portraits of the dynamics near the wall: for sufficiently strong short-ranged repulsion, the sliding steady states of the dynamics are transformed into hovering states. Furthermore, our studies provide evidence for an additional "oscillatory" wall-bound steady state of motion for chemically active particles due to a strong, short-ranged, and direct repulsion. This kind of particle translates along the wall at a distance from it which oscillates between a minimum and a maximum.
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http://dx.doi.org/10.1039/c9sm00488bDOI Listing
July 2019

Survival analysis and functional annotation of long non-coding RNAs in lung adenocarcinoma.

J Cell Mol Med 2019 08 18;23(8):5600-5617. Epub 2019 Jun 18.

Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) are a subclass of non-protein coding transcripts that are involved in several regulatory processes and are considered as potential biomarkers for almost all cancer types. This study aims to investigate the prognostic value of lncRNAs for lung adenocarcinoma (LUAD), the most prevalent subtype of lung cancer. To this end, the processed data of The Cancer Genome Atlas LUAD were retrieved from GEPIA and circlncRNAnet databases, matched with each other and integrated with the analysis results of a non-small cell lung cancer plasma RNA-Seq study. Then, the data were filtered in order to separate the differentially expressed lncRNAs that have a prognostic value for LUAD. Finally, the selected lncRNAs were functionally annotated using a bioinformatic and systems biology approach. Accordingly, we identified 19 lncRNAs as the novel LUAD prognostic lncRNAs. Also, based on our results, all 19 lncRNAs might be involved in lung cancer-related biological processes. Overall, we suggested several novel biomarkers and drug targets which could help early diagnosis, prognosis and treatment of LUAD patients.
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http://dx.doi.org/10.1111/jcmm.14458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652661PMC
August 2019

Chemotaxis mediated interactions can stabilize the hydrodynamic instabilities in active suspensions.

Soft Matter 2019 Apr;15(15):3248-3255

Department of Physics, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45137-66731, Iran.

Ordered phases in active suspensions of polar swimmers are under long-wavelength hydrodynamic mediated instabilities. In this article, we show that chemical molecules dissolved in aqueous suspensions, as an unavoidable part of most wet active systems, can mediate long-range interactions and subsequently stabilize the polar phase. Chemoattractants in living suspensions and dissolved molecules in synthesized Janus suspensions are reminiscent of such chemical molecules. Communication between swimmers through the gradients of such chemicals is the foundation of this stabilization mechanism. To classify the stable states of such active systems, we investigate the detailed phase diagrams for two classes of systems with momentum conserving and non-conserving dynamics. Our linear stability analysis shows that the proposed stabilization mechanism can work for swimmers with different dynamical properties, e.g., pushers or pullers and with various static characteristics, e.g., spherical, oblate or prolate geometries.
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http://dx.doi.org/10.1039/c9sm00058eDOI Listing
April 2019

Appropriate Interventions for Pregnant Women with Indicators of Metabolic Syndrome on Pregnancy Outcomes: A Systematic Review.

Int J Prev Med 2019 15;10. Epub 2019 Jan 15.

Shahroud University of Medical Sciences, Shahroud, Iran.

Metabolic syndrome (MetS), a series of symptoms, including abdominal obesity, impaired glucose tolerance and insulin metabolism, hypertension, and dyslipidemia, is considered as the risk of developing cardiovascular disease and diabetes that can predispose a pregnant women to serious health problem, women in the developed as well as the developing countries. This study was aimed to investigate the effects of appropriate interventions on pregnant women with indicators of MetS to further improve the outcome of pregnancy. This systematic review was performed to extract articles of randomized controlled trials (RCT) on pregnant women with indicators of (MetS) and focusing on physical activity, dietary or lifestyle interventions on maternal health or perinatal outcomes, with searching in the Web of Science, PubMed, CDSR, Scopus, and Google Scholar were investigated. Two researchers independently evaluated the quality of the studies, being presented in all the articles and ranked the studies as high/low quality; the level of evidence was based on the number of high-quality studies and the coordination of the obtained results. Then, 17 articles, which met the inclusion criteria, were selected; among these, 7 articles studied the physical activity, 3 articles reviewed diets, 6 probed the lifestyle interventions, and 1 article was on counseling. In general, evidence suggested how the physical activity and proper diet impacts on proper weight gain during pregnancy, prevents maternal complications, and improves the outcome of pregnancy. According to the results of this systematic review, proper interventions during pregnancy can have a positive effect on maternal weight gain and the general health condition of pregnant women with indicators of MetS.
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http://dx.doi.org/10.4103/ijpvm.IJPVM_46_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360852PMC
January 2019

Species Composition and Some Biological Features of Scorpions in Kazerun District, Southern Iran.

J Arthropod Borne Dis 2018 Sep 30;12(3):296-309. Epub 2018 Sep 30.

Department of Medical Entomology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Scorpions have medical importance in the studied area with 2377 cases of envenoming during past six years. This study was the first to explore the scorpion species and dispersion in the Kazerun District during 2014-2015.

Methods: The studied sites were selected based on different topographic conditions such as plain, foothill and mountainous which formed four geographical zones with three villages in each zone. The sampling was carried out twice each month throughout the year. Daytime collections were carried out using hand digging tools for moving stones and excavate the borrows, as well as night sampling, is done with the black light device. The coordinate of locations was recorded with a GPS. The collected specimens were maintained in 70% ethanol and identified using authorized keys.

Results: Overall, 800 scorpions were sampled from different parts of Kazerun District, bringing the species richness to 9 belonged to 3 families of Buthidae, Scorpionidae, and Hemiscorpionidae. The (84.6%) was prominent vice versa (0.1%) had lowest abundance. Other species comprised (5.3%), (5.0%), (2.0%), (1.5%), sp (0.9%), (0.4%), and (0.3%). The seasonal activity of the scorpions showed a lower peak in Mar, with the main peaks in Aug for the dominant species. is recorded for the first time in the Fars Province, southern Iran.

Conclusion: All the known dangerous scorpions, including , and were revealed in the studied area.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297727PMC
September 2018

Influence of the T to S mutation at the STMK motif on antibiotic resistance of penicillin binding protein 1A: A comprehensive computational study.

J Mol Graph Model 2019 03 7;87:185-191. Epub 2018 Dec 7.

Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

The emergence of antibiotic resistance has attracted the attention of scientists and scientific circles over the decades. β-Lactam antibiotics resistance is a worldwide therapeutic challenge in bacterial infections, mediated through several mechanisms of which mutations in Penicillin Binding Proteins (PBPs) are an important issue, making critical therapeutic problems in the human population. Accordingly, investigating the dynamic structures of mutant variants could result in a profound understanding of such a specific resistance. Therefore, this work investigated structural properties sampled by all-atom molecular dynamics (MD) simulations, umbrella sampling, and binding free energy calculations for both a wild-type and a cefotaxime-resistant T to S mutant of PBP1A. The T to S mutation significantly reduces the binding affinity of cefotaxime (a frequently clinically-administrated β-lactam antibiotic) as the PBP1A inhibitor. In the conventional MD simulations presented here, more fluctuations of the mutant's active site cleft margins were detected. The cleft of the mutant protein also opened remarkably more than the wild-type's cleft and displayed more flexibility. Thus, our findings have shown that flexibility of cleft margins of the active site in the mutant PBP1A immediately results in the catalytic cleft opening. In addition, binding free energy calculation suggests that reducing hydrophobic contacts and increasing the polar contribution in the binding energy may play an important role in cefotaxime resistance.
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http://dx.doi.org/10.1016/j.jmgm.2018.12.002DOI Listing
March 2019

Evaluation of the analgesic effects of duloxetine in burn patients: An open-label randomized controlled trial.

Burns 2019 05 20;45(3):598-609. Epub 2018 Nov 20.

Herbal and Traditional Medicines Research Center and Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

Objectives: To evaluate efficacy of addition of duloxetine to usual analgesic regimens in management of burn pain.

Methods: In a 3-week open label randomized controlled trial, burn patients were assigned to the intervention (duloxetine 60mg/day+usual analgesic regimens) or control group (usual analgesic regimens: morphine±acetaminophen±gabapentin). Intensity and quality of background pain and severity of procedural pain were evaluated using neuropathic pain scale (NPS) and visual analog scale (VAS), respectively. The primary outcome measure was "intensity" item of the NPS (evaluating intensity of the background pain).

Results: Forty six patients (age: 35.5±6.3 years, TBSA: 36.7±15%) (23 per group) completed the study. At baseline, scores of the "intensity" item were 9.13±1.42 and 9.13±1.86 (P=1) in the intervention and control group, respectively. Comparison of difference in mean changes from baseline to the end of the study showed that addition of duloxetine only significantly reduced the scores of the "intensity" {1.74 (95% CI: 0.61 to 2.86); P=0.003}, and "hot" {1.39 (95% CI: 0.166 to 2.614) P=0.02} items and score of the VAS {2.13 (95% CI: 1.476 to 2.784) P<0.001}. The most reported adverse effects were nausea and insomnia in the both groups.

Conclusion: Addition of duloxetine may increase efficacy of the other analgesics in reduction of the burn pain.
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http://dx.doi.org/10.1016/j.burns.2018.10.011DOI Listing
May 2019

A potential clinical significance of DAB2IP and SPRY2 transcript variants in prostate cancer.

Pathol Res Pract 2018 Dec 29;214(12):2018-2024. Epub 2018 Sep 29.

Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, 1417613151, Iran. Electronic address:

Deregulation of key signaling pathways is one of the primary phenomena in carcinogenesis. DAB2IP and SPRY2 are regulatory elements, which act as feedback inhibitors of receptor tyrosine kinases signaling in mitogen-activated protein kinase pathway. These elements have also been implicated in the pathophysiology of cancer. Therefore, this study is aimed to investigate the expression of all known splice variants of DAB2IP and SPRY2 in prostate tissue. Fresh Prostate tissue samples (50 prostate cancer/ matched normal tissue and 30 BPH) were collected and total RNA was extracted followed by cDNA synthesis. The expression of DAB2IP and SPRY2 transcript variants were evaluated using RT-PCR and quantitative Real-time PCR. The results indicated significant down-regulation of DAB2IP transcript variant 1 in cancerous tissues compared to paired normal tissues (P = 0.001) as well as SPRY2 transcript variant 2 in cancerous tissues in comparison with the normal counterparts and BPH (P = 0.008 and P = 0.025, respectively). In addition, there was a significant negative correlation between DAB2IP.1 and SPRY2.2 expression with PSA levels in prostate cancer (P = 0.039 ρ =-0.24 and P = 0.045 ρ =-0.3, respectively). Interestingly, the down-regulation of DAB2IP.1 mRNA and SPRY2.2 mRNA was positively correlated in tumor samples (P = 0.002 ρ = 0.434). For the first time, this experiment highlights the deregulation of DAB2IP and SPRY2 transcript variants in human prostate cancer. The present study confirms and extends the previous reports through indicating transcript-specific down-regulation and significant association of DAB2IP and SPRY2 in prostate tumorigenesis.
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http://dx.doi.org/10.1016/j.prp.2018.09.019DOI Listing
December 2018

A lentiviral vaccine expressing KMP11-HASPB fusion protein increases immune response to Leishmania major in BALB/C.

Parasitol Res 2018 Jul 29;117(7):2265-2273. Epub 2018 May 29.

Skin Diseases and Leishmaniasis Research Center, Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Hydrophilic acylated surface protein B (HASPB) is an immunogenic Leishmania-specific protein that antibodies are produced against it in the sera of Leishmania-infected individuals. Kinetoplastid membrane protein 11 (KMP11) is another Leishmania antigen and considered as the suitable candidate for vaccine development Leishmaniasis. It is a highly conserved surface protein expressed in both promastigotes and amastigotes. In this study, KMP11 and HASPB coding sequences were cloned into a pCDH-cGFP lentiviral vector as a fusion protein to be used as a DNA vaccine against L. major. The KMP11-HASPB fusion protein was successfully expressed as evidenced by RT-PCR and Western blot assays. The effect of the vaccine was determined by evaluating the level of IFN-γ, IL-10, IgG1, and IgG2a performed using ELISA as well as determining the parasite load after challenge with L. major in vaccinated mice. The results revealed that IFN-γ, IL-10, IgG1, and IgG2a significantly increased after vaccination using KMP11-HASPB-expressing lentiviruses in BALB/c mice. It is noteworthy that the level of IFN-γ and IgG2a was higher than that of IL-10 and IgG1, respectively, which indicates the activation Th1 cells, macrophages, and cellular immunity. Moreover, the parasite load in the spleen and lymph node of vaccinated mice after challenge was significantly lower than that of controls.
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http://dx.doi.org/10.1007/s00436-018-5915-6DOI Listing
July 2018

Molecular dynamics simulation (MDS) analysis of ToxT virulence factor complexed with docked potential inhibitors.

Bioinformation 2018 31;14(3):101-105. Epub 2018 Mar 31.

Molecular Biology Research Center, Systems Biology and Poisonings institute, Baqiyatallah University of Medical Sciences, Tehran, IRAN.

The ToxT transcription factor mediates the transcription of the two major virulence factors in Vibrio cholerae. It has a DNA binding domain made of α4, α5, α6, α7, α8, α9 and α10 helices that is responsible for the transcription of virulence genes. Therefore, it is of interest to screen ToxT against the ZINC ligand database containing data for a million compounds. The QSAR model identified 40 top hits for ToxT. Two target protein complexes with ligands Lig N1 and Lig N2 with high score were selected for molecular dynamics simulation. Simulation data shows that ligands are stable in the DNA binding domain of ToxT. Moreover, Lig N1 and Lig N2 passed pharmacological as well as ADME filters along with g-mmpbsa analysis with binding affinity of -199.831 kJ/mol for Lig N1 and - 286.951 kJ/mol for Lig N2. Moreover, no Lipinski and PhysChem violations were identified. It is further observed that these compounds were not inhibitors of P-glycoprotein, CYP450 and renal organic cation transporters. The LD50 of 2.5804 mol/kg for Lig N1 and 2.7788 mol/kg for Lig N2 was noted with acceptable toxicity index.
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http://dx.doi.org/10.6026/97320630014101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953856PMC
March 2018

Bacterial CRISPR Regions: General Features and their Potential for Epidemiological Molecular Typing Studies.

Open Microbiol J 2018 23;12:59-70. Epub 2018 Apr 23.

Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Introduction: CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) loci as novel and applicable regions in prokaryotic genomes have gained great attraction in the post genomics era.

Methods: These unique regions are diverse in number and sequence composition in different pathogenic bacteria and thereby can be a suitable candidate for molecular epidemiology and genotyping studies. Results:Furthermore, the arrayed structure of CRISPR loci (several unique repeats spaced with the variable sequence) and associated genes act as an active prokaryotic immune system against viral replication and conjugative elements. This property can be used as a tool for RNA editing in bioengineering studies.

Conclusion: The aim of this review was to survey some details about the history, nature, and potential applications of CRISPR arrays in both genetic engineering and bacterial genotyping studies.
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http://dx.doi.org/10.2174/1874285801812010059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5925864PMC
April 2018

Design and construction of a new recombinant fusion protein (2b2t+EPC1) and its assessment for serodiagnosis of cystic echinococcosis.

APMIS 2018 May;126(5):428-439

Paramedical Faculty, Golestan University of Medical Sciences, Gorgan, Iran.

The immunodiagnostic tests for cystic echinococcosis (CE) are mostly serological tests based on ELISA that use hydatid cyst antigens for primary screening because of its simple preparation and availability. The challenge to develop new serological methods (as compared to those based on the hydatid cyst fluid antigens) to meet the gold standard remains. Appropriate sources of antigenic material are necessary for application to improve the efficacy of immunodiagnostic tests at a population level. In the current study, a fusion protein containing the coding sequence of antigen B2t and two sequences of EPC1 antigen with some modifications was reconstructed. Using bioinformatics tools, these sequences were joined together by applying the sequence of a rigid α-helix-forming linker to obtain an appropriate structure of a fusion protein. Synthetic recombinant fusion protein was expressed using pET28a as a vector and evaluated by indirect ELISA test for sera from patients with hepatic CE and other parasitic infections. The sensitivity of the fusion protein was lower (88.46%) than the available ELISA kit (96.15%). However, the differences in sensitivity were not statistically significant as compared to the recombinant fusion peptide with the commercial kit (p = 0.269). The specificity of the recombinant fusion protein (95.45%) was not significantly lower than the commercial kit (96.59%; p = 1.000). Moreover, surprisingly there was no difference in the cross-reactivity values of performance between the recombinant-ELISA and commercial kit. The positive and negative predictive values of the recombinant antigen were achieved as 92% and 93.33%, respectively, while for the commercial kit, they were obtained as 94.33% and 97.70%, respectively. In conclusion, as an early evaluation of these antigens the performance of our recombinant fusion protein in ELISA is relatively promising. Although, it seemed that this peptide with specific antigenic epitopes might be more appropriate for the serological evaluation of CE by use of bioinformatics tools, our findings showed that cross-reactions and a negative reaction could occur in clinical performance. This fusion protein may have utility for diagnosis in humans, but further evaluation is needed using the WHO ultrasound classification for CE.
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http://dx.doi.org/10.1111/apm.12838DOI Listing
May 2018

MicroRNA expression in serum samples of sulfur mustard veterans as a diagnostic gateway to improve care.

PLoS One 2018 22;13(3):e0194530. Epub 2018 Mar 22.

Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Sulfur mustard is a vesicant chemical warfare agent, which has been used during Iraq-Iran-war. Many veterans and civilians still suffer from long-term complications of sulfur mustard exposure, especially in their lung. Although the lung lesions of these patients are similar to Chronic Obstructive Pulmonary Disease (COPD), there are some differences due to different etiology and clinical care. Less is known on the molecular mechanism of sulfur mustard patients and specific treatment options. microRNAs are master regulators of many biological pathways and proofed to be stable surrogate markers in body fluids. Based on that microRNA expression for serum samples of sulfur mustard patients were examined, to establish specific microRNA patterns as a basis for diagnostic use and insight into affected molecular pathways. Patients were categorized based on their long-term complications into three groups and microRNA serum levels were measured. The differentially regulated microRNAs and their corresponding gene targets were identified. Cell cycle arrest, ageing and TGF-beta signaling pathways showed up to be the most deregulated pathways. The candidate microRNA miR-143-3p could be validated on all individual patients. In a ROC analysis miR-143-3p turned out to be a suitable diagnostic biomarker in the mild and severe categories of patients. Further microRNAs which might own a link to the biology of the sulfur mustard patients are miR-365a-3p, miR-200a-3p, miR-663a. miR-148a-3p, which showed up only in a validation study, might be linked to the airway complications of the sulfur mustard patients. All the other candidate microRNAs do not directly link to COPD phenotype or lung complications. In summary the microRNA screening study characterizes several molecular differences in-between the clinical categories of the sulfur mustard exposure groups and established some useful microRNA biomarkers. qPCR raw data is available via the Gene Expression Omnibus https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110797.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194530PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864010PMC
July 2018

Classification and Biomarker Genes Selection for Cancer Gene Expression Data Using Random Forest.

Iran J Pathol 2017 1;12(4):339-347. Epub 2017 Oct 1.

Dept. of Biostatistics, Public Health School, Mashhad University of Medical Sciences, Mashhad, Iran.

Background & Objective: Microarray and next generation sequencing (NGS) data are the important sources to find helpful molecular patterns. Also, the great number of gene expression data increases the challenge of how to identify the biomarkers associated with cancer. The random forest (RF) is used to effectively analyze the problems of large-p and small-n. Therefore, RF can be used to select and rank the genes for the diagnosis and effective treatment of cancer.

Methods: The microarray gene expression data of colon, leukemia, and prostate cancers were collected from public databases. Primary preprocessing was done on them using limma package, and then, the RF classification method was implemented on datasets separately in R software. Finally, the selected genes in each of the cancers were evaluated and compared with those of previous experimental studies and their functionalities were assessed in molecular cancer processes.

Result: The RF method extracted very small sets of genes while it retained its predictive performance. About colon cancer data set , , , and key genes with the accuracy of 87.39 and precision of 85.45 were selected. The , , and genes were selected for prostate cancer with the accuracy of 73.33 and precision of 66.67. Also, key genes of leukemia data set were , -, , and genes, and the accuracy and precision were 100 and 95.24, respectively.

Conclusion: The current study results showed most of the selected genes involved in the processes and cancerous pathways were previously reported and had an important role in shifting from normal cell to abnormal.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844678PMC
October 2017

Understanding the resistance mechanism of penicillin binding protein 1a mutant against cefotaxime using molecular dynamic simulation.

J Biomol Struct Dyn 2019 Feb 22;37(3):741-749. Epub 2018 Feb 22.

a Molecular Biology Research Center, Systems Biology and Poisonings Institute , Baqiyatallah University of Medical Sciences , Tehran , Iran.

Antibiotic resistance is a threatening challenge for global health, as the expansion of resistance to current antibiotics has made serious therapeutic problems. Genome mutations are key evolutionary mechanisms conferring antibiotic resistance in bacterial pathogens. For example, penicillin and cephalosporins resistance is mostly mediated by mutations in penicillin binding proteins to change the affinity of the drug. Accordingly, threonine point mutations were reported to develop antibiotic resistance in various bacterial infections including pneumococcal infections. In this study, conventional molecular dynamics simulations, umbrella sampling simulations and MM/GBSA free energy calculations were applied to figure out how the Threonine to Alanine mutation (T to A) at STMK motif affects the binding of cefotaxime to Penicillin Binding Protein 1a and to reveal the resistance mechanism induced by the T to A mutation. The results obtained from the computational methods demonstrate that the T to A mutation increases the flexibility of the binding pocket and changes its conformation, which leads to increased conformational entropy change (-TΔS) and attenuates the bonds between the ligand and the receptor. In brief, our findings indicate that both of the alterations of the conformational enthalpy and entropy contribute to the T to A-induced resistance in the binding of cefotaxime into penicillin binding protein 1a.
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http://dx.doi.org/10.1080/07391102.2018.1439404DOI Listing
February 2019

Inducing Apoptosis and Decreasing Cell Proliferation in Human Acute Promyelocytic Leukemia Through Regulation Expression of by Let-7a-5p Blockage.

Indian J Hematol Blood Transfus 2018 Jan 29;34(1):70-77. Epub 2017 Mar 29.

2Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, 81744-176 Iran.

MicroRNAs (miRNAs) are short and single strand non-coding RNAs that involved in post-transcriptional regulation of gene expression. Dysregulation of miRNA expression is important event in the many of malignant diseases. Up-regulation of Let-7a-5p expression in acute myeloid leukemia in human in previous studies was reported. In this study blockage of Let-7a-5p in human acute promyelocytic leukemia cell line (HL60) was done by using locked nucleic acid (LNA) method and subsequently expression of Let-7a-5p, cell proliferation, apoptosis, necrosis, and expression was measured. At three time points 24, 48 and 72 h after LNA anti- Let-7a-5p transfection, assessment of Let-7a-5p expression by qRT real-time PCR was completed. The MTT assay and annexin/PI staining have been performed. Also, expression at different time points after LNA anti-Let-7a-5p transfection in HL60 cell line was measured. The results at three-time points after LNA transfection were represented that Let-7a-5p expression was lower in the LNA-anti-Let-7a group compared to the control groups. The cell viability significantly was different between LNA-anti-Let-7a group and control groups. Increasing apoptotic ratio was associated with Let-7a-5p blockage in the LNA-anti-Let-7a group compared with control groups. Also, the necrotic ratio was higher in the LNA-anti-Let-7a group rather than the other groups. Western blotting revealed that CASP3 expression associated with Let-7a-5p inhibition. Our results displayed that blockage of Let-7a-5p can reduced cell viability mainly due to the induction of apoptosis and up-regulation in HL60 cells. These results can be useful in translational medicine for research of antisense therapy in leukemia.
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http://dx.doi.org/10.1007/s12288-017-0809-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786606PMC
January 2018