Publications by authors named "Mehrdad Moosazadeh Moghaddam"

27 Publications

  • Page 1 of 1

Conjugation of imipenem to silver nanoparticles for enhancement of its antibacterial activity against multi-drugresistant isolates of .

J Biosci 2021 ;46

Young Researchers and Elite Club, Saveh Branch, Islamic Azad University, Saveh, Iran.

Due to the broad-spectrum of antibiotic resistance, herein we investigated the possibility of using imipenemconjugated silver nanoparticles (IMP-AgNPs) against multidrug-resistant isolates of . For this purpose, 200 clinical isolates were tested against different antibiotics to determine the antimicrobial susceptibility. To identify and resistance genes, PCR was used. The synthesized AgNPs and conjugants were characterized using UV-vis spectroscopy, XRD, SEM, TEM, DLS, and FTIR. The stability, drug release kinetics, cytotoxicity, hemolytic and apoptotic effects of NPs were also investigated. MIC of the imipenem, AgNPs, and conjugants were evaluated versus isolates. Finally, the effects of the IMP-AgNPs to heal burn wounds in rats was evaluated. According to the results, about 68% of isolates showed resistance to imipenem (MIC ≥ 64 μg/ml to ≥ 512 μg/ml). Analytical results verified the synthesis of AgNPs and IMP-AgNPs. A Dose-dependent decrease happened in terms of the MIC values of IMP-AgNPs were also affected by the existence of resistant genes. Low cytotoxic was observed regarding AgNPs which lead to apoptosis. The histopathological results showed a considerable epithelization in treated groups with IMPAgNPs. Accordingly, IMP-AgNPs can be considered as a powerful antibacterial agent to treat the infections caused by multidrug-resistant .
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January 2021

Antiviral peptides against Coronaviridae family: A review.

Peptides 2021 05 4;139:170526. Epub 2021 Mar 4.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

The Coronaviridae family comprises large enveloped single-stranded RNA viruses. The known human-infecting coronaviruses; severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), novel SARS-CoV-2, human coronavirus (HCoV)-NL63, HCoV-229E, HCoV-OC43 and HKU1 cause mild to severe respiratory infections. The viral diseases induced by mammalian and avian viruses from Coronaviridae family pose significant economic and public health burdens. Due to increasing reports of viral resistance, co-infections and the emergence of viral epidemics such as COVID-19, available antiviral drugs show low or no efficacy, and the production of new treatments or vaccines are also challenging. Therefore, demand for the development of novel antivirals has considerably increased. In recent years, antiviral peptides have generated increasing interest as they are from natural and computational sources, are highly specific and effective, and possess the broad-spectrum activity with minimum side effects. Here, we have made an effort to compile and review the antiviral peptides with activity against Coronaviridae family viruses. They were divided into different categories according to their action mechanisms, including binding/attachment inhibitors, fusion and entry inhibitors, viral enzyme inhibitors, replication inhibitors and the peptides with direct and indirect effects on the viruses. Reported studies suggest optimism with regard to the design and production of therapeutically promising antiviral drugs. This review aims to summarize data relating to antiviral peptides particularly with respect to their applicability for development as novel treatments.
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http://dx.doi.org/10.1016/j.peptides.2021.170526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931737PMC
May 2021

Response to Mechanical Cues by Interplay of YAP/TAZ Transcription Factors and Key Mechanical Checkpoints of the Cell: A Comprehensive Review.

Cell Physiol Biochem 2021 Jan;55(1):33-60

Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran,

Many factors including growth factors (GF), scaffold materials, and chemical and physical cues determine the cell behaviors. For many years, growth factors have been considered as the pivotal cell behavior regulators, whereas recent studies emphasize also the key role of physical factors such as mechanical forces, cell shape, surface topographies, and extracellular matrix (ECM) in regulating the cell proliferation, apoptosis, differentiation, etc. through mechanotransduction pathways. In this process, the cell morphology and mechanical properties of the cell's micro/ nano-environments and ECM can be conveyed to the nucleus by regulating transcriptional factors such as Yes-associated protein and transcriptional coactivator with PDZ-binding motif (TAZ). Generally, YAP/TAZ activity is considered as the key factor for the growth of whole organs, however, recent studies have also repeatedly addressed the role of YAP/TAZ in mechanotransduction. In this review, the biological functions of the YAP/TAZ pathway and its contribution to the mechanotransduction and cell behavior regulation in response to the mechanical cues have been summarized. Also, the role of key mechanical checkpoints in the cell including focal adhesions, cytoskeletal tension, Rho small GTPases, and nuclear membrane protein elements involved in the transfer of environmental mechanical cues from the cell surface to the nucleus and their effect in regulating the YAP/TAZ activity are discussed.
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http://dx.doi.org/10.33594/000000325DOI Listing
January 2021

Molecular and serological detection and of in small ruminants of southwest Iran and the potential risks for consumers.

J Verbrauch Lebensm 2021 Jan 2:1-11. Epub 2021 Jan 2.

Department of Food Hygiene, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

Toxoplasmosis is one of the most important zoonotic diseases with serious health risks for humans, especially for immunodeficient patients, and can lead to abortion in pregnant women worldwide. The oral uptake of sporulated oocysts and/or consumption of undercooked/raw meat of animals infected with can infect other animals and humans Heart, liver, and meat tissues of 150 sheep and 150 goats from a slaughterhouse in Ahvaz, Iran, were collected during autumn 2018 and analyzed via polymerase chain reaction (PCR) to detect parasitic DNA in the animal tissues. Moreover, antibodies against of 150 sera samples were detected as the targets by in-house enzyme-linked immunosorbent assay (in-house ELISA). A total of 26 (17.3%), 33 (22%), and 48 (32%) of liver, meat, and heart samples in sheep, and a total of 24 (16%), 26 (17.3%), and 36 (24%) of liver, meat, and heart samples in goats, respectively, showed positive PCR results. Besides, the ELISA evaluation of sera samples from 150 sheep and 150 goats resulted in 26 (13.3%) and 16 (10.6%) positive cases, respectively. A significant difference was also found between PCR-positive heart samples and ELISA-positive sera samples of both animal species (p < 0.05), but no significant difference existed between PCR-positive liver samples and ELISA-positive sera samples of both species (p > 0.05). The results of this study confirm the presence of in sheep and goats' consumable organs, highlighting the need to avoid consuming raw or uncooked organs of these animal species to prevent human infection with .
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http://dx.doi.org/10.1007/s00003-020-01306-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776314PMC
January 2021

Protective Effect of Vitamin D3 Against Pb-Induced Neurotoxicity by Regulating the Nrf2 and NF-κB Pathways.

Neurotox Res 2021 Jun 5;39(3):687-696. Epub 2021 Jan 5.

Azad Islamic University, Damghan Branch, Damghan, Iran.

Lead (Pb) is a known toxic heavy metal which accumulates in different tissues and causes oxidative stress (OS) and inflammation. The brain tissue is considered as one of the most vulnerable organs to the Pb-induced toxicity. The aim of this study was to investigate the therapeutic effects of vitamin D3 (VD) supplementation against the damages caused by chronic Pb toxicity in the cerebral cortex. Forty Wistar rats were divided into four equal groups and were treated as follows: control group received no treatment, VD group received 1000 IU/kg of VD by intramuscular injection every other day, Pb group received 1000 mg/L of Pb in drinking water, and Pb + VD group received VD and Pb simultaneously. The experiment lasted for 4 weeks and the analyses were conducted 24 h after the last administrations. The obtained results demonstrated that Pb significantly increased cortical lipid peroxidation and reactive oxygen species (ROS) levels. At the same time, there was a significant reduction in glutathione (GSH) content, catalase (CAT), and superoxide dismutase (SOD) activities, as well as a significant increase in the tissue level of inflammatory cytokines. Furthermore, Pb increased the messenger RNA (mRNA) expression level of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB). Anyhow, VD administration during the period of Pb exposure suppressed the OS and inflammation by increasing the antioxidant molecules and decreasing the inflammatory cytokines and consequently repaired Pb-induced cortical tissue damages. Remarkably, these responses were concomitant with the alterations in Nrf2 and NF-κB gene expressions. In conclusion, the present study discloses the potential protective effects for VD against Pb-induced neurotoxicity via anti-inflammatory and antioxidative mechanisms.
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http://dx.doi.org/10.1007/s12640-020-00322-wDOI Listing
June 2021

Clinical characteristics and outcome of hospitalized COVID-19 patients with diabetes: A single-center, retrospective study in Iran.

Diabetes Res Clin Pract 2020 Nov 24;169:108467. Epub 2020 Sep 24.

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

Aim: To describe the epidemiological and clinical characteristics along with outcomes of hospitalized Coronavirus Disease 2019 (COVID-19) patients with and without diabetes.

Methods: This retrospective, single-center study included 595 consecutive hospitalized patients with confirmed COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from February 26, 2020 to March 26, 2020. Demographic data, clinical, laboratory, and radiological findings were collected and compared between patients based on diabetes status. Complications and clinical outcomes were followed up until April 4, 2020.

Results: From among the 595 hospitalized patients with COVID-19, the median age was 55 years and 401 (67.4%) were male. The most common symptoms included fever (419 [70.4%]), dry cough (368 [61.8%]) and dyspnea (363 [61%]). A total of 148 patients (24.9%) had diabetes, and compared with patients without diabetes, these patients had more comorbidities (eg, hypertension [48.6% vs. 22.3%; P < 0.001]); had higher levels of white blood cell count, neutrophil count, C-reactive protein, erythrocyte sedimentation rate and blood urea nitrogen, and had a higher proportion of patchy ground-glass opacity in chest computed tomography findings (52.7% vs. 25.7%; P < 0.001). Significantly, patients with diabetes had more complications and needed more respiratory support than those without diabetes (P < 0.001). At the end of the follow-up, treatment failure and death was significantly higher in patients with diabetes compared to those without diabetes (17.8% vs. 8.7%; P = 0.003).

Conclusion: COVID-19 patients with diabetes are at a higher risk of complications and a higher in-hospital mortality during hospitalization. Diabetes status of COVID-19 patients and frequent monitoring of glycemia would be helpful to prevent deteriorating clinical conditions.
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http://dx.doi.org/10.1016/j.diabres.2020.108467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513687PMC
November 2020

Integrative role of traditional and modern technologies to combat COVID-19.

Expert Rev Anti Infect Ther 2021 01 23;19(1):23-33. Epub 2020 Aug 23.

Halal Research Center of IRI, FDA , Tehran, Iran.

Introduction: With the development of various branches of sciences, we will be able to resolve different clinical aspects of various diseases better. The convergence of these sciences can potentially tackle the new corona crisis.

Areas Covered: In this review, we attempted to explore and describe various scientific branches studying COVID-19. We have reviewed the literature focusing on the prevention, diagnosis, and treatment of COVID-19. The primary databases targeted were Science Direct, Scopus and PubMed. The most relevant reports from the recent two decades were collected utilizing keywords including SARS-CoV, MERS-CoV, COVID-19, epidemiology, therapeutics and diagnosis.

Expert Opinion: Based on this literature review, both traditional and emerging approaches are vital for the prevention, diagnosis and treatment of COVID-19. The traditional sciences play an essential role in the preventive and supportive care of corona infection, and modern technologies appear to be useful in the development of precise diagnosis and powerful treatment approaches for this disease. Indeed, the integration of these sciences will help us to fight COVID-19 disease more efficiently.
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http://dx.doi.org/10.1080/14787210.2020.1799784DOI Listing
January 2021

Assessment of Susceptibility to Five Common Antibiotics and Their Resistance Pattern in Clinical Enterococcus Isolates.

Iran J Pathol 2020 19;15(2):96-105. Epub 2020 Feb 19.

Department of Microbiology, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch Islamic Azad University, Tehran, Iran (IAUPS).

Background & Objective: Enterococcus Species are the common cause of nosocomial infections, which are highly resistant to different antibiotics. Therefore, determination of their antibiotic susceptibility patterns and simultaneous resistance to antibiotics is important for better treatment strategies.

Methods: 400 clinical isolates were collected from different hospitals in Tehran, Iran. Standard phenotypic-biochemical tests and PCR were used to identify the species. The antimicrobial susceptibility patterns and simultaneous resistance to selected antibiotics were determined by disk diffusion method according to the CLSI guidelines. All data analysis was performed using Python packages Scipy and Stats models.

Results: According to the biochemical and PCR analyses, among 400 species, 72% of samples were , 10.75% , and 17.25% other species. The results determined antimicrobial resistances of these strains against gentamicin, vancomycin, fosfomycin trometamol, teicoplanin, and quinupristin/dalfopristin. Results confirmed a significant correlation between resistance to vancomycin and resistance to teicoplanin. This correlation remains significant when including only or species. We also found a negative correlation between resistance to teicoplanin and quinupristin/dalfopristin. Additionally, Quinupristin/dalfopristin was the least effective antibiotic while vancomycin and teicoplanin were the most effective ones.

Conclusion: Based on the results and association between simultaneous resistance to some antibiotics such as vancomycin and teicoplanin, in the case of antibiotic resistance, the choice of a second antibiotic can be very important which can lead to good or bad effects.
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http://dx.doi.org/10.30699/IJP.2020.114009.2236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081761PMC
February 2020

Polymeric nanoparticles as carrier for targeted and controlled delivery of anticancer agents.

Ther Deliv 2019 08 9;10(8):527-550. Epub 2019 Sep 9.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

In recent decades, many novel methods by using nanoparticles (NPs) have been investigated for diagnosis, drug delivery and treatment of cancer. Accordingly, the potential of NPs as carriers is very significant for the delivery of anticancer drugs, because cancer treatment with NPs has led to the improvement of some of the drug delivery limitations such as low blood circulation time and bioavailability, lack of water solubility, drug adverse effect. In addition, the NPs protect drugs against enzymatic degradation and can lead to the targeted and/or controlled release of the drug. The present review focuses on the potential of NPs that can help the targeted and/or controlled delivery of anticancer agents for cancer therapy.
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http://dx.doi.org/10.4155/tde-2019-0044DOI Listing
August 2019

A biomaterials approach to Schwann cell development in neural tissue engineering.

J Biomed Mater Res A 2019 11 7;107(11):2425-2446. Epub 2019 Jul 7.

National Cell Bank Department, Pasteur Institute of Iran, Tehran, Iran.

Schwann cells, in addition to forming myelin sheaths, have pivotal roles in regeneration of injured axons in the peripheral nervous system such as producing a natural permissive conduit between distal and proximal stumps and secreting nerve growth factors. Due to the atrophy and senescence of Schwann cells in long nerve gap, and the need to ensure the presence of nerve growth factors and basal lamina tubes for axon regeneration in a critical time, injection of Schwann cells with the aid of an engineered conduit seems to be an effective approach to induce axon regrowth. Stem cells with high differentiation and proliferation capability can provide an adequate number of Schwann cells in healthy state for regeneration purposes. Guidance of stem cells differentiation into desired lineages, control of implanted Schwann cells fate, maintenance of nerve growth factors expression, and guidance of axon regrowth are possible with the aid of biomaterials with appropriate chemical, physical, and mechanical properties. Biomaterials' surface chemistry and biomolecules interacting with cells' receptors initiate specific intracellular signaling cascades and direct cells fate. In addition, biomaterials' surface topography in association with cells contact area, focal adhesion, and cytoskeletal remodeling by mechanotransduction process influences cells behavior and induces specific differentiation. The main objective of this review is to investigate the chemical, topographical, and mechanical properties of biomaterials which influence the fate of Schwann cells and the nerve regeneration process.
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http://dx.doi.org/10.1002/jbm.a.36749DOI Listing
November 2019

Crosstalk between chitosan and cell signaling pathways.

Cell Mol Life Sci 2019 Jul 27;76(14):2697-2718. Epub 2019 Apr 27.

Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran.

The field of tissue engineering (TE) experiences its most exciting time in the current decade. Recent progresses in TE have made it able to translate into clinical applications. To regenerate damaged tissues, TE uses biomaterial scaffolds to prepare a suitable backbone for tissue regeneration. It is well proven that the cell-biomaterial crosstalk impacts tremendously on cell biological activities such as differentiation, proliferation, migration, and others. Clarification of exact biological effects and mechanisms of a certain material on various cell types promises to have a profound impact on clinical applications of TE. Chitosan (CS) is one of the most commonly used biomaterials with many promising characteristics such as biocompatibility, antibacterial activity, biodegradability, and others. In this review, we discuss crosstalk between CS and various cell types to provide a roadmap for more effective applications of this polymer for future uses in tissue engineering and regenerative medicine.
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http://dx.doi.org/10.1007/s00018-019-03107-3DOI Listing
July 2019

Engineered substrates with imprinted cell-like topographies induce direct differentiation of adipose-derived mesenchymal stem cells into Schwann cells.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):1022-1035

a Stem Cell and Regenerative Medicine Group , National Institute of Genetic Engineering and Biotechnology (NIGEB) , Tehran , Iran.

Differentiation of stem cells to Schwann is considered efficient way for nerve regeneration since the sources of human Schwann cells are limited for clinical application. It is demonstrated that mimicking micromechanical forces or micro/nanotopographical environments that stem cells are experienced in vivo could control their fate. Here, the potency of substrates with imprinted cell-like topographies for direct differentiation of adipose-derived mesenchymal stem cells (ADSCs) into Schwann cells (SCs) is reported. For the preparation of substrates with imprinted SC-Like topographies, SCs are isolated from the sciatic nerve, grown, fixed, and then SC morphologies are transferred to polydimethylsiloxane (PDMS) substrates by mold casting. Subsequently, mesenchymal stem cells (MSCs) are seeded on the SC-imprinted substrates and their differentiation to SCs is evaluated by immunocytochemistry, real-time PCR, and western blotting. Analysis of morphology and expression of SC-specific markers show that MSCs cultured on the imprinted substrates have the typical SC-like morphology and express SC-specific markers including S100b, p75NTR, and Sox10. It is believed that specific cell-like topographies and related micromechanical cues can be sufficient for direct differentiation of ADSCs into Schwann cells by cell-imprinting method as a physical technique.
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http://dx.doi.org/10.1080/21691401.2019.1586718DOI Listing
December 2019

Antimicrobial activity of an antimicrobial peptide against amastigote forms of .

Vet Res Forum 2018 15;9(4):323-328. Epub 2018 Dec 15.

Zoonosis Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Zoonotic cutaneous leishmaniasis caused by is a most common type of vector-borne disease in Iran. The pentavalent antimonial drugs have been used in the treatment of cutaneous leishmaniasis for a long time, but drug resistance and some of serious side effects have been reported. Thus, discovery and development of new therapeutic candidates are needed. The CM11 peptide is one of these peptides that its anti-bacterial activity has been proven. This peptide is a short cecropin-melittin hybrid peptide obtained through a sequence combination approach. The aim of this study was to evaluate anti-leishmanial activity of CM11 peptide against amastigote forms of . In this study, amastigote forms of Iranian strain of (MRHO/IR/75/ER) were cultured in the presence of different concentrations of meglumine antimoniate (Glucantime) to find the most appropriate concentration of Glucantime against amastigotes. Then, the anti-leishmanial activities of various concentrations of CM11 peptide (8, 16, 32 and 64 µM) were evaluated for 24, 48 and 72 hr by DAPI staining. In addition, MTT assay was used to determine the cytotoxic effects of CM11 peptide on murine fibroblast cell line. The results showed that CM11 peptide has antimicrobial activity against Iranian isolate of in the laboratory conditions. It seems that the CM11 peptide has significant potential to be used as a new anti-leishmanial agent.
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http://dx.doi.org/10.30466/vrf.2018.33107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346494PMC
December 2018

Investigation of the antimicrobial activity of a short cationic peptide against promastigote and amastigote forms of Leishmania major (MHRO/IR/75/ER): An in vitro study.

Exp Parasitol 2019 Jan 26;196:48-54. Epub 2018 Nov 26.

Zoonosis Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Cutaneous leishmaniasis is one of the most endemic global health problems in many countries all around the world. Pentavalent antimonial drugs constitute the first line of leishmaniasis treatment; however, resistance to these drugs is a serious problem. Therefore, new therapies with new modes of action are urgently needed. In the current study, we examined antimicrobial activity of CM11 hybrid peptide (WKLFKKILKVL-NH2) against promastigote and amastigote forms of L. major (MHRO/IR/75/ER). In vitro anti-leishmanial activity was identified against L. major by parasite viability and metabolic activity after exposure to different peptide concentration. In the presentt study, we demostrated that different concentrations of CM11 result in dose dependent growth inhibition of Leishmania promastigotes. Furthermore, we demostrated that CM11 peptide has significant anti-leishmanial activities on amastigotes. Our results demonstrated that CM11 antimicrobial peptide may provide an alternative therapeutic approach for L. major treatment.
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http://dx.doi.org/10.1016/j.exppara.2018.11.006DOI Listing
January 2019

CdS nanocrystals/graphene oxide-AuNPs based electrochemiluminescence immunosensor in sensitive quantification of a cancer biomarker: p53.

Biosens Bioelectron 2019 Feb 18;126:7-14. Epub 2018 Oct 18.

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

An ultrahigh sensitive, simple and reliable Electrochemiluminescence (ECL) immunosensor for selective quantification of p53 protein was designed according to the enhancement effects of AuNPs on ECL emission of CdS nanocrystals (CdS NCs). CdS NCs were immobilized on the glassy carbon electrode and AuNPs introduced to the process through formation of a sandwich-type immunocomplex between first anti-p53/p53/ secondary anti-p53. ECL of CdS NCs firstly evoked the SPR of AuNPs which in return amplified the CdS NCs ECL intensity. By using graphene oxide in immunosensor fabrication procedure, and attaching more AuNPs on the surface of the electrode, the ECL intensity was further increased resulting in much higher sensitivity. After applying the optimum conditions, the linear range of the developed immunosensor was found between 20 and 1000 fg/ml with a calculated limit of detection of 4 fg/ml. Moreover, the interference, reproducibility and storage stability studies of the immunosensor were investigated. Finally, immunosensor's authenticity was evaluated by detecting the p53 protein in human spikes which offers it as a potential in early detection of cancer, monitoring the cancer progress and clinical prognosis.
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http://dx.doi.org/10.1016/j.bios.2018.10.031DOI Listing
February 2019

Comparison of the antibacterial effects of a short cationic peptide and 1% silver bioactive glass against extensively drug-resistant bacteria, Pseudomonas aeruginosa and Acinetobacter baumannii, isolated from burn patients.

Amino Acids 2018 Nov 25;50(11):1617-1628. Epub 2018 Aug 25.

Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran.

We have already established that a short cationic peptide (CM11) has high antimicrobial activity against a number of bacterial pathogens. Considering the untreatable problem of burn infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii, this study evaluated and compared antibacterial effects of the CM11 peptide and 1% silver-doped bioactive glass (AgBG) against extensively drug-resistant strains of these bacteria which were isolated from burn patients. Accordingly, the bacteria were isolated from burn patients and their antibiotic resistance patterns and mechanisms were fully determined. The isolated bacterial from patients were resistant to almost all commonly used antibiotics and silver treatment. The isolates acquired their resistance through inactivation of their porin, the overexpression of efflux pump, and beta-lactamase. CM11 peptide and 1% AgBG had minimum inhibitory concentration (MIC) of ≥ 16 μg ml and ≥ 4 mg ml for clinical isolates, respectively. The minimum bactericidal concentration (MBC) of peptide and 1% AgBG for resistant bacteria was ≥ 32 μg ml and ≥ 4 mg ml, respectively. Among the clinical isolates, two P. aeruginosa isolates and one A. baumannii isolate were resistant to 1% AgBG disk. The CM11 peptide also showed high biocompatibility in vivo and no cytotoxicity against fibroblasts and adipose-derived mesenchymal stem cells in concentrations ≤ 64 μg ml and ≤ 32 μg ml, respectively, while the safe concentration of 1% AgBG for these cells was ≤ 16 μg ml. In conclusion, these findings indicated that the 1% silver is not safe and effective for treatment of such infections. The data suggest that CM11 peptide therapy is a reliable and safe strategy that can be used for the treatment of burn infections caused by antimicrobial-resistant isolates. The next stage of the study will be a multicenter clinical trial.
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http://dx.doi.org/10.1007/s00726-018-2638-zDOI Listing
November 2018

Stem cell therapy for lung diseases: From fundamental aspects to clinical applications.

Cell Mol Biol (Noisy-le-grand) 2018 Jul 30;64(10):92-101. Epub 2018 Jul 30.

Faculty of Veterinary Medicine, Islamic azad university, Karaj, Iran.

The respiratory system is a complex group of organs in the human body, all of which are necessary in breathing. Due to its special anatomy and composition, after exposure to various damaging factors such as micro particles, carbon granules and toxic gases, the respiratory system can be affected by a variety of damage without return to its original state. Currently, the prevalence of lung diseases, including asthma, and chronic obstructive pulmonary diseases, such as emphysema, has increased remarkably. New therapeutic approaches are desperately needed to discover regenerative medicine approaches, especially cell therapy. This review summarizes the recent advances in stem cell treatments and the research efforts conducted through the application of stem cell therapy for respiratory system diseases. In particular, researchers have used animal models to gather data about treating lung injury by stem cell transplantation. This review concentrated on the findings about route, timing and adjustment of cell transplantation dose, optimum stem cell type selection and potency marker of cells as therapeutic agents. These factors are essential subjects for approval and clinical transplantation. The current clinical trials aiming at treatment of lung diseases by stem cells are mentioned and discussed.
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July 2018

Antimicrobial Peptides: Features, Action, and Their Resistance Mechanisms in Bacteria.

Microb Drug Resist 2018 Jul/Aug;24(6):747-767. Epub 2018 Jun 29.

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

In recent years, because of increased resistance to conventional antimicrobials, many researchers have started to study the synthesis of new antibiotics to control the disease-causing effects of infectious pathogens. Antimicrobial peptides (AMPs) are among the newest antibiotics; these peptides are integral compounds in all kinds of organisms and play a significant role in microbial ecology, and critically contribute to the innate immunity of organisms by destroying invading microorganisms. Moreover, AMPs may encourage cells to produce chemokines, stimulate angiogenesis, accelerate wound healing, and influence programmed cell death in multicellular organisms. Bacteria differ in their inherent susceptibility and resistance mechanisms to these peptides when responding to the antimicrobial effects of AMPs. Generally, the development of AMP resistance mechanisms is driven by direct competition between bacterial species, and host and pathogen interactions. Several studies have shown diverse mechanisms of bacterial resistance to AMPs, for example, some bacteria produce proteases and trapping proteins; some modify cell surface charge, change membrane fluidity, and activate efflux pumps; and some species make use of biofilms and exopolymers, and develop sensing systems by selective gene expression. A closer understanding of bacterial resistance mechanisms may help in developing novel therapeutic approaches for the treatment of infections caused by pathogenic organisms that are successful in developing extensive resistance to AMPs. Based on these observations, this review discusses the properties of AMPs, their targeting mechanisms, and bacterial resistance mechanisms against AMPs.
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http://dx.doi.org/10.1089/mdr.2017.0392DOI Listing
October 2018

In vitro synergistic effects of a short cationic peptide and clinically used antibiotics against drug-resistant isolates of Brucella melitensis.

J Med Microbiol 2017 Jul 12;66(7):919-926. Epub 2017 Jul 12.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Purpose: In the last few decades, increasing microbial resistance to common antibiotics has attracted researchers' attention to the development of new classes of antibiotics such as antimicrobial peptides. Accordingly, the aim of the current study was to evaluate antimicrobial effects of the CM11 peptide alone and combined with common antibiotics against drug-resistant isolates of Brucella melitensis.

Methodology: A total of 50 pathogenic samples of B. melitensis were isolated from patients and their antibiotic susceptibility pattern was evaluated by E-test. Then, the synergistic reaction of the peptide with selected antibiotics was evaluated using a chequerboard procedure.

Results: Based on the susceptibility pattern of isolates, ciprofloxacin, rifampin, streptomycin and co-trimoxazole were used for synergistic study. According to the results, synergic effect was observed for streptomycin and co-trimoxazole in combination with the peptide while ciprofloxacin and rifampin showed partial synergy and additive effect, respectively. Consistent with these results, in the time-killing assay, a decrease in colony counts for streptomycin-peptide and co-trimoxazole-peptide was >2 Log10 while for ciprofloxacin-peptide and rifampin-peptide it was about 1.5 Log10 and <2 Log10, which represents synergy, partial synergy and additive interaction, respectively.

Conclusion: These results showed that by antibiotic-CM11 combination, their effective dose can be reduced particularly for drug-resistant isolates. In conclusion, considering the importance of brucellosis caused by B. melitensis in the Middle East beside reports on antibiotic resistance strains, especially against rifampin, which may literally lead to an increase in resistant strains of Mycobacterium tuberculosis in endemic areas, our findings can be used to develop a suitable alternative treatment for brucellosis, and with less risk.
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http://dx.doi.org/10.1099/jmm.0.000524DOI Listing
July 2017

Natural antisense RNAs as mRNA regulatory elements in bacteria: a review on function and applications.

Cell Mol Biol Lett 2016 28;21. Epub 2016 Jul 28.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Naturally occurring antisense RNAs are small, diffusible, untranslated transcripts that pair to target RNAs at specific regions of complementarity to control their biological function by regulating gene expression at the post-transcriptional level. This review focuses on known cases of antisense RNA control in prokaryotes and provides an overview of some natural RNA-based mechanisms that bacteria use to modulate gene expression, such as mRNA sensors, riboswitches and antisense RNAs. We also highlight recent advances in RNA-based technology. The review shows that studies on both natural and synthetic systems are reciprocally beneficial.
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http://dx.doi.org/10.1186/s11658-016-0007-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415839PMC
July 2017

Identification of novel bacterial DNA gyrase inhibitors: An in silico study.

Res Pharm Sci 2016 May-Jun;11(3):250-8

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, I.R. Iran.

Owing to essential role in bacterial survival, DNA gyrase has been exploited as a validated drug target. However, rapidly emerging resistance to gyrase-targeted drugs such as widely utilized fluoroquinolones reveals the necessity to develop novel compounds with new mechanism of actions against this enzyme. Here, an attempt has been made to identify new drug-like molecules for Shigella flexneri DNA gyrase inhibition through in silico approaches. The structural similarity search was carried out using the natural product simocyclinone D8, a unique gyrase inhibitor, to virtually screen ZINC database. A total of 11830 retrieved hits were further screened for selection of high-affinity compounds by implementing molecular docking followed by investigation of druggability according to Lipinski's rule, biological activity and physiochemical properties. Among the hits initially identified, three molecules were then confirmed to have reasonable gyrase-binding affinity and to follow Lipinski's rule. Based on these in silico findings, three compounds with different chemical structures from previously identified gyrase inhibitors were proposed as potential candidates for the treatment of fluoroquinolone-resistant strains and deserve further investigations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962306PMC
August 2016

Identification and characterization of a cathepsin L-like cysteine protease from Rhipicephalus (Boophilus) annulatus.

Exp Appl Acarol 2016 Feb 23;68(2):251-65. Epub 2015 Nov 23.

Department of Parasitology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

The tick Rhipicephalus (Boophilus) annulatus is one of the most important ectoparasites of bovines and is responsible for the transmission of different pathogens such as Babesia and Anaplasma. Cysteine proteases are involved in several host-tick interactions including invasion of host tissues, immune evasion, pathogen transmission, embryogenesis and blood digestion. In this study, the gene encoding R. annulatus cathepsin L-like enzyme (RaCL1) was cloned into pTZ57R/T vector, sequenced and analyzed using bioinformatics approaches. The nucleotide length of RaCL1 was 999 bp. Bioinformatics analysis showed 332 amino acids with an approximate molecular weight of 36.3 kDa which contained a signal peptide sequence (18 amino acids), pro-region (97 amino acids) and mature enzyme (217 amino acids). Multiple sequence alignment of the RaCL1 revealed high similarity to cathepsin L-like cysteine proteases from other tick species such as Rhipicephalus (Boophilus) microplus and Amblyomma variegatum. Based on bioinformatics analyses, results of this work suggest that RaCL1 can be a suitable candidate for the development of vaccine against R. annulatus.
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http://dx.doi.org/10.1007/s10493-015-9993-1DOI Listing
February 2016

Analysis of Healing Effect of Alginate Sulfate Hydrogel Dressing Containing Antimicrobial Peptide on Wound Infection Caused by Methicillin-Resistant Staphylococcus aureus.

Jundishapur J Microbiol 2015 Sep 7;8(9):e28320. Epub 2015 Sep 7.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran.

Background: Wound infections caused by methicillin-resistant Staphylococcus aureus are a health problem worldwide; therefore, it is necessary to develop new antimicrobial compounds. Considering broad-spectrum antimicrobial activity and low probability of drug resistance to peptides, applications these peptides are being studied extensively.

Objectives: In this study, to control drug release over time, an alginate sulfate-based hydrogel impregnated with the CM11 peptide as the antimicrobial agent was developed, and its healing effects were tested on skin infections caused by methicillin-resistant S. aureus strains in a mouse model.

Materials And Methods: Minimum inhibitory and minimum bactericidal concentrations of the CM11 peptide and alginate hydrogel in combination with the peptide were determined. Forty mice were divided into 4 groups: 1 group as a negative control (without treatment; however, 5 mice received hydrogel dressing without peptide), 1 group as a positive control (2% mupirocin treatment), and 2 groups as test groups. To establish skin infection, 200 μL of bacterial suspension with 3 × 10(8) CFU/mL concentration was subcutaneously injected in the scapular region of the mice. On the basis of the in vitro minimal bactericidal concentration of the alginate hydrogel containing peptide for 15 clinical isolates, hydrogel containing 128 mg/L of peptide was used for wound dressing over an 8-day period.

Results: The highest and lowest numbers of wounds were observed on day 2 in the negative and positive control groups, respectively. During the 8-day period, the positive control and hydrogel containing peptide treatment groups showed similar levels of wound healing.

Conclusions: This study showed that compared to standard drug treatment, treatment with hydrogel containing peptide had substantial antibacterial effects on S. aureus wound infections in mice.
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http://dx.doi.org/10.5812/jjm.28320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609035PMC
September 2015

Comparison of bacterial biodiversity and enzyme production in three hypersaline lakes; urmia, howz-soltan and aran-bidgol.

Indian J Microbiol 2014 Dec 17;54(4):444-9. Epub 2014 Jul 17.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

This research is a comparative study on the diversity of halophilic bacteria with hydrolytic activities in three significant hypersaline lakes; Urmia in the northwest and Howz-Soltan and Aran-Bidgol in the central desert in Iran. Isolated strains from these saline lakes were found to be halotolerant, moderately and extremely halophilic bacteria. The bacteria in each saline lake were able to produce different hydrolytic enzymes including amylase, protease, lipase, DNase, inulinase, xylanase, carboxy methyl cellulase, pectinase and pullulanase. 188, 302, 91 halophilic strains were isolated from Urmia Lake, Howz-Soltan and Aran-Bidgol playa, respectively. The numbers of Gram-positive strains were more than Gram-negatives, and among Gram-positive bacteria; spore-forming bacilli were most abundant. Due to the unique physico-chemical conditions of the lake environments, the hydrolytic activities of isolated strains were significantly different. For instance, isolated strains from Howz-Soltan playa did not produce pectinase, DNase, amylase, lipase and inulinase, while the isolates from Aran-Bidgol playa had a great ability to produce pectinase and DNase. The strains from Urmia Lake were also good producers of DNase but failed to show any chitinase activity. The diversity of halophilic bacteria from the mentioned three saline lakes was also determined using PCR-amplified 16S rRNA followed by phylogenetic analysis of the partial 16S rRNA sequences.
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http://dx.doi.org/10.1007/s12088-014-0481-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186938PMC
December 2014

Investigation of caspase-1 activity and interleukin-1β production in murine macrophage cell lines infected with Leishmania major.

Asian Pac J Trop Med 2014 Sep;7S1:S70-3

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address:

Objective: To investigate the caspase-1 dependent inflammatory pathway activity and interleukin-1β (IL-1β) secretion in murine macrophage cell lines J774G8 infected with Leishmania major (L. major) using caspase-1 activity assay and ELISA.

Methods: Novy-MacNeal-Nicolle biphasic medium was applied to produce promastigote form of L. major. Metacyclic promastigotes in the stationary phase were applied to infect macrophage. Caspase-1 activity and IL-1β secretion were assessed by the CPP32/caspase-1 fluorometric protease assay and ELISA IL-1β kits, respectively, with time intervals of 6, 18 and 30 h.

Results: Our study showed an increase in caspase-1 activity and IL-1β secretion in infected samples compared to non-infected macrophages. The highest increase in IL-1β production was observed after 6 h of infection.

Conclusions: These results arise that the activation of inflammasome pathway could be one of the innate immunity pathways against L. major.
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http://dx.doi.org/10.1016/S1995-7645(14)60205-4DOI Listing
September 2014

Investigation of the antibacterial activity of a short cationic peptide against multidrug-resistant Klebsiella pneumoniae and Salmonella typhimurium strains and its cytotoxicity on eukaryotic cells.

World J Microbiol Biotechnol 2014 May 10;30(5):1533-40. Epub 2013 Dec 10.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, P.O. Box 19395-5487, Tehran, Iran,

With the growing microbial resistance to conventional antimicrobial agents, the development of novel and alternative therapeutic strategies are vital. During recent years novel peptide antibiotics with broad spectrum activity against many Gram-positive and Gram-negative bacteria have been developed. In this study, antibacterial activity of CM11 peptide (WKLFKKILKVL-NH2), a short cecropin-melittin hybrid peptide, is evaluated against antibiotic-resistant strains of Klebsiella pneumoniae and Salmonella typhimurium as two important pathogenic bacteria. To appraise the antibacterial activity, minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and bactericidal killing assay were utilized with different concentrations (2-128 mg/L) of peptide. To evaluate cytotoxic effect of peptide, viability of RAJI, Hela, SP2/0, CHO, LNCAP cell lines and primary murine macrophage cells were also investigated with MTT assay in different concentrations (3-24 and 0.5-16 mg/L, respectively). MICs of K. pneumoniae and S. typhimurium isolates were in range of 8-16 and 4-16 mg/L, respectively. In bactericidal killing assay no colonies were observed at 2X MIC for K. pneumoniae and S. typhimurium isolates after 80-90 min, respectively. Despite the fact that CM11 reveals no significant cytotoxicity on RAJI, Hela, SP2/0, and CHO cell lines beneath 6 mg/L at first 24 and 48 h, the viability of LNCAP cells are about 50 % at 3 mg/L, which indicates strong cytotoxicity of the peptide. In addition, macrophage toxicity by MTT assay showed that LD50 of CM11 peptide is 12 μM (16 mg/L) after 48 h while in this concentration after 24 h macrophage viability was about 70 %.
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http://dx.doi.org/10.1007/s11274-013-1575-yDOI Listing
May 2014

Cloning and expression of a region of vesicle associated membrane protein2 (VAMP2) gene and its use as a recombinant peptide substrate for assaying clostridial neurotoxins in contaminated biologicals.

Biologicals 2010 Jan 14;38(1):113-9. Epub 2009 Dec 14.

Applied Biotechnology & Environmental Research Center, Baqiyatallah Medical Science University, Tehran, Iran.

An assay for the endopeptidase activities of clostridial neurotoxins in contaminated biotherapeutic products has been developed. Based on a synthetic peptide substrate representing amino acid residues 60-94 of the intracellular vesicle associated membrane protein2 (VAMP2), RT-PCR was used to amplify the VAMP2 sequence. The extended insert was digested with EcoRI and SalI and ligated into pGEX4T-1 vector for construction of the pGEX4T-1/VAMP plasmid for expressing in Escherichia coli a fusion protein linked to glutathione S-transferase (GST). The fusion protein was purified by affinity chromatography and used in an ELISA assay for comparison with the commercially available synthetic VAMP peptide and rabbit polyclonal antiserum. The identity of the immunoreactivity of recombinant VAMP2 protein with the chemically synthesized peptide was demonstrated by western blot. Our results indicated that recombinant VAMP2 peptide not only reacted with specific polyclonal antibody in a dose-dependent manner, without any remarkable difference observed between the reactivity of the fusion protein and commercial VAMP2 segment peptide, but also cleaved by botulinum neurotoxin type B (BONT/B) after endopeptidase assay. Thus, recombinant VAMP2 could serve as a replacement for VAMP2 synthetic peptide, potentially useful in endopeptidase assays for replacement of the currently used mouse bioassay for clostridial neurotoxins contaminating biotherapeutic products.
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http://dx.doi.org/10.1016/j.biologicals.2009.04.004DOI Listing
January 2010