Publications by authors named "Sadegh Shirian"

61 Publications

Therapeutic potential of mesenchymal stem cell-derived exosomes as a cell-free therapy approach for the treatment of skin, bone, and cartilage defects.

Connect Tissue Res 2021 Feb 23:1-14. Epub 2021 Feb 23.

Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

: The aim of this study was to collect the articles concerning mesenchymal stem cell (MSC)-derived exosomes for regeneration of bone, cartilage and skin defects.: Scopus, PubMed, EMBASE, and Web of Science were searched for keywords "Exosome, MSC, Skin, Bone and Cartilage defects, Regenerative medicine, and extracellular vesicles.: MSC-derived exosomes can emulate the biological activity of MSCs by horizontal transfer of multiple functional molecules including mRNAs, miRNAs, proteins, and lipids to the local microenvironment and recipient cells, and subsequently mediate restoring homeostasis and tissue regeneration through various mechanisms. Compared to MSCs, MSC-derived exosomes reveal many advantages such as non-immunogenicity, easy access, easy preservation, and extreme stability under various conditions.: Hence, exosomes could be considered as an alternative strategy for cell-based therapies in regenerative medicine. In this paper, after describing the characteristics of exosomes, we will review the recent literature on the therapeutic potentials of MSC-derived exosomes in skin, bone, and cartilage repair.
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http://dx.doi.org/10.1080/03008207.2021.1887855DOI Listing
February 2021

Effect of different muscle contraction mode on the expression of Myostatin, IGF-1, and PGC-1 alpha family members in human Vastus Lateralis muscle.

Mol Biol Rep 2020 Dec 22;47(12):9251-9258. Epub 2020 Nov 22.

Department of Exercise Physiology & Health Science, University of Tehran, Tehran, Iran.

Muscle contraction stimulates a transient change of myogenic factors, partly related to the mode of contractions. Here, we assessed the response of IGF-1Ea, IGF-1Eb, IGF-1Ec, PGC1α-1, PGC1α-4, and myostatin to the eccentric Vs. the concentric contraction in human skeletal muscle. Ten healthy males were performed an acute eccentric and concentric exercise bout (n = 5 per group). For each contraction type, participants performed 12 sets of 10 repetitions knee extension by the dominant leg. Baseline and post-exercise muscle biopsy were taken 4 weeks before and immediately after experimental sessions from Vastus Lateralis muscle. Genes expression was measured by real-time PCR technique. There was a significant increase in PGC1α-1, PGC1α-4, IGF-1Ea and, IGF-1Eb mRNA after concentric contraction (p ≤ 0.05), while the PGC1α-4 and IGF-1Ec significantly increased after eccentric contraction (p ≤ 0.05). It is intriguing to highlight that; no significant differences between groups were evident for changes in any variables following exercise bouts (p ≥ 0.05). Our results found that concentric and eccentric contractions presented different responses in PGC1α-1, IGF-1Ea, IGF-1Eb, and IGF-1Ec mRNA. However, a similar significant increase in mRNA content was observed in PGC1α-4. Further, no apparent differences could be found between the response of genes to eccentric and concentric contraction.
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http://dx.doi.org/10.1007/s11033-020-06017-xDOI Listing
December 2020

Reconstruction of necrotic submandibular salivary gland using mesenchymal stem cells.

Heliyon 2020 Oct 8;6(10):e05162. Epub 2020 Oct 8.

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: The efficacy of mesnchymal stem cells (MSCs) to treat the necrotic tissue of salivary glands (SGs) has yet investigated.

Objective: This study was conducted to investigate the potential capacity of MSCs to restore the function and regenerate the necrotic submandiular gland in the rat animal model.

Methods: Twenty-one Sprague-Dawley rats were provided from a breeding colony and randomly divided into three groups including the positive control or induced SG atrophy without treatment, the treatment group or induced SG atrophy with MSCs isolated transplantation and the negative control group consists of healthy rats. The atrophic and necrotic submandiular gland was induced using intraoral duct ligation of the main duct of submandiular gland for one month. The isolated stem cells were confirmed using flow cytometry for CD90 and CD 105. The isolated MSCs were cultured and injected to submandiular gland and the potential efficacy of MSCs to treat the atrophic submandibular glands was evaluated using histopathology on two weeks post-transplantation. To detect the acinar cell protein secretory granules, Alcian Blue and periodic acid shift (PAS) staining were done. For the demonstration of mitotic index or proliferation rate of the SG epithelia tissue, Ki-67 and Smbg proteins expression were evaluated using immunohistochemistry.

Results: The locally injected MSCs could regenerate the overall histological structure of the necrotic submandibular gland tissue within 2 weeks of post-transplantation. Alcian Blue and PAS staining indicated that the mean amount of serous and mucin secretions in the treatment group was significantly increased compared to the positive control groups. We have also found that the treatment group significantly express higher Ki-67 protein, as a diagnostic marker for cell mitosis and proliferation rate, and lower Smbg protein, as a diagnostic marker, for damage to the submandibular gland than that of control group.

Conclusion: This study demonstrates the therapeutic benefits of MSCs isolated from the SG in treating atrophic and necrotic SGs in a rat model. MSCs may be potential candidates for cell-based therapies targeting hypofunction of SG induced by a range of diseases or because of surgery and radiotherapy of head and neck cancers.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551326PMC
October 2020

Alginate hydrogel containing hydrogen sulfide as the functional wound dressing material: In vitro and in vivo study.

Int J Biol Macromol 2020 Dec 1;164:3323-3331. Epub 2020 Sep 1.

Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran; Tissue Engineering and Stem Cells Research Center, Shahroud University of Medical Sciences, Shahroud, Iran; Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran. Electronic address:

Functional and bioactive wound dressing materials are revolutionary for wound care and healing applications. In this concept, we fabricated alginate hydrogel (Alg) containing HS as the wound dressing materials and assessed the morphology, swelling, degradation, and release behavior, as well as the biocompatibility, cytocompatibility, and wound healing activity. The results depicted that the prepared hydrogels have a porous structure with the pore size in the range of 50 to 100 μm. Swelling and degradation studies showed that the hydrogel absorbed water about 179 ± 5% of initial dry weight during 96 h and loos about 80% of the initial dry weight after 7 days. The in vitro assessments illustrated that the optimum concentration of HS was 0.5% and the higher concentration induced hemolysis and cell toxicity. The in vivo study revealed that the treatment by Alg/HS 0.5% induced the highest wound closure percent with a value of 98 ± 1.22%. Moreover, the treatment by Alg/HS 0.5% elicited the formation of sebaceous glands, hair follicles, and complete epithelization without any fibroplasia or inflammation, revealed by the histopathological observations. Accordingly, these results illustrated that the prepared Alg/HS 0.5% could be applied as the functional and bioactive wound dressing materials.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.08.233DOI Listing
December 2020

Effects of concurrent use of royal jelly with hydroxyapatite on bone healing in rabbit model: radiological and histopathological evaluation.

Heliyon 2020 Jul 30;6(7):e04547. Epub 2020 Jul 30.

Department of Veterinary Pathology, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

Background: Bone grafts have been used to enhance bone fracture healing in orthopedic surgery. Bone grafts enhance bone healing either by mechanical support or acting as a scaffold for bone formation. Fresh autograft is the most effective biomaterial because it is histocompatible with less complication about transmissible disease. Hydroxyapatite is a well-established material for bone repair and very comparable to natural apatite providing a strong biomechanical interlock with host tissue. Royal jelly is the principal food for the honeybee queen. This biomaterial has been demonstrated to have several pharmacological activities, such as antiallergic, antitumor and anti-inflammatory effects.

Objectives: This study was design to evaluate the effect of concurrent using of Royal jelly with hydroxyapatite on bone healing in rabbit model.

Methods: 15 adult rabbits weighting approximately 2 kg had been used. They were divided into three groups randomly. In first group (N = 5) mid radius bone defect created and left empty. The second group (N = 5) filled with hydroxy apatite alone and the last group (N = 5) filled with royal jelly and hydroxy apatite combination. Radiological evaluation performed on days14th, 28th and 42nd after operation. Histopathological evaluation was done on 56 postoperative day.

Results: Radiological evaluation showed significant superior bone healing in hydroxyapatite and hydroxyapatite-Royal jelly groups in comparison to control group. Control group was the inferior group between three groups. There were not any significant differences between three groups in histopathological group.

Conclusion: In conclusion our study showed the best results with using the hydroxyl apatite and Royal-jelly group because they provide not only scaffold for bone healing but also do, they provide some osteoinduction materials for bone healing.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394860PMC
July 2020

Peripheral Cytotoxic T Cell Lymphoma of the Appendix Presenting as Acute Appendicitis.

Case Rep Oncol Med 2020 16;2020:8569426. Epub 2020 Jun 16.

Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

Introduction: Lymphoma of the appendix is a rare cause of acute appendicitis; however, acute appendicitis is a common first manifestation of appendiceal lymphomas. Cytotoxic peripheral T cell lymphoma (PTCL) is a type of aggressive non-Hodgkin lymphoma that portends a generally poor outcome. Cytotoxic PTCL of the appendix is extremely rare with few cases reported in the literature. . This is the report of a 23-year-old man who had experienced lower abdominal pain for three months before presenting to the emergency department with severe right lower abdominal pain, nausea, vomiting, and anorexia since the day prior to admission. The patient was diagnosed with acute appendicitis, and the pathology report confirmed cytotoxic PTCL of the appendix.

Conclusion: Patients with appendiceal PTCL commonly present with signs and symptoms of acute appendicitis due to luminal obstruction by the tumor. Therefore, appendiceal tumors such as PTCL should be considered in the differential diagnosis of patients presenting as acute appendicitis. In addition, since there is no standard chemotherapy regimen for cytotoxic PTCL, this and other case reports hopefully help in providing the clinical evidence needed for establishing appropriate treatment guidelines.
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http://dx.doi.org/10.1155/2020/8569426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317332PMC
June 2020

Dual spinneret electrospun nanofibrous/gel structure of chitosan-gelatin/chitosan-hyaluronic acid as a wound dressing: In-vitro and in-vivo studies.

Int J Biol Macromol 2020 Nov 20;162:359-373. Epub 2020 Jun 20.

Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Structural and compositional similarity to the natural extracellular matrix (ECM) is a main characteristic of an ideal scaffold for tissue regeneration. In order to resemble the fibrous/gel structure of skin ECM, a multicomponent scaffold was fabricated using biopolymers with structural similarity to ECM and wound healing properties i.e., chitosan (CS), gelatin (Gel) and hyaluronic acid (HA). The CS-Gel and CS-HA nanofibers were simultaneously electrospun on the collector through dual-electrospinning technique. The presence of polymers, possible interactions, and formation of polyelectrolyte complex were proven by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and thermogravimetric analysis (TGA). The noncomplex component of CS-HA fibers formed a gel state when the scaffold was exposed to the aqueous media, while the CS-Gel fibers reserved their fibrous structure, resulting in formation of fibrous/gel structure. The CS-Gel/CS-HA scaffold showed significantly higher cell proliferation (109%) in the first 24 h comparing with CS (90%) and CS-Gel (96%) scaffolds. Additionally, the initial cell adhesion improved by incorporation of HA. The in-vivo wound healing results in rat elucidated more wound healing capability of the CS-Gel/CS-HA scaffold in which new tissue with most similarity to the normal skin was formed.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.181DOI Listing
November 2020

Early diagnosis of breast and ovarian cancers by body fluids circulating tumor-derived exosomes.

Cancer Cell Int 2020 24;20:187. Epub 2020 May 24.

Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

Exosomes (EXs) are small extracellular vesicles, a size range of 40-100 nm in diameter, actively secreted by most eukaryotic cells into surrounding body fluids like blood, saliva, urine, bile, breast milk and etc. These endosomal-derived vesicles mediate cell-cell communication between various cell populations through transmitting different signaling molecules such as lipids, proteins, and nucleic acids, and participate in a wide range of physiological and pathological body processes. Tumor-derived EXs (TDEs) are vehicles for intercellular communications by transferring bioactive molecules; they deliver oncogenic molecules and contain different molecular cargoes compared to EXs delivered from normal cells, therefore, they can be used as non-invasive invaluable biomarkers for early diagnosis and prognosis of most cancers, including breast and ovarian cancers. Their presence and stability in different types of body fluids highlight them as a suitable diagnostic biomarker for distinguishing various cancer stages. In addition, EXs can predict the therapeutic efficacy of chemotherapy agents and drug resistance in cancer cells, as well as determine the risk of metastasis in different disease stages. In this study, the recent literature on the potential role of TDEs in the diagnosis and prognosis of ovarian and breast cancers is summarized, and then exosome isolation techniques including traditional and new approaches are briefly discussed.
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http://dx.doi.org/10.1186/s12935-020-01276-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247259PMC
May 2020

Kaolin-loaded chitosan/polyvinyl alcohol electrospun scaffold as a wound dressing material: and studies.

J Wound Care 2020 May;29(5):270-280

Department of Tissue Engineering, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran.

Objective: To evaluate the application of a fabricated dressing containing kaolin for skin regeneration in a rat model of excisional wounds.

Method: In the present study, kaolin was loaded into electrospun polyvinyl alcohol (PVA)/chitosan polymer blend to develop a composite nanofibrous dressing. To make the yarns, kaolin with weight ratio of 5% was added to PVA/chitosan polymer blend and subsequently formed into nanofibres using the electrospinning method. Scaffolds were evaluated for to their microstructure, mechanical properties, surface wettability, water vapour transmission rate, water-uptake capacity, blood uptake capacity, blood compatibility, microbial penetration test, the number of colonies, and cellular response with the L929 cell line. Rats with full-thickness excisional wounds were treated with kaolin-containing and kaolin-free dressings.

Results: The study showed that rats treated with the kaolin-incorporated mats demonstrated a significant closure to nearly 97.62±4.81% after 14 days compared with PVA/chitosan and the sterile gauze, which showed 86.15±8.11% and 78.50±4.22% of wound closure, respectively. The histopathological studies showed that in the PVA/chitosan/kaolin group, dense and regular collagen fibres were formed, while wounds treated with sterile gauze or PVA/chitosan scaffolds had random and loose collagen fibres.

Conclusion: Our results show the potential applicability of PVA/chitosan/kaolin scaffolds as a wound care material.
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http://dx.doi.org/10.12968/jowc.2020.29.5.270DOI Listing
May 2020

The Role of Forced and Voluntary Training on Accumulation of Neural Cell Adhesion Molecule and Polysialic Acid in Muscle of Mice with Experimental Autoimmune Encephalomyelitis.

Evid Based Complement Alternat Med 2020 8;2020:5160958. Epub 2020 Apr 8.

Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

It has been suggested that depletion of adhesion molecules is one of the factors associated with or possibly responsible for multiple sclerosis (MS) progression. The aim of this study was to investigate the effect of forced and voluntary training before and after induction of experimental autoimmune encephalomyelitis (EAE) on accumulation of neural cell adhesion molecule (NCAM) and polysialic acid (PSA) in neuromuscular junction denervation in plantaris and soleus muscles in C57BL/6 female mice. A total of 40 female C57BL/6 mice, 10-week-old, were randomly divided into four groups, including induced control groups without EAE induction, induced EAE without training, and forced and voluntary training groups. Myelin oligodendrocyte glycoprotein peptide 35-55 (300 g in saline; MOG 35-55; KJ Ross-Petersen ApS, Denmark) was injected subcutaneously at the base of the tail of each mouse. Clinical assessment of EAE was performed daily using a 15-point scoring system following immunization. Training groups performed the swimming program for 30 min/day, 5 times/week, for 4 weeks. Mice had access to a treadmill for one hour per day, 5times/week, for 4 weeks in individual cage. The mice were scarified, and the plantaris and soleus muscles were then isolated for investigation of proteins expression using IHC. An analysis of the preventive exercise (before) and recovery exercise (after) of the EAE was performed. Images of the stained sections were taken using a fluorescent microscope. Quantitative image analysis was performed using ImageJ software package. The obtained data from the mean percentage expression of PSA and NCAM in pre- and post-soleus and plantaris muscles showed that the highest and lowest expression levels of PSA and NCAM belonged to control and swim EAE (SE) groups, respectively. The low expression levels of PSA and NCAM were detected in rat with MS without intervention. In conclusion, the relationship between increasing levels of NCAM and PSA protein expression and voluntary and compulsory activity were detectable both in pre and post-soleus and plantaris. However, voluntary activity resulted in more expression levels of NCAM and PSA than that of compulsory. In conclusion, since it has been suggested that depletion of NCAM is one of the factors associated with or possibly responsible for MS progression, these findings show exercise MS progression may be reduced by increasing expression of exercise-related adhesion molecule such as NCAM and PSA (a glycan modification of the NCAM).
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http://dx.doi.org/10.1155/2020/5160958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168727PMC
April 2020

Proteomic and genomic biomarkers for Non-Small Cell Lung Cancer: Peroxiredoxin, Haptoglobin, and Alpha-1 antitrypsin.

Cancer Med 2020 06 30;9(11):3974-3982. Epub 2020 Mar 30.

Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

Background: The development of lung cancer is a multifactorial process that involves the environmental and genetic factors. The mortality rate of this cancer is higher than breast, colorectal, and prostate cancers. In this study, we try to analyze the proteome of patients with Non-Small Cell Lung Cancer (NSCLC) and compare it with the healthy samples.

Methods: This study has compared 30 lung tissue samples from patients with NSCLC and 30 healthy samples using proteomics and RT-PCR. Hence, tissue samples were obtained from the surgical ward in sterile conditions, and then, protein extraction applied to them. At the next stage, two-dimensional electrophoresis and mass spectrometry LCMS/MS were performed for protein isolation and sequencing, respectively.

Results: The proteome analysis identified more than 40 differences in proteomic pattern of normal lung tissues compared to lung tissues with NSCLC. Peroxiredoxin, Haptoglobin, and Alpha-1 antitrypsin proteins were identified. Molecularly, it has also been shown that the two main proteins of Peroxiredoxin-2 and Alpha-1 antitrypsin were upregulated, and the expression of Haptoglobin protein was downregulated in cancer tissue.

Conclusion: The results of this study showed that there are some differences in term of protein content between the normal and cancerous lung tissues. Further studies are needed to evaluate these proteins that investigate whether these proteins can candidate as biomarkers to use in the early diagnosis of patients with NSCLC.
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http://dx.doi.org/10.1002/cam4.3019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286458PMC
June 2020

Enhanced sciatic nerve regeneration by poly-L-lactic acid/multi-wall carbon nanotube neural guidance conduit containing Schwann cells and curcumin encapsulated chitosan nanoparticles in rat.

Mater Sci Eng C Mater Biol Appl 2020 Apr 17;109:110564. Epub 2019 Dec 17.

Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The main aim of this study was to improve the efficacy of peripheral nerve regeneration by an artificial neural guidance conduit (NGC) as a carrier to transplant allogeneic Schwann cells (SCs) and curcumin encapsulated chitosan nanoparticles (nanocurcumin). The conduit was prepared by poly-L-lactic acid (PLLA) and surface-modified multi-wall carbon nanotubes (mMWCNT) and filled with SCs and nanocurcumin. SCs play an important role in the regeneration of injured peripheral nerve and controlled curcumin release can decrease SCs apoptosis, and enhance the regeneration and functional recovery of injured peripheral nerves. The mechanical properties, contact angle, and cell biocompatibility experiments showed that the optimized concentration of mMWCNT inside PLLA wall of conduits was 0.15 wt%. The drug release experiments showed slower release of curcumin from nanocurcumin samples compared to nanocurcumin encapsulated inside NGC wrapped fibrin gel sample. It was found that simultaneous using of both SCs and curcumin inside NGC had a significant role in sciatic nerve regeneration in vivo. Histological examination revealed a significant increase in the number of axons in injured sciatic nerve following treatment by SCs and nanocurcumin compared to negative control group. Histological evaluation also revealed a significant decrease in the number of vessels in fibrin groups compared to positive control group. The results showed that there was no significant difference between the reaction time and sciatic functional index (SFI) values of rats with injured sciatic nerve treated by NGC/SCs/nanocurcumin sample and autograft sample. In conclusion, our results strongly showed that PLLA/mMWCNT nanofibrous conduit filled with fibrin gel containing SCs and nanocurcumin is a proper strategy for improving nerve regeneration after a nerve transaction in the rat.
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http://dx.doi.org/10.1016/j.msec.2019.110564DOI Listing
April 2020

Osteogenic differentiation of follicular stem cells on nano-Saghez scaffold containing BMP2.

J Orthop Surg Res 2019 Dec 16;14(1):442. Epub 2019 Dec 16.

Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Bone tissue is one of the tissues that are capable of self-regeneration. However, bone self-regeneration is defeated in the case of broad lesion of bone structure. Isolated stem cells from wisdom tooth follicles can potentially differentiate into ectodermal and mesodermal cells. Saghez is a natural substance that has been extracted from Pistacia terebinthus with unique features, such as high temperature and mechanical stability, adhesive structure, biocompatibility, and anti-neoplastic properties.

Methods: In this study, Saghez-encapsulated BMP2 was applied as a scaffold for wisdom tooth follicle stem cell differentiation into the osteocyte. A total of three wisdom tooth follicles were obtained for stem cell isolation. For verification of differentiation of the isolated stem cells into osteocyte and adipocyte, Oil Red and Alizarin staining were applied, respectively. Moreover, mesenchymal stem cells were distinguished by profiling their cell surface markers, includingCD73, CD90, CD44, and CD105, by flow cytometry. Saghez scaffold loaded with BMP2 factor was prepared using sol-gel method. Four experimental groups were considered in this study: cells seeded on BMP2 encapsulated in Saghez scaffold, Saghez scaffold, osteogenic medium, and DMEM medium.

Results: Mechanical properties of Saghez scaffold, including tensile Young's modulus, ultimate tensile stress, compression Young's modulus, and complex shear modulus, were 19 MPa, 32 MPa, 0.42 MPa, and 0.9 MPa, respectively. The porosity of the scaffold was 70-140 μm, and the percentage of porosity was 75-98%. The results of flow cytometry studies indicated that CD44, CD73, CD90, and CD105 were positively expressed on the membrane of the tooth follicles' stem cell. The results indicated that the rate of differentiation of the follicle stem cells into osteocyte was the highest in the Saghez-BMP2 scaffold containing differentiation medium groups. These findings were verified by morphological studies, osteoblast and osteocalcin gene and protein expression investigations, and alkaline phosphatase activity measurement. The highest osteopontin and osteocalcin genes expression levels (1.7 and 1.9) were seen in positive control, followed by DMEM + differentiation factor (1.5 and 1.6), scaffold + BMP2 (1.2 and 1.4), DMEM + stem cell (1 and 1) and scaffold (0.4 and 0.5), and negative control respectively.

Conclusion: This study provides a novel system for differentiation of the stem cell into osteocytes. The results of this study suggest that loaded BMP2 in Saghez scaffold possibly acts as an osteocyte differentiator factor.
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http://dx.doi.org/10.1186/s13018-019-1507-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916075PMC
December 2019

Enhancing the Therapeutic Efficacy of Daunorubicin and Mitoxantrone with Bavachinin, Candidone, and Tephrosin.

Evid Based Complement Alternat Med 2019 7;2019:3291737. Epub 2019 Nov 7.

Department of Pharmacology, Qazvin University of Medical Sciences, Qazvin, Iran.

The capability of flavonoids in sensitizing cancer cells was demonstrated in numerous works to chemotherapy and converse multidrug resistance by modulating efflux pumps and apoptosis mechanisms. Three flavonoids, namely, bavachinin, tephrosin, and candidone, have been recently introduced to cancer treatment research presenting various activities, such as antibacterial, immunomodulatory, cell death, and anticancer. Less information exists regarding the therapeutic significance of these flavonoids in cancer treatment, especially in overcoming multidrug resistance (MDR). Here, we tempted to investigate the potency of these agents in reversing MDR by analyzing their effects as chemosensitizers on cell cytotoxicity, P-gp and ABCG2 protein expression levels, and their function on two multidrug-resistant cell lines, P-gp-overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB) and ABCG2-overexpressing human epithelial breast cancer cell line (MCF7/MX). The inhibitory concentration of 10% (IC) of bavachinin, tephrosin, and candidone in EPG85.257RDB cells was 1588.7 ± 202.2, 264.8 ± 86.15, and 1338.6 ± 114.11 nM, respectively. Moreover, these values in MCF7/MX cell were 2406.4 ± 257.63, 38.8 ± 4.28, and 27.9 ± 5.59 nM, respectively. Expression levels of ABCG2 and P-gp were not significantly downregulated by these flavonoids. Maximum levels of daunorubicin and mitoxantrone accumulations and minimum rates of drug efflux in both cell lines were detected 48 hrs posttreatment with tephrosin and bavachinin, respectively. Chemosensitization to mitoxantrone and daunorubicin treatments was, respectively, achieved in MCF7/MX and EPG85.257RDB cells in response to IC of bavachinin and tephrosin, independently. These effects did not follow time-dependent manner, and each flavonoid had its cell-dependent patterns. Overall, bavachinin, tephrosin, and candidone showed potency to sensitize MDR cells to daunorubicin and mitoxantrone and could be considered as attractive MDR modulators for cancer treatment. However, their action was time and cell specific.
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http://dx.doi.org/10.1155/2019/3291737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877970PMC
November 2019

CD93 hematopoietic stem cells improve diabetic wound healing by VEGF activation and downregulation of DAPK-1.

J Cell Physiol 2020 03 24;235(3):2366-2376. Epub 2019 Sep 24.

Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Diabetes is associated with numerous complications, such as diabetic skin wounds or ulcerations. The aim of this study was to evaluate experimentally the effectiveness of applying polycaprolactone (PCL)-gelatin scaffold, with or without rat CD93 hematopoietic stem cells (HSCs), in diabetic wound healing in a rat model. CD93 HSCs were aseptically isolated from rat bone marrow using fluorescent activated cell sorting (FACS) method and FACS-SORTER. A total of 25 Wistar rats were divided into five groups including Group I (sham, nondiabetic, and wound covered only with sterile dressing), II (control, diabetic rat), III (CD93 HSCs alone), IV (PCL-gelatin scaffold), and V (CD93 HSCs+PCL-gelatin scaffold). Animals were killed on Days 7, 14, or 28 posttreatment and histological sections were blindly evaluated by two expert pathologists. Death-associated protein kinase 1 (DAPK-1) gene and vesicular endothelial growth factors (VEGF) protein expression were evaluated using reverse transcription-polymerase chain reaction and western blot, respectively. The thickest and the thinnest epidermises microscopically were belonged to CD93+HSCs+scaffold and the control group, respectively. The growth rate of the epidermis and adnexal epithelia was the highest in both the cell and cell+scaffold groups. Evaluation of the protein expression level of VEGF indicated that the expression levels of this growth factor were the most on Day 7 posttreatment in sham, HSCs alone, and HSCs cell+scaffold groups. While the lowest expression levels of this growth factor was detected in the control and scaffold groups. The gene expression level of DAPK-1 on Day 7 posttreatment was higher than that of the Day 14 posttreatment in all groups. The highest and lowest gene expression levels of DAPK-1 belonged to control and sham groups, respectively. According to our findings, CD93 HSCs offer new prospects for the treatment of diabetic ulcers and concomitant application of these cells with PCL-gelatin nanofiber scaffold significantly improves diabetic wound treatment.
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http://dx.doi.org/10.1002/jcp.29142DOI Listing
March 2020

Zimmermann-Laband syndrome: Clinical and cytogenetic study in two related patients.

J Clin Exp Dent 2019 May 1;11(5):e452-e456. Epub 2019 May 1.

Shiraz Molecular Pathology Research Center, Dr Daneshbod Pathology Laboratory, Shiraz, Iran.

Background: Zimmermann-Laband Syndrome (ZLS) is an extremely rare autosomal dominant congenital disorder. It is a craniofacial malformation syndrome with predominant intraoral involvement consisting of gingival fibromatosis diffusion in early development. The molecular basis of ZLS is still unknown. Although familial aggregation with different inheritance patterns is detected in ZLS patients, most of the cases are sporadic.

Material And Methods: We report on two sibling patients with clinical manifestations of ZLS. Blood samples of both patients were obtained in EDTA-tubes followed by performing cytogenetic study using Cyto2.7M array. Analysis of the copy number was performed using the Chromosome Analysis Suite Software (version 1.0.1, annotation file na 30, Affymetrix) and interpreted with recourse to the UCSC genome browser (http://genome.ucsc.edu/; Human Mar. 2006NCBI Build 36.1/hg18 assembly).

Results: The array analysis revealed overlapping regions of chromosomal aberrations in both patients. We detected a 258-kb deletion at 3q13.13, a 89-kb duplication at 1q25.2 as well as two 67-kb duplications at 1p12 and 19q12. These altered regions do not contain any known genes and protein-coding sequences.

Conclusions: In conclusion, the findings of this report revealed new chromosomal aberrations, including a deletion at 3q13.13 and duplications at 1q25.2, 1p12 and 19q12, in the two patients with ZLS. Such findings indicate that whole genome screening for genomic rearrangements is fruitful in typical and atypical patients with ZLS. Zimmermann-Laband syndrome, cytogenetic array, whole genome screening, chromosomal aberration, gingival fibromatosis.
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http://dx.doi.org/10.4317/jced.55214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599695PMC
May 2019

Expression and localization of transient receptor potential channels in the bovine uterus epithelium throughout the estrous cycle.

Mol Biol Rep 2019 Aug 13;46(4):4077-4084. Epub 2019 May 13.

Weill Cornell Medical College Qatar, Qatar Foundation, Education City, PO Box 24144, Doha, Qatar.

Transient receptor potential (TRP) channels are expressed in the endometrium but it is unknown if they are modulated through the estrous cycle (EC). This study was undertaken to identify the modulation of the TRPC gene and protein isoforms in bovine uterine epithelium, as a model for human, throughout the EC. Changes in the expression of TRPC genes in bovine uterine epithelium throughout the EC were measured using Real-Time PCR, while immunohistochemistry and immunocytochemistry were used to determine the localization of these channels. Out of the 7 members of the TRPC family, TRPC1, 2, 3, 4 and 6 genes were expressed in bovine uterine epithelial tissue and TRPC 5 and 7 were not. Gene expression levels of all TRPC isoforms underwent cyclical changes throughout the EC. Moreover, cyclical changes were detected in the protein levels of TRPC1 and TRPC6 throughout the EC. These findings show that TRPC channels are modulated through the EC and therefore may have a role in reproductive events.
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http://dx.doi.org/10.1007/s11033-019-04857-wDOI Listing
August 2019

Natural Infection with Rabies Virus: A Histopathological and Immunohistochemical Study of Human Brains.

Osong Public Health Res Perspect 2019 Feb;10(1):6-11

Department of Virology, Pasteur Institute of Iran, Tehran, Iran.

Objectives: Despite all the efforts and increased knowledge of rabies, the exact mechanisms of infection and mortality from the rabies virus are not well understood. To understand the mechanisms underlying the pathogenicity of rabies virus infection, it is crucial to study the tissue that the rabies virus naturally infects in humans.

Methods: Cerebellum brain tissue from 9 human post mortem cases from Iran, who had been infected with rabies virus, were examined histopathologically and immunohistochemically to evaluate the innate immune responses against the rabies virus.

Results: Histopathological examination revealed inflammation of the infected cerebellum and immunohistochemical analyses showed an increased immunoreactivity of heat shock protein 70, interleukin-6, interleukin-1, tumor necrosis factor-alpha, caspase-3, caspase-9, toll-like receptor3 and toll-like receptor4 in the infected brain tissue.

Conclusion: These results indicated the involvement of innate immunity in rabies infected human brain tissue, which may aggravate the progression of this deadly disease.
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http://dx.doi.org/10.24171/j.phrp.2019.10.1.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396821PMC
February 2019

Sexual dimorphism in the expression of GKN2 and FOXA2 genes in the human stomach.

Mol Biol Rep 2019 Apr 18;46(2):2355-2362. Epub 2019 Feb 18.

Department of Genetics, School of Medicine, Kazerun Branch, Islamic Azad University, P.O. Box: 73135-168, Kazerun, Iran.

A large proportion of the transcriptome is sex biased in a wide range of taxa. Sexually dimorphic genes expression is highly tissue-dependent. Although gastric cancer exhibits sex bias to some extent, sexually dimorphic gene expression in the stomach is yet to be fully understood. The aim of the present study was to compare the expression levels of 12 genes in the gastric tissue between age-matched healthy men and women of different age groups. A total of 70 human antrum gastric tissue samples were obtained by endoscopy. The difference in expression levels of the 12 intended genes between two genders was investigated using quantitative Real-Time PCR, following total RNA extraction. The results indicated that the expression levels of both the GKN2 (7.2-fold, p < 0.001) and FOXA2 (3.7-fold, p = 0.003) were significantly higher in men compared to those in women. In addition, FOXA1 gene expression was age-dependent only in women. Interestingly, the expression level of FOXA1 was significantly higher in premenopausal women compared to postmenopausal women (2.53-fold, p = 0.016). The expression levels of some of the investigated genes in this study were sex-dependent in the stomach. This sexual dimorphism in gene expression might influence the differential susceptibility to the gastric cancer between the sexes.
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http://dx.doi.org/10.1007/s11033-019-04692-zDOI Listing
April 2019

Human unrestricted somatic stem cells ameliorate sepsis-related acute lung injury in mice.

J Cell Physiol 2019 08 9;234(8):13942-13950. Epub 2019 Jan 9.

Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background Aims: Sepsis and related disorders, especially acute lung injury (ALI), are the most challenging life-threatening diseases in the hospital intensive care unit. Complex pathophysiology, unbalanced immune condition, and high rate of mortality complicate the treatment of sepsis. Recently, cell therapy has been introduced as a promising option to recover the sepsis symptoms. The aim of this study was to investigate the therapeutic potential of human unrestricted somatic stem cells (USSCs) isolated from human umbilical cord blood in the mouse model of ALI. USSCs significantly enhanced the survival rate of mice suffering from ALI and suppressed concentrations of proinflammatory mediators TNF-α, and interleukin (IL)-6, and the level of anti-inflammatory cytokine IL-10. ALI mice injected by USSCs showed notable reduction in lung and liver injury, pulmonary edema, and hepatic enzymes, compared with the control group. These results determined the in vivo immunomodulatory effect of USSCs for recovery of immune balance and reduction of tissue injury in the mouse model of ALI. Therefore, USSCs can be a suitable therapeutic approach to manage sepsis disease through the anti-inflammatory potential.
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http://dx.doi.org/10.1002/jcp.28077DOI Listing
August 2019

Non-replicating Newcastle Disease Virus as an adjuvant for DNA vaccine enhances antitumor efficacy through the induction of TRAIL and granzyme B expression.

Virus Res 2019 02 29;261:72-80. Epub 2018 Dec 29.

Department of Virology, Pasteur Institute of Iran, Tehran, Iran; Infectious Diseases Research Center, Department of Microbiology, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address:

The potential of non-replicating Newcastle Disease Virus (NDV) as an adjuvant for DNA vaccination remains to be elucidated. To assess the therapeutic effects of DNA vaccine (HPV-16 E7 gene) adjuvanted with NDV, female C57/BL6 mice were inoculated with murine TC-1 cells of human papillomavirus (HPV)-related carcinoma, expressing human papillomavirus 16 (HPV-16) E6/E7 antigens, and immunized with DNA vaccine alone or pretreated with NDV. One week after third immunization, Cytotoxic T lymphocytes (CTLs), splenocyte proliferation, cytokine balance (IFN-γ, IL-4 and IL-12 secretions) and intratumoral expression of cytotoxicity related proteins in tumor lysates were investigated. The results showed that treatment with non-replicating NDV prior to DNA vaccine induced tumor-specific cytolytic and splenocyte proliferation responses. The levels of cytokines IL-12, IL-4 and IFN-γ after treating with combined E7-DNA -non-replicating NDV (NDV-DNA Vaccine) were significantly higher than those of control groups. The intratumoral granzyme B and Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL)-mediated apoptosis was also significantly increased. Tumor therapeutic experiments showed that the NDV pretreatment could reduce the tumor progression of established E7-expressing TC-tumors. Taken together these data suggest that the significant antitumor responses evidenced during treatment with non-replicating NDV prior to DNA vaccine are due, in part, to strong E7-induced cellular immunity and enhanced expression of cytotoxicity related proteins in the tumor microenvironment. These observations indicated the potential of non-replicating NDV as an adjuvant for enhancing therapeutic DNA vaccines -induced immunity and antitumor responses.
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http://dx.doi.org/10.1016/j.virusres.2018.12.014DOI Listing
February 2019

Antitumor Immunity Induced by Genetic Immunization with Chitosan Nanoparticle Formulated Adjuvanted for HPV-16 E7 DNA Vaccine.

Iran J Immunol 2018 Dec;15(4):269-280

Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

Background: In recent years attention has been paid to develop effective adjuvant systems for DNA vaccines. Co-formulation of a gene delivery vector with an immunostimulator can enhance therapeutic efficiency of DNA vaccine.

Objective: To investigate the efficacy of chitosan as a nanodelivery system to enhance antitumor effects of human papilloma virus (HPV)-16 DNA vaccine with IL-12 gene for protection against TC-1 tumor using an animal model.

Methods: The mice were challenged by subcutaneous injection of TC-1 cells and immunized intramuscularly with DNA vaccine thrice at seven-day intervals. One week after the last immunization, mice were sacrificed and antitumor effects were assessed through measuring lymphocyte proliferation, cytotoxicity, cytokines production, and tumor regression.

Results: We found that co-formulation and co-administration of chitosan nanoparticles and IL-12 with HPV-16 E7 DNA vaccine induced higher antitumor effects compared with chitosan or IL-12 alone. E7-specific lymphocyte proliferation index and CTL activity were found to be significantly higher in combination group in comparison to single vaccination with either chitosan or IL-12. Co-formulation of chitosan and IL-12 resulted in higher IFN-γ and IL-4, and decreased IL-10 production. Furthermore, combined vaccination highly inhibited the tumor progression compared with chitosan or IL-12 alone.

Conclusion: Chitosan nanoparticle is a promising delivery system for DNA vaccine and IL-12 is an effective genetic adjuvant for the induction of strong antitumor immune response.
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http://dx.doi.org/10.22034/IJI.2018.39396DOI Listing
December 2018

Combination therapy of mesenchymal stromal cells and sulfasalazine attenuates trinitrobenzene sulfonic acid induced colitis in the rat: The S1P pathway.

J Cell Physiol 2019 07 23;234(7):11078-11091. Epub 2018 Dec 23.

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Adipose derived mesenchymal stem cells (ASCs) transplantation is a novel immunomodulatory therapeutic tool to ameliorate the symptom of inflammatory bowel disease (IBD). The objective of this study was to investigate the therapeutic effects of combined sufasalazine and ASCs therapy in a rat model of IBD. After induction of colitis in rats, ASCs were cultured and intraperitoneally injected (3 × 10 cells/kg) into the rats on Days 1 and 5 after inducing colitis, in conjunction with daily oral administration of low dose of sulfasalazine (30 mg/kg). The regenerative effects of combination of ASCs and sulfasalazine on ulcerative colitis were assessed by measuring body weight, colonic weight/length ratio, disease activity index, macroscopic scores, histopathological examinations, cytokine, and inflammation markers profiles. In addition, western blot analysis was used to assess the levels of nuclear factor-kappa B (NF-κB) and apoptosis related proteins in colitis tissues. Simultaneous treatment with ASCs and sulfasalazine was associated with significant amelioration of disease activity index, macroscopic and microscopic colitis scores, as well as inhibition of the proinflammatory cytokines in trinitrobenzene sulfonic acid (TNBS)-induced colitis. Moreover, combined ASCs and sulfasalazine therapy effectively inhibited the NF-κB signaling pathway, reduced the expression of Bax and prevented the loss of Bcl-2 proteins in colon tissue of the rats with TNBS-induced colitis. Furthermore, combined treatment with ASCs and sulfasalazine shifted inflammatory M1 to anti-inflammatory M2 macrophages by decreasing the levels of MCP1, CXCL9 and increasing IL-10, Arg-1 levels. In conclusion, combination of ASCs with conventional IBD therapy is potentially a much more powerful strategy to slow the progression of colitis via reducing inflammatory and apoptotic markers than either therapy alone.
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http://dx.doi.org/10.1002/jcp.27944DOI Listing
July 2019

Electrospun Nanofibers for Diabetes: Tissue Engineering and Cell-Based Therapies.

Curr Stem Cell Res Ther 2019 ;14(2):152-168

Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.

Diabetes mellitus is an autoimmune disease which causes loss of insulin secretion producing hyperglycemia by promoting progressive destruction of pancreatic β cells. An ideal therapeutic approach to manage diabetes mellitus is pancreatic β cells replacement. The aim of this review article was to evaluate the role of nanofibrous scaffolds and stem cells in the treatment of diabetes mellitus. Various studies have pointed out that application of electrospun biomaterials has considerably attracted researchers in the field of tissue engineering. The principles of cell therapy for diabetes have been reviewed in the first part of this article, while the usability of tissue engineering as a new therapeutic approach is discussed in the second part.
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http://dx.doi.org/10.2174/1574888X13666181018150107DOI Listing
July 2019

Combinational immune-cell therapy of natural killer cells and sorafenib for advanced hepatocellular carcinoma: a review.

Cancer Cell Int 2018 10;18:133. Epub 2018 Sep 10.

5Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

Background: High prevalence of hepatocellular carcinoma (HCC) and typically poor prognosis of this disease that lead to late stage diagnosis when potentially curative therapies are least effective; therefore, development of an effective and systematic treatment is an urgent requirement.

Main Body: In this review, several current treatments for HCC patients and their advantages or disadvantages were summarized. Moreover, various recent preclinical and clinical studies about the performances of "two efficient agents, sorafenib or natural killer (NK) cells", against HCC cells were investigated. In addition, the focus this review was on the chemo-immunotherapy approach, correlation between sorafenib and NK cells and their effects on the performance of each other for better suppression of HCC.

Conclusion: It was concluded that combinational therapy with sorafenib and NK cells might improve the outcome of applied therapeutic approaches for HCC patients. Finally, it was also concluded that interaction between sorafenib and NK cells is dose and time dependent, therefore, a careful dose and time optimizing is necessary for development of a combinational immune-cell therapy.
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http://dx.doi.org/10.1186/s12935-018-0624-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131874PMC
September 2018

Molecular Characterization and Phylogenetic Analysis of Theileria spp. and Babesia spp. Isolated from Various Ticks in Southeastern and Northwestern Regions of Iran.

Vector Borne Zoonotic Dis 2018 11 9;18(11):595-600. Epub 2018 Jul 9.

1 Department of Medical Entomology and Vector Control, School of Public Health , Tehran, Iran .

Introduction: Piroplasms are hemoprotozoa comprising heterogeneous tick-borne parasites, which are differentiated into three genera, namely Babesia, Theileria, and Cytauxzoon. The aim of this study was to determine the prevalence, molecular identification, and phylogenetic relationship of both Theileria spp. and Babesia spp. in tick species isolated from different domestic animals from two different geographical locations of Iran.

Materials And Methods: A total of 930 ticks collected from goats, sheep, and cattle were examined for the presence of Theileria spp. and Babesia spp. using PCR targeting 18S rRNA gene followed by sequencing. Sequence analysis was performed based on the data published in the GenBank on Theileria spp. and Babesia spp. isolates using bioinformatic tools, such as the standard nucleotide BLAST.

Results: A 390 or 430 base pair fragment of 18S rRNA gene of Theileria and Babesia species was successfully amplified in 17.2% of the examined ticks (16of 93). Genome of Theileria or Babesia species was detected in 4 ticks collected in Heris, including 3 Dermacentor marginatus and 1 Rhipicephalus sanguineus, and also in 12 ticks collected in Chabahar, including 10 R. sanguineus and 2 D. marginatus. Partial analysis of 18S rRNA gene sequence of the four D. marginatus, collected from goats and sheep in Heris, showed that they were infected with Theileria spp. that were 95-97% identical to Iranian Theileria ovis present in the GenBank database (GenBank acc. no. KP019206.1). While the five R. sanguineus, collected from sheep and goats in Chabahar, were infected with Babesia spp. that were 91-97% identical to Iranian Babesia ovis present in the GenBank database (GenBank acc. no. AY362829.1: KT587794.1).

Conclusion: The prevalence of Babesia and Theileria is different in southeastern and northwestern parts of Iran, with higher prevalence of babesiosis in the southeastern region and that of theileriosis in the northwestern region. Sequence analysis of 18S rRNA gene revealed that T. ovis and B. ovis are genetically polymorphic in these regions.
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http://dx.doi.org/10.1089/vbz.2018.2271DOI Listing
November 2018

Cowden syndrome.

Br J Hosp Med (Lond) 2018 Jun;79(6):352-353

Assistant Professor, Department of Emergency Medicine, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.12968/hmed.2018.79.6.352DOI Listing
June 2018

Effect of Selenium Nanoparticle Supplementation on Tissue Inflammation, Blood Cell Count, and IGF-1 Levels in Spinal Cord Injury-Induced Rats.

Biol Trace Elem Res 2019 Jan 5;187(1):202-211. Epub 2018 May 5.

Department of Veterinary Surgery and Radiology, Faculty of Veterinary Medicine, Shahrekord University, P.O. 88186-34141, Shahrekord, Iran.

Selenium is known to be a neuroprotective agent in respect to a number of neuronal diseases and pain. The aim of this study was to evaluate the neuroprotective effect of the oral administration of selenium nanoparticles in rats with spinal cord injury (SCI). Forty adult female rats were randomly assigned to two equal groups as experimental and control. Under general inhalation anesthesia, in both groups, SCI was created, at the T9-10 level of the column. On the third day after the operation, a supplement of selenium nanoparticle was administered to the experimental group at 0.2 mg/kg per day. The histology of the site of injury, IGF-1 serum concentrations, and changes in the white blood cells were examined in both groups at different pre-surgical and post-surgical times. The results of the current study showed a significant decrease in the total white blood cells, including lymphocyte, neutrophil, and monocyte in the experimental group compared to the control group. Histological evaluation showed that the inflammatory responses reduced significantly in the experimental group compared to the control group. In conclusion, we speculate that the decrease in the number of inflammatory cells after oral administration of the selenium nanoparticles is due to the neuroprotective effects of this nanoparticle.
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http://dx.doi.org/10.1007/s12011-018-1371-5DOI Listing
January 2019

A comparison study on the behavior of human endometrial stem cell-derived osteoblast cells on PLGA/HA nanocomposite scaffolds fabricated by electrospinning and freeze-drying methods.

J Orthop Surg Res 2018 Mar 27;13(1):63. Epub 2018 Mar 27.

Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: An engineered tissue structure is an artificial scaffold combined with cells and signaling factors. Among various polymers, the polylactide-co-glycolide/hydroxyapatite (PLGA/HA) has attracted much attention due to their optimal properties. The aim of this study was to study the behavior of human endometrial stem cell (hEnSC)-derived osteoblast cells cultured on PLGA/HA nanocomposite scaffolds.

Methods: hEnSCs were isolated and exposed to osteogenic media for 21 days. Differentiated cells were cultured on PLGA/HA synthetic scaffolds. The PLGA/HA-based nanocomposite scaffolds were fabricated using either electrospinning or freeze-drying methods. Behavior of the cells was evaluated a week after seeding hEnSC-derived osteoblast-like cells on these scaffolds. Osteogenesis was investigated in terms of alkaline phosphatase activity, gene expression, immunocytochemistry (ICC), proliferation, and scanning electron microscopy (SEM). Moreover, scaffold properties, such as pore size and morphology of the cells, onto the scaffolds were evaluated using SEM. Furthermore, biocompatibility of these scaffolds was confirmed by 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

Results: The matrix mineralization was proved by alizarin red staining, and the osteogenic media-treated cultures positively expressed osteocalcin and osteopontin markers. Moreover, qRT-PCR results confirmed the positive gene expression of osteopontin and osteonectin in the differentiated osteoblast-like cells. The results of behavior assessment of the cultured cells on electrospinning and freeze-dried scaffolds showed that the behavior of the cultured cells on the freeze-dried PLGA/HA scaffolds was significantly better than the electrospinning PLGA/HA scaffolds.

Conclusion: It has been shown that the freeze-dried PLGA/HA nanocomposite scaffolds can appropriately support the attachment and proliferation of the differentiated osteoblast cells and are a suitable candidate for bone tissue engineering.
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http://dx.doi.org/10.1186/s13018-018-0754-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870175PMC
March 2018

Molecular Characterization and Phylogenetic Analysis of Anaplasma spp. and Ehrlichia spp. Isolated from Various Ticks in Southeastern and Northwestern Regions of Iran.

Vector Borne Zoonotic Dis 2018 05 20;18(5):252-257. Epub 2018 Mar 20.

9 Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences , Tehran, Iran .

Introduction: Anaplasma/Ehrlichia species are tick-transmitted pathogens that cause infections in humans and numerous domestic and wild animal species. There is no information available on the molecular characteristics and phylogenetic position of Anaplasma/Ehrlichia spp. isolated from tick species from different geographic locations in Iran. The aim of this study was to determine the prevalence, molecular characteristics, and phylogenetic relationship of both Anaplasma spp. and Ehrlichia spp. in tick species isolated from different domestic animals from two different geographical locations of Iran.

Methods: A total of 930 ticks were collected from 93 cattle, 250 sheep, and 587 goats inhabiting the study areas. The collected ticks were then investigated for the presence of Anaplasma/Ehrlichia spp. using nested PCR based on the 16S rRNA gene, followed by sequencing. Sequence analysis was done based on the data published in the GenBank on Anaplasma/Ehrlichia spp. isolates using bioinformatic tools such as the standard nucleotide BLAST.

Results: Genome of Anaplasma or Ehrlichia spp. was detected in 14 ticks collected in Heris, including 5 Dermacentor marginatus, 1 Haemaphysalis erinacei, 3 Hyalomma anatolicum, and 4 Rhipicephalus sanguineus, also in 29 ticks collected in Chabahar, including 14 R. sanguineus, 8 D. marginatus, 3 Hyalomma Anatolicum, and 4 Hyalomma dromedarii. Partial analysis of the 16S rRNA gene sequence of positive samples collected from goats and sheep showed that they were infected with Anaplasma/Ehrlichia spp. that were 94-98% identical to ovine Anaplasma and 91-96% identical to Neoehrlichia and Ehrlichia spp.

Conclusion: The various ticks identified in this study suggest the possible emergence of tick-borne diseases in animals and humans in these regions. R. sanguineus and D. marginatus seem to be predominant vectors responsible for anaplasmosis in these regions. Partial sequence analysis of the 16S rRNA gene showed that A. ovis is genetically polymorphic in these regions. Furthermore, an association between the genetic heterogeneity of this microorganism and the geographical regions of Anaplasma strains was found. This study also showed that those ticks that were collected from the same geographical origin were infected with closely related strains of Anaplasma.
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http://dx.doi.org/10.1089/vbz.2017.2219DOI Listing
May 2018