Publications by authors named "Ehsan Saburi"

43 Publications

Genetics and molecular biology of male infertility among Iranian population: an update.

Am J Transl Res 2021 15;13(6):5767-5785. Epub 2021 Jun 15.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences Mashhad, Iran.

Infertility is one of the main social and health problems among young couples. Although a noticeable ratio of infertilities are asymptomatic, about half of the cases are observed among males. Various environmental factors such as life style, dietary patterns, and pathogens are associated with male infertility. Mutations and chromosomal abnormalities are also the most important genetic risk factors of male infertility. Similar to other populations, there is a dramatically rising trend of male infertility among Iranian. Regarding the high ratio of asymptomatic cases, it is required to clarify the molecular biology and cellular processes involved in male infertility in this population to suggest an efficient panel of diagnostic markers. In this review, we have summarized all of the cellular and molecular processes which have been reported among Iranian infertile males to clarify the molecular biology of male infertility in this population. It was observed that the stress response, cellular detoxification, and DNA repair processes were the most common aberrant cellular mechanisms among Iranian infertile males. This review paves the way of introducing a population-based diagnostic panel of genetic markers among Iranian infertile males.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290737PMC
June 2021

MAEL as a diagnostic marker for the early detection of esophageal squamous cell carcinoma.

Diagn Pathol 2021 Apr 26;16(1):36. Epub 2021 Apr 26.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Esophageal cancer is one of the most common malignancies among Iranians and is categorized as adenocarcinoma and squamous cell carcinoma. Various environmental and genetic factors are involved in this malignancy. Despite the recent advances in therapeutic modalities there is still a noticeable mortality rate among such patients which can be related to the late diagnosis. Regarding high ratio of esophageal squamous cell carcinoma (ESCC) in Iran, therefore it is required to assess molecular biology of ESCC to introduce novel diagnostic markers. In present study we assessed the role of Maelstrom (MAEL) cancer testis gene in biology of ESCC among Iranian patients.

Methods: Forty-five freshly normal and tumor tissues were enrolled to evaluate the levels of MAEL mRNA expression using Real time polymerase chain reaction.

Results: MAEL under and over expressions were observed in 12 (26.7%) and 9 (20%) of patients, respectively. MAEL fold changes were ranged between -4.33 to -1.87 (mean SD: -2.90± 0.24) and 1.92 to 7.72 (mean SD: 3.97± 0.69) in under and over expressed cases, respectively. There was a significant association between stage and MAEL expression in which majority of MAEL over expressed tumors (8/9, 88.9%) were in stage I/II (p<0.001). There was also a significant correlation between MAEL expression and depth of invasion in which tumor with T1/2 had higher levels of MAEL expression compared with T3/4 tumors (p=0.017). Moreover, there were significant correlations between MAEL expression, tumor size (p=0.028), and grade (p=0.003) among male patients.

Conclusions: Our data showed that the MAEL was mainly involved in primary stages of tumor progression and it has a declining expression levels toward the advanced stages and higher depth of tumor invasions. Therefore, MAEL can be efficiently introduced as an early detection marker among Iranian ESCC patients.
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http://dx.doi.org/10.1186/s13000-021-01098-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077922PMC
April 2021

Immunoregulatory Effects of Tolerogenic Probiotics in Multiple Sclerosis.

Adv Exp Med Biol 2021 ;1286:87-105

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Gut microbiota has essential roles in the prevention and progression of multiple sclerosis (MS). The association between the gut microbiota and the central nervous system (CNS) or immune system response of MS patients has been documented in many studies. The composition of the gut microbiota could lead to sensitization or resistance against promotion and development of MS disease. Probiotics are the major part of gut microflorapopulation and could be substituted with tolerogenic probiotics that protect the CNS against autoimmune responses. Tolerogenic probiotics with anti-inflammatory and immuno-modulatory properties have effects on intestinal flora and can reestablish regulatory mucosal and systemic immune responses. Probiotics are able to prevent and restore excessive activation of inflammatory responses, especially autoreactive T cells and inflammatory cytokines. Tolerogenic probiotics, through induction of regulatory T cells and increase of anti-inflammatory cytokines, play a crucial role in controlling inflammation and maintaining tolerance and hemostasis. Therefore, probiotics can be considered as a preventive or therapeutic tool in MS. In the present review, we focus on the immunoregulatory effects of tolerogenic probiotics on the severity of disease, as well as Th1, Th2, and Treg populations in different experimental and human studies of MS.
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http://dx.doi.org/10.1007/978-3-030-55035-6_6DOI Listing
March 2021

Chemokines as the critical factors during bladder cancer progression: an overview.

Int Rev Immunol 2021 16;40(5):344-358. Epub 2021 Feb 16.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Bladder cancer (BCa) is one of the most frequent urogenital malignancies which is mainly observed among men. There are various genetic and environmental risk factors associated with BCa progression. Transurethral endoscopic resection and open ablative surgery are the main treatment options for muscle invasive BCa. BCG therapy is also employed following the endoscopic resection to prevent tumor relapse. The tumor microenvironment is the main interaction site of tumor cells and immune system in which the immune cells are recruited via chemokines and chemokine receptors. In present review we summarized the main chemokines and chemokine receptors which have been associated with histopathological features of BCa patients in the world. This review highlights the chemokines and chemokine receptors as critical markers in early detection and therapeutic purposes among BCa patients and clarifies their molecular functions during BCa progression and metastasis.
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http://dx.doi.org/10.1080/08830185.2021.1877287DOI Listing
October 2021

The use of mesenchymal stem cells in the process of treatment and tissue regeneration after recovery in patients with Covid-19.

Gene 2021 Apr 4;777:145471. Epub 2021 Feb 4.

Immunogenetics Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Department of Medical Biotechnology, Faculty of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

In addition to causing health concerns, the new coronavirus has been considered in the world with its unknown mechanism of physiopathogenesis and long-term effects after patient recovery. Pulmonary, renal, hepatic and cardiac complications have been reported so far. Beside the researchers' focus on finding vaccines and using conventional therapies, cell-based therapy might be an effective therapeutic strategy. The use of mesenchymal stem cells (MSCs) is one of the options due to their immunomodulatory properties and their proven effects in the treatment of many diseases. As MSCs are not infected with covid-19, there is evidence that it modulates the immune system and prevents the virus from clotting. Despite the beginning of numerous clinical trials in the use of mesenchymal stem cells, it is necessary to set a practical guideline that specifies items such as cell origin, number of cells, frequency of injection, injection site, etc.
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http://dx.doi.org/10.1016/j.gene.2021.145471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860931PMC
April 2021

Genetic and molecular biology of systemic lupus erythematosus among Iranian patients: an overview.

Auto Immun Highlights 2021 Jan 30;12(1). Epub 2021 Jan 30.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Systemic lupus erythematosus (SLE) is a clinicopathologically heterogeneous chronic autoimmune disorder affecting different organs and tissues. It has been reported that there is an increasing rate of SLE incidence among Iranian population. Moreover, the Iranian SLE patients have more severe clinical manifestations compared with other countries. Therefore, it is required to introduce novel methods for the early detection of SLE in this population. Various environmental and genetic factors are involved in SLE progression.

Main Body: In present review we have summarized all of the reported genes which have been associated with clinicopathological features of SLE among Iranian patients.

Conclusions: Apart from the reported cytokines and chemokines, it was interestingly observed that the apoptosis related genes and non-coding RNAs were the most reported genetic abnormalities associated with SLE progression among Iranians. This review clarifies the genetics and molecular biology of SLE progression among Iranian cases. Moreover, this review paves the way of introducing an efficient panel of genetic markers for the early detection and better management of SLE in this population.
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http://dx.doi.org/10.1186/s13317-020-00144-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847600PMC
January 2021

Withdrawal Notice: Anti-cancer Effect of Urginea Maritima Bulb Extract In Vitro through Cell Cycle Arrest and Induction of Apoptosis in Human Breast Cancer Cell Lines

Curr Drug Discov Technol 2020 08 17. Epub 2020 Aug 17.

Department of Immunogenetics, Buali Institute, Mashhad University of Medical Sciences, Mashhad. Iran.

The article has been withdrawn by agreement between the editors and publisher of Current Drug Discovery Technologies. The authors are not responding to the editor’s requests to provide the language-edited version.

Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.

The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php

Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
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http://dx.doi.org/10.2174/1570163817666200817111703DOI Listing
August 2020

Potential inhibitory effect of lycopene on prostate cancer.

Biomed Pharmacother 2020 Sep 30;129:110459. Epub 2020 Jun 30.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Studying prostate cancer is important due to its high annual incidences and mortality rates in the world. Although prostate cancer mortality rates are reduced using new therapy, complicated routes and side effects of these current drugs require a daily available treatment for prevention. Lycopene is a natural, prominent, and effective product which has a high value in diet. The anti-cancer effect, non-toxicity, safety and preventive or therapeutic roles of lycopene have been investigated in several studies. In the current review, we have collected information about the anti-cancer, anti-progressive and apoptotic effects of lycopene on prostate cancer. This article is a summary of the most important original and review articles on lycopene and its anticancer effects that are systematically categorized and presents information about the molecular structure, different sources, biological functions, and its in-vivo and in-vitro effects of lycopene on variety of cancerous and normal cells. The clinical studies provide a clear image for continuous use of this adjunctive dietary for different type of cancers, especially prostate cancer in men. In addition, this article discusses the various molecular pathways activated by lycopene that eventually prevent or suppress cancer. Lycopene has been found to effectively suppress the progression and proliferation, arrest in-cell cycle, and induce apoptosis of prostate cancer cells in both in-vivo and in-vitro conditions. Additionally, lycopene showed that it could modulate the signaling pathways and their protein for the treatment or prevention of prostate cancer.
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http://dx.doi.org/10.1016/j.biopha.2020.110459DOI Listing
September 2020

Aloe Vera-Derived Gel-Blended PHBV Nanofibrous Scaffold for Bone Tissue Engineering.

ASAIO J 2020 08;66(8):966-973

Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Today, composite scaffolds fabricated by natural and synthetic polymers have attracted a lot of attention among researchers in the field of tissue engineering, and given their combined properties that can play a very useful role in repairing damaged tissues. In the current study, aloe vera-derived gel-blended poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibrous scaffold was fabricated by electrospinning, and then, PHBV and PHBV gel fabricated scaffolds characterized by scanning electron microscope, protein adsorption, cell attachment, tensile and cell's viability tests. After that, osteogenic supportive property of the scaffolds was studied by culturing of human-induced pluripotent stem cells on the scaffolds under osteogenic medium and evaluating of the common bone-related markers. The results showed that biocompatibility of the PHBV nanofibrous scaffold significantly improved when combined with the aloe vera gel. In addition, higher amounts of alkaline phosphatase activity, mineralization, and bone-related gene and protein expression were detected in stem cells when grown on PHBV-gel scaffold in comparison with those stem cells grown on the PHBV and culture plate. Taken together, it can be concluded that aloe vera gel-blended PHBV scaffold has a great promising osteoinductive potential that can be used as a suitable bioimplant for bone tissue engineering applications to accelerate bone regeneration and also degraded completely along with tissue regeneration.
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http://dx.doi.org/10.1097/MAT.0000000000001094DOI Listing
August 2020

The Role of MicroRNAs in the Induction of Pancreatic Differentiation.

Curr Stem Cell Res Ther 2021 ;16(2):145-154

Diabetes Research Center, Department of Medical Biotechnology, Faculty of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Stem cell-based therapy is one of the therapeutic options with promising results in the treatment of diabetes. Stem cells from various sources are expanded and induced to generate the cells capable of secreting insulin. These insulin-producing cells [IPCs] could be used as an alternative to islets in the treatment of patients with diabetes. Soluble growth factors, small molecules, geneencoding transcription factors, and microRNAs [miRNAs] are commonly used for the induction of stem cell differentiation. MiRNAs are small non-coding RNAs with 21-23 nucleotides that are involved in the regulation of gene expression by targeting multiple mRNA targets. Studies have shown the dynamic expression of miRNAs during pancreatic development and stem cell differentiation. MiR- 7 and miR-375 are the most abundant miRNAs in pancreatic islet cells and play key roles in pancreatic development as well as islet cell functions. Some studies have tried to use these small RNAs for the induction of pancreatic differentiation. This review focuses on the miRNAs used in the induction of stem cells into IPCs and discusses their functions in pancreatic β-cells.
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http://dx.doi.org/10.2174/1574888X15666200621173607DOI Listing
October 2021

Probiotics with ameliorating effects on the severity of skin inflammation in psoriasis: Evidence from experimental and clinical studies.

J Cell Physiol 2020 12 28;235(12):8925-8937. Epub 2020 Apr 28.

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

Experimental and clinical studies have confirmed safety and the medical benefits of probiotics as immunomodulatory medications. Recent advances have emphasized the critical effect of gastrointestinal bacteria in the pathology of inflammatory disorders, even, outside the gut. Probiotics have shown promising results for curing skin-influencing inflammatory disorders through modulating the immune response by manipulating the gut microbiome. Psoriasis is a complex inflammatory skin disease, which exhibits a microbiome distinct from the normal skin. In the present review, we considered the impact of gastrointestinal microbiota on the psoriasis pathogenesis, and through literature survey, attempted to explore probiotic species utilized for psoriasis treatment.
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http://dx.doi.org/10.1002/jcp.29737DOI Listing
December 2020

Different osteogenic differentiation potential of mesenchymal stem cells on three different polymeric substrates.

Gene 2020 May 4;740:144534. Epub 2020 Mar 4.

Department of Oral & Maxillofacial Surgery, Dental School, Shahid Beheshti University Of Medical Sciences, Tehran, Iran. Electronic address:

The function of tissue cells is strongly depends on the extracellular matrix (ECM) that can guide and support cell structure. This support plays a crucial role in the process of cell proliferation and differentiation. Herein, three different nanofibrous scaffolds that are highly attractive for tissue engineering were selected and then osteogenic related genes and protein expression patterns of human adipose-derived mesenchymal stem cells (AT-MSCs) were investigated when grown on substrates. Polycaprolactone, Poly (L-lactic acid) and Polyvinylidene-fluoride nanofibrous scaffolds were fabricated using Electrospinning method and then AT-MSCs viability and osteogenic differentiation were evaluated while cultured on them. The highest AT-MSCs survival rate when grown on the scaffolds was detected when grown on Polyvinylidene-fluoride. In addition, the highest ALP activity and mineralization were also observed in differentiated AT-MSCs has grown on Polyvinylidene-fluoride. The expression levels of Runx2, osteonectin and osteocalcin genes and osteocalcin protein in the AT-MSCs has grown on the Polyvinylidene-fluoride were also significantly higher than the rest of the scaffolds. Based on the results, it seems that since the studied substrate have a similar structural characteristics, their nature may have an important role in the stem cell's osteogenesis process, where the Polyvinylidene-fluoride piezoelectricity was a most distinguished characteristic.
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http://dx.doi.org/10.1016/j.gene.2020.144534DOI Listing
May 2020

Potential cytotoxic and anti-metastatic effects of berberine on gynaecological cancers with drug-associated resistance.

Eur J Med Chem 2020 Feb 4;187:111951. Epub 2019 Dec 4.

Halal Research Center of IRI, FDA, Tehran, Iran; Nanotechnology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Biotechnology, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Gynaecological disorders, such as cervical, ovarian, and endometrial cancers are the second most prevalent cancer types in women worldwide. Therapeutic approaches for gynaecological cancers involve chemotherapy, radiation, and surgery. However, lifespan is not improved, and novel medications are required. Among various phytochemicals, berberine, a well-known natural product, has been shown to be a promising cancer chemopreventive agent. Pharmacokinetics, safety, and efficacy of berberine have been investigated in the several experiments against numerous diseases. Here, we aimed to provide a literature review from available published investigations showing the anticancer effects of berberine and its various synthetic analogues against gynaecological disorders, including cervical, ovarian, and endometrial cancers. In conclusion, berberine has been found to efficiently inhibit viability, proliferation, and migration of cancer cells, mainly, via induction of apoptosis by both mitochondrial dependent and -independent pathways. Additionally, structural modification of berberine showed that berberine analogues can improve its antitumor effects against gynaecological cancers.
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http://dx.doi.org/10.1016/j.ejmech.2019.111951DOI Listing
February 2020

Prevalence of Integrons and Antibiotic Resistance Pattern in Isolated from Clinical Samples of Iranian Patients: A Systematic Review and Meta-analysis.

Ethiop J Health Sci 2019 Sep;29(5):639-648

Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Acinetobacter baumannii is an important opportunistic nosocomial pathogen. Class 1 integrons in A. baumannii plays a significant role in antibiotic resistance. Therefore, this study aimed to investigate the prevalence of integrons and antibiotic resistance pattern in A. baumannii isolated from clinical samples of Iranian patients.

Methods: The Medical Subject Headings (MeSH) and the keywords with the help of Boolean operators ("AND" or "OR") were used alone or in combination to conduct the search. The searching process was conducted in the Web of Science, PubMed, Cochrane Library, Scopus, and Google Scholar databases and, also Iranian databases. The search was restricted to relevant English and Persian cross-sectional publications reporting the prevalence of Int1 in A. baumannii isolated from clinical samples from 1 January 2000 to 31 December 2018. The data were analyzed using Comprehensive Meta-Analysis software. Regarding the heterogeneity of studies, the random effects model was used. Cochrane Q and I tests was used to evaluate statistical heterogeneity between the studies.

Results: Fifteen studies were included in the analysis. The combined prevalence of class 1 integrons in A. baumannii was 55.2% (95% CI: 44.8-65.1). The pooled prevalence of MDR A. baumannii isolates was 68.1%. The highest resistance belonged to Aztreonam, followed by Ciprofloxacin, and Ceftazidime with a resistance rate of 97.6%, 92.8%, and 91.6%, respectively. Tobramycin was reported as an effective antibiotic.

Conclusions: The present study reported an alarmingly high prevalence of class 1 Integrons, and MDR isolates of A. baumannii recovered from clinical samples that should be considered.
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http://dx.doi.org/10.4314/ejhs.v29i5.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813273PMC
September 2019

Micro-RNA-incorporated electrospun nanofibers improve osteogenic differentiation of human-induced pluripotent stem cells.

J Biomed Mater Res A 2020 02 11;108(2):377-386. Epub 2019 Nov 11.

Department of Immunogenetics, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Smart scaffolds have a great role in the damaged tissue reconstruction. The aim of this study was developing a scaffold that in addition to its fiber's topography has also content of micro-RNAs (miRNAs), which play a regulatory role during osteogenesis. In this study, we inserted two important miRNAs, including miR-22 and miR-126 in the electrospun polycaprolactone (PCL) nanofibers and after scaffold characterization, osteoinductivity of the fabricated nanofibers was investigated by evaluating of the osteogenic differentiation potential of induced pluripotent stem cells (iPSCs) when grown on miRNAs-incorporated PCL nanofibers (PCL-miR) and empty PCL. MiRNAs incorporation had no effect on the fibers size and morphology, cell attachment, and protein adsorption, although viability and proliferation rate of the human iPSCs were increased after a week in PCL-miR compared to the empty PCL. The results obtained from alkaline phosphatase activity, calcium content, bone-related genes, and proteins expression assays demonstrated that the highest osteogenic markers were observed in iPSCs grown on the PCL-miR compared to the cells cultured on PCL and culture plate. According to the results, miR-incorporated PCL nanofibers could be considered as a promising potential tissue-engineered construct for the treatment of patients with bone lesions and defects.
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http://dx.doi.org/10.1002/jbm.a.36824DOI Listing
February 2020

Comparison of human-induced pluripotent stem cells and mesenchymal stem cell differentiation potential to insulin producing cells in 2D and 3D culture systems in vitro.

J Cell Physiol 2020 05 15;235(5):4239-4246. Epub 2019 Oct 15.

Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran.

Diabetes is one of the most common diseases in the world that is chronic, progressive, and costly, and causes many complications. Common drug therapies are not able to cure it, and pancreas transplantation is not responsive to the high number of patients. The production of the insulin producing cells (IPCs) from the stem cells in the laboratory and their transplantation to the patient's body is one of the most promising new approaches. In this study, the differentiation potential of the induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) into IPCs was compared to each other while cultured on poly(lactic-co-glycolic) acid (PLGA)/polyethylene glycol (PEG) nanofibrous scaffold as a 3D substrate and tissue culture polystyrene (TCPS) as a 2D substrate. Although the expression level of the insulin, Glut2 and pdx-1 genes in stem cells cultured on 3D substrate was significantly higher than the stem cells cultured on 2D substrate, the highest expression level of these genes was detected in the iPSCs cultured on PLGA-PEG. Insulin and C-peptide secretions from differentiated cells were also investigated and the results showed that secretions in cultured iPSCs on the PLGA-PEG were significantly higher than cultured iPSCs on the TCPS and cultured MSCs on both PLGA-PEG and TCPS. In addition, insulin protein was also expressed in the cultured iPSCs on the PLGA-PEG significantly higher than cultured MSCs on the PLGA-PEG. It can be concluded that differentiation potential of iPSCs into IPCs is significantly higher than human MSCs at both 2D and 3D culture systems.
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http://dx.doi.org/10.1002/jcp.29298DOI Listing
May 2020

Unfolded protein response-mediated modulation of mesenchymal stem cells.

IUBMB Life 2020 02 24;72(2):187-197. Epub 2019 Aug 24.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

The endoplasmic reticulum (ER) receives unfolded proteins predestined for the secretory pathway or to be incorporated as transmembrane proteins. The ER has to accommodate the proper folding and glycosylation of these proteins and also to properly incorporate transmembrane proteins. However, under various circumstances, the proteins shuttling through the ER can be misfolded and undergo aggregation, which causes activation of the unfolded protein response (UPR). The UPR is mediated through three primary pathways: activating transcription factor-6, inositol-requiring enzyme-1 (IRE1), and PKR-like endoplasmic reticulum kinase, which up-regulate ER folding chaperones and temporarily suppress protein translation. The UPR can be both cytoprotective and/or cytotoxic depending on the duration of UPR activation and the type of host cell. Proteostasis controls stem cell function, while stress responses affect stem cell identity and differentiation. The present review aimed to explore and discuss the effects of the UPR pathways on mesenchymal stem cells.
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http://dx.doi.org/10.1002/iub.2154DOI Listing
February 2020

The trip of a drug inside the body: From a lipid-based nanocarrier to a target cell.

J Control Release 2019 09 21;309:59-71. Epub 2019 Jul 21.

Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. Electronic address:

To date, enormous investigations have been conducted to enhance medicines' target-oriented delivery to improve their therapeutic index. In this regard, lipid-based carrier system might have been regarded as prime delivery systems that are very close to the naturally cell-derived vesicles used for biomolecular communication among cells from occasionally remote tissues. Upon examination of the literature, we found a chasm between groups of investigations in drug pharmaceutics and thought that maybe holistic research could provide better information with respect to drug delivery inside the body, especially when they are going to be injected directly into the bloodstream for systemic distribution. While a collection of older research in most cases dealt with the determination of drug partition coefficient between the aqueous and cell membrane compartments, the link has been overlooked in newer investigations that were mostly focused on drug formulation optimization and their association with particle biodistribution. This gap in the literature motivated us to present the current opinion paper, in which drug physicochemical properties like drug lipophilicity/hydrophilicity is considered as an important element in designing drug-carrying liposomes or micelles. How a hypothetical high throughput cell-embedded chromatographic technique might help to investigate a nanocarrier tissue distribution and to design 'multi-epitope grafted lipid-based drug carrier systems' are discussed. Whenever we would need support for our opinions, we have provided analogy from hydrophobic biomolecules like cholesterol, steroid hormones, and sex hormones and encouraged readers to consider our principle hypothesis: If these molecules could reach their targets far away from the site of production, then a large list of hydrophobic drugs could be delivered to their targets using the same principles.
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http://dx.doi.org/10.1016/j.jconrel.2019.07.027DOI Listing
September 2019

Synergistic effects of polyaniline and pulsed electromagnetic field to stem cells osteogenic differentiation on polyvinylidene fluoride scaffold.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):3058-3066

i Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences , Karaj , Iran.

Repairing the lost or damaged mandible is very difficult and time-consuming, so there is a great hope for tissue engineering to accelerate it. At the present study, electrospinning was applied to fabricate polyvinylidene fluoride (PVDF) and PVDF-polyaniline (PANI) composite scaffolds. In addition, extremely low frequency pulsed electromagnetic field (PEMF) was applied for treating the stem cells derived from dental pulp (DPSCs) when cultured on the nanofibrous scaffolds. Osteoinductive property of the fabricated PVDF, PVDF-PANI scaffold at the presence and absence of the PEMF was investigated by evaluating the common osteogenic differentiation markers in seeded-DPSCs on the scaffold. Results demonstrated that cell attachment, protein adsorption and cells viability were increased when PEMF was applied. In addition, ALP activity, calcium content, osteogenic genes and protein evaluations confirmed that PEMF could significantly increase osteoinductivity of the PVDF while composite with PANI. According to the results, the use of polymers with piezoelectricity and conductivity features plus PEMF exposure has a promising potential to improve the current treatment methods in bone and mandibular defects.
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http://dx.doi.org/10.1080/21691401.2019.1645154DOI Listing
December 2019

A Meta-Analysis of the Prevalence of Class 1 Integron and Correlation with Antibiotic Resistance in Pseudomonas aeruginosa Recovered from Iranian Burn Patients.

J Burn Care Res 2019 10;40(6):972-978

Infectious Diseases Research Center, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

The role of integrons has been highlighted in antibiotic resistance among Pseudomonas aeruginosa isolates. Therefore, we here reviewed the prevalence of class 1 integrons and their correlations with antibiotic resistance of P. aeruginosa isolated from Iranian burn patients. This review was conducted according to the guidelines of Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). Cross-sectional and cohort studies published from January 1, 2000 until December 31, 2018 were enrolled. Meta-analysis was performed by Comprehensive Meta-Analysis (CMA) software using the random effects model, Cochran's Q, and I2 tests. Publication bias was estimated by Funnel plot and Egger's linear regression test. Nine out of 819 studies met the eligibility criteria. The overall combined prevalence of class 1 integrons in P. aeruginosa isolates was 69% (95% confidence interval [CI]: 50.5-83%). The highest combined resistance was reported against Cloxacillin (87.7%), followed by Carbenicillin (79.1%) and Ceftriaxone (77.3%). The combined prevalence of multidrug-resistant (MDR) isolates was 79.3% (95% CI: 31.1-97%). Also, a significant correlation was noted between the presence of class 1 integrons and antibiotic resistance in 55.5% of the included studies (P < .05). The results showed high prevalence of class 1 integrons, antibiotic resistance, and MDR strains in P. aeruginosa isolated from Iranian burn patients. Also, most of the included studies showed a significant correlation between the presence of class 1 integrons and antibiotic resistance.
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http://dx.doi.org/10.1093/jbcr/irz135DOI Listing
October 2019

Cell cytotoxicity, immunostimulatory and antitumor effects of lipid content of liposomal delivery platforms in cancer immunotherapies. A comprehensive in-vivo and in-vitro study.

Int J Pharm 2019 Aug 2;567:118492. Epub 2019 Jul 2.

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

Liposome is one of the promising technologies for antigen delivery in cancer immunotherapies. It seems that the phospholipid content of liposomes can act as immunostimulatory molecules in cancer immunotherapy. In the present study, the immunological properties of different phospholipid content of liposomal antigen delivery platforms were investigated. To this aim, F1 to F4 naïve liposomes (without tumor-specific loaded antigens) of positively charged DOTAP/Cholesterol/DOPE (4/4/4 mol ratio), negatively charged DMPC/DMPG/Cholesterol/DOPE (15/2/3/5), negatively charged DSPC/DSPG/Cholesterol/DOPE (15/2/3/5) and PEGylated HSPC/mPEG2000-DSPE/Cholesterol (13/110) liposomal compositions were administered in mice bearing C26 colon carcinoma to assess tumor therapy. Moreover, In-vitro studies were conducted, including cytotoxicity assay, serum cytokines measurements, IFN-γ and IL-4 ELISpot assay, T cells subpopulation frequencies assay. The liposomes containing DOTAP and DOPE (F1 liposomes) were able to stimulate cytotoxic T lymphocytes signals such as IFN-γ secretions. In parallel, the aforementioned phospholipids stimulated secretion of IL-4 and IL-17 cytokines from T helper cells. However, these liposomes did not improve survival indices in mice. As conclusion, DOTAP and DOPE contained liposomes (F1 liposomes) stimulate a mixture of Th1 and Th2 immune responses in a tumor-specific antigens-free manner in mice bearing C26 colon carcinoma. Therefore, phospholipid composition of liposomes merits consideration in designing antigen-containing liposomes for cancer immunotherapy.
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http://dx.doi.org/10.1016/j.ijpharm.2019.118492DOI Listing
August 2019

Improved osteogenic differentiation of human induced pluripotent stem cells cultured on polyvinylidene fluoride/collagen/platelet-rich plasma composite nanofibers.

J Cell Physiol 2020 02 27;235(2):1155-1164. Epub 2019 Jun 27.

Department of Biology, Varamin-Pishva Branch, Islamic Azad University, Varamin, Iran.

Blood transfusion or blood products, such as plasma, have a long history in improving health, but today, platelet-rich plasma (PRP) is used in various medical areas such as surgery, orthopedics, and rheumatology in many ways. Considering the high efficiency of tissue engineering in repairing bone defects, in this study, we investigated the combined effect of nanofibrous scaffolds in combination with PRP on the osteogenic differentiation potential of human induced pluripotent stem cells (iPSCs). Electrospinning was used for fabricating nanofibrous scaffolds by polyvinylidene fluoride/collagen (PVDF/col) with and without PRP. After scaffold characterization, the osteoinductivity of the fabricated scaffolds was studied by culturing human iPSCs under osteogenic medium. The results showed that PRP has a considerable positive effect on the biocompatibility of the PVDF/col nanofibrous scaffold when examined by protein adsorption, cell attachment, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. In addition, the results obtained from alkaline phosphatase activity and calcium content assays demonstrated that nanofibers have higher osteoinductivity while grown on PRP-incorporated PVDF/col nanofibers. These results were also confirmed while the osteogenic differentiation of the iPSCs was more investigated by evaluating the most important bone-related genes expression level. According to the results, it can be concluded that PVDF/col/PRP has much more osteoinductivity while compared with the PVDF/col, and it can be introduced as a promising bone bio-implant for use in bone tissue engineering applications.
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http://dx.doi.org/10.1002/jcp.29029DOI Listing
February 2020

Fucosylated umbilical cord blood hematopoietic stem cell expansion on selectin-coated scaffolds.

J Cell Physiol 2019 12 17;234(12):22593-22603. Epub 2019 May 17.

Department of Medical Biotechnology, Faculty of Medicine, Arak University of Medical Science, Arāk, Iran.

Despite the advantages of transplantation of umbilical cord blood's (UCB's) hematopoietic stem cells (uHSCs) for hematologic malignancy treatment, there are two major challenges in using them: (a) Insufficient amount of uHSCs in a UCB unit; (b) a defect in uHSCs homing to bone marrow (BM) due to loose binding of their surface glycan ligands to BM's endothelium selectin receptors. To overcome these limitations, after poly l-lactic acid (PLLA) scaffold establishment and incubation of uHSCs with fucosyltransferase-VI and GDP-fucose, ex vivo expansion of these cells on selectin-coated scaffold was done. The characteristics of the cultured fucosylated and nonfucosylated cells on a two-dimensional culture system, PLLA, and a selectin-coated scaffold were evaluated by flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony-forming unit (CFU) assay, and CXCR4 expression at the messenger RNA and protein levels. According to the findings of this study, optimized attachment to the scaffold in scanning electron microscopy micrograph, maximum count of CFU, and the highest 570 nm absorption were observed in fucosylated cells expanded on selectin-coated scaffolds. Furthermore, real-time polymerase chain reaction showed the highest expression of the CXCR4 gene, and immunocytochemistry data confirmed that the CXCR4 protein was functional in this group compared with the other groups. Considered together, the results showed that selectin-coated scaffold could be a supportive structure for fucosylated uHSC expansion and homing by nanotopography. Fucosylated cells placed on the selectin-coated scaffold serve as a basal surface for cell-cell interaction and more homing potential of uHSCs. Accordingly, this procedure can also be considered as a promising technique for the hematological disorder treatment and tissue engineering applications.
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http://dx.doi.org/10.1002/jcp.28825DOI Listing
December 2019

Incorporated-bFGF polycaprolactone/polyvinylidene fluoride nanocomposite scaffold promotes human induced pluripotent stem cells osteogenic differentiation.

J Cell Biochem 2019 10 13;120(10):16750-16759. Epub 2019 May 13.

Department of Genetics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.

Bioactive scaffolds that can increase transplanted cell survival time at the defect site have a great promising potential to use clinically since tissue regeneration or secretions crucially depend on the transplanted cell survival. In this study embedded basic fibroblast growth factor (bFGF)-polycaprolactone-polyvinylidene fluoride (PCL-PVDF) hybrid was designed and fabricated by electrospinning as a bio-functional nanofibrous scaffold for bone tissue engineering. After morphological characterization of the PCL-PVDF (bFGF) scaffold, nanofibers biocompatibility was investigated by culturing of the human induced pluripotent stem cells (iPSCs). Then, the bone differentiation capacity of the iPSCs was evaluated when grown on the PCL-PVDF and PCL-PVDF (bFGF) scaffolds in comparison with culture plate as a control using evaluating of the common osteogenic markers. The viability assay displayed a significant increase in iPSCs survival rate when grown on the bFGF content scaffold. The highest alkaline phosphatase activity and mineralization were detected in the iPSCs while grown on the PCL-PVDF (bFGF) scaffolds. Obtained results from gene and protein expression were also demonstrated the higher osteoinductive property of the bFGF content scaffold compared with the scaffold without it. According to the results, the release of bFGF from PCL-PVDF nanofibers increased survival and proliferation rate of the iPSCs, which followed by an increase in its osteogenic differentiation potential. Taking together, PCL-PVDF (bFGF) nanofibrous scaffold demonstrated that can be noted as a promising candidate for treating the bone lesions by tissue engineering products.
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http://dx.doi.org/10.1002/jcb.28933DOI Listing
October 2019

Cardioprotective microRNAs: Lessons from stem cell-derived exosomal microRNAs to treat cardiovascular disease.

Atherosclerosis 2019 06 23;285:1-9. Epub 2019 Mar 23.

Halal Research Center of IRI, FDA, Tehran, Iran; Nanotechnology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Biotechnology, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

The stem cell-based therapy has emerged as a promising therapeutic strategy for treating cardiovascular ischemic diseases (CVIDs), such as myocardial infarction (MI). However, some important functional shortcomings of stem cell transplantation, such as immune rejection, tumorigenicity and infusional toxicity, have overshadowed stem cell therapy in the setting of cardiovascular diseases (CVDs). Accumulating evidence suggests that the therapeutic effects of transplanted stem cells are predominately mediated by secreting paracrine factors, importantly, microRNAs (miRs) present in the secreted exosomes. Therefore, novel cell-free therapy based on the stem cell-secreted exosomal miRs can be considered as a safe and effective alternative tool to stem cell therapy for the treatment of CVDs. Stem cell-derived miRs have recently been found to transfer, via exosomes, from a transplanted stem cell into a recipient cardiac cell, where they regulate various cellular process, such as proliferation, apoptosis, stress responses, as well as differentiation and angiogenesis. The present review aimed to summarize cardioprotective exosomal miRs secreted by transplanted stem cells from various sources, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and cardiac stem/progenitor cells, which showed beneficial modulatory effects on the myocardial infracted heart. In summary, stem cell-exosomal miRs, including miR-19a, mirR-21, miR-21-5p, miR-21-a5p, miR-22 miR-24, miR-26a, miR-29, miR-125b-5p, miR-126, miR-201, miR-210, and miR-294, have been shown to have cardioprotective effects by enhancing cardiomyocyte survival and function and attenuating cardiac fibrosis. Additionally, MCS-exosomal miRs, including miR-126, miR-210, miR-21, miR-23a-3p and miR-130a-3p, are found to exert cardioprotective effects through induction of angiogenesis in ischemic heart after MI.
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http://dx.doi.org/10.1016/j.atherosclerosis.2019.03.016DOI Listing
June 2019

Comparison of osteogenic differentiation potential of induced pluripotent stem cells on 2D and 3D polyvinylidene fluoride scaffolds.

J Cell Physiol 2019 08 9;234(10):17854-17862. Epub 2019 Mar 9.

Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

In recent decades, tissue engineering has been the most contributor for introducing 2D and 3D biocompatible osteoinductive scaffolds as bone implants. Polyvinylidene fluoride (PVDF), due to the unique mechanical strength and piezoelectric properties, can be a good choice for making a bone bioimplant. In the present study, PVDF nanofibers and film were fabricated as 3D and 2D scaffolds, and then, osteogenic differentiation potential of the human induced pluripotent stem cells (iPSCs) was investigated when grown on the scaffolds by evaluating the common osteogenic markers in comparison with tissue culture plate. Biocompatibility of the fabricated scaffolds was confirmed qualitatively and quantitatively by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and scanning electron microscopy assays. Human iPSCs cultured on PVDF nanofibers showed a significantly higher alkaline phosphate activity and calcium content compared with the iPSCs cultured on PVDF film. Osteogenic-related genes and proteins were also expressed in the iPSCs seeded on PVDF nanofibers significantly higher than iPSCs seeded on PVDF film, when investigated by real-time reverse transcription polymerase chain reaction and western blot analysis, respectively. According to the results, the PVDF nanofibrous scaffold showed a greater osteoinductive property compared with the PVDF film and due to the material similarity of the scaffolds, it could be concluded that the 3D structure could lead to better bone differentiation. Taken together, the obtained results demonstrated that human iPSC-seeded PVDF nanofibrous scaffold could be considered as a promising candidate for use in bone tissue engineering applications.
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http://dx.doi.org/10.1002/jcp.28415DOI Listing
August 2019

In vitro osteogenic differentiation potential of the human induced pluripotent stem cells augments when grown on Graphene oxide-modified nanofibers.

Gene 2019 May 15;696:72-79. Epub 2019 Feb 15.

Department of Tissue engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Due to the several limitations that surgeons are faced during bone tissue implantation there are daily increases in introducing new cell-co-polymer composites for use in bone tissue engineering approaches. In this study tried to develop a suitable nanostructured bio-composite for enhancing osteogenic differentiation of the human induced pluripotent stem cells (iPSCs). Polyvinylidene fluoride-Graphene oxide (PVDF-GO) nanofibers was fabricated by electrospinning and then characterized using scanning electron microscope, tensile and viability assays. After that osteogenic differentiation of the iPSCs was investigated in three groups, including PVDF, PVDF-GO and tissue culture plate as a control group. Alkaline phosphatase activity and calcium content of the iPSCs cultured on PVDF-GO were significantly higher than those cultured on other groups. In addition, Runx2, osteocalcin and osteonectin genes were up regulated in iPSCs cultured on PVDF-GO significantly higher than those cells cultured on PVDF and control. Finally, osteocalcin and osteopontin proteins expression evaluated and the results confirmed higher osteoinductivity of the PVDF-GO nanofibers in comparison with the PVDF nanofibers. According to the results, it was demonstrated that PVDF-GO nanofibers have a great osteoinductive potential and taking together iPSCs-PVDF-GO nanofibrous construct can be an appropriate bio-implant to use for bone tissue engineering applications.
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http://dx.doi.org/10.1016/j.gene.2019.02.028DOI Listing
May 2019

Improved chondrogenic response of mesenchymal stem cells to a polyethersulfone/polyaniline blended nanofibrous scaffold.

J Cell Biochem 2019 Feb 11. Epub 2019 Feb 11.

Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran.

Owing to the fact that the cartilage tissue is not able to repair itself, the treatment of the joint damages is very difficult by current methods. Induction of tissue repair requires suitable cell and extracellular matrix. Providing these two parts can only be done using tissue engineering. In the present study, polyethersulfone (PES) and polyaniline (PANI) blend was electrospined for nanofibrous scaffold fabrication. Mesenchymal stem cells were isolated from human adipose tissue (AT-MSCs), and after characterization cultured on the PES-PANI scaffold and culture plate. Electron microscopic and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assays were used for biocompatibility evaluation of the scaffold and the chondrogenic differentiation potential of AT-MSCs were investigated by staining of proteoglycans and gene and protein expression evaluation. Alcian blue staining, real-time reverse-transcriptase polymerase chain reaction and Western blot results showed that chondrogenic differentiation potential of AT-MSCs was significantly increased when grown on PES-PANI nanofibers and was compared to the one grown on a culture plate. According to the results, PES-PANI has a promising potential to be used as a biomedical implant in patients with joints lesion, such as arthritis and osteoarthritis.
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http://dx.doi.org/10.1002/jcb.28412DOI Listing
February 2019

Bladder smooth muscle cell differentiation of the human induced pluripotent stem cells on electrospun Poly(lactide-co-glycolide) nanofibrous structure.

Gene 2019 Apr 6;694:26-32. Epub 2019 Feb 6.

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

Smooth muscle cell (SMC) regeneration plays an important role in retrieving the bladder-wall functionality and it can be achieved by a proper cell-co-polymer constructed by tissue engineering. Human induced pluripotent stem cells (iPSCs), which can be specifically prepared for the patient, was considered as cells in this study, and Poly(lactide-co-glycolide) (PLGA) as a most interesting polymer in biomedical applications was applied to the scaffold fabrication by electrospinning. After scaffold characterization, SMC differentiation potential of the human iPSCs was investigated while cultured on the PLGA nanofibrous scaffold by evaluation of the SMC related important gene and protein markers. Alpha-smooth muscle actin (ASMA), Smooth muscle 22 alpha (SM-22a) as two early SMC markers were significantly up regulated either two and three weeks after differentiation induction in human iPSCs cultured on PLGA compared to those cells cultured on the tissue culture polystyrene (TCPS). But Calponin-1, Caldesmon1 and myosin heavy chain (MHC) expression differences in human iPSCs cultured on PLGA and TCPS were significant only three weeks after differentiation induction based on its lately expression in the differentiation process. ASMA and MHC proteins were also considered for evaluation by immunocytochemistry on differentiated iPSCs whereas results showed higher expression of these proteins in stem cells grown on PLGA compared to the TCPS. According to the results, human iPSCs demonstrated a great SMC differentiation potential when grown on PLGA and it could be considered as a promising cell-co-polymer for use in bladder tissue engineering.
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http://dx.doi.org/10.1016/j.gene.2019.01.037DOI Listing
April 2019

Therapeutic Aspects of Squill; An Evidence-Based Review.

Curr Drug Discov Technol 2020 ;17(3):318-324

Department of Pharmaceutical Sciences in Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

From ancient times, medicinal plants have been usually utilized to treat many disorders, but today, interest in these herbs is again aroused, because of their fewer side effects and low-cost. In traditional medicine, for many diseases, various medicinal herbs have been suggested so far. Drimia maritime, also named squill, is an important medicinal plant for the treatment of many diseases, especially respiratory diseases. In the current evidence-based study, we conducted a review of the general characteristics, ingredients, administration form, and side effects of squill in traditional medicine. For this purpose, traditional Persian medicine literatures and electronic databases were examined including PubMed, Scopus, and Google Scholar. Many compounds are isolated from D.maritima, including scillaren, scillirubroside, scillarenin, and bufadienolide glycosides. Oxymel is the most commonly used form of squill for various diseases, especially respiratory diseases. Besides, squill has been used in the treatment of cardiovascular, digestive, and dermatological disorders, it is also used against various cancer cells for its antioxidant and cytotoxic properties. Moreover, there is relatively reliable evidence of its benefits for bacterial and helminthic infections, rheumatism, edema, gout, abortion induction, healing of wounds and urine induction. It seems that supplementary studies are required to explore the bioactive agents and their effective mechanisms.
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http://dx.doi.org/10.2174/1570163816666190125154745DOI Listing
September 2021
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