Bahareh Rajaei - Academia.edu (original) (raw)

Papers by Bahareh Rajaei

Diabetologia

Aims/hypothesis Wolfram syndrome is a rare autosomal recessive disorder caused by pathogenic vari... more Aims/hypothesis Wolfram syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the WFS1 gene. It is characterised by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing loss and neurodegeneration. Considering the unmet treatment need for this orphan disease, this study aimed to evaluate the therapeutic potential of glucagon-like peptide 1 receptor (GLP-1R) agonists under wolframin (WFS1) deficiency with a particular focus on human beta cells and neurons. Methods The effect of the GLP-1R agonists dulaglutide and exenatide was examined in Wfs1 knockout mice and in an array of human preclinical models of Wolfram syndrome, including WFS1-deficient human beta cells, human induced pluripotent stem cell (iPSC)-derived beta-like cells and neurons from control individuals and individuals affected by Wolfram syndrome, and humanised mice. Results Our study shows that the long-lasting GLP-1R agonist dulaglutide reverses impaired glucos...

Background and aims: Pancreatic β-cell failure is central in the pathogenesis of diabetes. In vit... more Background and aims: Pancreatic β-cell failure is central in the pathogenesis of diabetes. In vitro differentiation of human induced pluripotent stem cells (iPSCs) into β-cells represents a novel cell source for diabetes research. Here we differentiated iPSC-β-cells and tested their function in vitro and in vivo in humanized mice [...

A total eighty four epidemiologically unrelated clinical isolates of Salmonella enterica serovars... more A total eighty four epidemiologically unrelated clinical isolates of Salmonella enterica serovars were subjected to antimicrobial susceptibility testing and molecular detection of class 1 and 2 integrons. Eleven isolates (13.1%) which were resistant to at least 4 groups of antimicrobial agents considered as MDR (multidrug resistant) Salmonella serovars. PCR assays detected intI1 and intI2 genes in 50 (59.5%) and 14 (16.7%) of Salmonella clinical isolates respectively. Emergence of MDR Salmonella serovars demonstrates that antimicrobial selection pressure is widespread and increased distribution of integron carrying gene cassettes which confer resistance to different antibiotics confirms that integron-mediated antibiotic resistance is considerable in our clinical settings.

Journal of Fasa University of Medical Sciences, 2012

Background & Objective: Molecular typing is an important tool in surveillance and outbreak invest... more Background & Objective: Molecular typing is an important tool in surveillance and outbreak investigations of human Salmonella infections. In this study, Subtyping of Salmonella Paratyphi B and C isolates derived from Iranian patients was carried out by RAPD-PCR to assess the extent of genetic diversity of these isolates. Materials & Methods: Fourteen Salmonella isolates including 6 strains of Salmonella paratyphi B and 8 strains of Salmonella paratyphi C were characterized using RAPD-PCR. Two arbitrary primers, namely OPP-16 and P1254 were used for RAPD analysis and the dendrograms were constructed with NTsys 2.0 computer software. Results: Both primers showed high discriminatory power in differentiating of the related strains of Salmonella. The dendrograms constructed based on RAPD-PCR profiles (with both primers) involving 14 salmonella strains revealed 4 distinct patterns, indicating that these isolates are genetically heterogeneous. Furthermore, a good correlation was not observed between the serotype and the molecular profiles obtained from RAPD data of the Salmonella isolates. Conclusion: The findings of the present study verify the usefulness of RAPD-PCR in characterizing and comparing strains of Salmonella Paratyphi B and C.

Medical Microbiology and Immunology, 2017

HCs. In contrast to the IL-21 mRNA expression, the serum level of the IL-21 protein was significa... more HCs. In contrast to the IL-21 mRNA expression, the serum level of the IL-21 protein was significantly lower in the HAM/TSP patients than in ACs and HCs (p < 0.05). Furthermore, higher expression of Tax and PVL was observed in the HAM/TSP subjects than ACs (p < 0.05). In addition, Tax gene expression was positively correlated with PVL (R = 0.595, p = 0.000) and IL-21 gene expression (R = 0.395, p = 0.021) in the HTLV-1-infected subjects. In conclusion, the increase in IL-21 mRNA expression may reflect the attempt of infected T cells to induce an appropriate antiviral response, and the decrease in IL-21 protein expression may reflect the inhibition of IL-21 mRNA translation by viral factors in favour of virus evasion and dissemination.

Journal of Biomedicine, 2016

Background: Human somatic cells are reprogrammed to induced pluripotent stem (iPS) cells when fou... more Background: Human somatic cells are reprogrammed to induced pluripotent stem (iPS) cells when four transcription factors (Oct4, Sox2, Klf4, and Myc) are ectopically expressed in them. These iPS cells, which evade immunological rejection, are a valuable source for patient-specific cell therapy. Lentiviral systems have been proved to be powerful tools for cellular reprogramming, an example of which is the induction of iPS cells from somatic cells that requires a high transduction efficiency of lentiviruses harboring the four reprogramming factors. Objectives: The purpose of this study was to define an optimized calcium phosphate transfection method to produce high-titer lentiviral vectors for the generation of human iPS cells. Materials and Methods: In this study, the calcium phosphate transfection method was used to generate lentiviruses. The virus supernatant was concentrated using Amicon Ultra-4 column. Results: This method resulted in 80% GFP-positive cells and viral preparations of 2.4 × 10 8 viral particles/mL. Conclusions: This method is both cost effective and simple to adopt.

Journal of cellular physiology, Jan 16, 2016

Human induced pluripotent stem cells (hiPSCs) can potentially serve as an invaluable source for c... more Human induced pluripotent stem cells (hiPSCs) can potentially serve as an invaluable source for cell replacement therapy and allow the creation of patient- and disease-specific stem cells without the controversial use of embryos and avoids any immunological incompatibility. The generation of insulin-producing pancreatic β-cells from pluripotent stem cells in vitro provides an unprecedented cell source for personal drug discovery and cell transplantation therapy in diabetes. A new five-step protocol was introduced in this study, effectively induced hiPSCs to differentiate into glucose-responsive insulin-producing cells. This process mimics in vivo pancreatic organogenesis by directing cells through stages resembling definitive endoderm, primitive gut-tube endoderm, posterior foregut, pancreatic endoderm and endocrine precursor. Each stage of differentiation were characterized by stage-specific markers. The produced cells exhibited many properties of functional β-cells, including expr...

BMC Microbiology, 2015

Background: To investigate antibiotic resistance, the occurrence and distribution of class 1 and ... more Background: To investigate antibiotic resistance, the occurrence and distribution of class 1 and 2 integrons in multidrug-resistant Staphylococcus aureus isolates from hospitals in Tehran, Iran. The isolates were examined for susceptibility to antimicrobial agents. The mecA gene, class 1 and 2 integrons were detected by PCR. Integrase positive strains were further analysed for the presence of resistance gene cassettes using specific primers and were sequenced. Results: Among 139 S.aureus isolates, 109 (78.4 %) and 112 (80.5 %) strains were considered as multidrug resistant and mecA positive, respectively. Class 1 integrons and internal variable regions were found in 72.6 % (101/139) and 97 % (98/101) and class 2 integrons and variable regions also in 35.2 % (49/139) and 65.3 % (32/49) of S.aureus clinical isolates, respectively. Twelve distinct cassette arrays were found, containing genes encoding resistance to β-lactams, aminoglycosides, streptothricin, trimethoprim, chloramphenicol,a putative glucose dehydrogenase precursor and a protein with unknown function. Gene cassette arrays aadB, aadA2 and dhfrA1-sat2-aadA1 were common in S.aureus isolates. We detected a completely new gene cassettes which contained aadB, oxa2, aacA4, orfD-aacA4-catB8, aadB-catB3, orfD-aacA4 and aadB-aadA1-cmlA6 of class 1 and dhfrA1-sat2-aadA1, dhfrA11, dhfrA1-sat2 of class 2 integrons. Conclusions: This is the first study to report carriage of class 1 and 2 integrons and associated gene cassettes among in S.aureus isolates from Iran.

British Microbiology Research Journal, 2014

This study was carried out to detect the distribution of antibiotic-resistant genes in Escherichi... more This study was carried out to detect the distribution of antibiotic-resistant genes in Escherichia coli isolates from slaughtered commercial chickens in Iran by PCR. The investigated genes included aadA1, tet(A), tet(B), dfrA1, qnrA, aac(3)-IV, sul1, bla SHV , bla CMY , ere(A), catA1 and cmlA. According to biochemical experiments, 57 isolates from 360 chicken meat samples were recognized as E. coli. The distribution of antibiotic-resistance genes in the E. coli isolates included tet(A) and tet(B) (52.63%), dfrA1, qnrA, catA1 and cmlA (36.84%) and sul1 and ere(A) (47.36%), respectively. Nine strains (15.78%) were resistant to a single antimicrobial agent and 11 strains (19.29%) showed resistance to two antimicrobial agents. Multi-resistance which was defined as resistance to three or more tested agents was found in 64.91% of E. coli strains. The results indicate that all isolates harbour one or more of antibiotic resistance genes and that the PCR technique is a fast, practical and appropriate method for determining the presence of antibiotic-resistance genes.

Current Research in Bacteriology, 2012

Salmonella enterica serotypes are one of the most important food borne pathogens and significant ... more Salmonella enterica serotypes are one of the most important food borne pathogens and significant public health concerns around the world in humans and other animal species. A total of eighty three epidemiologically unrelated clinical isolates of Salmonella enterica serovars were subjected to antimicrobial susceptibility testing. Eleven isolates (13.1%) which were resistant to at least 4 groups of antimicrobial agents considered as multidrug resistant (MDR) Salmonella serovars. Emergence of MDR Salmonella serovars demonstrates that antimicrobial selection pressure is widespread in our clinical settings. According to the results of antimicrobial susceptibility testing, Salmonella clinical isolates are more susceptible to fluoroquinolones and third generation cephalosporins and these drugs may be used as drugs of choice to treat Salmonella infections.

Advances in Microbiology, 2014

Prevalence of three plasmid-mediated quinolone resistance determinant qnrA, qnrB, qnrS and extend... more Prevalence of three plasmid-mediated quinolone resistance determinant qnrA, qnrB, qnrS and extended spectrum Cephalosporins determinant blaCMY, among eighty-five isolates of Salmonella spp. collected in the community between 2008 and 2010 was determined by PCR. Not only qnr genes but also bla genes were positive in twenty-four different isolates. PCR assay detected that 22 of 85 (25.8%) Salmonella spp. carried the qnrA, 1 (1.17%) of 85 isolates harbored the qnrB, 1 (1.17%) of them contained the qnrS, 1 (1.17%) isolate carried all the three qnrA, qnrB, qnrS genes, 24 of 85 (28.2%) Salmonella carried blaCMY and 5 (5.88%) isolates carried qnrA and blaCMY. Antimicrobial susceptibility patterns of isolates were as follows: 49 (57.6%) exhibited resistance to Nalidixic acid and none of them to Ciprofloxacin. 33 (38.82%) isolates exhibited resistance to Cephalosporins and 2 (2.35%) of them exhibited ESBL phenotype and 12 (14.1%) isolates resistance to Ampicilin. These results were confirmed by MIC determination test as well. Having detected qnr and bla genes suggested that these genes spread antibiotic resistance among pathogenic bacteria.

African Journal of Microbiology Research, 2012

The incidence of methicillin resistance has risen among nosocomial isolates of Staphylococcus aur... more The incidence of methicillin resistance has risen among nosocomial isolates of Staphylococcus aureus and coagulase negative staphylococci. The present study was carried out to investigate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase negative staphylococci (MRCoNS) and to determine their antibiotic susceptibility pattern. A total of one hundred and thirty clinical staphylococcal isolates recovered from blood, tracheal aspirate, urine and wound specimens were evaluated for susceptibility to penicillin, amikacin, ciprofloxacin, vancomycin, erythromycin, ceftriaxone, methicillin, rifampin and gentamicin by Disk diffusion method and molecular detection of mecA gene. The results showed that MRCoNS were more resistant to these antibiotics as compared to MRSA and the most effective antibiotic to use for staphylocoocal isolates is vancomycin showing (100% of S. aureus and 90% of CoNS) efficacy. The mecA gene was detected in 56% of the isolated S. aureus and 70% of the CONS isolates. The prevalence of methicillin resistant staphylococci in Iran was very high and 45.4% of MRSA and MRCoNS isolates were at least resistance to 3 or more classes of antibiotics. The high prevalence of MRSA immerged in Iran could be originated due to antibiotic pressure and poor control measures on the application of antibiotics such as methicillin.

Endocrine Abstracts

info:eu-repo/semantics/nonPublishe

Current protocols in human genetics, Jan 18, 2018

The International Diabetic Federation estimated that 415 million adults currently have diabetes a... more The International Diabetic Federation estimated that 415 million adults currently have diabetes and 318 million adults had impaired glucose tolerance, putting them at high risk of developing diabetes in the future. In Type 1 Diabetes (T1D), the β cells are lost because of autoimmune reactions. Although islet transplantation has been a promising therapy for T1D, it is greatly limited by pancreatic donors. Here, we describe a protocol to generate glucose- responsive pancreatic β-like (GRPβ-L) cells from human-induced pluripotent stem (iPS) cells. We recapitulate in vivo pancreas development by in vitro induction of differentiating human (iPS) cells with stage-specific signaling molecules and proteins. Inhibition of Tyrosine Kinase receptor AXL, TGF-β, and Notch signaling pathways in the final stage of the five-stage protocol could efficiently generate GRPβ-L from the endocrine progenitor. Differentiation of human iPS cells through the protocol could result in functional GRPβ-L cells, ...

ASAIO journal (American Society for Artificial Internal Organs : 1992), Jan 27, 2017

Pancreatic and duodenal homeobox 1 (PDX1), a member of the homeodomain-containing transcription f... more Pancreatic and duodenal homeobox 1 (PDX1), a member of the homeodomain-containing transcription factor family, is a key transcription factor for pancreas development and mature β-cell function. In this study, induced overexpression of PDX1 resulted in producing susceptible cells for pancreatic differentiation and was well beneficial to enhance β-cell production, maturation, function, and survival. Induced PDX1 overexpression in harmony with a set of signaling molecules involves in guiding the signaling pathways toward pancreas development, leaded to high-efficient in vitro generation of ectopic insulin-producing cells (IPCs) with the effectively reduced number of polyhormonal cells and increased number of INS single-positive cells. This strategy yielded 85.61% glucose-responsive insulin-positive cells in vitro, which was seven times higher than the basal level, and electron microscopy images revealed the presence of mature β-cell secretory granules. The generation of glucose-respons...

Neuroscience Letters, 2016

Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disea... more Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD) is a neurodegenerative disorder, in which the nigro-striatal Dopaminergic (DAergic) neurons are selectively lost. Treatment of neurodegenerative diseases with Pluripotent Stem Cells (PSCs) is a big interest in cell therapy. Here, we used induced Pluripotent Stem Cells (iPSCs) expressing two master Dopaminergic (DAergic) transcription factors, i.e. Nurr1 and Pitx3, to generate functional in vitro DAergic-like neurons. After establishment and characterization of Doxycycline-inducible iPSCs from mouse fibroblasts, the cells were transduced by NURR1- and PITX3-harboring lentiviruses. The Nurr1/Pitx3 -iPSCs were differentiated through a five-stage protocol to generate DAergic-like neurons. The results confirmed the efficient expression of DAergic neuron markers in the end of protocol. Beside, the generated cells could exclusively synthesize and secrete Dopamine in response to secretagogues. In conclusion, overexpression of Nurr1 and Pitx3 in iPSCs could efficiently program iPSCs into functional DAergic-like neurons. This finding may have an impact on future stem cell therapy of PD.